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26 Jun 2019 at 01:33
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Bibliography on: Invasive Ductal Carcinoma


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RJR: Recommended Bibliography 26 Jun 2019 at 01:33 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: 2019-06-20

Lodd E, Wiggenhauser LM, Morgenstern J, et al (2019)

The combination of loss of glyoxalase1 and obesity results in hyperglycemia.

JCI insight, 4(12): pii:126154.

The increased formation of methylglyoxal (MG) under hyperglycemia is associated with the development of microvascular complications in patients with diabetes mellitus; however, the effects of elevated MG levels in vivo are poorly understood. In zebrafish, a transient knockdown of glyoxalase 1, the main MG detoxifying system, led to the elevation of endogenous MG levels and blood vessel alterations. To evaluate effects of a permanent knockout of glyoxalase 1 in vivo, glo1-/- zebrafish mutants were generated using CRISPR/Cas9. In addition, a diet-induced-obesity zebrafish model was used to analyze glo1-/- zebrafish under high nutrient intake. Glo1-/- zebrafish survived until adulthood without growth deficit and showed increased tissue MG concentrations. Impaired glucose tolerance developed in adult glo1-/- zebrafish and was indicated by increased postprandial blood glucose levels and postprandial S6 kinase activation. Challenged by an overfeeding period, fasting blood glucose levels in glo1-/- zebrafish were increased which translated into retinal blood vessel alterations. Thus, the data have identified a defective MG detoxification as a metabolic prerequisite and glyoxalase 1 alterations as a genetic susceptibility to the development of type 2 diabetes mellitus under high nutrition intake.

RevDate: 2019-06-18

Saleh Gargari S, Taheri M, Kholghi Oskooei V, et al (2019)

Transcription Levels of nicotinamide nucleotide transhydrogenase and Its Antisense in Breast Cancer Samples.

Cell journal, 21(3):331-336.

Objective: To evaluate association of patients' clinicopathological data with expression of nicotinamide nucleotide transhydrogenase (NNT) and naturally occurring antisense RNA of the same gene locus (NNT-AS1) in breast cancer samples.

Materials and Methods: In the current case-control study, mean expressions of NNT and NNT-AS1 were assessed in 108 breast tissue samples including 54 invasive ductal carcinoma samples and 54 adjacent non-cancerous tissues (ANCTs) by quantitative reverse transcription-polymerase chain reaction (qRT-PCR).

Results: NNT expression was not significantly different between tumor tissues and ANCTs. However, NNT-AS1 expression was significantly down-regulated in tumor tissues compared to ANCTs (expression ratio=0.51, P=0.01). NNT-AS1 expression was significantly higher in estrogen receptor (ER) negative samples, in comparison with ER positives (P=0.01). No considerable difference was found in the gene expressions between other subcategories of patients. Considerable correlations were detected between expression levels of these two genetic loci in both tumor tissues and ANCTs.

Conclusion: In the current study, for the first time we simultaneously assessed expression of NNT and NNT-AS1 in breast cancer tissues. This study highlights association of ER status with dysregulation of NNT-AS1 in breast cancer tissues. Future researches are necessary to explore the function of this long non-coding RNA (lncRNA) in the pathogenesis of breast cancer.

RevDate: 2019-06-17

Blanc-Durand P, Milliner M, Huchet V, et al (2019)

18F-FDG Whole-body PET/MRI of a 30-Week Pregnant Woman With Breast Cancer Revealed Interesting Fetal Findings.

Clinical nuclear medicine [Epub ahead of print].

A 35-year-old 30-week pregnant woman was referred to our institution for initial staging of a triple negative invasive ductal carcinoma of the left breast. To avoid fetal radiation exposure from CT, a whole-body F-FDG PET/MRI was performed. Simultaneous acquisition of PET, T1-, T2-, and diffusion-weighted sequences revealed left axillary node extension and no distant metastases. Fetal radiation dose was estimated at 1.9 mGy. Interestingly, low fetal brain uptake and high symmetrical myocardial metabolism in both ventricles were found. Delivery was induced at 37 weeks of amenorrhea, and the patient underwent 4 cycles of neoadjuvant chemotherapy.

RevDate: 2019-06-16

Raetz AG, SS David (2019)

When you're strange: Unusual features of the MUTYH glycosylase and implications in cancer.

DNA repair, 80:16-25 pii:S1568-7864(19)30098-9 [Epub ahead of print].

MUTYH is a base-excision repair glycosylase that removes adenine opposite 8-oxoguanine (OG). Variants of MUTYH defective in functional activity lead to MUTYH-associated polyposis (MAP), which progresses to cancer with very high penetrance. Whole genome and whole exome sequencing studies have found MUTYH deficiencies in an increasing number of cancer types. While the canonical OG:A repair activity of MUTYH is well characterized and similar to bacterial MutY, here we review more recent evidence that MUTYH has activities independent of OG:A repair and appear centered on the interdomain connector (IDC) region of MUTYH. We summarize evidence that MUTYH is involved in rapid DNA damage response (DDR) signaling, including PARP activation, 9-1-1 and ATR signaling, and SIRT6 activity. MUTYH alters survival and DDR to a wide variety of DNA damaging agents in a time course that is not consistent with the formation of OG:A mispairs. Studies that suggest MUTYH inhibits the repair of alkyl-DNA damage and cyclopyrimidine dimers (CPDs) is reviewed, and evidence of a synthetic lethal interaction with mismatch repair (MMR) is summarized. Based on these studies we suggest that MUTYH has evolved from an OG:A mispair glycosylase to a multifunctional scaffold for DNA damage response signaling.

RevDate: 2019-06-15

Jeyapala R, Savio AJ, Olkhov-Mitsel E, et al (2019)

GBX2 Methylation Is a Novel Prognostic Biomarker and Improves Prediction of Biochemical Recurrence Among Patients with Prostate Cancer Negative for Intraductal Carcinoma and Cribriform Architecture.

European urology oncology, 2(3):231-238.

BACKGROUND: Tumor intraductal carcinoma/cribriform architecture (IDC/C) is associated with an unfavorable prognosis and biochemical recurrence (BCR) in prostate cancer (PCa). Up to 70% of PCa patients are IDC/C-negative, but it is estimated that 20% of these cases still experience BCR. Thus, biomarkers for better detection of aggressive disease in IDC/C-negative patients are required.

OBJECTIVE: To investigate tumor-specific methylation of the transcription factor GBX2 as a novel prognosticator and predictor of BCR in PCa patients stratified by histopathologic features including IDC/C.

Using genome-wide methylome profiling, we identified higher GBX2 methylation in grade group (GG) 4 tumors compared to GG1 (discovery cohort). The prognostic nature of GBX2 methylation was validated in silico using The Cancer Genome Atlas data (n=478) and a quantitative methylation assay for radical prostatectomy samples (n=254). Regulation of GBX2 methylation was investigated in prostate cells using methyl-CpG-binding domain sequencing and methylation analysis in functional knockouts of TET2, a key epigenetic player in prostate carcinogenesis.

The association of GBX2 methylation with Gleason score (GS), pathologic stage (pT), IDC/C, and BCR was analyzed using Kruskal-Wallis and Mann-Whitney tests. Univariate and multivariate Cox regression analyses were used to predict BCR.

RESULTS: GBX2 methylation was associated with GS (p<0.05), pT (p<0.01), and BCR (p<0.05). GBX2 methylation (p=0.004), GS (p<0.001), pT (p=0.012), and prostate-specific antigen (p=0.005) were independent predictors of BCR. Among IDC/C-negative patients, GBX2 methylation improved prediction of BCR (p=0.002). Loss of TET2 in prostate cells resulted in greater GBX2 methylation.

CONCLUSIONS: We identified GBX2 methylation as a novel prognostic factor in PCa and an independent predictor of BCR. We demonstrated the additive value of GBX2 methylation in predicting BCR among IDC/C-negative patients and elucidated a novel TET2-mediated upstream epigenetic regulatory mechanism of GBX2.

PATIENT SUMMARY: We identified GBX2 methylation as a promising prognostic biomarker that could improve the identification of prostate cancer patients at higher risk of biochemical recurrence.

RevDate: 2019-06-14

Tan QT, AG Mihir (2019)

A case of invasive ductal carcinoma presenting as an exophytic nipple mass.

The breast journal [Epub ahead of print].

RevDate: 2019-06-14

Sherbuk JE, McManus D, Topal JE, et al (2019)

Improved mortality in Staphylococcus aureus bacteremia with the involvement of antimicrobial stewardship team and infectious disease consultation.

Infection control and hospital epidemiology pii:S0899823X19001363 [Epub ahead of print].

A retrospective study was conducted to evaluate the value of the antimicrobial stewardship team (AST) combined with infectious diseases consultation (IDC) on management and outcomes of Staphylococcus aureus bacteremia (SAB) in a tertiary-care academic center. Involvement of AST or IDC was associated with reduced mortality of SAB.

RevDate: 2019-06-13

Erel H, Ronen T, Freedman G, et al (2019)

Preserved left and upper visual field advantages in older adults' orienting of attention.

Experimental gerontology pii:S0531-5565(19)30097-X [Epub ahead of print].

Lateralization of the distribution of attentional function in the brain is asserted to lead to asymmetry in attentional allocation. This is expressed in the phenomenon of pseudoneglect, in which line and object bisection judgments indicate left visual field (and presumably right hemisphere) dominance. Several studies indicate that this asymmetry is not found in old age, which is taken as an indication of decline in attentional function with aging. We examined this assertion using a more comprehensive assay of attentional asymmetry. We contrasted the spatial distribution of older and younger adults' visual attention using the Starry Night Task, a speeded visual search task in which targets must be located across a wide spatial distribution against a dynamic background of distracters. As expected, compared to younger adults, older adults' response times were longer overall. However, we found that older adults exhibited a graded left visual field advantage, even more distinctly than did younger adults. Additionally, older adults exhibited a graded upper visual field advantage equivalent to that of younger adults. These results indicate that aging may not necessarily compromise basic patterns of distribution of spatial attention. They do not support claims of aging-related loss of attentional lateralization.

RevDate: 2019-06-13

Horimoto Y, Terao T, Tsutsumi Y, et al (2019)

Estrogen Receptor-positive Ductal Carcinoma In Situ Frequently Overexpresses HER2 Protein Without Gene Amplification.

The American journal of surgical pathology [Epub ahead of print].

Overexpression of human epidermal growth factor receptor 2 (HER2) protein is well known to be more frequent in ductal carcinoma in situ (DCIS) than in invasive ductal carcinoma (IDC). However, the reasons for this difference are poorly understood. On the basis of the high frequency of estrogen receptor-positive (ER+) and HER2-positive (HER2+) DCIS, we hypothesized that this tumor type overexpresses HER2 protein without gene amplification and retrospectively investigated the HER2/neu gene status of 71 ER(+)HER2(+) DCIS, surgically removed during the 2007 to 2017 period, employing fluorescence in situ hybridization (FISH). To compare HER2 protein expressions between in situ and invasive components of individual tumors, 86 pT1mi/1a IDC with predominantly in situ disease were also examined. Furthermore, for comparison of FISH status between in situ and coexisting invasive components, another patient cohort, 78 FISH-positive IDC cases, were employed. To elucidate biological differences among DCIS with various combinations of ER and HER2 protein expressions, we also analyzed public microarray data of mRNA. HER2 gene amplification was observed in 35% of ER(+) and HER2 protein-overexpressing specimens, significantly lower than the 94% in ER-negative (ER-) and HER2 protein-overexpressing specimens (P<0.001). HER2 protein expression was decreased in the invasive component as compared with coexisting in situ portions in 40% of individual tumors, whereas the FISH status of these 2 components was well preserved. Moreover, ER(+) and HER2 protein-overexpressing DCIS showed significantly higher hypoxia-inducible factor-1α protein expression than the ER(+) and HER2 protein-nonoverexpressing tumors (P=0.016). We revealed that ER(+) and HER2 protein-overexpressing DCIS, especially ER-high tumors, frequently overexpress HER2 protein without gene amplification. Our data may provide novel insights for understanding the biology of DCIS.

RevDate: 2019-06-13

Zhang J, Zhao B, F Jin (2019)

The assessment of 8th edition AJCC prognostic staging system and a simplified staging system for breast cancer: The analytic results from the SEER database.

The breast journal [Epub ahead of print].

The prognostic value of the prognostic staging system that incorporated estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor-2 (Her-2), and histological grade has been validated in breast cancer (BC) patients, but the staging system seems to be somewhat complex. Recently, an updated bioscore system based on these tumor biological factors was proposed. The purpose of this study was to compare the prognostic stratification between prognostic staging system of American Joint Commission on Cancer (AJCC) and a simplified staging system based on the bioscore system and anatomic TNM staging for BC patients. A total of 44 593 patients with invasive ductal carcinoma who underwent radical resection between 2010 and 2011 were reviewed using the SEER database. The patients were reclassified into different groups according to the anatomic staging system, prognostic staging system, risk bioscore system, and simplified staging system, respectively. The prognostic differences between different groups were compared and clinicopathologic features were analyzed. The anatomic TNM staging failed to clearly distinguish the prognostic difference between stage IIIB and stage IIIC. Therefore, we proposed an adjusted anatomic staging, in which T1N3 and T2N3 were downstaged from stage IIIC to stage IIIB, and T4N2 was upstaged from stage IIIB to stage IIIC. Histological grade III, ER(-), PR(-), and Her-2(-) were identified as independent prognostic factors in the multivariate analysis, and these factors were separately marked as 1 point. There were significant survival differences among different risk points except for the comparison between 0 and 1 point. The higher the risk points, the poorer the prognosis of BC patients. In addition, the curve distance between stage IIA and stage IIB was not significantly broaden according to the prognostic staging system. However, the prognostic stratification for BC patients could be significantly improved by the simplified staging system incorporated the bioscore system and adjusted anatomic staging. Several drawbacks may still exist in the prognostic staging system of AJCC. A simplified staging system that incorporated risk score system and the anatomic staging could provide more accurate prognostic information for BC patients.

RevDate: 2019-06-12

Zhu L, Ma N, Wang B, et al (2019)

Clinical analysis of 21-gene recurrence score test in hormone receptor-positive early-stage breast cancer.

Oncology letters, 17(6):5469-5480.

The 21-gene recurrence score (RS) predicts the prognosis of patients with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative early-stage breast cancer and the effectiveness of adding adjuvant chemotherapy on the basis of endocrine therapy to avoid excessive chemotherapy. The present study aimed to analyze clinicopathological characteristics and chemotherapeutic efficacy-related target genes with the 21-gene RS in hormone receptor-positive early-stage breast cancer in China. The prognostic value of chemotherapeutic efficacy-related target genes was also examined. In addition, this study investigated the postoperative adjuvant therapeutic decision-oriented role of 21-gene RS in hormone receptor-positive and lymph node-negative early-stage breast cancer. In the present retrospective study, 110 ER+/HER2- early-stage breast cancer patients were tested with the 21-gene RS. The analyses of clinicopathological characteristics and chemotherapeutic efficacy-related target genes with the 21-gene RS were performed using the χ2 test, the Wilcoxon rank-sum test and binary logistic regression. Kaplan-Meier survival plots were drawn in www.kmplot.com. Furthermore, the McNemar χ2 test was used to compare the changes of treatment decisions before and after the 21-gene test. The median RS of 110 patients was 16 (range, 2-47), and patients were categorized as low (59.1%), intermediate (34.5%) or high risk (6.4%). The results revealed that higher body mass index, invasive ductal carcinoma type, higher histological grade, luminal B molecular type and higher thymidylate synthetase (TYMS) and DNA topoisomerase IIα (TOP2A) gene expression levels were more likely to have a higher RS. Kaplan-Meier plots suggested that expression of TYMS, tubulin β3 class III (TUBB3) and TOP2A genes was significantly associated with relapse-free survival for ER+ breast cancer. Additionally, prior to 21-gene RS testing, 61 patients (55%) were recommended adjuvant chemotherapy and endocrine therapy; however, following 21-gene test, 32 patients (29%) were treated with only adjuvant endocrine therapy. TYMS, TUBB3 and TOP2A gene expression may have prognostic value for ER+ breast cancer. In addition, 21-gene RS testing may aid to avoid excessive postoperative adjuvant chemotherapy.

RevDate: 2019-06-12

Cuesta Cuesta AB, Martín Ríos MD, Noguero Meseguer MR, et al (2019)

Accuracy of tumor size measurements performed by magnetic resonance, ultrasound and mammography, and their correlation with pathological size in primary breast cancer.

Cirugia espanola pii:S0009-739X(19)30145-9 [Epub ahead of print].

INTRODUCTION: The objective of this study was to determine which image test used to measure the size of pre-operative primary breast cancer (mammography, ultrasound or magnetic resonance imaging [MRI]) correlated best with the size of the tumor in the postoperative surgical specimen.

METHODS: A retrospective analysis was conducted of women diagnosed with breast cancer for which primary surgical treatment was indicated and who underwent surgical intervention between January 2014 and December 2016. Sociodemographic, imaging and histological variables were collected. The results are presented by age group, tumor size and histological type.

RESULTS: In the 224 women studied, mammography and MRI tumor sizes were compared with pathology study tumor measurements, revealing no significant differences, both overall and based on histologic type or age. However, both significantly underestimated large tumors and significantly overestimated small tumors. Ultrasound significantly underestimated tumor size, especially in large tumors, older patients and in infiltrating ductal carcinoma (IDC) and infiltrating ductal carcinoma with associated ductal carcinoma in situ (IDC+DCIS). MRI correlated best with histological tumor size, although with no statistically significant differences.

CONCLUSIONS: MRI is the best predictor of tumor size in breast cancer. Histologic type and tumor size are key parameters when estimating tumor size and should be taken into account when planning surgery. Patient age does not interfere with the interpretation of imaging tests.

RevDate: 2019-06-11

Troisi J, Landolfi A, Vitale C, et al (2019)

A metabolomic signature of treated and drug-naïve patients with Parkinson's disease: a pilot study.

Metabolomics : Official journal of the Metabolomic Society, 15(6):90 pii:10.1007/s11306-019-1554-x.

INTRODUCTION: About 90% of cases of Parkinson's disease (PD) are idiopathic and attempts to understand pathogenesis typically assume a multifactorial origin. Multifactorial diseases can be studied using metabolomics, since the cellular metabolome reflects the interplay between genes and environment.

OBJECTIVE: The aim of our case-control study is to compare metabolomic profiles of whole blood obtained from treated PD patients, de-novo PD patients and controls, and to study the perturbations correlated with disease duration, disease stage and motor impairment.

METHODS: We collected blood samples from 16 drug naïve parkinsonian patients, 84 treated parkinsonian patients, and 42 age matched healthy controls. Metabolomic profiles have been obtained using gas chromatography coupled to mass spectrometry. Multivariate statistical analysis has been performed using supervised models; partial least square discriminant analysis and partial least square regression.

RESULTS: This approach allowed separation between discrete classes and stratification of treated patients according to continuous variables (disease duration, disease stage, motor score). Analysis of single metabolites and their related metabolic pathways revealed unexpected possible perturbations related to PD and underscored existing mechanisms that correlated with disease onset, stage, duration, motor score and pharmacological treatment.

CONCLUSION: Metabolomics can be useful in pathogenetic studies and biomarker discovery. The latter needs large-scale validation and comparison with other neurodegenerative conditions.

RevDate: 2019-06-11

Bao Y, Wang L, Shi L, et al (2019)

Transcriptome profiling revealed multiple genes and ECM-receptor interaction pathways that may be associated with breast cancer.

Cellular & molecular biology letters, 24:38 pii:162.

Background: Exploration of the genes with abnormal expression during the development of breast cancer is essential to provide a deeper understanding of the mechanisms involved. Transcriptome sequencing and bioinformatics analysis of invasive ductal carcinoma and paracancerous tissues from the same patient were performed to identify the key genes and signaling pathways related to breast cancer development.

Methods: Samples of breast tumor tissue and paracancerous breast tissue were obtained from 6 patients. Sequencing used the Illumina HiSeq platform. All. Only perfectly matched clean reads were mapped to the reference genome database, further analyzed and annotated based on the reference genome information. Differentially expressed genes (DEGs) were identified using the DESeq R package (1.10.1) and DEGSeq R package (1.12.0). Using KOBAS software to execute the KEGG bioinformatics analyses, enriched signaling pathways of DEGs involved in the occurrence of breast cancer were determined. Subsequently, quantitative real time PCR was used to verify the accuracy of the expression profile of key DEGs from the RNA-seq result and to explore the expression patterns of novel cancer-related genes on 8 different clinical individuals.

Results: The transcriptomic sequencing results showed 937 DEGs, including 487 upregulated and 450 downregulated genes in the breast cancer specimens. Further quantitative gene expression analysis was performed and captured 252 DEGs (201 downregulated and 51 upregulated) that showed the same differential expression pattern in all libraries. Finally, 6 upregulated DEGs (CST2, DRP2, CLEC5A, SCD, KIAA1211, DTL) and 6 downregulated DEGs (STAC2, BTNL9, CA4, CD300LG, GPIHBP1 and PIGR), were confirmed in a quantitative real time PCR comparison of breast cancer and paracancerous breast tissues from 8 clinical specimens. KEGG analysis revealed various pathway changes, including 20 upregulated and 21 downregulated gene enrichment pathways. The extracellular matrix-receptor (ECM-receptor) interaction pathway was the most enriched pathway: all genes in this pathway were DEGs, including the THBS family, collagen and fibronectin. These DEGs and the ECM-receptor interaction pathway may perform important roles in breast cancer.

Conclusion: Several potential breast cancer-related genes and pathways were captured, including 7 novel upregulated genes and 76 novel downregulated genes that were not found in other studies. These genes are related to cell proliferation, movement and adhesion. They may be important for research into breast cancer mechanisms, particularly CST2 and CA4. A key signaling pathway, the ECM-receptor interaction signal pathway, was also identified as possibly involved in the development of breast cancer.

RevDate: 2019-06-11

Arabpour M, Ghods A, Shariat M, et al (2019)

Correlation of 4-1BBL+ B Cells in Tumor Draining Lymph Nodes with Pathological Characteristics of Breast Cancer.

Iranian journal of immunology : IJI, 16(2):108-116.

BACKGROUND: B cells can increase the expression of granzyme B in CD8+ T cells through 4-1BBL/4-1BB interaction and promote anti-tumor immunity.

OBJECTIVE: To investigate the expression of 4-1BBL on B cells in the breast tumor draining lymph nodes (TDLNs) and its association with disease parameters.

METHODS: Using Ficoll-Hypaque gradient centrifugation, mononuclear cells were isolated from axillary lymph nodes of 42 patients. Cells received 4 hours of PMA/Ionomycin stimulation, in vitro. Both unstimulated and stimulated cells were stained with anti‒CD19 and anti‒4-1BBL antibodies and subjected to flow cytometry.

RESULTS: 4-1BBL expression was detected on 2.8 ± 1.7% of unstimulated B cells, while 27.4 ± 11.9% of B cells expressed this co-stimulatory molecule following stimulation. In steady state, the percentage of 4-1BBL+ B cells was not associated with cancer characteristics. However, in patients with invasive ductal carcinoma, the percentage of 4-1BBL expressing B cells in stimulated condition had a decreasing trend in grade III, compared to grade II+I. In addition, significantly higher frequency of 4-1BBL+ B cells was seen in the TDLNs of ER+ or PR+ compared with ER‒ or PR‒ patients (p=0.021 and p=0.015, respectively). No significant associations were observed between the frequency of 4-1BBL+ B cells and the number of involved LNs, Her2 expression or disease stage.

CONCLUSIONS: The frequency of 4-1BBL+ B cells significantly increased following a short time activation, and showed relative and significant associations with tumor grade and estrogen receptor status, respectively. More investigations are required to evaluate the potential of 4-1BBL+ B cells for use in immunotherapy.

RevDate: 2019-06-09

Gilleron J, Gerdes JM, A Zeigerer (2019)

Metabolic regulation through the endosomal system.

Traffic (Copenhagen, Denmark) [Epub ahead of print].

The endosomal system plays an essential role in cell homeostasis by controlling cellular signaling, nutrient sensing, cell polarity and cell migration. However, its place in the regulation of tissue, organ and whole body physiology is less well understood. Recent studies have revealed an important role for the endosomal system in regulating glucose and lipid homeostasis, with implications for metabolic disorders such as type-2 diabetes, hypercholesterolemia and non-alcoholic fatty liver disease. By taking insights from in vitro studies of endocytosis and exploring their effects on metabolism, we can begin to connect the fields of endosomal transport and metabolic homeostasis. In this review, we explore current understanding of how the endosomal system influences the systemic regulation of glucose and lipid metabolism in mice and humans. We highlight exciting new insights that help translate findings from single cells to a wider physiological level and open up new directions for endosomal research. This article is protected by copyright. All rights reserved.

RevDate: 2019-06-09

Downes MR, Xu B, TH van der Kwast (2019)

Gleason grade patterns in nodal metastasis and corresponding prostatectomy specimens: impact on patient outcome.

Histopathology [Epub ahead of print].

BACKGROUND: Lymph node metastases at the time of prostatectomy are an infrequent finding. The correlation of the pattern of nodal metastases with patient outcome has yet to be explored.

METHODS: Lymph node positive prostatectomies were retrospectively reviewed. The presence of cribriform carcinoma (CC), intraductal carcinoma (IDC) and ISUP grade (G) were documented. The largest nodal metastasis was assessed for morphologic patterns present. G was assigned to the metastasis based on percentage morphologic patterns present. Statistical analysis used SPSS to assess disease specific survival (DSS), disease free survival (DFS) and distant metastasis free survival (DMFS).

RESULTS: 110 cases were identified: G5 (n=52), G4 (n=8), G 3 (n=34), G2 (n=10), no G (n=6; treatment effect). IDC or CC was present in 103 (94%) specimens. >1 positive node correlated with worse DFS (p=0.012, hazard ratio HR=1.951, 95% confidence interval 1.142-3.331) and DMFS (p=0.009, HR=2.647, 95% CI 1.239-5.651). G in the prostate and nodal metastasis were poorly correlated (kappa= 0.073, p=0.195). The presence of pattern 5 was seen in 33 nodes (30%) and correlated with DFS (p=0.020, HR=1.903, 95% CI 1.091-3.320), DSS (p=0.021, HR=5.937, 95% CI 1.084-32.533) and DMFS (p=0.007, HR=2.695, 95% CI 1.269-5.726). Nodal cribriform pattern showed no prognostic correlation and pattern 3 metastasis showed a significant trend towards better outcome (DMFS p=0.033, HR=0.431, 95% CI 0.194-0.958).

CONCLUSIONS: IDC or CC is identified in 94% of node positive prostate cancers. Although G in the largest nodal metastasis has prognostic significance, its G does not reflect that of the primary prostatic adenocarcinoma. This article is protected by copyright. All rights reserved.

RevDate: 2019-06-10

Stohl S, Sprung CL, Lippert A, et al (2019)

Impact of triage-to-admission time on patient outcome in European intensive care units: A prospective, multi-national study.

Journal of critical care, 53:11-17 pii:S0883-9441(19)30306-5 [Epub ahead of print].

PURPOSE: Ubiquitous bed shortages lead to delays in intensive care unit (ICU) admissions worldwide. Assessing the impact of delayed admission must account for illness severity. This study examined both the relationship between triage-to-admission time and 28-day mortality and the impact of controlling for Simplified Acute Physiology Score (SAPS) II scores on that relationship.

METHODS: Prospective cross-sectional analysis of referrals to eleven ICUs in seven European countries between 2003 and 2005. Outcomes among patients admitted within versus after 4 h were compared using a Chi-square test. Triage-to-admission time was also analyzed as a continuous variable; outcomes were assessed using a non-parametric Kruskal-Wallis test.

RESULTS: Among 3175 patients analyzed, triage-to-admission time was 2.1 ± 3.9 h. Patients admitted within 4 h had higher SAPS II scores (33.6 versus 30.6, Pearson correlation coefficient -0.07, p < 0.0001). 28-day mortality was surprisingly higher among patients admitted earlier (29.6 vs 25.2%, OR 1.25, 95% CI 0.99-1.58, p = 0.06). Even after adjusting for SAPS II scores, delayed admission was not associated with higher mortality (OR 1.08, CI 0.83-1.41, p = 0.58).

CONCLUSIONS: Even after accounting for quantifiable parameters of illness severity, delayed admission did not negatively impact outcome. Triage practices likely influence outcomes. Severity scores may not fully reflect illness acuity or trajectory.

RevDate: 2019-06-07

Hamzah JL, Ong KW, BY Tan (2019)

Isolated invasive ductal carcinoma of the nipple-areolar complex: A rare occurrence yet to be reported in current literature.

Invasive ductal carcinoma of the nipple-areolar complex is exceedingly rare. Patients who present with bloody nipple discharge with or without the presence of Paget's disease constitute one-third of all symptomatic in situ patients. Only rarely does an invasive cancer cause nipple discharge in the absence of a clinical mass. Even more obscure is the case of the invasive cancer involving solely the nipple-areolar complex. Sir James Paget first described 'an eczematous change in the skin of the nipple preceding an underlying mammary cancer' in 1874, which is now known as Paget's disease, considered to be ductal carcinoma in situ of the nipple-areolar region. There are two competing theories as to the pathogenesis of Paget's disease of the breast-one suggests that Pagetoid cells are keratinocytes that have undergone malignant transformation. According to this theory, Paget's disease of the breast represents an in situ carcinoma of the skin-and that overlying skin changes and underlying malignancy are discontinuous. The second theory suggests that cells migrate along basement membranes and enter the epidermis and dermis of the nipple-areola complex. Pagetoid cells and underlying carcinomas demonstrate similar immunohistochemical staining patterns.

RevDate: 2019-06-07

Chavez DE, Gronau I, Hains T, et al (2019)

Comparative genomics provides new insights into the remarkable adaptations of the African wild dog (Lycaon pictus).

Scientific reports, 9(1):8329 pii:10.1038/s41598-019-44772-5.

Within the Canidae, the African wild dog (Lycaon pictus) is the most specialized with regards to cursorial adaptations (specialized for running), having only four digits on their forefeet. In addition, this species is one of the few canids considered to be an obligate meat-eater, possessing a robust dentition for taking down large prey, and displays one of the most variable coat colorations amongst mammals. Here, we used comparative genomic analysis to investigate the evolutionary history and genetic basis for adaptations associated with cursoriality, hypercanivory, and coat color variation in African wild dogs. Genome-wide scans revealed unique amino acid deletions that suggest a mode of evolutionary digit loss through expanded apoptosis in the developing first digit. African wild dog-specific signals of positive selection also uncovered a putative mechanism of molar cusp modification through changes in genes associated with the sonic hedgehog (SHH) signaling pathway, required for spatial patterning of teeth, and three genes associated with pigmentation. Divergence time analyses suggest the suite of genomic changes we identified evolved ~1.7 Mya, coinciding with the diversification of large-bodied ungulates. Our results show that comparative genomics is a powerful tool for identifying the genetic basis of evolutionary changes in Canidae.

RevDate: 2019-06-11

Haythorne E, Rohm M, van de Bunt M, et al (2019)

Diabetes causes marked inhibition of mitochondrial metabolism in pancreatic β-cells.

Nature communications, 10(1):2474 pii:10.1038/s41467-019-10189-x.

Diabetes is a global health problem caused primarily by the inability of pancreatic β-cells to secrete adequate levels of insulin. The molecular mechanisms underlying the progressive failure of β-cells to respond to glucose in type-2 diabetes remain unresolved. Using a combination of transcriptomics and proteomics, we find significant dysregulation of major metabolic pathways in islets of diabetic βV59M mice, a non-obese, eulipidaemic diabetes model. Multiple genes/proteins involved in glycolysis/gluconeogenesis are upregulated, whereas those involved in oxidative phosphorylation are downregulated. In isolated islets, glucose-induced increases in NADH and ATP are impaired and both oxidative and glycolytic glucose metabolism are reduced. INS-1 β-cells cultured chronically at high glucose show similar changes in protein expression and reduced glucose-stimulated oxygen consumption: targeted metabolomics reveals impaired metabolism. These data indicate hyperglycaemia induces metabolic changes in β-cells that markedly reduce mitochondrial metabolism and ATP synthesis. We propose this underlies the progressive failure of β-cells in diabetes.

RevDate: 2019-06-07

Kim SJ, JY Kim (2019)

An Unusual Cutaneous Recurrence of Carcinoma in the Mastectomy Bed and Its Imaging Features: A Case Report.

The American journal of case reports, 20:800-805 pii:916609.

BACKGROUND Chest wall recurrences of carcinoma after mastectomy usually involve subcutaneous tissue or the deep muscular layer. Recurrences arising in the skin are rare, and there are few reports of the associated radiologic features. This report presents an unusual case of cutaneous recurrence in the mastectomy bed and demonstrates its radiologic features using sonography and magnetic resonance imaging (MRI). CASE REPORT A 44-year-old woman presented with a palpable lump in the inferomedial area of the right chest wall. Six years ago, she had undergone total mastectomy for ductal carcinoma in situ in her right breast. Sonography showed an indistinct, oval, heterogeneous echoic mass measuring 0.9 cm, confined within the skin layer, corresponding to the palpable lump. A color Doppler sonogram showed minimal, spotted vascularity in and around the mass. Sonography-guided fine-needle aspiration biopsy was performed, revealing multiple clusters of atypical cells, suggestive of ductal carcinoma. On subsequent breast MRI, the mass, measuring 1.3 cm, was again localized to the skin; dynamic contrast-enhanced scans showed a circumscribed margin, oval shape, and rim enhancement (morphology) and slow initial enhancement and persistent delayed enhancement (kinetics). The mass was surgically excised and the pathological examination confirmed the diagnosis as recurrent invasive ductal carcinoma in the dermis. CONCLUSIONS Cutaneous recurrence in the mastectomy bed can manifest as a mass with suspicious radiologic features: indistinct margin on the sonogram and rim enhancement on the MRI. Awareness of such radiologic features may aid in differentiating between the various cutaneous manifestations encountered after mastectomy.

RevDate: 2019-06-06

Yamashita H, Kurita A, Azuma S, et al (2019)

Usefulness of immunohistochemical staining for MUC5AC in differentiating primary pancreatic cancer from pancreatic metastasis of breast cancer.

Diagnostic cytopathology [Epub ahead of print].

Diagnosis of pancreatic ductal adenocarcinoma (PDAC) and its differentiation from metastases to the pancreas from other organs remains challenging. We report a case in which immunohistochemical staining for MUC5AC was useful in distinguishing primary pancreatic cancer from breast cancer metastasis. A 51-year-old Japanese woman who underwent curative resection of her breast cancer was referred to our hospital with a pancreatic head tumor. Although we surmised her pancreatic tumor to be metastatic breast cancer based on her past history and imaging studies, she was subsequently diagnosed with PDAC on the basis of immunohistochemical staining for MUC5AC using specimens obtained by endoscopic ultrasound-fine-needle aspiration. Thus, MUC5AC may be a useful diagnostic marker for discriminating PDAC from a secondary malignancy.

RevDate: 2019-06-05

Suzuki Y, Sakurai K, Adachi K, et al (2019)

[Usefulness of Automated Breast Ultrasound for Deciding on a Surgical Approach in a Patient with Breast Cancer- A Case Report].

Gan to kagaku ryoho. Cancer & chemotherapy, 46(4):778-780.

Since breast reconstruction has been covered by health insurance, we can choose a procedure that combines the cosmetic satisfaction of patients with curability. We report about a patient with breast cancer that who underwent nipple-sparing mastectomy after evaluating the intraductal spread by automated breast ultrasound system(ABUS), while hand held ultrasound(HHUS)showed only limited information on the intraductal spread of the lesion. A 52-year old woman with an abnormal screening finding was referred to our hospital. HHUS showed an irregular and poorly defined hypoechoic mass lesion with a lactiferous duct extending to directly under the nipple. A core needle biopsy revealed invasive ductal carcinoma. We performed ABUS to assess the intraductal spread in the lesion because the patient requested breast reconstruction. The coronal section of the breast in the ABUS did not showintraductal spread. We, therefore, decided to perform a nipple-sparing mastectomy and sentinel lymph node biopsy. Intraoperative evaluation by frozen and permanent sections showed negative margins. The ABUS findings helped in the evaluation of the intraductal spread of the lesion and in the choice of the optimal procedure for the patient.

RevDate: 2019-06-05

Yamamoto K, Hayashi K, Waraya M, et al (2019)

[A Patient with Breast Cancer Who Achieved Continued Clinical Complete Response after Systemic Therapy Alone].

Gan to kagaku ryoho. Cancer & chemotherapy, 46(4):757-759.

A 53-year-old woman presented at our hospital because of a mass in the left breast. A mass measuring 2 cm in diameter was palpated in the upper outer region(C region)of the left breast. Mammography showed a mass with calcification. Mammary ultrasonography showed a mass measuring 18×16×14mm and enlarged lymph nodes in the left axillary region. Core needle biopsy revealed Luminal B invasive ductal carcinoma(scirrhous type). The estrogen receptor(ER)positivity was 95%, progesterone receptor(PgR)positivity was 60%, human epidermal growth factor receptor type 2(HER2)score was 2+, fluorescence in situ hybridization(FISH)showed no amplification, and Ki-67 index was 60%. Clinical T1N1M0, StageⅡA cancer was thus diagnosed. As preoperative chemotherapy, the patient received 4 courses of treatment containing epirubicin (100mg/m2), 5-fluorouracil(500mg/m2), and cyclophosphamide(500mg/m2; FEC100), and 4 courses of treatment containing docetaxel and cyclophosphamide(TC). Clinical complete response(cCR)was confirmed on imaging studies. The patient was explained about the need for surgery, but she refused to undergo surgery. The patient is being followed up while receiving endocrine therapy, and there has been no recurrence or metastasis as of 2 years. We described our encounter with a patient with breast cancer who refused surgery after preoperative chemotherapy and has had no recurrence or metastasis during follow-up.

RevDate: 2019-06-10

Khan RN, Parvaiz MA, Khan AI, et al (2019)

Invasive carcinoma in accessory axillary breast tissue: A case report.

International journal of surgery case reports, 59:152-155 pii:S2210-2612(19)30284-6 [Epub ahead of print].

INTRODUCTION: Accessory or ectopic breast tissue is an aberration of normal breast development. It is known to be a rare entity present anywhere along the embryologic mammary streak or milk line but more common in axilla.

PRESENTATION OF CASE: We report a case of 36 year old female with accessory breast carcinoma who presented with a progressive lump in her left axilla for 1 year. On examination a 2 cm solitary mass was palpable in axilla. Ultrasound confirmed a 19 mm mass with no other lesion in breast and axilla. Core biopsy showed invasive ductal carcinoma. She was discussed in multidisciplinary board meeting and was offered upfront surgery with excision of accessory breast tissue and sentinel lymph node biopsy. Axillary lymph node dissection was omitted following ACOSG Z0011 criteria. She was offered adjuvant chemotherapy and radiation post operatively along with endocrine treatment as she was hormone receptor positive.

DISCUSSION: Accessory breast development is hormone dependent just like normal breast. Breast cancer in accessory breast tissue is very rare. The incidence is around 6%. Most common pathology is invasive ductal carcinoma (50-75%). The most common location is axilla (60-70%) although it can present in other less common locations like infra-mammary region (5-10%) and rarely in thighs, perineum, groin, and vulva.

CONCLUSION: Since accessory axillary breast tissue is out of the image of screening breast examination, it is necessary for the oncologists to be aware of this entity and associated pathologies. Their preventive excision in high risk women can also be considered.

RevDate: 2019-06-02

Zhu B, RT Farouki (2019)

A general framework for solving inverse dynamics problems in multi-axis motion control.

ISA transactions pii:S0019-0578(19)30234-4 [Epub ahead of print].

An inverse dynamics compensation (IDC) scheme for the execution of curvilinear paths by multi-axis motion controllers is proposed. For a path specified by a parametric curve r(ξ), the IDC scheme computes a real-time path correction Δr(ξ) that (theoretically) eliminates path deviations incurred by the inertia and damping of the machine axes. To exploit the linear time-invariant nature of the dynamic equations, the correction term is computed as a function of elapsed time t, and the corresponding curve parameter values ξ are only determined as the final step of the IDC scheme, through a real-time interpolator algorithm. It is shown that, in general, the correction term for P, PI, and PID controllers consists of derivative, natural, and integral terms (the integrand of the latter involving only the path r(ξ), and not its derivatives). The use of lead segments to minimize transient effects associated with the initial conditions is also discussed, and the performance of the method is illustrated by simulation results. The IDC scheme is expressed in terms of a linear differential operator formalism to provide a clear, general, and systematic development, amenable to further adaptations and extensions.

RevDate: 2019-05-30

Zhu J, Sun K, Xu X, et al (2019)

A preliminary attempt of non-intervention in the treatment of patients with intervertebral disc calcification combined with ossification of the posterior longitudinal ligament.

World neurosurgery pii:S1878-8750(19)31446-9 [Epub ahead of print].

BACKGROUND: Calcification of intervertebral disc is a common impairment, which has been considered as the degenerative condition of the spine. In clinical practice, we note that the onset of intervertebral disc calcification (IDC) and ossification of the posterior longitudinal ligament (OPLL) can exist simultaneously in some cases, especially in younger children. However, only 8 cases have been reported in detail previously. In addition, contrary remains in terms of the best way to treat this condition.

CASE DESCRIPTION: An eight-year-old female child was referred to our department in March 2018 complaining of severe back pain and neck pain with a sign of neurological dysfunction. CT and MRI revealed the calcified intervertebral disc and OPLL at C5/6 level and the spinal cord compression. We performed a non-intervention strategy for the patient. The patient's symptom recovered significantly in approximately 1 month. At 6 months of follow-up, the patient felt no discomfort, and CT revealed the complete resorption of ossified lesion. MRI also showed no sign of compression on the spinal cord and nerve root at the involved segment.

CONCLUSIONS: Pediatric IDC accompanied with OPLL is much less frequent, but we must be aware of this disease. Since the distribution of this disease is age-specific and gender-specific, further research is necessary. Ladder therapy, as described in the text, may be an acceptable treatment for IDC combined with OPLL.

RevDate: 2019-06-10

Piasecka D, Braun M, Kitowska K, et al (2019)

FGFs/FGFRs-dependent signalling in regulation of steroid hormone receptors - implications for therapy of luminal breast cancer.

Journal of experimental & clinical cancer research : CR, 38(1):230 pii:10.1186/s13046-019-1236-6.

Stromal stimuli mediated by growth factor receptors, leading to ligand-independent activation of steroid hormone receptors, have long been implicated in development of breast cancer resistance to endocrine therapy. Mutations in fibroblast growth factor receptor (FGFR) genes have been associated with a higher incidence and progression of breast cancer. Increasing evidence suggests that FGFR-mediated interaction between luminal invasive ductal breast carcinoma (IDC) and its microenvironment contributes to the progression to hormone-independence. Therapeutic strategies based on FGFR inhibitors hold promise for overcoming resistance to the ER-targeting treatment. A series of excellent reviews discuss a potential role of FGFR in development of IDC. Here, we provide a concise updated summary of existing literature on FGFR-mediated signalling with an emphasis on an interaction between FGFR and estrogen/progesterone receptors (ER/PR) in IDC. Focusing on the regulatory role of tumour microenvironment in the activity of steroid hormone receptors, we compile the available functional data on FGFRs-mediated signalling, as a fundamental mechanism of luminal IDC progression and failure of anti-ER treatment. We also highlight the translational value of the presented findings and summarize ongoing oncologic clinical trials investigating FGFRs inhibition in interventional studies in breast cancer.

RevDate: 2019-05-30

Zhao JG, Nie L, Chen XQ, et al (2019)

[The subgroup analysis of the prognostic value of the intraductal carcinoma of the prostate in patients with metastatic prostate cancer].

Zhonghua wai ke za zhi [Chinese journal of surgery], 57(6):422-427.

Objective: To determine the prognostic value of the intraductal carcinoma of the prostate IDC-P in metastatic prostate cancer (mPCa) patients of different subgroups. Methods: Data of 582 de novo mPCa patients between January 2011 and December 2017 diagnosed at Departments of Urology, West China Hospital, Sichuan University were retrospectively analyzed. The age was (70±8) years (range: 45 to 89 years). IDC-P was identified from 12-core prostate biopsy. The prognostic role of IDC-P was assessed by Kaplan-Meier curves and Cox regression. Subgroup analysis was conducted by the forest plot. The endpoints were castration-resistant prostate cancer free survival (CFS) and overall survival (OS). Results: In total, 177/582 (30.4%) patients harbored IDC-P. Patients with IDC-P had poorer CFS and OS than those without IDC-P (mCFS: 12.1 months vs. 16.9 months, P=0.000; mOS: 39.7 months vs. not reached, P=0.000). Multivariate Cox regression analysis indicated that, the existence of IDC-P was an independent prognosticator of both CFS (HR=1.40, 95% CI: 1.10 to 1.79, P=0.006) and OS (HR=1.51, 95% CI: 1.02 to 2.25, P=0.041). Subanalysis indicated that, in most subgroups, IDC-P was an adverse prognosticator of both CFS and OS. Even in subgroups with adverse clinicopathological features, e.g. Gleason score 9 to 10 (CFS: HR=1.467, P=0.007; OS: HR=1.807, P=0.013), baseline prostate specific antigen≥50 μg/L (CFS: HR=1.616, P=0.000; OS: HR=1.749, P=0.006), anemia (CFS: HR=1.653, P=0.036; OS: HR=2.100, P=0.038), alkaline phosphatase≥160 U/L (CFS: HR=1.326, P=0.038; OS: HR=1.725, P=0.010) or abnormal lactate dehydrogenase level (CFS: HR=1.614, P=0.001; OS: HR=1.900, P=0.003), IDC-P was still closely associated with shorter CFS and OS. Conclusions: The presence of IDC-P was closely related to poor survival outcomes for patients with mPCa. IDC-P was an adverse prognosticator in most subgroup patients. The description of IDC-P in the pathological report of prostate biopsy would help clinicians to evaluate the prognosis of mPCa patients more accurately and make better treatment choices.

RevDate: 2019-05-28

Chen S, Chen H, Yi Y, et al (2019)

Comparative study of breast cancer with or without concomitant Paget disease: An analysis of the SEER database.

Cancer medicine [Epub ahead of print].

BACKGROUND: Most mammary Paget disease (MPD) is associated with underlying in situ or invasive breast cancer. The objective of this study was to compare the clinicopathological characteristics and survival outcomes between breast cancer with Paget disease (PD) and breast cancer alone.

METHODS: From the Surveillance, Epidemiology, and End Results (SEER) database, 2000-2015, of the US National Cancer Institute, we identified 1569 women who had PD with invasive ductal carcinoma (PD-IDC) and 1489 women who had PD with ductal carcinoma in situ (PD-DCIS). Independent demographic and clinicopathological variables as well as survival outcomes of these patients were compared to patients with the corresponding breast cancer without concomitant PD.

RESULTS: PD-IDC and PD-DCIS both had worse survival outcomes and poorer tumor characteristics than the corresponding disease without PD. Contrary to in the breast cancer alone groups, in the breast cancer with PD groups, the HR status (P = 0.182 in PD-IDC and P = 0.371 in PD-DCIS), HER2 status (P = 0.788 in PD-IDC and P = 0.643 in PD-DCIS), and combined molecular subtype (P = 0.196 in PD-IDC and P = 0.853 in PD-DCIS) were not found to affect disease prognosis. After matching tumor characteristics and treatment approaches, PD-IDC as well as PD-DCIS exhibited no significant difference in disease prognosis with corresponding IDC and DCIS. Finally, by comparative analysis, a kind of PD-DCIS (ICD-O-3 code 8543/3) showed many invasive behaviors (31.8% of 8543/3 patients had stage I-III cancer) and was associated with worse survival outcomes than the other type of PD-DCIS.

CONCLUSIONS: Breast cancer with concomitant PD was associated with more aggressive tumor characteristics and worse survival outcomes. The HR status, HER2 status, and combined molecular subtype could not affect the prognosis of breast cancer with PD. Moreover, a portion of the PD-DCIS cases were invasive breast cancer cases that required special treatment.

RevDate: 2019-06-01

Yokoi T, Morimoto R, Oishi H, et al (2019)

Left Ventricular Relaxation Half-Time as a Predictor of Cardiac Events in Idiopathic Dilated Cardiomyopathy and Hypertrophic Cardiomyopathy With Left Ventricular Systolic and/or Diastolic Dysfunction.

The American journal of cardiology pii:S0002-9149(19)30505-3 [Epub ahead of print].

PURPOSE: Diastolic dysfunction preceding systolic dysfunction is considered an important interaction in cardiomyopathy with poor prognosis. The aim of this study was to compare left ventricular (LV) isovolumic relaxation with the other parameters as a potential prognostic marker for patients with idiopathic dilated cardiomyopathy (IDC) and hypertrophic cardiomyopathy (HC).

METHODS: A total of 145 patients with IDC and 116 with HC were evaluated for hemodynamic parameters; LV pressure was directly measured by a micromanometer catheter, and relaxation half-time (T1/2) was used to determine LV isovolumic relaxation. The median follow-up period was 4.7 years.

RESULTS: The mean ages of the patients with IDC and HC were 52.0 ± 12.0 and 57.1 ± 12.4 years, respectively. Each patient group was further divided into 2 groups based on the median value of T1/2: (1) <41.0 ms (D-L group) and ≥41.0 ms (D-H group) (2) <38.5 ms (H-L group) and ≥38.5 ms (H-H group). Kaplan-Meier analysis showed a significantly higher probability of cardiac events in the D-H group than in the D-L group (p = 0.001) and in the H-H group than in the H-L group (p = 0.028). Further, Cox proportional hazard regression analysis revealed that T1/2 was an independent predictor of cardiac events for patients with IDC (hazard ratio 1.109; p = 0.007) and HC (hazard ratio 1.062; p = 0.041). In conclusion, regardless of the type of cardiomyopathy, T1/2 as a measure of LV isovolumic relaxation function was found to be associated with the occurrence of cardiac events.

RevDate: 2019-05-27

Li JP, Zhang XM, Zhang YS, et al (2019)

The prognostic value of the 8th edition of the American Joint Committee on Cancer (AJCC) staging system in triple-negative breast cancer.

Neoplasma pii:190107N26 [Epub ahead of print].

The American Joint Committee on Cancer (AJCC) released its 8th edition of cancer staging which is to be implemented in early 2018. This study aims to compare anatomic staging (AS) with prognostic staging (PS) based on the updated AJCC 8th edition staging manual. A retrospective single-center analysis of 313 triple-negative breast invasive ductal carcinoma patients who received surgery at department of breast surgery in the Fourth Hospital of Hebei Medical University from 2010-01 to 2012-12 was performed. All cases were restaged using the AJCC 8th edition AS and PS system. The 7-year DFS and the 7-year OS rates were 76.30% and 78.27%, respectively. Applying the PS system, 277 (88.5%) patients of the AS groups were up-staged to the PS groups, 31 cases with IIIC and 5 cases with IV unchanged (11.5%), and no cases down-staged. Both 7-year DFS and 7-year OS were significantly different in the different AS and PS groups (all, P<0.001). The PS system was found to provide better prognostic information in patients with AS group IIB. A total of 43 patients with AS group IIB were up-staged by PS system, in which 30 patients were +2 up-staged to PS IIIB, and 13 patients were +3 up-staged to PS IIIC. PS IIIB and IIIC from AS IIB had significant differences in 7‑year DFS (χ2 = 5.628, P = 0.014) and 7‑year OS (χ2 = 6.037, P = 0.018). Both AS and PS systems proposed in the 8th edition of the AJCC breast cancer staging manual had prognostic value in TNBC. Moreover, the PS system predicts clinical outcomes of TNBC patients more accurately than the traditional AS system.

RevDate: 2019-05-24

Tao WJ, Zhang HX, Zhang LM, et al (2019)

Combined application of pharamcokinetic DCE-MRI and IVIM-DWI could improve detection efficiency in early diagnosis of ductal carcinoma in situ.

Journal of applied clinical medical physics [Epub ahead of print].

PURPOSE: Ductal carcinoma in situ (DCIS) is a precursor of invasive ductal breast carcinoma (IDC). This study aimed to use pharamcokinetic dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) for the early diagnosis of DCIS.

METHODS: Forty-seven patients, including 25 with DCIS (age: 28-70 yr, mean age: 48.7 yr) and 22 with benign disease (age: 25-67 yr, mean age: 43.1 yr) confirmed by pathology, underwent pharamcokinetic DCE-MRI and IVIM-DWI in this study. The quantitative parameters Ktrans , Kep , Ve , Vp , and D, f, D* were obtained by processing of DCE-MRI and IVIM-DWI images with Omni-Kinetics and MITK-Diffusion softwares, respectively. Parameters were analyzed statistically using GraphPad Prism and MedCalc softwares.

RESULTS: All low-grade DCIS lesions demonstrated mass enhancement with clear boundaries, while most middle-grade and high-grade DCIS lesions showed non-mass-like enhancement (NMLE). DCIS lesions were significantly different from benign lesions in terms of Ktrans , Kep , and D (t = 5.959, P < 0.0001; t = 5.679, P < 0.0001; and t = 5.629, P < 0.0001, respectively). The AUC of Ktrans , Kep , D and the combined indicator of Ktrans , Kep, and D were 0.936, 0.902, 0.860, and 0.976, respectively. There was a significant difference in diagnostic efficacy only between D and the combined indicator (Z = 2.408, P = 0.016).

CONCLUSION: DCE-MRI and IVIM-DWI could make for the early diagnosis of DCIS, and reduce the misdiagnosis of DCIS and over-treatment of benign lesions.

RevDate: 2019-05-23

Henry NL, LA Cannon-Albright (2019)

Breast cancer histologic subtypes show excess familial clustering.

Cancer [Epub ahead of print].

BACKGROUND: The inherited predisposition to developing specific histologic subtypes of invasive breast carcinoma has been incompletely investigated. By using a large, population-based database, the authors sought to investigate familial clustering of breast cancer by histologic subtype.

METHODS: By using the Utah Population Database, which links genealogy records to the National Cancer Institute's statewide Surveillance, Epidemiology, and End Results cancer registry, the authors identified patients with breast cancer by histology and tested for evidence of shared genetic predisposition to histologic specific subtypes by examining pairwise relatedness and estimating the relative risk (RR) among first-degree, second-degree, and third-degree relatives.

RESULTS: The authors identified 23,629 individuals in the Utah Population Database who had at least 3 generations of genealogy and at least 1 primary breast cancer, 2883 (12.2%) of which were specific histologic subtypes other than invasive ductal carcinoma (including inflammatory [n = 178], lobular [n = 1688], and mucinous [n = 542]). Statistically significant excess distant relatedness was identified for the mucinous subtype (P = .011) as well as for inflammatory breast cancers (P = .024). The RR for breast cancer of any histology in second-degree relatives was significantly increased for patients with inflammatory (RR, 1.32; 95% CI, 1.02-1.68; P = .03), lobular (RR, 1.36; 95% CI, 1.25-1.47; P < .001), and mucinous (RR, 1.27; 95% CI, 1.12-1.44; P = .00021) subtypes.

CONCLUSIONS: These findings provide evidence for significant familial clustering within histological subtypes for lobular, mucinous, and inflammatory breast carcinomas. Further research is required to identify the underlying genetic variants responsible for the increased risk. Studies of high-risk pedigrees segregating a specific histologic subtype could be a powerful design for predisposition gene identification.

RevDate: 2019-06-10

Li L, Wu N, Li F, et al (2019)

Clinicopathologic and molecular characteristics of 44 patients with pure secretory breast carcinoma.

Cancer biology & medicine, 16(1):139-146.

Objective: Secretory breast carcinoma (SBC) is a rare type of breast malignancy, accounting for less than 0.02% of all infiltrating breast malignancies. The pure SBC, a type of SBC without another type of breast malignant neoplasm, is particularly rare. This study aimed to investigate the clinicopathologic and molecular features of pure SBC.

Methods: The main pathological parameters such as estrogen receptor (ER), progesterone receptor (PR), and human epithelial growth factor receptor 2 (C-erbB-2) were detected by immunohistochemistry (IHC), and the clinicopathologic and prognostic difference were compared with invasive ductal carcinoma (IDC). Fluorescent in situ hybridization (FISH) and reverse transcription polymerase chain reaction (RT-PCR) was performed to identify the ETV6-NTRK3 rearrangement of SBC.

Results: We found that the positivity rates of ER, PR, C-erbB-2, p53, and S-100 were 47.7% (21/44), 52.3% (23/44), 36.4% (16/44), 27.3% (12/44), and 95.5% (42/44), respectively, which were higher than those reported in previous studies. Special periodic acid-Schiff analysis was performed in 36 patients, and the value of the Ki-67 index ranged from 1% to 50% (mean value: 10%). Interestingly, most patients with pure SBC harbored an ETV6-NTRK3 rearrangement with an 88.6% (39/44) expression rate. Compared with IDC, the tumor size of most patients with SBC was larger than 2 cm (P = 0.024). Ultrasound showed benign lesions, and the total misdiagnosis rate was higher (P = 0.020). Although the pathological classification was mostly triple-negative breast cancers (P = 0.036), there was less metastasis (P = 0.029), and the overall prognosis was better than that of the IDC group.

Conclusions: Although axillary lymph node metastasis, local recurrence, or distant metastasis may occur, SBC is also considered an indolent neoplasm with a good prognosis. Once diagnosed, surgical treatment should be performed as soon as possible, followed by appropriate adjuvant chemotherapy, irradiation, and endocrine therapies.

RevDate: 2019-05-21

Kosik I, Brackstone M, Kornecki A, et al (2019)

Intraoperative photoacoustic screening of breast cancer: a new perspective on malignancy visualization and surgical guidance.

Journal of biomedical optics, 24(5):1-12.

High re-excision rates in breast-conserving surgery call for a new intraoperative approach to the lumpectomy margin evaluation problem. The unique intraoperative imaging system, presented here, demonstrated the capability of photoacoustic tomography (PAT) to deliver optical sensitivity and specificity, along with over 2-cm imaging depth, in a clinical setting. The system enabled the evaluation of tumor extent, shape, morphology, and position within lumpectomy specimens measuring up to 11 cm in diameter. The investigation included all major breast cancer-related lesions, such as invasive ductal carcinoma (IDC), multifocal IDC, ductal carcinoma in situ and combinations of these variants. Coregistration with established ultrasound (US) technology, as well as comparison to specimen radiography, validated the performance of PAT, which appeared to facilitate better tumor visualization. Contrary to expected PA contrast mechanisms, PAT images of hemoglobin distribution correlated poorly with US-determined tumor location, while hypointense regions in lipid-weighted PAT images were in better agreement with US.

RevDate: 2019-05-21

Shah RB, Shore KT, Yoon J, et al (2019)

PTEN loss in prostatic adenocarcinoma correlates with specific adverse histologic features (intraductal carcinoma, cribriform Gleason pattern 4 and stromogenic carcinoma).

The Prostate [Epub ahead of print].

BACKGROUND: The loss of PTEN tumor suppressor gene is one of the most common somatic genetic aberrations in prostate cancer (PCa) and is frequently associated with high-risk disease. Deletion or mutation of at least one PTEN allele has been reported to occur in 20% to 40% of localized PCa and up to 60% of metastases. The goal of this study was to determine if somatic alteration detected by PTEN immunohistochemical loss of expression is associated with specific histologic features.

METHODS: Two hundred sixty prostate core needle biopsies with PCa were assessed for PTEN loss using an analytically validated immunohistochemical assay. Blinded to PTEN status, each tumor was assessed for the Grade Group (GG) and the presence or absence of nine epithelial features. Presence of stromogenic PCa was also assessed and defined as grade 3 reactive tumor stroma as previously described: the presence of carcinoma associated stromal response with epithelial to stroma ratio of greater than 50% reactive stroma.

RESULTS: Eight-eight (34%) cases exhibited PTEN loss while 172 (66%) had intact PTEN. PTEN loss was significantly (P < 0.05) associated with increasing GG, poorly formed glands (74% of total cases with loss vs 49% of intact), and three well-validated unfavorable pathological features: intraductal carcinoma of the prostate (IDC-P) (69% of total cases with loss vs 12% of intact), cribriform Gleason pattern 4 (38% of total cases with loss vs 10% of intact) and stromogenic PCa (23% of total cases with loss vs 6% of intact). IDC-P had the highest relative risk (4.993, 95% confidence interval, 3.451-7.223, P < 0.001) for PTEN loss. At least one of these three unfavorable pathological features were present in 67% of PCa exhibiting PTEN loss, while only 11% of PCa exhibited PTEN loss when none of these three unfavorable pathological features were present.

CONCLUSIONS: PCa with PTEN loss demonstrates a strong correlation with known unfavorable histologic features, particularly IDC-P. This is the first study showing the association of PTEN loss with stromogenic PCa.

RevDate: 2019-06-10

Tan W, Tao L, Zhou Z, et al (2019)

Tumor-to-tumor metastasis: a rare case of breast carcinoma metastasizing to a pheochromocytoma, and a literature review.

Diagnostic pathology, 14(1):46 pii:10.1186/s13000-019-0816-2.

BACKGROUND: Tumor-to-tumor metastasis is a well-recognized but uncommon entity. Breast carcinoma is one of the most common metastatic donors. Breast carcinoma metastasizes commonly to adrenal glands. However, the co-existence of a metastatic lesion with an existing adrenal tumor is a rare finding.

CASE PRESENTATION: A 35-year-old woman was diagnosed with pheochromocytoma using computed tomography and ultrasound examinations. The tumor was surgically removed. Histological and immunohistochemical staining suggested that there were two components in the tumor: pheochromocytoma and metastatic cancer.

CONCLUSION: This is the second published case of pheochromocytoma with tumor-to-tumor metastasis from an invasive ductal carcinoma of the breast. Furthermore, we highlight the importance of awareness of tumor-to-tumor metastasis in pathological diagnosis.

RevDate: 2019-05-20

Nasir A, Lehrke HD, Mounajjed T, et al (2019)

Albumin In Situ Hybridization Can Be Positive in Adenocarcinomas and Other Tumors From Diverse Sites.

American journal of clinical pathology pii:5492096 [Epub ahead of print].

OBJECTIVES: Albumin messenger RNA (mRNA) expression is a marker of hepatocellular differentiation. Most published data are from review of tissue microarrays, and albumin in situ hybridization (ISH) expression across several tumor types is incompletely characterized.

METHODS: Sections from 221 tumors were evaluated for albumin mRNA. Immunohistochemistry was used to confirm diagnoses. Albumin ISH was performed according to manufacturer-provided instructions. Fifty-nine cases were evaluated with both commercial ISH assays.

RESULTS: Albumin mRNA was detected in all hepatocellular carcinomas (HCCs) and 81% of intrahepatic cholangiocarcinomas. Lung (20%), gallbladder (39%), hepatoid pancreatic (n = 1 of 1) adenocarcinoma, breast invasive ductal carcinoma (18%), yolk sac tumor (25%), and acinar cell carcinoma (29%) showed expression. Both assays were concordant in 93% of cases.

CONCLUSIONS: Albumin ISH was expressed in all HCCs studied. It was also positive in intrahepatic cholangiocarcinoma and patchy positive in gallbladder adenocarcinoma and a subset of other neoplasms, which can be a potential pitfall.

RevDate: 2019-05-20

Yokoyama T, Makino H, Hirakata A, et al (2019)

Metastatic pancreatic mucinous carcinoma responding to systemic chemotherapy with modified FOLFIRINOX and undergoing conversion surgery: A case report.

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

We report a case of metastatic pancreatic-head mucinous carcinoma (with multiple lymph node and bone metastases), as well as a literature review. Endoscopic ultrasound - fine needle aspiration (EUS-FNA) was useful for diagnosis in this patient, and a satisfactory outcome was achieved using systemic chemotherapy with FOLFIRINOX followed by resection of the primary lesion as conversion surgery. The patient was a 55-year-old man. Hematological findings included elevated serum tumor marker levels: CEA at 12.7 ng/ml and DUPAN-2 at 400 U/ml. With several modalities and EUS - FNA, the patient received a clinicopathological diagnosis of metastatic pancreatic mucinous carcinoma with multiple bone and lymph node metastases. For systemic chemotherapy, five courses of modified FOIFIRINOX (m-FFX) were given, and an antitumor effect was obtained; therefore, subtotal stomach-preserving pancreaticoduodenectomy and extensive lymph-node dissection were performed. Histopathologically, the results were invasive ductal carcinoma, muc (pT3, pN1b, cM1). After surgery, the clinical course was notable for the absence of complications. Tegafur/gimeracil/oteracil (S-1) was started as maintenance adjuvant chemotherapy postoperatively. And, the patient is still ongoing progression-free survival 10 months after the surgery.

RevDate: 2019-05-20

Kanat-Maymon Y, BM Ben-David (2019)

Small numbers are not predictive: Congenital blindness may or may not be protective for schizophrenia.

Schizophrenia research pii:S0920-9964(19)30156-2 [Epub ahead of print].

RevDate: 2019-05-20

Park SY, Kim HJ, Kim WH, et al (2019)

Feasibility of ultrasound-guided absorbable retaining thread needle localization for nonpalpable breast lesions.

Ultrasonography (Seoul, Korea) pii:usg.18059 [Epub ahead of print].

Purpose: Absorbable retaining thread (ART) needle localization utilizes a guiding needle with a thread; this technique was invented to reduce patient discomfort and wire migration. We investigated the feasibility of ultrasound (US)-guided ART needle localization for nonpalpable breast lesions.

Methods: ART needle localization was performed for 26 nonpalpable breast lesions in 26 patients who were scheduled to undergo surgical excision the day after localization. Seventeen breast lesions were initially diagnosed as invasive ductal carcinoma, six as ductal carcinomas in situ, and one as fibrocystic change. The other two cases without an initial pathologic diagnosis had suspicious US features, and excision was planned concomitantly with contralateral breast cancer surgery. The primary outcome was the technical success rate of ART needle localization confirmed by US immediately after the procedure, and the secondary outcomes were the percentage of clear margins on pathology and the complication rate of ART needle localization.

Results: The technical success rate of ART needle localization was 96.2% (25 of 26 patients), and the ART was located 1 cm away from the mass in one patient (3.8%). The lesions were successfully removed with clear margins in all 26 patients. No significant complications related to ART needle localization were observed.

Conclusion: ART needle localization can be an alternative to wire needle localization for nonpalpable breast lesions.

RevDate: 2019-05-18

Tonttila PP, Ahtikoski A, Kuisma M, et al (2019)

Multiparametric magnetic resonance imaging prior to radical prostatectomy identifies intraductal and cribriform growth pattern of prostate cancer.

BJU international [Epub ahead of print].

OBJECTIVES: To evaluate the diagnostic value of multiparametric prostate magnetic resonance imaging (MP-MRI) prior to radical prostatectomy with curative intent for detection of cribriform architecture (CA) and intraductal prostate cancer (IDC), which have recently been demonstrated to be adverse pathologic factors.

PATIENTS AND METHODS: This study included 124 men who underwent MP-MRI prior to radical prostatectomy at our centre. Preoperative MP-MRI, prostatectomy histology, and clinical follow-up details were reviewed retrospectively. The diagnostic value of MP-MRI was evaluated on the basis of the detection rate. Secondly, the prognostic significance of CA/IDC among grade group 2 cancers with regard to biochemical recurrence-free survival was assessed using Kaplan-Meier analysis with the log rank test and Fisher's exact test.

RESULTS: Pathologic examination of radical prostatectomy specimens identified CA/IDC in 89 (71%) of 124 cases and MP-MRI identified 86/95 of tumours including any CA/IDC with a sensitivity of 90.5% (95% confidence interval 82.8%-95.6%). When localization of the lesions was compared, there was an association between the highest Prostate Imaging-Reporting and Data System (PI-RADS) classification and the highest pathologic grade in 106 (85.5%) of the 124 cases. In patients with grade group 2 lesions, biochemical recurrence occurred in 11 of 31 (35.5%) with CA/IDC and 2 of 21 (9.5%) without CA/IDC (p=0.034).

CONCLUSION: MP-MRI has good sensitivity for detection of pathologic primary prostate cancer, including most cases with CA/IDC. However, reliable prediction of grade group 2 tumours with CA/IDC for individual risk stratification remains challenging. This article is protected by copyright. All rights reserved.

RevDate: 2019-05-17

Montironi R, Zhou M, Magi-Galluzzi C, et al (2018)

Features and Prognostic Significance of Intraductal Carcinoma of the Prostate.

European urology oncology, 1(1):21-28.

CONTEXT: Intraductal carcinoma of the prostate (IDC-P) is an intraglandular/ductal neoplastic growth of glandular epithelial cells characterized by marked abnormality of the glandular architecture and/or cytological atypia that exceeds what is typically seen in high-grade prostatic intraepithelial neoplasia (HPGIN). It has been shown that IDC-P is a strong independent indicator of poor prognosis for prostate carcinoma (PCa).

OBJECTIVE: To review the pathological and genetic features, diagnostic criteria and differential diagnosis, and clinical significance of IDC-P.

EVIDENCE ACQUISITION: PubMed was searched using keywords including prostate carcinoma, intraductal carcinoma, IDC, histology, diagnostic criteria, and prognosis. The references in relevant articles were also reviewed.

EVIDENCE SYNTHESIS: IDC-P is a distinct entity with characteristic morphological and genetic features. It is strongly associated with aggressive PCa with high Gleason score/grade groups and large tumor volume, and portends unfavorable clinical outcomes. Morphological diagnostic criteria have been established to distinguish it from other lesions with similar histological features. IDC-P is an uncommon finding in prostate biopsies, and is even rarer as an isolated finding without concomitant PCa. However, patients with isolated IDC-P in biopsy specimens are recommended to have either definitive treatment or immediate repeat biopsy.

CONCLUSIONS: It is critical to recognize and report IDC-P, especially in prostate biopsies, where the clinical impact of such a diagnosis is greatest.

PATIENT SUMMARY: Intraductal carcinoma is a unique form of aggressive prostate cancer. In this report, we review its pathological and genetic features and poor prognostic significance. It is critical for pathologists to recognize and report this lesion in prostate specimens, especially in prostate biopsies for patient management.

RevDate: 2019-05-23
CmpDate: 2019-05-23

Rusak A, Jablonska K, Piotrowska A, et al (2019)

Correlation of Expression of CHI3L1 and Nogo-A and their Role in Angiogenesis in Invasive Ductal Breast Carcinoma.

Anticancer research, 39(5):2341-2350.

BACKGROUND/AIM: Chitinase 3 like 1 (CHI3L1) is a secretion glycoprotein. Elevated levels of this protein are observed in cancer diseases. The biological role of CHI3L1 is not yet fully known, but the connection between CHI3L1 and angiogenesis has been shown. Recent reports also describe the association of Nogo isoforms and Nogo-B receptor (NgBR) with a proliferative potential, cancer cell invasiveness, and angiogenesis. The aim of this study was to evaluate the levels of CHI3L1, Nogo-A, Nogo-A/B, and NgBR and correlate them with clinical-pathological data, to study their role in angiogenesis in invasive ductal breast carcinoma (IDC).

MATERIALS AND METHODS: A total of 77 IDC cases were used in the study. Immunohistochemistry was used to determine the level of expression of CHI3L1, Nogo-A, Nogo-A/B, NgBR and vascular endothelial growth factors (VEGFA, VEGFC and VEGFD). The obtained results were subjected to statistical analysis including clinicalpathological data.

RESULTS: A statistically significant positive correlation of CHI3L1 and Nogo-A expression (r=0.474, p>0.0001) and a positive correlation of Nogo-A and VEGFC expression (r=0.280, p=0.013) were found.

CONCLUSION: CHI3L1 and Nogo-A are important in angiogenesis in IDC.

RevDate: 2019-06-06

Shachar T, D Greenbaum (2019)

When a Push Becomes a Shove: Nudging in Elderly Care.

The American journal of bioethics : AJOB, 19(5):78-80.

RevDate: 2019-05-15

Goh CW, Wu J, Ding S, et al (2019)

Invasive ductal carcinoma with coexisting ductal carcinoma in situ (IDC/DCIS) versus pure invasive ductal carcinoma (IDC): a comparison of clinicopathological characteristics, molecular subtypes, and clinical outcomes.

Journal of cancer research and clinical oncology pii:10.1007/s00432-019-02930-2 [Epub ahead of print].

PURPOSE: Ductal carcinoma in situ (DCIS) is widely recognized as the precursor of invasive ductal carcinoma (IDC). We aimed to analyze the clinicopathological characteristics and clinical outcomes of coexisting DCIS component in IDC and its clinical significance according to molecular subtypes.

METHODS: Data from 3001 patients with IDC (79.4%) and IDC/DCIS (20.6%) who underwent surgery from January 2009 to June 2016 were retrospectively assessed. The clinical outcomes of IDC with coexistent DCIS in different molecular subtypes were evaluated.

RESULTS: IDC/DCIS patients were more likely to be younger (P < 0.001), had low tumor grade (P = 0.001), had less lymph node involvement (P = 0.038) and received more mastectomy (P = 0.002) than IDC patients. In the comparison of molecular subtype prevalence, IDC/DCIS patients were more frequently presented with luminal B/HER2 positive (12.5% vs 11.0%, P < 0.001) and HER2 positive subtypes (20.9% vs 9.8%, P < 0.001). The 5-year disease-free survival (DFS, 90.9% vs 87.5%, P = 0.021) and 5-year overall survival (OS 96.1% vs 94.0%, P = 0.018) were significantly improved in IDC/DCIS patients compared to IDC patients. In multivariate analysis, the presence of coexisting DCIS (P = 0.048), tumor size (P < 0.001), lymph node status (P < 0.001), lymphovascular invasion (P = 0.007) and molecular subtypes (P < 0.001) were independent prognostic factors for DFS. Furthermore, coexistence of DCIS component in IDC significantly improved DFS in HER2 positive (94.8% vs 78.5%, P = 0.003), but had no association in luminal and triple negative subtypes.

CONCLUSIONS: IDC with coexisting DCIS was associated with improved prognosis. Patients with IDC/DCIS presented with more HER2 positive expression and might improve DFS in HER2 positive breast cancer.

RevDate: 2019-05-15

Li JP, Zhang XM, Zhang YS, et al (2019)

The prognostic value of the 8th edition of the American Joint Committee on Cancer (AJCC) staging system in triple-negative breast cancer.

Neoplasma, 2019: pii:190107N26.

The American Joint Committee on Cancer (AJCC) released its 8th edition of cancer staging which is to be implemented in early 2018. This study aims to compare anatomic staging (AS) with prognostic staging (PS) based on the updated AJCC 8th edition staging manual. A retrospective single-center analysis of 313 triple-negative breast invasive ductal carcinoma patients who received surgery at department of breast surgery in the Fourth Hospital of Hebei Medical University from 2010-01 to 2012-12 was performed. All cases were restaged using the AJCC 8th edition AS and PS system. The 7-year DFS and the 7-year OS rates were 76.30% and 78.27%, respectively. Applying the PS system, 277 (88.5%) patients of the AS groups were up-staged to the PS groups, 31 cases with IIIC and 5 cases with IV unchanged (11.5%), and no cases down-staged. Both 7-year DFS and 7-year OS were significantly different in the different AS and PS groups (all, P<0.001). The PS system was found to provide better prognostic information in patients with AS group IIB. A total of 43 patients with AS group IIB were up-staged by PS system, in which 30 patients were +2 up-staged to PS IIIB, and 13 patients were +3 up-staged to PS IIIC. PS IIIB and IIIC from AS IIB had significant differences in 7‑year DFS (χ2 = 5.628, P = 0.014) and 7‑year OS (χ2 = 6.037, P = 0.018). Both AS and PS systems proposed in the 8th edition of the AJCC breast cancer staging manual had prognostic value in TNBC. Moreover, the PS system predicts clinical outcomes of TNBC patients more accurately than the traditional AS system.

RevDate: 2019-05-15

Baydoun S, Gonzalez P, Whitman GJ, et al (2019)

Is Ductography Still Warranted in the 21st century?.

The breast journal [Epub ahead of print].

OBJECTIVE: To determine the utility of ductography in conjunction with mammography and ultrasound in patients with pathologic nipple discharge, and the incremental role of MRI after triple-modality evaluation.

MATERIALS AND METHODS: We retrospectively reviewed the medical records of patients who had presented with pathologic nipple discharge and had undergone mammography and/or ultrasound and ductography between January 1, 2005, and October 31, 2010. We tested the diagnostic sensitivity, specificity and accuracy of combined triple-modality evaluation as well as of MRI performed in addition to these imaging techniques. We used the gold standard of image-guided biopsies, surgical excision, or long-term clinical and imaging follow-up.

RESULTS: Among 94 study patients, benign papillomas were identified in 42 (44.7%), abscess in one (1%), duct ectasia in four (4.3%), and malignancy (invasive ductal carcinoma or ductal carcinoma in situ) or high-risk lesion (atypical ductal hyperplasia) in 10 (10.6%). Forty-six patients (49%) underwent surgical excision; 89.1% of which had presurgical planning with ductography. In 35 (37.2%) with negative imaging, resolution of nipple discharge was confirmed on median clinical and imaging follow-up of 36 months. Two patients with negative imaging were lost to follow-up. Sensitivity, specificity, PPV, and NPV for accurately demonstrating the etiology of pathologic nipple discharge were 13%, 97%, 89%, and 37% respectively for mammography; 73%, 97%, 98%, and 64% respectively for ultrasound; 76%, 72%, 84%, and 61% respectively for ductography; 86%, 70%, 85%, and 72% respectively for combined ultrasound and ductography; and 75%, 100%, 100% and 67% respectively for DCE-MRI.

CONCLUSION: The combination of mammography, ultrasound and ductography is highly accurate for identifying the etiology of pathologic nipple discharge. DCE-MRI can be used as an alternate to ductography if necessary.

RevDate: 2019-05-10

Schmöhl F, Peters V, Schmitt CP, et al (2019)

CNDP1 knockout in zebrafish alters the amino acid metabolism, restrains weight gain, but does not protect from diabetic complications.

Cellular and molecular life sciences : CMLS pii:10.1007/s00018-019-03127-z [Epub ahead of print].

The gene CNDP1 was associated with the development of diabetic nephropathy. Its enzyme carnosinase 1 (CN1) primarily hydrolyzes the histidine-containing dipeptide carnosine but other organ and metabolic functions are mainly unknown. In our study we generated CNDP1 knockout zebrafish, which showed strongly decreased CN1 activity and increased intracellular carnosine levels. Vasculature and kidneys of CNDP1-/- zebrafish were not affected, except for a transient glomerular alteration. Amino acid profiling showed a decrease of certain amino acids in CNDP1-/- zebrafish, suggesting a specific function for CN1 in the amino acid metabolisms. Indeed, we identified a CN1 activity for Ala-His and Ser-His. Under diabetic conditions increased carnosine levels in CNDP1-/- embryos could not protect from respective organ alterations. Although, weight gain through overfeeding was restrained by CNDP1 loss. Together, zebrafish exhibits CN1 functions, while CNDP1 knockout alters the amino acid metabolism, attenuates weight gain but cannot protect organs from diabetic complications.

RevDate: 2019-05-09

Zhao Z, Liu Q, Wu C, et al (2019)

[Expression of G9a in breast cancer and its effect on proliferation of breast cancer cells in vitro].

Nan fang yi ke da xue xue bao = Journal of Southern Medical University, 39(4):477-484.

OBJECTIVE: To study the expression of G9a in human breast cancer, its association with the clinicopathological characteristics of breast cancer, and its effect on the proliferation of breast cancer cells.

METHODS: A total of 122 specimens of breast cancer tissues and 61 adjacent normal tissues resected between October, 2016 and October, 2017 were obtained from the Tissue Bank of Ningxia Medical University General Hospital. Immunohistochemistry and real-time PCR were used to detect the expression of G9a in the breast cancer tissues. The relationship of G9a with the clinicopathological features of the patients, molecular subtypes of breast cancer and the immunohistochemical markers was analyzed. A bioinformatics approach was used to analyze the expression of G9a in breast tissues and its association with the prognosis of the patients with breast cancer. UNC0631, a G9a inhibitor, was used to investigate the effect of G9a on the proliferation of breast cancer cells in vitro.

RESULTS: The results of immunohistochemical study, real-time PCR and bioinformatics analysis showed that G9a was highly expressed in human breast cancer tissues. G9a was highly expressed in breast invasive ductal carcinoma, and its expression was negatively correlated with age (P < 0.05). Her-2-overexpressing breast cancer showed high expressions of G9a, which was positively correlated with the expressions of Her-2, Ki-67 and E-cadherin (P < 0.05). Bioinformatics analysis suggested that a high G9a expression was an independent risk factor for poor prognosis of breast cancer. In cultured breast cancer cells, the application of the G9a inhibitor significantly inhibited the cell proliferation.

CONCLUSIONS: G9a is highly expressed in breast cancer tissues to promote the development and progression of breast cancer. A high G9a expression is an independent risk factor for poor prognosis of breast cancer, and G9a may serve as a new target for early diagnosis and treatment of breast cancer.

RevDate: 2019-05-09

Saguy T, Fernández S, Branscombe NR, et al (2019)

Justice Agents: Discriminated Group Members Are Perceived to be Highly Committed to Social Justice.

Personality & social psychology bulletin [Epub ahead of print].

We propose that because members of discriminated (vs. advantaged) groups have a history of dealing with injustice, majority group members expect them to be more committed to social justice. By commitment to social justice, we mean supporting, and caring for, the basic rights of virtually any marginalized group. Studies 1a (N = 145) and 1b (N = 120) revealed that members of discriminated (vs. relatively advantaged) groups were seen as having a stronger commitment to social justice. This was explained by participants' perception of discriminated groups as having a tradition of fighting injustice (Study 2; N = 174). Demonstrating implications of these perceptions, discriminated (relative to advantaged) group members were assigned more justice-related roles in the workplace (Study 3a: N = 120; Study 3b: N = 126; Study 4: N = 133), and their justice-related initiatives were rated more negatively (Study 5: N = 259). Theoretical and practical implications regarding minority-majority relations and minorities' ability to advance in workplace hierarchies are discussed.

RevDate: 2019-05-10

Wang J, Xu Y, Mesa KJ, et al (2018)

Complementary use of polarization-sensitive and standard OCT metrics for enhanced intraoperative differentiation of breast cancer.

Biomedical optics express, 9(12):6519-6528 pii:346713.

We report the development and implementation of an intraoperative polarization-sensitive optical coherence tomography (PS-OCT) system for enhancing breast cancer detection. A total of 3440 PS-OCT images were intraoperatively acquired from 9 human breast specimens diagnosed by H&E histology as healthy fibro-adipose tissue (n = 2), healthy stroma (n = 2), or invasive ductal carcinoma (IDC, n = 5). A standard OCT-based metric (coefficient of variation (CV)) and PS-OCT-based metrics sensitive to biological tissue from birefringence (i.e., retardation and degree of polarization uniformity (DOPU)) were derived from 398 statistically different and independent images selected by correlation coefficient analysis. We found the standard OCT-based metric and PS-OCT-based metrics were complementary for the differentiation of healthy fibro-adipose tissue, healthy stroma, and IDC. While the CV of fibro-adipose tissue was significantly higher (p<0.001) than those of either stroma or IDC, the CV difference between stroma and IDC was minimal. On the other hand, stroma was associated with significantly higher (p<0.001) retardation and significantly lower (p<0.001) DOPU as compared to IDC. By leveraging the complementary information acquired by the intraoperative PS-OCT system, healthy fibro-adipose tissue, healthy stroma, and IDC can be differentiated with an accuracy of 89.4%, demonstrating the potential of PS-OCT as an adjunct modality for enhanced intraoperative differentiation of human breast cancer.

RevDate: 2019-05-10

Allen WM, Foo KY, Zilkens R, et al (2018)

Clinical feasibility of optical coherence micro-elastography for imaging tumor margins in breast-conserving surgery.

Biomedical optics express, 9(12):6331-6349 pii:342473.

It has been demonstrated that optical coherence micro-elastography (OCME) provides additional contrast of tumor compared to optical coherence tomography (OCT) alone. Previous studies, however, have predominantly been performed on mastectomy specimens. Such specimens typically differ substantially in composition and geometry from the more clinically relevant wide-local excision (WLE) specimens excised during breast-conserving surgery. As a result, it remains unclear if the mechanical contrast observed is maintained in WLE specimens. In this manuscript, we begin to address this issue by performing a feasibility study of OCME on 17 freshly excised, intact WLE specimens. In addition, we present two developments required to sustain the progression of OCME towards intraoperative deployment. First, to enable the rapid visualization of en face images required for intraoperative assessment, we describe an automated segmentation algorithm to fuse en face micro-elastograms with OCT images to provide dual contrast images. Secondly, to validate contrast in micro-elastograms, we present a method that enables co-registration of en face images with histology of WLE specimens, sectioned in the orthogonal plane, without any modification to the standard clinical workflow. We present a summary of the observations across the 17 specimens imaged in addition to representative micro-elastograms and OCT images demonstrating contrast in a number of tumor margins, including those involved by invasive ductal carcinoma, mucinous carcinoma, and solid-papillary carcinoma. The results presented here demonstrate the potential of OCME for imaging tumor margins.

RevDate: 2019-05-07

Ciurea AI, Boca I, Rogojan L, et al (2019)

Pectoralis muscle metastases from breast cancer in a young patient detected by automated breast ultrasound.

Medical ultrasonography, 21(2):200-203.

Metastases to the skeletal muscle from breast cancer represent an unusual and rare condition. We present the case of a 27-year-old female with left breast cancer (IDC NST G3) who underwent neoadjuvant chemotherapy followed by conservativesurgery (sectorectomy and lymphadenectomy) and radiation therapy. Two months after the end of radiotherapy she presented with a 2 mm skin lesion and she was referred for a screening ultrasound. The screening automated breast ultrasound (ABUS) revealed local recurrence and pectoralis metastases, lesions evaluated also by magnetic resonance imaging. The diagnosis was confirmed by the ultrasound-guided biopsy.

RevDate: 2019-05-07

Ichihara S, Moritani S, Nishimura R, et al (2019)

Polygon method: A systematic margin assessment for breast conservation.

Cancer medicine [Epub ahead of print].

BACKGROUND: Radiation therapy (RT) for women with ductal carcinoma in situ (DCIS) undergoing breast-conserving surgery (BCS) may be overtreatment for some, especially for those in which DCIS is eradicated, and ipsilateral breast tumor recurrence (IBTR) risk approaches the contralateral breast cancer (CBC) level. The aim of this study was to clarify whether the polygon method, a new systematic method of en face (tangential, shaved) margin assessment, can identify a subset of DCIS that can be safely treated by BCS alone.

METHODS: A key tool of the polygon method is an adjustable mold that prevents the "pancake phenomenon" (flattening) of breast tissue after surgical removal so that the specimen is fixed in the shape of a polygonal prism. This preanalytical procedure enables us to command a panoramic view of entire en face margins 3-5-mm deep from the real peripheral cut surfaces. Competing risk analysis was used to quantify rates of IBTR and CBC and to evaluate risk factors.

RESULTS: From 2000 to 2013, we identified 146 DCIS patients undergoing BCS with a contralateral breast at risk. In 100 DCIS patients whose margin was negative by the polygon method, 5 IBTR (3 DCIS and 2 invasive ductal carcinoma [IDC]) and 10 CBC (6 DCIS and 4 IDC) cases were identified during a median follow-up of 7.6 years (range, 0.9-17.4). Five- and 10-year cumulative incidence rates were 3.0% and 5.3% for IBTR, and 7.1% and 13.3% for CBC, respectively. Thus, patients with a negative margin consistently showed at least twofold lower IBTR than CBC despite omission of RT.

CONCLUSIONS: Japanese women classified with a negative margin by the polygon method show a very low risk of IBTR and account for approximately half of CBC cases. In this subset of DCIS patients, additional RT is not beneficial.

RevDate: 2019-05-12

Petridis C, Arora I, Shah V, et al (2019)

Frequency of pathogenic germline variants in BRCA1, BRCA2, PALB2, CHEK2 and TP53 in ductal carcinoma in situ diagnosed in women under the age of 50 years.

Breast cancer research : BCR, 21(1):58 pii:10.1186/s13058-019-1143-y.

INTRODUCTION: Ductal carcinoma in situ (DCIS) is a non-obligate precursor of invasive ductal breast cancer, and approximately 20% of screen-detected tumours are pure DCIS. Most risk factors for breast cancer have similar associations with DCIS and IDC; however, there is limited data on the prevalence of the known high and moderate penetrance breast cancer predisposition genes in DCIS and which women with DCIS should be referred for genetic screening. The aim of this study was to assess the frequency of germline variants in BRCA2, BRCA1, CHEK2, PALB2 and TP53 in DCIS in women aged less than 50 years of age.

METHODS: After DNA extraction from the peripheral blood, Access Array technology (Fluidigm) was used to amplify all exons of these five known breast cancer predisposition genes using a custom made targeted sequencing panel in 655 cases of pure DCIS presenting in women under the age of 50 years together with 1611 controls.

RESULTS: Case-control analysis revealed an excess of pathogenic variants in BRCA2 (OR = 27.96, 95%CI 6.56-119.26, P = 2.0 × 10-10) and CHEK2 (OR = 8.04, 95%CI 2.93-22.05, P = 9.0 × 10-6), with weaker associations with PALB2 (P = 0.003), BRCA1 (P = 0.007) and TP53 (P = 0.02). For oestrogen receptor (ER)-positive DCIS the frequency of pathogenic variants was 9% under the age of 50 (14% with a family history of breast cancer) and 29% under the age of 40 (42% with a family history of breast cancer). For ER-negative DCIS, the frequency was 9% (16% with a family history of breast cancer) and 8% (11% with a family history of breast cancer) under the ages of 50 and 40, respectively.

CONCLUSIONS: This study has shown that breast tumourigenesis in women with pathogenic variants in BRCA2, CHEK2, PALB2, BRCA1 and TP53 can involve a DCIS precursor stage and that the focus of genetic testing in DCIS should be on women under the age of 40 with ER-positive DCIS.

RevDate: 2019-06-10

Tom MC, Nguyen JK, Lucianò R, et al (2019)

Impact of Cribriform Pattern and Intraductal Carcinoma on Gleason 7 Prostate Cancer Treated with External Beam Radiotherapy.

The Journal of urology [Epub ahead of print].

PURPOSE: To assess the impact of cribriform pattern and/or intraductal carcinoma (IDC) on Gleason 7 prostate cancer (PCa) treated with external beam radiotherapy (EBRT).

METHODS: We evaluated men with Gleason 7 (Grade Group 2 and 3) PCa treated with dose-escalated EBRT +/- androgen deprivation, and reviewed biopsies for the presence of cribriform pattern and/or IDC. Endpoints included biochemical recurrence free survival (BRFS), distant metastasis free survival (DMFS), and disease specific survival (DSS).

RESULTS: Of 237 patients, median follow up was 117 months (range 3-236), and NCCN risk group was 24% favorable-intermediate risk, 53% unfavorable-intermediate risk, and 23% high risk. Rates of cribriform pattern without IDC, cribriform pattern with IDC, IDC without cribriform pattern, and neither morphology, were 36%, 13%, 0%, and 51%, respectively. On multivariable analysis (MVA), presence of cribriform pattern with IDC (HR 4.22; 95% CI 2.08-8.53; p<0.0001), PSA 10-20 ng/ml (1.97; 1.03-3.79; p=0.04), and PSA >20 ng/ml (2.26; 1.21-4.23; p=0.01) were associated with worse BRFS. On MVA, only cribriform pattern with IDC was associated with inferior DMFS (4.18; 1.43-12.28; p=0.01) and DSS (14.26; 2.75-74.04; p=0.0016). Factors associated with having cribriform pattern +/- IDC included Grade Group 3, high risk group, and ≥50% positive biopsy cores. When stratified by neither morphology present, cribriform pattern without IDC, and cribriform pattern with IDC, differences in BRFS (p=0.00042), DMFS (p=0.017), and DSS (p<0.0001) were statistically significant.

CONCLUSIONS: Cribriform pattern with IDC was associated with adverse outcomes among men with Gleason 7 PCa treated with ERBT, whereas cribriform pattern without IDC was not. Future studies may benefit from dichotomizing these two histologic entities.

RevDate: 2019-05-09

Aplin FP, GY Fridman (2019)

Implantable Direct Current Neural Modulation: Theory, Feasibility, and Efficacy.

Frontiers in neuroscience, 13:379.

Implantable neuroprostheses such as cochlear implants, deep brain stimulators, spinal cord stimulators, and retinal implants use charge-balanced alternating current (AC) pulses to recover delivered charge and thus mitigate toxicity from electrochemical reactions occurring at the metal-tissue interface. At low pulse rates, these short duration pulses have the effect of evoking spikes in neural tissue in a phase-locked fashion. When the therapeutic goal is to suppress neural activity, implants typically work indirectly by delivering excitation to populations of neurons that then inhibit the target neurons, or by delivering very high pulse rates that suffer from a number of undesirable side effects. Direct current (DC) neural modulation is an alternative methodology that can directly modulate extracellular membrane potential. This neuromodulation paradigm can excite or inhibit neurons in a graded fashion while maintaining their stochastic firing patterns. DC can also sensitize or desensitize neurons to input. When applied to a population of neurons, DC can modulate synaptic connectivity. Because DC delivered to metal electrodes inherently violates safe charge injection criteria, its use has not been explored for practical applicability of DC-based neural implants. Recently, several new technologies and strategies have been proposed that address this safety criteria and deliver ionic-based direct current (iDC). This, along with the increased understanding of the mechanisms behind the transcutaneous DC-based modulation of neural targets, has caused a resurgence of interest in the interaction between iDC and neural tissue both in the central and the peripheral nervous system. In this review we assess the feasibility of in-vivo iDC delivery as a form of neural modulation. We present the current understanding of DC/neural interaction. We explore the different design methodologies and technologies that attempt to safely deliver iDC to neural tissue and assess the scope of application for direct current modulation as a form of neuroprosthetic treatment in disease. Finally, we examine the safety implications of long duration iDC delivery. We conclude that DC-based neural implants are a promising new modulation technology that could benefit from further chronic safety assessments and a better understanding of the basic biological and biophysical mechanisms that underpin DC-mediated neural modulation.

RevDate: 2019-06-10

Cohen EN, Fouad TM, Lee BN, et al (2019)

Elevated serum levels of sialyl Lewis X (sLeX) and inflammatory mediators in patients with breast cancer.

Breast cancer research and treatment pii:10.1007/s10549-019-05258-0 [Epub ahead of print].

PURPOSE: The carbohydrate sialyl LewisX (sLeX) mediates cell adhesion, is critical in the normal function of immune cells, and is frequently over-expressed on cancer cells. We assessed the association, differential levels, and prognostic value of sLeX and inflammatory cytokines/chemokines in breast cancer sera.

METHODS: We retrospectively measured sLeX and a panel of cytokines/chemokines in the sera of 26 non-invasive ductal carcinoma in situ (DCIS), 154 invasive non-metastatic breast cancer (non-MBC), 63 metastatic breast cancer (MBC) patients, and 43 healthy controls. Differences in sLeX and inflammatory cytokines among and between patient groups and healthy controls were assessed with nonparametric tests and we performed survival analysis for the prognostic potential of sLeX using a cut-off of 8 U/mL as previously defined.

RESULTS: Median serum sLeX was significantly higher than controls for invasive breast cancer patients (MBC and non-MBC) but not DCIS. In univariate analysis, we confirmed patients with serum sLeX > 8 U/mL have a significantly shorter progression-free survival (PFS) (P = 0.0074) and overall survival (OS (P = 0.0003). Similarly, patients with high serum MCP-1 and IP-10 had shorter OS (P = 0.001 and P < 0.001, respectively) and PFS (P = 0.010 and P < 0.001, respectively). sLeX, MCP-1 and IP-10 remained significant in multivariate survival analysis.

CONCLUSION: Elevated serum sLeX was associated with invasive cancer but not DCIS. High serum sLeX levels were associated with inflammatory mediators and may play a role in facilitating local invasion of breast tumor. Furthermore, serum MCP-1, IP-10 and sLeX may have prognostic value in breast cancer.

RevDate: 2019-05-16

Sanderink WBG, Laarhuis BI, Strobbe LJA, et al (2019)

A systematic review on the use of the breast lesion excision system in breast disease.

Insights into imaging, 10(1):49 pii:10.1186/s13244-019-0737-3.

PURPOSE: To outline the current status of and provide insight into possible future research on the breast lesion excision system (BLES) as a diagnostic and therapeutic device.

METHODS: A systematic search of the literature was performed using PubMed, Embase, and the Cochrane databases to identify relevant studies published between January 2002 and April 2018. Studies were considered eligible for inclusion if they evaluated the diagnostic or therapeutic accuracy or safety of BLES.

RESULTS: Ultimately, 17 articles were included. The reported underestimation rates of atypical ductal hyperplasia and ductal carcinoma in situ (DCIS) ranged from 0 to 14.3% and from 0 to 22.2%, respectively. Complete excision rates for invasive ductal carcinoma and DCIS ranged from 5.3 to 76.3%. Bleeding was the most frequently reported complication (0-11.8%). Device-related complications may arise, with an empty basket being the most common (0.6-3.6%). Thermal damage of the specimen, caused by the use of a radiofrequency cutting wire, was reported in eight of the included studies. Most thermal artifacts were reported as superficial and small (0.1-1.9 mm).

CONCLUSIONS: The BLES, an automated, image-guided, single-pass biopsy system for breast lesions using radiofrequency is designed to excise and retrieve an intact tissue specimen. It is an efficient and safe breast biopsy method with acceptable complication rates, which may be used as an alternative to vacuum-assisted biopsies. The variable rate of complete excision raises questions about the possibility to use BLES as a therapeutic device for the excision of small lesions. Further research should focus on this aspect of BLES.

RevDate: 2019-05-11

Aras S, Maroun MC, Song Y, et al (2019)

Mitochondrial autoimmunity and MNRR1 in breast carcinogenesis.

BMC cancer, 19(1):411 pii:10.1186/s12885-019-5575-7.

BACKGROUND: Autoantibodies function as markers of tumorigenesis and have been proposed to enhance early detection of malignancies. We recently reported, using immunoscreening of a T7 complementary DNA (cDNA) library of breast cancer (BC) proteins with sera from patients with BC, the presence of autoantibodies targeting several mitochondrial DNA (mtDNA)-encoded subunits of the electron transport chain (ETC) in complexes I, IV, and V.

METHODS: In this study, we have characterized the role of Mitochondrial-Nuclear Retrograde Regulator 1 (MNRR1, also known as CHCHD2), identified on immunoscreening, in breast carcinogenesis. We assessed the protein as well as transcript levels of MNRR1 in BC tissues and in derived cell lines representing tumors of graded aggressiveness. Mitochondrial function was also assayed and correlated with the levels of MNRR1. We studied the invasiveness of BC derived cells and the effect of MNRR1 levels on expression of genes associated with cell proliferation and migration such as Rictor and PGC-1α. Finally, we manipulated levels of MNRR1 to assess its effect on mitochondria and on some properties linked to a metastatic phenotype.

RESULTS: We identified a nuclear DNA (nDNA)-encoded mitochondrial protein, MNRR1, that was significantly associated with the diagnosis of invasive ductal carcinoma (IDC) of the breast by autoantigen microarray analysis. In focusing on the mechanism of action of MNRR1 we found that its level was nearly twice as high in malignant versus benign breast tissue and up to 18 times as high in BC cell lines compared to MCF10A control cells, suggesting a relationship to aggressive potential. Furthermore, MNRR1 affected levels of multiple genes previously associated with cancer metastasis.

CONCLUSIONS: MNRR1 regulates multiple genes that function in cell migration and cancer metastasis and is higher in cell lines derived from aggressive tumors. Since MNRR1 was identified as an autoantigen in breast carcinogenesis, the present data support our proposal that both mitochondrial autoimmunity and MNRR1 activity in particular are involved in breast carcinogenesis. Virtually all other nuclear encoded genes identified on immunoscreening of invasive BC harbor an MNRR1 binding site in their promoters, thereby placing MNRR1 upstream and potentially making it a novel marker for BC metastasis.

RevDate: 2019-06-10
CmpDate: 2019-05-28

Li JP, Zhang XM, Zhang Z, et al (2019)

Association of p53 expression with poor prognosis in patients with triple-negative breast invasive ductal carcinoma.

Medicine, 98(18):e15449.

TP53 gene is mutated in approximately 80% of triple-negative breast cancer (TNBC). However, the prognostic significance of immunohistochemical (IHC)-detected p53 protein expression remains controversial in TNBC. In this study, we retrospectively analyzed the association between IHC-detected p53 expression and the prognosis in a cohort of 278 patients with stage I-III triple-negative breast invasive ductal carcinoma (IDC), who received surgery at the department of breast surgery in the Fourth Hospital of Hebei Medical University from 2010-01 to 2012-12. We found a positive expression ratio of IHC-detected p53 in triple-negative breast IDC of 58.6% (163/278). Furthermore, levels of expression were significantly associated with vessel tumor emboli and higher histologic grade (P = .038, P = .043, respectively), with the highest expression level observed in G3 breast cancer (64.7%). Additionally, Kaplan-Meier analysis showed that p53 expression indicated worse overall survival (OS) in the whole cohort (79.6% vs 89.6%, Log-rank test P = .025) as well as in stratified prognostic stage II patients (90.8% vs 100%, Log-rank test P = .027). The mortality risk of p53 expression patients was 2.22 times higher than that of p53 negative patients (HR: 2.222; 95%CI: 1.147-4.308). In addition, p53 expression was also associated with poor disease-free survival (DFS) (76.7% vs 86.8%, P = .020). Cox proportional hazard ratio model showed p53 expression was an independent risk factor for OS (P = .018) and DFS (P = .018) after controlling for tumor size, lymph node status, and vessel tumor emboli. Altogether, our data showed that IHC-detected p53 expression is a promising prognostic candidate for poor survival in triple-negative breast IDC patients. However, more studies are needed to determine if p53 may be applied to clinical practice as a biomarker and/or novel therapeutic target for TNBC.

RevDate: 2019-05-03

Hinnen D, DF Kruger (2019)

Cardiovascular risks in type 2 diabetes and the interpretation of cardiovascular outcome trials.

Diabetes, metabolic syndrome and obesity : targets and therapy, 12:447-455 pii:dmso-12-447.

Background: Patients with type 2 diabetes (T2D) are at increased cardiovascular (CV) risk compared to subjects without diabetes, with some data estimating that CV disease (CVD) risk is doubled in these individuals. Additionally, CVD remains the leading cause of death in patients with T2D, so it is paramount to determine the relationship between these two diseases.

Purpose: Older diabetes treatments have limited CV safety data. In 2008, the US Food and Drug Administration published guidance for manufacturers on antihyperglycemic agents, requiring studies to ensure CV safety of new therapies. Since then, manufacturers of many newer agents have conducted and published results from CV outcomes trials (CVOTs), with more trials due to publish soon. This review discusses the relationship between CVD and T2D and explores findings from the latest CVOTs of glucose-lowering agents to guide nurse practitioners in their prescribing patterns for patients with T2D.

Conclusion: Patients with T2D are at high risk of CVD, so CV risk should be carefully considered when managing these patients, and CV risks and benefits of antidiabetic drugs should be included in prescribing decisions.

RevDate: 2019-05-01

Trihia HJ, Novkovic N, Provatas I, et al (2019)

Primary Alveolar Rhabdomyosarcoma of the Breast in an Adult: An Extremely Rare Case.

Case reports in pathology, 2019:6098747.

Sarcomas of the breast constitute less than 1% of all malignant breast tumors and primary rhabdomyosarcoma (RMS) is a very rare entity with limited case reports in the literature. RMS is common in children and adolescents and rare in adults. Primary RMS arising from the breast is exceedingly rare in adults. We report a case of a primary RMS of the breast in a 60-year-old woman, who presented in an early stage, mimicking invasive ductal carcinoma clinically and is in complete remission after three years of diagnosis and one year of treatment.

RevDate: 2019-05-13

Yao Y, Sun L, Meng Y, et al (2019)

Breast-Conserving Surgery in Patients With Mammary Paget's Disease.

The Journal of surgical research, 241:178-187 pii:S0022-4804(19)30142-8 [Epub ahead of print].

BACKGROUND: We aimed to analyze the association between Paget's disease (PD) and breast cancer (BC) subtypes and compare the effect of breast-conserving surgery (BCS) as a local treatment with mastectomy for PD.

MATERIALS AND METHODS: Data of patients with histologic type International Classification of Diseases-0-3 8540-8543 who were treated from 1973 to 2014 were retrieved from the Surveillance, Epidemiology, and End Results database of the National Cancer Institute. A chi-square test was used to identify differences in categorical data among different groups. Overall survival (OS) was analyzed using the Kaplan-Meier method, log-rank test, Cox proportional hazards models, sequential landmark analysis, and propensity score-matched analysis.

RESULTS: The study cohort included 5398 patients. Triple-negative BC accounted for the fewest patients with PD-only (1/22, 4.54%), Paget's disease-ductal carcinoma in situ (PD-DCIS) (3/48, 6.25%), and Paget's disease-invading ductal carcinoma (PD-IDC) (23/352, 6.53%). According to the results of the log-rank test and Cox analysis, the 10-year OS rates were similar for the BCS and mastectomy subgroups among patients with PD-DCIS or PD-IDC. Furthermore, there were no significant differences in survival benefits among the different surgeries after propensity score matching. Landmark analyses for OS of patients with PD-DCIS or PD-IDC surviving more than 1, 3, and 5 y showed no significant differences in survival. There were statistical differences in 10-year OS rates for patients with PD-DCIS or PD-IDC who underwent radiation therapy, or not, following BCS (both, P < 0.001).

CONCLUSIONS: For patients with PD-DCIS or PD-IDC, breast conservation therapy with lumpectomy and radiation is an effective local treatment strategy, compared with mastectomy.

RevDate: 2019-05-14
CmpDate: 2019-05-14

Marull J, Herrando S, Brotons L, et al (2019)

Building on Margalef: Testing the links between landscape structure, energy and information flows driven by farming and biodiversity.

The Science of the total environment, 674:603-614.

The aim of this paper is to test two methodologies, applicable to different spatial scales (from regional to local), to predict the capacity of agroecosystems to provide habitats for the species richness of butterflies and birds, based on the ways their socio-metabolic flows change the ecological functionality of bio-cultural landscapes. First, we use the more general Intermediate Disturbance-Complexity (IDC) model to assess how different levels of human appropriation of photosynthetic production affect the landscape functional structure that hosts biodiversity. Second, we apply a more detailed Energy-Landscape Integrated Analysis (ELIA) model that focusses on the energy storage carried out by the internal biomass loops, and the energy information held in the network of energy flows driven by farmers, in order to correlate both (the energy reinvested and redistributed) with the energy imprinted in the landscape patterns and processes that sustain biodiversity. The results obtained after applying both models in the province and the metropolitan region of Barcelona support the Margalef's energy-information-structure hypothesis by showing positive relations between butterflies' species richness, IDC and ELIA, and between birds' species richness and energy information. Our findings support the view that strong relationships between farming energy flows, agroecosystem functioning and biodiversity can be detected, and highlight the importance of farmers' knowledge and labour to maintain bio-cultural landscapes.

RevDate: 2019-05-29

Kato M, Hirakawa A, Kobayashi Y, et al (2019)

The influence of the presence of intraductal carcinoma of the prostate on the grade group system's prognostic performance.

The Prostate, 79(10):1065-1070.

BACKGROUND: Although the presence of intraductal carcinoma of the prostate (IDC-P) influences biochemical failure in radical prostatectomy patients, no data are available regarding the impact of its integration into the classification grade group system. Thus, the aim of this study was to enhance the utility of the grade group system by integrating the presence of IDC-P.

METHODS: This study was a retrospective evaluation of 1019 patients with prostate cancer who underwent radical prostatectomy between 2005 and 2013 without neoadjuvant or adjuvant therapy. The data on age, prostate-specific antigen (PSA) level at diagnosis, pathological T stage (pT), presence of Gleason pattern 5 (GP5), presence of IDC-P, and surgical margin status were analyzed to predict PSA recurrence after prostatectomy.

RESULTS: The median patient age was 67 (range, 45-80) years and the median initial PSA level was 6.8 (range, 0.4-82) ng/mL. The median follow-up period was 82 (range, 0.7-148) months. IDC-P was detected in 157 patients (15.4%). Among these patients, the increase in the positive rate of IDC-P correlated with tumor upgrading. The grade groups (GGs) were as follows: GG1 without IDC-P, 16.0% (n = 163); GG2 without IDC-P, 46.1% (n = 470); GG3 without IDC-P, 15.7% (n = 160); GG4 without IDC-P, 2.6% (n = 27); GG5 without IDC-P, 4.1% (n = 42); any GG with IDC-P, 15.4% [n = 157; GG 2 (n = 29); GG3 (n = 60); GG4 (n = 13); GG5 (n = 55)]. Any grade Group with IDC-P showed significantly worse prognosis than any other group without IDC-P (P < 0.0001). In a multivariate analysis, integration of the IDC-P into the Grade Groups, the PSA level at diagnosis, and the surgical margin status were significant prognostic predictors (P < 0.0001, < 0.0001 and < 0.0001, respectively).

CONCLUSIONS: Integrating the presence of IDC-P into the grade group system will result in more accurate predictions of patient outcome.

RevDate: 2019-04-26

Albayrak M, Senol O, Demirkaya-Miloglu F, et al (2019)

Novel chemometrics‑assisted spectroscopic methods for diagnosis and monitoring of invasive ductal carcinoma in breast tissue.

Bratislavske lekarske listy, 120(3):184-187.

OBJECTIVES: Early diagnosis of breast cancer is extremely important because it is the most common female cancer and a leading cause of cancer death in adult women. In this study, it is aimed to create Raman mapping with developed chemometrics‑assisted Raman and FT-IR spectroscopy methods for the diagnosis of invasive ductal carcinoma (IDC) in breast tissue samples.

METHODS: Samples were deparaffinized and 20‑micron layers of each tissue were located on a coverslip. Mapping of both healthy and cancerous tissues were performed by exposing them to Raman laser at 532 and 758 nm while excitation was recorded at wavenumbers in range of 100-4,000 cm-1. Orthogonal partial least square (OPLS) algorithm was applied to evaluate obtained Raman spectra. Latent variable was selected to explain the whole model.

RESULTS: Healthy and IDC tissues were accurately and precisely clustered with Raman mapping and obtained results were compared to those obtained by means of histopathology and FT-IR methods. It is claimed that the proposed method has a great potential in clustering and separating IDC tissues from the healthy ones.

CONCLUSION: This novel, rapid, precise, easy and objective diagnosis method may be an alternative to conventional diagnostic methods for IDC in breast tissue (Fig. 5, Ref. 22).

RevDate: 2019-05-10

Ishikane M, Hayakawa K, Kutsuna S, et al (2019)

The impact of infectious disease consultation in candidemia in a tertiary care hospital in Japan over 12 years.

PloS one, 14(4):e0215996 pii:PONE-D-19-00696.

BACKGROUND: Candidemia is one of the major causes of morbidity and mortality as a hospital acquired infection. Infectious diseases consultation (IDC) might be beneficial to improve candidemia outcomes; however, only limited data from short periods of time are available thus far.

METHODS: An observational study of all candidemia patients at a large tertiary care hospital between 2002 and 2013 was conducted. A candidemia episode was defined as ≥ 1 positive result for Candida spp. in blood culture. Patients who died or transferred to another hospital within two days after their first positive blood culture were excluded. Independent risk factors for 30-day mortality were determined.

RESULTS: Among 275 patients with 283 episodes of candidemia, 194 (68.6%) were male, and the mean age was 70.0 ± 15.8 years. Central line-associated bloodstream infections, peripheral line-associated bloodstream infections, intra-abdominal infection, and unknown source comprised 220 (77.7%), 35 (12.4%), 13 (4.7%), and 15 (5.3%) episodes, respectively. A total of 126 patients (44.5%) received IDC. Factors independently associated with 30-day mortality in patients with candidemia were urinary catheters use (adjusted hazard ratio [HR] = 2.94; 95% confidence interval [CI] = 1.48-5.87; P = 0.002) and severe sepsis/septic shock (adjusted HR = 2.10; 95% CI = 1.20-3.65; P = 0.009). IDC was associated with a 46% reduction in 30-day mortality (adjusted HR = 0.54; 95% CI = 0.32-0.90; P = 0.017).

CONCLUSION: IDC was independently associated with a reduction in 30-day mortality. Only 44.5% of patients with candidemia in this cohort received IDC. Routine IDC should be actively considered for patients with candidemia.

RevDate: 2019-05-03

Trinh VQ, Benzerdjeb N, Chagnon-Monarque S, et al (2019)

Retrospective study on the benefit of adjuvant radiotherapy in men with intraductal carcinoma of prostate.

Radiation oncology (London, England), 14(1):60 pii:10.1186/s13014-019-1267-3.

BACKGROUND: Intraductal carcinoma of the prostate (IDC-P) is an independent biomarker of recurrence and survival with particular treatment response, yet no study has tested its response to radiotherapy. The aim of our project was to test the impact of adjuvant radiotherapy (ART) in patients with localized to locally advanced prostate cancer (PC) and IDC-P.

MATERIALS AND METHODS: We performed a retrospective study of men with pT2-T3 PC treated by radical prostatectomy (RP) with or without ART, from two centres (1993-2015). Exclusion criteria were the use of another type of treatment prior to biochemical recurrence (BCR), and detectable prostate- specific antigen (PSA) following RP or ART. Primary outcome was BCR (2 consecutive PSA ≥ 0.2 ng/ml). Patients were grouped by treatment (RPonly/RP + ART), IDC-P status, and presence of high-risk features (HRF: Grade Groups 4-5, positive margins, pT3 stage).

RESULTS: We reviewed 293 RP specimens (median follow-up 99 months, 69 BCR). Forty-eight patients (16.4%) were treated by RP + ART. Multivariate Cox regression for BCR indicated that IDC-P had the strongest impact (hazard ratio [HR] = 2.39, 95% confidence interval [CI]:1.44-3.97), while ART reduced the risk of BCR (HR = 0.38, 95%CI: 0.17-0.85). Other HRF were all significant except for pT3b stage. IDC-P[+] patients who did not receive ART had the worst BCR-free survival (log-rank P = 0.023). Furthermore, IDC-P had the same impact on BCR-free survival as ≥1 HRF (log-rank P = 0.955).

CONCLUSION: Men with IDC-P who did not receive ART had the highest BCR rates, and IDC-P had the same impact as ≥1 HRF, which are often used as ART indications. Once validated, ART should be considered in patients with IDC-P.

RevDate: 2019-06-03

Zenan H, Zixiong L, Zhicheng Y, et al (2019)

Clinical prognostic evaluation of immunocytes in different molecular subtypes of breast cancer.

Journal of cellular physiology [Epub ahead of print].

To retrospectively analyze the relationship between preoperative blood parameters and postoperative clinical outcomes in patients with different molecular subtypes of breast cancer (BC), a cohort of 601 patients with BC in the Third Affiliated Hospital, Sun Yat-sen University, was retrospectively reviewed. They were categorized into four subtypes according to the expression of ER, PR, HER-2, and KI-67%. White blood cell, neutrophil, lymphocyte, monocyte, eosinophil, basophil, and platelet counts, the neutrophil-to-lymphocyte ratio (NLR), the neutrophil-to-monocyte ratio (NMR), the lymphocyte-to-monocyte ratio (LMR), and the platelet-to-lymphocyte ratio (PLR) were recorded. Univariate and multivariate analyses were performed to identify the relationship between parameters and ratios and disease-free survival (DFS) and overall survival (OS). Luminal subtypes of BC had smaller tumor volume, better differentiation degree of invasive ductal carcinoma, less lymph node metastasis, and better clinical outcome than the HER-2 overexpression and triple-negative BC (TNBC) subtypes. In multivariate analysis, age and LMR were the independent prognostic factors of DFS in patients with luminal A (age, p = 0.005; LMR, P = 0.026); PLR in patients with luminal B (DFS; p = 0.032; OS, p= 0.012); LMR in patients with HER-2 overexpression (DFS; p = 0.008; OS, p = 0.017); and NLR for DFS (p = 0.014); and WBC for OS (p = 0.008) in patients with TNBC. LMR was the benign predictor of luminal A and HER-2 overexpression. PLR was the adverse predictor of luminal B. WBC and NLR were the adverse predictors of TNBC. Therefore, these peripheral blood parameters can play an important role in the diagnosis and treatment of patients with different molecular subtypes of BC.

RevDate: 2019-04-26

Jones EF, Ray KM, Li W, et al (2019)

Initial experience of dedicated breast PET imaging of ER+ breast cancers using [F-18]fluoroestradiol.

NPJ breast cancer, 5:12 pii:107.

Dedicated breast positron emission tomography (dbPET) is an emerging technology with high sensitivity and spatial resolution that enables detection of sub-centimeter lesions and depiction of intratumoral heterogeneity. In this study, we report our initial experience with dbPET using [F-18]fluoroestradiol (FES) in assessing ER+ primary breast cancers. Six patients with >90% ER+ and HER2- breast cancers were imaged with dbPET and breast MRI. Two patients had ILC, three had IDC, and one had an unknown primary tumor. One ILC patient was treated with letrozole, and another patient with IDC was treated with neoadjuvant chemotherapy without endocrine treatment. In this small cohort, we observed FES uptake in ER+ primary breast tumors with specificity to ER demonstrated in a case with tamoxifen blockade. FES uptake in ILC had a diffused pattern compared to the distinct circumscribed pattern in IDC. In evaluating treatment response, the reduction of SUVmax was observed with residual disease in an ILC patient treated with letrozole, and an IDC patient treated with chemotherapy. Future study is critical to understand the change in FES SUVmax after endocrine therapy and to consider other tracer uptake metrics with SUVmax to describe ER-rich breast cancer. Limitations include variations of FES uptake in different ER+ breast cancer diseases and exclusion of posterior tissues and axillary regions. However, FES-dbPET has a high potential for clinical utility, especially in measuring response to neoadjuvant endocrine treatment. Further development to improve the field of view and studies with a larger cohort of ER+ breast cancer patients are warranted.

RevDate: 2019-04-23

Shah RB, Nguyen JK, Przybycin CG, et al (2019)

Atypical Intraductal Proliferation Detected in Prostate Needle Biopsy is a Marker of Unsampled Intraductal Carcinoma and Other Adverse Pathological Features.

Histopathology [Epub ahead of print].

AIMS: Intraductal proliferations of the prostate with more complexity and/or cytologic atypia than high-grade prostate intraepithelial neoplasia (HGPIN), but falling short of intraductal carcinoma (IDC-P) are described as "atypical intraductal proliferation" (AIP). When present in needle biopsy (NBX) without IDC-P, clinical significance is not known.

METHODS AND RESULTS: Sixty-two NBX cases were diagnosed as AIP over 7 years with estimated incidence of 1%. AIP was characterized by loose cribriform architecture (90%) or non-cribriform architecture exhibiting significant nuclear atypia that fell short of IDC-P. Fifty patients had concomitant PCa (20% Grade Group (GG) 1, 48% GG2, 14% GG3, 8% GG4 and 10% GG 5), and 12 had AIP alone. Of 40 patients who were candidates for no therapy (AIP alone) or active surveillance (AIP with GG1 or GG2 PCa without cribriform pattern 4), 20 had subsequent follow-up pathology [7 NBXs and 13 radical prostatectomy (RP)]. Of the 12 AIP only patients, 6 had subsequent biopsy diagnosis of: benign prostate (2), IDC-P with PCa (1), and PCa (3). One or more adverse pathologic features at subsequent RP were present in 93% of patients with AIP and GG1 or GG2 PCa, defined as: GG >3 (15%), IDC-P (77%), cribriform Gleason pattern 4 (69%), pT3a (77%), or pT3b (8%).

CONCLUSIONS: AIP in NBX may be a marker of unsampled IDC-P and/or other adverse pathologic features in suspected low to intermediate risk PCa. AIP should be considered distinct from HGPIN for risk assessment and warrant consideration for further work-up to detect unsampled high risk PCa. This article is protected by copyright. All rights reserved.

RevDate: 2019-04-26

Mouchli M, Grider DJ, P Yeaton (2019)

Gallbladder Metastases: A Report of Two Cases.

Case reports in oncology, 12(1):235-240 pii:cro-0012-0235.

Introduction: Metastasis to the gallbladder is not common and usually manifests an advanced stage of malignancy. Herein, we report a case of triple negative high grade invasive ductal carcinoma of breast with a metastatic lesion to the gallbladder.

Case Presentation: The patient is a 52-year-old female diagnosed with invasive ductal carcinoma treated with mastectomy and chemotherapy. After 12 months, she presented to the emergency department with right upper quadrant pain and elevated liver chemistries. Abdominal enhanced computed tomography showed periportal and gallbladder wall edema. After cholecystectomy, the resected gallbladder was histologically considered to be a metastatic lesion arising from the primary lung cancer. The second case describes a case of a 77-year-old woman with multiple co-morbidities who presented to the hospital with sepsis secondary to biliary source. Abdominal enhanced computed tomography findings were concerning for acute cholecystitis. After cholecystectomy, the pathology of the resected gallbladder demonstrated cholecystitis and plasmacytoma.

Conclusion: The atypical presentation of gallbladder metastases could mislead treating providers. The diagnosis might alter management decisions and prognosis.

RevDate: 2019-04-20

Harbertson J, Scott PT, Lemus H, et al (2019)

Cross-Sectional Study of Sexual Behavior, Alcohol Use, and Mental Health Conditions Associated With Sexually Transmitted Infections Among Deploying Shipboard US Military Personnel.

Military medicine pii:5475521 [Epub ahead of print].

INTRODUCTION: Limited comprehensive data exist on risk behavior associated with sexually transmitted infections (STI) among ship-assigned US military personnel during the predeployment time period (PDT). This study examined whether sexual risk behaviors, alcohol use, involuntary drug consumption (IDC), posttraumatic stress disorder (PTSD), and depression during the 12 months prior to deployment were associated with provider-diagnosed STIs in this population.

MATERIALS AND METHODS: Using cross-sectional data collected during 2012-2014 among sexually active personnel, multivariable regression assessed factors associated with STIs among all men (n = 1,831). Stratified analyses were conducted among men who have sex with women (MSW, n = 1,530), men who have sex with men or men and women (MSM, n = 83), and excluded those not reporting sexual partner gender (n = 218).

RESULTS: Among MSW, transactional sex (AOR 3.8, 95% CI 1.5-9.4) meeting sexual partners at work (AOR 4.3, 95% CI 2.0-9.2), IDC (AOR 6.6, 95% CI 3.0-14.5), and incomplete mental health assessments (AOR 4.4, 95% CI 1.6-12.0) were significantly associated with STIs after adjustment. Among all men, those who identified as MSM (AOR 4.6, 95% CI 1.9-11.2) and drug screen positive (AOR 3.3, 95% CI 1.3-8.6) were significantly more likely to report an STI.

CONCLUSIONS: Previously unreported factors significantly associated with STIs at the PDT among MSW in the adjusted analysis were meeting sexual partners at work and IDC. IDC during the PDT warrants further exploration. These results can inform tailored STI reduction interventions among shipboard personnel and similarly aged civilians undergoing similar transition/travel experiences.

RevDate: 2019-04-28

Zinger E, Gueijman A, Obolski U, et al (2019)

Less fit Lamium amplexicaule plants produce more dispersible seeds.

Scientific reports, 9(1):6299 pii:10.1038/s41598-019-42158-1.

Theory predicts that less fit individuals would disperse more often than fitter ones (Fitness Associated Dispersal, FAD hypothesis). To test this prediction under laboratory conditions, an entire life cycle of Lamium amplexicaule plants and the preferences of its dispersal agent, Messor ebeninus ants, were tracked. Characterization of individual L. amplexicaule plant revealed high variability in spot cover on the surface of the seeds, where less fit plants produce "unspotted seeds" (see Fig. 1 in Introduction). Unspotted L. amplexicaule seeds showed higher variation in germination time and lower germination rate. Moreover, M. ebeninus ants preferably collected these unspotted seeds. Our results show that low fitness L. amplexicaule plants produce seeds with higher potential for dispersal, supporting the FAD hypothesis in a plant-animal system.

RevDate: 2019-05-05

Pare R, Soon PS, Shah A, et al (2019)

Differential expression of senescence tumour markers and its implications on survival outcomes of breast cancer patients.

PloS one, 14(4):e0214604 pii:PONE-D-18-34030.

Breast cancer is a heterogeneous disease displaying different histopathological characteristics, molecular profiling and clinical behavior. This study describes the expression patterns of senescence markers P53, DEC1 and DCR2 and assesses their significance on patient survival as a single or combined marker with P16 or P14 using breast cancer progression series. One thousand and eighty (1080) patients with primary invasive ductal carcinoma, no special type, were recruited through an 11-year retrospective study period. We constructed tissue microarrays of normal, benign hyperplasia, ductal carcinoma in situ and invasive ductal carcinoma from each patient and performed immunohistochemical staining to study the protein expression. Statistical analysis includes Pearson chi-square, Kaplan-Meier log ran test and Cox proportional hazard regression were undertaken to determine the associations and predict the survival outcomes. P53, DEC1 and DCR2 expression correlated significantly with normal, benign, premalignant and malignant tissues with (p<0.05). The expression profile of these genes increases from normal to benign to premalignant and plateaued from premalignant to malignant phenotype. There is a significant association between P53 protein expression and age, grade, staging, lymphovascular invasion, estrogen receptor, progesterone receptor and HER2 whereas DCR2 protein expression significantly correlated with tumour grade, hormone receptors status and HER2 (p<0.05 respectively). P53 overexpression correlated with increased risk of relapse (p = 0.002) specifically in patients who did not receive hormone therapy (p = 0.005) or chemotherapy (p<0.0001). The combination of P53+/P16+ is significantly correlated with poor overall and disease-free survival, whereas a combination of P53+/P14+ is associated with worse outcome in disease-free survival (p<0.05 respectively). P53 overexpression appears to be a univariate predictor of poor disease-free survival. The expression profiles of DEC1 and DCR2 do not appear to correlate with patient survival outcomes. The combination of P53 with P16, rather P53 expression alone, appears to provide more useful clinical information on patient survival outcomes in breast cancer.

RevDate: 2019-04-18

Oğuz Kapicibaşi H (2019)

The role of mediastinoscopy in the diagnosis of thoracic disease: 107-case analysis.

Medicinski glasnik : official publication of the Medical Association of Zenica-Doboj Canton, Bosnia and Herzegovina, 16(2): [Epub ahead of print].

Aim To evaluate the efficacy, safety and feasibility of mediastinoscopy in 107 cases with mediastinal lesions that could not be diagnosed histopathologically with other methods. Methods A total of 107 cases (73 males, 34 females; mean age 57.4, range 30-88 years) with mediastinal lymphadenopathy, who underwent mediastinoscopy between 12 September 2012 and 29 November 2018 were examined retrospectively. The cases were evaluated in terms of age, gender, complaint, operation time, histopathological diagnosis, postoperative morbidity and mortality parameters. Results Upon histopathological examination 32 (30%) patients were diagnosed with lung cancer metastasis (N2 stage), which was the most common diagnosis. With this diagnosis unnecessary thoracotomy was prevented. In patients with pathological lymphadenopathy found by imaging histopathological results were examined to evaluate the presence of N2 stage. In 25 (23.5%) cases biopsy results were reported as reactive lymph nodes. In addition, 23 (21.4%) patients had sarcoidosis, 16 (15%) had tuberculosis lymphadenitis, seven (6.5%) had lymphoma, one of each (0.9%) had benign epithelial cyst (0.9%), malign epithelial tumour (invasive ductal carcinoma of breast), chronic lymphocytic leukaemia (CLL), and adenocarcinoma metastasis (renal cell cancer). Conclusion When other non-invasive procedures are ineffective, mediastinoscopy is an efficient diagnostic method with high diagnostic value, which is applicable also in places other than advanced centres, with low morbidity and mortality.

RevDate: 2019-06-05

Flores-Díaz D, Arce C, Flores-Luna L, et al (2019)

Impact of invasive lobular carcinoma on long-term outcomes in Mexican breast cancer patients.

Breast cancer research and treatment, 176(1):243-249.

PURPOSE: The aim of this study was to compare the difference in disease-free survival (DFS) and overall survival (OS) between invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC) in our Hispanic population with breast cancer (BC).

METHODS: We retrospectively analyzed a database of 4533 non-metastatic BC patients treated for BC at the National Cancer Institute in Mexico (INCan) between 2006 and 2016. We compared clinical characteristics, treatment and survival between women with invasive ductal and invasive lobular BC. We evaluated differences between survival curves with the log-rank test and used Cox's proportional hazards model for the multivariate analysis.

RESULTS: Median follow-up time was 42.13 months (IQ25 25.2-IQ75 72.06). The median age was 50.9 years (IQ25 43.5-IQ75 59.8). DFS at 5 years was 80.8% for IDC versus 76.2% for ILC. 5 years OS was 88.7% for IDC versus 84.3% for ILC. Multivariate analysis showed that factors that negatively affected the 5-year DFS include: clinical stage III [hazard ratio (HR) 4.2, 95% CI 3.36-5.35; p < 0.001], triple negative phenotype (HR 1.4, 95% CI 1.08-1.81; p = 0.009), Ki67 ≥ 18 (HR 1.6, 95% CI 1.28-2.11; p < 0.001), and lobular histological type (HR 1.6, 95% CI 1.09-2.49; p = 0.017). Factors associated with a negative impact on OS were: clinical stage III (HR 4.5, 95% CI 3.15-6.54; p < 0.001), triple negative phenotype (HR 2.4, 95% CI 1.69-3.48; p < 0.001), and Ki67 ≥ 18% (HR 1.9, 95% CI 1.27-2.92; p = 0.02).

CONCLUSION: Our results highlight the different biology of ILC and show that long-term prognosis in terms of DFS is not as favorable as previously reported.

RevDate: 2019-04-18

Mikudova V, Rejlekova K, Gyarfas J, et al (2019)

Leptomeningeal Metastasis in a Breast Cancer Treated with Two Lines of Intrathecal Chemotherapy - a Case Report.

Klinicka onkologie : casopis Ceske a Slovenske onkologicke spolecnosti, 32(2):139-142.

BACKGROUND: Leptomeningeal metastasis (LM) in breast cancer is associated with a poor prognosis. Although no randomised trial has demonstrated that intrathecal chemotherapy actually prolongs survival, this treatment is considered standard of care in this setting. The prognosis of patients with LM is poor, with a median overall survival time of less than 6 months.

METHODS: Herein, we report a case of a young woman with breast cancer who presented with LM at the time of relapse and was subsequently treated with two lines of intrathecal chemotherapy that prolonged survival.

RESULTS: A 28-year old woman without a significant past medical history was diagnosed with triple-negative invasive ductal carcinoma. Eight months after adjuvant treatment she developed multiple brain metastases and LM developed subsequently 1 month after finishing whole brain irradiation. Initially, she was treated with a combination of methotrexate, cytarabine and dexamethasone intrathecally but after 3 months she presented with a worsening clinical status and increased numbers of cancer cells in cerebrospinal fluid. Subsequently, she received a combination of thiotepa and methotrexate intrathecally, which resulted in a prolonged response lasting 10 months. The patient died 32 months after initial diagnosis and 18 months from LM infiltration due to disease progression in the liver and lungs as well as LM.

CONCLUSION: The prognosis of patients with LM remains poor because of the limited effectiveness of currently available therapies; however, intrathecal chemotherapy could substantially prolong survival in selected patients.

RevDate: 2019-05-24

Khani F, Wobker SE, Hicks JL, et al (2019)

Intraductal carcinoma of the prostate in the absence of high-grade invasive carcinoma represents a molecularly distinct type of in situ carcinoma enriched with oncogenic driver mutations.

The Journal of pathology [Epub ahead of print].

Intraductal carcinoma of the prostate (IDC-P) most often appears associated with high-grade invasive prostate carcinoma (PCa), where it is believed to represent retrograde spread. However, IDC-P rarely occurs as an isolated finding at radical prostatectomy or with concurrent low-grade (Grade Group 1) invasive carcinoma. We hypothesized that isolated IDC-P (iIDC-P) in these unusual cases may represent a distinct in situ lesion and molecularly profiled 15 cases. iIDC-P was characterized by copy number alteration (CNA) profiling and targeted next generation sequencing in cases with sufficient tissue (n = 7). Immunohistochemistry for PTEN and ERG was performed on the total cohort (n = 15), where areas of iIDC-P and associated invasive disease were evaluated separately (n = 9). By copy number profiling, iIDC-P alterations were similar to those previously described in high-grade invasive PCa (PTEN, RB1, and CHD1 loss; MYC gain). However, in four cases, targeted sequencing revealed a striking number of activating oncogenic driver mutations in MAPK and PI3K pathway genes, which are extraordinarily rare in conventional PCa. In addition, pathogenic mutations in DNA repair genes were found in two cases of iIDC-P (BRCA2, CHEK2, CDK12) and other known PCa-associated mutations (FOXA1, SPOP) in two cases. Overall, ERG was expressed in 7% (1/15) of the iIDC-P lesions and PTEN was lost in 53% (8/15). Discordance for ERG or PTEN status between IDC-P and the low-grade PCa was observed in five of nine cases, with intact PTEN in the invasive tumor and PTEN loss in IDC-P in four. Despite a CNA profile similar to conventional PCa, iIDC-P is enriched with potentially targetable oncogenic driver mutations in MAPK/PI3K genes. Based on PTEN and ERG status, iIDC-P is not likely a precursor to the associated low-grade invasive PCa, but represents a molecularly unique in situ tumor of unclear clinical significance. Copyright © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

RevDate: 2019-05-05

Aldossary MY, Alquraish F, J Alazhri (2019)

A Case of Locally Advanced Breast Cancer in a 59-Year-Old Man Requiring a Modified Approach to Management.

The American journal of case reports, 20:531-536 pii:915377.

BACKGROUND Male breast cancer is rare, accounting for approximately 1% of all malignancies in men. The lack of awareness of this rare cancer results in delayed diagnosis and its aggressive behavior can result in poor prognosis. This report is of a case of locally advanced, high-grade breast cancer in a 59-year-old man who was reluctant to undergo diagnostic procedures, and describes the approach to clinical management. CASE REPORT A 59-year-old man presented with a large left breast mass with enlarged axillary lymph nodes. The patient had ignored the mass and declined all diagnostic procedures. After modifying the diagnostic workup and involving a psychiatrist, the patient agreed to undergo a modified radical mastectomy. Histopathology showed a high-grade invasive ductal carcinoma with lymph node metastasis. The breast cancer was triple-positive for human epidermal growth factor receptor 2 (HER2), estrogen receptor (ER), and progesterone receptor (PR). Adjuvant treatment included herceptin, tamoxifen, and radiation therapy. CONCLUSIONS This case demonstrates the importance of raising public awareness of breast cancer in men, and to assess and overcome the factors leading to delay in accessing medical attention. In challenging cases, modifying the diagnostic workup and the treatment approach with the least deviation from the standard of care, including counseling may be required.

RevDate: 2019-06-05

Lee J, Kim HE, Song YS, et al (2019)

miR-106b-5p and miR-17-5p could predict recurrence and progression in breast ductal carcinoma in situ based on the transforming growth factor-beta pathway.

Breast cancer research and treatment, 176(1):119-130.

PURPOSE: Ductal carcinoma in situ (DCIS) is well-known precursor of invasive ductal carcinoma (IDC). Parts of patients show recurrence as DCIS or IDC after local treatment, but there are no established markers predicting relapse. We analyzed changes in miRNA and oncogene expression during DCIS progression/evolution to identify potential markers predicting recurrence.

METHODS: Forty archival tissues diagnosed as primary or recurrent DCIS and DCIS adjacent to IDC were analyzed. MiRNA hierarchical clustering showed up-regulation of miR-17-5p and miR-106b-5p in recurrent DCIS and DCIS adjacent to IDC. Target genes were predicted based on pre-formed miRNA databases and PanCancer Pathway panel. MiRNAs were transfected into MCF-10A and MCF-7 cells; western blot analysis was performed with MCF-7 cell line to evaluate the effects on TGF-β downstream pathway.

RESULTS: miRNA hierarchical clustering showed 17 dysregulated miRNAs, including miR-17-5p and miR-106b-5p. Based on miRNA database and nCounter Pancancer pathway analysis, TGFβRII was selected as target of miR-106b-5p and miR-17-5p. MiR-106b-5p- and miR-17-5p-transfected MCF-7 cells showed decreased expression of TGFβRII, especially in cells transfected with both miRNAs.

CONCLUSION: miR-106b-5p and miR-17-5p might have a role in breast cancer recurrence and progression by suppressing TGF-β activity, leading to early breast cancer carcinogenesis.

RevDate: 2019-04-16

Raplee ID, Evsikov AV, C Marín de Evsikova (2019)

Aligning the Aligners: Comparison of RNA Sequencing Data Alignment and Gene Expression Quantification Tools for Clinical Breast Cancer Research.

Journal of personalized medicine, 9(2): pii:jpm9020018.

The rapid expansion of transcriptomics and affordability of next-generation sequencing (NGS) technologies generate rocketing amounts of gene expression data across biology and medicine, including cancer research. Concomitantly, many bioinformatics tools were developed to streamline gene expression and quantification. We tested the concordance of NGS RNA sequencing (RNA-seq) analysis outcomes between two predominant programs for read alignment, HISAT2, and STAR, and two most popular programs for quantifying gene expression in NGS experiments, edgeR and DESeq2, using RNA-seq data from breast cancer progression series, which include histologically confirmed normal, early neoplasia, ductal carcinoma in situ and infiltrating ductal carcinoma samples microdissected from formalin fixed, paraffin embedded (FFPE) breast tissue blocks. We identified significant differences in aligners' performance: HISAT2 was prone to misalign reads to retrogene genomic loci, STAR generated more precise alignments, especially for early neoplasia samples. edgeR and DESeq2 produced similar lists of differentially expressed genes, with edgeR producing more conservative, though shorter, lists of genes. Gene Ontology (GO) enrichment analysis revealed no skewness in significant GO terms identified among differentially expressed genes by edgeR versus DESeq2. As transcriptomics of FFPE samples becomes a vanguard of precision medicine, choice of bioinformatics tools becomes critical for clinical research. Our results indicate that STAR and edgeR are well-suited tools for differential gene expression analysis from FFPE samples.

RevDate: 2019-05-17

Erro R, Picillo M, Amboni M, et al (2019)

Comparing postural instability and gait disorder and akinetic-rigid subtyping of Parkinson disease and their stability over time.

European journal of neurology [Epub ahead of print].

BACKGROUND AND PURPOSE: Parkinson disease (PD) patients are classically classified according to two alternative motor subtyping methods: (i) tremor-dominant versus postural instability and gait disorder; (ii) tremor-dominant versus akinetic-rigid. The degree of overlap between the two classification systems at diagnosis of PD and their temporal stability, as well as the correspondence between the two systems, were examined over a follow-up period of 4 years.

METHODS: Newly diagnosed, untreated PD patients were classified as tremor-dominant versus postural instability and gait disorder and tremor-dominant versus akinetic-rigid at baseline and after 2 and 4 years.

RESULTS: There was a poor overlap between the two classification systems at any time point and baseline subtype status could not predict 4-year subtype membership. In fact, about half of our cohort shifted category during the first 2 years, regardless of the classification scheme adopted. A lower rate of shift was observed from 2- to 4-year follow-up.

CONCLUSIONS: The two classical motor subtyping methods of PD poorly overlap, which implies that a patient can be categorized as tremor-dominant in one classification system but not in the other. Moreover, their temporal instability undermines their prognostic value in the early stage of PD.

RevDate: 2019-05-19

Ren W, Guan W, Zhang J, et al (2019)

Pyridoxine 5'-phosphate oxidase is correlated with human breast invasive ductal carcinoma development.

Aging, 11(7):2151-2176.

Pyridoxine 5'-phosphate oxidase (PNPO) is a converting enzyme for an active form of vitamin B6. This study aims to evaluate the biological function and the regulatory mechanism of PNPO in human breast invasive ductal carcinoma (IDC). We unveiled for the first time that PNPO was upregulated in patients with IDC and was correlated with the overall survival of patients with metastasis at the later stages. Suppression of PNPO inhibited breast cancer cell proliferation, migration, invasion and colony formation, arrested cell cycle at the G2/M phase and induced cell apoptosis. PNPO was positively correlated with lncRNA MALAT1 which was negatively correlated with miR-216b-5p. PNPO was down-regulated and up-regulated by miR-216b-5p mimics and inhibitors, respectively, in breast cancer cells. A microRNA response element was found in both PNPO and MALAT1 transcripts for miR-216b-5p and the dual-luciferase reporter assay confirmed the binding of these transcripts. Knockdown of MALAT1 resulted in an increase of miR-216b-5p and a decrease of PNPO mRNA, indicating a regulatory mechanism of competing endogenous RNAs. Taken together, these results reveal the biological function and a regulatory mechanism of PNPO, in which the MALAT1/miR-216b-5p/PNPO axis may be important in IDC development. Targeting this axis may have therapeutic potential for breast cancer.

RevDate: 2019-05-10

Heeren N, T Fishman (2019)

A database seed for a community-driven material intensity research platform.

Scientific data, 6(1):23 pii:10.1038/s41597-019-0021-x.

The data record contains Material Intensity data for buildings (MI). MI coefficients are often used for different types of analysis of socio-economic systems and in particular for environmental assessments. Until now, MI values were compiled and reported ad-hoc with few cross-study comparisons. We extracted and converted more than 300 material intensity data points from 33 studies and provide the results in a comprehensive and harmonized database. Material intensity is reported as kilograms per gross floor area for 32 materials as primary data points. Furthermore, we augmented the data with secondary attributes for regional information, such as climate and socioeconomic indicators. The data are hosted on the version control platform GitHub using accessible data formats and providing detailed contribution guidelines. This "database seed" facilitates data analysis, accessibility, and future data contributions by the research community. In the Technical Validation we illustrate that consistency of the data and opportunities for further analysis. This database can serve scientists from various disciplines as a benchmark to determine typical ranges and identify outliers.

RevDate: 2019-06-03

Tollow P, Williams VS, Harcourt D, et al (2019)

"It felt like unfinished business, it feels like that's finished now": Women's experiences of decision making around contralateral prophylactic mastectomy (CPM).

Psycho-oncology, 28(6):1328-1334.

OBJECTIVE: Increasing numbers of women in the United Kingdom are choosing to have a contralateral prophylactic mastectomy (CPM) after diagnosis of breast cancer. Whilst research suggests that many experience high rates of psychological well-being after CPM, professional guidelines suggest CPM is "not required" for the majority of unilateral breast cancer patients, and some individuals consider the surgery to be controversial. Existing research has explored patients' reasons for seeking CPM; however, little is known about their experiences of decision making. This study aimed to investigate women's experiences of decision making around CPM in the United Kingdom.

METHODS: Semistructured qualitative interviews were conducted with 27 women, recruited through breast cancer support charities. All participants had CPM in the United Kingdom after a diagnosis of unilateral breast cancer, ductal carcinoma in situ (DCIS), or invasive ductal carcinoma. Data were analysed using thematic analysis.

RESULTS: Two main themes were generated from the analytic process: "sanity check" ("battling for CPM," "feeling stigmatised," "seeking similar others") and "reclaiming the body" ("being true to self," "moving forward"). Women described defending their decision to have CPM, concerns that their thoughts about surgery may be considered "abnormal," and seeking support from peers. The decision to have CPM was discussed in terms of their future relationship with their body and moving forward after cancer.

CONCLUSIONS: This study highlights the importance of interactions with health care professionals in the decision-making experience, the role of peer support, and the need to fully understand the potentially complex and multifaceted nature of each woman's decision to seek CPM.

RevDate: 2019-04-11

Wu SG, Zhang WW, Wang J, et al (2019)

Effect of 21-gene recurrence score in decision-making for surgery in early stage breast cancer.

OncoTargets and therapy, 12:2071-2078 pii:ott-12-2071.

Aim: We aimed to assess the role of 21-gene recurrence score (RS) in the decision-making for surgical treatment in early stage breast cancer and compared the outcomes between breast-conserving surgery (BCS) and mastectomy (MAST) among various 21-gene RS groups.

Methods: We included patients with stage T1-2M0M0 and estrogen receptor-positive breast invasive ductal carcinoma who underwent BCS + radiotherapy or MAST between 2004 and 2012 as part of the Surveillance, Epidemiology, and End Results program. Data were analyzed using binomial logistic regression, multivariate Cox proportional hazards models, and propensity score matching (PSM).

Results: We enrolled 34,447 patients including 22,681 (65.8%) and 11,766 (34.2%) who underwent BCS and MAST, respectively. Patients with high-risk RS were more likely to receive MAST. Multivariate analysis indicated that patients with intermediate-risk (P<0.001) and high-risk (P<0.001) RS had poor breast cancer-specific survival (BCSS), as compared to those with low-risk RS. Moreover, patients who underwent MAST also exhibited poor BCSS (P<0.001), as compared to those who underwent BCS. In low-risk (P<0.001) and intermediate-risk (P=0.020) RS groups, patients who underwent MAST had poor BCSS, as compared to those treated with BCS. However, BCSS was comparable between patients who underwent MAST and BCS (P=0.952); similar trends were also observed after PSM.

Conclusion: The 21-gene RS may impact the decision-making for surgery in early stage breast cancer. Our study provides additional support for a shared decision-making process for BCS when both local management options are appropriate choices regardless of the 21-gene RS.

RevDate: 2019-06-10

Deva Magendhra Rao AK, Patel K, Korivi Jyothiraj S, et al (2019)

Identification of lncRNAs associated with early-stage breast cancer and their prognostic implications.

Molecular oncology, 13(6):1342-1355.

Breast cancer is the most common malignancy among women, with the highest incidence rate worldwide. Dysregulation of long noncoding RNAs during the preliminary stages of breast carcinogenesis is poorly understood. In this study, we performed RNA sequencing to identify long noncoding RNA expression profiles associated with early-stage breast cancer. RNA sequencing was performed on six invasive ductal carcinoma (IDC) tissues along with paired normal tissue samples, seven ductal carcinoma in situ tissues, and five apparently normal breast tissues. We identified 375 differentially expressed lncRNAs (DElncRNAs) in IDC tissues compared to paired normal tissues. Antisense transcripts (~ 58%) were the largest subtype among DElncRNAs. About 20% of the 375 DElncRNAs were supported by typical split readings leveraging their detection confidence. Validation was performed in n = 52 IDC and paired normal tissue by qRT-PCR for the identified targets (ADAMTS9-AS2, EPB41L4A-AS1, WDFY3-AS2, RP11-295M3.4, RP11-161M6.2, RP11-490M8.1, CTB-92J24.3, and FAM83H-AS1). We evaluated the prognostic significance of DElncRNAs based on TCGA datasets and report that overexpression of FAM83H-AS1 was associated with patient poor survival. We confirmed that the downregulation of ADAMTS9-AS2 in breast cancer was due to promoter hypermethylation through in vitro silencing experiments and pyrosequencing.

RevDate: 2019-04-07

Shams R, Seifi-Alan M, Bandehpour M, et al (2019)

C-X-C Chemokine Receptor Type 7 (CXCR-7) Expression in Invasive Ductal Carcinoma of Breast in Association with Clinicopathological Features.

Pathology oncology research : POR pii:10.1007/s12253-019-00649-6 [Epub ahead of print].

C-X-C chemokine receptor type 7 (CXCR-7) is an atypical receptor for chemokines whose role in different stages of carcinogenesis has been evaluated in breast cancer cell lines and animal models. Moreover, it has been demonstrated to be a target of regulation by the tumor suppressor microRNA (miR)-100. In the present study, we assessed CXCR-7 expression in 60 breast cancer patients in association with clinicopathological and demographic data of patients. We also extracted the results of our previous work on miR-100 expression in the same cohort of patients to assess the correlation between miR-100 and CXCR-7 expression levels. Transcript levels of CXCR-7 were significantly higher in tumoral tissues compared with adjacent non-cancerous tissues (ANCTs) (Tumoral vs. ANCTs: 3.64 ± 1.8 vs. 0.73 ± 1.3, P = 0.000). A significant negative correlation was detected between CXCR-7 protein and miR-100 transcript levels (r = -0.526, P < 0.05). High CXCR-7 mRNA levels were significantly associated with tumor size (P = 0.01). Besides, high protein levels were more prevalent in higher TNM stages (P = 0.000). Moreover, high CXCR-7 protein levels were significantly associated with ER (P = 0.005) and PR (P = 0.02) status. The present work provides further evidence for the role of CXCR-7 in breast cancer and proposes the elimination of inhibitory effects of miR-100 on CXCR-7 expression as a mechanism for its up-regulation in breast cancer tissues.

RevDate: 2019-04-05

Tiiri E, Luntamo T, Mishina K, et al (2019)

Did Bullying Victimization Decrease After Nationwide School-Based Anti-Bullying Program? A Time-Trend Study.

Journal of the American Academy of Child and Adolescent Psychiatry pii:S0890-8567(19)30220-5 [Epub ahead of print].

OBJECTIVE: We assessed changes in traditional and cyberbullying victimization, and their associations with mental health, before and after the introduction of a nationwide anti-bullying program in Finnish schools in 2009.

METHOD: This time-trend assessment comprised two methodologically identical cross-sectional survey studies, with 2,061 adolescents in 2008 (response rate 90.2%) and 1,936 in 2014 (91.8%). Their mean age was 14.4 years. They completed questionnaires about traditional and cyberbullying, mental health and perceptions of school safety. Odds ratios (OR) and 95% confidence intervals are presented with 2008 as the reference year.

RESULTS: From 2008 to 2014, traditional victimization decreased from 28.9% to 19.1% (OR 0.5, 95% CI 0.4-0.7) among boys and from 23.2% to 17.4% (OR 0.7, 95% CI 0.6-0.9) among girls. Cyberbullying victimization remained fairly stable at 3.3% and 3.0% (OR 0.7, 95% CI 0.4-1.2) for boys and at 2.7% and 4.1% (OR 1.4, 95% CI 0.9-2.4) for girls. Combined traditional and cyberbullying victimization decreased from 6.1% to 3.9% (OR 0.5, 95% CI 0.4-0.8) among boys and from 7.5% to 6.7% (OR 0.8, 95% CI 0.6-1.2) among girls. Those suffering from both traditional and cyberbullying reported the highest mental health problems. Perceived school safety improved among boys, but not girls. Both reported greater efforts by teachers and fellow students to stop bullying.

CONCLUSION: Combined traditional and cyberbullying victimization was an indicator of comorbid mental health problems. Interventions that target both types of bullying, and are integrated with mental health promotion, are needed.

RevDate: 2019-04-05

Reddy A, Mullapudi NA, Kabeer KK, et al (2019)

Treatment of elderly breast cancer patients in a breast center in India.

Indian journal of cancer, 56(1):45-49.

CONTEXT: The management of breast cancer in older patients is challenging due to factors such as comorbidities, limited mobility, functional dependence, cognitive functions, and socioeconomic aspects. Data about the outcomes in elderly patients with breast cancer in our country are sparse.

AIMS: The aim of this study was to evaluate and compare the clinical and pathological variables, treatment, and survival outcomes of elderly women (those of 70 years and above) with women under 50 years and those between the ages of 50 and 69 years treated at our center.

SUBJECTS AND METHODS: Prospectively collected clinical and pathological data from January 2007 to December 2014 were recorded and entered into OncoCollect™ software. Statistical analysis was done using Microsoft R Open software. Survival analysis was estimated using Kaplan-Meier curves.

RESULTS: A total of 1226 Stage I-III breast cancer patients were treated between January 2007 and December 2014. Of these, 11.3% (139) were aged 70 years and above. Invasive ductal carcinoma was predominant and majority had Stage II disease and grade 1 tumors. Receptor positivity was observed in 79% of elderly patients and 9% had triple-negative disease. Primary hormone therapy was given to 7% of the patients and chemotherapy was administered to 12%. The 5-year overall survival for patients 70 years and older is 85%.

CONCLUSIONS: Elderly patients are more likely to have an indolent course with low grade and estrogen receptor-positive tumors. For healthy older women, treatment according to standard guidelines including surgery, chemotherapy, and radiation should be followed. However, for those who are unfit and cannot tolerate surgery, primary endocrine therapy is a suitable option.

RevDate: 2019-04-05

Te'Eni-Harari T, K Eyal (2019)

The Role of Food Advertising in Adolescents' Nutritional Health Socialization.

Health communication [Epub ahead of print].

Adolescents are heavily exposed to food advertising in their daily lives. Food ads tend to juxtapose unhealthy food products with overly thin models who promote these foods. This paradoxical presentation of food and body raises important questions about adolescents' perceptions of food ads and the body, as part of the larger realm of nutritional health. The study sheds light on adolescents' nutritional health socialization by exploring the role of food advertising as it intersects with other socialization agents, namely parents and peers. Adolescent's perceptions of and reactions to food ads, and the food products and models in these ads, are examined using the media practice model as the theoretical framework. In-depth interviews were conducted with 82 adolescents in middle- and high-school, taking into consideration their development, heightened vulnerability to messages about the body and appearances, and their lived experiences. The study's findings suggest that adolescents, though skeptical of ads, internalize the mediated thin ideal and expect models in ads to be thin, beautiful, and famous. Parents emerged as positive role models for nutritional health whereas peers are more paradoxical, emphasizing the importance of exercising along with a socially-oriented consumption of junk food. Socialization messages from parents, peers, and the media interact in shaping adolescents' reactions to food ads. Only minimal gender differences were found in adolescents' reactions to food ads and their approach to nutritional health. Mostly, female models are expected to meet more stringent standards of thinness and beauty than male models, especially among female adolescents.

RevDate: 2019-04-16

Campbell EJ, Dachs GU, Morrin HR, et al (2019)

Activation of the hypoxia pathway in breast cancer tissue and patient survival are inversely associated with tumor ascorbate levels.

BMC cancer, 19(1):307 pii:10.1186/s12885-019-5503-x.

BACKGROUND: The transcription factor hypoxia inducible factor (HIF) -1 drives tumor growth and metastasis and is associated with poor prognosis in breast cancer. Ascorbate can moderate HIF-1 activity in vitro and is associated with HIF pathway activation in a number of cancer types, but whether tissue ascorbate levels influence the HIF pathway in breast cancer is unknown. In this study we investigated the association between tumor ascorbate levels and HIF-1 activation and patient survival in human breast cancer.

METHODS: In a retrospective analysis of human breast cancer tissue, we analysed primary tumor and adjacent uninvolved tissue from 52 women with invasive ductal carcinoma. We measured HIF-1α, HIF-1 gene targets CAIX, BNIP-3 and VEGF, and ascorbate content. Patient clinical outcomes were evaluated against these parameters.

RESULTS: HIF-1 pathway proteins were upregulated in tumor tissue and increased HIF-1 activation was associated with higher tumor grade and stage, with increased vascular invasion and necrosis, and with decreased disease-free and disease-specific survival. Grade 1 tumors had higher ascorbate levels than did grade 2 or 3 tumors. Higher ascorbate levels were associated with less tumor necrosis, with lower HIF-1 pathway activity and with increased disease-free and disease-specific survival.

CONCLUSIONS: Our findings indicate that there is a direct correlation between intracellular ascorbate levels, activation of the HIF-1 pathway and patient survival in breast cancer. This is consistent with the known capacity of ascorbate to stimulate the activity of the regulatory HIF hydroxylases and suggests that optimisation of tumor ascorbate could have clinical benefit via modulation of the hypoxic response.

RevDate: 2019-04-04

Zhang L, Hao C, Wu Y, et al (2019)

Microcalcification and BMP-2 in breast cancer: correlation with clinicopathological features and outcomes.

OncoTargets and therapy, 12:2023-2033 pii:ott-12-2023.

Background: Microcalcification is a very important diagnostic information in breast cancer. The purpose of this study was to determine the relationship of clinicopathological features and prognosis of breast cancer with microcalcification and to detect biomarkers related to the possible mechanisms of microcalcifications.

Patients and methods: All 529 subjects with microcalcifications were selected from patients who had been examined using breast mammography. The control group did not have detectable microcalcifications, and was matched in a ratio of 1:3. The clinicopathological factors, progression-free survival (PFS), and overall survival were evaluated by SPSS.

Results: There was a significant difference in tumor size between the two groups, with larger tumors in the calcification group than the control group, and the proportion of patients in the calcification group with tumors of >5 cm was 20.4% vs 17.2% in the control group (P=0.041). The proportion of patients with lymph node metastasis in the calcification group was higher than that of the control group (35% vs 27.9%, P=0.027). The recurrence rate in ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) patients with microcalcification was higher than that in the control group (P=0.035 and 0.044). BMP-2 expression was higher in breast cancer tissues, especially in breast cancer tissues with microcalcifications. The recurrence rate in the BMP-2(+) group was higher than that in the BMP-2(-) group both in DCIS and IDC (P=0.044 and 0.049). Microcalcifications and the positive expression of BMP-2 were independent factors affecting the PFS of the breast cancer patients.

Conclusion: Through the analysis of this study, it was found that the prognosis of the patients with microcalcification was relatively poor. BMP-2 was highly expressed in the breast cancer with microcalcification and was associated with poor prognosis.

RevDate: 2019-04-08

Herent P, Schmauch B, Jehanno P, et al (2019)

Detection and characterization of MRI breast lesions using deep learning.

Diagnostic and interventional imaging, 100(4):219-225.

PURPOSE: The purpose of this study was to assess the potential of a deep learning model to discriminate between benign and malignant breast lesions using magnetic resonance imaging (MRI) and characterize different histological subtypes of breast lesions.

MATERIALS AND METHODS: We developed a deep learning model that simultaneously learns to detect lesions and characterize them. We created a lesion-characterization model based on a single two-dimensional T1-weighted fat suppressed MR image obtained after intravenous administration of a gadolinium chelate selected by radiologists. The data included 335 MR images from 335 patients, representing 17 different histological subtypes of breast lesions grouped into four categories (mammary gland, benign lesions, invasive ductal carcinoma and other malignant lesions). Algorithm performance was evaluated on an independent test set of 168 MR images using weighted sums of the area under the curve (AUC) scores.

RESULTS: We obtained a cross-validation score of 0.817 weighted average receiver operating characteristic (ROC)-AUC on the training set computed as the mean of three-shuffle three-fold cross-validation. Our model reached a weighted mean AUC of 0.816 on the independent challenge test set.

CONCLUSION: This study shows good performance of a supervised-attention model with deep learning for breast MRI. This method should be validated on a larger and independent cohort.

RevDate: 2019-04-26

Dekel S, Ein-Dor T, Ruohomäki A, et al (2019)

The dynamic course of peripartum depression across pregnancy and childbirth.

Journal of psychiatric research, 113:72-78.

OBJECTIVE: Peripartum depression (PPD) pertaining to depression in pregnancy and postpartum is one of the most common complications around childbirth with enduring adverse effects on mother and child health. Although psychiatric symptoms may improve or worsen over time, relatively little is known about the course of PPD symptoms and possible fluctuations.

METHODS: We applied a person-centered approach to examine PPD symptom patterns across pregnancy and childbirth. 824 women were assessed at three time points: first trimester (T1), third trimester (T2), and again at eight weeks (T3) postpartum. We assessed PPD symptoms, maternal mental health history, and childbirth variables.

RESULTS: Growth mixture modeling (GMM) analysis revealed four discrete PPD symptom trajectory classes including chronic PPD (1.1%), delayed (10.2%), recovered (7.2%), and resilient (81.5%). Delivery complications were associated with chronic PPD but also with the recovered PPD trajectory class. History of mental health disorders was associated with chronic PPD and the delayed PPD class.

CONCLUSION: The findings underscore that significant changes in a woman's depression level can occur across pregnancy and childbirth. While a minority of women experience chronic PDD, for others depression symptoms appear to significantly alleviate over time, suggesting a form of recovery. Our findings support a personalized medicine approach based on the woman's symptom trajectory. Future research is warranted to identify the mechanisms underlying modifications in PPD symptoms severity and those implicated in recovery.


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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