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21 Oct 2019 at 01:37
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Bibliography on: Invasive Ductal Carcinoma


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RJR: Recommended Bibliography 21 Oct 2019 at 01:37 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: 2019-10-17

Kanyılmaz G, Yavuz BB, Aktan M, et al (2019)

Prognostic Importance of Ki-67 in Breast Cancer and Its Relationship with Other Prognostic Factors.

European journal of breast health, 15(4):256-261 pii:ejbh-15-4-256.

Objective: The clinical feature of breast cancer is very heterogeneous because of the variable prognostic factors impact its behaviour. The aim of study is to find the prognostic importance of Ki-67 and to analyse the correlation between Ki-67 index and the other conventional prognostic factors in breast cancer patients.

Materials and Methods: Between 2010 and 2017, patients with invasive ductal carcinoma who received radiotherapy after surgery were included in study. A single pathologist re-defined of all cases retrospectively. Ki-67 were established three categories based on Ki-67 levels: low (<10%), intermediate (10-25%) and high (>25%).

Results: A total of 258 patients were included. 46 of 258 (18%) patients were in low, 82 of 258 (32%) patients were in intermediate and 130 of 258 (50%) patients were in high Ki-67 group. There were no correlations between menopausal status, age, and Ki-67 level. Low-pT stages tended to have low Ki-67 expression (p=0.07). Low-pN stages correlated with low Ki-67 values (p=0.007). Patients with ECE (+) were prone to have higher Ki-67 values (p=0.02). The significant correlation was seen between Ki-67 and tumour grading (p=<0.0001). Patients with LVI (+) had higher Ki-67 expression (p=0.007). Luminal A tumours were correlated with low Ki-67 group (p=<0.0001). Ki-67 values had significant effect on DFS (p=0.03) but not OS (p=0.09).

Conclusion: This study showed that high Ki-67 expression is associated with higher pT-stage, higher pN-stage, higher grade, ER/PR negativity, HER2/neu positivity, ECE and LVI positivity. The prognostic impact of Ki-67 was only demonstrated for DFS.

RevDate: 2019-10-17

Bao X, Shi R, Zhang K, et al (2019)

Immune Landscape of Invasive Ductal Carcinoma Tumor Microenvironment Identifies a Prognostic and Immunotherapeutically Relevant Gene Signature.

Frontiers in oncology, 9:903.

Background: Invasive ductal carcinoma (IDC) is a clinically and molecularly distinct disease. Tumor microenvironment (TME) immune phenotypes play crucial roles in predicting clinical outcomes and therapeutic efficacy. Method: In this study, we depict the immune landscape of IDC by using transcriptome profiling and clinical characteristics retrieved from The Cancer Genome Atlas (TCGA) data portal. Immune cell infiltration was evaluated via single-sample gene set enrichment (ssGSEA) analysis and systematically correlated with genomic characteristics and clinicopathological features of IDC patients. Furthermore, an immune signature was constructed using the least absolute shrinkage and selection operator (LASSO) Cox regression algorithm. A random forest algorithm was applied to identify the most important somatic gene mutations associated with the constructed immune signature. A nomogram that integrated clinicopathological features with the immune signature to predict survival probability was constructed by multivariate Cox regression. Results: The IDC were clustered into low immune infiltration, intermediate immune infiltration, and high immune infiltration by the immune landscape. The high infiltration group had a favorable survival probability compared with that of the low infiltration group. The low-risk score subtype identified by the immune signature was characterized by T cell-mediated immune activation. Additionally, activation of the interferon-α response, interferon-γ response, and TNF-α signaling via the NFκB pathway was observed in the low-risk score subtype, which indicated T cell activation and may be responsible for significantly favorable outcomes in IDC patients. A random forest algorithm identified the most important somatic gene mutations associated with the constructed immune signature. Furthermore, a nomogram that integrated clinicopathological features with the immune signature to predict survival probability was constructed, revealing that the immune signature was an independent prognostic biomarker. Finally, the relationship of VEGFA, PD1, PDL-1, and CTLA-4 expression with the immune infiltration landscape and the immune signature was analyzed to interpret the responses of IDC patients to immunotherapy. Conclusion: Taken together, we performed a comprehensive evaluation of the immune landscape of IDC and constructed an immune signature related to the immune landscape. This analysis of TME immune infiltration landscape has shed light on how IDC respond to immunotherapy and may guide the development of novel drug combination strategies.

RevDate: 2019-10-17

Kavesh MH, Sanchez D, JR Asirvatham (2019)

Invasive Lobular Carcinoma With Extensive Clear Cells: A Pitfall in Diagnosis.

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

Carcinomas in the breast with a predominantly clear cytoplasm are rare. In this article, we review the differential diagnosis of clear cell breast neoplasms and report a case of invasive lobular carcinoma with extensive clear cell morphology that was diagnosed as invasive ductal carcinoma, not otherwise specified, on ultrasound-guided biopsy. Lobular carcinomas with extensive clear cell change are unusual, but must be considered when evaluating a clear cell neoplasm in the breast.

RevDate: 2019-10-16

Sethy C, Goutam K, Nayak D, et al (2019)

Clinical significance of a pvrl 4 encoded gene Nectin-4 in metastasis and angiogenesis for tumor relapse.

Journal of cancer research and clinical oncology pii:10.1007/s00432-019-03055-2 [Epub ahead of print].

PURPOSE: In the present study, we have systematically examined the clinical significance of Nectin-4 (encoded by the PVRL-4 gene), a marker for breast cancer stem cells (CSCs), in cancer metastasis and angiogenesis using a variety of human specimens, including invasive duct carcinoma (IDC) with multiple grades, several types of primary tumors to local and distant relapses, lymph node metastases and circulating tumor cells (CTCs).

METHODS: Nectin-4 was overexpressed in more than 92% of samples with 65.2% Nectin-4-positive cells. The level of expression was increased with increasing tumor grade (GI-III) and size (T1-4) of IDC specimens.

RESULTS: More induction of Nectin-4 was noted in relapsed samples from a variety of tumors (colon, tongue, liver, kidney, ovary, buccal mucosa) in comparison to primary tumors, while paired adjacent normal tissues do not express any Nectin-4. A high expression of Nectin-4 along with other representative markers in CTCs and lymph node metastasis was also observed in cancer specimens. An increased level of Nectin-4 along with representative metastatic (CD-44, Sca1, ALDH1, Nanog) and angiogenic (Ang-I, Ang-II, VEGF) markers were noted in metastatic tumors (local and distant) in comparison to primary tumors that were correlated with different grades of tumor progression. In addition, greater expression of Nectin-4 was observed in secondary tumors (distant metastasis, e.g., breast to liver or stomach to gall bladder) in comparison to primary tumors.

CONCLUSION: Our study demonstrated a significant correlation between Nectin-4 expression and tumor grade as well as stages (p < 0.001), suggesting its association with tumor progression. Nectin-4 was overexpressed at all stages of metastasis and angiogenesis, thus appearing to play a major role in tumor relapse through the PI3K-Akt-NFκβ pathway.

RevDate: 2019-10-15

Shimmura H, Kuramochi H, Jibiki N, et al (2019)

Dramatic response of FOLFIRINOX regimen in a collision pancreatic adenocarcinoma patient with a germline BRCA2 mutation: a case report.

Japanese journal of clinical oncology pii:5587305 [Epub ahead of print].

Germline BRCA1 and BRCA2 mutations are the most common gene mutations in familial pancreatic adenocarcinoma. Several reports have demonstrated the utility of platinum-based chemotherapy for treating cancer patients who harbour a BRCA mutation. Here we discuss a 47-year-old Japanese female with no relevant past history who presented with epigastralgia and fever in September 2016. A computed tomography scan revealed a low-density, low-enhanced tumour 15 mm in diameter in the head of the pancreas. The pathological diagnosis was a ductal pancreatic carcinoma. A 6 mm low-enhanced metastatic tumour was also detected in segment 4 of the liver. Because she had early onset of the disease and a family history-her mother died of pancreatic adenocarcinoma at age 48-we considered a diagnosis of familial pancreatic adenocarcinoma. She received modified FOLFIRINOX. Two months after starting chemotherapy, she was diagnosed with an invasive ductal carcinoma in the right breast. FOLFIRINOX was continued for 8 cycles (4 months); the primary pancreatic adenocarcinoma shrank and the liver metastatic foci disappeared, but the size of the breast tumour increased. Total right breast excision and sentinel lymph node dissection were performed. FOLFIRINOX was continued and after 12 cycles (6 months), both her pancreatic adenocarcinoma and liver metastasis were no longer visible using imaging. Pancreatoduodenectomy was performed and the primary tumour had shrunk to 2.5 mm. Genetic testing revealed a germline BRCA2 mutation. The FOLFIRINOX regimen showed dramatic effects on the collision pancreatic but not on the breast cancer.

RevDate: 2019-10-15

Schmidt H, Connolly C, Jaffer S, et al (2019)

Evaluation of surgically excised breast tissue microstructure using wide-field optical coherence tomography.

The breast journal [Epub ahead of print].

BACKGROUND: Currently, positive margins at lumpectomy contribute to health care cost, patient anxiety, and treatment delay. Multiple technology solutions are being explored with the aim of lowering re-excision rates for breast-conserving surgery (BCS). We examined wide-field optical coherence tomography (WF-OCT), an innovative adjunct intraoperative imaging tool for tissue visualization of margins.

METHODS: This IRB-approved pilot study included women with invasive or in situ carcinoma scheduled for primary BCS. Lumpectomy specimens and any final/revised margins were imaged by optical coherence tomography immediately prior to standard histological processing. The optical coherence tomography used provided two-dimensional, cross-sectional, real-time depth visualization of the margin widths around excised specimens. A volume of images was captured for 10 × 10 cm tissue surface at high resolution (sub-30 μm) to a depth of 2 mm. Integrated interpretation was performed incorporating final pathology linked with the optical image data for correlation.

RESULTS: Wide-field optical coherence tomography was performed on 185 tissue samples (50 lumpectomy specimens and 135 additional margin shaves) in 50 subjects. Initial diagnosis was invasive ductal carcinoma (IDC) in 10, ductal carcinoma in situ (DCIS) in 14, IDC/DCIS in 22, invasive lobular carcinoma (ILC) in 2, ILC/DCIS in 1, and sarcoma in 1. Optical coherence tomography was concordant with final pathology in 178/185 tissue samples for overall accuracy of 86% and 96.2% (main specimen alone and main specimen + shave margins). Of seven samples that were discordant, 57% (4/7) were considered close (DCIS < 2 mm from margin) per final pathology.

CONCLUSION: Wide-field optical coherence tomography demonstrated concordance with histology at tissue margins, supporting its potential for use as a real-time adjunct intraoperative imaging tool for margin assessment. Further studies are needed for comprehensive evaluation in the intraoperative setting.

RevDate: 2019-10-12

Bartelt A, Leipsic J, C Weber (2019)

The new age of radiomic risk profiling: perivascular fat at the heart of the matter.

European heart journal pii:5585943 [Epub ahead of print].

RevDate: 2019-10-10

An J, Yoo Y, Kim HG, et al (2019)

Human Epidermal Growth Factor Receptor 2-Subtype Invasive Ductal Carcinoma Recurring as Basal-Human Epidermal Growth Factor Receptor 2-Subtype Squamous Cell Carcinoma.

Journal of breast cancer, 22(3):484-490.

Squamous cell carcinoma of the breast and its subtype, basal-human epidermal growth factor receptor 2 (HER2) phenotype, are very rare. Herein, we report a patient who developed recurrence of squamous cell carcinoma of the breast with basal-HER2 subtype 6 years after the initial diagnosis of invasive ductal carcinoma of the HER2 subtype. To the best of our knowledge, recurrence of invasive ductal carcinoma in the form of metaplastic squamous cell carcinoma of basal-HER2 subtype has not been reported previously. We present a pathological perspective of our experience.

RevDate: 2019-10-10

Ginter PS, Karagiannis GS, Entenberg D, et al (2019)

Tumor Microenvironment of Metastasis (TMEM) Doorways Are Restricted to the Blood Vessel Endothelium in Both Primary Breast Cancers and Their Lymph Node Metastases.

Cancers, 11(10): pii:cancers11101507.

Cancer cells metastasize from primary tumors to regional lymph nodes and distant sites via the lymphatic and blood vascular systems, respectively. Our prior work has demonstrated that in primary breast tumors, cancer cells utilize a three-cell complex (known as tumor microenvironment of metastasis, or TMEM) composed of a perivascular macrophage, a tumor cell expressing high levels of the actin-regulatory protein mammalian enabled (Mena), and an endothelial cell as functional "doorways" for hematogenous dissemination. Here, we studied a well-annotated case-control cohort of human invasive ductal carcinoma of the breast and metastatic lymph nodes from a separate breast cancer cohort. We demonstrate that in primary breast tumors, blood vessels are always present within tumor cell nests (TCNs) and tumor-associated stroma (TAS), while lymphatic vessels are only occasionally present in TCN and TAS. Furthermore, TMEM doorways not only exist in primary tumors as previously reported but also in lymph node metastases. In addition, we show that TMEM intravasation doorways are restricted to the blood vascular endothelium in both primary tumors and lymph node metastases, suggesting that breast cancer dissemination to distant sites from both primary tumors and metastatic foci in lymph nodes occurs hematogenously at TMEM doorways. TMEMs are very rarely detected at lymphatic vessels and do not confer clinical prognostic significance, indicating they are not participants in TMEM-associated hematogenous dissemination. These findings are consistent with recent observations that hematogenous dissemination from lymph nodes occurs via blood vessels.

RevDate: 2019-10-09

Moutinho-Guilherme R, Oyola JH, Sanz-Rosa D, et al (2019)

Correlation between apparent diffusion coefficient values in breast magnetic resonance imaging and prognostic factors of breast invasive ductal carcinoma.

Porto biomedical journal, 4(1):e27 pii:PBJ-D-18-00024.

Background: We wanted to examine whether the apparent diffusion coefficient values obtained by diffusion-weighted imaging techniques could indicate an early prognostic assessment for patients with Invasive Ductal Carcinoma and, therefore, influence the treatment decision making.

Objective: The main objective was to evaluate the correlation between the apparent diffusion coefficient values obtained by diffusion-weighted imaging and the key prognostic factors in breast invasive ductal carcinoma. Secondary objectives were to analyze the eventual correlations between magnetic resonance imaging findings and prognostic factors in breast cancer; and to perform a comparison between results in 1.5 and 3.0 T scanners.

Methods: Breast magnetic resonance imaging with diffusion-weighted imaging sequence was performed on 100 patients, who were proven histopathologically to have breast invasive ductal carcinoma. We compared the apparent diffusion coefficient values, obtained previous to biopsy, with the main prognostic factors in breast cancer: tumor size, histologic grade, hormonal receptors, Ki67 index, human epidermal growth factor receptor type 2, and axillary lymph node status. The Mann-Whitney U test and the Kruskal-Wallis analysis were used to establish these correlations.

Results: The mean apparent diffusion coefficient value was inferior in the estrogen receptor-positive group than in the estrogen receptor-negative group (1.04 vs 1.17 × 10-3 mm2/s, P = .004). Higher histologic grade related to larger tumor size (P = .002). We found association between spiculated margins and positive axillary lymph node status [odds ratio = 4.35 (1.49-12.71)]. There were no differences in apparent diffusion coefficient measurements between 1.5 and 3.0 T magnetic resonance imaging scanners (P = .513).

Conclusions: Low apparent diffusion coefficient values are related with positive expression of estrogen receptor. Larger tumors and spiculated margins are associated to worse prognosis. Rim enhancement is more frequently observed in estrogen receptor-negative tumors. There are no differences in apparent diffusion coefficient measurements between different magnetic resonance imaging scanners.

RevDate: 2019-10-09

Jakharia-Shah A, Wheatley H, M Beesley (2019)

Reminder of an important clinical lesson: breast cancer metastasis to the parotid gland.

BMJ case reports, 12(10): pii:12/10/e226494.

A 59-year-old woman presented to an otolaryngology clinic with an 8-week history of a painless lump over her left parotid gland. Her medical history included an invasive ductal carcinoma (33 mm) and a ductal carcinoma in situ (70 mm) of the right breast, for which she had a mastectomy and various adjuvant therapies. The primary tumour presented 8 years prior to the metachronous metastasis. This patient was a non-smoker and had no significant family history. Post-superficial parotidectomy pathology revealed the parotid gland tumour to be oestrogen receptor-positive and HER2 receptor-positive, thus ruling out the initial differential diagnosis of a pleomorphic adenoma. A consequential total parotidectomy with a posterolateral neck dissection was performed with sparing of the facial nerve. The patient recovered well having only encountered a self-resolving salivary fistula. She portrayed no signs of facial nerve palsy and subsequent imaging scans showed no abnormalities.

RevDate: 2019-10-09

Liu RL, Shi ZQ, Wang XY, et al (2019)

Two Highly Stable Proton Conductive Cobalt(II)-Organic Frameworks as Impedance Sensors for Formic Acid.

Chemistry (Weinheim an der Bergstrasse, Germany) [Epub ahead of print].

Metal-organic frameworks (MOFs) have been extensively explored as advanced chemical sensors in recent years. However, there are few studies on MOFs as acidic gas sensors, especially proton conductive MOFs. In this work, two new proton-conducting 3D MOFs, {[Co3 (p-CPhHIDC)2 (4,4'-bipy)(H2 O)]⋅2 H2 O}n (1) (p-CPhH4 IDC=2-(4-carboxylphenyl)-1 H-imidazole-4,5-dicarboxylic acid; 4,4'-bipy=4,4'-bipyridine) and {[Co3 (p-CPhHIDC)2 (bpe)(H2 O)]⋅3 H2 O}n (2) (bpe=trans-1,2-bis(4-pyridyl)ethylene) have been solvothermally prepared and investigated their formic acid sensing properties. Both MOFs 1 and 2 show temperature- and humidity-dependent proton conductive properties and exhibit optimized proton conductivities of 1.04×10-3 and 7.02×10-4 S cm at 98 % relative humidity (RH) and 100 °C, respectively. The large number of uncoordinated carboxylic acid sites, free and coordination water molecules, and hydrogen-bonding networks inside the frameworks are favorable to the proton transfer. By measuring the impedance values after exposure to formic acid vapor at 98 % or 68 % RH and 25 °C, both MOFs indicate reproducibly high sensitivity to the analyte. The detection limit of formic acid vapor is as low as 35 ppm for 1 and 70 ppm for 2. Meanwhile, both MOFs also show commendable selectivity towards formic acid among interfering solutions. The proton conducting and formic acid sensing mechanisms have been suggested according to the structural analysis, Ea calculations, N2 and water vapor absorptions, PXRD and SEM measurements. This work will open a new avenue for proton-conductive MOF-based impedance sensors and promote the potential application of these MOFs for indirectly monitoring the concentrations of formic acid vapors.

RevDate: 2019-10-04

Xu Q, Rangaswamy US, Wang W, et al (2019)

Evaluation of Newcastle Disease Virus Mediated Dendritic Cell Activation and Cross-priming Tumor-specific Immune Responses Ex Vivo.

International journal of cancer [Epub ahead of print].

We have developed an oncolytic Newcastle disease virus (NDV) that has potent in vitro and in vivo anti-tumor activities and attenuated pathogenicity in chickens. In this ex vivo study using the same recombinant NDV backbone with GFP transgene (rNDV), we found that rNDV induces maturation of monocyte-derived immature dendritic cells (iDCs) by both direct and indirect mechanisms, which promote development of antigen-specific T cell responses. Addition of rNDV directly to iDCs culture induced DC maturation, as demonstrated by the increased expression of costimulatory and antigen-presenting molecules as well as the production of type I interferons (IFNs). rNDV infection of the HER-2 positive human breast cancer cell line (SKBR3) resulted in apoptotic cell death, release of proinflammatory cytokines, and danger-associated molecular pattern molecules (DAMPs) including high-mobility group protein B1 (HMGB1) and heat shock protein 70 (HSP70). Addition of rNDV-infected SKBR3 cells to iDC culture resulted in greatly enhanced upregulation of the maturation markers and release of type I IFNs by DCs than NDV infected DCs only. When co-cultured with autologous T cells, DCs pre-treated with NDV-infected SKBR3 cells cross-primed T cells in an antigen-specific manner. Altogether, our data strongly support the potential of oncolytic NDV as efficient therapeutic agent for cancer treatment This article is protected by copyright. All rights reserved.

RevDate: 2019-10-04

Jayarajah U, Basnayake O, Wijerathne P, et al (2019)

A Rare Occurrence of Three Primary Malignancies of the Rectum, Breast, and Kidney in the Same Patient: A Case Report and Review of the Literature.

Case reports in surgery, 2019:1716029.

An increasing number of patients with multiple primary cancers are encountered due to improved cancer detection, widespread cancer screening, and better cancer treatment. Here, we report such a patient without a family history of malignancies or a known genetic predisposition developing three primary malignancies of the rectum, breast, and kidney. A 63-year-old female who underwent an anterior resection for rectal cancer was detected to have an elevated carcinoembryonic antigen (CEA) level during a routine follow-up, 8 years after the initial surgery. Clinical examination revealed a left breast lump which was confirmed as invasive ductal carcinoma (pT3 pN0 cM0). Imaging and colonoscopy excluded a local recurrence. However, a right renal lesion suggestive of a renal cell carcinoma was detected (pT1a). She underwent left mastectomy with a sentinel lymph node biopsy and a right partial nephrectomy with a curative intent. Postoperatively, CEA levels declined to normal limits. Management of multiple primary malignancies poses a major challenge. A multidisciplinary approach and tailored decision-making for the individual patient help with the optimum outcome.

RevDate: 2019-10-04

Al Khudari R, Homsi M, Al Zohaily H, et al (2019)

Primary Stromal Breast Sarcoma with Concomitant Contralateral Carcinoma: A Rare Case from Syria.

Case reports in oncological medicine, 2019:6460847.

Bilateral breast cancers are rare cases encountered and are usually the same type in both sides. Only very few cases were reported to have different histological types of neoplasia involving sarcoma. Moreover, sarcomas rarely originate from the breast as a primary lesion whereas the common presentation is having angiosarcoma following radiotherapy. In this report, we present a rare case of a Syrian 43-year-old woman having two distinct primary lesions in the breasts: invasive ductal carcinoma and contralateral stromal sarcoma.

RevDate: 2019-10-04

Jafarian AH, Kooshkiforooshani M, Rasoliostadi A, et al (2019)

Vascular Mimicry Expression in Invasive Ductal Carcinoma; A New Technique for Prospect of Aggressiveness.

Iranian journal of pathology, 14(3):232-235.

Background & Objective: In vascular (vasculogenic) mimicry (VM), tumoral cells mimic the endothelial cells and form the extracellular matrix-rich tubular networks. It has been proposed that VM is more extensive in aggressive tumors. This study was designed to investigate the rate of VM expression in the stromal cells of invasive ductal carcinoma (IDC) and to find its relationship with other clinicopathological factors.

Methods: In this cross-sectional study, 120 patients with histopathologic diagnosis of IDC who received mastectomy were included. The VM expression was determined by immunohistochemistry (IHC). The clinicopathologic data including age, tumor size, histological grade, clinical stage, axillary lymph node metastasis, hormonal receptors, and survival were documented.

Results: The mean (±SD) age of the patients was 51 (±13.83) years old. The stromal VM expression was detected in 16 of 120 patients (13.3%). Twelve specimens (75%) of positive VM expression group had grade 3 which was higher than negative VM expression group (9 cases, 8.65%; P<0.001). The VM expression showed statistically significant relationship with higher histologic grade higher clinical stage (stage 3) of the tumor (62.5% vs. 87%; P=0.003), the presence of axillary lymph node metastasis (95.6% vs. 55.8%; P<0.001), and positive HER-2 (100% vs. 31.1%; P<0.001); but not estrogen receptor (ER) or progesterone receptor (PR). However, age, tumor size and mortality rate were not significantly different among the patients with and without VM expression.

Conclusion: The stromal VM expression showed significant relationship with higher stage and grade of the tumor and the presence of nodal metastasis. The VM expression in IDC can be used as a marker for tumor aggressiveness.

RevDate: 2019-10-03

Patel DP, Herrick JS, Stoffel JT, et al (2019)

Reasons for cessation of clean intermittent catheterization after spinal cord injury: Results from the Neurogenic Bladder Research Group spinal cord injury registry.

Neurourology and urodynamics [Epub ahead of print].

INTRODUCTION: Clean intermittent catheterization (CIC) is recommended for bladder management after spinal cord injury (SCI) since it has the lowest complication rate. However, transitions from CIC to other less optimal strategies, such as indwelling catheters (IDCs) are common. In individuals with SCI who stopped CIC, we sought to determine how individual characteristics affect the bladder-related quality of life (QoL) and the reasons for CIC cessation.

METHODS: The Neurogenic Bladder Research Group registry is an observational study, evaluating neurogenic bladder-related QoL after SCI. From 1479 participants, those using IDC or urinary conduit were asked if they had ever performed CIC, for how long, and why they stopped CIC. Multivariable regression, among participants discontinuing CIC, established associations between demographics, injury characteristics, and SCI complications with bladder-related QoL.

RESULTS: There were 176 participants who had discontinued CIC; 66 (38%) were paraplegic and 110 (63%) were male. The most common reasons for CIC cessation among all participants were inconvenience, urinary leakage, and too many urine infections. Paraplegic participants who discontinued CIC had higher mean age, better fine motor scores, and lower educational attainment and employment. Multivariable regression revealed years since SCI was associated with worse bladder symptoms (neurogenic bladder symptom score), ≥4 urinary tract infections (UTIs) in a year was associated with worse satisfaction and feelings about bladder symptoms (SCI-QoL difficulties), while tetraplegia was associated better satisfaction and feelings about bladder symptoms (SCI-QoL difficulties).

CONCLUSIONS: Tetraplegics who have discontinued CIC have an improved QoL compared with paraplegics. SCI individuals who have discontinued CIC and have recurrent UTIs have worse QoL.

RevDate: 2019-10-02

Marsili C, Wilson CM, N Gura (2019)

Prospective Surveillance Screenings to Identify Physical Therapy Needs During Breast Cancer Diagnosis and Surviviorship: A Case Report.

Cureus, 11(7):e5265.

Breast cancer and its treatments can cause detrimental effects to function and quality of life (QoL). These patients do not conventionally receive physical therapy services until impairments and functional limitations have become extensive. Emerging treatment models advocate for early rehabilitation screenings and proactive interventions, which are termed prospective surveillance. The purpose of this case report was to describe two prospective surveillance screenings at initial diagnosis and survivorship and subsequent physical therapy episodes of care for a patient with breast cancer. A 39-year-old female was diagnosed with invasive ductal carcinoma of the right breast. Approximately three months after the initial diagnosis, the patient had a right nipple-sparing mastectomy and immediate reconstruction with an expander. In addition, one lymph node was removed and underwent a biopsy, which was negative for metastases. The patient was screened by a physical therapist after her initial cancer diagnosis at the breast multidisciplinary clinic. This was after her mastectomy with an expander; the therapist recommended an episode of outpatient physical therapy due to impairments in pain, fatigue, loss of range of motion, weakness, and limitations in performance of her activities of daily living. The patient was seen initially for five visits. She underwent her final reconstructive surgery one month after discharge from physical therapy. Six months after her final reconstructive surgery, she was screened by the same physical therapist in the cancer survivorship clinic. Once again, therapy was recommended due to pain as well as deficits to her range of motion, strength, and functional status. The second episode of care lasted 14 visits and the patient showed improvements in pain, range of motion, shoulder strength and gains in the patient-specific functional scale and upper extremity functional index. This case reflects the importance of prospective surveillance screenings to overall patient outcomes. This patient may not have otherwise received physical therapy and its associated benefits without the prospective screenings by the physical therapist.

RevDate: 2019-10-01

Gribsholt SB, Pedersen L, Richelsen B, et al (2019)

Validity of ICD-10 diagnoses of overweight and obesity in Danish hospitals.

Clinical epidemiology, 11:845-854 pii:214909.

Purpose: Health care databases may be a valuable source for epidemiological research in obesity, if diagnoses are valid. We examined the validity and completeness of International Classification of Diseases, 10th revision [ICD-10] diagnosis coding for overweight/obesity in Danish hospitals.

Patients and methods: We linked data from the Danish National Patient Registry on patients with a hospital diagnosis code of overweight/obesity (ICD-10 code E66) with computerized height and weight measurements made during hospital contacts in the Central Denmark Region Clinical Information System. We computed the positive predictive value (PPV) of the IDC-10 diagnosis of overweight/obesity, using a documented body mass index (BMI) ≥25 kg/m2 as gold standard. We also examined the completeness of obesity/overweight diagnosis coding among all patients recorded with BMI ≥25 kg/m2.

Results: Of all 19,672 patients registered with a first diagnosis code of overweight/obesity in the National Patient Registry, 17,351 patients (88.2%) had any BMI measurement recorded in the Central Denmark Region Clinical Information System, and 17,240 patients (87.6%) had a BMI ≥25 kg/m2, yielding a PPV of 87.6% (95% CI: 87.2-88.1). The PPV was slightly higher for primary diagnosis codes of overweight/obesity: 94.1% (95% CI: 93.3-94.8) than for secondary diagnosis codes: 86.1% (95% CI: 85.6-86.6). The PPV increased with higher patient age: from 75.3% (95% CI: 73.8-76.9) in those aged 18-29 years to 94.7% (95% CI: 92.6-96.9) in patients aged 80 years and above. Completeness of obesity/overweight diagnosis coding among patients recorded with BMI ≥25 kg/m2 was only 10.9% (95% CI: 10.8-11.0).

Conclusion: Our findings indicate a high validity of the ICD-10 code E66 for overweight/obesity when recorded; however, completeness of coding was low. Nonetheless, ICD-10 discharge codes may be a suitable source of data on overweight/obesity for epidemiological research.

RevDate: 2019-09-30

Sylvester-Armstrong KR, Rasmussen SA, Shoraka M, et al (2019)

Fetal sex discordance between noninvasive prenatal screening results and sonography: A single institution's experience and review of the literature.

Birth defects research [Epub ahead of print].

BACKGROUND: With the increasing availability of noninvasive prenatal screening (NIPS) and high-resolution ultrasound, more cases of sex discordance are being identified in routine clinical practice. This can be a source of much concern for families and clinicians. Knowledge about the limitations of NIPS and reasons for discordant results are critical for counseling parents.

AIMS: Here, we present three cases from a single tertiary care referral center. We also review the literature to address potential limitations of NIPS in correctly identifying fetal sex chromosomes.

MATERIALS AND METHODS: After Institutional Review Board approval, cases of discordant fetal sex were identified using ICD-9 and ICD-10 codes. In addition, departmental counseling database and cytogenetics laboratory logbooks were reviewed.

RESULTS: In our first case, a 37-year-old G4 P2012 underwent NIPS at 11 weeks gestation and Monosomy X (associated with Turner syndrome) was identified. Morphological sonographic assessment at 20 weeks gestation was consistent with a female fetus following an amniocentesis at 16 weeks that revealed normal 46, XX karyotype. During the third trimester, the patient was diagnosed with Stage IV invasive ductal carcinoma of the breast. Postnatal follow-up of the neonate was consistent with a phenotypic female. In the second case, a 22-year-old G2 P1001 obese female underwent NIPS at 14 weeks gestation and normal 46, XY karyotype was identified. Morphological sonographic assessment at 20 weeks was not consistent with a male fetus. The patient declined invasive testing. Postnatally, the karyotype was 46, XX and the neonate was phenotypically female. The reason for the discordant results was not identified. In the third case, a 25-year-old G1 P0 obese female underwent NIPS at 13 weeks gestation and normal 46, XY karyotype was identified. Morphological sonographic assessment at 20 weeks was indeterminate; however, follow-up at 24 weeks was consistent with a female fetus. The patient declined invasive prenatal testing. Postnatally, the karyotype was 46, XX, and the neonate was phenotypically female with uterus present on ultrasound. The reason for the discordant results was not identified.

DISCUSSION: Our cases demonstrate possible limitations of NIPS in correctly identifying sex chromosomes.

CONCLUSIONS: Providers and patients need to be aware of these limitations, and invasive diagnostic prenatal testing should be offered in cases of discordance between NIPS and sonographic sex assessment.

RevDate: 2019-09-30

Guo R, Si J, Xue J, et al (2019)

Changing patterns and survival improvements of young breast cancer in China and SEER database, 1999-2017.

Chinese journal of cancer research = Chung-kuo yen cheng yen chiu, 31(4):653-662.

Objective: Breast cancer in young females was usually considered more aggressive and requires aggressive therapy. We investigated whether early detection and improved treatments changed the patterns of characteristics, management and outcomes of young breast cancer patients over time.

Methods: Females under 40 years of age diagnosed with breast cancer during the periods 1999-2017 and 1999-2015 were identified in the Fudan University Shanghai Cancer Center (FUSCC) and the population-based Surveillance, Epidemiology, and End Results (SEER) registry, respectively. Clinicopathologic characteristics and treatment information were collected. Patients diagnosed before 2013 were followed up.

Results: The proportions of young breast cancer patients were 15.0% and 5.3% in the FUSCC and SEER cohorts, respectively. In the FUSCC cohort, there was a significant increase in the proportion of ductal carcinoma in situ (DCIS) (from 8.8% to 16.9%; P<0.0001) and it remained stable in SEER cohort. The proportion of T1-stage tumors increased dramatically in the FUSCC cohort (from 35.3% to 41.9%; P=0.008), whereas it decreased in SEER cohort (from 42.4% to 33.0%; P<0.0001). The percentage of estrogen receptor (ER)-positive cancers was consistently increased in both the invasive ductal carcinoma (IDC) and DCIS patients in the two cohorts. Breast-conserving surgery and immediate implant reconstruction after mastectomy both exhibited increased use over time in the FUSCC cohort. Both the FUSCC and SEER cohorts showed a significantly better prognosis in the recent time period.

Conclusions: With the increased early-stage and ER-positive diseases in young patients as well as better systemic treatment strategies, improved survival has been observed in recent years. There has been a substantial de-escalation in surgical therapies in young breast cancer patients.

RevDate: 2019-09-28

Srour MK, Donovan C, Chung A, et al (2019)

Flat epithelial atypia on core needle biopsy does not always mandate excisional biopsy.

The breast journal [Epub ahead of print].

Flat Epithelia Atypia (FEA) is a proliferative lesion of the breast where cells demonstrate columnar change and cytologic atypia. This lesion has been identified as distinct from the classic atypical hyperplasias (AH). While many patients undergo excisional biopsy, management of FEA identified on core needle biopsy (CNB) is controversial, and the rate of associated ductal carcinoma in situ (DCIS) or invasive cancer is not well defined. The aim of this study was to determine the upstage rate of FEA diagnosed by CNB. We identified patients from a prospectively maintained data base who had FEA diagnosed by CNB from 01/2010 to 07/2015. Patient variables collected included age at presentation, imaging findings, pathologic findings following surgical excision, and subsequent development of breast cancer. Of 132 patients, 62 (n = 62/132, 47.0%) patients had FEA associated with DCIS and invasive ductal carcinoma (IDC) on CNB and were excluded from analysis. Of the remaining 70 patients, median age was 52 (range 31-84) years. Thirty-two (45.7%) patients had FEA plus AH, 4 (5.7%) patients had FEA plus lobular carcinoma in situ (LCIS), and 34 (48.6%) patients had FEA alone or with another non-pathologic finding (pure FEA). Two (6.3%) patients with FEA plus AH had DCIS or IDC on subsequent excisional biopsy. Of the 34 patients with pure FEA who underwent excisional biopsy, only one (2.9%) was found to have IDC. Twenty-two (64.7%) patients with pure FEA who underwent excisional biopsy presented with calcifications on mammography. None of these patients had cancer on excisional biopsy, and 10 (45.5%) patients had AH (3 ADH, 3 ALH, and 4 both ALH and ADH). Twelve (n = 12/34, 35.3%) patients with pure FEA underwent CNB for a mass or asymmetry noted on imaging. Of these 12 patients, 9 (75.0%) had benign findings on excisional biopsy, two (16.7%) patients had AH, and one (8.3%) patient had IDC. Median follow-up was 4.6 years (IQR 3.1-6.5 years). Three (4.3%) patients subsequently developed IDC, two of which were in the contralateral breast. FEA is often found in combination with ADH and ALH as well as carcinoma on CNB. In our study, pure FEA was upstaged to cancer in only 2.9% of patients. Mammographic findings unlikely predict upstaging to malignancy. These findings suggest that excisional biopsy may not be warranted in patients with pure FEA and could be managed with close imaging surveillance.

RevDate: 2019-09-28

Ward WH, DeMora L, Handorf E, et al (2019)

Preoperative Delays in the Treatment of DCIS and the Associated Incidence of Invasive Breast Cancer.

Annals of surgical oncology pii:10.1245/s10434-019-07844-4 [Epub ahead of print].

BACKGROUND: Although treatment delays have been associated with survival impairment for invasive breast cancer, this has not been thoroughly investigated for ductal carcinoma in situ (DCIS). With trials underway to assess whether DCIS can remain unresected, this study was performed to determine whether longer times to surgery are associated with survival impairment or increased invasion.

METHODS: A population-based study of prospectively collected national data derived from women with a clinical diagnosis of DCIS between 2004 and 2014 was conducted using the National Cancer Database. Overall survival (OS) and presence of invasion were assessed as functions of time by evaluating five intervals (≤ 30, 31-60, 61-90, 91-120, 121-365 days) between diagnosis and surgery. Subset analyses assessed those having pathologic DCIS versus invasive cancer on final pathology.

RESULTS: Among 140,615 clinical DCIS patients, 123,947 had pathologic diagnosis of DCIS and 16,668 had invasive ductal carcinoma. For all patients, 5-year OS was 95.8% and unadjusted median delay from diagnosis to surgery was 38 days. With each delay interval increase, added relative risk of death was 7.4% (HR 1.07; 95% CI 1.05-1.10; P < 0.001). On final pathology, 5-year OS for noninvasive patients was 96.0% (95% CI 95.9-96.1%) versus 94.9% (95% CI 94.6-95.3%) for invasive patients. Increasing delay to surgery was an independent predictor of invasion (OR 1.13; 95% CI 1.11-1.15; P < 0.001).

CONCLUSIONS: Despite excellent OS for invasive and noninvasive cohorts, invasion was seen more frequently as delay increased. This suggests that DCIS trials evaluating nonoperative management, which represents infinite delay, require long term follow up to ensure outcomes are not compromised.

RevDate: 2019-09-27

Glantschnig C, Mattijssen F, Vogl ES, et al (2019)

The glucocorticoid receptor in brown adipocytes is dispensable for the systemic control of energy homeostasis through brown adipose tissue.

EMBO reports [Epub ahead of print].

Aberrant activity of the glucocorticoid (GC)/glucocorticoid receptor (GR) endocrine system has been linked to obesity-related metabolic dysfunction. Traditionally, the GC/GR axis has been believed to play a crucial role in adipose tissue formation and function in both, white (WAT) and brown adipose tissue (BAT). While recent studies have challenged this notion for WAT, the contribution of GC/GR signaling to BAT-dependent energy homeostasis remained unknown. Here, we have generated and characterized a BAT-specific GR-knockout mouse (GRBATKO), for the first time allowing to genetically interrogate the metabolic impact of BAT-GR. The HPA axis in GRBATKO mice was intact, as was the ability of mice to adapt to cold. BAT-GR was dispensable for the adaptation to fasting-feeding cycles and the development of diet-induced obesity. In obesity, glucose and lipid metabolism, insulin sensitivity, and food intake remained unchanged, aligning with the absence of changes in thermogenic gene expression. Together, we demonstrate that the GR in UCP1-positive BAT adipocytes plays a negligible role in systemic metabolism and BAT function, thereby opposing a long-standing paradigm in the field.

RevDate: 2019-09-27

Saadallah F, Bouraoui I, Naija L, et al (2019)

Coexistence of invasive ductal breast carcinoma and fibroadenoma.

The Pan African medical journal, 33:139 pii:PAMJ-33-139.

Fibroadenomas are the most common breast disease that occurs usually in young. The coexistence of an invasive ductal carcinoma and a fibroadenoma in the ipsilateral breast is extremely rare. We present the case of a 52 years woman, presented to us for an upper-outer breast lump. Breast imaging concluded to tow contiguous lesions, one of them was suspicious. She had a conservative surgery. Histology concluded to a fibroadenoma and an invasive ductal carcinoma.

RevDate: 2019-09-24

Wang YT, Chen ZJ, Zhang D, et al (2019)

[Effect of the primary tumor location on the prognosis of breast invasive ductal carcinoma patients treated with radical mastectomy].

Zhonghua zhong liu za zhi [Chinese journal of oncology], 41(9):686-692.

Objective: To analyze the clinicopathological features and prognosis of breast invasive ductal carcinoma patients receiving radical mastectomy according to the primary tumor location. Methods: From January 2008 to December 2008, 993 patients with breast invasive ductal carcinoma received radical mastectomy in Tianjin Medical University Cancer Institute and Hospital. Patients were grouped according to the primary tumor location when breast cancer was diagnosed. The clinicopathological characteristics and follow-up information of them was collected and analyzed retrospectively. Results: Of the 993 patients, primary tumor located in the upper-outer quadrant (UOQ) in 556 patients (56.0%), the lower-outer quadrant (LOQ) in 97 (9.8%), the central portion in 99 (10.0%), the upper-inner quadrant (UIQ) in 186 (18.7%), and the lower-inner quadrant (LIQ) in 55 (5.5%). Patients in the central portion tended to have larger tumors, and more patients in the upper-inner quadrant received endocrine therapy. The estimated 5-year disease-free survival (DFS) rates of patients with primary lesion in the UOQ, LOQ, central portion, UIQ and LIQ were 90.3%, 88.7%, 79.8%, 86.0% and 72.7%, respectively, with significant differences (P<0.001). The 5-year overall survival (OS) rates were 97.5%, 96.9%, 90.9%, 94.1% and 87.3%, respectively, with significant differences (P<0.001). Multivariate analysis showed that 5-year recurrence and metastasis risks were significantly increased in patients with primary lesion in the central portion, UIQ and LIQ compared to other groups (P<0.001), and 5-year mortality risks were increased in these three groups (P=0.002). Conclusion: Primary lesion located in central portion and inner quadrant is an independent adverse prognostic factor for patients with breast invasive ductal carcinoma patients receiving radical mastectomy.

RevDate: 2019-09-12

Peng GL, Li L, Guo YW, et al (2019)

CD8+ cytotoxic and FoxP3+ regulatory T lymphocytes serve as prognostic factors in breast cancer.

American journal of translational research, 11(8):5039-5053.

BACKGROUND: There is conflicting evidence regarding the prognostic value of cytotoxic T cell infiltration in breast cancer. The aims of this study were to detect the expression levels and localization of FoxP3 and CD8 in invasive ductal carcinoma of the breast and to investigate the correlations among FoxP3+ regulatory T cells (Tregs), CD8+ cytotoxic T lymphocytes (CTLs), clinicopathological features, and prognosis in patients with breast cancer.

METHODS: Immunohistochemistry was used to detect the expression levels and localization of FoxP3 and CD8. One-sample t-test, one-way analysis of variance, and Kaplan-Meier log-rank tests were used to analyze correlations between the expression levels of CD8 and FoxP3; Kaplan-Meier Log-rank test was used to analyze clinicopathological features to explore the prognostic significance of CD8 and FoxP3 in patients with breast cancer.

RESULTS: FoxP3 expression in the tumor bed was higher than that in the stroma, while CD8 was primarily expressed in the stroma. CD8 expression was associated with favorable prognostic factors. However, FoxP3 expression and an increased ratio of total FoxP3+ Tregs to CD8+ CTLs were significantly correlated with unfavorable prognostic factors. Additionally, an increased ratio was associated with molecular subtypes (ER+Her2+, ER+Her2-, ER-Her2+, and ER-Her2-) of breast cancer. Overexpression of FoxP3 and a high FoxP3+/CD8+ ratio were correlated with poor overall survival (OS) and disease-free survival (DFS). However, CD8 expression only affected OS in patients with breast cancer.

CONCLUSIONS: Tumor-infiltrating lymphocytes are localized variously depending on the subtype. CD8+ CTLs were associated with a good prognosis, while FoxP3+ Tregs were associated with adverse outcomes in patients with breast cancer. CD8+ CTLs and FoxP3+ Tregs are potential predictive prognostic factors for patients with breast cancer.

RevDate: 2019-09-23

Sherman M, Idan Z, D Greenbaum (2019)

Who Watches the Step-Watchers: The Ups and Downs of Turning Anecdotal Citizen Science into Actionable Clinical Data.

The American journal of bioethics : AJOB, 19(8):44-46.

RevDate: 2019-09-21

Santos CS, Ozgur R, Uzilday B, et al (2019)

Understanding the Role of the Antioxidant System and the Tetrapyrrole Cycle in Iron Deficiency Chlorosis.

Plants (Basel, Switzerland), 8(9): pii:plants8090348.

Iron deficiency chlorosis (IDC) is an abiotic stress often experienced by soybean, owing to the low solubility of iron in alkaline soils. Here, soybean lines with contrasting Fe efficiencies were analyzed to test the hypothesis that the Fe efficiency trait is linked to antioxidative stress signaling via proper management of tissue Fe accumulation and transport, which in turn influences the regulation of heme and non heme containing enzymes involved in Fe uptake and ROS scavenging. Inefficient plants displayed higher oxidative stress and lower ferric reductase activity, whereas root and leaf catalase activity were nine-fold and three-fold higher, respectively. Efficient plants do not activate their antioxidant system because there is no formation of ROS under iron deficiency; while inefficient plants are not able to deal with ROS produced under iron deficiency because ascorbate peroxidase and superoxide dismutase are not activated because of the lack of iron as a cofactor, and of heme as a constituent of those enzymes. Superoxide dismutase and peroxidase isoenzymatic regulation may play a determinant role: 10 superoxide dismutase isoenzymes were observed in both cultivars, but iron superoxide dismutase activity was only detected in efficient plants; 15 peroxidase isoenzymes were observed in the roots and trifoliate leaves of efficient and inefficient cultivars and peroxidase activity levels were only increased in roots of efficient plants.

RevDate: 2019-09-20

Gonzalez SM, Aguilar-Jimenez W, Alvarez N, et al (2019)

Cholecalciferol modulates the phenotype of differentiated monocyte-derived dendritic cells without altering HIV-1 transfer to CD4+ T cells.

Hormone molecular biology and clinical investigation pii:/j/hmbci.ahead-of-print/hmbci-2019-0003/hmbci-2019-0003.xml [Epub ahead of print].

Background Dendritic cells (DCs) play a crucial role during HIV-1 transmission due to their ability to transfer virions to susceptible CD4+ T cells, particularly in the lymph nodes during antigen presentation which favors the establishment of systemic infection. As mature dendritic cells (mDCs) exhibit a greater ability to transfer virions, compared to immature DCs (iDCs), maintenance of an iDC phenotype could decrease viral transmission. The immunomodulatory vitamin D (VitD) has been shown to reduce activation and maturation of DCs; hence, we hypothesized that it would reduce viral transference by DCs. Materials and methods We evaluated the effect of in vitro treatment with a precursor of VitD, cholecalciferol, on the activation/maturation phenotype of differentiated monocyte-derived DCs and their ability to transfer HIV-1 to autologous CD4+ T cells. Results Our findings show that although cholecalciferol decreases the activation of iDCs, it did not impact the maturation phenotype after LPS treatment nor iDCs' ability to transfer viral particles to target cells. Conclusion These findings suggest that despite cholecalciferol potentially modulates the phenotype of mucosal iDCs in vivo, such modulation might not impact the ability of these cells to transfer HIV-1 to target CD4+ T cells.

RevDate: 2019-09-20

Haynes HR, DSC Rose (2019)

Synchronous small lymphocytic lymphoma and metastatic breast carcinoma in axillary lymph nodes: Preservation of follicular architecture only in the portions of affected lymph nodes involved by metastatic carcinoma.

We present a case of metastatic ductal carcinoma of breast with the incidental discovery of small lymphocytic lymphoma (SLL) in regional axillary nodes. The co-occurence of metastatic carcinoma and low-grade lymphoma in lymph nodes is rare but well recognized. However, in this case, in the lymph nodes in which sizeable metastatic carcinoma deposits were present, the follicular structures between the sinusoidal carcinomatous infiltrates were preserved, whereas the uninvolved portions of the nodes were overrun by SLL. This is the first description of this phenomenon. We suggest that further cases displaying this previously unpublished pattern are collated in order that we may begin to investigate the underlying etiological mediators.

RevDate: 2019-09-19

Ardi Z, Richter-Levin A, Xu L, et al (2019)

The role of the GABAA receptor Alpha 1 subunit in the ventral hippocampus in stress resilience.

Scientific reports, 9(1):13513 pii:10.1038/s41598-019-49824-4.

Pre-pubertal stress increases post-traumatic stress disorder (PTSD) susceptibility. We have previously demonstrated that enriched environment (EE) intervention immediately after pre-pubertal stress protects from the effects of trauma in adulthood. Here, we examined whether exposure to EE would also be beneficial if applied after exposure to trauma in adulthood. We have recently shown that exposure to juvenile stress and under-water trauma (UWT) is associated with increased expression of GABAA receptor subunit α1 in the ventral hippocampus. However, differentiating between affected and unaffected individuals, this increased expression was confined to stress-exposed, behaviorally unaffected individuals, suggesting upregulation of α1 expression as a potential mechanism of resilience. We now examined whether EE-induced resilience renders increased expression of α1 in the ventral hippocampus redundant when facing a trauma later in life. Adult rats were exposed to UWT, with pre-exposure to juvenile stress, and tested in the open field and elevated plus maze paradigms four weeks later. EE exposure during juvenility prevented pre-pubertal stress-induced vulnerability, but not if performed following UWT in adulthood. Furthermore, juvenile EE exposure prevented the trauma-associated increase in α1 expression levels. Our findings emphasize the importance of early interventions in order to reduce the likelihood of developing psychopathologies in adulthood.

RevDate: 2019-09-19

Mackeprang PH, Vuong D, Volken W, et al (2019)

Benchmarking Monte-Carlo dose calculation for MLC CyberKnife treatments.

Radiation oncology (London, England), 14(1):172 pii:10.1186/s13014-019-1370-5.

BACKGROUND: Vendor-independent Monte Carlo (MC) dose calculation (IDC) for patient-specific quality assurance of multi-leaf collimator (MLC) based CyberKnife treatments is used to benchmark and validate the commercial MC dose calculation engine for MLC based treatments built into the CyberKnife treatment planning system (Precision MC).

METHODS: The benchmark included dose profiles in water in 15 mm depth and depth dose curves of rectangular MLC shaped fields ranging from 7.6 mm × 7.7 mm to 115.0 mm × 100.1 mm, which were compared between IDC, Precision MC and measurements in terms of dose difference and distance to agreement. Dose distributions of three phantom cases and seven clinical lung cases were calculated using both IDC and Precision MC. The lung PTVs ranged from 14 cm3 to 93 cm3. Quantitative comparison of these dose distributions was performed using dose-volume parameters and 3D gamma analysis with 2% global dose difference and 1 mm distance criteria and a global 10% dose threshold. Time to calculate dose distributions was recorded and efficiency was assessed.

RESULTS: Absolute dose profiles in 15 mm depth in water showed agreement between Precision MC and IDC within 3.1% or 1 mm. Depth dose curves agreed within 2.3% / 1 mm. For the phantom and clinical lung cases, mean PTV doses differed from - 1.0 to + 2.3% between IDC and Precision MC and gamma passing rates were > =98.1% for all multiple beam treatment plans. For the lung cases, lung V20 agreed within ±1.5%. Calculation times ranged from 2.2 min (for 39 cm3 PTV at 1.0 × 1.0 × 2.5 mm3 native CT resolution) to 8.1 min (93 cm3 at 1.1 × 1.1 × 1.0 mm3), at 2% uncertainty for Precision MC for the 7 examined lung cases and 4-6 h for IDC, which, however, is not optimized for efficiency but used as a gold standard for accuracy.

CONCLUSIONS: Both accuracy and efficiency of Precision MC in the context of MLC based planning for the CyberKnife M6 system were benchmarked against MC based IDC framework. Precision MC is used in clinical practice at our institute.

RevDate: 2019-09-18

Mikulincer M, Agam T, PR Shaver (2019)

A secure base for mindful dreaming: dispositional and contextually variable attachment security and the experiential quality of dreams.

Attachment & human development [Epub ahead of print].

In this study, we examined the utility of attachment theory for explaining individual differences in dream experiences. Seventy-six Israeli undergraduates completed a measure of attachment anxiety and avoidance and participated in a daily diary study for 15 consecutive days. Each evening, they rated their daily sense of attachment security. Each morning, they described in writing any dreams they recalled and rated the extent to which they (a) were aware of their sensations and mental states while dreaming and (b) reflected on their subjective experience during the dream. Two judges made similar ratings for each dream. Dispositional attachment anxiety and avoidance were associated with lower levels of within-dream awareness and reflection across the 15-day period. In addition, attachment security on a given day was associated with higher within-dream awareness and reflection that night. The findings provide new evidence concerning the contribution of attachment orientations to the experiential quality of dreams.

RevDate: 2019-09-18

van Kooten XF, Petrini LFT, Kashyap A, et al (2019)

Spatially Resolved Genetic Analysis of Tissue Sections Enabled by Microscale Flow Confinement Retrieval and Isotachophoretic Purification.

Angewandte Chemie (International ed. in English) [Epub ahead of print].

We have developed a method for spatially resolved genetic analysis of formalin-fixed paraffin-embedded (FFPE) cell block and tissue sections. This method involves local sampling using hydrodynamic flow confinement of a lysis buffer, followed by electrokinetic purification of nucleic acids from the sampled lysate. We characterized the method by locally sampling an array of points with a circa 200 μm diameter footprint, enabling the detection of single KRAS and BRAF point mutations in small populations of RKO and MCF-7 FFPE cell blocks. To illustrate the utility of this approach for genetic analysis, we demonstrate spatially resolved genotyping of FFPE sections of human breast invasive ductal carcinoma.

RevDate: 2019-09-18

Abbasi S, Le M, Sonier B, et al (2019)

All-optical Reflection-mode Microscopic Histology of Unstained Human Tissues.

Scientific reports, 9(1):13392 pii:10.1038/s41598-019-49849-9.

Surgical oncologists depend heavily on visual field acuity during cancer resection surgeries for in-situ margin assessment. Clinicians must wait up to two weeks for results from a pathology lab to confirm a post-operative diagnosis, potentially resulting in subsequent treatments. Currently, there are no clinical tools that can visualize diagnostically pertinent tissue information in-situ. Here, we present the first microscopy capable of non-contact label-free visualization of human cellular morphology in a reflection-mode apparatus. This is possible with the recently reported imaging modality called photoacoustic remote sensing microscopy which enables non-contact detection of optical absorption contrast. By taking advantage of the 266-nanometer optical absorption peak of DNA, photoacoustic remote sensing is efficacious in recovering qualitatively similar nuclear information in comparison to that provided by the hematoxylin stain in the gold-standard hematoxylin and eosin (H&E) prepared samples. A photoacoustic remote sensing system was employed utilizing a 266-nanometer pulsed excitation beam to induce photoacoustic pressures within the sample resulting in refractive index modulation of the optical absorber. A 1310-nanometer continuous-wave interrogation beam detects these perturbed regions as back reflected intensity variations due to the changes in the local optical properties. Using this technique, clinically useful histologic images of human tissue samples including breast cancer (invasive ductal carcinoma), tonsil, gastrointestinal, and pancreatic tissue images were formed. These were qualitatively comparable to standard H&E prepared samples.

RevDate: 2019-09-16

Ohe R, Aung NY, Tamura Y, et al (2019)

Diagnostic utility of CD205 in breast cancer: Simultaneous detection of myoepithelial cells and dendritic cells in breast tissue by CD205.

Histology and histopathology pii:HH-18-164 [Epub ahead of print].

BACKGROUND: CD205 can be used to detect myoepithelial cells (MECs) and dendritic cells (DCs) in breast tissue. However, the usefulness of CD205 immunostaining in the pathological diagnosis of breast tumors is not fully understood. The objective of this study was to re-evaluate CD205 co-expression with other MEC markers, such as p63 and CD10, in nonneoplastic and neoplastic breast tissue and to evaluate its pathological diagnostic utility in these types of breast cancer.

MATERIAL AND METHODS: Nonneoplastic breast tissue samples with a terminal duct lobular unit and duct were obtained from fibroadenoma and mastopathy patients. Neoplastic breast tissue samples included ductal carcinoma in situ (DCIS) (n=43) and invasive ductal carcinoma (IDC) (n=60), including the tubule-forming type (n=20). These specimens were investigated by CD205, p63, and CD10 immunostaining.

RESULTS: In addition to p63 and CD10, CD205 was expressed on MECs in nonneoplastic breast and DCIS tissue samples; CD205 was simultaneously detected on DCs that had infiltrated DCIS and IDC tumor nests. CD205 was expressed on cancer cells themselves in only 7.3% of the breast cancer samples. The number of intratumoral CD205⁺ DCs in tubular IDC was significantly higher than that in DCIS (P<0.01).

CONCLUSION: Because CD205 was simultaneously detected on MECs and DCs in the same breast tissue sections, it may be useful for distinguishing tubular IDC from DCIS.

RevDate: 2019-09-13

Gemici AA, Ozal ST, Hocaoglu E, et al (2019)

Relationship Between Shear Wave Elastography Findings and Histologic Prognostic Factors of Invasive Breast Cancer.

Ultrasound quarterly [Epub ahead of print].

OBJECTIVE: Shear wave elastography (SWE) is an adjunct to grayscale ultrasound examinations for evaluating breast masses. This study aimed to determine the SWE features that correlated with prognostic parameters for breast cancer.

METHODS: Between January 2018 and May 2018, 80 patients who were confirmed to have invasive cancers by core-needle biopsy and who were scheduled for surgery were imaged using B-mode ultrasound and SWE. Measurements were taken from a region of interest positioned over the stiffest part of the peripheral zone and mass. Three measurements were taken, and the average of the mean stiffness value was used for analysis.

RESULTS: The mean tumor size, elasticity value of tumors, and elasticity of the peripheral zone were 2.9 ± 1.48 cm (range, 0.6-8 cm), 154.8 ± 8.55 kPa (range, 116.25-179 kPa), and 171.34 ± 5.22 kPa (range, 150.95-182.43 kPa), respectively. The types of breast cancer included were invasive ductal carcinoma (n = 71 [88.75%]; 69 invasive ductal carcinoma not otherwise specified, 1 solid papillary carcinoma, and 1 invasive micropapillary carcinoma), invasive lobular carcinoma (n = 2 [2.5%]), mixed invasive ductal and lobular carcinoma (n = 4 [5%]), mucinous carcinoma (n = 2 [2.5%]), and metaplastic cancer (n = 1 [1.25%]). A strong correlation was found between mean elasticity values and tumor grade (P = 0.018) and between mean elasticity values and lymphovascular invasion (LVI) positivity (P = 0.008). There were no significant differences between SWE values and tumor diameter or between histological tumor characteristics and SWE.

CONCLUSIONS: We found that some clinicohistopathologic features of poor prognosis had higher elasticity values than those of favorable prognosis.

RevDate: 2019-09-12

Abdel Hadi M, Al Muhanna A, Alratroot J, et al (2019)

Angiocentric invasive ductal carcinoma: Breast images.

The breast journal [Epub ahead of print].

RevDate: 2019-09-12

Ali Mlees M (2019)

Diagnosis and surgical treatment of pathologic nipple discharge using ultrasound-guided wire localization of focal ductal dilatation.

The breast journal [Epub ahead of print].

Nipple discharge is the third breast complaint after pain and lumps. The modern high-resolution ultrasound techniques are becoming more sensitive for the visualization of intraductal changes especially focal ductal dilatation (FDD), hypothesized as a radiographic manifestation of the lesion itself and that ultrasound-guided wire localization of this finding would enable identification and excision of the causative lesion. The aim of this study was to evaluate the safety, feasibility, efficiency and outcome of ultrasound-guided wire localization of FDD as possible cause of pathological nipple discharge (PND). The present study was conducted on 56 patients with PND presented to Surgical Oncology Unit at General Surgery Department, Tanta University Hospital from January 2018 to January 2019. The patients subjected to ultrasound-guided wire localization of FDD on the day of surgery, the involved duct was cannulated with a lacrimal duct probe, the targeted tissue was excised, and the specimen was sent for histopathological examination. The patients' age ranged between 26 and 71 years with a mean age of 48 years. The bloody nipple discharge was the commonest presenting symptom in 44 out of 56 patients (78.5%). The duct dilatation on study ultrasound ranged from 2.1 to 3.7 mm with a mean of 2.6 mm. Preoperative ultrasound-guided wire localization of the site of FDD was successfully performed in all cases. Papilloma alone founded in 40 out of 56 patients (71.4%), papilloma + ductal carcinoma in situ (DCIS) in six patients (10.7%), papilloma + invasive ductal carcinoma in six patients (10.7%), DCIS in two patients (3.6%) and duct ectasia in two patients (3.6%). Ultrasound-guided wire localization of FDD is an easy and safe technique for evaluation, precise localization, and targeted excision of the underlying lesions of PND.

RevDate: 2019-09-11

Couto MSA, Firme VAC, Guerra MR, et al (2019)

The effect of redistribution of ill-defined causes of death on the mortality rate of breast cancer in Brazil.

Ciencia & saude coletiva, 24(9):3517-3528 pii:S1413-81232019000903517.

The relevance of breast cancer for women has driven research about mortality of this disease. However, these studies are affected by problems generated by deaths due to ill-defined causes (IDC). To highlight distortions caused by IDC in studies that evaluate mortality, we calculated the age-standardized mortality rates of breast cancer, with and without adjustment for IDC for the years 1990, 2000, and 2010. Then, panel data regression models were estimated and enabled us to identify that the adjustment for IDC: has elevated breast cancer mortality rate of Brazilian municipalities by 9% in the period considered; has drawn mortality rates of the South, Southeast, Northeast and North regions closer; has reduced the increasing trend of mortality by almost 60%, mainly in the Southeast and South regions; has increased, more sharply, the mortality in cities with less than 5 thousand inhabitants; has curbed the significance of most factors associated with breast cancer; has revealed that the effect of longevity and the public health expenditure may be overestimated. These results highlight the importance of adjustment for IDC in producing reliable mortality indicators.

RevDate: 2019-09-10

Shabihkhani M, Simpson JF, White MJ, et al (2019)

Artifactual Displacement of Ductal Carcinoma In Situ (ADDCIS) (Toothpaste Effect): A Mimicker of Invasive Ductal Carcinoma.

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

Needle tract displacement is a recognized mimicker of invasive ductal carcinoma (IDC). Artifactual displacement of ductal carcinoma in situ (ADDCIS) unassociated with needle tracts may occur secondary to mechanical compression of breast specimens but has not been systematically studied. We identified 16 cases of ADDCIS unassociated with needle tract changes; the majority (75%) were internal referrals to the breast pathology service to rule out IDC, 19% were received as external diagnostic consultations to rule out IDC, and 6% were routine second review cases originally diagnosed as IDC at an outside hospital. The majority (62.5%) of ADDCIS occurred in lumpectomies, whereas 25% occurred in mastectomies and 12.5% in core biopsies. ADDCIS foci ranged from <1 to 5 mm; however, all ADDCIS spanning >4 mm demonstrated a linear pattern of displacement. In all cases, ADDCIS involved mammary stroma in a nonlobular distribution; in half, ADDCIS extended between benign lobules. Immunohistochemistry revealed no myoepithelial cells around the ADDCIS (n=7), adding to the concern for IDC. However, in contrast to most IDC, ADDCIS lacked stromal reaction and showed degenerative, smudged chromatin. None of the 9 patients with significant follow-up (mean, 7 y) developed metastasis. All received further local therapy for DCIS (5 radiation, 4 completion mastectomy); 1 received adjuvant systemic therapy (hormone therapy for contralateral IDC). In conclusion, ADDCIS mimics IDC, particularly given its permeative pattern and absence of myoepithelial cells. ADDCIS is most common in lumpectomies but can occur in mastectomies or core biopsies. Diagnostic clues include smudged nuclear chromatin, lack of stromal response, and linear pattern of displacement in larger lesions. The benign follow-up without systemic therapy supports our view that ADDCIS does not represent true IDC.

RevDate: 2019-09-10

Hou R, Mazurowski MA, Grimm LJ, et al (2019)

Prediction of Upstaged Ductal Carcinoma in situ Using Forced Labeling and Domain Adaptation.

IEEE transactions on bio-medical engineering [Epub ahead of print].

OBJECTIVE: The goal of this study is to use adjunctive classes to improve a predictive model whose performance is limited by the common problems of small numbers of primary cases, high feature dimensionality, and poor class separability. Specifically, our clinical task is to use mammographic features to predict whether ductal carcinoma in situ (DCIS) identified at needle core biopsy will be later upstaged or shown to contain invasive breast cancer.

METHODS: To improve the prediction of pure DCIS (negative) versus upstaged DCIS (positive) cases, this study considers the adjunctive roles of two related classes: atypical ductal hyperplasia (ADH), a non-cancer type of breast abnormity, and invasive ductal carcinoma (IDC), with 113 computer vision based mammographic features extracted from each case. To improve the baseline Model A classification of pure vs. upstaged DCIS, we designed three different strategies (Models B, C, D) with different ways of embedding features or inputs.

RESULTS: Based on ROC analysis, the baseline Model A performed with AUC of 0.614 (95% CI, 0.496-0.733). All three new models performed better than the baseline, with domain adaptation (Model D) performing the best with an AUC of 0.697 (95% CI, 0.595-0.797).

CONCLUSION: We improved the prediction performance of DCIS upstaging by embedding two related pathology classes in different training phases.

SIGNIFICANCE: The three new strategies of embedding related class data all outperformed the baseline model, thus demonstrating not only feature similarities among these different classes, but also the potential for improving classification by using other related classes.

RevDate: 2019-09-06

McQuerry JA, Jenkins DF, Yost SE, et al (2019)

Pathway activity profiling of growth factor receptor network and stemness pathways differentiates metaplastic breast cancer histological subtypes.

BMC cancer, 19(1):881 pii:10.1186/s12885-019-6052-z.

BACKGROUND: Gene expression profiling of rare cancers has proven challenging due to limited access to patient materials and requirement of intact, non-degraded RNA for next-generation sequencing. We customized a gene expression panel compatible with degraded RNA from formalin-fixed, paraffin-embedded (FFPE) patient cancer samples and investigated its utility in pathway activity profiling in patients with metaplastic breast cancer (MpBC).

METHODS: Activity of various biological pathways was profiled in samples from nineteen patients with MpBC and 8 patients with invasive ductal carcinoma with triple negative breast cancer (TNBC) phenotype using a custom gene expression-based assay of 345 genes.

RESULTS: MpBC samples of mesenchymal (chondroid and/or osteoid) histology demonstrated increased SNAI1 and BCL2L11 pathway activity compared to samples with non-mesenchymal histology. Additionally, late cornified envelope and keratinization genes were downregulated in MpBC compared to TNBC, and epithelial-to-mesenchymal transition (EMT) and collagen genes were upregulated in MpBC. Patients with high activity of an invasiveness gene expression signature, as well as high expression of the mesenchymal marker and extracellular matrix glycoprotein gene SPARC, experienced worse outcomes than those with low invasiveness activity and low SPARC expression.

CONCLUSIONS: This study demonstrates the utility of gene expression profiling of metaplastic breast cancer FFPE samples with a custom counts-based assay. Gene expression patterns identified by this assay suggest that, although often histologically triple negative, patients with MpBC have distinct pathway activation compared to patients with invasive ductal TNBC. Incorporation of targeted therapies may lead to improved outcome for MpBC patients, especially in those patients expressing increased activity of invasiveness pathways.

RevDate: 2019-09-05

Delaunay T, Achard C, Grégoire M, et al (2020)

A Functional Assay to Determine the Capacity of Oncolytic Viruses to Induce Immunogenic Tumor Cell Death.

Methods in molecular biology (Clifton, N.J.), 2058:127-132.

Oncolytic immunotherapy efficacy relies partially on the induction of immunogenic tumor cell death following infection with oncolytic viruses (OV) to induce an antitumor immune response. Here, we describe a method to determine if an OV is able to induce such an immunogenic tumor cell death. This method consists in testing whether tumor cells lysed by an OV are able to induce the maturation of human monocyte-derived immature dendritic cells (Mo-iDC).

RevDate: 2019-09-04

Ericson KJ, Wu S, Lundy SD, et al (2019)

Diagnostic Accuracy of Prostate Biopsy for Detecting Cribriform Gleason Pattern 4 Carcinoma and Intraductal Carcinoma in Paired Radical Prostatectomy Specimens: Implications for Active Surveillance.

The Journal of urology [Epub ahead of print].

PURPOSE: Prostatic adenocarcinomas with cribriform morphology and/or intraductal carcinoma (CC/IDC) have higher recurrence and mortality rates after radiation and surgery. While the prognostic impact of these features is well-studied, concordance between CC/IDC on biopsy and prostatectomy has only recently gained attention. Our primary objective was to evaluate the diagnostic performance of biopsy for detecting CC/IDC in paired biopsy and prostatectomy specimens in a large contemporary cohort.

MATERIALS AND METHODS: Patients who underwent prostate biopsy or had biopsies reviewed prior to prostatectomy at a tertiary hospital between November 2017 and November 2018 were included. Sensitivity and specificity were calculated to assess concordance between CC/IDC on biopsy and prostatectomy. The association of biopsy-diagnosed CC/IDC with adverse pathology was assessed by multivariable regression.

RESULTS: 216/455 (47.5%) men that underwent prostatectomy had biopsy-identified CC/IDC. Biopsy sensitivity for CC/IDC was 56.5% and specificity was 87.2%. For active surveillance eligible men, sensitivity was 34.1% and specificity 88.1%. MRI-targeted biopsies did not improve sensitivity (53.5%). While the presence of prostatectomy-identified CC/IDC correlated with adverse pathologic findings, biopsy-identified CC/IDC (compared to CC/IDC negative biopsies) was not independently associated with adverse pathology, likely due to the low sensitivity of biopsy.

CONCLUSIONS: In this cohort, biopsy was not sensitive for CC/IDC detection and was not improved by MRI fusion; however, specificity was high suggesting that, when present on biopsy, CC/IDC may be considered in treatment planning algorithms.

RevDate: 2019-09-04

Cohen R, Moed A, Shoshani A, et al (2019)

Teachers' Conditional Regard and Students' Need Satisfaction and Agentic Engagement: A Multilevel Motivation Mediation Model.

Journal of youth and adolescence pii:10.1007/s10964-019-01114-y [Epub ahead of print].

Teachers' conditional positive regard and conditional negative regard are common motivational techniques in the classroom. This study investigated their respective effects on adolescent students' agentic engagement, while considering students' basic psychological needs for autonomy and relatedness as potential mediators. Data collected from 30 teachers and 651 7th to 10th graders (52% female) were used to test a multilevel mediation model. The results indicated that teachers' conditional negative regard undermined students' agentic engagement by frustrating both of their autonomy and relatedness needs. Teachers' conditional positive regard thwarted students' sense of autonomy, which consequently undermined their agentic engagement. The findings are discussed in terms of conditional positive and negative regard as undesirable classroom motivational practices and the mechanisms through which they operate. The discussion also notes the importance of investigating contextual factors at the classroom level.

RevDate: 2019-08-30

Fan M, Liu Z, Xie S, et al (2019)

Integration of dynamic contrast-enhanced magnetic resonance imaging and T2-weighted imaging radiomic features by a canonical correlation analysis-based feature fusion method to predict histological grade in ductal breast carcinoma.

Physics in medicine and biology [Epub ahead of print].

Tumour histological grade has prognostic implications in breast cancer. Tumour features in dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and T2-weighted (T2W) imaging can provide related and complementary information in the analysis of breast lesions to improve MRI-based histological status prediction in breast cancer. A dataset of 167 patients with invasive ductal carcinoma (IDC) was assembled, consisting of 72 low/intermediate-grade and 95 high-grade cases with preoperative DCE-MRI and T2W images. The data cohort was separated into development (n=111) and validation (n=56) cohorts. Each tumour was segmented in the precontrast and the intermediate and last postcontrast DCE-MR images and was mapped to the tumour in the T2W images. Radiomic features, including texture, morphology, and histogram distribution features in the tumour image, were extracted for those image series. Features from the DCE-MR and T2W images were fused by a canonical correlation analysis (CCA)-based method. The support vector machine (SVM) classifiers were trained and tested on the development and validation cohorts, respectively. SVM-based recursive feature elimination (SVM-RFE) was adopted to identify the optimal features for prediction. The areas under the ROC curves (AUCs) for the T2W images and the DCE-MRI series of precontrast, intermediate and last postcontrast images were 0.750±0.047, 0.749±0.047, and 0.788±0.045, respectively, for the development cohort and 0.715±0.068, 0.704±0.073, and 0.744±0.067, respectively, for the validation cohort. After the CCA-based fusion of features from the DCE-MRI series and T2W images, the AUCs increased to 0.751±0.065, 0.803±0.0600 and 794±0.060 in the validation cohort. Moreover, the method of fusing features between DCE-MRI and T2W images using CCA achieved better performance than the concatenation-based feature fusion or classifier fusion methods. Our results demonstrated that anatomical and functional MR images yield complementary information, and feature fusion of radiomic features by matrix transformation to optimize their correlations produced a classifier with improved performance for predicting the histological grade of IDC.

RevDate: 2019-08-30

Giles M, Graham L, Ball J, et al (2019)

Variations in indwelling urinary catheter use in four Australian acute care hospitals.

Journal of clinical nursing [Epub ahead of print].

AIMS AND OBJECTIVES: To identify the point prevalence of indwelling urinary catheters (IDCs) in adult inpatients in acute care hospitals, and to describe the indications for IDC insertion based on patient age, gender, specialty and hospital.

BACKGROUND: Catheter-associated urinary tract infections (CAUTIs) are preventable healthcare-associated infections. IDC duration is the strongest predictor of CAUTI, and little is known about characteristics of patients who receive an IDC.

DESIGN: Two single-day point prevalence surveys collected baseline patient data as part of a larger pre-post control-intervention study.

METHODS: Surveys were conducted at four acute care hospitals in NSW, Australia for all adult patients. Data collection included IDC presence, insertion details and urine culture collection. Point prevalence data were linked with electronically extracted patient demographic data. This study is presented in line with STROBE checklist (See Supplementary File 1).

RESULTS: Data from 1,630 patients were analysed; with 196 patients (12%) identified as having an IDC on the survey dates. IDC prevalence rates were higher in males (13%) than females (11%). Critical care had the highest rate of patients with IDCs (42%). Urine cultures were collected in 70 patients with an IDC (43%).

CONCLUSIONS: Findings indicated similar rates of IDC use in males and females, and there was no significant difference in age between patients with or without an IDC. However, indication for IDC varied by patient age and gender. High rates of urine culture collection may represent routine collection.

IDC use is found across genders, all age groups, and specialties. Nurses should be aware that any of their patients may have an IDC, and be particularly aware of certain indications based on patient age and gender. Routine urine culture collection is not advised, and instead nurses should be guided by clinical decision-making tools. This article is protected by copyright. All rights reserved.

RevDate: 2019-08-30

Sarhan MS, Mourad EF, Nemr RA, et al (2019)

An inoculum-dependent culturing strategy (IDC) for the cultivation of environmental microbiomes and the isolation of novel endophytic Actinobacteria.

The Journal of antibiotics pii:10.1038/s41429-019-0226-4 [Epub ahead of print].

The recent introduction of plant-only-based culture media enabled cultivation of not-yet-cultured bacteria that exceed 90% of the plant microbiota communities. Here, we further prove the competence and challenge of such culture media, and further introduce "the inoculum-dependent culturing strategy, IDC". The strategy depends on direct inoculating plant serial dilutions onto plain water agar plates, allowing bacteria to grow only on the expense of natural nutrients contained in the administered inoculum. Developed colonies are successively transferred/subcultured onto plant-only-based culture media, which contains natural nutrients very much alike to those found in the prepared plant inocula. Because of its simplicity, the method is recommended as a powerful tool in screening programs that require microbial isolation from a large number of diverse plants. Here, the method comfortably and successfully recovered several isolates of endophytic Actinobacteria represented by the six genera of Curtobacterium spp., Plantibacter spp., Agreia spp., Herbiconiux spp., Rhodococcus spp., and Nocardioides spp. Furthermore, two of the isolates are most likely novel species belonging to Agreia spp. and Herbiconiux spp.

RevDate: 2019-08-28

Mamtani A, Zabor EC, Rosenberger LH, et al (2019)

Was Reexcision Less Frequent for Patients with Lobular Breast Cancer After Publication of the SSO-ASTRO Margin Guidelines?.

Annals of surgical oncology pii:10.1245/s10434-019-07751-8 [Epub ahead of print].

BACKGROUND: The Society of Surgical Oncology and American Society for Radiation Oncology consensus guidelines defined a negative margin for breast-conserving surgery (BCS) as no ink on tumor, and implementation has reduced rates of additional surgery for patients with invasive ductal cancer (IDC). The outcomes for invasive lobular cancer (ILC) patients are uncertain.

METHODS: This study identified patients who had stage 1 or 2 ILC treated with BCS from January 2010 to February 2018. The guidelines were adopted 1 January 2014. Clinicopathologic characteristics, margin status, and reexcisions were compared before and after adoption of the guidelines and with those of IDC patients treated from May 2013 to February 2015.

RESULTS: Among 745 early-stage ILC patients undergoing BCT, 312 (42%) were treated before the guidelines and 433 (58%) after the guidelines. Most clinicopathologic characteristics were similar between the two groups, with differences in lobular carcinoma in situ, lymphovascular invasion, and node-positivity rates. The overall rates of additional surgery declined significantly after the guidelines (31.4 to 23.1%; p = 0.01), but the difference did not reach significance for reexcisions (19.9 to 15.2%; p = 0.12) or conversions to mastectomy (11.5 to 7.9%; p = 0.099) individually. Between eras, no difference in incidence or number of tumor on ink or ≤ 2 mm margins was observed (all p = 0.2). Larger tumors, younger age, and pre-guideline era were independently associated with additional surgery. Only younger age was predictive of mastectomy. Among 431 pre-guideline and 601 post-guideline IDC patients, reexcisions declined from 21.3 to 14.8% (p = 0.008), and conversion to mastectomy was rare (0.6%). The magnitude of reduction in any additional surgery (interaction, p = 0.92) and reexcisions (interaction, p = 0.56) was similar between ILC and IDC.

CONCLUSIONS: Despite differences in growth pattern and conspicuity, guideline adoption significantly reduced additional surgery among ILC patients, with a magnitude of benefit similar to that among IDC patients.

RevDate: 2019-08-29

Dobbels AA, AJ Lorenz (2019)

Soybean iron deficiency chlorosis high throughput phenotyping using an unmanned aircraft system.

Plant methods, 15:97 pii:478.

Background: Iron deficiency chlorosis (IDC) is an abiotic stress in soybean [Glycine max (L.) Merr.] that causes significant yield reductions. Symptoms of IDC include interveinal chlorosis and stunting of the plant. While there are management practices that can overcome these drastic yield losses, the preferred way to manage IDC is growing tolerant soybean varieties. To develop varieties tolerant to IDC, breeders may easily phenotype up to thousands of candidate soybean lines every year for severity of symptoms related to IDC, a task traditionally done with a 1-5 visual rating scale. The visual rating scale is subjective and, because it is time consuming and laborious, can typically only be accomplished once or twice during a growing season.

Results: The goal of this study was to use an unmanned aircraft system (UAS) to improve field screening for tolerance to soybean IDC. During the summer of 2017, 3386 plots were visually scored for IDC stress on two different dates. In addition, images were captured with a DJI Inspire 1 platform equipped with a modified dual camera system which simultaneously captures digital red, green, blue images as well as red, green, near infrared (NIR) images. A pipeline was created for image capture, orthomosaic generation, processing, and analysis. Plant and soil classification was achieved using unsupervised classification resulting in 95% overall classification accuracy. Within the plant classified canopy, the green, yellow, and brown plant pixels were classified and used as features for random forest and neural network models. Overall, the random forest and neural network models achieved similar misclassification rates and classification accuracy, which ranged from 68 to 77% across rating dates. All 36 trials in the field were analyzed using a linear model for both visual score and UAS predicted values on both dates. In 32 of the 36 tests on date 1 and 33 of 36 trials on date 2, the LSD associated with UAS image-based IDC scores was lower than the LSD associated with visual scores, indicating the image-based scores provided more precise measurements of IDC severity.

Conclusions: Overall, the UAS was able to capture differences in IDC stress and may be used for evaluations of candidate breeding lines in a soybean breeding program. This system was both more efficient and precise than traditional scoring methods.

RevDate: 2019-08-26

Nomikos A, Husain EA, AD Graham (2019)

Occult disease in reduction mammoplasties and prophylactic mastectomies.

The breast journal [Epub ahead of print].

The aim of this study was to determine the incidence of occult breast carcinoma and significant breast disease in clinically and radiologically unremarkable breast reduction specimens and prophylactic mastectomies. A retrospective search using specimen type codes was performed in the computerized histopathology archive from April 2007 to April 2016. The pathology results of 505 patients were analyzed (782 specimens). A total of 267 patients underwent simple reduction mammoplasties (10 unilateral), 20 had bilateral prophylactic mastectomies and 218 undertook contralateral symmetrizing or prophylactic mastectomy surgery following a history of breast cancer. Overall, normal (unremarkable) breast tissue was found in 42.6% of patients (n = 215), benign tissue (nonproliferative/proliferative disease without atypia) in 51.1% (n = 258), significant disease (LCIS/proliferative disease with atypia) in 5.5% (n = 28), and malignant disease (invasive/ductal carcinoma in situ) in 0.8% (n = 4). The incidence of significant breast pathology was statistically higher (P value < .0001) in prophylactic mastectomies (12.4%) compared to reduction mammoplasties (2.3%). There was however no significant increase in the incidence of malignancy between prophylactic mastectomies (1.2%) and reduction mammoplasties (0.6%). Even though the clear majority of resected tissue in reduction mammoplasties and prophylactic mastectomies is benign, our findings support the continued need for histological examination of these specimens for occult carcinoma and precursor lesions.

RevDate: 2019-08-24

Sadeh-Sharvit S (2019)

Use of Technology in the Assessment and Treatment of Eating Disorders in Youth.

Child and adolescent psychiatric clinics of North America, 28(4):653-661.

For countless young people, technology plays an essential role in their lives. However, its many advantages have not yet been widely applied to the treatment of youth with eating disorders. This article looks at how smartphone applications, Web conferencing, and other developments could widen the range of care available in a field where suitable support can be hard to find. Various barriers to treatment exist, such as cost, access, and the stigma attached to eating disorders, but existing and new technologies could overcome those obstacles, if clinicians are willing and able to meet the requirements associated with digitally enhanced treatment.

RevDate: 2019-09-02

Lahat E, Mikulincer M, Lifshin U, et al (2019)

Mothers never retire: Contextual priming of working models of mother affects adults' representations of self and romantic partners.

Journal of personality [Epub ahead of print].

OBJECTIVES: The main goal of these studies is to provide an experimental test of a core hypothesis based on attachment theory: Working models of mother are active in adults' minds and can bias their views of self and romantic partners.

METHOD: In two studies, we conducted clinical interviews to identify positive and negative core traits that participants used to describe their mothers. We then implicitly primed either positive or negative traits extracted from the interviews and compared this priming condition to control conditions in which we primed either positive or negative control traits (traits that described the mother of another study participant). Following this manipulation, we assessed participants' self-appraisals (Study 1) and explanations of their romantic partner's hurtful behaviors (Study 2).

RESULTS: Priming with one's mother's positive traits led to more positive views of self and romantic partner (compared with the effects of priming with positive control traits). In contrast, as compared to negative control traits, the priming of one's mother's negative traits led to less positive views of self and romantic partner.

CONCLUSIONS: Findings support the hypothesis that working models of mother play a causal role in shaping adults' representations of self and romantic partners.

RevDate: 2019-08-25

Escoter-Torres L, Caratti G, Mechtidou A, et al (2019)

Fighting the Fire: Mechanisms of Inflammatory Gene Regulation by the Glucocorticoid Receptor.

Frontiers in immunology, 10:1859.

For many decades, glucocorticoids have been widely used as the gold standard treatment for inflammatory conditions. Unfortunately, their clinical use is limited by severe adverse effects such as insulin resistance, cardiometabolic diseases, muscle and skin atrophies, osteoporosis, and depression. Glucocorticoids exert their effects by binding to the Glucocorticoid Receptor (GR), a ligand-activated transcription factor which both positively, and negatively regulates gene expression. Extensive research during the past several years has uncovered novel mechanisms by which the GR activates and represses its target genes. Genome-wide studies and mouse models have provided valuable insight into the molecular mechanisms of inflammatory gene regulation by GR. This review focusses on newly identified target genes and GR co-regulators that are important for its anti-inflammatory effects in innate immune cells, as well as mutations within the GR itself that shed light on its transcriptional activity. This research progress will hopefully serve as the basis for the development of safer immune suppressants with reduced side effect profiles.

RevDate: 2019-08-23

van Leenders GJLH, Kweldam CF, Hollemans E, et al (2019)

Improved Prostate Cancer Biopsy Grading by Incorporation of Invasive Cribriform and Intraductal Carcinoma in the 2014 Grade Groups.

European urology pii:S0302-2838(19)30612-8 [Epub ahead of print].

BACKGROUND: Grade groups (GGs) are an important parameter for therapeutic decision making in prostate cancer (Pca) patients. Invasive cribriform and/or intraductal carcinoma (CR/IDC) has an independent prognostic value for disease outcome, but are not included in the GG limiting their clinical use.

OBJECTIVE: To perform a proof-of-principle study incorporating CR/IDC in the current GG.

All prostate biopsies of 1031 men with screen-detected Pca between 1993 and 2000 were reviewed for the current GG (ranging from 1 to 5) and CR/IDC. The cribriform grade (cGrade) was equal to the GG if CR/IDC was present and GG minus 1 if not. GG1 was cGrade1 if intraductal carcinoma was absent.

INTERVENTION: Biopsy review for GG and CR/IDC. A total of 406 patients had received radical prostatectomy (RP), 508 radiotherapy (RT), 108 surveillance, and eight hormonal therapy, and the treatment was unknown for one patient. Outcome measurements and statistical analysis disease-specific survival (DSS), metastasis-free survival (MFS), and biochemical recurrence-free survival (BCRFS) after 15.1 yr (interquartile range 10.9-19.7 yr) follow-up were compared using Harrell's C-statistic.

RESULTS AND LIMITATIONS: The biopsy GGs were 486 GG1, 310 GG2, 104 GG3, 64 GG4, and 67 GG5; cGrade distributions were 738 cGrade1, 102 cGrade2, 91 cGrade3, 58 cGrade4, and 42 cGrade5. The cGrade had a better discriminative value than the GG for DSS (C-index 0.79; 95% confidence interval 0.74-0.83 vs 0.76; 0.71-0.82) and MFS (0.79; 0.74-0.84 vs 0.77; 0.72-0.82). The discriminative value for BCRFS after RP and RT was similar for both models. Different diagnostic, such as use of sextant biopsies, and therapeutic strategies in the 1990s are the limitations of this study.

CONCLUSIONS: The cGrade is a simple Pca grade modification with better discriminative values for DSS and MFS than the GG, particularly impacting decision making in men with current GG2 Pca.

PATIENT SUMMARY: Microscopic grading is an important factor for decision making in prostate cancer (Pca) patients. We show that a simple grade modification better predicts Pca outcome and might improve treatment choices.

RevDate: 2019-09-05

Santos Junior OR, da Costa Rocha MO, Rodrigues de Almeida F, et al (2019)

Speckle tracking echocardiographic deformation indices in Chagas and idiopathic dilated cardiomyopathy: Incremental prognostic value of longitudinal strain.

PloS one, 14(8):e0221028 pii:PONE-D-19-05931.

BACKGROUND: Chagas cardiomyopathy (CDC) is associated with a poor prognosis compared to other cardiomyopathies. Speckle tracking echocardiography (STE), which provides direct assessment of myocardial fiber deformation, may be useful in predicting prognosis.

OBJECTIVE: This study assessed STE in CDC and compared with idiopathic cardiomyopathy (IDC), and also examined the incremental prognostic information of STE over left ventricular ejection fraction (LVEF) in these patients.

METHODS: We enrolled 112 patients, age of 56.7 ± 11.8 years, 81 with CDC and 31 with IDC. STE indices were obtained at baseline in all patients. The endpoint was a composite of death, hospitalization for heart failure, or need for heart transplantation.

RESULTS: Patients with IDC had worse LV systolic function compared to CDC, with LVEF of 34.5% vs 41.3%, p = 0.004, respectively. After adjustment for LVEF, there were no differences in STE values between CDC and IDC. During a median follow-up of 18.2 months (range, 11 to 22), 26 patients met the composite end point (24%). LV longitudinal strain was a strong predictor of adverse events, incremental to LVEF and E/e' ratio (HR 1.463, 95% CI 1.130-1.894; p = 0.004). The risk of cardiac events increased significantly in patients with GLS > - 12% (log-rank p = 0.035).

CONCLUSIONS: STE indices were abnormal in patients with dilated cardiomyopathy, without differences between CDC and IDC. LV longitudinal strain was a powerful predictor of outcome, adding prognostic information beyond that provided by LVEF and E/e' ratio.

RevDate: 2019-08-22

Korzets Y, Lee G, Espin-Garcia O, et al (2019)

The Role of Partial Breast Radiation in the Previously Radiated Breast.

American journal of clinical oncology [Epub ahead of print].

OBJECTIVES: The aim of this study was to analyze breast cancer patients who previously had mantle-field or breast radiation (RT) followed by retreatment with external beam partial breast irradiation (EB PBI).

MATERIALS AND METHODS: We retrospectively reviewed all women with newly diagnosed early-stage breast cancer treated with lumpectomy and partial breast irradiation between 2007 and 2017 who had undergone prior chest or breast RT.

RESULTS: Of 11 patients recorded, 8 (73%) had Hodgkin lymphoma, and 3 (27%) had ipsilateral breast cancer diagnosis. Median age at initial and second diagnosis was 28 and 48 years, respectively. The lymphoma patients received a dose of 35 Gy in 16 to 20 fractions to a classic mantle-upper abdomen field. Patients with an initial diagnosis of breast cancer received whole-breast RT (2 with 50 Gy/25 fractions, 1 with 40 Gy in 16 fractions). Median time from initial to second diagnosis was 22.6 years (range, 13.5 to 32.6 y). All had early-stage (I to II) invasive ductal carcinoma and were treated with lumpectomy or repeat lumpectomy and EB PBI. Four received a dose of 45 Gy/25 fractions, 4 to 50 Gy/25 fractions, and 3 to 42.4 Gy/16 fractions. All patients received adjuvant systemic treatment. Two patients had toxicity, 1 had grade 1 induration, and the other had grade 2 fat atrophy and grade 1 fibrosis. One patient developed a contralateral breast cancer. No locoregional recurrences were reported at the median follow-up of 4.6 years (range, 0.6 to 10.5 y).

CONCLUSION: EB PBI after lumpectomy seems to be a safe and effective RT treatment option for selected patients with prior RT and localized early-stage breast cancer.

RevDate: 2019-08-22

Zhao S, Shao G, Chen P, et al (2019)

Diagnostic performance of minimum apparent diffusion coefficient value in differentiating the invasive breast cancer and ductal carcinoma in situ.

Journal of cancer research and therapeutics, 15(4):871-875.

Background: This study is to explore the role of the minimum apparent diffusion coefficient (ADC-min) value in the diagnosis of invasive breast cancer and ductal carcinoma in situ (DCIS).

Materials and Methods: A total of 196 breast cancer patients with pathologically verified lesions were included. They received diffusion-weighted imaging and dynamic breast magnetic resonance imaging before the pathological confirmation. The ADC-min value and its relationship with invasive ductal carcinoma (IDC), IDC-DCIS, and DCIS were analyzed.

Results: Of the 196 breast cancer patients, there were 115 (58.67%) cases of IDC, 53 (27.04%) cases of IDC-DCIS, and 28 (14.29%) cases of DCIS. The mean ADC-min values for IDC, IDC-DCIS, and DCIS were (0.96 ± 0.16) × 10-3, (1.10 ± 0.13) × 10-3, and (1.24 ± 0.17) × 10-3 mm 2/s, respectively. The mean ADC-min value of IDC was significantly lower than that of IDC-DCIS and that of IDC-DCIS was significantly lower than that of DCIS (P < 0.01). The mean ADC-min value was also significantly different between invasive cancer and DCIS (P < 0.01). The mean ADC-min value can be used in the differential diagnosis of DCIS, with a cutoff point of 1.02 × 10-3 mm 2/s (sensitivity of 92.9% and specificity of 57.7%).

Conclusions: The ADC-min values are significantly different among IDC, IDC-DCIS, and DCIS, with the lowest ADC-min values in IDC, followed by IDC-DCIS and DCIS. The ADC-min maybe used as a promising parameter to differentiate DCIS and invasive cancer.

RevDate: 2019-09-03
CmpDate: 2019-09-03

Cheng X, Yu RS, Xu M, et al (2019)

[The correlation between functional magnetic resonance imaging features and expression of Her-2 in breast cancer].

Zhonghua yi xue za zhi, 99(31):2440-2444.

Objective: To explore the correlation between dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), magnetic resonance diffusion-weighted imaging (DWI) images of breast cancer and human epidermal growth factor receptor-2 (Her-2) expression. Methods: A retrospective analysis of 84 patients with breast cancer confirmed by biopsy from January 2012 to December 2016 in Zhejiang University Lishui Hospital was conducted. The data of DCE-MRI, DWI scanning were collected before surgery and Her-2 was detected by immunohistochemistry (IHC). Then, all the patients were divided into Her-2 positive group and Her-2 negative group according to Her-2 expression. There were 44 cases in the Her-2 positive group and 40 cases in the Her-2 negative group. The differences in the characteristics of the lesion morphology, time-signal intensity curve (TIC), early enhancement rate and apparent diffusion coefficient (ADC) were compared, and their correlation with Her-2 expression was analyzed. Results: Of the 84 lesions, 12 were orthotopic ductal carcinoma, 6 were lobular carcinoma, and 66 were invasive ductal carcinoma. There were significant differences in lesion morphology (P=0.012) and TIC curve morphology (P=0.038) between Her-2 positive group and negative group. At the same time, the early enhancement rate (P=0.012) and ADC value (P=0.038) of Her-2 positive group were significantly higher than those of negative group. Except morphology of segmental lesions and TIC curve morphology, other characteristic parameters were correlated to Her-2 (all P<0.05). The correlation coefficients between early enhancement rate, ADC value and Her-2 expression were as high as 0.758 and 0.809 (all P<0.05). Conclusions: The morphology of breast cancer lesions, time-signal intensity curve, early enhancement rate and ADC value are all correlated with Her-2 expression.The early enhancement rate and ADC value are significantly positively correlated with Her-2 expression.

RevDate: 2019-08-21

Yetkin G, Celayir MF, Tanik C, et al (2019)

Male breast cancer: A 10 year retrospective case series in a tertiary care hospital.

JPMA. The Journal of the Pakistan Medical Association, 69(8):1209-1212.

Male breast cancer is a rare disease and it differs from breast cancer in women by some characteristics. The incidence of the disease has increased in the last 25 years. The records of male patients who underwent surgery for breast cancer between 2007 and 2017 were retrospectively reviewed in a tertiary care hospital in Istanbul, Turkey. The patients' ages, background, family history, clinical features, histopathological features of the tumour, its stage, the treatment and the survival were investigated. SPSS 15.0 for Windows programme was used for statistical analysis.Survival analysis was performed with Kaplan-Meier method.Determinants were analysed by univariate Cox regression analysis. A total of 15 patients were evaluated in our study. Fourteen patients had invasive ductal carcinoma and one patient had intraductal papillary carcinoma. The median followup period of the patients was 36 months The axillary lymph node metastasis positivity rate (number of metastatic lymph nodes/number of lymph nodes dissected) was statistically significantly higher in patients who died than in patients who survived.In univariate Cox regression analysis, the effects of age, tumour size, estrogen, progesterone, the presence of HER2/neu receptor and axillary metastasis on survival were not determined. We believe that raising awareness on male breast cancer in the community, genetic testing and screening mammography in high-risk patients will be useful in early diagnosis of the disease and improvement of its prognosis.

RevDate: 2019-08-20

Shenkman G, Stein Y, H Bos (2019)

The Mediating Role of Attachment Avoidance in the Association between Sexual Orientation and Mental Health.

Journal of homosexuality [Epub ahead of print].

The current study examined whether attachment avoidance mediates the association between being a sexual minority (gay men or lesbian women) and poorer mental health outcomes. For this purpose a community-dwelling sample of 350 gay men and lesbian women (M = 30.39, SD = 6.82) and 445 heterosexual men and women (M = 26.95, SD = 3.11) completed measures of attachment avoidance, depressive symptoms, anxiety symptoms and life satisfaction. Results showed that gay men and lesbians reported poorer mental health. Moreover, attachment avoidance had a mediating effect on the association between being a sexual minority and depressive symptoms, anxiety symptoms and life satisfaction. These findings are some of the first to suggest empirical support for the role of attachment avoidance in accounting for the mental health vulnerability of gay men and lesbians. The results contribute to a better understanding of the minority stress model and should be addressed by practitioners.

RevDate: 2019-08-22

Vaughan K, Ozaltin A, Mallow M, et al (2019)

The costs of delivering vaccines in low- and middle-income countries: Findings from a systematic review.

Vaccine: X, 2:100034 pii:100034.

Introduction: Information on immunization delivery costs (IDCs) is essential for better planning and budgeting for the sustainability and performance of national programs. However, delivery cost evidence is fragmented and of variable quality, making it difficult for policymakers, planners, and other stakeholders to understand and use. This study aimed to consolidate and summarize the evidence on delivery costs, answering the question: What are the unit costs of vaccine delivery across low- and middle-income countries (LMICs) and through a variety of delivery strategies?

Methods: We conducted a systematic review of over 15,000 published and unpublished resources from 2005 to 2018 that included IDCs in LMICs. We quality-rated and extracted data from 61 resources that contained 410 immunization delivery unit costs (e.g., cost per dose, cost per fully immunized child). We converted cost findings to a common year (2016) and currency (U.S. dollars) to ensure comparability across studies and settings. We performed a descriptive and gap analysis and developed immunization delivery cost ranges using comparable unit costs for single vaccines and schedules of vaccines.

Results: The majority of IDC evidence comes from low-income countries and Sub-Saharan Africa. Most unit costs are presented as cost per dose and represent health facility-based delivery.

Discussion: The cost ranges may be higher than current estimates used in many LMICs for budgeting: $0.16-$2.54 incremental cost per dose (including economic, financial, and fiscal costs) for single, newly introduced vaccines, and $0.75-$9.45 full cost per dose (economic costs) for schedules of four to eight vaccines delivered to children under one.

Conclusions: Despite increased attention on improving coverage and strengthening immunization delivery, evidence on the cost of delivery is nascent but growing. The cost ranges can inform planning and policymaking, but should be used with caution given their width and the few unit costs used in their development.

RevDate: 2019-08-20

Sun Y, Lei B, Q Huang (2019)

SOX18 Affects Cell Viability, Migration, Invasiveness, and Apoptosis in Hepatocellular Carcinoma (HCC) Cells by Participating in Epithelial-to-Mesenchymal Transition (EMT) Progression and Adenosine Monophosphate Activated Protein Kinase (AMPK)/Mammalian Target of Rapamycin (mTOR).

Medical science monitor : international medical journal of experimental and clinical research, 25:6244-6254 pii:915729.

BACKGROUND Hepatocellular carcinoma (HCC) is one of the most common malignancies around the world. It has been verified that the expression of SOX18 is correlated to poor clinical prognosis in patients with ovarian cancer, non-small cell lung cancer, or breast invasive ductal carcinoma. However, the expression pattern and biological function of SOX18 in HCC tissues remains unclear. In this study, we set out to investigate the associated biological function and potential molecular mechanism of the SOX18 gene in HCC cells. MATERIAL AND METHODS The mRNA and protein expression levels of experimental related genes were detected by real-time polymerase chain reaction and western blotting assay, respectively. The MTT method was used to assess cell viability, and cell apoptosis analysis was performed by means of FACScan flow cytometry. Wound-healing assay and Transwell analysis were performed to evaluate the ability of cell migration and invasiveness, respectively. RESULTS SOX18 was highly expressed in various HCC cell lines. In addition, SOX18 promoted cell viability, migration, and invasion and simultaneously induce cell apoptosis. SOX18 promoted epithelial-to-mesenchymal transition (EMT) progression, and SOX18 downregulation activated the autophagy signaling pathway AMPK/mTOR in HCC cells. CONCLUSIONS SOX18 downregulation in HCC cells suppressed cell viability and metastasis, induced cell apoptosis and hindered the occurrence and progression of tumor cells by participating in the EMT process and regulating the autophagy signaling pathway AMPK/mTOR.

RevDate: 2019-08-20

Lin SC, Ko RT, Kang BH, et al (2019)

Intraductal Carcinoma of Salivary Gland Originating from an Intraparotid Lymph Node: A Case Report.

The Malaysian journal of pathology, 41(2):207-211.

INTRODUCTION: Salivary gland intraductal carcinoma (IDC) is rare. We present the second case of IDC originating from an intraparotid lymph node (LN) with a more detailed description of the histogenesis, immunohistochemistry (IHC) and updated molecular information.

CASE REPORT: An 87-year-old male had a tumour nodule over the left parotid tail for about 20 years. Physical examinations revealed a 4.5 cm soft, non-tender and fixed mass. After the left parotidectomy, pathology confirmed the diagnosis of IDC arising within an intraparotid lymph node. The cystic component of the tumour was lined by single to multilayered ductal cells with micropapillary growth pattern. The solid part showed intraductal proliferation of neoplastic cells in solid, cribriform, micropapillary and Roman bridge-like structure. By immunohistochemistry (IHC), the tumour cells were positive for S-100, CK (AE1/AE3), mammaglobin, SOX10, and estrogen receptor (ER), with myoepithelial cell rimming highlighted by positive p63 and calponin IHC stains. The prognosis of this patient is excellent after complete excision.

DISCUSSION: The mechanism of salivary gland tumour arising in the intra-parotid gland LN was assumed to be related to salivary duct inclusion within the intraparotid gland LN which is a normal occurrence during embryology development. Although the terminology may raise some confusion about the relationship between IDC and conventional salivary duct carcinoma (SDA), they are different in immunophenotype and clinicopathologic features. IDC is characterised by S100 (+) ER (+) with predominant intraductal growth and excellent prognosis; while SDC features S100 (-) androgen receptor (+) with predominant invasive growth and aggressive behavior. Recent discovery of recurrent RET gene rearrangement in IDC but not SDC also supports that IDC is not precursor lesion of the SDC.

RevDate: 2019-08-19

Chen JR, Zhao JG, Zhu S, et al (2019)

Clinical and oncologic findings of extraprostatic extension on needle biopsy in de novo metastatic prostate cancer.

Asian journal of andrology pii:264574 [Epub ahead of print].

This study aimed to explore the clinical and oncologic findings in patients with de novo metastatic prostate cancer (mPCa) and extraprostatic extension (EPE) on biopsy. We retrospectively evaluated data on 630 patients with de novo mPCa between January 2009 and December 2017 in the West China Hospital (Chengdu, China), including evaluating the relationships between EPE and other variables and the association of EPE with survival outcomes by the Chi-square test, Kaplan-Meier curves, and the Cox proportional-hazards model. EPE was found in 70/630 patients, making a prevalence of 11.1%. The presence of EPE on biopsy was associated with higher Gleason scores and higher incidence of neuroendocrine differentiation (NED), intraductal carcinoma of the prostate (IDC-P), and perineural invasion (PNI). Compared with those without EPE, patients with EPE had shorter castration-resistant prostate cancer-free survival (CFS; median: 14.1 vs 17.1 months, P = 0.015) and overall survival (OS; median: 43.7 vs 68.3 months, P = 0.032). According to multivariate analysis, EPE was not an independent predictor for survival. Subgroup analyses demonstrated that patients with favorable characteristics, including negative NED or IDC-P status, Eastern Cooperative Oncology Group (ECOG) score <2, and prostate-specific antigen (PSA) <50 ng ml-1, had worse prognoses if EPE was detected. In patients with PSA <50 ng ml-1, EPE was a negative independent predictor for OS (hazard ratio [HR]: 4.239, 95% confidence interval [CI]: 1.218-14.756, P = 0.023). EPE was strongly associated with other aggressive clinicopathological features and poorer CFS and OS. These data suggest that EPE may be an indicator of poor prognosis, particularly in patients, otherwise considered likely to have favorable survival outcomes.

RevDate: 2019-08-22

Maciolek LM, Harmon TS, He J, et al (2019)

Pseudoangiomatous Stromal Hyperplasia of the Breast: A Rare Finding in a Male Patient.

Cureus, 11(6):e4923.

Pseudoangiomatous stromal hyperplasia (PASH) in male patients is a rare condition that represents a hormonally-induced proliferation of mesenchymal tissue of the breast. This benign pathology is often undiagnosed due to many reasons. When PASH presents as a breast mass, it appears innocent, developing as a smooth and well-circumscribed tumor. Furthermore, it does not elicit suspicious findings on imaging. These points often halt further investigation of many breast abnormalities. Breast masses are statistically most likely to be gynecomastia when they arise in men. However, they are important to investigate because, although rare, breast cancer can occur in men. Furthermore, the benign conditions of the breast that commonly affect women can also impact male patients. It is oftentimes overlooked that men too can experience hormonal stimulation of the breast tissue. The following case describes this rare but important instance of a male patient diagnosed with PASH following a previous diagnosis of infiltrative ductal carcinoma in situ of the contralateral breast.

RevDate: 2019-08-16

Cohen OBS, Shahar G, A Brunstein Klomek (2019)

Peer Victimization, Coping Strategies, Depression, and Suicidal Ideation Among Young Adolescents.

Crisis [Epub ahead of print].

Background: Victimization by bullying among adolescents is a widespread phenomenon associated with depression and suicidal ideation. Coping with bullying may include aggressive responding and self-blame. Aims: The purpose of this study was to examine the role adolescent self-blame and aggression - representing coping with peer bullying - in depression and suicide ideation. Method: We recruited 97 "pure" victims (41 girls; mean age = 12.69, SD = .80) identified from a sample of 505 adolescents (242 girls; mean age = 12.73, SD = .81) from two Israeli high schools. Self-report questionnaires were used to assess victimization, aggressive responses, self-blame, depression, and suicide ideation. Results: Self-blame in the face of peer bullying was uniquely associated with both depression and suicide ideation. The effect was robust even after controlling for level of victimization. No direct effect of aggressive coping or moderating effects of self-blame or aggression on the association between victimization and depression/suicide ideation were found. Limitations: This study used a cross-sectional design and made exclusive use of self-report measures. Conclusion: Adolescents who blame themselves for being bullied might be at a heightened risk for depression and suicidality compared to adolescents who did not use self-blame.

RevDate: 2019-08-16

Bozkurt H, Karakaya IB, Aktas E, et al (2019)

Coexistence of phylloides tumour and invasive ductal cancer in the breast.

Nigerian journal of clinical practice, 22(8):1169-1171.

Phylloides tumor in the breast is a rare fibroepithelial tumor, which is often seen in young adult women. Phylloides tumor of the breast accounts for about 1% of all breast tumors and approximately 3% of all fibroepithelial tumors. Pre-operative diagnosis is difficult. Since there aren't any specific mammography and ultrasound findings, they cannot be distinguished from fibroadenomas through these imaging methods and are mostly followed up as if they are fibroadenomas. Patients often present with the complaint of a mass that has been present for a long time and had started to grow suddenly. The primary preferred approach for treatment is wide local excision with negative surgical margins. Coexistence of invasive ductal carcinoma with phylloides tumor in the same breast is a very rare occurrence. We present in this article, a 42-year-old female patient with an invasive ductal carcinoma inside a phylloides tumor in the same breast.

RevDate: 2019-08-14

Balbinot EDCA, Pereira MFCC, Skupien JA, et al (2019)

Analysis of transmittance and degree of conversion of composite resins.

Microscopy research and technique [Epub ahead of print].

The objective of this study was to evaluate and correlate light transmittance (T), initial degree of conversion (IDC), and degree of conversion after 24 hr (DC24) for 22 composite resins (CR) for enamel and dentin use. The transmittance (n = 10) was measured with a spectrometer at a wavelength of 468.14 nm. The degree of conversion (DC; n = 5) was measured with Fourier Transform Near-Infrared Spectroscopy before polymerization, immediately after photoactivation, and 24 hr after photoactivation. Both sets of values are provided as percentages. ANOVA and Games-Howell (α = 5%) tests showed that Filtek Supreme Ultra gave the highest T values of all enamel CRs, while Esthet-X HD presented the lowest. Meanwhile, Venus diamond gave the highest values of all dentin CRs, while Esthet-X HD gave the lowest. For IDC and DC24, ANOVA showed differences between individual CRs and the two CR types (p < .0001). Despite the limitations of this study, it can be concluded that there was no correlation between T and either IDC or DC24 (p > .05); however, IDC and DC24 were strongly correlated (p < .05) by Pearson's correlation. That being said, as a higher DC reflects better mechanical properties, certain conclusions can be drawn about overall performance. The best IDC values were observed for the Opallis enamel resin and the Opallis and Premise dentin resins. Meanwhile, the best DC24 values were observed for the Opallis, Charisma, and Premise enamel resins and the Opallis and Premise dentin resins. Degree of conversion and light transmittance showed differences between composite resin types (enamel and dentin) and brands. It is important to know at the moment of composite choice taking into account mechanical and optical properties.

RevDate: 2019-08-14

Walsh L, Haley KE, Moran B, et al (2019)

BET inhibition as a rational therapeutic strategy for invasive lobular breast cancer.

Clinical cancer research : an official journal of the American Association for Cancer Research pii:1078-0432.CCR-19-0713 [Epub ahead of print].

PURPOSE: Invasive lobular carcinoma (ILC) is a subtype of breast cancer accounting for 10% of breast tumors. The majority of patients are treated with endocrine therapy; however, endocrine resistance is common in ER-positive breast cancer and new therapeutic strategies are needed. Bromodomain and extra-terminal inhibitors (BETi) are effective in diverse types of breast cancer but they have not yet been assessed in ILC.

EXPERIMENTAL DESIGN: We assessed whether targeting the BET proteins with JQ1 could serve as an effective therapeutic strategy in ILC in both 2D and 3D models. We used dynamic BH3 profiling and RNA-sequencing to identify transcriptional reprograming enabling resistance to JQ1-induced apoptosis. As part of the RATHER study, we obtained copy number alterations and RNA-seq on 61 ILC patient samples.

RESULTS: Certain ILC cell lines were sensitive to JQ1, while others were intrinsically resistant to JQ1-induced apoptosis. JQ1 treatment led to an enhanced dependence on anti-apoptotic proteins and a transcriptional rewiring inducing Fibroblast Growth Factor Receptor 1 (FGFR1). This increase in FGFR1was also evident in invasive ductal carcinoma (IDC) cell lines. The combination of JQ1 and FGFR1 inhibitor was highly effective at inhibiting growth in both 2D and 3D models of ILC and IDC. Interestingly, we found in the RATHER cohort of 61 ILC patients that 20% hadFGFR1amplification and we showed that high BRD3 mRNA expression was associated with poor survival specifically in ILC.

CONCLUSIONS: We provide evidence that BETi either alone or in combination with FGFR1 inhibitors or BH3 mimetics may be a useful therapeutic strategy for recurrent ILC patients.

RevDate: 2019-08-15
CmpDate: 2019-08-15

Cernadas Curotto P, Halperin E, Sander D, et al (2019)

Emotions in attacker-defender conflicts.

The Behavioral and brain sciences, 42:e120 pii:S0140525X19000918.

The distinction between attackers and defenders might help refine the understanding of the role of emotions in conflicts. Here, we briefly discuss differences between attackers and defenders in terms of appraisals, action tendencies, emotional preferences, and brain activities. Finally, we outline how attackers and defenders may differ in their response to emotion-based interventions that aim to promote conflict resolution.

RevDate: 2019-08-13

Wan N, Liu D, Lu L, et al (2019)

[Application of pedicled omentum flap in breast reconstruction of breast cancer patients].

Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery, 33(8):1006-1010.

Objective: To explore the clinical application of the pedicled omentum flap in breast reconstruction of breast cancer patients.

Methods: Between May 2013 and October 2017, 205 patients with breast cancer received modified mastectomy. The pedicled omentum flap was used to reconstruct breast at the same time. All patients were female with an average age of 34.9 years (mean, 26-58 years). The tumor located at left breast in 127 cases and right side in 78 cases. The diameter of the tumor was 2-5 cm (mean, 2.9 cm). The 120 cases of breast cancer were at stage Ⅰ and 85 cases were at stage Ⅱ; and 126 cases were invasive ductal carcinoma and 79 cases were invasive lobular carcinoma. The course of disease ranged from 10 to 92 days (mean, 38.5 days). The size of defect after tumor ablation ranged from 9 cm× 6 cm to 18 cm×12 cm; the size of pedicled omentum flap ranged from 18 cm×10 cm to 22 cm×16 cm.

Results: According to the anatomical basis, the omentum was divided into 4 types, including thin type (42 cases, 20.5%), medium type (133 cases, 64.9%), hypertrophy type (24 cases, 11.7%), and absence type (6 cases, 2.9%). All omentum flaps survived successfully and the incisions healed by first intention. All patients were followed up 6-74 months (mean, 24.5 months); 83 cases were followed up more than 5 years. The shape, texture, and elasticity of the reconstructed breast were good and no flap contracture deformation happened. Only linear scar left at the donor sites, and the function of abdomen was not affected. No local recurrence happened.

Conclusion: The pedicled omentum flap can be harvested safely and reliable, which is the one of ideal option for breast reconstruction in breast cancer patients.

RevDate: 2019-08-10

Onuba L, M Perez-Machado (2019)

Pancreas FNA.

Cytopathology : official journal of the British Society for Clinical Cytology [Epub ahead of print].

67-year-old lady diagnosed with right breast invasive ductal carcinoma with axillary node involvement. Staging FDG PET identified a small enhancing 1.2cm 'indeterminate' nodule within pancreatic tail, which CT pancreas with contrast revealed to be hypervascular. This article is protected by copyright. All rights reserved.

RevDate: 2019-08-10

Winer LK, Hinrichs BH, Lu S, et al (2019)

Flat epithelial atypia and the risk of sampling error: Determining the value of excision after image-guided core-needle biopsy.

American journal of surgery pii:S0002-9610(19)30175-8 [Epub ahead of print].

BACKGROUND: We determined the sampling error rate of flat epithelial atypia (FEA) and evaluated current guidelines recommending excisional biopsy.

METHODS: A retrospective review of consecutive excisional biopsies after image-guided core-needle biopsy identified patients with isolated FEA diagnosed between 2014 and 2018. Clinical and pathologic parameters were evaluated.

RESULTS: Twenty-five women with 27 biopsies were included. Based on pathologic review of original core specimens, 44.4% (N = 12) were accurately diagnosed as FEA. Upon excision, lesions were upgraded to ductal carcinoma in situ (N = 2) or invasive ductal carcinoma (N = 1) in 11.1% of cases. Older age, black race, hormone replacement, and calcifications in the image-guided biopsy specimen were associated with the presence of high-risk or malignant lesions in the excisional biopsy (all p ≤ 0.05).

CONCLUSIONS: In this study, FEA was frequently overcalled. However, lesions suspicious for FEA warrant excision due to their association with malignancy or high-risk lesions, which may necessitate further surgical management and/or risk-reducing strategies.

RevDate: 2019-08-26

Tan X, Li Z, Ren S, et al (2019)

Dynamically decreased miR-671-5p expression is associated with oncogenic transformation and radiochemoresistance in breast cancer.

Breast cancer research : BCR, 21(1):89 pii:10.1186/s13058-019-1173-5.

BACKGROUND: Understanding the molecular alterations associated with breast cancer (BC) progression may lead to more effective strategies for both prevention and management. The current model of BC progression suggests a linear, multistep process from normal epithelial to atypical ductal hyperplasia (ADH), to ductal carcinoma in situ (DCIS), and then invasive ductal carcinoma (IDC). Up to 20% ADH and 40% DCIS lesions progress to invasive BC if left untreated. Deciphering the molecular mechanisms during BC progression is therefore crucial to prevent over- or under-treatment. Our previous work demonstrated that miR-671-5p serves as a tumor suppressor by targeting Forkhead box protein M1 (FOXM1)-mediated epithelial-to-mesenchymal transition (EMT) in BC. Here, we aim to explore the role of miR-671-5p in the progression of BC oncogenic transformation and treatment.

METHODS: The 21T series cell lines, which were originally derived from the same patient with metastatic BC, including normal epithelia (H16N2), ADH (21PT), primary DCIS (21NT), and cells derived from pleural effusion of lung metastasis (21MT), and human BC specimens were used. Microdissection, miRNA transfection, dual-luciferase, radio- and chemosensitivity, and host-cell reactivation (HCR) assays were performed.

RESULTS: Expression of miR-671-5p displays a gradual dynamic decrease from ADH, to DCIS, and to IDC. Interestingly, the decreased expression of miR-671-5p detected in ADH coexisted with advanced lesions, such as DCIS and/or IDC (cADH), but not in simple ADH (sADH). Ectopic transfection of miR-671-5p significantly inhibited cell proliferation in 21NT (DCIS) and 21MT (IDC), but not in H16N2 (normal) and 21PT (ADH) cell lines. At the same time, the effect exhibited in time- and dose-dependent manner. Interestingly, miR-671-5p significantly suppressed invasion in 21PT, 21NT, and 21MT cell lines. Furthermore, miR-671-5p suppressed FOXM1-mediated EMT in all 21T cell lines. In addition, miR-671-5p sensitizes these cell lines to UV and chemotherapeutic exposure by reducing the DNA repair capability.

CONCLUSIONS: miR-671-5p displays a dynamic decrease expression during the oncogenic transition of BC by suppressing FOXM1-mediated EMT and DNA repair. Therefore, miR-671-5p may serve as a novel biomarker for early BC detection as well as a therapeutic target for BC management.

RevDate: 2019-08-07

Goodes LM, King GK, Rea A, et al (2019)

Early urinary tract infection after spinal cord injury: a retrospective inpatient cohort study.

Spinal cord pii:10.1038/s41393-019-0337-6 [Epub ahead of print].

STUDY DESIGN: Retrospective audit.

OBJECTIVES: Examine factors associated with urinary tract infection (UTI), UTI incidence and impact on hospital length of stay (LOS) in new, inpatient adult traumatic spinal cord injury (SCI).

SETTING: Western Australian Hospitals managing SCI patients.

METHODS: Data on UTIs, bladder management and LOS were obtained from hospital databases and medical records over 26 months. Adherence to staff-administered intermittent catheterisation (staff-IC) was determined from fluid balance charts.

RESULTS: Across the cohort (n = 70) UTI rate was 1.1 starts/100 days; UTI by multi-resistant organisms 0.1/100 days. Having ≥1 UTIs compared with none and longer duration of initial urethral indwelling catheterisation (IDC) were associated with longer LOS (p-values < 0.001). For patients with ≥1 UTIs (n = 43/70), longer duration of initial IDC was associated with shorter time to first UTI (1 standard deviation longer [SD, 45.0 days], hazard ratio (HR): 0.7, 95% confidence interval [CI] 0.5-1.0, p-value 0.044). In turn, shorter time to first UTI was associated with higher UTI rate (1 SD shorter [30.7 days], rate ratio (RR): 1.32, 95%CI 1.0-1.7, p-value 0.039). During staff-IC periods (n = 38/70), protocols were followed (85.7% ≤ 6 h apart, 96.1% < 8 h), but 26% of IC volumes exceeded 500 mL; occasional volumes > 800 mL and interruptions requiring temporary IDC were associated with higher UTI rates the following week (odds ratios (ORs): 1.6, 95%CI 1.1-2.3, p-value 0.009; and 3.9, 95%CI 2.6-5.9, p-value < 0.001 respectively).

CONCLUSIONS: Reducing initial IDC duration and limiting staff-IC volumes could be investigated to possibly reduce inpatient UTIs and LOS.


RevDate: 2019-08-08

Forte S, Ritz A, Kubik-Huch R, et al (2019)

Invasive ductal carcinoma detected within a fibroadenolipoma through digital breast tomosynthesis.

Acta radiologica open, 8(7):2058460119865905 pii:10.1177_2058460119865905.

A 52-year-old patient referred to our hospital for a screening mammogram showed a suspicious new architectural distortion. Previously, a fibroadenolipoma within the right breast was diagnosed clinically and radiologically. Further work-up with tomosynthesis, magnetic resonance imaging, and magnetic resonance-guided biopsy showed an invasive ductal carcinoma within the fibroadenolipoma, which are usually benign breast lesions not associated with malignancy. This case report offers a review of the literature and a discussion of signs, which should alert the radiologist.

RevDate: 2019-08-03

Borelli JL, Shai D, Fogel Yaakobi S, et al (2019)

Interpersonal physiological regulation during couple support interactions: Examining the role of respiratory sinus arrhythmia and emotional support.

Psychophysiology [Epub ahead of print].

In times of need, people seek comfort and support from close others. Support provision is an integral component of attachment relationships, one that is linked with physical and psychological well-being. Successful support provision is believed to be grounded in transactions of sensitive, caring behavior between caregivers and support seekers and to serve a profound regulatory function. However, physiological processes underlying support transactions have not been previously studied. We assessed autonomic vagal regulation and coded spontaneous emotional support behaviors in N = 100 heterosexual couples involved in a support interaction. We focused on cardiac vagal activation, operationalized as the increase in respiratory sinus arrhythmia (RSA) from baseline to interaction, as an indicator of regulatory efforts. Analyses revealed a negative association between caregivers' and support seekers' regulatory efforts, which was mediated by emotional support behaviors. We found that caregivers with greater increases in RSA from baseline to interaction provided more emotional support to their partners. Such emotional support was associated with smaller increases in support seekers' RSA and with support seekers' perceptions of their partners as being more sensitive to their needs. Finally, these links were only significant among dyads in which caregivers reported lower levels of attachment anxiety. We interpret these results in the framework of interpersonal regulatory processes, suggesting that provision of support may impose regulatory demands on the side of the caregivers, which in turn could result in attenuated regulatory efforts and positive partner perceptions for the support seekers.

RevDate: 2019-08-04

Levy J, JF Démonet (2019)

MEG data representing a gamma oscillatory response during the hold/release paradigm.

Data in brief, 23:103787 pii:103787.

The article presents magnetoencephalography (MEG) data from healthy participants while undergoing the Hold/Release paradigm. During the paradigm, participants visually perceived a sequence of two letter strings which either assembled into real words (Hold condition) or pseudowords (Release condition). If the first letter string was morphologically valid, they held their attention (and/or held the item in working-memory) to wait for the second string, whereas if it were invalid, they could release it, respectively. We present data on high-frequency neuronal oscillations of the Hold condition compared to the Release condition. Making this information publicly available could allow other researchers to perform analyses and contribute to understanding the cognitive processes such as language, mnemonic or attentional processes.

RevDate: 2019-08-04

Liu J, Zhao J, Zhang M, et al (2019)

The validation of the 2014 International Society of Urological Pathology (ISUP) grading system for patients with high-risk prostate cancer: a single-center retrospective study.

Cancer management and research, 11:6521-6529 pii:196286.

Introduction: Since the new 2014 grading system was recommended by the International Society of Urological Pathology (ISUP), it has been validated in patients with localized prostate cancer (PCa) and it has shown excellent prognostic value. However, its predictive power in high-risk PCa remains unclear.

Methods: A total of 420 patients with high-risk PCa who underwent radical prostatectomy (RP) were included in this study. Biochemical recurrence-free survival (BRFS) was set as the endpoint.

Results: Biochemical recurrence occurred in 84/420 (20.0%) patients at the end of follow-up. Compared to the three-tier grouping system, the five-tier grouping system could more effectively distinguish the BRFS of patients with higher predictive accuracy (C-index: 0.599 vs 0.646). The BRFS of patients with grade group (GG) 1 and GG 2 was similar (P=0.593). Also, the prognosis between those with GG 2 and GG 3 could be clearly distinguished (P=0.001). However, the discrimination capacity between patients with GG 3 and GG 4 was limited (P=0.681). When tertiary Gleason pattern (TGP5) and intraductal carcinoma of the prostate (IDC-P) were excluded, the HR value of the GG 4 group vs the GG 3 group increased from 1.15 (95% CI: 0.59-2.22) to 1.49 (95% CI: 0.72-3.10) and 1.36 (95% CI:0.65-2.83), respectively.

Conclusions: This study is the first to validate the new 2014 ISUP grading system in patients with high-risk PCa who underwent RP. The 2014 system could effectively classify patients into five groups with high predictive accuracy. Notably, the existence of TGP5 and IDC-P needs to be routinely reported in clinical practice, which could help to support the predictive value of the new grading system.

RevDate: 2019-07-31

Can C, H Komek (2019)

Metabolic and volume-based parameters of (18F)FDG PET/CT for primary mass and axillary lymph node metastasis in patients with invasive ductal carcinoma: a retrospective analysis in relation to molecular subtype, axillary lymph node metastasis and immunohistochemistry and inflammatory markers.

Nuclear medicine communications [Epub ahead of print].

OBJECTIVE: To evaluate metabolic and volume-based parameters of 18-Fluorodeoxyglucose positron emission tomography/computed tomography ((F)FDG PET/CT) for primary mass and axillary lymph node (ALN) metastasis in relation to molecular subtype, and immunohistochemistry and inflammatory markers in patients with invasive ductal carcinoma.

METHODS: A total of 129 patients (mean±SD age: 49.2±13.0 years) with invasive ductal breast cancer who had (F)FDG PET/CT imaging prior to chemotherapy or surgery were included in this single-center retrospective study. Data on patient age, molecular subtype, ALN metastasis status, inflammatory markers, immunohistochemistry markers and (F)FDG PET/CT imaging parameters for primary mass and ALN were recorded.

RESULTS: ALN metastasis was evident in 52.7% of patients and associated with significantly higher median diameter (P=0.027), MTV (P<0.001) and TLG (P<0.001). NLR was positively correlated with all primary mass (p ranged from 0.041 to 0.001) and ALN (P ranged from 0.026 to <0.001) PET parameters. PET parameters did not change with respect to molecular subtype or immunohistochemistry markers. Primary mass and ALN metastasis PET parameters showed significant positive correlations for TLG (r=0.274, P=0.001) and SUVmax (r=0.358, P<0.001).

CONCLUSION: In conclusion, our findings in a retrospective cohort of invasive ductal breast cancer patients revealed primary mass PET parameters to significantly differ with respect to ALN metastasis status and NLR levels, but not according to molecular subtype or immunohistochemistry markers. Accordingly, our findings highlight the value of acquisition of preoperative PET/CT imaging and role of both metabolic and volume-based parameters in predicting aggressiveness of the tumor as correlated with presence of ALN metastasis and high NLR.

RevDate: 2019-08-09

Metaxa L, Healy NA, SA O'Keeffe (2019)

Breast microcalcifications: the UK RCR 5-point breast imaging system or BI-RADS; which is the better predictor of malignancy?.

The British journal of radiology [Epub ahead of print].

OBJECTIVE: In the UK RCR 5-point breast imaging system (UKS), radiologists grade mammograms from 1 to 5 according to suspicion for malignancy, however unlike BI-RADS, no lexicon of descriptors is published. The aim of this study was to determine whether strict categorisation of microcalcifications (MCC) according to BI-RADS was a better predictor of malignancy than the UKS and whether these descriptors could be used within the UKS.

METHODS: A retrospective review of 241 cases, with MCC on mammography, who underwent biopsy was performed. Morphology, distribution, extent, UKS score, BI-RADS category and pathology were recorded. The positive predictive value (PPV) of each classification system for malignancy was calculated.

RESULTS: 28.6% were diagnosed with DCIS/IDC. The PPV for malignancy using the UKS was 18.9%, 69.4%, 100% for M3-5 respectively (p < 0.001) and using ΒI-RADS morphology was amorphous: 7.1%, coarse heterogeneous: 33.3%, fine pleomorphic: 48.1% and fine linear/fine linear branching: 85.2% (p < 0.001). The PPV based on distribution was grouped: 14.2%, regional: 32.3%, diffuse: 33.3% and linear/segmental: 77.8% (p < 0.001). Combining all cases of benign-appearing, amorphous and grouped coarse heterogenous and grouped fine pleomorphic MCC gave a PPV of 12.8%. Combining regional, linear or segmental coarse heterogenous and fine pleomorphic and all fine linear/branching MCC resulted in a PPV of 83.3% for malignancy.

CONCLUSION: Combining morphology and distribution of MCC is accurate in malignancy prediction. Use of BI-RADS descriptors could help standardise reporting within the UKS and an algorithm using these within the UKS is proposed. Better prediction would enable more appropriate counselling and help to identify discrepancies.

ADVANCES IN KNOWLEDGE: No guidance exists on scoring of suspicious MCC in the UK breast imaging system. Use of BI-RADS morphologic/distribution descriptors can aid malignancy prediction. Findings other than morphology of MCC are important in malignancy prediction. An algorithm for use by the UK radiologist when evaluating MCC is provided.

RevDate: 2019-08-02

Sinha A, SS Gill (2019)

Cytological Correlates of Axillary Nodal Involvement in Invasive Ductal Carcinoma of Breast.

Journal of cytology, 36(3):142-145.

Context: Fine needle aspiration cytology (FNAC) plays an important role in the diagnosis of breast carcinoma. However, its role as a prognostic tool needs to be explored. This can be achieved by studying its correlation with an established prognostic marker such as axillary nodal metastasis.

Aims: This study was undertaken to correlate the cytological features of invasive ductal carcinoma (IDC) of breast with axillary lymph node status.

Settings and Design: Tertiary care hospital, retrospective analytical study.

Materials and Methods: The study group included 150 cases of IDC of breast diagnosed on FNAC, who had subsequently undergone modified radical mastectomy. Cytologic grades were assigned as per Robinson's grading system. Histopathological sections of axillary lymph nodes were assessed for metastasis.

Statistical Analysis Used: The cytologic grade and each feature of the cytologic grade were correlated with the lymph node metastasis using χ2 test. Values of P < 0.05 were considered significant.

Result: A statistically significant correlation was noted between cytologic grade of tumor and axillary lymph node metastasis (P < 0.05). In addition, a positive correlation was found between two of the individual features of cytologic grade, namely, nuclear size and cell uniformity with axillary lymph node metastasis (P < 0.05).

Conclusion: Robinson's cytologic grade of breast carcinoma correlates well with the presence of axillary lymph node metastasis and hence can be used as a prognostic tool. As there is an increasing trend toward conservative approach to management of breast carcinoma, patients receive preoperative neoadjuvant therapy which may alter the nodal status on the resected specimen. Hence, a high cytological grade of primary tumor, as assessed on FNAC before initiation of therapy, should alert the treating team of the possibility of axillary lymph nodal metastasis.

RevDate: 2019-08-04

Chang CC, Chen CJ, Hsu WL, et al (2019)

Prognostic Significance of Metabolic Parameters and Textural Features on 18F-FDG PET/CT in Invasive Ductal Carcinoma of Breast.

Scientific reports, 9(1):10946 pii:10.1038/s41598-019-46813-5.

To investigate the prognostic significance of metabolic parameters and texture analysis on 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) in patients with breast invasive ductal carcinoma (IDC), from August 2005 to May 2015, IDC patients who had undergone pre-treatment FDG PET/CT were enrolled. The metabolic parameters, including maximal standardized uptake value of breast tumor (SUVbt) and ipsilateral axillary lymph node (SUVln), metabolic tumor volume (MTVbt) and total lesion glycolysis (TLGbt) of breast tumor, whole-body MTV (MTVwb) and whole-body TLG (TLGwb) were recorded. Nine textural features of tumor (four co-occurrence matrices and five SUV-based statistics) were measured. The prognostic significance of above parameters and clinical factors was assessed by univariate and multivariate analyses. Thirty-five patients were enrolled. Patients with low and high MTVwb had 5-year progression-free survival (PFS) of 81.0 and 14.3% (p < 0.0001). The 5-year overall survival for low and high MTVwb was 88.5% and 43.6% (p = 0.0005). Multivariate analyses showed MTVwb was an independent prognostic factor for PFS (HR: 8.29, 95% CI: 2.17-31.64, p = 0.0020). The SUV, TLG and textural features were not independently predictive. Elevated MTVwb was an independent predictor for shorter PFS in patients with breast IDC.

RevDate: 2019-07-30

Li TT, Kang CS, Li HZ, et al (2019)

[Value of shear wave elastrography image classification in the diagnosis of breast masses].

Zhonghua zhong liu za zhi [Chinese journal of oncology], 41(7):540-545.

Objective: To analyze the image features of shear wave elastrography (SWE) in breast masses, and to evaluate their values in the differentiation of benign and malignant breast lesions. Methods: A total of 361 patients with 403 breast lesions who simultaneously underwent conventional ultrasound and SWE examination from February 2015 to January 2018 were selected. Diagnosis in all patients was confirmed by aspiration biopsy or operative pathology. The SWE images were collected and the elastic images were divided into 5 types. The SWE image features of different breast pathological types were summarized, and their values in benign and malignant breast lesion diagnoses were evaluated. Results: The main features of benign breast lesion were type Ⅰ and Ⅱ, the main features of the malignant lesion were type Ⅳ and Ⅴ, and the proportion of which were 43.6% (71/163), 37.4% (61/163), 22.1% (53/240) and 57.9% (139/240), respectively. Type Ⅲ accounted for a certain proportion in both benign and malignant lesions. The SWE image features of benign and malignant lesions were compared and a significant difference was observed (P<0.001). The type Ⅴ features were mainly observed in invasive ductal carcinoma, invasive lobular carcinoma and other types of invasive carcinoma, while the type Ⅳ features were mostly presented in ductal carcinoma in situ and mucinous carcinoma. Fibroadenoma, fibroadenosis accompanied with fibroadenoma, and fibroadenosis were featured with type Ⅰ. Both intraductal papilloma and benign phyllodes tumor were mostly type Ⅱ, while type Ⅲ and Ⅴ were more common in chronic granulomatous mastitis. When type Ⅰ and typeⅡof breast lesions were classified as benign features while type Ⅳ and Ⅴ were malignant features, the sensitivity and specificity of breast malignant lesion diagnosis were 91.2% and 84.7% by application of SWE combined with breast imaging reporting and data system (BI-RADS). The sensitivity of combined diagnosis was slightly lower than that of conventional ultrasound (P>0.05), but the specificity was significantly higher than conventional ultrasound (P<0.01). Conclusion: The SWE is a simple and effective method. Combination of SWE with conventional ultrasound may improve the diagnostic differentiation of benign and malignant breast lesions.

RevDate: 2019-09-04

Arabpour M, Rasolmali R, Talei AR, et al (2019)

Granzyme B production by activated B cells derived from breast cancer-draining lymph nodes.

Molecular immunology, 114:172-178 pii:S0161-5890(19)30137-3 [Epub ahead of print].

B lymphocytes with regulatory or effector functions synthesize granzyme B (GZMB). We investigated the frequency and phenotype of GZMB-producing B cells in breast tumor-draining lymph nodes (TDLNs). Mononuclear cells were isolated from 48 axillary lymph nodes and were stimulated with anti-BCR (B cell receptor), recombinant interleukin (IL)-21 and CD40 L alone or in combination. Flow cytometry was used to evaluate the expression of GZMB in B cells, and in 4 samples the phenotype of GZMB+ B cells was determined. B cells produced GZMB only when stimulated with a combination of IL-21 and anti-BCR for at least 16 h. Adding CD40 L to IL-21 and anti-BCR stimuli resulted in lower GZMB production in B cells. A small fraction of B cells was able to produce perforin in all stimulation conditions, and the majority of GZMB+ B cells were perforin-negative. Both naïve (CD24lowCD27-) and active/memory (CD24hiCD27+) B cells expressed GZMB. In patients with invasive ductal carcinoma, the frequency of GZMB+ B cells was significantly lower in metastatic compared to non-metastatic lymph nodes. The frequency of GZMB+ B cells did not significantly correlate with prognostic factors such as stage, tumor size or Her2 expression. In summary, a subpopulation of both naïve and memory B cells expressed GZMB in breast TDLNs. Our findings underscore the need to investigate the function of GZMB+ B cells in breast tumor immunity.

RevDate: 2019-08-02

Ogunleye AJ, Olanrewaju AJ, Arowosegbe M, et al (2019)

Molecular docking based screening analysis of GSK3B.

Bioinformation, 15(3):201-208 pii:97320630015201.

GSK3B has been an interesting drug target in the pharmaceutical industry. Its dysfunctional expression has prognostic significance in the top 3 cause of death associated with non-communicable diseases (cancer, Alzheimer's disease and type 2 diabetes). Previous studies have shown clearly that inhibiting GSK3B has proven therapeutic significance in Alzheimer's disease, but its contribution to various cancers has not been clearly resolved. In this study we report the contribution and prognostic significance of GSK3B to two breast cancer subtypes; ductal carcinoma in-situ (DCIS) and invasive ductal carcinoma (IDC) using the Oncomine platform. We performed high throughput screening using molecular docking. We identified BT-000775, a compound that was subjected to further computational hit optimization protocols. Through computational predictions, BT-000775 is a highly selective GSK3B inhibitor, with superior binding affinity and robust ADME profiles suitable for the patho-physiological presentations.

RevDate: 2019-07-28

Zacharioudakis K, Kontoulis T, Vella JX, et al (2019)

Can we see what is invisible? The role of MRI in the evaluation and management of patients with pathological nipple discharge.

Breast cancer research and treatment pii:10.1007/s10549-019-05321-w [Epub ahead of print].

INTRODUCTION: The aim of this study was to determine the ability of MRI to identify and assess the extent of disease in patients with pathological nipple discharge (PND) with an occult malignancy not evident on standard pre-operative evaluation with mammography and ultrasound.

METHODS: Patients presenting to the breast unit of Imperial College Healthcare NHS Trust between December 2009 and December 2018 with PND and normal imaging were enrolled in the study. Pre-operative bilateral breast MRI was performed in all patients as part of our protocol and all patients were offered diagnostic microdochectomy.

RESULTS: A total of 82 patients fulfilled our selection criteria and were enrolled in our study. The presence of an intraductal papilloma (IDP) was identified as the cause of PND in 38 patients (46.3%), 14 patients had duct ectasia (DE-17%) and 5 patients had both an IDP and DE. Other benign causes were identified in 11 patients (13.4%). Despite normal mammography and ultrasound a malignancy was identified in 14 patients (17%). Eleven patients had DCIS (13.4%), two had invasive lobular carcinoma and one patient had an invasive ductal carcinoma. The sensitivity of MRI in detecting an occult malignancy was 85.71% and the specificity was 98.53%. The positive predictive value was 92.31% and the negative predictive value was 97.1%.

CONCLUSIONS: Although a negative MRI does not exclude the presence of an occult malignancy the high sensitivity and specificity of this diagnostic modality can guide the surgeon and alter the management of patients with PND.

RevDate: 2019-07-27

Ding Q, Chen H, Lim B, et al (2019)

HER2 somatic mutation analysis in breast cancer: correlation with clinicopathological features.

Human pathology pii:S0046-8177(19)30128-5 [Epub ahead of print].

HER2 mutations have been reported in approximately 2% of breast cancers. Regardless of HER2 overexpression or amplification status, breast cancer with HER2 mutations may respond to HER2-targeted therapy. As HER2 mutation is rare, the clinical and pathological features of HER2-mutated breast cancers, such as hormonal status, histological grade, and metastasis, remain poorly defined. Therefore, the identification of HER2-mutated breast cancer has clinical significance. We retrospectively screened patients with metastatic breast cancer in whom molecular profiling had been performed using next-generation sequencing from 2012 to 2015; we identified 18 patients with HER2 mutation. Mutations were found on next-generation sequencing-based panels, including Ion AmpliSeq Cancer Hotspot, Oncomine, FoundationOne, and Guardant360. HER2 mutations were identified in both the tyrosine kinase (n=14) and extracellular (n=4) domains. Of the 14 cases with tyrosine kinase domain mutations, 13 were estrogen receptor (ER) positive; the 4 cases with extracellular domain mutations were exclusively ER negative. In addition, 11 of 14 patients with tyrosine kinase domain mutations had bone metastasis, whereas no patients with HER2 extracellular domain mutations had bone metastasis. Histologically, 13 patients had invasive ductal carcinoma, 1 had metaplastic carcinoma, and 4 had invasive lobular carcinoma (ILC). All 4 ILCs were high grade and pleomorphic, and not only had an HER2 mutation in the kinase domain but also had an HER2 mutation involving the L755 site. Specific mutation sites may be involved in the pathogenesis of non-classic ILC.

RevDate: 2019-08-13

Lourenco C, Kalkat M, Houlahan KE, et al (2019)

Modelling the MYC-driven normal-to-tumour switch in breast cancer.

Disease models & mechanisms, 12(7): pii:12/7/dmm038083.

The potent MYC oncoprotein is deregulated in many human cancers, including breast carcinoma, and is associated with aggressive disease. To understand the mechanisms and vulnerabilities of MYC-driven breast cancer, we have generated an in vivo model that mimics human disease in response to MYC deregulation. MCF10A cells ectopically expressing a common breast cancer mutation in the phosphoinositide 3 kinase pathway (PIK3CAH1047R) led to the development of organised acinar structures in mice. Expressing both PIK3CAH1047R and deregulated MYC led to the development of invasive ductal carcinoma. Therefore, the deregulation of MYC expression in this setting creates a MYC-dependent normal-to-tumour switch that can be measured in vivo These MYC-driven tumours exhibit classic hallmarks of human breast cancer at both the pathological and molecular level. Moreover, tumour growth is dependent upon sustained deregulated MYC expression, further demonstrating addiction to this potent oncogene and regulator of gene transcription. We therefore provide a MYC-dependent model of breast cancer, which can be used to assay invivo tumour signalling pathways, proliferation and transformation from normal breast acini to invasive breast carcinoma. We anticipate that this novel MYC-driven transformation model will be a useful research tool to better understand the oncogenic function of MYC and for the identification of therapeutic vulnerabilities.

RevDate: 2019-07-28

Champion CD, Ren Y, Thomas SM, et al (2019)

DCIS with Microinvasion: Is It In Situ or Invasive Disease?.

Annals of surgical oncology pii:10.1245/s10434-019-07556-9 [Epub ahead of print].

BACKGROUND: Ductal carcinoma in situ (DCIS) with microinvasion (DCISM) can be challenging in balancing the risks of overtreatment versus undertreatment. We compared DCISM, pure DCIS, and small volume (T1a) invasive ductal carcinoma (IDC) as related to histopathology, treatment patterns, and survival outcomes.

METHODS: Women ages 18-90 years who underwent breast surgery for DCIS, DCISM, or T1a IDC were selected from the SEER Database (2004-2015). Multivariate logistic regression and Cox proportional hazards models were used to estimate the association of diagnosis with treatment and survival, respectively.

RESULTS: A total of 134,569 women were identified: 3.2% DCISM, 70.9% DCIS, and 25.9% with T1a IDC. Compared with invasive disease, DCISM was less likely to be ER+ or PR+ and more likely to be HER2+. After adjustment, DCIS and invasive patients were less likely to undergo mastectomy than DCISM patients (DCIS: OR 0.53, 95% CI 0.49-0.56; invasive: OR 0.86, CI 0.81-0.92). For those undergoing lumpectomy, the likelihood of receiving radiation was similar for DCISM and invasive patients but lower for DCIS patients (OR 0.57, CI 0.52-0.63). After adjustment, breast-cancer-specific survival was significantly different between DCISM and the other two groups (DCIS: HR 0.59, CI 0.43-0.8; invasive: HR 1.43, CI 1.04-1.96). However, overall survival was not significantly different between DCISM and invasive disease, whereas patients with DCIS had improved OS (HR 0.83, CI 0.75-0.93).

CONCLUSIONS: Although DCISM is a distinct entity, current treatment patterns and prognosis are comparable to those with small volume IDC. These findings may help providers counsel patients and determine appropriate treatment plans.

RevDate: 2019-08-02

Mamtani A, Zabor EC, Stempel M, et al (2019)

Lobular Histology Does Not Predict the Need for Axillary Dissection Among ACOSOG Z0011-Eligible Breast Cancers.

Annals of surgical oncology pii:10.1245/s10434-019-07536-z [Epub ahead of print].

BACKGROUND: The American College of Surgeons Oncology Group (ACOSOG) Z0011 trial demonstrated that axillary lymph node dissection (ALND) may be omitted for women with two or fewer positive sentinel nodes (SLNs) undergoing breast-conservation therapy (BCT). Lobular histology comprises a minority of patients, and applicability to these discohesive cancers has been questioned.

METHODS: From August 2010 to March 2017, patients undergoing BCT for cT1-2N0 cancer with positive SLNs were prospectively managed with ALND for three or more positive SLNs or gross extracapsular extension (ECE). In this study, clinicopathologic characteristics and nodal burden were compared between pure/mixed invasive lobular cancer (ILC) and invasive ductal cancer (IDC) patients.

RESULTS: Among 813 consecutive patients, 104 (12.8%) had ILC and 709 (87.2%) had IDC. ILC was more often multifocal and low grade, and less frequently had lymphovascular invasion (all p < 0.001). ILC more often had SLN macrometastases (81.7% ILC vs. 69.4% IDC; p = 0.01) and more than 2 mm of ECE (30.8% ILC vs. 19.5% IDC; p = 0.03), but the proportions of cases with three or more positive SLNs were similar in the two groups (14.4% ILC vs. 9.9% IDC; p = 0.2). The ALND procedure was performed for 20 ILC patients (19.2%) compared with 97 IDC patients (13.7%) (p = 0.2). Additional positive nodes were found in 80% of the ILC patients versus 56.7% of the IDC patients (p = 0.09). The ALND and nodal burden rates were similar in the estrogen receptor-positive (ER+) subset analysis. In the multivariable analysis, lobular histology (p = 0.03) and larger tumors (p = 0.03) were associated with additional positive nodes. During a median follow-up period of 42 months, there were no isolated axillary recurrences.

CONCLUSIONS: Despite a higher proportion of SLN macrometastases and association with more positive nodes at ALND, lobular histology does not predict the need for ALND. ALND is not indicated on the basis of histology among patients otherwise meeting Z0011 criteria.

RevDate: 2019-07-28

Oluogun WA, Adedokun KA, Oyenike MA, et al (2019)

Histological classification, grading, staging, and prognostic indexing of female breast cancer in an African population: A 10-year retrospective study.

International journal of health sciences, 13(4):3-9.

Background: Breast cancer (BC) is a heterogeneous disease characterized with diverse genetic and ethnic/racial variations that may influence tumor characteristics and prognosis. We studied different histological types of BC and their prognostic indicators in part of Southwestern Nigeria.

Materials and Methods: A 10-year retrospective study of archival tissue-paraffin blocks and records of surgical cases (documented as BCs) between January 2005 and December 2014 was done. Tumor classification was made after the World Health Organization guidelines. Modified Bloom-Richardson score and TNM staging system were used in grading and staging the tumors. Nottingham prognostic index was employed in scoring the prognosis.

Results: The mean age was 49.7 years (20-89 years). The age group from 50 to 59 years was most affected. Out of 343 total cases, the most common histological type was invasive ductal carcinoma of no special type (88.9%). The majority (51.9%) had tumor sizes ranging 2-5 cm (pT2) and some (39.1%) with >5 cm (pT3) were all at palpable stages. The tumors were mostly Grades II and III types. Observation for lymph node metastasis confirmed that 261 (76.1%) were pN0 (negative), 77 (22.4%) were pN1, and 5 (1.5%) were pN2. Prediction of a chance of survival showed moderate prognosis in the majority (48.7%) of the cases.

Conclusion: Although early detection of BC in this region was considerably poor, there was a better outcome compared with some other black populations. Clinical presentation, histological type, and prognostic indices varied from existing reports in many ethnic/racial groups. Indexing of BC pattern on a regional standpoint may serve a new direction toward better management considering the associated geographic disparity.

RevDate: 2019-07-24

Lurie I, Nakash O, Gerber Y, et al (2019)


Harefuah, 158(7):432-436.

INTRODUCTION: In 2012, 183,896 work migrants and 47,704 asylum-seekers and work-migrants arrived in Israel. These populations are at high-risk for depression, anxiety and posttraumatic stress disorder (PTSD). The Open Clinic of Physicians for Human Rights (PHR) delivers free medical and mental health services to these individuals.

AIMS: To evaluate exposure to traumatic events, and compare the prevalence and risk for PTSD, depression and anxiety symptoms between work-migrants and asylum-seekers.

METHODS: An analytical cross-sectional study of adults visiting the Open Clinic was conducted. Participants completed self-report questionnaires including information on demographics and exposure to traumas, depression, anxiety and PTSD. Statistical models were constructed to predict outcome variables of PTSD, depression and anxiety as dichotomist variables using a logistic regression, and association odds ratio (OR) and confidence interval (CI) on 95% level.

RESULTS: There were 241 participants; 165 asylum-seekers, 76 work-migrants. Work-migrants were exposed to more traumatic events. A total of 17-31% met PTSD criteria. Significantly more asylum-seekers met PTSD criteria. A total of 43%-50% met criteria for depression and/or anxiety, with no between-group differences. Significant association was found between immigration status and PTSD risk. Exposure to traumatic events was significantly associated with the prediction of PTSD, depression and anxiety.

DISCUSSION: Exposure to traumatic events was high among the Open Clinic service users, specifically work-migrants. Prevalence and risk for post-traumatic symptoms were significantly higher among asylum-seekers. It is important to conduct further research, in order to characterize risk and resilience factors in this excluded population, and to plan language and culture-competent mental health services.

RevDate: 2019-07-26

Rodriguez J, Schulz S, Giraldo BF, et al (2019)

Risk Stratification in Idiopathic Dilated Cardiomyopathy Patients Using Cardiovascular Coupling Analysis.

Frontiers in physiology, 10:841.

Cardiovascular diseases are one of the most common causes of death; however, the early detection of patients at high risk of sudden cardiac death (SCD) remains an issue. The aim of this study was to analyze the cardio-vascular couplings based on heart rate variability (HRV) and blood pressure variability (BPV) analyses in order to introduce new indices for noninvasive risk stratification in idiopathic dilated cardiomyopathy patients (IDC). High-resolution electrocardiogram (ECG) and continuous noninvasive blood pressure (BP) signals were recorded in 91 IDC patients and 49 healthy subjects (CON). The patients were stratified by their SCD risk as high risk (IDCHR) when after two years the subject either died or suffered life-threatening complications, and as low risk (IDCLR) when the subject remained stable during this period. Values were extracted from ECG and BP signals, the beat-to-beat interval, and systolic and diastolic blood pressure, and analyzed using the segmented Poincaré plot analysis (SPPA), the high-resolution joint symbolic dynamics (HRJSD) and the normalized short time partial directed coherence methods. Support vector machine (SVM) models were built to classify these patients according to SCD risk. IDCHR patients presented lowered HRV and increased BPV compared to both IDCLR patients and the control subjects, suggesting a decrease in their vagal activity and a compensation of sympathetic activity. Both, the cardio -systolic and -diastolic coupling strength was stronger in high-risk patients when comparing with low-risk patients. The cardio-systolic coupling analysis revealed that the systolic influence on heart rate gets weaker as the risk increases. The SVM IDCLR vs. IDCHR model achieved 98.9% accuracy with an area under the curve (AUC) of 0.96. The IDC and the CON groups obtained 93.6% and 0.94 accuracy and AUC, respectively. To simulate a circumstance in which the original status of the subject is unknown, a cascade model was built fusing the aforementioned models, and achieved 94.4% accuracy. In conclusion, this study introduced a novel method for SCD risk stratification for IDC patients based on new indices from coupling analysis and non-linear HRV and BPV. We have uncovered some of the complex interactions within the autonomic regulation in this type of patient.

RevDate: 2019-07-23

Machado J, Silveira WA, Gonçalves DA, et al (2019)

α-Calcitonin gene-related peptide inhibits autophagy and calpain systems and maintains the stability of neuromuscular junction in denervated muscles.

Molecular metabolism pii:S2212-8778(19)30254-6 [Epub ahead of print].

OBJECTIVE: Although it is well established that a-calcitonin gene-related peptide (CGRP) stabilizes muscle-type cholinergic receptors nicotinic subunits (AChR), the underlying mechanism by which this neuropeptide regulates muscle protein metabolism and neuromuscular junction (NMJ) morphology is unclear.

METHODS: To elucidate the mechanisms how CGRP controls NMJ stability in denervated mice skeletal muscles, we carried out physiological, pharmacological, and molecular analyses of atrophic muscles induced by sciatic nerve transection.

RESULTS: Here, we report that CGRP treatment in vivo abrogated the deleterious effects on NMJ upon denervation (DEN), an effect that was associated with suppression of skeletal muscle proteolysis, but not stimulation of protein synthesis. CGRP also blocked the DEN-induced increase in endocytic AChR vesicles and the elevation of autophagosomes per NMJ area. The treatment of denervated animals with rapamycin blocked the stimulatory effects of CGRP on mTORC1 and its inhibitory actions on autophagic flux and NMJ degeneration. Furthermore, CGRP inhibited the DEN-induced hyperactivation of Ca2+-dependent proteolysis, a degradative system that has been shown to destabilize NMJ. Consistently, calpain was found to be activated by cholinergic stimulation in myotubes leading to the dispersal of AChR clusters, an effect that was abolished by CGRP.

CONCLUSION: Taken together, these data suggest that the inhibitory effect of CGRP on autophagy and calpain may represent an important mechanism for the preservation of synapse morphology when degradative machinery is exacerbated upon denervation conditions.

RevDate: 2019-08-02

Nkinda L, Patel K, Njuguna B, et al (2019)

C - reactive protein and interleukin - 6 levels among human immunodeficiency virus -infected patients with dysglycemia in Tanzania.

BMC endocrine disorders, 19(1):77 pii:10.1186/s12902-019-0407-y.

BACKGROUND: Chronic inflammation has been associated with dysglycemia among people living with HIV (PLHIV). There is however, limited data regarding this phenomenon in sub-Sahara Africa (SSA). Therefore we assessed the levels of C-reactive protein (CRP) and Interleukin 6 (IL-6) on a cohort of PLHIV and its associations with dysglycemia in Tanzania.

METHODS: We conducted a cross-sectional study at the Infectious Disease Clinic (IDC) in Tanzania from March to May 2018. Purposive sampling was used to identify participants who had an undetectable viral load, were on 1st line anti-retroviral therapy (ART) and had an overnight fast. The WHO stepwise approach for non-communicable disease (NCD) surveillance was used to collect data. Fasting blood glucose and blood glucose after 75 g oral glucose load was measured, and Enzyme-linked immunosorbent assay (ELISA) was used to test for inflammatory markers (IL-6 and CRP). Associations were explored using the Chi square test and binary logistic regression was performed to estimate the odds ratios. A p-value less than 0.05 was considered statistically significant.

RESULTS: A total of 240 participants were enrolled. Forty two percent were overweight/obese (> 25 kg/m2), 89% had a high waist to height ratio. The median ART duration was 8(5-10) years. The prevalence of dysglycemia among our cohort of PLHIV was 32%. High CRP was associated with a 2.05 increased odds of having dysglycemia OR 2.05 (1.15-3.65) (p = 0.01). Taking stavudine was associated with a 1.99 odds of having dysglycemia OR 1.99 (1.04-3.82) (p = 0.03).We did not find a significant association between IL-6 and dysglycemia.

CONCLUSION: High CRP and taking stavudine were significantly associated with dysglycemia among PLHIV with undetectable viral load.

RevDate: 2019-07-20

Mojahed D, Ha RS, Chang P, et al (2019)

Fully Automated Postlumpectomy Breast Margin Assessment Utilizing Convolutional Neural Network Based Optical Coherence Tomography Image Classification Method.

Academic radiology pii:S1076-6332(19)30324-1 [Epub ahead of print].

BACKGROUND: The purpose of this study was to develop a deep learning classification approach to distinguish cancerous from noncancerous regions within optical coherence tomography (OCT) images of breast tissue for potential use in an intraoperative setting for margin assessment.

METHODS: A custom ultrahigh-resolution OCT (UHR-OCT) system with an axial resolution of 2.7 μm and a lateral resolution of 5.5 μm was used in this study. The algorithm used an A-scan-based classification scheme and the convolutional neural network (CNN) was implemented using an 11-layer architecture consisting of serial 3 × 3 convolution kernels. Four tissue types were classified, including adipose, stroma, ductal carcinoma in situ, and invasive ductal carcinoma.

RESULTS: The binary classification of cancer versus noncancer with the proposed CNN achieved 94% accuracy, 96% sensitivity, and 92% specificity. The mean five-fold validation F1 score was highest for invasive ductal carcinoma (mean standard deviation, 0.89 ± 0.09) and adipose (0.79 ± 0.17), followed by stroma (0.74 ± 0.18), and ductal carcinoma in situ (0.65 ± 0.15).

CONCLUSION: It is feasible to use CNN based algorithm to accurately distinguish cancerous regions in OCT images. This fully automated method can overcome limitations of manual interpretation including interobserver variability and speed of interpretation and may enable real-time intraoperative margin assessment.


RJR Experience and Expertise


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


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


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


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


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


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


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


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

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

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Collection of publications by R J Robbins

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

Research Gate page for R J Robbins

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

Curriculum Vitae for R J Robbins

short personal version

Curriculum Vitae for R J Robbins

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RJR Picks from Around the Web (updated 11 MAY 2018 )