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Παρασκευή 3 Νοεμβρίου 2017
Founder Effect of the RETC611Y Mutation in Multiple Endocrine Neoplasia 2A in Denmark: A Nationwide Study
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Perioperative bleeding and blood transfusion are major risk factors for venous thromboembolism following bariatric surgery
Abstract
Background
Morbidly obese patients are at increased risk for venous thromboembolism (VTE) after bariatric surgery. Perioperative chemoprophylaxis is used routinely with bariatric surgery to decrease the risk of VTE. When bleeding occurs, routine chemoprophylaxis is often withheld due to concerns about inciting another bleeding event. We sought to evaluate the relationship between perioperative bleeding and postoperative VTE in bariatric surgery.
Methods
The American College of Surgeons-National Surgical Quality Improvement Program (NSQIP) dataset between 2012 and 2014 was queried to identify patients who underwent bariatric surgery. Gastric bypass (n = 28,145), sleeve gastrectomy (n = 30,080), bariatric revision (n = 324), and biliopancreatic diversion procedures (n = 492) were included. Univariate and multivariate regressions were used to determine perioperative factors predictive of postoperative VTE within 30 days in patients who experience a bleeding complication necessitating transfusion.
Results
The rate of bleeding necessitating transfusion was 1.3%. Bleeding was significantly more likely to occur in gastric bypass compared to sleeve gastrectomy (1.6 vs. 1.0%) (p < 0.0001). For all surgeries, increased age, length of stay, operative time, and comorbidities including hypertension, dyspnea with moderate exertion, partially dependent functional status, bleeding disorder, transfusion prior to surgery, ASA class III/IV, and metabolic syndrome increased the perioperative bleeding risk (p < 0.05). Multivariate analysis revealed that the rate of VTE was significantly higher after blood transfusion [Odds Ratio (OR) = 4.7; 95% CI 2.9–7.9; p < 0.0001). Predictive risk factors for VTE after transfusion included previous bleeding disorder, ASA class III or IV, and COPD (p < 0.05).
Conclusions
Bariatric surgery patients who receive postoperative blood transfusion are at a significantly increased risk for VTE. The etiology of VTE in those who are transfused is likely multifactorial and possibly related to withholding chemoprophylaxis and the potential of a hypercoagulable state induced by the transfusion. In those who bleed, consideration should be given to reinitiating chemoprophylaxis when safe, extending treatment after discharge, and screening ultrasound.
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Uncomplicated common bile duct stone removal guided by cholangioscopy versus conventional endoscopic retrograde cholangiopancreatography
Abstract
Background
Although previous studies have reported the possibility of therapeutic ERCP without fluoroscopy, more robust documentation of fluoroscopy-free common bile duct stone (CBDS) clearance is needed. Technically, "digital cholangioscopy" (DCS) may be used to confirm CBDS clearance. We aimed to compare the feasibility, safety, and radiation exposure between patients with CBDS undergoing stone removal by DCS and conventional ERCP (cERCP).
Methods
Fifty (50) consecutive patients with a CBDS size < 15 mm underwent DCS (SpyGlass DS Direct Visualization System, Boston Scientific, Marlboro, MA, USA) between December 2015 and October 2016. Of 202 consecutive patients undergoing cERCP during the same time frame, 50 matched pairs were created using propensity score matching analysis. In the DCS group, patients underwent biliary cannulation and CBDS removal without fluoroscopy followed by DCS to confirm complete CBDS clearance. A final occlusion cholangiogram was performed as the current standard of care to confirm CBDS clearance.
Results
Cannulation success rates were similar between the DCS and cERCP groups (98 vs. 98%). By intention-to-treat analysis, CBDS clearance in the DCS and cERCP groups was not different (90 vs. 98%; p = 0.20, respectively). DCS had successful CBDS removal in 45 cases, whereas 5 (10%) failed for clearance by DCS due to technical limitations. Adverse events were not different between both groups.
Conclusions
In the management of uncomplicated CBDS, our data confirmed the feasibility of DCS for CBDS clearance as it showed efficacy and safety comparable to those of cERCP. Although certain conditions may limit its effectiveness, DCS offers the ability to perform CBDS clearance without the need for fluoroscopy unit and can avoid radiation exposure while ERCP under fluoroscopy remains the current standard of care in patients with CBDS.
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Laparoscopic right posterior sectionectomy (LRPS): surgical techniques and clinical outcomes
Abstract
Background
Right posterior sectionectomy is one of the most technically challenging laparoscopic liver resections. Currently, there is limited published data regarding the technique and results required to better understand its safety and feasibility.
Aim
To report our experience, results and techniques, highlighting a variety of tips and tricks to facilitate this resection. A video is attached for technical demonstration.
Methods
Retrospective review of prospectively maintained databases from June 2006 to June 2016. Three different techniques were used: resection following hilar inflow control, inflow control at Rouviere's sulcus and resection with intra parenchymal control.
Results
29 LRPS were performed over a 10-year period. Median operative time was 240 min (150–480). Pringle's manoeuvre was performed in 19 (65.5%) with a median total duration of 35 (20–75) min. Median perioperative blood loss was 600 (100–2500) ml. Additional liver resections were performed in 16 (55.1%). There were two(6.9%) laparoscopic to open conversions. Median postoperative hospital stay was 5 (2–30) days. The median size of the tumour resected was 25 (10–54) mm with median number of resected lesions were 2 (1–4), median free resection margin was 9.5 (1–45) mm, margins were infiltrated (R1) in two (6.7%) cases. There was one death within 30-days (3.4%).
Conclusion
LRPS is feasible, efficient and safe. However, it is a technically challenging procedure and requires advance skills in liver and laparoscopic surgery. Surgeons should be familiar with a variety of approaches as each offers different advantages depending on the location and nature of the lesion, surgical preference and intraoperative findings.
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Discussion: Optimizing Patient Selection for Direct-to-Implant Immediate Breast Reconstruction Using Wise-Pattern Skin-Reducing Mastectomy in Large and Ptotic Breasts
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Proteomic Features of Colorectal Cancer Identify Tumor Subtypes Independent of Oncogenic Mutations and Independently Predict Relapse-Free Survival
Abstract
Background
The directed study of the functional proteome in colorectal cancer (CRC) has identified critical protein markers and signaling pathways; however, the prognostic relevance of many of these proteins remains unclear.
Methods
We determined the prognostic implications of the functional proteome in 263 CRC tumor samples from patients treated at MD Anderson Cancer Center (MDACC) and 462 patients from The Cancer Genome Atlas (TCGA) to identify patterns of protein expression that drive tumorigenesis. A total of 163 validated proteins were analyzed by reverse phase protein array (RPPA). Unsupervised hierarchical clustering of the tumor proteins from the MDACC cohort was performed, and clustering was validated using RPPA data from TCGA CRC. Cox regression was used to identify predictors of tumor recurrence.
Results
Clustering revealed dichotomization, with subtype A notable for a high epithelial-mesenchymal transition (EMT) protein signature, while subtype B was notable for high Akt/TSC/mTOR pathway components. Survival data were only available for the MDACC cohort and were used to evaluate prognostic relevance of these protein signatures. Group B demonstrated worse relapse-free survival (hazard ratio 2.11, 95% confidence interval 1.04–4.27, p = 0.039), although there was no difference in known genomic drivers between the two proteomic groups. Proteomic grouping and stage were significant predictors of recurrence on multivariate analysis. Eight proteins were found to be significant predictors of tumor recurrence on multivariate analysis: Collagen VI, FOXO3a, INPP4B, LcK, phospho-PEA15, phospho-PRAS40, Rad51, phospho-S6.
Conclusion
CRC can be classified into distinct subtypes by proteomic features independent of common oncogenic driver mutations. Proteomic analysis has identified key biomarkers with prognostic importance, however these findings require further validation in an independent cohort.
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Expression of 3β-Hydroxysteroid Dehydrogenase Type 1 in Breast Cancer is Associated with Poor Prognosis Independent of Estrogen Receptor Status
Abstract
Background
Human 3β-hydroxysteroid dehydrogenase type 1 (HSD3B1) plays a vital role in steroidogenesis in breast tumors and may therefore be a suitable target for treatment of breast cancer. This study investigated the role of HSD3B1 in the pathogenesis of breast cancer in clinical and experimental settings.
Methods
Expression of HSD3B1 in primary tumors of 258 breast cancer patients was evaluated by immunohistochemistry. Screening of breast cancer cell lines indicated that triple-negative MDA-MB-231 cells expressed HSD3B1. The effects from genetic and pharmacologic inhibition of HSD3B1 were assessed in vitro and in vivo.
Results
The findings showed that 44% of the 258 breast cancers were HSD3B1-positive. The HSD3B1-positivity was associated with advanced-stage disease (p = 0.009) and reduced recurrence-free survival (p = 0.048) but not with tumor subtype or estrogen receptor status. Silencing of HSD3B1 or treatment with an HSD3B1 inhibitor (trilostane) reduced colony formation in breast cancer cells. Knockdown of HSD3B1 inhibited cell proliferation and migration. Analysis of a murine xenograft tumor model indicated that trilostane significantly slowed tumor growth.
Conclusions
Expression of HSD3B1 in breast cancer is negatively associated with prognosis. The study found HSD3B1 to be a potential therapeutic target for breast cancer independent of estrogen receptor status.
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Identification of Patients for Adjuvant Therapy After Resection of Carcinoma of the Extrahepatic Bile Ducts: A Propensity Score-Matched Analysis
Abstract
Background
Resectability rates for extrahepatic cholangiocarcinoma have increased over time, but long-term survival after resection alone with curative intent remains poor. Recent series suggest improved survival with adjuvant therapy. Patient subsets benefiting most from adjuvant therapy have not been clearly defined.
Methods
Patients with extrahepatic cholangiocarcinoma who underwent resection with curative intent and received adjuvant therapy (chemotherapy ± radiotherapy) or surgery alone (SA) were identified in the U.S. National Cancer Data Base (2004–2014). Cox regression identified covariates associated with overall survival (OS). Adjuvant therapy and SA cohorts were matched (1:1) by propensity scores based on the survival hazard in Cox modeling. Overall survival was compared by Kaplan–Meier estimates.
Results
Of 4872 patients, adjuvant chemotherapy was used frequently for 2416 (49.6%), often in conjunction with radiotherapy (RT) (n = 1555, 64.4%). Adjuvant chemotherapy with or without RT was used increasingly for cases with higher T classification [reference: T1–2; T3: 1.36; 95% confidence interval (CI), 1.19–1.55; T4: 1.77; 95% CI 1.38–2.26], nodal positivity [odds ratio (OR), 1.26; 95% CI 1.01–1.56], lymphovascular invasion (OR 1.21; 95% CI 1.01–1.46), or margin-positive resection (OR 1.85; 95% CI 1.61–2.12), and was associated with significant improvements in OS for each high-risk subset in the propensity score-matched cohort. Adjuvant therapy was associated with improved median OS for hilar tumors (40.0 vs 30.6 months; p = 0.025) but not distal tumors (33.0 vs 30.3 months; p = 0.123). Chemoradiotherapy was associated with superior outcomes compared with chemotherapy alone in the subset of margin-positive resection [hazard ratio (HR), 0.63; 95% CI 0.42–0.94].
Conclusions
Adjuvant multimodality therapy is associated with improved survival for patients with resected extrahepatic cholangiocarcinoma and high-risk features.
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High STMN1 Expression is Associated with Cancer Progression and Chemo-Resistance in Lung Squamous Cell Carcinoma
Abstract
Background
Known as a microtubule-destabilizing protein, STMN1 (gene symbol: STMN1) regulates the dynamics of microtubules, cell cycle progress, and chemo-resistance against taxane agents. It is highly expressed in various human cancers and involved in cancer progression as well as poor prognosis.
Methods
Expression of STMN1 was examined by immunohistochemistry using FFPE tissue sections from 186 patients with lung squamous cell carcinoma (LSCC). Analysis of STMN1 suppression was performed for STMN1 small interfering RNA (siRNA)-transfected LSCC cell lines to determine the change in proliferation, invasive and apoptosis abilities, and paclitaxel sensitivity.
Results
The cytoplasmic STMN1 expression in LSCC was higher than in normal tissues. The high expression was significantly associated with vascular invasion (P = 0.0477) and poor prognosis. In addition, the proliferating and invasive abilities were decreased, and the apoptosis ability and paclitaxel sensitivity were increased in STMN1-suppressed LSCC cells compared with control cells.
Conclusion
The results suggest that STMN1 is a prognostic factor that also is associated with caner progression and chemo-resistance. Therefore, STMN1 could be a predictor for poor prognosis and a potential therapeutic target in LSCC.
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Discussion: Optimizing Patient Selection for Direct-to-Implant Immediate Breast Reconstruction Using Wise-Pattern Skin-Reducing Mastectomy in Large and Ptotic Breasts
from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2iugUpP
Proteomic Features of Colorectal Cancer Identify Tumor Subtypes Independent of Oncogenic Mutations and Independently Predict Relapse-Free Survival
Abstract
Background
The directed study of the functional proteome in colorectal cancer (CRC) has identified critical protein markers and signaling pathways; however, the prognostic relevance of many of these proteins remains unclear.
Methods
We determined the prognostic implications of the functional proteome in 263 CRC tumor samples from patients treated at MD Anderson Cancer Center (MDACC) and 462 patients from The Cancer Genome Atlas (TCGA) to identify patterns of protein expression that drive tumorigenesis. A total of 163 validated proteins were analyzed by reverse phase protein array (RPPA). Unsupervised hierarchical clustering of the tumor proteins from the MDACC cohort was performed, and clustering was validated using RPPA data from TCGA CRC. Cox regression was used to identify predictors of tumor recurrence.
Results
Clustering revealed dichotomization, with subtype A notable for a high epithelial-mesenchymal transition (EMT) protein signature, while subtype B was notable for high Akt/TSC/mTOR pathway components. Survival data were only available for the MDACC cohort and were used to evaluate prognostic relevance of these protein signatures. Group B demonstrated worse relapse-free survival (hazard ratio 2.11, 95% confidence interval 1.04–4.27, p = 0.039), although there was no difference in known genomic drivers between the two proteomic groups. Proteomic grouping and stage were significant predictors of recurrence on multivariate analysis. Eight proteins were found to be significant predictors of tumor recurrence on multivariate analysis: Collagen VI, FOXO3a, INPP4B, LcK, phospho-PEA15, phospho-PRAS40, Rad51, phospho-S6.
Conclusion
CRC can be classified into distinct subtypes by proteomic features independent of common oncogenic driver mutations. Proteomic analysis has identified key biomarkers with prognostic importance, however these findings require further validation in an independent cohort.
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Tumor Biology Predicts Pathologic Complete Response to Neoadjuvant Chemotherapy in Patients Presenting with Locally Advanced Breast Cancer
Abstract
Background
Neoadjuvant chemotherapy (NAC) is used to convert patients with inoperable locally advanced breast cancer (LABC) to operability, but has not traditionally been used to avoid mastectomy or axillary dissection in this subset.
Objective
The purpose of this study was to determine the rates of pathologic complete response (pCR) in LABC patients, and identify factors predictive of pCR to determine if responding patients might be suitable for limited surgery.
Methods
From 2006 to 2016, 1522 patients received NAC followed by surgery; 321 had advanced disease in the breast (cT4) and/or in the nodes (cN2/N3). pCR rates were assessed by T and N stage, and receptor subtype.
Results
Of 321 LABC patients, 223 were cT4, 77 were cN2, and 82 were cN3. Forty-three percent were hormone receptor (HR) positive/human epidermal growth factor receptor 2 (HER2) negative (HR+/HER2−), 23% were triple negative, and 34% were HER2+. The overall pCR rate was 25% and differed by receptor subtype (HR+/HER2− 7%, triple negative 23%, HER2+ 48%; p < 0.001). Breast pCR occurred in 27% of patients and was similar in T4 versus non-T4 disease (29% vs. 22%; p = 0.26). Nodal pCR was achieved in 38% of cN+ patients and did not differ by nodal stage (cN1 43%, cN2 36%, cN3 32%; p = 0.23). Nodal pCR was significantly more common than breast pCR (p = 0.014) across all tumor subtypes. Receptor subtype was the only predictor of overall pCR (p < 0.001).
Conclusion
In patients with LABC, pCR after NAC was seen in 25%, and did not differ by T or N stage. Tumor biology, but not extent of disease, predicted pCR. Studies assessing the feasibility of surgical downstaging with NAC in LABC patients are warranted.
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Expression of 3β-Hydroxysteroid Dehydrogenase Type 1 in Breast Cancer is Associated with Poor Prognosis Independent of Estrogen Receptor Status
Abstract
Background
Human 3β-hydroxysteroid dehydrogenase type 1 (HSD3B1) plays a vital role in steroidogenesis in breast tumors and may therefore be a suitable target for treatment of breast cancer. This study investigated the role of HSD3B1 in the pathogenesis of breast cancer in clinical and experimental settings.
Methods
Expression of HSD3B1 in primary tumors of 258 breast cancer patients was evaluated by immunohistochemistry. Screening of breast cancer cell lines indicated that triple-negative MDA-MB-231 cells expressed HSD3B1. The effects from genetic and pharmacologic inhibition of HSD3B1 were assessed in vitro and in vivo.
Results
The findings showed that 44% of the 258 breast cancers were HSD3B1-positive. The HSD3B1-positivity was associated with advanced-stage disease (p = 0.009) and reduced recurrence-free survival (p = 0.048) but not with tumor subtype or estrogen receptor status. Silencing of HSD3B1 or treatment with an HSD3B1 inhibitor (trilostane) reduced colony formation in breast cancer cells. Knockdown of HSD3B1 inhibited cell proliferation and migration. Analysis of a murine xenograft tumor model indicated that trilostane significantly slowed tumor growth.
Conclusions
Expression of HSD3B1 in breast cancer is negatively associated with prognosis. The study found HSD3B1 to be a potential therapeutic target for breast cancer independent of estrogen receptor status.
from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2hCpDqb
Identification of Patients for Adjuvant Therapy After Resection of Carcinoma of the Extrahepatic Bile Ducts: A Propensity Score-Matched Analysis
Abstract
Background
Resectability rates for extrahepatic cholangiocarcinoma have increased over time, but long-term survival after resection alone with curative intent remains poor. Recent series suggest improved survival with adjuvant therapy. Patient subsets benefiting most from adjuvant therapy have not been clearly defined.
Methods
Patients with extrahepatic cholangiocarcinoma who underwent resection with curative intent and received adjuvant therapy (chemotherapy ± radiotherapy) or surgery alone (SA) were identified in the U.S. National Cancer Data Base (2004–2014). Cox regression identified covariates associated with overall survival (OS). Adjuvant therapy and SA cohorts were matched (1:1) by propensity scores based on the survival hazard in Cox modeling. Overall survival was compared by Kaplan–Meier estimates.
Results
Of 4872 patients, adjuvant chemotherapy was used frequently for 2416 (49.6%), often in conjunction with radiotherapy (RT) (n = 1555, 64.4%). Adjuvant chemotherapy with or without RT was used increasingly for cases with higher T classification [reference: T1–2; T3: 1.36; 95% confidence interval (CI), 1.19–1.55; T4: 1.77; 95% CI 1.38–2.26], nodal positivity [odds ratio (OR), 1.26; 95% CI 1.01–1.56], lymphovascular invasion (OR 1.21; 95% CI 1.01–1.46), or margin-positive resection (OR 1.85; 95% CI 1.61–2.12), and was associated with significant improvements in OS for each high-risk subset in the propensity score-matched cohort. Adjuvant therapy was associated with improved median OS for hilar tumors (40.0 vs 30.6 months; p = 0.025) but not distal tumors (33.0 vs 30.3 months; p = 0.123). Chemoradiotherapy was associated with superior outcomes compared with chemotherapy alone in the subset of margin-positive resection [hazard ratio (HR), 0.63; 95% CI 0.42–0.94].
Conclusions
Adjuvant multimodality therapy is associated with improved survival for patients with resected extrahepatic cholangiocarcinoma and high-risk features.
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High STMN1 Expression is Associated with Cancer Progression and Chemo-Resistance in Lung Squamous Cell Carcinoma
Abstract
Background
Known as a microtubule-destabilizing protein, STMN1 (gene symbol: STMN1) regulates the dynamics of microtubules, cell cycle progress, and chemo-resistance against taxane agents. It is highly expressed in various human cancers and involved in cancer progression as well as poor prognosis.
Methods
Expression of STMN1 was examined by immunohistochemistry using FFPE tissue sections from 186 patients with lung squamous cell carcinoma (LSCC). Analysis of STMN1 suppression was performed for STMN1 small interfering RNA (siRNA)-transfected LSCC cell lines to determine the change in proliferation, invasive and apoptosis abilities, and paclitaxel sensitivity.
Results
The cytoplasmic STMN1 expression in LSCC was higher than in normal tissues. The high expression was significantly associated with vascular invasion (P = 0.0477) and poor prognosis. In addition, the proliferating and invasive abilities were decreased, and the apoptosis ability and paclitaxel sensitivity were increased in STMN1-suppressed LSCC cells compared with control cells.
Conclusion
The results suggest that STMN1 is a prognostic factor that also is associated with caner progression and chemo-resistance. Therefore, STMN1 could be a predictor for poor prognosis and a potential therapeutic target in LSCC.
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Cooperative antitumor activities of carnosic acid and Trastuzumab in ERBB2+ breast cancer cells
ERBB2 is overexpressed in up to 20–30% of human breast cancers (BCs), and it is associated with aggressive disease. Trastuzumab (Tz), a humanized monoclonal antibody, improves the prognosis associated with ERB...
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Bioethicist: History Tells Us CRISPR Fears Are Overblown
Worries that gene editing will lead to designer babies parallel fears from previous decades about amniocentesis, which, a renowned bioethicist and TEDMED speaker points out, were never realized.
Medscape Medical News
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Conjugated Bilirubin Upregulates TIM-3 Expression on CD4+CD25+ T Cells: Anti-Inflammatory Implications for Hepatitis A Virus Infection
Viral Immunology , Vol. 0, No. 0.
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Representation and processing of multi-word expressions in the brain
Source:Brain and Language, Volume 175
Author(s): Anna Siyanova-Chanturia, Kathy Conklin, Sendy Caffarra, Edith Kaan, Walter J.B. van Heuven
Language comprehension is sensitive to the predictability of the upcoming information. Prediction allows for smooth, expedient and successful communication. While general discourse-based constraints have been investigated in detail, more specific phrase-level prediction has received little attention. We address this gap by exploring the ERPs elicited during the comprehension of English binomials – familiar and predictable multi-word expressions. In Experiment 1a, participants read binomial expressions (knife and fork), infrequent strongly associated phrases (spoon and fork), and semantic violations (theme and fork). In Experiment 1b, participants read the same stimuli without "and". Experiment 1a revealed that binomials elicited larger P300s and smaller N400s compared to the other conditions, reflecting the activation of a 'template' that matches the upcoming information (P300) and pointing to easier semantic integration (N400). In contrast, no differences were observed between binomials and associates in Experiment 1b. We conclude that distinct mechanisms underlie the processing of predicable and novel sequences.
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Neural correlates for naming disadvantage of the dominant language in bilingual word production
Source:Brain and Language, Volume 175
Author(s): Yongben Fu, Di Lu, Chunyan Kang, Junjie Wu, Fengyang Ma, Guosheng Ding, Taomei Guo
The present study investigated the neural correlates of naming disadvantage of the dominant language under the mixed language context. Twenty one unbalanced Chinese-English bilinguals completed a cued picture naming task while being scanned with functional magnetic resonance imaging (fMRI). Behavioral results showed that naming pictures in the second lanuage (L2) was significantly slower than naming pictures in the first language (L1) under a single language context. When comparing picture naming in L2 to naming in L1, enhanced activity in the left inferior parietal lobule and left cerebellum was observed. On the contrary, naming pictures in Chinese (L1) was significantly slower than naming in English (L2) under the mixed language context. The fMRI results showed that bilateral inferior frontal gyri, right middle frontal gyrus, and right supplementary motor area were activated to a greater extent in L1 than in L2. These results suggest that the dominant language is inhibited to a greater extent to ensure the production of the second language under the mixed language context. Therefore, more attentional control resources are recruited when bilinguals produced the dominant language. The present study, for the first time, reveals neural correlates of L1 naming disadvantage under the mixed language context.
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