Electrothermal bipolar vessel ligation improves operative time during laparoscopic total proctocolectomy: a large single-center experience.

Background: Laparoscopic total proctocolectomy (TPC) with or without ileoanal pouch is a major operation for which the traditional benefits of laparoscopy were not immediately apparent, in part due to the longer operating times. The use of energy devices has been shown to improve operative outcomes for patients who undergo laparoscopic segmental colectomies, but there are limited data for laparoscopic TPC (LTPC).

Methods: All patients who underwent LTPC between January 2002 and July 2011 were identified from a prospectively maintained institutional-review-board-approved database.

caRpools: an R package for exploratory data analysis and documentation of pooled CRISPR/Cas9 screens.

Motivation: Genetic screens by CRISPR/Cas9-mediated genome engineering have become a powerful tool for functional genomics. However, there is currently a lack of end-to-end software pipelines to analyze CRISPR/Cas9 screens based on next generation sequencing.

Results: The CRISPR-AnalyzeR for pooled screens (caRpools) is an R package for exploratory data analysis that provides a complete workflow to analyze CRISPR/Cas9 screens.

Biliary leakage from gallbladder bed after cholecystectomy: Luschka duct or hepaticocholecystic duct?

Anatomic variations in the biliary tract are common and can cause difficulties when a cholecystectomy is performed. One of the most common ones are hepaticocholecystic ducts and Luschka ducts, connecting the gallbladder or its bed to the bile ducts but distinction between these two types of ducts can be difficult. We do discuss here the differences between these anatomical variations, their origin and their clinical implications.

Functional fingerprinting of human mesenchymal stem cells using high-throughput RNAi screening.

Mesenchymal stem cells (MSCs) are promising candidates for cellular therapies ranging from tissue repair in regenerative medicine to immunomodulation in graft versus host disease after allogeneic transplantation or in autoimmune diseases. Nonetheless, progress has been hampered by their enormous phenotypic as well as functional heterogeneity and the lack of uniform standards and guidelines for quality control. In this study, we describe a method to perform cellular phenotyping by high-throughput RNA interference in primary human bone marrow MSCs.

Amplicon sequencing of colorectal cancer: variant calling in frozen and formalin-fixed samples.

Next generation sequencing (NGS) is an emerging technology becoming relevant for genotyping of clinical samples. Here, we assessed the stability of amplicon sequencing from formalin-fixed paraffin-embedded (FFPE) and paired frozen samples from colorectal cancer metastases with different analysis pipelines. 212 amplicon regions in 48 cancer related genes were sequenced with Illumina MiSeq using DNA isolated from resection specimens from 17 patients with colorectal cancer liver metastases.

REPTOR and REPTOR-BP Regulate Organismal Metabolism and Transcription Downstream of TORC1.

TORC1 regulates growth and metabolism, in part, by influencing transcriptional programs. Here, we identify REPTOR and REPTOR-BP as transcription factors downstream of TORC1 that are required for ∼ 90% of the transcriptional induction that occurs upon TORC1 inhibition in Drosophila. Thus, REPTOR and REPTOR-BP are major effectors of the transcriptional stress response induced upon TORC1 inhibition, analogous to the role of FOXO downstream of Akt.

Normalization of CEA Levels Post-Neoadjuvant Therapy is a Strong Predictor of Pathologic Complete Response in Rectal Cancer.

Background: Recent attention has been focused on the relationship between carcinoembryonic antigen (CEA) and pathological complete response (pCR), without consensus regarding its predictive value. This study aims to examine the association between CEA and pCR.

Methods: We conducted a retrospective review of a prospectively maintained database of all patients who underwent primary rectal cancer resection after neo-adjuvant chemoradiotherapy (nCRT).

IPAA-related sepsis significantly increases morbidity of ileoanal pouch excision.

Background: Perineal wound complications after ileoanal pouch excision remain a significant cause of morbidity.

Objective: The purpose of this work was to describe the incidence, outcomes, and predictors of perineal wound complications after pouch excision.

Design: This was a retrospective medical chart review.

A map of directional genetic interactions in a metazoan cell.

Gene-gene interactions shape complex phenotypes and modify the effects of mutations during development and disease. The effects of statistical gene-gene interactions on phenotypes have been used to assign genes to functional modules. However, directional, epistatic interactions, which reflect regulatory relationships between genes, have been challenging to map at large-scale.

A high-throughput RNAi screen for detection of immune-checkpoint molecules that mediate tumor resistance to cytotoxic T lymphocytes.

The success of T cell-based cancer immunotherapy is limited by tumor's resistance against killing by cytotoxic T lymphocytes (CTLs). Tumor-immune resistance is mediated by cell surface ligands that engage immune-inhibitory receptors on T cells. These ligands represent potent targets for therapeutic inhibition.

A novel inflammatory pathway mediating rapid hepcidin-independent hypoferremia.

Regulation of iron metabolism and innate immunity are tightly interlinked. The acute phase response to infection and inflammation induces alterations in iron homeostasis that reduce iron supplies to pathogens. The iron hormone hepcidin is activated by such stimuli causing degradation of the iron exporter ferroportin and reduced iron release from macrophages, suggesting that hepcidin is the crucial effector of inflammatory hypoferremia.

Dpp/Gbb signaling is required for normal intestinal regeneration during infection.

Maintaining tissue homeostasis is a critical process during infection and inflammation. Tissues with a high intrinsic turnover, such as the intestinal epithelium, must launch a rapid response to infections while simultaneously coordinating cell proliferation and differentiation decisions. In this study, we searched for genes required for regeneration of the Drosophila intestine, and thereby affecting overall organism survival after infection with pathogenic bacteria.

Cost-effectiveness of Enhanced Recovery Versus Conventional Perioperative Management for Colorectal Surgery.

Objective: To determine the cost-effectiveness of enhanced recovery pathways (ERPs) versus conventional care for patients undergoing elective colorectal surgery.

Background: ERPs for colorectal surgery are clinically effective, but their cost-effectiveness is unknown.

Methods: A multi-institutional prospective cohort cost-effectiveness analysis was performed.

Measuring genetic interactions in human cells by RNAi and imaging.

Observation of how genetic interactions modulate phenotypes is a powerful method for dissecting their underlying molecular and functional networks. Whereas in model organisms genetic interaction studies are well established, systematic analysis of genetic interactions in human cells has remained challenging. Here we provide a detailed protocol for large-scale mapping of genetic interactions in human cells using a high-throughput phenotyping approach.

Small bowel adenocarcinoma and Crohn's disease: any further ahead than 50 years ago?

This review of the literature on small bowel carcinoma associated with Crohn's disease specifically addresses the incidence, risk factors, and protective factors which have been identified. It also reviews the clinical presentation, the current modalities of diagnosis, the pathology, treatment, and surveillance. Finally, the prognosis and future direction are addressed.

Functional analysis of the Drosophila embryonic germ cell transcriptome by RNA interference.

In Drosophila melanogaster, primordial germ cells are specified at the posterior pole of the very early embryo. This process is regulated by the posterior localized germ plasm that contains a large number of RNAs of maternal origin. Transcription in the primordial germ cells is actively down-regulated until germ cell fate is established.

Molecular dissection of Wnt3a-Frizzled8 interaction reveals essential and modulatory determinants of Wnt signaling activity.

Background: Wnt proteins are a family of secreted signaling molecules that regulate key developmental processes in metazoans. The molecular basis of Wnt binding to Frizzled and LRP5/6 co-receptors has long been unknown due to the lack of structural data on Wnt ligands. Only recently, the crystal structure of the Wnt8-Frizzled8-cysteine-rich-domain (CRD) complex was solved, but the significance of interaction sites that influence Wnt signaling has not been assessed.

CAGS and ACS evidence based reviews in surgery. Is a diverting loop ileostomy and colonic lavage an alternative to colectomy for the treatment of severe Clostridium difficile-associated disease?

The term “evidence-based medicine” was first coined by Sackett and colleagues as “the conscientious, explicit and judicious use of current best evidence in making decisions about the care of individual patients.”1 The key to practising evidencebased medicine is applying the best current knowledge to decisions in individual patients. Medical knowledge is continually and rapidly expanding.

Endothelial cell-derived non-canonical Wnt ligands control vascular pruning in angiogenesis.

Multiple cell types involved in the regulation of angiogenesis express Wnt ligands. Although β-catenin dependent and independent Wnt signaling pathways have been shown to control angiogenesis, the contribution of individual cell types to activate these downstream pathways in endothelial cells (ECs) during blood vessel formation is still elusive. To investigate the role of ECs in contributing Wnt ligands for regulation of blood vessel formation, we conditionally deleted the Wnt secretion factor Evi in mouse ECs (Evi-ECKO).

A synthetic lethal screen identifies FAT1 as an antagonist of caspase-8 in extrinsic apoptosis.

The extrinsic apoptosis pathway is initiated by binding of death ligands to death receptors resulting in the formation of the death-inducing signaling complex (DISC). Activation of procaspase-8 within the DISC and its release from the signaling complex is required for processing executor caspases and commiting cell death. Here, we report that the atypical cadherin FAT1 interacts with caspase-8 preventing the association of caspase-8 with the DISC.