Stercoral perforation proximal to the stapled anastomosis after low anterior resection with an intraluminal device

Stercoral perforation of the colon is a rare phenomenon and a potential life-threatening condition requiring acute intervention. A little more than 200 cases have been described to date. The mechanism is not completely understood. In this short communication, we present three patients with a colon perforation proximal to the anastomosis, similar to a stercoral perforation, following colorectal cancer resection with application of an intraluminal device, the C-seal

Colorectal anastomotic leak:Transcriptomic profile analysis

BACKGROUND: Anastomotic leakage in patients undergoing colorectal surgery is associated with morbidity and mortality. Although multiple risk factors have been identified, the underlying mechanisms are mainly unknown. The aim of this study was to perform a transcriptome analysis of genes underlying the development of anastomotic leakage. METHODS: A set of human samples from the anastomotic site collected during stapled colorectal anastomosis were used in the study. Transcriptomic profiles were generated for patients who developing anastomotic leakage and case-matched controls with normal anastomotic healing to identify genes and biological processes associated with the development of anastomotic leakage. RESULTS: The analysis included 22 patients with and 69 without anastomotic leakage. Differential expression analysis showed that 44 genes had adjusted P < 0.050, consisting of two upregulated and 42 downregulated genes. Co-functionality analysis of the 150 most upregulated and 150 most downregulated genes using the GenetICA framework showed formation of clusters of genes with different enrichment for biological pathways. The enriched pathways for the downregulated genes are involved in immune response, angiogenesis, protein metabolism, and collagen cross-linking. The enriched pathways for upregulated genes are involved in cell division. CONCLUSION: These data indicate that patients who develop anastomotic leakage start the healing process with an error at the level of gene regulation at the time of surgery. Despite normal macroscopic appearance during surgery, the transcriptome data identified several differences in gene expression between patients who developed anastomotic leakage and those who did not. The expressed genes and enriched processes are involved in the different stages of wound healing. These provide therapeutic and diagnostic targets for patients at risk of anastomotic leakage

Peribiliary glands are key in regeneration of the human biliary epithelium after severe bile duct injury

Peribiliary glands (PBG) are a source of stem/progenitor cells organized in a cellular network encircling large bile ducts. Severe cholangiopathy with loss of luminal biliary epithelium has been proposed to activate PBG, resulting in cell proliferation and differentiation to restore biliary epithelial integrity. However, formal evidence for this concept in human livers is lacking. We, therefore, developed a novel ex vivo model using precision-cut slices of extrahepatic human bile ducts obtained from discarded donor livers, providing an intact anatomical organization of cell structures, to study spatiotemporal differentiation and migration of PBG cells after severe biliary injury. Post-ischemic bile duct slices were incubated in oxygenated culture medium for up to a week. At baseline, severe tissue injury was evident with loss of luminal epithelial lining and mural stroma necrosis. In contrast, PBG remained relatively well preserved and different reactions of PBG were noted, including PBG dilatation, cell proliferation and maturation. Proliferation of PBG cells increased after 24 h of oxygenated incubation, reaching a peak after 72 h. Proliferation of PBG cells was paralleled by a reduction in PBG apoptosis and differentiation from a primitive and pluripotent (Nanog+/Sox9+) to a mature (CFTR+/secretin receptor+) and activated phenotype (increased expression of HIF-1α, Glut-1, and VEGF-A). Migration of proliferating PBG cells in our ex vivo model was unorganized, but resulted in generation of epithelial monolayers at stromal surfaces. CONCLUSION: Human PBG contain biliary progenitor cells and are able to respond to bile duct epithelial loss with proliferation, differentiation, and maturation to restore epithelial integrity. The ex vivo spatiotemporal behaviour of human PBG cells provides evidence for a pivotal role of PBG in biliary regeneration after severe injury. This article is protected by copyright. All rights reserved

Infliximab Does Not Promote the Presence of Collagenolytic Bacteria in a Mouse Model of Colorectal Anastomosis

BACKGROUND: Previous work from our group has suggested a pivotal role for collagenolytic bacteria in the development of anastomotic complications. Tumor necrosis factor antagonists are a mainstay of treatment for patients with inflammatory bowel disease. The reported impact of these agents on key surgical outcomes such as anastomotic leak has been inconsistent. The objective of this study is to assess the impact of infliximab on the anastomotic microbiome in a mouse model of colon resection. DESIGN: BALB/c mice underwent colon resection with primary anastomosis. Mice were randomly assigned to receive either an intraperitoneal dose of saline (control) or 10 mg/kg of infliximab for 8 weeks prior to surgery. On postoperative day 7, the animals were sacrificed. Anastomotic tissues were analyzed by histology with TUNNEL staining as a marker of epithelial apoptosis. In order to assess compositional and functional changes of the local microbiome, anastomotic tissues were further analyzed by 16S rRNA V4 region sequencing and for the presence of collagenolytic strains that may impair anastomotic healing. The main outcome measures were microbiome community structure and the presence of collagenolytic bacteria. RESULTS: Infliximab-treated mice demonstrated an increase in epithelial apoptosis, consistent with the expected drug effect. Although infliximab modified the perianastomotic microbiome, no increase in the presence of collagenolytic bacteria was observed. CONCLUSIONS: Infliximab did not promote the emergence of collagenolytic bacteria or demonstrably impair anastomotic healing in a mouse model of colon resection and anastomosis

Mucus Microbiome of Anastomotic Tissue During Surgery Has Predictive Value for Colorectal Anastomotic Leakage

OBJECTIVE: The aim of the present study is to investigate the association of gut microbiota, depending on treatment method, with the development of colorectal anastomotic leakage (AL). BACKGROUND: AL is a major cause for morbidity and mortality after colorectal surgery, but the mechanism behind this complication still is not fully understood. METHODS: Bacterial DNA was isolated from 123 "donuts" of patients where a stapled colorectal anastomosis was made and was analyzed using 16S MiSeq sequencing. In 63 patients, this anastomosis was covered with a C-seal, a bioresorbable sheath stapled to the anastomosis. RESULTS: In non-C-seal patients, AL development was associated with low microbial diversity (P = 0.002) and correspondingly with a high abundance of the dominant Bacteroidaceae and Lachnospiraceae families (P = 0.008 and 0.010, respectively). In C-seal samples, where AL rates were slightly higher (25% vs 17%), an association with the gut microbiota composition was almost undetectable. Only a few opportunistic pathogenic groups of low abundance were associated with AL in C-seal patients, in particular Prevotella oralis (P = 0.007). CONCLUSIONS: AL in patients without a C-seal can be linked to the intestinal microbiota, in particular with a low microbial diversity and a higher abundance of especially mucin-degrading members of the Bacteroidaceae and Lachnospiraceae families. In C-seal patients, however, it seems that any potential protective benefits or harmful consequences of the gut microbiota composition in regard to wound healing are negated, as progression to AL is independent of the initially dominant bacterial composition.This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0

Prognostic significance of a complete pathological response after induction chemotherapy in operable breast cancer

Only a few papers have been published concerning the incidence and outcome of patients with a pathological complete response after cytotoxic treatment in breast cancer. The purpose of this retrospective study was to assess the outcome of patients found to have a pathological complete response in both the breast and axillary lymph nodes after neoadjuvant chemotherapy for operable breast cancer. Our goal was also to determine whether the residual pathological size of the tumour in breast could be correlated with pathological node status. Between 1982 and 2000, 451 consecutive patients were registered into five prospective phase II trials. After six cycles, 396 patients underwent surgery with axillary dissection for 277 patients (69.9%). Pathological response was evaluated according to the Chevallier's classification. At a median follow-up of 8 years, survival was analysed as a function of pathological response. A pathological complete response rate was obtained in 60 patients (15.2%) after induction chemotherapy. Breast tumour persistence was significantly related to positive axillary nodes (P=5.10−6). At 15 years, overall survival and disease-free survival rates were significantly higher in the group who had a pathological complete response than in the group who had less than a pathological complete response (P=0.047 and P=0.024, respectively). In the absence of pathological complete response and furthermore when there is a notable remaining pathological disease, axillary dissection is still important to determine a major prognostic factor and subsequently, a second non cross resistant adjuvant regimen or high dose chemotherapy could lead to a survival benefit

Strategies of the honeybee Apis mellifera during visual search for vertical targets presented at various heights: a role for spatial attention?

When honeybees are presented with a colour discrimination task, they tend to choose swiftly and accurately when objects are presented in the ventral part of their frontal visual field. In contrast, poor performance is observed when objects appear in the dorsal part. Here we investigate if this asymmetry is caused by fixed search patterns or if bees can use alternative search mechanisms such as spatial attention, which allows flexible focusing on different areas of the visual field. We asked individual honeybees to choose an orange rewarded target among blue distractors. Target and distractors were presented in the ventral visual field, the dorsal field or both. Bees presented with targets in the ventral visual field consistently had the highest search efficiency, with rapid decisions, high accuracy and direct flight paths. In contrast, search performance for dorsally located targets was inaccurate and slow at the beginning of the test phase, but bees increased their search performance significantly after a few learning trials: they found the target faster, made fewer errors and flew in a straight line towards the target. However, bees needed thrice as long to improve the search for a dorsally located target when the target's position changed randomly between the ventral and the dorsal visual field. We propose that honeybees form expectations of the location of the target's appearance and adapt their search strategy accordingly. Different possible mechanisms of this behavioural adaptation are discussed.L.M. was recipient of a DOC-fFORTE fellowship of the Austrian Academy of Science at the Department of Integrative Zoology, University of Vienna. L.C. is supported by an ERC Advanced Grant and a Royal Society Wolfson Research Merit Award

Anthropometric and Physical Qualities of Elite Male Youth Rugby League Players

Rugby league is a collision team sport played at junior and senior levels worldwide, whereby players require highly developed anthropometric and physical qualities (i.e., speed, change of direction speed, aerobic capacity, muscular strength and power). Within junior levels, professional clubs and national governing bodies implement talent identification and development programmes to support the development of youth (i.e., 13-20 years) rugby league players into professional athletes. This review presents and critically appraises the anthropometric and physical qualities of elite male youth rugby league players aged between 13 and 20 years by age category, playing standard and playing position. Height, body mass, body composition, linear speed, change of direction speed, aerobic capacity, muscular strength and power characteristics are presented and demonstrate that qualities develop with age and differentiate between playing standard and playing position. This highlights the importance of anthropometric and physical qualities for the identification and development of youth rugby league players. However, factors such as maturity status, variability in development, longitudinal monitoring and career attainment should be considered to help understand, identify and develop the physical qualities of youth players. Further extensive research is required into the anthropometric and physical qualities of youth rugby league players, specifically considering national standardized testing batteries, links between physical qualities and match performance, together with intervention studies, to inform the physical development of youth rugby league players for talent identification and development purposes