Global overview of the management of acute cholecystitis during the COVID-19 pandemic (CHOLECOVID study)

There was no funding support for this study. Disclosure. The authors declare no conflict of interest.Peer reviewedPublisher PD

Mechanisms of bacterial internalization in the stressed enterocyte

The 'leaky gut' hypothesiS proposes that disruption of the intestinal barrier is critical to the development of inflammatory bowel disease, and characterises the response to severe injury and infection, where local release of inflammatory mediators arid increased gut permeability lead to multiple organ failure. The mechanisms by which commensal gut bacteria enter entehocytes during inflammatory stress and the consequences for enterocyte function are unclear. The purpose of this study was to define the mechanisms by which inflammatory stimuli induce internalization of commensal bacteria within enterocytes, the signalling pathways involved, and the effects of internalized bacteria on the t~nterocyte. Caco-2 monolayers were exposed to an inflammatory stimulus in the form of IFN-y and then incubated with a variety of non-pathogenic commensal microflora. Bacterial internalization and translocation across these monolayers was .quantified by serial dilution culture, signalling mechanisms were investigated using signalling inhibitors, and US~l integrin antibody was used to determine the role of inte.grins. DNA was extracted from the different strains and screened for common bacterial adhesins. The effect of commensal E. coli strains on enterocyte IL-8 secretion was also investigated using ELISA. The translocation of bacteria appears to be strain-specific and depends on a change in the enterocyte brought about by exposure. to IFN-y. It involves interaction with US~l integrin, and utilises a Src-kinase and PI3-kinase dependent process. IFN·y does not appear to increase the expression of usn. integrin but may stimulate redistribution from the basolateral to apical membrane. Most bacterial strains possess the Type 1 fimbrial adhesin, but there appears to be nIJ difference between translocating and nontranslocating strains of E. coli. Most E. coli strains stimulate IL-8 secretion by enterocytes however, E. coli C25 inhi.bits the secretion of IL-8 in all enterocyte cell lines which is a novel finding and is worthy of further investigation. The in vitro model appears consistent and will allow the n1echanistic pathway of bacterial translocation to be elucidated.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

T-Cell Infiltration and Clonality May Identify Distinct Survival Groups in Colorectal Cancer: Development and Validation of a Prognostic Model Based on The Cancer Genome Atlas (TCGA) and Clinical Proteomic Tumor Analysis Consortium (CPTAC)

Predicting the survival outcomes of patients with colorectal cancer (CRC) remains challenging. We investigated the prognostic significance of the transcriptome and tumour-infiltrating lymphocyte T-cell receptor (TIL/Tc-TCR) repertoire and analysed TIL/Tc-TCR sequences of The Cancer Genome Atlas (TCGA) and the Clinical Proteomic Tumor Analysis Consortium (CPTAC) CRC cohorts. Using a multivariate Cox regression, we tested whether TIL/Tc-TCR repertoire, patient and tumour characteristics (stage, sidedness, total non-synonymous mutations, microsatellite instability (MSI) and transcriptional signatures) correlated with patient overall survival (OS) and designed a prognostic nomogram. A multivariate analysis (C-index = 0.75) showed that only patient age, disease stage, TIL/Tc degree of infiltration and clonality were independent prognostic factors for OS. The cut-offs for patients’ allocation to TIL/Tc abundance subgroups were determined using a strategy of maximally selected rank statistics with the OptimalCutpoints R package. These were “high”, “low” and “very high” (90 th percentile) TIL/Tc infiltration-stratified OS (median not reached, 67 and 44.3 months; p < 0.001); the results were validated in the CPTAC cohort. TIL/Tc clonality was prognostic (median OS in “high” vs. “low” clonality not reached and 67.3 months; p = 0.041) and independent of TIL/Tc infiltration. Whilst tumour sidedness was not prognostic, the “very highly” infiltrated tumours were prevalent among right-sided CRCs (p = 0.039) and showed distinct immunological features, with lower Th1 signature (p = 0.004), higher PD-L1 expression (p < 0.001) and likely enrichment in highly suppressory IL1R1+ Tregs (FoxP3 and IL1R1 overexpression, p < 0.001). TIL/Tc abundance and clonality are independent prognosticators in CRC and, combined with clinical variables, refine risk stratification. We identified a subset of CRCs with “very high” TIL/Tc infiltration, poor prognosis and distinct genetic and immunologic features, which may benefit from alternative therapeutic approaches. These results need validation in prospective patient cohorts

The first international Delphi consensus statement on Laparoscopic Gastrointestinal surgery

BACKGROUND: Laparoscopic surgery has almost replaced open surgery in many areas of Gastro-Intestinal (GI) surgery. There is currently no published expert consensus statement on the principles of laparoscopic GI surgery. This may have affected the training of new surgeons. This exercise aimed to achieve an expert consensus on important principles of laparoscopic GI surgery. METHODS: A committee of 38 international experts in laparoscopic GI surgery proposed and voted on 149 statements in two rounds following a strict modified Delphi protocol. RESULTS: A consensus was achieved on 133 statements after two rounds of voting. All experts agreed on tailoring the first port site to the patient, whereas 84.2% advised avoiding the umbilical area for pneumoperitoneum in patients who had a prior midline laparotomy. Moreover, 86.8% agreed on closing all 15 mm ports irrespective of the patient's body mass index. There was a 100% consensus on using cartridges of appropriate height for stapling, checking the doughnuts after using circular staplers, and keeping the vibrating blade of the ultrasonic energy device in view and away from vascular structures. An 84.2% advised avoiding drain insertion through a ≥10 mm port site as it increases the risk of port-site hernia. There was 94.7% consensus on adding laparoscopic retrieval bags to the operating count and ensuring any surgical specimen left inside for later removal is added to the operating count. CONCLUSION: Thirty-eight experts achieved a consensus on 133 statements concerning various aspects of laparoscopic GI Surgery. Increased awareness of these could facilitate training and improve patient outcomes

The first international Delphi consensus statement on Laparoscopic Gastrointestinal surgery: Laparoscopic GI Surgery Consensus

Background: Laparoscopic surgery has almost replaced open surgery in many areas of Gastro-Intestinal (GI) surgery. There is currently no published expert consensus statement on the principles of laparoscopic GI surgery. This may have affected the training of new surgeons. This exercise aimed to achieve an expert consensus on important principles of laparoscopic GI surgery. Methods: A committee of 38 international experts in laparoscopic GI surgery proposed and voted on 149 statements in two rounds following a strict modified Delphi protocol. Results: A consensus was achieved on 133 statements after two rounds of voting. All experts agreed on tailoring the first port site to the patient, whereas 84.2% advised avoiding the umbilical area for pneumoperitoneum in patients who had a prior midline laparotomy. Moreover, 86.8% agreed on closing all 15 mm ports irrespective of the patient's body mass index. There was a 100% consensus on using cartridges of appropriate height for stapling, checking the doughnuts after using circular staplers, and keeping the vibrating blade of the ultrasonic energy device in view and away from vascular structures. An 84.2% advised avoiding drain insertion through a ≥10 mm port site as it increases the risk of port-site hernia. There was 94.7% consensus on adding laparoscopic retrieval bags to the operating count and ensuring any surgical specimen left inside for later removal is added to the operating count. Conclusion: Thirty-eight experts achieved a consensus on 133 statements concerning various aspects of laparoscopic GI Surgery. Increased awareness of these could facilitate training and improve patient outcomes

The first international Delphi consensus statement on Laparoscopic Gastrointestinal surgery

Background: laparoscopic surgery has almost replaced open surgery in many areas of Gastro-Intestinal (GI) surgery. There is currently no published expert consensus statement on the principles of laparoscopic GI surgery. This may have affected the training of new surgeons. This exercise aimed to achieve an expert consensus on important principles of laparoscopic GI surgery. Methods: a committee of 38 international experts in laparoscopic GI surgery proposed and voted on 149 statements in two rounds following a strict modified Delphi protocol. Results: a consensus was achieved on 133 statements after two rounds of voting. All experts agreed on tailoring the first port site to the patient, whereas 84.2% advised avoiding the umbilical area for pneumoperitoneum in patients who had a prior midline laparotomy. Moreover, 86.8% agreed on closing all 15 mm ports irrespective of the patient's body mass index. There was a 100% consensus on using cartridges of appropriate height for stapling, checking the doughnuts after using circular staplers, and keeping the vibrating blade of the ultrasonic energy device in view and away from vascular structures. An 84.2% advised avoiding drain insertion through a ≥10 mm port site as it increases the risk of port-site hernia. There was 94.7% consensus on adding laparoscopic retrieval bags to the operating count and ensuring any surgical specimen left inside for later removal is added to the operating count. Conclusion: thirty-eight experts achieved a consensus on 133 statements concerning various aspects of laparoscopic GI Surgery. Increased awareness of these could facilitate training and improve patient outcomes.</p