High risk of complications and acute-on-chronic liver failure in cirrhosis patients with acute pancreatitis.

BACKGROUND & AIMS: Acute pancreatitis (AP) is a frequent indication for hospitalization and may present with varying degrees of severity. AP often coincides with hepatic disease, yet the impact of liver cirrhosis (LC) on the course of AP is uncertain, and early identification of patients at risk for complications remains challenging. We aimed to assess the impact of LC on the development of pancreatic and extra-pancreatic complications of AP, and to identify predictors of adverse outcomes in cirrhotic patients. METHODS: All adult patients with LC and AP (LC-AP, n = 52) admitted to our institution between 01/2011-03/2020 were subjected to a 1:2 matched-pair analysis with patients with AP but without LC (NLC-AP, n = 104). RESULTS: At hospital admission, Glasgow-Imrie and Ranson scores as well as markers of systemic inflammation were comparable in LC-AP and NLC-AP patients, and both groups had similar rates of necrotizing AP. Infectious complications were more prevalent, and medical interventions were performed more often and with higher complication rates in LC-AP patients. While only 12.5% of NLC-AP patients developed organ failures, 48% of LC-AP patients developed single (7.7%) or multiple organ failure (40.4%), resulting in 44% of LC-AP patients with acute-on-chronic liver failure (ACLF). Patients with overt portal hypertension were particularly prone for decompensation. Mortality was higher among LC-AP compared to NLC-AP patients (6-month mortality 25% vs. 1.9%, p < 0.001), and SOFA and MELD scores at admission most accurately predicted outcomes in LC-AP. CONCLUSION: Among AP patients, concomitant cirrhosis substantially increases the risk for infections, periprocedural complications, multiorgan failure and death.

Computer-aided detection versus advanced imaging for detection of colorectal neoplasia: a systematic review and network meta-analysis.

BACKGROUND: Computer-aided detection (CADe) techniques based on artificial intelligence algorithms can assist endoscopists in detecting colorectal neoplasia. CADe has been associated with an increased adenoma detection rate, a key quality indicator, but the utility of CADe compared with existing advanced imaging techniques and distal attachment devices is unclear. METHODS: For this systematic review and network meta-analysis, we did a comprehensive search of PubMed/Medline, Embase, and Scopus databases from inception to Nov 30, 2020, for randomised controlled trials investigating the effectiveness of the following endoscopic techniques in detecting colorectal neoplasia: CADe, high definition (HD) white-light endoscopy, chromoendoscopy, or add-on devices (ie, systems that increase mucosal visualisation, such as full spectrum endoscopy [FUSE] or G-EYE balloon endoscopy). We collected data on adenoma detection rates, sessile serrated lesion detection rates, the proportion of large adenomas detected per colonoscopy, and withdrawal times. A frequentist framework, random-effects network meta-analysis was done to compare artificial intelligence with chromoendoscopy, increased mucosal visualisation systems, and HD white-light endoscopy (the control group). We estimated odds ratios (ORs) for the adenoma detection rate, sessile serrated lesion detection rate, and proportion of large adenomas detected per colonoscopy, and calculated mean differences for withdrawal time, with 95% CIs. Risk of bias and certainty of evidence were assessed with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. FINDINGS: 50 randomised controlled trials, comprising 34 445 participants, were included in our main analysis (six trials of CADe, 18 of chromoendoscopy, and 26 of increased mucosal visualisation systems). HD white-light endoscopy was the control technique in all 50 studies. Compared with the control technique, the adenoma detection rate was 7·4% higher with CADe (OR 1·78 [95% CI 1·44-2·18]), 4·4% higher with chromoendoscopy (1·22 [1·08-1·39]), and 4·1% higher with increased mucosal visualisation systems (1·16 [1·04-1·28]). CADe ranked as the superior technique for adenoma detection (with moderate confidence in hierarchical ranking); cross-comparisons of CADe with other imaging techniques showed a significant increase in the adenoma detection rate with CADe versus increased mucosal visualisation systems (OR 1·54 [95% CI 1·22-1·94]; low certainty of evidence) and with CADe versus chromoendoscopy (1·45 [1·14-1·85]; moderate certainty of evidence). When focusing on large adenomas (≥10 mm) there was a significant increase in the detection of large adenomas only with CADe (OR 1·69 [95% CI 1·10-2·60], moderate certainty of evidence) when compared to HD white-light endoscopy; CADe ranked as the superior strategy for detection of large adenomas. CADe also seemed to be the superior strategy for detection of sessile serrated lesions (with moderate confidence in hierarchical ranking), although no significant increase in the sessile serrated lesion detection rate was shown (OR 1·37 [95% CI 0·65-2·88]). No significant difference in withdrawal time was reported for CADe compared with the other techniques. INTERPRETATION: Based on the published literature, detection rates of colorectal neoplasia are higher with CADe than with other techniques such as chromoendoscopy or tools that increase mucosal visualisation, supporting wider incorporation of CADe strategies into community endoscopy services. FUNDING: None.

What gastroenterologists should know about SARS-CoV 2 vaccine: World Endoscopy Organization perspective.

BACKGROUND: The novel Coronavirus (SARS-CoV-2) has caused almost 2 million deaths worldwide. Both Food and Drug Administration and European Medicines Agency have recently approved the first COVID-19 vaccines, and a few more are going to be approved soon. METHODS: Several different approaches have been used to stimulate the immune system in mounting a humoral response. As more traditional approaches are under investigation (inactivated virus vaccines, protein subunit vaccines, recombinant virus vaccines), more recent and innovative strategies have been tried (non-replicating viral vector vaccines, RNA based vaccines, DNA based vaccines). RESULTS: Since vaccinations campaigns started in December 2020 in both the US and Europe, gastroenterologists will be one of the main sources of information regarding SARS-CoV 2 vaccination for patients in their practice, including vulnerable patients such as those with Inflammatory Bowel Disease (IBD), patients with chronic liver disease, and GI cancer patients. CONCLUSIONS: Thus, we must ourselves be well educated and updated in order to provide unambiguous counseling to these categories of vulnerable patients. In this commentary, we aim to provide a comprehensive review of both approved COVID-19 vaccines and the ones still under development, and explore potential risks, benefits and prioritization of vaccination.

Risk factors associated with bleeding after prophylactic endoscopic variceal ligation in cirrhosis.

BACKGROUND: Prophylactic endoscopic variceal band ligation (EVL) is frequently performed in patients with liver cirrhosis. The aim of our study was to identify factors associated with early upper gastrointestinal bleeding (UGIB) in cirrhosis patients after prophylactic EVL. METHODS: 787 nonemergency EVLs performed in 444 patients in two German University medical centers were analyzed retrospectively. RESULTS: Within 30 days after EVL, 38 UGIBs were observed (4.8 % of all procedures). Bilirubin levels (hazard ratio [HR] 1.5, 95 % confidence interval [CI] 1.2-2.0 for a 2-fold increase) and presence of varices grade III/IV according to Paquet (HR 2.6, 95 %CI 1.3-5.0 compared with absence or smaller sized varices) were independently associated with UGIB following EVL. International normalized ratio (INR) was associated with bleeding events in the univariate analysis but did not reach statistical significance after adjustment for bilirubin and presence of varices grade III/IV (HR 1.2, 95 %CI 0.9-1.6 for an increase by 0.25). There was no statistically significant association between platelet count or fibrinogen levels and UGIB. Substitution of coagulation products did not affect incidence of bleeding after EVL, which also applied to patients with "coagulopathy" (INR > 1.5 and/or platelet count < 50 × 109/L). No association between proton pump inhibitor therapy and post-EVL UGIB was observed. CONCLUSIONS: EVL is a safe procedure and immediate bleeding complications are rare. Serum bilirubin levels and size of varices, rather than coagulation indices, are associated with UGIB after EVL. Our data do not support the preventive substitution of blood or coagulation products.

Prevalence of Gastrointestinal Symptoms and Fecal Viral Shedding in Patients With Coronavirus Disease 2019: A Systematic Review and Meta-analysis.

Importance: Coronavirus disease 2019 (COVID-19) is a global pandemic and can involve the gastrointestinal (GI) tract, including symptoms like diarrhea and shedding of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in feces. Objective: To provide a pooled estimate of GI symptoms, liver enzyme levels outside reference ranges, and fecal tests positive for SARS-CoV-2 among patients with COVID-19. Data Sources: An electronic literature search was performed for published (using MEDLINE/PubMed and Embase) and preprint (using bioRxiv and medRxiv) studies of interest conducted from November 1, 2019, to March 30, 2020. Search terms included "COVID-19," "SARS-Cov-2," and/or "novel coronavirus." Study Selection: Eligible studies were those including patients with SARS-CoV-2 infection who reported GI symptoms. Data Extraction and Synthesis: Data on patients with GI symptoms (ie, diarrhea, nausea, or vomiting), liver enzyme level changes, and fecal shedding of virus were extracted. Quality of studies was examined using methodological index for nonrandomized studies. Pooled estimates (%) were reported with 95% CIs with level of heterogeneity (I2). Main Outcomes and Measures: Study and patient characteristics with pooled detection rates for diarrhea, nausea or vomiting, liver enzyme levels outside reference ranges, and SARS-CoV-2 positivity in feces tests were analyzed. Results: Of 1484 records reviewed, 23 published and 6 preprint studies were included in the analysis, with a total of 4805 patients (mean [SD] age, 52.2 [14.8] years; 1598 [33.2%] women) with COVID-19. The pooled rates were 7.4% (95% CI, 4.3%-12.2%) of patients reporting diarrhea and 4.6% (95% CI, 2.6%-8.0%) of patients reporting nausea or vomiting. The pooled rate for aspartate aminotransferase levels outside reference ranges was 20% (95% CI, 15.3%-25.6%) of patients, and the pooled rate for alanine aminotransferase levels outside reference ranges was 14.6% (95% CI, 12.8%-16.6%) of patients. Fecal tests that were positive for SARS-CoV-2 were reported in 8 studies, and viral RNA shedding was detected in feces in 40.5% (95% CI, 27.4%-55.1%) of patients. There was high level of heterogeneity (I2 = 94%), but no statistically significant publication bias noted. Conclusions and Relevance: These findings suggest that that 12% of patients with COVID-19 will manifest GI symptoms; however, SAR-CoV-2 shedding was observed in 40.5% of patients with confirmed SARS-CoV-2 infection. This highlights the need to better understand what measures are needed to prevent further spread of this highly contagious pathogen.

Anti-inflammatory microenvironment of esophageal adenocarcinomas negatively impacts survival.

OBJECTIVE: Reflux promotes esophageal adenocarcinomas (EACs) creating a chronic inflammatory environment. Survival rates are low due to early local recurrences and distant metastasis. Hence, there is a need for new potential treatment options like immunotherapies. However, the inflammatory microenvironment in EACs and its impact on patient outcome remain to be fully understood. METHODS: mRNA expression levels of pro- and anti-inflammatory markers in 39 EAC patients without neoadjuvant radio-chemotherapy were measured. Data were confirmed using flow cytometric analysis of freshly resected surgical specimens. Inflammatory alterations in premalignant lesions of Barrett's esophagus were analyzed by immunohistochemistry. RESULTS: Expression levels of IL22 were reduced in EAC, while expression levels of FOXP3, IL10 and CTLA4 were increased. Flow cytometry demonstrated a strong infiltration of CD4+ T cells with a reduction in CD4+ T cells producing IL-22 or IL-17A. We also observed an increase in CD4+CD127lowFOXP3+ cells producing IL-10. Accumulation of FOXP3+ T cells occurred prior to malignant changes. High expression of IL10 and low expression of IL22 in EAC were associated with reduced overall survival. Moreover, increased expression of IL10, CTLA4 and PD1 in the unaltered esophageal mucosa distant to the EAC was also linked with an unfavorable prognosis. CONCLUSION: EAC shows an anti-inflammatory environment, which strongly affects patient survival. The microscopically unaltered peritumoral tissue shows a similar anti-inflammatory pattern indicating an immunological field effect, which might contribute to early local recurrences despite radical resection. These data suggest that using checkpoint inhibitors targeting anti-inflammatory T cells would be a promising therapeutic strategy in EAC.

Molecular and functional heterogeneity of IL-10-producing CD4+ T cells.

IL-10 is a prototypical anti-inflammatory cytokine, which is fundamental to the maintenance of immune homeostasis, especially in the intestine. There is an assumption that cells producing IL-10 have an immunoregulatory function. However, here we report that IL-10-producing CD4+ T cells are phenotypically and functionally heterogeneous. By combining single cell transcriptome and functional analyses, we identified a subpopulation of IL-10-producing Foxp3neg CD4+ T cells that displays regulatory activity unlike other IL-10-producing CD4+ T cells, which are unexpectedly pro-inflammatory. The combinatorial expression of co-inhibitory receptors is sufficient to discriminate IL-10-producing CD4+ T cells with regulatory function from others and to identify them across different tissues and disease models in mice and humans. These regulatory IL-10-producing Foxp3neg CD4+ T cells have a unique transcriptional program, which goes beyond the regulation of IL-10 expression. Finally, we found that patients with Inflammatory Bowel Disease demonstrate a deficiency in this specific regulatory T-cell subpopulation.

Performance measures for lower gastrointestinal endoscopy: a European Society of Gastrointestinal Endoscopy (ESGE) quality improvement initiative.

The European Society of Gastrointestinal Endoscopy and United European Gastroenterology present a short list of key performance measures for lower gastrointestinal endoscopy. We recommend that endoscopy services across Europe adopt the following seven key performance measures for lower gastrointestinal endoscopy for measurement and evaluation in daily practice at a center and endoscopist level: 1 rate of adequate bowel preparation (minimum standard 90%); 2 cecal intubation rate (minimum standard 90%); 3 adenoma detection rate (minimum standard 25%); 4 appropriate polypectomy technique (minimum standard 80%); 5 complication rate (minimum standard not set); 6 patient experience (minimum standard not set); 7 appropriate post-polypectomy surveillance recommendations (minimum standard not set). Other identified performance measures have been listed as less relevant based on an assessment of their importance, scientific acceptability, feasibility, usability, and comparison to competing measures.

Performance measures for lower gastrointestinal endoscopy: a European Society of Gastrointestinal Endoscopy (ESGE) Quality Improvement Initiative.

The European Society of Gastrointestinal Endoscopy and United European Gastroenterology present a short list of key performance measures for lower gastrointestinal endoscopy. We recommend that endoscopy services across Europe adopt the following seven key performance measures for lower gastrointestinal endoscopy for measurement and evaluation in daily practice at a center and endoscopist level: 1 Rate of adequate bowel preparation (minimum standard 90 %); 2 Cecal intubation rate (minimum standard 90 %); 3 Adenoma detection rate (minimum standard 25 %); 4 Appropriate polypectomy technique (minimum standard 80 %); 5 Complication rate (minimum standard not set); 6 Patient experience (minimum standard not set); 7 Appropriate post-polypectomy surveillance recommendations (minimum standard not set). Other identified performance measures have been listed as less relevant based on an assessment of their importance, scientific acceptability, feasibility, usability, and comparison to competing measures.

Duodenal Electric Stimulation: Results of a First-in-Man Study.

BACKGROUND: The aim of this study was to demonstrate feasibility and safety of a new electric duodenal stimulation system (EDS, BALANCE) in humans. Secondary objectives were to evaluate the effect on glycemic control and weight loss in patients with obesity and type 2 diabetes mellitus (T2DM). METHODS: In an open-labeled, prospective, single-arm, non-randomized multicenter study, 12 obese T2DM patients with a mean HbA1c of 8.0% received laparoscopic implantation of the BALANCE duodenal stimulating device. Adverse events, changes in glycemic control, cardiovascular parameters, and weight were collected. The follow-up period after implantation was 12 months. RESULTS: Device related severe adverse events did not occur. Mean HbA1c decreased by 0.8% (p = 0.02) and mean fasting blood glucose level (FBG) was reduced by 19% (p = 0.038) after the 12 months. Mean HDL level increased from 44 to 48 mg/dl (p = 0.033). CONCLUSIONS: EDS is a feasible and safe procedure. Positive effects on T2DM and some cardiovascular parameters (HDL, weight) were seen. However, further prospective randomized blinded studies are needed in order to evaluate the potential of this new minimally invasive method.

Transpancreatic precut sphincterotomy for cannulation of inaccessible common bile duct: a safe and successful technique.

OBJECTIVE: Obstruction of the biliary tract can lead to severe complications. The common treatment of patients with biliary tract obstruction is the decompression by endoscopic procedures. However, cannulation of the common bile duct can be difficult under certain instances because of anatomical variations or obstruction at the biliary entrance level. Needle-knife or precut sphincterotomy has been described as technique to facilitate biliary access in patients with difficult bile duct cannulation. In the current study, we evaluated success and complication rates of a wire-guided transpancreatic precut technique at our hospital. METHODS: Between January 2003 and June 2006, a total of 108 patients with jaundice but with inaccessible bile ducts using classic techniques (failed primary cannulation or failed needle-knife papillotomy) underwent a wire-guided transpancreatic precut sphincterotomy. Precuts were performed using a soft guide wire placed in the pancreatic duct without injection of contrast fluid into the pancreatic duct. RESULTS: We studied cannulation success and complications associated with postprocedural hospitalization. Bile duct cannulation was successful in 103 (95.4%) of the 108 patients. Five patients (4.6%) required a percutaneous transhepatic biliary drainage. In 108 patients, there were 12 patients (11.1%) with procedure-related complications including acute pancreatitis (n = 6) and bleeding (n=6). Four patients had a mild and transient pancreatitis (pain improvement after 2 days), 2 had severe pancreatitis that was reversible after 7 days of conservative treatment. In 4 cases, a blood transfusion (each with 2 erythrocyte concentrates) became necessary. Perforations and other severe procedure-related deaths did not occur. CONCLUSIONS: Transpancreatic precut sphincterotomy using a soft guide wire is a safe and effective procedure in patients with difficult bile duct access where classic sphincterotomy or needle-knife procedures fail.

Endoscopic ultrasonography: equipment and technique.

By definition, endoscopic ultrasonography (EUS) combines endoscopy and high-frequency ultrasound, incorporating a small ultrasonic transducer into the tip of endoscopes. For the upper gastrointestinal tract, mostly oblique-viewing endoscopes are used, although recently, forward viewing instruments have become available. For colorectal EUS, rigid probes for the rectum and a flexible forward-viewing echocolonoscope are available. EUS generates ultrasound either mechanically or electronically, depending on the type of instrument used. The electronic technique potentially allows the incorporation of (color) Doppler ultrasound, which allows for additional processing and postprocessing functions. This generally is considered the EUS technique of the future.