A Randomized Controlled Phase 2 Dose-Finding Trial to Evaluate the Efficacy and Safety of Camostat in the Treatment of Painful Chronic Pancreatitis: The TACTIC Study.

BACKGROUND & AIMS: Chronic pancreatitis (CP) causes an abdominal pain syndrome associated with poor quality of life. We conducted a clinical trial to further investigate the efficacy and safety of camostat, an oral serine protease inhibitor that has been used to alleviate pain in CP. METHODS: This was a double-blind randomized controlled trial that enrolled adults with CP with a baseline average daily worst pain score ≥4 on a numeric rating system. Participants were randomized (1:1:1:1) to receive camostat at 100, 200, or 300 mg 3 times daily or placebo. The primary end point was a 4-week change from baseline in the mean daily worst pain intensity score (0-10 on a numeric rating system) using a mixed model repeated measure analysis. Secondary end points included changes in alternate pain end points, quality of life, and safety. RESULTS: A total of 264 participants with CP were randomized. Changes in pain from baseline were similar between the camostat groups and placebo, with differences of least squares means of -0.11 (95% CI, -0.90 to 0.68), -0.04 (95% CI, -0.85 to 0.78), and -0.11 (95% CI, -0.94 to 0.73) for the 100 mg, 200 mg, and 300 mg groups, respectively. Multiple subgroup analyses were similar for the primary end point, and no differences were observed in any of the secondary end points. Treatment-emergent adverse events attributed to the study drug were identified in 42 participants (16.0%). CONCLUSION: We were not able to reject the null hypothesis of no difference in improvements in pain or quality of life outcomes in participants with painful CP who received camostat compared with placebo. Studies are needed to further define mechanisms of pain in CP to guide future clinical trials, including minimizing placebo responses and selecting targeted therapies. CLINICALTRIALS: gov, Number: NCT02693093.

Indirect comparison of various lumen-apposing metal stents for EUS-guided biliary and gallbladder drainage: a systematic review and meta-analysis.

BACKGROUND AND AIMS: Studies assessing EUS-guided biliary drainage (EUS-BD) or gallbladder drainage (EUS-GB) using lumen-apposing metal stents (LAMSs) have shown variable results based on the type of LAMS. We performed a meta-analysis of the available data. METHODS: Multiple online databases were searched for studies using LAMSs (Axios [Boston Scientific, Marlborough, Mass, USA] or Spaxus [Taewoong Medical Co, Gimpo, Korea]) for EUS-BD and EUS-GB. The outcomes of interest were technical success, clinical success, and adverse events. Pooled proportions along with 95% confidence intervals were calculated. RESULTS: A total of 18 observational studies were included: 11 for the Axios stent (433 patients; mean age, 72 years; 54% male) and 7 for the Spaxus stent (242 patients; mean age, 74 years; 50% male). The respective pooled outcomes for the Axios stent (EUS-BD and EUS-GB, respectively) were technical success, 96.2% and 96.2%; clinical success, 92.8% and 92.7%; total adverse events, 10.1% and 23.6%; and bleeding, 3.7% and 4.8%. The respective pooled outcomes for the Spaxus stent (EUS-BD and EUS-GB, respectively) were technical success, 93.8% and 95.9%; clinical success, 90.1% and 94.2%; total adverse events, 12.6% and 9.5%; and bleeding, 3.1% and 1.8%. CONCLUSIONS: Axios and Spaxus stents demonstrate similar pooled technical and clinical success rates. Adverse events occurred in 23.6% of patients (Axios stent) and 9.5% of patients (Spaxus stent) during EUS-GB.

Development of American Society for Gastrointestinal Endoscopy standards for training in advanced endoscopy within dedicated advanced endoscopy fellowship programs.

BACKGROUND AND AIMS: Training in interventional endoscopy is offered by nonaccredited advanced endoscopy fellowship programs (AEFPs). The number of these programs has increased dramatically with a concurrent increase in the breadth and complexity of interventional endoscopy procedures. Accreditation is governed by competency-based education, yet what constitutes a "high-quality" nonaccredited AEFP has not been defined. Using an evidence-based consensus process, we aimed to establish standards for AEFPs. METHODS: The RAND UCLA appropriateness method, a well-described modified Delphi process to develop quality indicators, was used. A task force established by the American Society for Gastrointestinal Endoscopy drafted potential quality indicators (structure, process, and outcome) in 6 categories: activity preceding training; structure of AEFPs; training in ERCP, EUS, and EMR; and luminal stent placement. Three rounds of iterative feedback from 20 experts were conducted. Round 0 involved discussion of project details. In round 1, experts independently ranked proposed quality indicators on a 9-point interval scale ranging from highly inappropriate (1) to highly appropriate (9). Next, proposed quality indicators were discussed and reworded in a group meeting followed by round 2, in which experts independently reranked proposed quality indicators and provided benchmarks (when applicable). The median score for each quality indicator was calculated. Mean absolute deviation from the median was calculated, and appropriateness of potential quality indicators was assessed using the BIOMED concerted action on appropriateness definition, P value method, and interpercentile range adjusted for symmetry definition. A quality indicator was deemed appropriate if the median score was ≥7 and met criteria for appropriateness using all 3 defined statistical methods. RESULTS: Of 89 proposed quality indicators, 37 statements met criteria as appropriate for a quality indicator (activity preceding training, 2; structure of AEFPs, 10; training in ERCP, 7; training in EUS, 8; training in EMR, 7; luminal stent placement, 3). Minimum thresholds were defined for 19 relevant quality indicators for number of trainers, procedures during fellowship, and procedures before assessment of competence. Among the final appropriate quality indicators were that all trainees should undergo qualitative and quantitative competence assessments using validated tools at least quarterly with documented feedback throughout the training period and that trainees should track outcomes and relevant quality metrics for specific procedures. CONCLUSIONS: This consensus process using validated methodology established standards for an AEFP in an effort to ensure adequate training in the most commonly taught interventional endoscopic procedures (ERCP, EUS, EMR, and luminal stent placement) during fellowship. An important component of an AEFP is the use of competency-based assessments that are compliant with the Accreditation Council for Graduate Medical Education's Next Accreditation System, with the goal of ensuring that trainees achieve specific milestones in their progression to achieving cognitive and technical competency.

Meta-Analysis of Endoscopic Full-Thickness Resection Versus Endoscopic Submucosal Dissection for Complex Colorectal Lesions.

BACKGROUND: Studies evaluating endoscopic full-thickness resection (EFTR) and endoscopic submucosal dissection (ESD) for complex colorectal lesions have shown variable results. We conducted a meta-analysis of the available data. METHODS: Online databases were searched for studies comparing EFTR versus ESD for complex colorectal lesions. The outcomes of interest were resection rates, procedure time (min), and complications. Pooled odds ratios (OR) and standardized mean difference (SMD) along with 95% CI were calculated. RESULTS: A total of 4 studies with 530 patients (n=215 EFTR, n=315 ESD) were included. The mean follow-up duration was 5 months. The mean age of the patients was 68 years and 64% were men. The EFTR and ESD groups had similar rates of en bloc resection (OR: 1.73, 95% CI: 0.60-4.97, P=0.31) and R0 resection (OR: 1.52, 95% CI: 0.55-4.14, P=0.42). The EFTR group had significantly reduced procedure time (SMD -1.87, 95% CI: -3.13 to -0.61, P=0.004), total complications (OR: 0.24, 95% CI: 0.13-0.44, P<0.00001), perforation (OR: 0.12, 95% CI: 0.03-0.39, P=0.0005) and postresection electrocoagulation syndrome (OR: 0.06, 95% CI: 0.01-0.48, P=0.008). Delayed bleeding was similar in the 2 groups (OR: 0.80, 95% CI: 0.30-2.12, P=0.66). Residual/recurrent lesions were significantly higher in the EFTR group (OR: 4.67, 95% CI: 1.39-15.66, P=0.01). DISCUSSION: This meta-analysis of small studies with high heterogeneity showed that EFTR and ESD have comparable resection rates for complex colorectal lesions. EFTR is faster and has fewer complications, but it increases residual or recurrent lesions.

Single Versus Second Observer vs Artificial Intelligence to Increase the ADENOMA Detection Rate of Colonoscopy-A Network Analysis.

BACKGROUND AND AIMS: Screening colonoscopy has significantly contributed to the reduction of the incidence of colorectal cancer (CRC) and its associated mortality, with adenoma detection rate (ADR) as the quality marker. To increase the ADR, various solutions have been proposed including the utilization of Artificial Intelligence (AI) and employing second observers during colonoscopies. In the interest of AI improving ADR independently, without a second observer, and the operational similarity between AI and second observer, this network meta-analysis aims at evaluating the effectiveness of AI, second observer, and a single observer in improving ADR. METHODS: We searched the Medline, Embase, Cochrane, Web of Science Core Collection, Korean Citation Index, SciELO, Global Index Medicus, and Cochrane. A direct head-to-head comparator analysis and network meta-analysis were performed using the random-effects model. The odds ratio (OR) was calculated with a 95% confidence interval (CI) and p-value < 0.05 was considered statistically significant. RESULTS: We analyzed 26 studies, involving 22,560 subjects. In the direct comparative analysis, AI demonstrated higher ADR (OR: 0.668, 95% CI 0.595-0.749, p < 0.001) than single observer. Dual observer demonstrated a higher ADR (OR: 0.771, 95% CI 0.688-0.865, p < 0.001) than single operator. In network meta-analysis, results were consistent on the network meta-analysis, maintaining consistency. No statistical difference was noted when comparing AI to second observer. (RR 1.1 (0.9-1.2, p = 0.3). Results were consistent when evaluating only RCTs. Net ranking provided higher score to AI followed by second observer followed by single observer. CONCLUSION: Artificial Intelligence and second-observer colonoscopy showed superior success in Adenoma Detection Rate when compared to single-observer colonoscopy. Although not statistically significant, net ranking model favors the superiority of AI to the second observer.

Continuing Medical Education Questions: May 2022.

Article Title: Evolutionary medicine perspectives: Helicobacter pylori lactose intolerance, and three hypotheses for functional and inflammatory gastrointestinal and hepatobiliary disorders.

Helicobacter pylori infection does not influence the progression from gastroesophageal reflux disease to Barrett's esophagus to esophageal adenocarcinoma.

INTRODUCTION: We conducted a meta-analysis evaluating the overall risk of esophageal adenocarcinoma (EAC) in individuals with Helicobacter pylori infection, and a network meta-analysis to assess the role of H. pylori infection in the progression from Barrett's esophagus (BE) to EAC. EVIDENCE ACQUISITION: The MEDLINE, EMBASE and Cochrane databases were searched between 1988 and June 2023 for observational studies of H. pylori infection and the risk of EAC. Summary odds ratios (OR) and 95% confidence intervals (95% CI) were calculated using the DerSimonian-Laird method. I2 statistics were calculated to examine heterogeneity. EVIDENCE SYNTHESIS: Thirteen studies were included in the meta-analysis and 3 additional studies were included in the network meta-analysis. For comparisons with controls, individuals with H. pylori infection were 46% less likely to develop EAC than individuals without H. pylori infection (OR, 0.54; 95% CI: 0.46, 0.64), with low heterogeneity between studies (I2=4.4%). The magnitude of the inverse association was stronger in the two large cohort studies (OR=0.31) than in the 11 case-control studies (OR=0.55). When comparing to controls, the network meta-analysis of 6 studies showed that H. pylori infection was associated with a lower risk of GERD (OR=0.68) or BE (OR=0.59) or EAC (OR=0.54); however, H. pylori infection was not associated with risk of EAC in patients with BE (OR=0.91; 95% CI: 0.68, 1.21). CONCLUSIONS: This meta-analysis provides the strongest evidence yet that H. pylori infection is inversely associated with EAC. H. pylori does not appear to be associated with BE progression to EAC.

Early and Late Readmissions of Radiation Proctitis in the United States: Are We Getting Better?

Background/Aims: Radiation proctitis (RP), a well-known complication of pelvic radiation therapy, may lead to recurrent hospitalizations. We aimed to assess readmissions of RP in the United States. Methods: We analyzed the Nationwide Readmission Database from 2016 to 2020 to identify all 30-, 60-, and 90-day readmissions of RP in the United States. Hospitalization characteristics, predictors, clinical outcomes, and healthcare burdens were assessed. Results: From 2016 to 2020, we noted a declining trend of 30-, 60-, and 90-day readmissions of RP in the US. However, the all-cause 30-, 60-, and 90-day readmission rates of RP were still high at 13.7%, 19.4%, and 23.16%, respectively. On readmission, RP was identified as the admitting diagnosis in only 20.61%, 17.87%, and 15.76% of 30-, 60-, and 90-day readmissions, respectively. The mean age for all readmissions was 70 years with a significant male dominance. Lower endoscopy at index admission reduced the risk of readmissions within 90 days, but this was not statistically significant. However, the Charlson Comorbidity Index (CCI) score was an independent predictor of all readmissions. Furthermore, the mean length of stay was 5.57 (95% CI 5.15-6), 5.50 (95% CI 5.12-5.89), and 5.47 (95% CI 5.07-5.87) days and the mean hospitalization charge was USD 60,451 (95% CI USD 54,728-66,174), USD 62,671 (95% CI USD 57,326-68,015), and USD 62,144 (95% CI USD 57,144-67,144) for 30-, 60-, and 90-day readmissions. The all-cause inpatient mortality for 30-, 60-, and 90-day readmissions was 3.58%, 3.89%, and 3.46%, respectively. Conclusions: RP readmissions are a significant healthcare burden. Further efforts must be directed toward improving management strategies to reduce readmission rates.

Basic Principles and Role of Endoscopic Ultrasound in Diagnosis and Differentiation of Pancreatic Cancer from Other Pancreatic Lesions: A Comprehensive Review of Endoscopic Ultrasound for Pancreatic Cancer.

Pancreatic cancer is one of the leading causes of cancer-related deaths worldwide. Pancreatic lesions consist of both neoplastic and non-neoplastic lesions and often pose a diagnostic and therapeutic challenge due to similar clinical and radiological features. In recent years, pancreatic lesions have been discovered more frequently as incidental findings due to the increased utilization and widespread availability of abdominal cross-sectional imaging. Therefore, it becomes imperative to establish an early and appropriate diagnosis with meticulous differentiation in an attempt to balance unnecessary treatment of benign pancreatic lesions and missing the opportunity for early intervention in malignant lesions. Endoscopic ultrasound (EUS) has become an important diagnostic modality for the identification and risk stratification of pancreatic lesions due to its ability to provide detailed imaging and acquisition of tissue samples for analysis with the help of fine-needle aspiration/biopsy. The recent development of EUS-based technology, including contrast-enhanced endoscopic ultrasound, real-time elastography-endoscopic ultrasound, miniature probe ultrasound, confocal laser endomicroscopy, and the application of artificial intelligence has significantly augmented the diagnostic accuracy of EUS as it enables better evaluation of the number, location, dimension, wall thickness, and contents of these lesions. This article provides a comprehensive overview of the role of the different types of EUS available for the diagnosis and differentiation of pancreatic cancer from other pancreatic lesions while discussing their key strengths and important limitations.