Recent evidence suggests a rising incidence of cancer in younger individuals. Herein, we report the epidemiologic, pathologic, and molecular characteristics of a patient cohort with early-onset pancreas cancer (EOPC). Institutional databases were queried for demographics, treatment history, genomic results, and outcomes. Overall survival from date of diagnosis was estimated using Kaplan-Meier method. Between 2008 and 2018, 450 patients with EOPC were identified at Memorial Sloan Kettering. Median overall survival was 16.3 (95% confidence interval [CI] = 14.6 to 17.7) months in the entire cohort and 11.3 (95% CI = 10.2 to 12.2) months for patients with stage IV disease at diagnosis. Of the patients, 132 (29.3% of the cohort) underwent somatic testing; 21 of 132 (15.9%) had RAS wild-type cancers with identification of several actionable alterations, including ETV6-NTRK3, TPR-NTRK1, SCLA5-NRG1, and ATP1B1-NRG1 fusions, IDH1 R132C mutation, and mismatch repair deficiency. A total of 138 patients (30.7% of the cohort) underwent germline testing; 44 of 138 (31.9%) had a pathogenic germline variant (PGV), and 27.5% harbored alterations in cancer susceptibility genes. Of patients seen between 2015 and 2018, 30 of 193 (15.5%) had a PGV. Among 138 who underwent germline testing, those with a PGV had a reduced all-cause mortality compared with patients without a PGV controlling for stage and year of diagnosis (hazard ratio = 0.42, 95% CI = 0.26 to 0.69). PGVs are present in a substantial minority of patients with EOPC. Actionable somatic alterations were identified frequently in EOPC, enriched in the RAS wild-type subgroup. These observations underpin the recent guidelines for universal germline testing and somatic profiling in pancreatic ductal adenocarcinoma.

INTRODUCTION: Endoscopic ultrasound–guided biliary drainage (EUS-BD) is an alternative to endoscopic retrograde cholangiopancreatography (ERCP)-guided transpapillary drainage in malignant distal biliary obstruction (MDBO). This meta-analysis of randomized controlled trials (RCTs) aims to compare the outcomes of these 2 approaches. METHODS: Electronic databases from January 2005 through December 2023 were searched for RCTs comparing outcomes of EUS-BD and ERCP for treating MDBO. Pooled proportions, risk ratio (RR), and odds ratio were calculated using random-effects models. RESULTS: Five RCTs comprising 519 patients were included in the final analysis. The pooled RR for overall technical success with EUS-BD compared with ERCP was 1.05 (95% confidence interval [CI] = 0.96–1.16, P = 0.246, I ² = 61%) and for clinical success was 0.99 (95% CI = 0.95–1.04, P = 0.850, I ² = 0%). The pooled rate of procedure-related pancreatitis was 7.20% (95% CI = 3.60–13.80, I ² = 34%) in the ERCP group compared with zero in the EUS-BD group. The pooled RR for stent dysfunction with EUS-BD compared with ERCP was 0.48 (95% CI = 0.28–0.83, P = 0.008, I ² = 7%). The weighted mean procedure time was 13.43 (SD = 10.12) minutes for EUS-BD compared with 21.06 (SD = 6.64) minutes for ERCP. The mean stent patency was 194.11 (SD = 52.12) days in the EUS-BD group and 187 (SD = 60.70) days in the ERCP group. DISCUSSION: EUS-BD is an efficient and safe alternative to ERCP in MDBO. An almost nonexistent risk of procedure-related pancreatitis, lower procedure time, and ease of use make this an attractive primary approach to biliary decompression in centers with expertise.

The endoscopic management armamentarium of gastrointestinal disruptions including perforations, leaks, and fistulas has slowly but steadily broadened in recent years. Previously limited to surgical or conservative medical management, innovations in advanced endoscopic techniques like natural orifice transluminal endoscopic surgery (NOTES) have paved the path towards development of endoscopic closure techniques. Early recognition of a gastrointestinal defect is the most important independent variable in determining successful endoscopic closure and patient outcome. Some devices including through the scope clips and stents have been well studied for other indications and have produced encouraging results in closure of gastrointestinal perforations, leaks and fistulas. Over the scope clips, endoscopic sutures, vacuum therapy, glue, and cardiac device occluders are other alternative techniques that can be employed for successful endoscopic closure.

Background and study aims The advantages of endoscopic submucosal dissection (ESD) over endoscopic mucosal resection for large colorectal neoplasms are well established; however, the technical challenges and lack of adequate training in ESD limit its widespread adoption in Western countries. Methods A literature search was performed in Medline, Embase, Web of Science, and the Cochrane Library for studies conducted in non-Asian countries evaluating the effectiveness of colorectal ESD. A random effects model was used to obtain pooled en bloc, R0 resection rates, and adverse events (AEs). Results Thirty-three studies comprising 3,958 ESD procedures met the inclusion criteria. Of the polyps, 96.7% (2,817 of 2913) were ≥ 2 cm. Pooled en bloc resection (31 studies), R0 resection (29 studies), and curative resection rates were 84.6% (95% confidence interval [CI] [83.3%–85.9%]), 75.6% (95% CI [74.1%–77.0%]), and 81.9% (95% CI [78.6%–84.9%]), respectively. Surgery for invasive cancer was performed in 4.8% (23 studies). ESD-related perforation (25 studies) was observed in 5.5% and bleeding in 4.1% (delayed bleeding 3.4%). 1.8% of patients underwent surgery for procedure-related complications. A high degree of heterogeneity was observed for en bloc resection, R0 resection, and curative resection. Heterogeneity for AEs (perforation [I² 13%], delayed bleeding [I² 30%], and overall bleeding [I² 49%]) was low to moderate. Conclusions The effectiveness of colorectal ESD for large colorectal polyps and early colorectal cancers is improving in Western countries, and recent resection rates are comparable to that seen in Asia. Colorectal perforation is still observed in about 5% of ESD; however, < 2% of patients need emergency surgery for AEs. Received: 22 February 2023 Accepted after revision: 11 September 2023 Article published online: 27 November 2023 © 2023. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/). Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany