Importance:Pancreas divisum is implicated as an obstructive cause for acute pancreatitis. Observational data suggest endoscopic retrograde cholangiopancreatography (ERCP) with minor papillotomy reduces the risk of pancreatitis episodes. Even though this endoscopic procedure is widely used in practice, clinical trials are lacking. Objective:To determine whether ERCP with minor papillotomy reduces the risk of acute pancreatitis among adults with unexplained acute recurrent pancreatitis and pancreas divisum. Design, Setting, and Participants:This multicenter, sham-controlled, double-blind randomized clinical trial enrolled adults with 2 or more episodes of acute pancreatitis and pancreas divisum. Adults with other etiologies for acute pancreatitis or concomitant chronic calcific pancreatitis were excluded. The trial was conducted between September 1, 2018, and August 30, 2024, at 21 referral centers in the US and Canada. Last follow-up occurred on February 15, 2025. Intervention:Participants were randomized in a 1:1 ratio to ERCP with minor papillotomy or sham ERCP. Main Outcomes and Measures:The primary outcome was development of acute pancreatitis more than 30 days after randomization as a time-to-event outcome. The secondary outcomes included acute pancreatitis episode frequency and development of chronic calcific pancreatitis, diabetes, and exocrine pancreatic dysfunction. Results:A total of 148 participants were randomized (mean age, 54 [SD, 19.5] years; 68.2% female; 95.3% non-Hispanic or Latino and 87.2% White; mean lifetime acute pancreatitis episodes, 3 [SD, 2]; mean duct diameter, 2.2 [SD, 1.3] mm) and followed up for a median of 34 months (IQR, 21.7-45.7 months). Of the 75 participants in the ERCP with minor papillotomy group, 26 (34.7%) developed acute pancreatitis compared with 32 of 73 participants (43.8%) in the sham ERCP group (adjusted hazard ratio, 0.83 [95% CI, 0.49 to 1.41]). The incidence rate ratio for acute recurrent pancreatitis episode frequency was 0.25 (95% CI, 0.18 to 0.34) in the ERCP with minor papillotomy group vs 0.30 (95% CI, 0.23 to 0.41) in the sham ERCP group. There were no between-group differences in frequency and incidence of chronic calcific pancreatitis (4.0% in the ERCP with minor papillotomy group vs 2.7% in the sham ERCP group; risk difference [RD], 0.01 [95% CI, -0.05 to 0.07]), diabetes (15.8% vs 12.8%, respectively; RD, 0.03 [95% CI, -0.13 to 0.19]), and exocrine pancreatic dysfunction (7.7% vs 17.2%; RD, -0.10 [95% CI, -0.27 to 0.08]). The adverse event of acute pancreatitis within 30 days of randomization occurred more frequently in the ERCP with minor papillotomy group (14.7%) vs the sham ERCP group (8.2%) (RD, 0.06 [95% CI, -0.04 to 0.17]). Conclusions and Relevance:Among patients with unexplained acute recurrent pancreatitis and pancreas divisum, ERCP with minor papillotomy does not reduce the risk of another episode of acute pancreatitis or related sequelae. Trial Registration:ClinicalTrials.gov Identifier: NCT03609944.

OBJECTIVES:Peri-procedural rectal indomethacin was shown to decrease the incidence of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) in adults undergoing ERCP. This practice was generalized to pediatric populations, despite an absence of data on safety or efficacy. This study evaluated the safety and efficacy of rectal indomethacin in pediatric patients undergoing ERCP. METHODS:We conducted a retrospective, cohort study of pediatric patients undergoing ERCP (single-endoscopist) at two tertiary academic hospitals from November 2009 to August 2024. Safety outcomes included bleeding and acute kidney injury (AKI). The efficacy outcome was incidence of PEP with and without indomethacin at 100 mg > 30 kg and 50 mg < 30 kg. Descriptive statistics, univariate analysis, and binary logistic regression adjusting for 18 covariates were performed. RESULTS:A total of 906 ERCPs were performed in 448 patients. Indomethacin was administered in 757 (83.6%) procedures and not in 148 (16.3%). Bleeding occurred in 3.2% versus 3.4% (p = 0.90), and AKI in 1.1% versus 0.7% (p = 0.67). PEP incidence was 3.0% with indomethacin versus 9.5% without (p < 0.05). On multivariate analysis, indomethacin significantly reduced PEP (odds ratio [OR] = 0.28, 95% confidence interval [CI] [0.11-0.71], p < 0.05; absolute risk reductions [ARR] = 6.5%; number needed to treat [NNT] = 16) without increasing bleeding or AKI. Findings were similar in subgroup analysis of index ERCPs with no increased odds of bleeding or AKI and significantly lower odds of PEP (OR = 0.16, 95%CI[0.05-0.53], p < 0.05; ARR = 12.7%; NNT = 8). CONCLUSIONS:The use of peri-procedural rectal indomethacin was safe and effective, with no increased bleeding or AKI and a greater than threefold reduction in PEP in pediatric patients. These findings support the use of indomethacin prophylaxis in pediatric patients at 100 mg > 30 kg and 50 mg < 30 kg.

BACKGROUND AND AIMS:Palliation of dysphagia associated with advanced esophageal cancer is challenging. Previous studies suggest liquid nitrogen spray cryotherapy (LNSC) is effective in palliating obstructive esophageal cancer. We sought to prospectively examine the utility, safety, and efficacy of serial applications of repeated palliative LNSC in this population. METHODS:We performed a prospective cohort trial of LNSC for persistent esophageal cancer without the possibility of resection for palliation of obstructive symptoms. We used repeated measures and competing risks analyses to study the course of patients treated over 2 years. Efficacy of treatment was assessed using quality-of-life scores 14 days after treatment, using general cancer (Quality of Life Questionnaire [QLQ]-C30) and esophageal cancer-specific (QLQ-esophageal subset [OES]18) quality-of-life questionnaires, as well as ordinal dysphagia scores. Adverse events (AEs) were assessed using structured interviews and classified according to Common Terminology Criteria. RESULTS:On repeated treatments, each participant (N = 49) improved their QLQ-C30 score by a mean of 1.7 (95% CI, 0.1-3.3) and improved their QLQ-OES18 score by a mean of 1.8 (95% CI, 0.4-3.3). For each subsequent round of treatment, the effect improved 0.1 (95% CI, 0.3-0.4) for the QLQ-C30 score and worsened -0.2 (95% CI, -0.5 to 0.2) for the QLQ-OES18 score. There was no significant improvement in the ordinal dysphagia score. Nineteen (39.6%) of 48 participants with a feeding tube at baseline required a feeding tube or stent at a mean of 8 months. Although unrelated serious AEs were common (38.8%), only 2 patients had events possibly related to LNSC (4.1%, melena and dysphagia). CONCLUSIONS:Spray cryotherapy had a durable and repeatable benefit for palliation of obstructive symptoms of esophageal cancer and quality of life in the majority of patients, without the need for feeding tube or esophageal stent placement. Treatments were generally well tolerated.

QuestionDoes endoscopic retrograde cholangiopancreatography (ERCP) with minor papillotomy reduce the risk of acute pancreatitis in patients with unexplained acute recurrent pancreatitis and pancreas divisum anatomy?FindingsIn this randomized trial including 148 individuals with unexplained acute recurrent pancreatitis and pancreas divisum followed up for a median of 34 months, ERCP with minor papillotomy did not significantly reduce the rate of acute pancreatitis during follow-up (34.7% vs 43.8% for sham ERCP; adjusted hazard ratio, 0.83 [95% CI, 0.49-1.41]). There was no between-group difference in acute pancreatitis episode frequency and development of chronic calcific pancreatitis, diabetes, or exocrine pancreatic dysfunction.MeaningAmong patients with unexplained acute recurrent pancreatitis and pancreas divisum, ERCP with minor papillotomy does not reduce the risk of another episode of acute pancreatitis or related sequelae. ImportancePancreas divisum is implicated as an obstructive cause for acute pancreatitis. Observational data suggest endoscopic retrograde cholangiopancreatography (ERCP) with minor papillotomy reduces the risk of pancreatitis episodes. Even though this endoscopic procedure is widely used in practice, clinical trials are lacking.ObjectiveTo determine whether ERCP with minor papillotomy reduces the risk of acute pancreatitis among adults with unexplained acute recurrent pancreatitis and pancreas divisum.Design, Setting, and ParticipantsThis multicenter, sham-controlled, double-blind randomized clinical trial enrolled adults with 2 or more episodes of acute pancreatitis and pancreas divisum. Adults with other etiologies for acute pancreatitis or concomitant chronic calcific pancreatitis were excluded. The trial was conducted between September 1, 2018, and August 30, 2024, at 21 referral centers in the US and Canada. Last follow-up occurred on February 15, 2025.InterventionParticipants were randomized in a 1:1 ratio to ERCP with minor papillotomy or sham ERCP.Main Outcomes and MeasuresThe primary outcome was development of acute pancreatitis more than 30 days after randomization as a time-to-event outcome. The secondary outcomes included acute pancreatitis episode frequency and development of chronic calcific pancreatitis, diabetes, and exocrine pancreatic dysfunction.ResultsA total of 148 participants were randomized (mean age, 54 [SD, 19.5] years; 68.2% female; 95.3% non-Hispanic or Latino and 87.2% White; mean lifetime acute pancreatitis episodes, 3 [SD, 2]; mean duct diameter, 2.2 [SD, 1.3] mm) and followed up for a median of 34 months (IQR, 21.7-45.7 months). Of the 75 participants in the ERCP with minor papillotomy group, 26 (34.7%) developed acute pancreatitis compared with 32 of 73 participants (43.8%) in the sham ERCP group (adjusted hazard ratio, 0.83 [95% CI, 0.49 to 1.41]). The incidence rate ratio for acute recurrent pancreatitis episode frequency was 0.25 (95% CI, 0.18 to 0.34) in the ERCP with minor papillotomy group vs 0.30 (95% CI, 0.23 to 0.41) in the sham ERCP group. There were no between-group differences in frequency and incidence of chronic calcific pancreatitis (4.0% in the ERCP with minor papillotomy group vs 2.7% in the sham ERCP group; risk difference [RD], 0.01 [95% CI, -0.05 to 0.07]), diabetes (15.8% vs 12.8%, respectively; RD, 0.03 [95% CI, -0.13 to 0.19]), and exocrine pancreatic dysfunction (7.7% vs 17.2%; RD, -0.10 [95% CI, -0.27 to 0.08]). The adverse event of acute pancreatitis within 30 days of randomization occurred more frequently in the ERCP with minor papillotomy group (14.7%) vs the sham ERCP group (8.2%) (RD, 0.06 [95% CI, -0.04 to 0.17]).Conclusions and RelevanceAmong patients with unexplained acute recurrent pancreatitis and pancreas divisum, ERCP with minor papillotomy does not reduce the risk of another episode of acute pancreatitis or related sequelae.Trial RegistrationClinicalTrials.gov Identifier: NCT03609944 This randomized clinical trial compares the use of endoscopic retrograde cholangiopancreatography (ERCP) with minor papillotomy vs a sham ERCP procedure for the treatment of patients with idiopathic acute pancreatitis with pancreas divisum.

Background and Aims:Studies assessing gastrointestinal stromal tumors (GISTs) have found no survival differences based on margin status; however, small sample sizes, merged anatomic locations, and limited follow-up have been limitations. This study examined the impact of margin status on overall survival in a large national cohort of patients with resected gastric GISTs. Methods:Data on patients with gastric GISTs were abstracted from the National Cancer Database, with data collected over a 16-year period (2004-2020). Exclusion criteria included the presence of other primary tumors, unknown patient/tumor characteristics, macroscopic residual margins, metastasis at diagnosis, and prior chemotherapy. The cohort was stratified according to tumor size. R0 is defined as microscopically negative margin, and R1 is microscopically positive margin. Results:After exclusions, there were 8448 patients in the analysis cohort: 8221 (97.3%) had R0 resections, and 227 (2.7%) had R1 resections. On univariate analysis, tumor size ≤5 cm (P < .001), T1 stage (P < .001), low grade (P < .001), and low mitotic index (P < .001) were associated with a decreased risk of death. Margin status (R0 vs R1) did not have an impact on survival in the combined (P = .249), ≤5 cm (P = .961), ≤3 cm (P = .595), or ≤2 cm (P = .614) cohorts. There was also no difference in the risk of death based on the resection margin, in which the hazard ratio (R1 vs R0) with a 95% confidence interval was 1.206 (.862-1.633). In multivariate analysis, the resection margin status did not affect overall survival (P = .666). Conclusions:Congruent with prior studies, there was no difference in survival when comparing R0 with R1 resections in gastric GIST patients without metastasis over an extended follow-up period. These data may be helpful in assessing suitability for endoscopic resection for patients with gastric GISTs.

Disconnected pancreatic duct (DPD) and the associated syndrome are increasingly recognized as complications of severe pancreatitis. Despite the increased appreciation for this disorder and its treatment, there remain many questions regarding definition, diagnosis, and management. We utilized the expertise of the U.S. Pancreatic Disease Study Group to address 7 important questions derived from review of the literature pertaining to DPD in the setting of endoscopic treatment for necrotizing pancreatitis. Seven important questions were derived and following review by each member, consensus was reached. The 7 questions, followed by recommendations, included the appropriate definition for the syndromes and the radiographic definition for diagnosis; the appropriate timing for evaluation for diagnosis; the ideal diagnostic method; the use of pancreatic duct stents in this syndrome; the utility and safety of double plastic stents following endoscopic transmural drainage; and the role of surgical therapy. Important diagnostic and therapeutic questions were derived, which should be useful for the management of these patients as well as important research questions going forward.

BACKGROUND AND AIMS:ERCP carries potential for serious adverse events, and there is risk for unplanned health encounters after the procedure. The primary objective of this study was to identify the rate of 30-day hospital admission after outpatient ERCP in patients at elevated risk for post-ERCP pancreatitis based on patient- and procedure-related risk factors. We also explored whether pancreatitis rates and lengths of hospital stay differ with delayed hospitalization (versus admission immediately after ERCP) and identified factors associated with 30-day hospital admission. METHODS:High-risk patients in the Stent Versus Indomethacin trial who underwent outpatient ERCP were identified. The primary outcome was hospital admission within 30 days after outpatient ERCP. Patient and procedural factors associated with 30-day hospital admission were explored by means of univariable analysis followed by multivariable analysis, controlling for potential known confounders. RESULTS:Among 768 patients at high risk for post-ERCP pancreatitis who underwent outpatient ERCP and were discharged home, 21.9% required hospitalization within 30 days. Compared with patients who underwent outpatient ERCP but were admitted immediately to the hospital after the procedure, patients who were discharged after ERCP and admitted later had a higher incidence of post-ERCP pancreatitis (40.5% vs 30.9%; P = .04), moderate to severe post-ERCP pancreatitis (24.4% vs 13.8%; P < .01), and longer length of hospital stay (6.2 d vs 3.7 d; P < .001). Factors associated with 30-day hospitalization included patient age (odds ratio [OR], 0.98; 95% CI, 0.97-0.99), biliary stent placement (OR, 1.62; 95% CI, 1.05-2.48), and attempt at pancreatic duct cannulation (OR, 1.64; 95% CI, 1.02-2.64). CONCLUSIONS:High-risk patients who undergo outpatient ERCP and are discharged home are at considerable risk for hospital admission within 30 days and have an increased rate of pancreatitis and longer length of hospital stay compared with outpatients admitted to the hospital immediately after ERCP, and some factors may predict this outcome. These findings should influence decision making and informed consent when electing to proceed with high-risk ERCP, recognizing that patients with sphincter of Oddi dysfunction were over-represented in this cohort, which may limit generalizability to a typical ERCP practice.