Association Between Concomitant Gallstones and Late Biliary Adverse Events After Endoscopic Papillectomy

ABSTRACT Background/Purpose Late adverse events (AEs) following endoscopic papillectomy (EP) are poorly characterized. We examined the association between concomitant gallstones (GS) and late AEs after EP. Methods We retrospectively analyzed patients undergoing EP for ampullary tumors between 2004 and 2025. Late AEs were symptomatic pancreatobiliary events occurring ≥ 30 days after EP and requiring medical intervention. Analyses included patients with intact gallbladders. The primary outcome was time to the first late AE; secondary analyses evaluated its biliary or pancreatic phenotype using age‐ and sex‐adjusted Cox models. Results Of 313 patients, 292 had intact gallbladders, including 54 with GS and 238 without GS. Late AEs occurred in 25.9% and 10.5%, respectively. GS was associated with the first late AE (adjusted hazard ratio [aHR], 2.97; 95% confidence interval [CI], 1.53–5.75) and its biliary phenotype (aHR, 3.58; 95% CI: 1.71–7.49) but not its pancreatic phenotype. One‐year cumulative incidence of the first late AE was 23.2% versus 5.7% (log‐rank, p < 0.001). Among the 43 patients with late AEs overall, 35 (81.4%) underwent endoscopic retrograde cholangiopancreatography, and nine (20.9%) experienced recurrence. Conclusions Concomitant GS was associated with late AEs after EP and may be a risk marker for late biliary events.