Clinical Outcomes of Endoscopic Resection for Large (>3 cm) Ampullary Tumors

Background and Study Aims Current guidelines recommend en bloc endoscopic resection (ER) for ampullary tumors up to 3 cm and surgery for those exceeding 4 cm, based on low-quality evidence. Robust clinical data and operative experience with ER for tumors >3 cm are relatively limited. This study aimed to investigate the safety and efficacy of ER for large ampullary tumors exceeding 3 cm. Patients and Methods This retrospective study included 28 patients with large ampullary tumors (>3 cm) treated with ER at two tertiary academic endoscopy centers from September 2017 to July 2025. Clinical, endoscopic, and pathological records and follow-up data were collected and analyzed. Results All 28 patients successfully underwent ER with a complete ER rate of 100% and an R0 resection rate of 67.9%. The overall postoperative delayed bleeding rate was 14.3% (4/28; 95% CI: 5.7-31.5%). In subgroup data, bleeding occurred in 2 of 24 patients (8.3%; 95% CI: 1.5-25.8%) with stent placement, in 2 of 4 patients (50.0%; 95% CI: 8.9-91.1%) without stent placement; bleeding occurred in 3 of 27 patients (11.1%; 95% CI: 3.9-28.1%) with wound closure, and in the single patient without wound closure (100%; 95% CI: 5.1-100.0%). All bleeding events were managed endoscopically. No other adverse events occurred. After a mean follow-up of 27.4 months (range 10.0-97.0 months), two patients (7.1%) developed recurrence and underwent surgical resection ( n = 1) or repeat ER ( n = 1). Conclusions ER appears safe and effective for ampullary tumors exceeding 3 cm. The potential roles of wound closure and stent placement in reducing adverse events require validation in larger comparative trials.