Although endoscopic papillectomy is an established minimally invasive alternative to surgical resection for ampullary lesions, its technical aspects are not well defined. This study aimed to evaluate technical and clinical factors influencing safety and outcomes.

A multicenter, retrospective analysis of consecutive patients who underwent endoscopic papillectomy in six tertiary Polish centers between 2011 and 2023. Primary outcomes included en bloc resection rate, tumour histology, recurrence rate, and adverse events; multivariate regression models were used to identify its independent predictors.

A total of 192 patients were included. En bloc resection was achieved in 66.1% of lesions. Larger tumour size (for 1 mm increase OR 1.06; 95% CI 1.02–1.11; p=0.002) and submucosal injection (OR 5.24; 95% CI 1.83–15.01; p=0.002) increased the odds of piecemeal resection. Adverse events occurred in 26.6% patients, mainly bleeding (17.2%) and pancreatitis (15.6%). Invasive adenocarcinoma was found in 5.6% of specimens; predictors were tumour size (for 1 mm increase OR 1.11; 95% CI 1.04–1.20; p=0.004) and jaundice (OR 20.20; 95% CI 3.94–103.68; p<0.001). Benign histology was observed in 17.9% lesions. Among 130 patients with follow-up (median 14.8 months), recurrence occurred in 39.2% and was independently associated with tumour size (OR 1.06; 95% CI 1.002–1.103; p=0.005) and prior resection attempts (OR 3.10; 95% CI 1.003–9.601; p=0.049).

Larger tumour size, submucosal injection, and previous resections were associated with lower en bloc resection and higher recurrence rates. High adverse event rates and inter-centre variability highlight the need for standardised techniques and follow-up strategies.