AIM:To investigate the clinical value of endoscopic papillectomy indicated by feasibility and safety of the procedure in various diseases of the papilla in a representative number of patients in a setting of daily clinical and endoscopic practice and care by means of a systematic prospective observational study. METHODS:Through a defined time period, all consecutive patients with tumor-like lesions of the papilla, who were considered for papillectomy, were enrolled in this systematic bicenter prospective observational study, and subdivided into 4 groups according to endoscopic and endoscopic ultrasonography (EUS) findings as well as histopathological diagnosis:adenoma; carcinoma/ neuroendocrine tumor (NET)/lymphoma; papilla into which catheter can not be introduced; adenomyomatosis, respectively. Treatment results and outcome were characterized by R0 resection, complication, recurrence rates and tumor-free survival.RESULTS:Over a 7-year period, 58 patients underwent endoscopic papillectomy. Main symptoms prompting to diagnostic measures were unclear abdominal pain in 50% and cholestasis with and without pain in 44%. Overall, 54/58 patients [inclusion rate, 93.1%; sex ratio, males/females = 25/29 (1:1.16); mean age, 65 (range, 22-88) years] were enrolled in the study. Prior to papillectomy, EUS was performed in 79.6% (n = 43/54). Group 1 (adenoma, n = 24/54; 44.4%):91.6% (n = 22/24) with R0 resection; tumor-free survival after a mean of 18.5 mo, 86.4% (n = 19/22); recurrence, 13.6% (n = 3/22); minor complications, 12.5% (n = 3/24). Group 2 (carcinoma/NET/lymphoma, n = 18/54; 33.3%):75.0% (n = 10/18) with R0 resection; tumor-free survival after a mean of 18.5 (range, 1-84) mo, 88.9% (n = 8/9); recurrence, 11.1% (n = 1/9). Group 3 (adenomyomatosis, n = 4/54; 7.4%). Group 4 (primarily no introducible catheter into the papilla, n = 8; 14.8%). The overall complication rate was 18.5% (n = 10/54; 1 subject with 2 complications):Bleeding, n = 3; pancreatitis, n = 7; perforation, n = 1 (intervention-related mortality, 0%). In summary, EUS is a sufficient diagnostic tool to preoperatively clarify diseases of the papilla including suspicious tumor stage in conjunction with postinterventional histopathological investigation of a specimen. Endoscopic papillectomy with curative intention is a feasible and safe approach to treat adenomas of the papilla. In high-risk patients with carcinoma of the papilla with no hints of deep infiltrating tumor growth, endoscopic papillectomy can be considered a reasonable treatment option with low risk and an approximately 80% probability of no recurrence if an R0 resection can be achieved. In patients with jaundice and in case the catheter can not be introduced into the papilla, papillectomy may help to get access to the bile duct. CONCLUSION:Endoscopic papillectomy is a challenging interventional approach but a suitable patientand local finding-adapted diagnostic and therapeutic tool with adequate risk-benefit ratio in experienced hands.