Ampullary Neuroendocrine Tumors: Multicenter Experience and Emerging Perspectives on Endoscopic Treatment

Aims Ampullary neuroendocrine tumors (a-NETs) are extremely rare (0.3-1% of all gastrointestinal NETs,<2% of periampullary cancers). Limited data on their natural history, optimal management, and long-term outcomes is available. Current standard treatment is pancreatoduodenectomy (PD), characterized by invasiveness, significant morbidity and mortality. Promising data on endoscopic approach are coming. This multicenter retrospective cohort study aimed to evaluate the feasibility and outcomes of endoscopic papillectomy (EP) [1] [2] [3].

Methods Data regarding a-NETs patients that underwent EP across three Italian tertiary centers between 2011 and 2022 were collected. Pre-procedural staging was performed using MRI and/or endoscopic ultrasound (EUS). EP was performed under deep sedation; standard polypectomy snares were used for en bloc resection; pancreatic and biliary stenting were performed if indicated. Post-procedural adverse events (AEs) were categorized according to ESGE guidelines. First time follow-up endoscopy was conducted after a median time of 3 months. Primary outcomes included complete (R0) resection rates and recurrence; secondary outcomes focused on AEs.

Results A total of 14 patients were included (median age 62.5 years), 7 of which with symptoms. Preoperative staging identified: dilated pancreatic duct (14.3%), dilated common bile duct (35.7%), intraductal extension (21.4%). Twelve patients (85.7%) had a a-NET diagnosis on the EP specimen, the remaining had a pre-endoscopic diagnosis but did not undergo surgery because unfit (1) or due to personal choice (1). Eight resected a-NET were G1 (median Ki-67 1%), 6 were G2 (median Ki-67 5%). Median tumor size was 18 mm (IQR 15-24.5 mm). Eleven (78.6%) resections achieved R0; 2 R1 (1 underwent PC with negative histology for residual tumor cells, 1 chose close follow-up with no recurrence after 24 months); 1 R2 resection underwent PC. At three-month endoscopic follow-up, residual disease was noted in 3 patients (21.4%): 2 were managed endoscopically, 1 required surgery. No further endoscopic recurrences were observed, with a median follow-up of 14.5 months (IQR 5-26 months). Overall AEs rate was 42.9% (3 mild and 3 moderate). Post-procedural bleeding occurred in 7 patients, all managed endoscopically. One patient developed mild acute pancreatitis, treated conservatively. Median hospital stay was 2.5 days (IQR 1-5 days).

Conclusions Our findings suggest that EP may be a viable and effective alternative to surgery for selected patients with a-NETs, achieving high R0 rates and favorable short-term outcomes. Despite the aggressive nature of a-NETs, the majority of patients in our cohort did not require additional surgical intervention. The use of endoscopic techniques allowed for effective management of residual disease and AEs, with no recurrences observed during the follow-up. Larger prospective studies are needed to further define the role of endoscopic therapy in the management of a-NETs and to develop more refined guidelines.

Publication History

Article published online:
27 March 2025

• References

• 1 Ruff SM, Standring O, Wu G. et al. Ampullary Neuroendocrine Tumors: Insight into a Rare Histology. Ann Surg Oncol 2021; 28 (13): 8318-28
• 2 Panzuto F, Ramage J, Pritchard DM. et al. European Neuroendocrine Tumor Society (ENETS) 2023 guidance paper for gastroduodenal neuroendocrine tumours (NETS) G1–G3. J Neuroendocrinol 2023; 35 (08): e13306
• 3 Shimai S, Yamamoto K, Sofuni A. et al. Three Cases of Ampullary Neuroendocrine Tumor Treated by Endoscopic Papillectomy: A Case Report and Literature Review. Intern Med 2020; 59 (19): 2369-74