Guideline sources The following summarized guidelines for the evaluation and management of ampullary cancer are prepared by our editorial team based on guidelines from the European Society of Gastrointestinal Endoscopy (ESGE 2021) and the American Society for Gastrointestinal Endoscopy (ASGE 2021; 2013). 1 2 3 Calculator Calculator Eastern Cooperative Oncology G Karnofsky performance status s Guidelines 1. Classification and risk stratification Staging: Obtain EUS and abdominal MRCP for the staging of ampullary tumors. B Consider using the latest TNM classification for the staging of ampullary tumors. C https://web.pathway.md/diseases/rec3CEGnDJZsVsVtK 1/4 6/23/23, 2:34 AM Ampullary cancer Pathway 2. Diagnostic procedures Upper gastrointestinal endoscopy: consider using the cap-assisted method when the papilla is not seen during forward-viewing endoscopy. C Show 2 more Endoscopic ultrasound: obtain EUS in patients with suspected ampullary adenocarcinoma if the EUS findings or positive FNA results would change management. B Intraductal ultrasound: consider obtaining intraductal ultrasound in selected patients with ampullary tumors; however, balance the routine use against training, costs, and risk of pancreatitis. C Biopsy and histopathology: Perform endoscopic biopsies for histological confirmation in the case of low-grade dysplasia adenoma before initiating any treatment. B Avoid obtaining immunohistochemistry, K-ras and p53 evaluation, PCR, and MSI testing of ampullary tumor biopsies to inform prognosis and/or potential response to treatment. D Evaluation after initial negative histopathology: Obtain follow-up with EUS, side-viewing endoscopy, and further sampling with repeated biopsies for an enlarged papilla without clinical or biochemical signs in the case of initial negative histopathology. B Consider obtaining further investigations, at first including endoscopic US-guided FNA/biopsy and then limited sphincterotomy with repeated biopsies, in patients with suspected obstructive ampullary tumor with initial negative histopathology. B 3. Therapeutic procedures Endoscopic biliary stenting: perform retrograde cholangiopancreatography with self-expandable metal stent insertion in patients with ampullary tumors and biliary obstruction in palliative settings. A Show 2 more Ablative techniques: consider using complementary techniques (thermal ablation by cystotome, or radiofrequency ablation) with temporary biliary stenting in patients with ampullary adenoma with 20 mm intraductal extension, and performed in expert centers. C 4. Surgical interventions Endoscopic papillectomy (indications): do not perform diagnostic/therapeutic papillectomy when adenoma has not been proven. D Show 4 more https://web.pathway.md/diseases/rec3CEGnDJZsVsVtK 2/4 6/23/23, 2:34 AM Ampullary cancer Pathway Endoscopic papillectomy (technical considerations): individualize the decision for prophylactic endoscopic hemostasis and the type of technique. B Show 5 more Endoscopic papillectomy (prevention and management of postprocedural complications): perform direct snare resection without submucosal injection for endoscopic papillectomy. B Show 4 more Surgical papillectomy: consider offering surgical treatment of ampullary adenomas when endoscopic resection is not feasible for technical reasons (such as diverticulum, size > 4 cm), and in the case of intraductal involvement (of > 20 mm). C Pancreaticoduodenectomy: perform pancreaticoduodenectomy (including lymphadenectomy) for malignant lesions of the ampulla of stage T1 or higher, including cases where pathology results following an endoscopic papillectomy or surgical transduodenal ampullectomy reveal ampullary T1 adenocarcinoma. B 5. Specific circumstances Patients with gastric outlet obstruction: consider placing self-expandable metallic stents or performing surgical gastrojejunostomy in patients with incurable malignant gastric outlet obstruction undergoing palliative intervention. Decide between these approaches based on patient characteristics and preferences, multidisciplinary input, and local expertise. C Show 2 more 6. Follow-up and surveillance Postoperative surveillance: obtain long-term monitoring of patients after endoscopic papillectomy or surgical ampullectomy, based on duodenoscopy with biopsies of the scar and of any abnormal area, within the first 3 months, at 6 and 12 months, and thereafter yearly for at least 5 years. B Management of recurrent disease: Obtain a careful assessment of local tumoral extent using endoscopic examination and biopsies, and EUS and MRCP before any treatment in patients with recurrence after endoscopic papillectomy. B Consider offering endoscopic treatment including ablative techniques and endoscopic mucosal resection in patients with benign residual or recurrent lesions. C References 1. Geoffroy Vanbiervliet, Marin Strijker, Marianna Arvanitakis et al. Endoscopic management of ampullary tumors: European Society of Gastrointestinal Endoscopy ESGE Guideline. Endoscopy. 2021 Apr;53 4 429 448. Open https://web.pathway.md/diseases/rec3CEGnDJZsVsVtK 3/4 6/23/23, 2:34 AM Ampullary cancer Pathway 2. Anderson MA, Appalaneni V, Ben-Menachem T et al. The role of endoscopy in the evaluation and treatment of patients with biliary neoplasia. Gastrointest Endosc. 2013 Feb;77 2 167 74. Open 3. ASGE Standards of Practice Committee, Terry L Jue, Andrew C Storm et al. ASGE guideline on the role of endoscopy in the management of benign and malignant gastroduodenal obstruction. Gastrointest Endosc. 2021 Feb;93 2 309 322.e4. Open https://web.pathway.md/diseases/rec3CEGnDJZsVsVtK 4/4