Ampullary Cancer: Causes, Symptoms, Diagnosis and Treatment — Overview, Diagnosis & Treatment Options | MyMedicPlus

Ampullary carcinoma arises at the ampulla of Vater — the confluence of the common bile duct and pancreatic duct at their entry into the duodenum. It accounts for approximately 0.2% of GI cancers and 5-10% of periampullary malignancies. Two molecular subtypes: intestinal-type (better prognosis) and pancreatobiliary-type (aggressive, mimics pancreatic cancer behavior).

Familial adenomatous polyposis (FAP) substantially increases risk: over 60% of FAP patients develop duodenal/ampullary adenomas (Spigelman classification), with cumulative cancer risk of approximately 4-5%. Lynch syndrome, MUTYH-associated polyposis, and chronic pancreatitis are additional risk factors. The majority of ampullary adenocarcinomas arise from pre-existing adenomas through an adenoma-carcinoma sequence.

Painless obstructive jaundice is the most common presenting symptom, occurring earlier than in pancreatic cancer (because the ampulla is the narrowest part of the biliary tract). Epigastric pain, weight loss, acute pancreatitis, and upper GI bleeding from duodenal ulceration also occur. Courvoisier's sign (palpable non-tender gallbladder with jaundice) is present in some patients.

CT pancreatic protocol and MRI/MRCP for imaging. ERCP enables direct visualization, tissue biopsy, and biliary stenting for palliation of jaundice. EUS provides superior T and N staging. Serum CA 19-9 and CEA as tumor markers. Tissue molecular profiling: MSI/MMR, KRAS/NRAS/BRAF, HER2 amplification, NTRK fusion for systemic therapy selection. TNM staging (AJCC 8th edition).

Pancreaticoduodenectomy (Whipple procedure) with regional lymphadenectomy is the standard curative resection. Adjuvant chemotherapy: FOLFOX (preferred based on ESPAC-3 trial) or gemcitabine plus capecitabine. Metastatic disease: FOLFOX or FOLFIRI as first-line; KRAS wild-type intestinal subtype may benefit from EGFR antibody addition. MSI-H tumors respond to pembrolizumab.

Overall 5-year OS after resection approximately 45-55% — significantly better than pancreatic ductal adenocarcinoma. Intestinal-type: 5-year OS approximately 60-70%. Pancreatobiliary-type: 5-year OS approximately 25-40%. Lymph node negative R0 resection: 5-year OS approximately 60-70%. Lymph node positive: approximately 30-40%. Resectability at diagnosis exceeds 50%, far better than pancreatic cancer.