Ampullary cancer (ampulla of Vater)
Ampullary cancer starts where the bile and pancreatic ducts empty into the small bowel. Because it blocks bile flow early it is often caught while still removable, and the Whipple operation cures a good share of patients. Tumours come in two flavours, intestinal-like and pancreas-like, and chemotherapy is increasingly chosen by which one the pathologist sees.
Overview
Ampullary adenocarcinoma arises from the ampulla of Vater, the papilla where the common bile duct and main pancreatic duct open into the duodenum. It is grouped with periampullary cancers (distal cholangiocarcinoma, duodenal adenocarcinoma, pancreatic head cancer) at surgery but behaves better than pancreatic cancer because it obstructs the bile duct and is diagnosed early. Two histomolecular subtypes matter: intestinal-type tumours resemble colorectal cancer (CDX2, MUC2; APC and KRAS mutations) and pancreatobiliary-type tumours resemble pancreatic cancer (MUC1, CK7; KRAS, TP53, SMAD4), with the latter behaving more aggressively. Familial adenomatous polyposis carries a large relative risk of ampullary adenoma and carcinoma, and endoscopic surveillance of the duodenum is part of FAP care.
Curative treatment is pancreatoduodenectomy (Whipple); small adenomas and some early T1 lesions can be removed endoscopically by papillectomy. Adjuvant chemotherapy is extrapolated: ESPAC-3 periampullary (JAMA 2012) showed a survival advantage for adjuvant gemcitabine or fluorouracil in multivariable analysis, and practice now leans on subtype, with oxaliplatin-fluoropyrimidine (FOLFOX or CAPOX) for intestinal-type and gemcitabine-based or modified FOLFIRINOX regimens for pancreatobiliary-type tumours. For metastatic disease the same logic applies, and tumour-agnostic biomarkers (MSI-high, HER2, NTRK, BRAF) should be tested because they are found more often than in pancreatic cancer.
The active questions are prospective subtype-directed adjuvant trials, ctDNA to guide adjuvant decisions, and neoadjuvant therapy for node-positive disease.
State of the art today
- Ampullary cancer got its own NCCN guideline in 2022, separating it from pancreatic cancer and formalising subtype-directed chemotherapy.
- Histomolecular subtyping is the key advance: it tells the oncologist whether to treat the tumour like a bowel cancer or like a pancreatic cancer.
- Endoscopic papillectomy spares many patients with adenomas or early lesions a Whipple operation.
- Because the disease is rare, most systemic-therapy evidence is retrospective; prospective subtype-stratified trials and ctDNA-guided adjuvant studies are the next step.
Where it starts and where it drains
Most pancreatic cancers arise in the head next to the bile duct, which is why jaundice is the presenting sign; bile duct cancers are named by where along the tree they sit.
- Pancreatic head (most PDAC)
- Body and tail
- AmpullaAmpullary adenoma (precursor; sporadic or FAP-associated) · Ampullary neuroendocrine tumour (rare; see neuroendocrine)
- Islets (pancreatic NET)Ampullary neuroendocrine tumour (rare; see neuroendocrine)
- Intrahepatic ducts
- Perihilar (Klatskin)
- Distal bile duct
- Gallbladder
- peripancreatic
- hepatic hilar
- coeliac and superior mesenteric
Same organ: Pancreatic ductal adenocarcinoma, Biliary tract cancer (cholangiocarcinoma), Neuroendocrine tumours, Gallbladder cancer
Rare: well under one case per 100,000 per year, but it makes up a disproportionate share of resectable pancreatoduodenectomies because it obstructs the bile duct early and presents with jaundice.
- Liquid biopsy (ctDNA)Standard of care
- AI in radiologyEstablished
- cfDNA fragmentomicsEstablished
- Colorectal cancer screening (colonoscopy, FIT, stool DNA, blood)Standard of care
- DNA methylation profilingEstablished
- HCC surveillance in cirrhosis (ultrasound + AFP)Standard of care
- A 28-day national pathway for people with a positive multi-cancer blood test
- A breath test to rule out cancer in people with vague symptoms
- A cancer blood test for older people arriving at A&E with unexplained symptoms
- A legislated, publicly reported 28-day standard from urgent referral to diagnosis
- A live national dashboard of stage at diagnosis as the scorecard for early detection
- A single 'cancer check at 60' appointment bundling all screening tests
Background: CA 19-9, Alpha-fetoprotein (AFP), Barrett's oesophagus, Early detection, Faecal immunochemical test (FIT). Also on OnCo: Symptoms and red flags · Early detection roadmap.
Where the cases are
No country-level case numbers. This cancer is not mapped to a GLOBOCAN site.
Endoscopic papillectomy with surveillance; surgery if invasive cancer or unfavourable features on pathology.
Pancreatoduodenectomy with regional lymphadenectomy; biliary stenting first only if cholangitis or delayed surgery.
Six months of chemotherapy chosen by subtype: oxaliplatin-fluoropyrimidine (FOLFOX or CAPOX) for intestinal-type; gemcitabine-based or modified FOLFIRINOX for pancreatobiliary-type; evidence is from ESPAC-3 periampullary and retrospective series.
Subtype-directed chemotherapy; pembrolizumab for MSI-high; HER2-, BRAF- or NTRK-directed therapy where present; clinical trials.
Subtypes & biomarkers
top- Intestinal-type adenocarcinoma
- Pancreatobiliary-type adenocarcinoma
- Mixed type
- Ampullary adenoma (precursor; sporadic or FAP-associated)
- Ampullary neuroendocrine tumour (rare; see neuroendocrine)
- Histomolecular subtype by IHC (CDX2, MUC2 vs MUC1, CK7)
- Lymph node status and margin status after Whipple
- MSI / mismatch repair
- HER2, BRAF V600E, NTRK fusions
- KRAS, TP53, SMAD4 (pancreatobiliary), APC (intestinal)
- CA 19-9 and CEA for monitoring
- Germline APC (FAP) where duodenal polyposis is present
Target prevalence in this cancer
- 1899Halsted resects an ampullary cancer
First successful local resection of a periampullary tumour.
- 1935Whipple's pancreatoduodenectomy
Allen Whipple reports the operation that became the standard for periampullary cancer.
- 1994Intestinal and pancreatobiliary subtypes described
Kimura and colleagues link histological type to prognosis.
- 2012ESPAC-3 periampullary
Adjuvant chemotherapy after resection of periampullary cancer; survival benefit in adjusted analysis.
- 2022NCCN publishes a dedicated ampullary adenocarcinoma guideline
Subtype-directed treatment recommendations formalised.
Open problems, and what is being done about each
No prospective randomised trial has compared subtype-directed adjuvant regimens; retrospective consortia and the NCCN guideline are the current basis.
Which patients with node-positive disease benefit from neoadjuvant therapy; extrapolation from pancreatic trials is being tested.
Surveillance intensity after Whipple and the role of ctDNA to select adjuvant therapy.
FAP-associated duodenal disease: timing of prophylactic surgery versus endoscopic control.
Trials
topRecruiting now (live from ClinicalTrials.gov)
Country and place are remembered in this browser only. A postcode is sent to OpenStreetMap's Nominatim service to find coordinates when you press the button; nothing else leaves your device.
Expert centres
topCentres linked to this cancer in OnCo
- Johns Hopkins Hospital / Sidney Kimmel Comprehensive Cancer CenterBaltimore, USNewsweek oncology #10NCI comprehensivevia Pembrolizumab
- Alliance for Clinical Trials in OncologyChicago, IL, USvia Pembrolizumab
- GOG FoundationPhiladelphia, PA, USvia Pembrolizumab
- Institut Jules BordetBrussels, BEvia Pembrolizumab
- via Pembrolizumab
- via Gemcitabine
- via Larotrectinib
Questions to ask
topQuestions to ask your oncologist about Ampullary cancer
Newly diagnosed
- What is my exact diagnosis, stage, and grade, and which tests established them?Why: Everything else follows from an accurate stage and subtype.
- Which biomarkers have been tested on my tumour (for example Histomolecular subtype by IHC, Lymph node status and margin status after Whipple, MSI / mismatch repair, HER2, BRAF V600E, NTRK fusions, KRAS, TP53, SMAD4, APC), and what were the results?Why: These results decide eligibility for targeted therapy, immunotherapy, and trials.
- Which subtype is my cancer, and does that change the recommended treatment?Why: Recognised subtypes for this cancer include Intestinal-type adenocarcinoma, Pancreatobiliary-type adenocarcinoma, Mixed type.
- Is germline (inherited) genetic testing recommended for me or my family?Why: Inherited variants can change treatment and matter for relatives.
Ampullary adenoma or early T1 lesion
- For my situation (ampullary adenoma or early t1 lesion), which of the standard options do you recommend and why?Why: Guideline options include: Endoscopic papillectomy with surveillance; surgery if invasive cancer or unfavourable features on pathology.
Resectable carcinoma
- For my situation (resectable carcinoma), which of the standard options do you recommend and why?Why: Guideline options include: Pancreatoduodenectomy with regional lymphadenectomy; biliary stenting first only if cholangitis or delayed surgery.
Adjuvant
- For my situation (adjuvant), which of the standard options do you recommend and why?Why: Guideline options include: Six months of chemotherapy chosen by subtype: oxaliplatin-fluoropyrimidine (FOLFOX or CAPOX) for intestinal-type; gemcitabine-based or modified FOLFIRINOX for pancreatobiliary-type; evidence is from ESPAC-3 periampullary and retrospective series.
- Am I a candidate for FOLFOX (5-FU, leucovorin, oxaliplatin), CAPOX (capecitabine, oxaliplatin), Gemcitabine or related drugs, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
Metastatic
- For my situation (metastatic), which of the standard options do you recommend and why?Why: Guideline options include: Subtype-directed chemotherapy; pembrolizumab for MSI-high; HER2-, BRAF- or NTRK-directed therapy where present; clinical trials.
- Am I a candidate for FOLFOX (5-FU, leucovorin, oxaliplatin), Gemcitabine + nab-paclitaxel, Pembrolizumab or related drugs, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
Any stage
- Are there clinical trials I could join, for example of FOLFIRINOX / mFOLFIRINOX, Pembrolizumab, Signatera?Why: Trials are how the next standard of care is set; asking early keeps options open.
- Would a second opinion at a high-volume centre change anything, and can you help arrange it?Why: Rare or high-stakes decisions benefit from a centre that treats many similar patients.
- What supportive care (symptom control, nutrition, exercise, mental health, financial help) is available from the start?Why: Supportive care improves quality of life and helps patients complete treatment.
- I read that “No prospective randomised trial has compared subtype-directed adjuvant regimens; retrospective consortia and the NCCN guideline are the current basis”. How does that affect my plan?Why: Open problems are where trials and second opinions matter most.
- I read that “Which patients with node-positive disease benefit from neoadjuvant therapy; extrapolation from pancreatic trials is being tested”. How does that affect my plan?Why: Open problems are where trials and second opinions matter most.
Print this page for your appointment (your browser's print command). These prompts are for discussion; your clinical team knows your case.
Direct links plus the targets, companies, and technologies of this cancer's products.
technologies
11targets
5drugs
9companies
5pathways
3terms
6bottlenecks
2Latest papers
topQuery for this cancer: (TITLE:"Ampullary cancer" OR ABSTRACT:"Ampullary cancer" OR TITLE:"ampulla of Vater" OR ABSTRACT:"ampulla of Vater" OR TITLE:"Ampulla of Vater carcinoma" OR ABSTRACT:"Ampulla of Vater carcinoma" OR TITLE:"Periampullary cancer" OR ABSTRACT:"Periampullary cancer" OR TITLE:"Ampullary adenocarcinoma" OR ABSTRACT:"Ampullary adenocarcinoma") AND (treatment OR therapy OR trial OR survival OR diagnosis). Results are unfiltered search hits about Ampullary cancer (ampulla of Vater), not a curated reading list.
Pages like this
not linked directly; found by shared links- CancerGallbladder cancer
Shares CA 19-9, Lymphadenectomy (lymph node dissection), Obstructive jaundice and biliary obstruction, Larotrectinib and the tags nci-coverage, rare, gastrointestinal.
- CancerAppendiceal cancer and pseudomyxoma peritonei
Shares CAPOX (capecitabine, oxaliplatin), FOLFOX (5-FU, leucovorin, oxaliplatin), RAS / RAF / MEK / ERK (MAPK), KRAS and the tags rare, gastrointestinal.
- CancerDesmoid tumour
Shares Wnt / β-catenin, Rare and paediatric cancers without markets, Cytotoxic chemotherapy and the tags nci-coverage, rare.
- CancerParathyroid carcinoma
Shares Hereditary cancer syndromes, Rare and paediatric cancers without markets and the tags nci-coverage, rare.
- CancerNasal cavity and paranasal sinus cancers (including esthesioneuroblastoma)
Shares Rare and paediatric cancers without markets, Cytotoxic chemotherapy, Pembrolizumab and the tags nci-coverage, rare.
- CancerUrethral cancer
Shares Rare and paediatric cancers without markets, Cytotoxic chemotherapy, Pembrolizumab and the tags nci-coverage, rare.
- CancerMale breast cancer
Shares Hereditary cancer syndromes, HER2, Rare and paediatric cancers without markets and the tags nci-coverage, rare.
- CancerPheochromocytoma and paraganglioma (PPGL)
Shares Hereditary cancer syndromes, Rare and paediatric cancers without markets, Cytotoxic chemotherapy and the tags nci-coverage, rare.