January 14, 2007

Carcinoma of the Ampulla of Vater

Synonyms and related keywords: periampullary carcinoma, periampullary malignancy, ampullary carcinoma, ampullary cancer, carcinoma of papilla of Vater, adenocarcinomas, neuroendocrine tumors, cystadenomas, adenomas, adenocarcinoma of the ampulla of Vater, Courvoisier sign, familial adenomatous polyposis, FAP, duodenal adenomas, endoscopic ultrasonography, EUS, endoscopic retrograde cholangiopancreatography, ERCP, percutaneous transhepatic cholangiography, PTC, kocherization, pancreaticoduodenectomy, pylorus-preserving pancreaticoduodenectomy, transduodenal excision


Background: Carcinoma of the ampulla of Vater is a malignant tumor arising within 2 cm of the distal end of the common bile duct, where it passes through the wall of the duodenum and ampullary papilla. The common bile duct merges with the pancreatic duct of Wirsung at this point and exits through the ampulla into the duodenum. The most distal portion of the common bile duct is dilated (ie, forms the ampulla of Vater) and is surrounded by the sphincter of Oddi, which spirals upward around the terminal portion of the duct. Because of biliary outflow obstruction, carcinoma of the ampulla of Vater tends to manifest early, as opposed to other pancreatic neoplasms that often are advanced at the time of diagnosis.

Curative surgical resection is the only option for long-term survival. Surgical or radiologic biliary decompression, relief of gastric outlet obstruction, and adequate pain control may improve the quality of life but do not affect overall survival rate.

Pathophysiology: Ninety percent of ampullary tumors are adenocarcinomas. Neuroendocrine tumors, cystadenomas, and adenomas represent additional, but uncommon, histologic types. Tumors originate from ductal epithelial cells and usually invade into the substance of the pancreas. In more advanced disease states, peripancreatic tissue and the adventitia of large neighboring vessels, such as the superior mesenteric and portal veins, may be involved.

Lymph nodes metastases are present in as many as half of patients. Pericanalicular lymph nodes usually are the first to be involved. Nodes along the superior mesenteric, gastroduodenal, common hepatic, and splenic arteries, as well as the celiac trunk, are the second station of lymph nodes. Perineural, vascular, and lymphatic invasion are associated with a poor prognosis. Liver is the most common site (66%) of distant metastasis, followed by lymph nodes (22%). In advanced cases, lung metastasis also may occur.











Bile Duct Strictures
Bile Duct Tumors
Biliary Disease
Biliary Obstruction
Duodenal Ulcers
Gallbladder Cancer
Gallbladder Tumors
Lymphoma, Non-Hodgkin
Pancreatic Cancer
Pancreatitis, Chronic
Papillary Necrosis
Papillary Tumors

Other Problems to be Considered:

Duodenal carcinoma
Adenoma at the ampulla of Vater


Lab Studies:

Imaging Studies:

Other Tests:


    • Disadvantages
      • ERCP is an invasive procedure, which requires an expert endoscopist/radiologist and a cooperative patient.
      • Very small tumors (less than 1 cm) can be missed.
      • ERCP is not possible if access to the duodenal papilla is difficult, eg, owing to diverticula, anatomical ductal variations, or prior surgical bypass.
      • This procedure can precipitate pancreatitis and cholangitis.
      • Perforation and hemorrhage are 2 of the more serious complications.
  • Percutaneous transhepatic cholangiography
    • Indications for this procedure, which is highly invasive, are very limited.
    • Percutaneous transhepatic cholangiography (PTC) is most useful when ERCP is unavailable or technically not feasible.
    • PTC can be useful in severely jaundiced patients when laparotomy or ERCP is not possible. Percutaneous transhepatic biliary drainage or transhepatic stenting may be the only option for some patients.
    • Biliary leakage may lead to peritonitis. Excessive bleeding from the puncture site and pneumothorax represent significant, but uncommon, complications.
Histologic Findings: In cases of ampullary tumors, preoperative endoscopic biopsy should be attempted, and carcinoma should be confirmed histologically or cytologically, if possible. If the specimen is insufficient or not representative, or if the histologic examination is inconclusive, surgery may be performed if a clinical suspicion exists. Approximately 90% of these tumors are adenocarcinomas. Neuroendocrine tumors, cystadenomas, and adenomas represent additional uncommon histologic types.

Staging: The tumor, node, metastases (TNM) classification and stage grouping is based on the Union Internationale Contre Cancrum (UICC) system, established in 1977, with separate classifications for pancreatic and periampullary carcinomas. The staging is important only to communicate a uniform definition of extent of disease. TNM classification and stage groups are as follows:

  • T - Primary tumor
    • Tx - The primary tumor cannot be assessed
    • T0 - No sign of primary tumor
    • Tis - Carcinoma in situ
    • T1 - Tumor limited to the ampulla or sphincter of Oddi
    • T2 - Tumor invading the wall of the duodenum
    • T3 - Tumor invasion into the pancreas 2 cm or less
    • T4 - More than 2 cm tumor invasion into the pancreas or any other adjacent organ

      Peripancreatic tissue includes the surrounding retroperitoneal fatty tissue (retroperitoneal soft tissue or retroperitoneal space), including the mesentery (mesenteric fat), mesocolon, greater and lesser omentum, and peritoneum. Direct invasion of the bile ducts and the duodenum includes involvement of the ampulla.

      Adjacent large vessels include the portal vein, the celiac trunk, the superior mesenteric artery and the common hepatic artery and vein (not the splenic vessels).

  • N - Regional lymph nodes
    • NX - Regional lymph nodes cannot be assessed
    • N0 - No regional lymph node metastases
    • N1 - Regional lymph node metastases

      Subclassification of the category N1 into N1a (only 1 metastatic lymph node) and N1b (2 or more lymph nodes affected by metastases) is recommended, as the 2 categories appear to have marked prognostic differences. Total number of peripancreatic lymph nodes found in the surgical specimen must be mentioned.

  • M - Distant metastases
    • MX - Distant metastases cannot be assessed
    • M0 - No distant metastases
    • M1 - Distant metastases

      Note: The splenic lymph nodes and those at the tail of the pancreas are not regional; metastases in these lymph nodes are classified as distant metastases (M1).

  • Stage grouping of periampullary carcinoma
    • Stage 1 - T1 N0 M0
    • Stage 2 - T2 N0 M0, T3 N0 M0
    • Stage 3 - T1 N1 M0, T2 NI M0, T3 N1 M0
    • Stage 4 - T4 every N and every M, Every T and N with M1
  • Martin proposed a 4-stage system, as follows:
    • Stage I - Vegetating tumor limited to the epithelium, with no involvement of the Oddi sphincter
    • Stage II - Tumor localized in the duodenal submucosa without involvement of the duodenal muscularis propria but possible involvement of the sphincter of Oddi
    • Stage III - Tumor involving the duodenal muscularis propria
    • Stage IV - Tumor involving the periduodenal area or the pancreas, with proximal or distal lymph node involvement


Medical Care: Hepatic metastasis, serosal implants, ascites, lymph node involvement outside the resectional field, and major vessel infiltration all are contraindications to surgical resection. Treatment options for advanced or unresectable stages are discussed below.

Surgical Care:

  • Pancreaticoduodenectomy
    • This is the classic and standard resection procedure for ampullary carcinoma.
    • In this operation, the pancreas is transected to the left of the portal vein, along with the uncinate process (in order to achieve lymph node dissection along the superior mesenteric artery). The lymph nodes along the common hepatic artery within the hepatoduodenal ligament and the precaval lymph nodes are removed. The gallbladder, along with the distal portion of the common bile duct and distal third of the stomach, is resected.
    • Restoration of the gastrointestinal continuity is completed with pancreaticojejunostomy, hepaticojejunostomy, and gastrojejunostomy.
  • Pylorus-preserving pancreaticoduodenectomy
    • This preserves the entire pylorus, along with 1-2 cm of the first part of the duodenum. GI continuity is restored with a duodenojejunostomy.
    • This represents a more physiologically acceptable procedure, with similar survival rates. Postgastrectomy complications, such as dumping and marginal ulceration, are reduced. Delayed gastric emptying may be exacerbated.
    • Postprandial release of gastrin and secretin is nearly normal in patients who undergo this procedure.
  • Transduodenal excision of ampullary tumors
    • Transduodenal excision rarely is indicated and is reserved for elderly patients, patients with significant comorbid conditions, and those with favorable tumors (generally less than 2 cm, polypoid).
    • This more limited resective technique is associated with compromised local control in many instances.
  • Palliative surgery
    • Palliative surgery is reserved for unresectable tumors or for patients who are unfit for curative surgery.
    • The goal is to alleviate biliary obstruction, duodenal obstruction, or pain.
    • Either cholecystojejunostomy or hepaticojejunostomy bypass is performed.
    • Duodenal obstruction may require gastrojejunostomy. Prophylactic gastrojejunostomy should be done, even in a duodenum unobstructed at the time of laparotomy, because as many as one third of patients develop obstruction later. However, prophylactic gastrojejunostomy adds significant morbidity risk to the procedure.
    • Chemical splanchnicectomy, using either 6% phenol or 50% ethanol, can be performed intraoperatively. This procedure controls pain in 80% of patients.


  • A nutrition specialist for tailoring the diet, when needed
  • Physiotherapist
  • Physician in cases of postoperative fever, chest infection, or other problems


  • Oral feeding usually can be started on the second postoperative day.
  • The diet should be started with sips of water, which can be increased gradually over 48 hours to a liquid diet. Patients can have a semisolid diet by roughly the sixth day.
  • Initially, the diet should be deficient in fat and protein.


  • The patient should ambulate from the first postoperative day.
  • Early ambulation and chest physiotherapy reduce morbidity.


Prophylactic and postoperative antibiotics are given according to hospital protocol.

Drug Category: Chemotherapeutic agents -- Fluorouracil can be used as a radiosensitizer for high-risk tumors of the ampulla of Vater.
Drug Name
Fluorouracil (Adrucil) -- Fluorinated pyrimidine antimetabolite that inhibits thymidylate synthase and interferes with RNA synthesis and function. Has some effect on DNA. Useful in symptom palliation for patients with progressive disease.
Adult Dose500 mg/m2 IV
Pediatric DoseNot established
ContraindicationsDocumented hypersensitivity; bone marrow suppression; serious infection
InteractionsIncreased risk of bleeding with anticoagulants, NSAIDs, platelet inhibitors, thrombolytic agents; other immunosuppressive agents may enhance bone marrow toxicity
Pregnancy D - Unsafe in pregnancy
PrecautionsNausea, oral and GI ulcers, depression of immune system, and hematopoiesis failure (bone marrow suppression) may occur; adjust dose in renal impairment
Drug Category: Antibiotics -- Initial empiric antimicrobial therapy must be comprehensive and should cover both aerobic and anaerobic gram-negative organisms.
Drug Name
Cefoxitin (Mefoxin) -- Second-generation cephalosporin indicated for gram-positive cocci and gram-negative rod infections. Infections caused by cephalosporin- or penicillin-resistant gram-negative bacteria may respond to cefoxitin.
Any second-generation cephalosporin may be used instead of cefoxitin.
Adult DoseBiliary stent present: 1 g IV preoperatively; continue until culture reported negative; if positive, adjust antibiotics on basis of culture sensitivity report
No biliary stent: 1 g IV preoperatively then 2 doses postoperatively
Pediatric DoseNot established
ContraindicationsDocumented hypersensitivity
InteractionsProbenecid may increase effects aminoglycosides or furosemide may increase nephrotoxicity (closely monitor renal function)
Pregnancy B - Usually safe but benefits must outweigh the risks.
PrecautionsAdjust dose in severe renal insufficiency (high doses may cause CNS toxicity); superinfections and promotion of nonsusceptible organisms may occur with prolonged use or repeated therapy


Further Inpatient Care:

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Patient Education:


Medical/Legal Pitfalls:

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