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Carcinoma of the Ampulla of Vater Workup

  • Author: Nafisa K Kuwajerwala, MD; Chief Editor: N Joseph Espat, MD, MS, FACS  more...
Updated: Dec 31, 2015

Laboratory Studies

Blood biochemistry

See the list below:

  • Test for anemia caused by bleeding from the ampullary mass.
  • Test for hyperbilirubinemia (conjugated type) due to blockage of the biliary outflow.
  • Test for a rise in alkaline phosphatase level, again due to biliary obstruction.
  • Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) rise in long-standing obstruction. Elevation of AST is significantly more common in unresectable lesions (83%) than in resected lesions (22%). [8]
  • A rise in serum amylase level may be seen in 30%. [8]
  • Alteration in coagulation profile (eg, increased prothrombin time, decreased prothrombin time, prolonged bleeding and clotting times) is associated with profound obstructive jaundice.

Urine chemistry

See the list below:

  • Urinalysis may show bile pigments.
  • Absence of urinary urobilinogen signifies complete obstruction.

Tumor markers

See the list below:

  • Currently, no tumor marker is sensitive or specific enough to serve as reliable screening tools for this carcinoma.
  • Carbohydrate antigen (CA) 19-9 is the most studied and sensitive marker for pancreaticobiliary neoplasms at present. However, a normal serum Ca 19-9 does not rule out pancreaticobiliary malignancy.
  • Carcinoembryonic antigen (CEA), DU-PAN-2, alpha-fetoprotein (AFP), and pancreatic oncofetal antigen (POA) also have been evaluated and found inaccurate.

Imaging Studies

Abdominal ultrasonography


  • Abdominal ultrasonography (US) is the most useful noninvasive initial investigation for distinguishing medical from surgical causes of jaundice. It is an inexpensive and readily available bedside procedure.
  • Abdominal US can identify dilated ducts, liver metastasis (in almost 90% of cases), ascites, and nodal metastasis.
  • Doppler US can be used to assess vascular involvement.
  • The level of obstruction can be assessed in 90% patients.
  • US-guided fine-needle aspiration (FNA) can be performed.


  • Effectiveness is related to the skill of the user.
  • Very superficial lesions and very deep lesions may be missed. Distinguishing a metastasis from a hemangioma may be difficult.
  • Sensitivity is 80-90%, and information is inferior to that obtained by CT scan or MRI. Poor bowel preparation may obscure the important pathology.
  • It has been found to be diagnostic of carcinoma of ampulla of Vater only in 23.8% cases.

Endoscopic ultrasonography and transpapillary ultrasonography

Endoscopic ultrasonography (EUS) is performed through a peroral route. EUS remains highly operator dependent. It offers an additional option for biopsy. The test is highly sensitive in detecting major vascular involvement, which can prevent unnecessary surgery.[14]

EUS may identify tumors less than 1 cm in size. EUS is the most sensitive tool for diagnosis and staging of carcinoma of the ampulla of Vater. The sensitivity for detection is 97%, for T staging, 72%; for nodal staging, 47%; and for determining vascular involvement, 100%. However, the presence of biliary stent can decrease the accuracy to some extent. It can also be coupled along with biliary stenting. However, the sensitivity is low for determining distant metastasis.

Laparoscopic sonography can detect occult liver metastasis. Staging laparoscopy with laparoscopic ultrasonography may be more specific and accurate in predicting tumor resectability than laparoscopy alone (88% and 89% vs 50% and 65%, respectively[15] ).

Computed tomography


  • CT is noninvasive.
  • CT scan is superior to US but inferior to EUS for carcinoma of the ampulla of Vater unless extensive tumor is present.
  • CT scan is better in evaluating resectability and preoperative staging. It gives better assessment of invasion, encasement, or compression of vessels and adjacent organs.
  • CT-guided biopsy may be obtained when mass lesions are present, but endoscopic biopsy is preferred.
  • The double duct sign is shown in the CTs below.
    Double duct sign of periampullary cancers. Note th Double duct sign of periampullary cancers. Note the dilated common bile duct as well as the pancreatic duct. Liver metastatic lesion is also seen.
    Distended gall bladder with double duct sign in a Distended gall bladder with double duct sign in a patient with periampullary cancer.


  • Very ill patients may be unable to lie still or arrest respiration for the long periods required for high-quality imaging.
  • CT scan is more expensive than US and requires expertise in interpretation.
  • Potential radiation hazards exist for patients and staff.
  • Rare contrast reactions or contrast nephropathy may occur.
  • Metal, stents, and clips may cause artifacts.
  • Very small tumors (< 1 cm) may be missed.

Magnetic resonance imaging

MRI is the most informative noninvasive method of evaluation currently available.

MRI cholangiopancreatography (MRCP) provides 94% accuracy in identifying the cause and extent of the pathology. Results are reproducible. An MRCP revealing a resectable mass may preclude the need for ERCP.


Chest radiography is performed to exclude pulmonary metastasis and other pulmonary diseases.


Other Tests

ECG is performed to assess cardiac status, since surgery will be considered as a means of treatment.

Nutritional studies should be ordered in preparation for surgery.



Endoscopic retrograde cholangiopancreatography


  • ERCP allows diagnostic and therapeutic access to both the common bile duct and pancreatic duct.
  • The procedure displays the details of ductal anatomy and accurately demonstrates the level and nature of the obstruction. Anatomical variations in ducts can be evaluated carefully.
    Endoscopic view of an ampullary carcinoma. Endoscopic view of an ampullary carcinoma.
  • ERCP allows therapeutic procedures, such as sphincterotomy, stenting, and nasobiliary drainage.
  • It permits sampling of pancreatic juice, bile, and brush/grasp biopsy.
  • Endoscopic excision of small periampullary tumors is gaining in popularity.


  • ERCP is an invasive procedure that requires an expert endoscopist/radiologist and a cooperative patient.
  • Very small tumors (< 1 cm) can be missed.
  • ERCP is not possible if access to the duodenal papilla is difficult to obtain because of 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 percutaneous transhepatic cholangiography (PTC), which is highly invasive, are very limited.

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

The SEER database indicates adenocarcinoma is the most frequently identified histology for ampullary cancer. Adenocarcinoma (NOS) was reported in 65% of cases. Carcinoma (NOS) was reported in 8.1%; adenocarcinoma arising from adenoma (adenocarcinoma in villous adenoma, in tubulovillous adenoma, in adenomatous polyp and villous adenocarcinoma) was third most common in 7.5%. Other pathologic diagnoses reported included papillary adenocarcinoma (5.6%), mucinous adenocarcinoma (4.7%), and signet ring cell carcinoma (2%).[1]

Furthermore, adenocarcinoma is categorized as intestinal type or biliopancreatic type, which may have prognostic implications. Intestinal type has columnar cells organized into tubular or cribriform glands. Biliopancreatic type consist of cuboidal or low columnar cells arranged into simple glands or papillary or micropapillary structures.[4]



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
Contributor Information and Disclosures

Nafisa K Kuwajerwala, MD Staff Surgeon, Breast Care Center, William Beaumont Hospital

Nafisa K Kuwajerwala, MD is a member of the following medical societies: American College of Surgeons, American Society of Breast Surgeons, American Society of Breast Disease

Disclosure: Nothing to disclose.


Ronald S Chamberlain, MD Chairman, Surgeon-in-Chief, Department of Surgery, Director, Gastrointestinal Care Center, Medical Student Clerkship Director, Medical Executive Committee Member, St Barnabas Medical Center; Associate Professor of Surgery, New York College of Osteopathic Medicine; Associate Professor of Surgery, University of Medicine and Dentistry of New Jersey-New Jersey Medical School

Ronald S Chamberlain, MD is a member of the following medical societies: Alpha Omega Alpha, American Association for the Study of Liver Diseases, American College of Surgeons, American Medical Association, Phi Beta Kappa, Society for Surgery of the Alimentary Tract, Society of Surgical Oncology

Disclosure: Received honoraria from Wyeth for speaking and teaching; Received honoraria from Pfizer for speaking and teaching; Received honoraria from Sanofi Aventis for speaking and teaching.

Gunateet Goswami, MD Consulting Staff, Internal Medicine Associates, Mount Clemens, Michigan; Consulting Staff, Department of Cardiology, Henry Ford Hospital

Gunateet Goswami, MD is a member of the following medical societies: American Medical Association, American Society of Echocardiography, Michigan State Medical Society

Disclosure: Nothing to disclose.

Pankaj Chaturvedi, MBBS, MS, FACS Professor of Head and Neck Surgery, Department of Head and Neck Surgery, Tata Memorial Hospital, India

Pankaj Chaturvedi, MBBS, MS, FACS is a member of the following medical societies: American Association for the Advancement of Science, American Head and Neck Society, Association of Surgeons of India

Disclosure: Nothing to disclose.

Uma Chaturvedi, MD, MBBS, DPB Lecturer, Department of Pathology, KJ Somaiya Hospital and Research Center, India

Disclosure: Nothing to disclose.

Venkata Subramanian Kanthimathinathan, MD Fellow in Bariatric/Advanced Laparoscopic Surgery, University of Missouri Healthcare

Disclosure: Nothing to disclose.

Julie A Stein, MD Clinical Faculty, Hepatobiliary and Pancreatic Surgery, Department of Surgery, William Beaumont Hospital

Julie A Stein, MD is a member of the following medical societies: American College of Surgeons, Society for Surgery of the Alimentary Tract, Society of American Gastrointestinal and Endoscopic Surgeons, Americas Hepato-Pancreato-Biliary Association, Pancreas Club, American College of Surgeons Oncology Group

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Benjamin Movsas, MD 

Benjamin Movsas, MD is a member of the following medical societies: American College of Radiology, American Radium Society, American Society for Radiation Oncology

Disclosure: Nothing to disclose.

Chief Editor

N Joseph Espat, MD, MS, FACS Harold J Wanebo Professor of Surgery, Assistant Dean of Clinical Affairs, Boston University School of Medicine; Chairman, Department of Surgery, Director, Adele R Decof Cancer Center, Roger Williams Medical Center

N Joseph Espat, MD, MS, FACS is a member of the following medical societies: Alpha Omega Alpha, American Association for Cancer Research, American College of Surgeons, American Medical Association, American Society for Parenteral and Enteral Nutrition, American Society of Clinical Oncology, Americas Hepato-Pancreato-Biliary Association, Association for Academic Surgery, Central Surgical Association, Chicago Medical Society, International Hepato-Pancreato-Biliary Association, Pancreas Club, Sigma Xi, Society for Leukocyte Biology, Society for Surgery of the Alimentary Tract, Society of American Gastrointestinal and Endoscopic Surgeons, Society of Surgical Oncology, Society of University Surgeons, Southeastern Surgical Congress, Southern Medical Association, Surgical Infection Society

Disclosure: Nothing to disclose.

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Endoscopic view of an ampullary carcinoma.
Kocherization of the duodenum. For ampullary malignancies greater than 1 cm in size, pancreaticoduodenectomy is the preferred operation. This figure demonstrates the process of kocherization of the duodenum. The second and third portions of the duodenum are mobilized en bloc with the periduodenal nodal tissue. The authors prefer to expose the inferior vena cava (IVC) and remove alveolar tissue, which lies above the IVC en bloc with the specimen.
Periampullary malignancy. Transected pancreas with head. Pancreaticoduodenectomy is the preferred treatment for most periampullary tumors. This picture depicts transection of the pancreas at the pancreatic neck. This particular patient presented with a periampullary malignancy accompanied by jaundice and pancreatitis. A preoperative pancreatic stent (usually unnecessary) is seen within the pancreatic duct.
Carcinoma of the ampulla of Vater. Roux-en-Y reconstruction following completion of a standard pancreaticoduodenectomy.
Double duct sign of periampullary cancers. Note the dilated common bile duct as well as the pancreatic duct. Liver metastatic lesion is also seen.
Distended gall bladder with double duct sign in a patient with periampullary cancer.
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