Gastroenterology and Hepatology Board Review: Pearls of Wisdom, Third Edition


CHAPTER 36. Gallbladder and Bile Duct Tumors

Jana G. Hashash, MD and Randall E. Brand, MD

Image What is the most common cancer involving the hepatobiliary tree?

Gallbladder adenocarcinoma. Gallbladder carcinoma is the fifth most common cancer of the gastrointestinal tract and is responsible for 2%–4% of all gastrointestinal malignancies and about half of all biliary tract tumors. It occurs most frequently in the sixth and seventh decades of life and is more common in women and Native Americans.

Image Identify two risk factors for the development of gallbladder carcinoma.

Gallstones larger than 2.5 cm and calcified or “porcelain” gallbladder. Other risk factors include gallbladder polyps (> 1 cm), obesity, anomalous pancreaticobiliary duct junction or choledochal cysts, and carcinogens such as nitrosamines and azotoluene.

Image Which chronic infections are associated with gallbladder cancer?

Salmonella typhi carrier state is an independent risk factor for gallbladder cancer (six-fold risk). There are reports that Helicobacter colonization of the biliary epithelium may be associated with gallbladder cancer.

Image What are the most common routes of gallbladder carcinoma metastasis?

Lymphatic spread and direct invasion.

Image True/False: The most common benign neoplasm of the gallbladder is an adenoma.

True. The most common benign, nonneoplastic gallbladder lesion is the cholesterol “polyp,” also known as cholesterosis followed by adenomyomas and inflammatory polyps.

Image What size of benign adenomas of the gallbladder is at an increased risk for gallbladder carcinoma?

Adenomas greater than 10 mm have been observed to have malignant foci.

Image True/False: Gallbladder polyps of any size require surgical removal.

False. Gallbladder polyps < 5 mm are usually benign and represent cholesterolosis, whereas lesions > 10 mm should be considered to possibly harbor malignancy. Lesions between 5 and 10 mm may be either benign or malignant. Serial imaging is recommended to determine stability of size. Lesions that increase in size should undergo cholecystectomy.

Image Name two carcinogens associated with the development of gallbladder carcinoma.

Dimethylnitrosamine and petroleum products.

Image Name the biliary tree cancer that a patient with anomalous pancreaticobiliary duct junction and no biliary cysts is prone to develop.

Gallbladder cancer. In those patients, a prophylactic cholecystectomy is recommended.

Image Name three clinical entities associated with extrahepatic bile duct tumors.

1) Choledochal cysts or polycystic liver disease; 2) primary sclerosing cholangitis; and 3) chronic infection with Clonorchis sinensis, Ascaris lumbricoides, and Opisthorcis viverrini (worldwide the most common cause). Other clinical entities are ulcerative colitis, hepatolithiasis, Caroli syndrome, and obesity.

Image What contrast agent can predispose to cholangiocarcinoma?


Image What is the second most common tumor of the biliary tract?

Cholangiocarcinoma. Cholangiocarcinoma follows gallbladder carcinoma as the second most common tumor of the biliary tract. Over 70% of patients are over the age of 65.

Image Patients with congenital biliary cysts are at an increased risk of developing which biliary tree cancer?


Image Name two nonspecific tumor markers of the gastrointestinal tract that may be elevated in cholangiocarcinoma.

CA 19-9 and carcinoembyonic antigen (CEA). Alpha fetoprotein is elevated in < 5% of cases of cholangiocarcinoma.

Image Name two physical exam findings occasionally seen with ampullary carcinoma besides jaundice and excoriations from pruritis.

Hepatomegaly and Courvoisier’s sign (a palpably enlarged, nontender gallbladder). These findings are found in 25%–40% of patients with ampullary carcinoma. Left supraclavicular lymphadenopathy (Virchow’s node) or a palpable rectal shelf may be present in patients with widespread disease. The 5-year survival of ampullary carcinoma ranges from 20% to 40%.

Image Alternating jaundice and gastrointestinal bleeding are suggestive of what biliary tumor?

Ulcerating ampullary carcinoma.

Image What histologic subtype of ampullary carcinoma has the best prognosis?

Intestinal type has a better prognosis than pancreatobiliary type.

Image Identify three risk factors for the development of ampullary carcinoma.

Ampullary adenoma, familial adenomatous polyposis, and Gardner’s syndrome.

Image What hormone receptor may be found in cholangiocarcinomas?


Image Recent studies have reported an association between hepatitis C viral infection and which biliary tract cancer?

Intrahepatic cholangiocarcinoma.

Image Which side of the intrahepatic biliary tree, the right or left system, is preferentially drained by the presence of only one stent in the setting of a proximal intrahepatic bile duct tumor?

The left hepatic ductal system can be drained with a single stent. The right hepatic duct bifurcates extensively proximal to the confluence with the left hepatic duct.

Image Apart from CT/MRI of the abdomen, what other anatomical region of imaging is important for the staging of both gallbladder cancer and cholangiocarcinoma?

Chest imaging.

Image What is the current first-line chemotherapy for locally advanced and metastatic gallbladder and cholangiocarcinomas?

Gemcitabine and cisplatin.

Image What is the primary concern regarding an externally obtained (ie, percutaneously or via endoscopic ultrasound [EUS]) fine needle aspiration (FNA) or biopsy of a biliary tract cancer, in particular extrahepatic tumors?

Tumor seeding. Most institutions will not perform FNA or biopsy of these lesions percutaneously due to concerns about tumor seeding. However, some institutions will do these procedures on distal common bile duct (CBD) lesions (intrapancreatic portions) if the FNA is done under EUS guidance since the tract would be removed at the time of surgical resection.


Heinrich S, Clavien PA. Ampullary cancer. Curr Opin Gastroenterol. 2010 May:26(3):280-285.

Charbel H, Al-Kawas FH. Cholangiocarcinoma: epidemiology, risk factors, pathogenesis, and diagnosis. Curr Gastroenterol Rep. 2011 Apr;13(2):182-187.

Rustagi T, Dasanu CA. Risk factors for gallbladder cancer and cholangiocarcinoma: similarities, differences and updates. J Gastrointest Cancer. 2011 May 20. [Epub ahead of print]

Gurusamy KS, Abu-Amara M, Farouk M, Davidson BR. Cholecystectomy for gallbladder polyp. Cochrane Database Syst Rev. 2009 Jan 21;(1):CD007052.