(See also Overview of Biliary Function Overview of Biliary Function The liver produces about 500 to 600 mL of bile each day. Bile is isosmotic with plasma and consists primarily of water and electrolytes but also organic compounds: bile salts, phospholipids... read more .)
Cholangiocarcinomas and other bile duct tumors are rare (1 to 2/100,000 people) but are usually malignant. Cholangiocarcinomas occur predominantly in the extrahepatic bile ducts: 60 to 70% in the perihilar region (Klatskin tumors), about 25% in the distal ducts, and the rest in the liver. Risk factors include primary sclerosing cholangitis Primary Sclerosing Cholangitis (PSC) Primary sclerosing cholangitis (PSC) is patchy inflammation, fibrosis, and strictures of the bile ducts that has no known cause. However, 80% of patients also have inflammatory bowel disease... read more , older age, infestation with liver flukes, and a choledochal cyst.
Gallbladder carcinoma is uncommon (2.5/100,000). It is more common among American Indians, patients with large gallstones (> 3 cm), and those with extensive gallbladder calcification due to chronic cholecystitis Chronic Cholecystitis Chronic cholecystitis is long-standing gallbladder inflammation almost always due to gallstones. (See also Overview of Biliary Function.) Chronic cholecystitis almost always results from gallstones... read more (porcelain gallbladder). Nearly all (70 to 90%) patients also have gallstones Cholelithiasis Cholelithiasis is the presence of one or more calculi (gallstones) in the gallbladder. In developed countries, about 10% of adults and 20% of people > 65 years have gallstones. Gallstones... read more 
. Median survival is 3 months. Cure is possible when cancer is found early (eg, incidentally at cholecystectomy).
Gallbladder polyps are usually asymptomatic benign mucosal projections that develop in the lumen of the gallbladder. Most are < 10 mm in diameter and composed of cholesterol ester and triglycerides; the presence of such polyps is called cholesterolosis. They are found in about 5% of people during ultrasonography. Other, much less common benign polyps include adenomas (causing adenomyomatosis) and inflammatory polyps. Small gallbladder polyps are incidental findings that do not require treatment. However, for polyps > 10 mm in diameter, surgery should be considered.
Symptoms and Signs of Gallbladder and Bile Duct Tumors
Most patients with cholangiocarcinomas present with pruritus and painless obstructive jaundice Jaundice Jaundice is a yellowish discoloration of the skin and mucous membranes caused by hyperbilirubinemia. Jaundice becomes visible when the bilirubin level is about 2 to 3 mg/dL (34 to 51 micromol/L)... read more 
, typically at age 50 to 70 years. Early perihilar tumors may cause only vague abdominal pain, anorexia, and weight loss. Other features include fatigue, acholic stool, a palpable mass, hepatomegaly, or a distended gallbladder (Courvoisier sign, with distal cholangiocarcinoma). Pain may resemble that of biliary colic (reflecting biliary obstruction) or may be constant and progressive. Sepsis Sepsis and Septic Shock Sepsis is a clinical syndrome of life-threatening organ dysfunction caused by a dysregulated response to infection. In septic shock, there is critical reduction in tissue perfusion; acute failure... read more (secondary to acute cholangitis), although unusual, may be induced by endoscopic retrograde cholangiopancreatography (ERCP).
Manifestations of gallbladder carcinoma may range from incidental findings at cholecystectomy done to relieve biliary pain to cholelithiasis to advanced disease with constant pain, weight loss, and an abdominal mass or obstructive jaundice.
Most gallbladder polyps cause no symptoms.
Diagnosis of Gallbladder and Bile Duct Tumors
Ultrasonography (sometimes endoscopic), followed by CT cholangiography or magnetic resonance cholangiopancreatography Magnetic resonance imaging (MRI)
(MRCP)Sometimes endoscopic retrograde cholangiopancreatography (ERCP)
Cholangiocarcinomas and gallbladder carcinomas are suspected when extrahepatic biliary obstruction is unexplained. Laboratory test results reflect the degree of cholestasis. In patients with primary sclerosing cholangitis Primary Sclerosing Cholangitis (PSC) Primary sclerosing cholangitis (PSC) is patchy inflammation, fibrosis, and strictures of the bile ducts that has no known cause. However, 80% of patients also have inflammatory bowel disease... read more , serum carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) levels 19-9 are measured periodically to check for cholangiocarcinoma.
Diagnosis is based on ultrasonography (or endoscopic ultrasonography), typically followed by MRCP (see Imaging Tests of the Liver and Gallbladder Imaging Tests of the Liver and Gallbladder Imaging is essential for accurately diagnosing biliary tract disorders and is important for detecting focal liver lesions (eg, abscess, tumor). It is limited in detecting and diagnosing diffuse... read more ). CT is sometimes done and may provide more information than ultrasonography, particularly for gallbladder carcinomas. When these methods are inconclusive or if cholangiocarcinoma is suspected, ERCP Endoscopic retrograde cholangiopancreatography (ERCP) Imaging is essential for accurately diagnosing biliary tract disorders and is important for detecting focal liver lesions (eg, abscess, tumor). It is limited in detecting and diagnosing diffuse... read more is necessary. ERCP not only detects the tumor but also, with brushings, can provide a tissue diagnosis, sometimes making ultrasonography- or CT-guided needle biopsy unnecessary. Contrast-enhanced CT assists in staging.
Open laparotomy is necessary to determine disease extent, which guides treatment.
Treatment of Gallbladder and Bile Duct Tumors
For cholangiocarcinomas, stenting (or another bypass procedure) or occasionally resection
For gallbladder carcinoma, usually symptomatic treatment
For cholangiocarcinoma, stenting or surgically bypassing the obstruction relieves pruritus, jaundice, and perhaps fatigue.
Hilar cholangiocarcinomas with CT evidence of spread are stented via percutaneous transhepatic cholangiography Percutaneous transhepatic cholangiography (PTC) Imaging is essential for accurately diagnosing biliary tract disorders and is important for detecting focal liver lesions (eg, abscess, tumor). It is limited in detecting and diagnosing diffuse... read more or endoscopic retrograde cholangiopancreatography (ERCP). Distal duct cholangiocarcinomas are stented endoscopically with ERCP. If cholangiocarcinoma appears localized, surgical exploration determines resectability by hilar resection or pancreaticoduodenectomy.
Liver transplantation Liver Transplantation Liver transplantation is the 2nd most common type of solid organ transplantation. (See also Overview of Transplantation.) Indications for liver transplantation include Cirrhosis (70% of transplantations... read more for localized hilar cholangiocarcinoma is available at some transplant centers as part of a specific protocol approved by the United Network for Organ Sharing (UNOS).
Many gallbladder carcinomas are treated symptomatically.
Key Points
Biliary tract cancer (usually cholangiocarcinoma or gallbladder carcinoma) is uncommon.
Suspect cancer if patients have an unexplained extrahepatic biliary obstruction or abdominal mass.
Diagnose cancers by imaging, beginning with ultrasonography, followed by MRCP.
Treat cancers symptomatically (eg, by stenting or bypassing obstructions in cholangiocarcinoma); occasionally, resection is warranted.
Consider liver transplantation for selected patients with hilar cholangiocarcinoma.
