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ESSENTIALS OF DIAGNOSIS

  • Presents with obstructive jaundice, usually painless, often with dilated biliary tract.

  • Pain is more common in gallbladder carcinoma than cholangiocarcinoma.

  • A dilated gallbladder may be palpable (Courvoisier sign).

  • Diagnosis by cholangiography with biopsy and brushings for cytology.

GENERAL CONSIDERATIONS

Carcinoma of the gallbladder occurs in approximately 2% of all people operated on for biliary tract disease; the incidence, like that of carcinoma of the bile ducts, had been decreasing in the United States but may be increasing again in some Western countries because of lifestyle changes. It is notoriously insidious, and the diagnosis is often made unexpectedly at surgery. Cholelithiasis (often large, symptomatic stones) is usually present. Other risk factors are chronic infection of the gallbladder with Salmonella typhi, gallbladder polyps over 1 cm in diameter (particularly with hypoechoic foci on EUS), mucosal calcification of the gallbladder (porcelain gallbladder), anomalous pancreaticobiliary ductal junction, and aflatoxin exposure. Genetic factors include K-ras and TP53 mutations. Spread of the cancer—by direct extension into the liver or to the peritoneal surface—may be seen on initial presentation. The TNM classification includes the following stages: Tis, carcinoma in situ; T1a, tumor invades lamina propria, and T1b, tumor invades muscle layer; T2, tumor invades perimuscular connective tissue with no extension beyond serosa (visceral peritoneum) (T2a) or into liver (T2b); T3, tumor perforates the serosa or directly invades the liver or adjacent organ or structure; T4, tumor invades the main portal vein or hepatic artery or invades two or more extrahepatic organs or structures; N1, metastasis to one to three regional lymph nodes; N2, metastasis to four or more regional lymph nodes; and M1, distant metastasis.

Carcinoma of the bile ducts (cholangiocarcinoma) accounts for 10–25% of all hepatobiliary malignancies and 3% of all cancer deaths in the United States. It is more prevalent in persons aged 50–70, with a slight male predominance, and more common in Asia. About 50% arise at the confluence of the hepatic ducts (perihilar, or so-called Klatskin, tumors), and 40% arise in the distal extrahepatic bile duct (the incidence of which has risen since 1990); the remainder are intrahepatic (the incidence of which rose dramatically from the 1970s to the early 2000s). The frequency of carcinoma in persons with a choledochal cyst has been reported to be over 14% at 20 years, and surgical excision is recommended. Most cases of cholangiocarcinoma are sporadic. There is an increased incidence of cholangiocarcinoma in patients with bile duct adenoma; biliary papillomatosis; Caroli disease; a biliary-enteric anastomosis; ulcerative colitis, especially those with primary sclerosing cholangitis; biliary cirrhosis; diabetes mellitus; hyperthyroidism; chronic pancreatitis; heavy alcohol consumption; smoking; and past exposure to Thorotrast, a contrast agent. Obesity and diabetes mellitus are risk factors for intrahepatic cholangiocarcinoma. Aspirin use is associated with a reduced risk of all types of cholangiocarcinoma, and in diabetic patients, metformin use is associated with a reduced risk of intrahepatic cholangiocarcinoma. In Southeast Asia, hepatolithiasis, chronic typhoid carriage, and infection ...

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