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This chapter focuses on gallbladder cancer and cholangiocarcinoma, including intrahepatic, perihilar, and extrahepatic variants. Because the epidemiology, clinical presentation and surgical approach for these tumors are distinct, they are discussed separately.



With an incidence of approximately 3000 cases annually in the United States (incidence 1.14 per 1000,000 people), gallbladder cancer it accounts for only 0.5% of all gastrointestinal tract malignancies in this country.1–3 Incidence increases with age and is two to three times higher in women than in men. Worldwide, the highest incidence rates (up to 8.0 per 100,000 in men and 22 per 100,000 in women) occur among populations in the Indian subcontinent, in the Western part of South America (eg, Colombia and Ecuador), and to a lesser extent in East Asia and Eastern Europe. In the United States, the incidence is higher in American Indians and in Hispanics.2,4 The best characterized risk factor for the development of gallbladder cancer is chronic inflammation associated with gallstones (Table 65-1). Although only a small fraction of patients with cholelithiasis will develop gallbladder cancer, gallstones are present in 70% to 90% of patients diagnosed with gallbladder cancer.4–6 Further, the geographic pattern of gallbladder cancer incidence correlates with that of cholelithiasis.


Other factors implicated to increase the risk of developing gallbladder cancer include porcelain gallbladder, adenomatous polyps of the gallbladder (in contrast, cholesterol and inflammatory polyps and adenomyomatosis are not believed to be the risk factors), chronic infection with Salmonella typhi, carcinogen exposure (eg, increased risk has been reported for miners exposed to radon), obesity, and abnormal pancreaticobiliary duct junction (APBDJ). In this latter condition, a long common channel, formed by an abnormally proximal junction between the pancreatic and common bile ducts (CBDs), and elevated sphincter of Oddi pressures create a predisposition to reflux pancreatic exocrine secretions into the bile ducts. APBDJ is most prevalent in Asian countries and appears to increase the risk of development of biliary cancers, especially gallbladder cancer.7 Gallbladder cancers arising in patients with APBDJ tends to occur at a younger age, to have a lesser degree of female predominance, and to be less often associated with cholelithiasis than those arising in patients without APBDJ.

Pathogenesis and Pathology

Chronic inflammation of the gallbladder mucosa related to gallstones is hypothesized to be the major factor leading to malignant transformation in most cases of gallbladder cancer. The progression from dysplasia to carcinoma in situ (CIS), then to invasive cancer has been described for gallbladder cancer, although a less ...

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