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This chapter focuses on biliary tract cancers, including those of the gallbladder and intrahepatic and extrahepatic bile ducts. Because the epidemiology, clinical presentation, and surgical approach associated with gallbladder cancer and bile duct cancer are distinct, these two cancers are discussed separately.

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Epidemiology

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With an incidence of 6500 cases annually in the United States, gallbladder cancer is the fifth most common gastrointestinal tract malignancy in this country.1 Incidence increases with age and is two to six times higher in women than in men. Worldwide, the highest incidence rates (up to 7.5 per 100,000 in men and 23 per 100,000 in women) occur among populations in the Western part of South America (eg, Chile and Peru), in North American Indians, in Mexican Americans, and in northern India.2 The best characterized risk factor for the development of gallbladder cancer is chronic inflammation associated with gallstones (Table 51-1). Although only 0.5–3% of patients with cholelithiasis will develop gallbladder cancer, gallstones are present in 70–90% of patients diagnosed with gallbladder cancer.2–4 Further, the geographic pattern of gallbladder cancer incidence correlates with that of cholelithiasis.

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Table 51-1: Risk Factors for Developing Gallbladder Cancer
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Other factors implicated to increase the risk of developing gallbladder cancer include porcelain gallbladder (the incidence of gallbladder cancer is reported to range from 12.5 to 60% in patients with this condition),2–4 adenomatous polyps of the gallbladder (in contrast, cholesterol and inflammatory polyps and adenomyomas 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), 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.5 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.

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Pathogenesis and Pathology

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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. The molecular changes associated with this progression are under investigation: K-ras mutations appear to be relatively uncommon, whereas p53...

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