Biliary tract cancers (BTCs) are invasive carcinomas that arise from the epithelial lining of the gallbladder and bile ducts. Cholangiocarcinomas are cancers arising in the intrahepatic, perihilar, or distal biliary tree, exclusive of cancers of the gallbladder and ampulla of Vater (Figure 47-1). Tumors involving the proper hepatic duct bifurcation are collectively referred to as Klatskin tumors, and are subdivided further using the Bismuth-Corlette Classification based on involvement of the left and right hepatic ducts, and focality versus multifocality of the tumor (1).
Classification of biliary tract cancers. (From de Groen PC, Gores GJ, LaRusso NF, et al. N Engl J Med. 1999; 341. Copyright © 1999 Massachusetts Medical Society. All rights reserved.)
The vast majority of cholangiocarcinomas and gallbladder cancers (GBCs) are adenocarcinoma. While anatomically these malignancies are related, each has a distinct clinical presentation, molecular features, metastatic pattern, and prognosis. This group of tumors is characterized by local invasion, extensive regional lymph node metastasis, vascular encasement, and, especially with GBC, distant metastasis. Complete surgical resection offers the only chance for cure; rates of surgical resectability vary by primary location. Extrahepatic cholangiocarcinomas have the highest resectability rates compared to Klatskin and intrahepatic tumors (2). Among GBCs, only 10% of patients present with T1 tumors (those confined to the gallbladder muscle wall) unless they are found incidentally at cholecystectomy (3). Among those patients who do undergo "curative" resection, recurrence rates are high. BTCs have a poor prognosis; their 5-year survival rates are 5%–10% or less. The median survival of patients with unresectable or metastatic BTC at diagnosis is less than a year.
EPIDEMIOLOGY AND RISK FACTORS
Assessing incidence and prevalence of cholangiocarcinoma is difficult because intrahepatic cholangiocarcinoma is grouped with hepatocellular carcinoma. Collectively, there are an estimated 28,700 liver and intrahepatic bile duct cancers annually in the United States. Approximately 10%–15% of these tumors are estimated to be intrahepatic cholangiocarcinoma (4, 5). Extrahepatic bile duct and gallbladder cancers are grouped together. They total about 13,000 new cases annually in the United States, of which 9810 cases are extrahepatic cholangiocarcinoma, the remainder primary GBC (4). For unclear reasons, the incidence of intrahepatic cholangiocarcinoma has been rising over the past two decades in Europe and North America, Asia, Japan, and Australia. The risk factors for cholangiocarcinoma and GBC are shown in Table 47-1. For cholangiocarcinoma, these factors include primary sclerosing cholangitis (PSC), congenital abnormalities of the biliary tree (Caroli's syndrome, congenital hepatic fibrosis, choledochal cysts), parasitic infection of the liver flukes of the genera Clonorchis and Opisthorchis, hepatolithiasis, toxic exposures including radiologic contrast agent thorotrast (a radiologic contrast agent banned in the 1960s for its carcinogenic properties), Lynch syndrome II and multiple biliary papillomatosis, and possibly hepatitis C infection (...