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INTRODUCTION

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Hepatobiliary malignancies comprise a diverse group of tumors, including hepatocellular carcinoma (HCC), variants such as fibrolamellar HCC (FLHCC) and cholangiocellular carcinoma, cholangiocarcinoma, carcinoma of the gallbladder, and rare cancers such as sarcoma, angiosarcoma, and hepatoblastoma. The relative frequency of these tumors is shown in Table 22-1. The estimated new cases and deaths from liver and intrahepatic bile duct cancer in the United States in 2014 totaled 33,190 and 23,000, respectively (1).

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Table 22-1Relative Frequency of Hepatobiliary Tumors Diagnosed in the United States
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The majority of primary liver tumors are HCC or cholangiocarcinoma. These tumor types have different etiologies, epidemiology, clinical presentations, and treatment options. Thus, they are discussed separately.

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HEPATOCELLULAR CARCINOMA

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Hepatocellular carcinoma is a malignancy of worldwide significance and has become increasingly important in the United States. It is the most common primary liver malignancy, the sixth most common cancer, and the third most common cause of cancer-related deaths worldwide (2). Eighty percent of new cases occur in developing countries, but the incidence is rising in economically developed regions, including Japan, Western Europe, and the United States (3,4,5,6). The worldwide distribution of HCC and its associated etiologies are summarized in Table 22-2. Liver cirrhosis is the seventh leading cause of death in the world, the tenth most common cause of death in the United States, and acknowledged as a premalignant condition for developing HCC (7,8,9).

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Table 22-2Incidence of Hepatocellular Carcinoma Worldwide
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In the United States, hepatitis C virus (HCV), alcohol use, and nonalcoholic fatty liver disease (NAFLD) are the most common causes of cirrhosis (9). The incidence of HCC doubled during the period 1975 to 1995 and continued to rise through 1998 (10,11). This trend was previously expected to continue due to the estimated 4 million US individuals who are hepatitis C seropositive and the known latency of HCC development from the initial HCV infection, which may take two to three decades (11). However, given the improved treatment regimens now available for patients with chronic hepatitis ...

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