Epidemiology of Cholangiocarcinoma and Gallbladder Carcinoma

Abstract

Cholangiocarcinoma (CCA) and gallbladder carcinoma (GBCA) are rare but lethal cancers of the liver and biliary tract. While surgical resection offers the best chance for cure, many cancers present late in the disease course when surgery does not alter patient survival or quality of life and is often unable to achieve a margin-negative (R0) resection. Despite advances in imaging and diagnostic modalities, appropriate screening protocols are yet to be developed due to the lack of known and modifiable risk factors. This chapter describes the epidemiology of cholangiocarcinoma and gallbladder carcinoma across world populations. Special attention is paid to describing the incidence, prevalence, and mortality of cholangiocarcinoma in the high-risk populations from Thailand, Japan, Korea, and China where infection with the liver flukes, O. viverrini and C. sinensis, and positive Hepatitis B and C infection are strongly implicated in CCA development. Intrahepatic stones, primary sclerosing cholangitis (PSC), biliary tree infection, and altered bilio-pancreatic anatomy may contribute to a chronic inflammatory state that promotes biliary epithelial metaplasia and CCA. In the last 10 - 15 years, there has been a trend of increased intrahepatic cholangiocarcinoma (ICC) and concurrent decreased extrahepatic cholangiocarcinoma (ECC) incidence, especially in low-risk populations of the United States, Europe, and Scandinavia. Gallbladder carcinoma incidence and mortality continues to be high in populations from northern India, Pakistan, and Eastern Europe, and is disproportionally higher in women. While the overall recent trend of GBCA incidence and mortality is on the decline, it remains high in women of high Amerindian ethnicity in South America and the United States. The differential decreased mortality in populations from the United States, Europe, and Scandinavia compared to South America and Asia is attributed to differential access and utilization of cholecystectomy. Specific risk factors for GBCA include longstanding cholelithiasis, S. typhi infection / chronic carrier state, and polypoid lesions of the gallbladder. However, these are not sensitive or specific modifiable risk factors are limited, thereby restricting the ability to design a screening protocol or mandate prophylactic surgery to protect against GBCA. Ongoing research efforts are focusing on the multifactorial contributions of environmental toxins, diet, obesity, and molecular mechanisms of CCA and GBCA development to improve early diagnosis and develop targeted therapies to complement surgical resection.