Cholangiocarcinoma: lessons from Thailand

Abstract

Purpose of review: To present the background of liver fluke-associated cholangiocarcinoma in Thailand focusing on recent epidemiological data and pathogenesis of this bile duct cancer.

Recent findings: More systematic tumor registration in Thailand nowadays uncovers new high-incidence areas that are confined to not only the northeastern part but also some provinces in northern Thailand. The link between the liver fluke, Opisthorchis viverrini, and cholangiocarcinoma, particularly in terms of cellular and molecular pathogenesis, is further elucidated.

Summary: Thailand is still the country with the highest incidence of cholangiocarcinoma in the world. Liver fluke induces chronic inflammation leading to oxidative DNA damage of the infected biliary epithelium and malignant transformation. Eradication of the fluke and identification of high-risk populations are urgently needed.

Figure 1

Age-standardized incidence rates (ASR) of liver and bile duct cancer in male and female in different regions of Thailand (1998–2000)

Figure 2

Mortality rate of liver cancer and O. viverrini infection rate in different regions of Thailand (2004). Note Northeast Thailand shows different high mortality rate particularly in the upper part and rank within the top ten provinces with high incidence in Thailand. Figure modified from [18^•, 21^•]

Figure 3

Life cycle of Opisthorchis viverrini. Embryonated eggs are discharged in the biliary ducts and in the stool Eggs are ingested by a suitable snail intermediate host there are more than 100 species of snails that can serve as intermediate hosts. Each egg releases a miracidium which goes through several developmental stages (sporocyst redia and cercaria ). The cercaria is released from the snail and after a short period of free-swimming time in water, it comes into contact with and penetrates the flesh of a freshwater fish, such as Cyclocheilichthys armatus or Puntius leiacanthus, where it encysts as a metacercaria Infection of humans occurs by ingestion of undercooked, salted, pickled, or smoked freshwater fishes . After ingestion, the metacercaria excysts in the duodenum and ascends the biliary tract through the ampulla of Vater. Maturation to adults, Opisthorchis viverrini takes approximately 1 month. The adult flukes (measuring 10 to 15 mm by 3 to 5 mm) reside in the small and medium sized biliary ducts. In addition to humans, carnivorous animals can serve as reservoir hosts. (Adapted from http://www.dpd.cdc.gov/DPDx/HTML/Opisthorchiasis.htm)

Figure 4

Histopathology of O. viverrini infected human liver showing periportal inflammation, adenomatous hyperplasia and periductal fibrosis. The adult parasite is seen in the bile duct lumen.

Figure 5

Proposed mechanisms of Opisthorchis induced cholangiocarcinoma. The liver fluke induces damage to the bile duct tissue at least by 2 pathways; mechanical (by parasite sucker/excretory-secretory products) and immunopathology to parasite antigens. Inflammation induced oxidative DNA damage occurs in concurrent with biliary epithelial proliferation driving by parasite molecules. Damaged DNA/genes after successive replication became fixed lead to malignant transformation.