Cholangiocarcinoma, secondary to infection of liver flukes (Clonorchis sinensis or Opisthorchis viverrini)
In the Far East, liver flukes are one of the major causes of health problems. Clonorchis sinensis is mainly found in China, Korea and Japan, whereas Opisthorchis viverrini is limited to Northeast Thailand, Laos and Cambodia. Reports of liver fluke infection in North America have increased recently, reflecting the increased number of immigrants from these endemic areas.
The life cycles of C. sinensis and O. viverrini are similar and may be considered together. Humans are infected by eating raw or undercooked fish containing the encysted larvae (metacercariae). After excystation in the duodenum, the immature flukes enter the biliary ducts and differentiate into adults. The hermaphroditic adults produce eggs, which are excreted in the feces. Upon reaching fresh water, the eggs are ingested by snails, hatch within the gut and differentiate into cercariae. The free-swimming cercariae penetrate the scales of fish and encyst as metacercariae, which are then eaten by humans. Of note, the adult fluke has a life span of more than 20 years, which explains persistent infection.
There is strong epidemiological evidence that infection with liver flukes is associated with chronic biliary tract disease and ultimately leads to the development of cholangiocarcinoma. For example, the prevalence of cholangiocarcinoma is significantly higher in areas endemic for liver fluke infection than in non-endemic areas. Furthermore, experimental studies demonstrated that animals infected with C. sinensis or O. viverrini develop biliary epithelial changes similar to those in humans, with progression to cholangiocarcinoma. It has been postulated that the presence of parasites could induce DNA damage and mutations as a result of forming carcinogens or free radicals and of causing cell proliferation in the bile ducts, which plays a critical role in tumorigenesis.
The diagnosis of liver fluke infection is usually established by microscopic examination of ova or adult forms in the stool. Occasionally the diagnosis is made through evaluation of the bile fluid, as shown in this case. The ova of C. sinensis and O. viverrini are closely similar to each other in terms of morphology and size. In practice, they are indistinguishable. The distinction between these two flukes is possible by comparing the morphologic differences in the adult forms or by serologic techniques.
Early detection of cholangiocarcinoma has been attempted to improve prognosis and reduce mortality. One possibility is to use tumor markers such as CA19-9 and CEA to identify early cancers. The drawback is that they have very low specificities. The feasibility of using anti-C. sinensis or anti-O. viverrini antibodies to identify high-risk individuals, followed up by ultrasound, is also under study.
Early diagnosis and treatment of liver fluke infection is crucial in reducing the occurrence of cholangiocarcinoma, especially in those endemic areas. Successful control requires concentrating upon individuals at highest risk, repeated treatment (drug of choice: Praziquantel) and changing traditional dietary patterns, although the latter have proved rather refractory. Improved public health efforts have also been proven effective in limiting these diseases. In developed countries such as U.S., it is important to recognize these parasites and their associated complications in immigrants and travelers from endemic areas.
Contributed by Su Zheng, MD, PhD, J Thomas Molina, MD, PhD, Karen Schoedel, MD, and Sheldon Bastacky, MD