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Point-mutational activation of the c-Ki-ras proto-oncogene has been shown to be rare in human hepatocellular carcinoma, the most common primary liver cancer and one usually associated with chronic viral infection. To reveal the association of c-Ki-ras activation with cholangiocarcinogenesis under different etiological backgrounds, the incidence of point mutation at codons 12 and 13 of the c-Ki-ras proto-oncogene was examined in three groups of human liver cancers with differentiation to biliary epithelial cells: Group 1, cholangiocellular carcinoma in Japanese with normal livers; Group 2, cholangiocellular carcinoma in Thais who had lived in an area where the liver fluke Opisthorchis viverrini is endemic; and Group 3, combined hepatocellular-cholangiocellular carcinoma, a rare type showing features of both hepatocellular and biliary epithelial differentiation, in Japanese with chronic viral hepatitis with or without cirrhosis. The polymerase chain reaction and direct sequencing of its product were used to detect the mutation. Point mutation at codon 12 of the c-Ki-ras gene was detected in five (56%) of nine cases in Group 1. In contrast, the mutation was not detected in any of the cases in Groups 2 and 3. Therefore, point-mutational activation of c-Ki-ras did not seem to be involved in the development of primary liver cancers associated with apparent chronic irritation of liver cells or biliary epithelial cells caused by exogenous liver-fluke or viral infection. On the other hand, point-mutational activation of the c-Ki-ras proto-oncogene may be involved in cholangiocarcinogenesis in liver without preexisting liver-fluke or viral infection.

The population of Northeast Thailand has one of the highest known rates of cholangiocarcinoma (cancer of the bile ducts). We sought firstly to obtain an estimate of the frequency of hospital-based diagnosis of cholangiocarcinoma in the northeastern province of Khon Kaen. All pathology, ultrasound and in-patient and out-patient records were searched for cases diagnosed in tertiary hospitals in a random calendar month in 1988. A total of 203 persons from various parts of northeastern Thailand were newly-diagnosed in the two hospitals, 75 of whom resided in Khon Kaen province. We estimated the minimal age-standardised annual incidence rate in this province to be 135.4 per 100,000 among males and 43.0 per 100,000 among females (world standard). Truncated standardised incidence rates (ages 35-64 years only) were 334.2 and 104.3 per 100,000 for males and females respectively. Secondly we aimed to assess the feasibility of secondary prevention by early clinical diagnosis. However, the symptoms and signs observed were typically non-specific and associated with advanced disease in patients with cholangiocarcinoma who presented to hospital. Primary preventive measures appear to be the key to decreasing the mortality from this disease.