Statistical Study on Thorotrast-induced Cancer of the Liver

Abstract

Epidemiological study of carcinogenesis of thorotrast was made in the following three ways of survey. 1) Prospective study: Of 147 thorotrast patients surveyed, 3 cases of liver cancer (cholangiocareinoma), 2 cases of liver cirrhosis and 1 case of leukemia were found, while, of 1,678 of non injected cases, 1 case of leukemia, 5 cases of liver cirrhosis and no liver cancer occurred more frequently in the thorotrast group than in controls.2) Retrospective study: Of 466 liver cancer patients surveyed, 4 or 0.85% had thorotrast shadow in the roentgenogram of the upper abdomen , while, of 1,938 controls, 1 or 0.07% the thorotrast shadow. Statistically, the thorotrast maintaining rate is higher in liver cancer patients than in contols.3) Autopsy case study: Of 38 autopsied cases of thorotrast, 21 were primary liver malignancy, which consisted of 4 hepatomas (19%), 14 cholangiocarcinomas (67%) and 3 endotheliomas (14%). As compared with the autopsy cases of Japanese, cholangiocarcinoma and endothelioma are extremely frequent in thorotrast cases with a statistically significant difference.Radiation carcinogenesis in man has been studied by the present research group since 1961. Of the results obtained, relationship between medical external irradiation and consequent human cancer was already published elsewhere in 1963 (Takahashi et al.1). The purpose of this paper is to describe a statistical study on carcinogenesis in patients who were irradiated for a long time by the internally introduced thorotrast, colloidal thorium dioxyde (Oka) ,2 for the diagnostic aid.

History note: tragedy of Thorotrast

“…Its distribution in the body depends on the route of administration, but, if administered through an intravascular route, it stays in the reticuloendothelial system with slow alpha decay (thorium-232 → radium-228 + α; physical half-life 1.405 × 10 10 years; biological half-life estimated to be 400 years) [17,18]. It was used widely for 2-10 million people in the world, and for 10-20 thousand people in Japan, mainly in Imperial Army hospitals [6][7][8].…”

“…Malignancy associated with Thorotrast deposition is various, including malignancy in the liver, biliary tracts, hematopoietic system, lymphoma, lung, peritoneum, bone and others [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16]. According to Ito and his associates [15] the hepatic tumors after Thorotrast deposition comprised cholangiocarcinoma (CCA) (44 cases, 43.1 %), angiosarcoma (AS) (39 cases, 38.3 %), hepatocellular carcinoma (HCC) (16 cases, 15.7 %), triple cancers (CCA + AS + HCC) (1 case, 1 %), and double cancers (CCA + HCC) (2 cases, 2 %).…”

“…Thorium dioxide suspension, trade name "Thorotrast", used to be considered an apparently innocent contrast medium that was used for angiography with adequate radiodensity and no significant acute or subacute adverse reactions at the clinical standard in the past. However, it was an alpha emitter which was deposited in the reticuloendothelial system, including the liver, spleen and lymph nodes, and it irradiated such organs for a lifelong period [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16]. Presented here is a tragic case that may be known to radiologists of older generations, but such experiences may not have been shared by younger radiologists, since almost all victims of Thorotrast injection are now dead.…”

Follow‐up Study of Thorium Dioxide Patients in Portugal*

“…However, some conclusions seem possible, even if more on biological than on epidemiological or statistical evidence. Among these conclusions we may point out particularly the fibrosis locally caused by thorotrast deposits in certain areas and organs of the body, which were certainly responsible for the local thorotrast granulomata (which has caused so far the deaths of 11 striking and important. though usually they become clinically evident as liver hemangioendotheliomata only.…”

Cancer mortality in Thorotrast-exposed patients in Japan: Aichi series

“…[11][12][13] Consequently, the Japanese Ministry of Health and Welfare set up a committee for the health care and financial support of Thorotrast patients, in 1966. [11][12][13] Consequently, the Japanese Ministry of Health and Welfare set up a committee for the health care and financial support of Thorotrast patients, in 1966.…”