1998 results of the first series of follow-up studies on Japanese thorotrast patients and their relationships to an autopsy series.

The 1998 survey of the first series of epidemiological studies of Japanese Thorotrast patients revealed that 18 (6.9%) were alive and 244 (93.1%) had died among 262 war-wounded veterans to whom Thorotrast had been administered intravascularly. Of 1,630 age- and sex-matched controls, 525 (32.2%) were alive and 1,105 (67.8%) had died. These results indicated a shortening of the life span in patients who had received Thorotrast compared to their controls. Of the patients in the Thorotrast group, the main causes of death were liver malignancies (79, 30.2%), liver cirrhosis (20, 7.6%), blood diseases (9, 3.4%), and cancers of the extrahepatic bile duct (5, 1.9%). Statistical analyses by the chi(2) test and estimation of the relative risk (risk ratio) showed that the incidences of these disorders were significantly higher in the Thorotrast group than in the controls. In the 54-year period from 1945 to 1998, our autopsy series was enlarged to include 398 individuals: 386 injected with Thorotrast intravascularly and 12 injected by other routes. Results of analyses of the 386 autopsy cases given Thorotrast intravascularly were as follows: 263 cases (68.1%) of liver malignancies, 28 cases (7.3%) of liver cirrhosis, 29 cases (7.5%) of blood diseases, 16 cases (4.1%) of lung cancer, 4 cases (1.0%) of malignant peritoneal tumors, 2 cases (0.5%) of bone sarcomas, and 1 case (0.3%) of hemangiosarcoma of the spleen. The relative risks of liver malignancies, blood diseases, bone sarcomas, malignant peritoneal tumors, and hemangiosarcoma of the spleen manifested significantly higher ratios in the Thorotrast autopsy cases (ratio of proportion) than in the autopsy control cases. Histological studies of these autopsied cases revealed that Thorotrast-induced liver malignancies showed remarkable differences in the proportions of histological types of tumors from those of non-Thorotrast liver malignancies since 1975. However, in this survey, we noted a remarkable increase in the incidence of liver malignancy of multiple histological types compared to that in histological controls. Based on the results of our 1998 survey, we estimated attributable risks of Thorotrast-inducedliver malignancies and blood diseases in the life span. Results showed 523 liver malignancies per 10(4) person Gy and 150 blood diseases per 10(4) person Gy for Japanese male Thorotrast carriers (wasted dose 10 years).