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PubMed1983

[Cancers caused by therapeutic noxae: cancer and radiotherapy].

Published reports have shown that there is an increased incidence of second malignancies, particularly sarcomas, following high dose radiotherapy in cancer treatment. However, this increased risk is very small and is relatively negligible when one considers the beneficial effects of radiotherapy in cancer treatment. This incidence of radiation induced cancer appears to be higher in certain groups of patients, such as children and patients with Hodgkin's disease. In view of scarcity of published data, controlled surveys remain necessary for the quantitative assessment of the cancer risk in various sub-groups of irradiated patients.

Adult↗
PubMed1983

Recent results of the German Thorotrast study--epidemiological results and dose effect relationships in Thorotrast patients.

The German Thorotrast Study includes 5159 Thorotrast patients and 5160 control patients. 887 Thorotrast patients and 660 control patients could be clinically and biophysically examined and followed-up. The mean age at injection or hospitalization in the case of the control group was 28 yr. The mean injected volume of Thorotrast was calculated to be 24.7 ml and the X-ray films of 249 Thorotrast patients showed paravascular deposits. In the meantime 432 Thorotrast patients and 122 patients of the control group have died. Among the deceased patients we have registered (Thorotrast vs control): hepatic tumors 152/0; myeloproliferative diseases 10/0; Hodgkin's diseases 2/0; non-Hodgkin's lymphomas 5/1; bronchogenic carcinomas 13/6; pleural mesothelioma 1/0; bone sarcoma 1/1(?); sarcoma at injection site 1/0; hepatic cirrhosis 90/6; bone marrow failure 8/1; other neoplastic diseases 46/19; other non-neoplastic diseases 151/88. The cumulative incidence of liver tumors depends on the dose rate to liver tissue and is not influenced by the age at injection. A dose effect relationship for the myeloproliferative diseases is not yet apparent.

Adolescent↗
PubMed1983

Recent results of the German Thorotrast study--pathoanatomical changes in animal experiments and comparison to human thorotrastosis.

A survival experiment is described in which 1920 Wistar rats were used. These rats were injected intravenously with different quantities and different alpha-doses of Thorotrast. The following observations were made: The distribution of Thorotrast in the liver of the experimental animals is similar to that in human livers. Liver fibrosis and liver cirrhosis are rarely seen in experimental animals. The liver cell carcinomas, intrahepatic bile duct carcinomas and haemangiosarcomas that developed in the liver of the rats showed an identical biology and morphology with those seen in corresponding Thorotrast tumours in human patients. One particular tumour type that occurred in the liver of the rats probably represents a Kupffer cell sarcoma: the tumour cells show a positive peroxidase reaction and the metastases contained Thorotrast. Unlike human Thorotrast liver tumours, rat liver tumours include benign tumours such as liver cell adenomas and intrahepatic bile duct adenomas. The animals of the control group did not develop these benign liver tumours. The total frequency of the liver and spleen tumours in the trial groups receiving 230Th enriched Thorotrast was dependent on the dose given. The relationship between dose and effect was almost linear. The volume of the injected Thorotrast quantity, given a constant dose rate, seems to have only a slight influence on the number of tumours.

Animals↗
PubMed1983

Recent results of the German Thorotrast study--statistical evaluation of animal experiments with regard to the nonradiation effects in human thorotrastosis.

Our first long-term animal experiment made use of 1920 female Wistar rats divided into 20 groups of 96 animals each. These were injected at 12 weeks of age with different volumes and different dosages of Thorotrast which was enriched with 230Th to enhance the alpha-energy emission rate. The purpose of the study was to evaluate the effects due to the colloidal substance and the radiation. In the main experiment, 12 groups of rats were injected intravenously with 60, 120 and 300 microliters Thorotrast. 230Th was added to some Thorotrast preparations so that the total alpha-energy emission rate varied by factors of 1, 2, 5 and 10 relative to normal Thorotrast. Two groups were injected with 12 and 60 microliters of 50-fold enriched Thorotrast. One group was given 600 microliters of normal Thorotrast. In addition, we had 5 control groups, 1 NaCl and 4 Dextrin groups. The latter were injected with 60, 120, 300 or 600 microliters of Dextrin. The first animals died 8 months after injection, and the last 11 animals were killed 41 months after starting the experiment. The number of animals that developed a hepatic or splenic tumor increased by a factor of 10 in the highest dose-rate groups compared to controls. Our results demonstrated a linear correlation between the dose-rate and the number of primary hepatic and splenic tumors. It appeared that the volume of injected Thorotrast, by itself, had little influence on the number of tumors. However, at a constant dose-rate of 10, a 50-fold increase in the volume of Thorotrast (12-600 microliters) decreased the minimal tumor-appearance time by about 250 days.

Animals↗