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PubMed1980

[Thorotrastosis: survey and CT pattern (author's transl)].

Following a historical survey of the discovery of late damages caused by the contrast medium Thorotrast which was commercially available from 1930 to 1951, the article reports on the possibilities of identifying Thorotrast in the computer tomogram. In a male patient aged 60 years, the size and anatomic dimensions of a hepatocholangiolar carcinoma induced by Thorotrast was determined by computer tomography 35 years after carotid angiography. Over and above this, a 20 times increased pathologic tissue density was measured in parapancreatic lymph nodes, whereas the density of tissue was only slightly increased in the liver and twice the normal value in the spleen. The sclerosing and malignoma-inducing properties of Thorotrast as well as the pathogenesis of late damages by foreign body irritation and chronic internal radiation, are discussed.

Humans↗
PubMed1978

[Thorotrast kidney as a precancerous condition].

9 cases of "thorotrast kidney" after retrograde pyelography with reflux are presented. In 6 patients carcinoma of the renal pelvis developed 47--31 years after thorotrast pyelography. Because of this high rate of carcinoma induction, thorotrast kidney must be classified as a precancerous condition with high-rate tumor manifestation. Thorotrast kidney is diagnosed on X-ray by very opaque linear densities following the calices and pyelon. Early ureteronephrectomy is the treatment of choice in unilateral thorotrast kidneys. If uretero-nephrectomy is not possible, the patient should be followed up regularly with urinary cytologic examinations for early detection of malignancy.

Aged↗
PubMed1995

[Simultaneous hepatic cholangiocarcinoma and bone fibrosarcoma 45 years after ingestion of Thorotrast].

This case of a 63 year old man reports the simultaneous development of hepatic cholangiocarcinoma and fibrosarcoma of the sacrum 45 years after the systemic injection of Thorotrast. The characteristic radiologic aspect was an important criteria for diagnosis. Biopsies have confirmed the histology of both tumors. We describe the way to thorotrastosis diagnosis and characteristic malignant tumors, especially cholangiocarcinoma, induced by Thorotrast.

Bone Neoplasms↗
PubMed1995

Mortality and cancer incidence after cerebral arteriography with or without Thorotrast.

Mortality and cancer incidence among 999 neurological patients exposed to chronic alpha-particle irradiation from 232ThO2 (Thorotrast) administered for cerebral angiography in 1935-1947 was compared to that of 1480 similar patients examined with cerebral angiography without Thorotrast in 1946-1963 (controls). The ratio of standardized mortality/morbidity ratios (SMRs) for patients exposed to Thorotrast and controls was the relative risk, which was analyzed by multiplicative regression (RRREG). For mortality from all causes, RRREG was significantly increased mainly due to cancer, benign and unspecified tumors and benign liver conditions, while RRREG for all other causes combined was not significantly increased. The RRREG was significantly associated with the injected amount of Thorotrast for cancer and for benign liver conditions, while no other dependence on the amount of Thorotrast was seen. Cancer incidence was significantly increased, caused mostly by liver cancer, leukemia, metastases and cancer at unspecified sites. The risk for cancer other than liver, hematological, brain, metastases and cancer at unspecified sites combined was also significantly increased, but the temporal trend of RR for this category of sites did not indicate a radiation effect. A significant association between relative risk of cancer and injected amount of Thorotrast was largely accounted for by liver cancer. Thus increased mortality among patients exposed to Thorotrast is due mainly to cancer and benign liver diseases, and increased cancer incidence is caused by high risks of liver cancer, leukemia and ill-defined types (metastases, etc.). The time trend and dependence of the amount of Thorotrast injected do not support that cancer at most other sites is related to radiation from Thorotrast.

Adolescent↗
PubMed1995

Antiepileptic treatment and risk for hepatobiliary cancer and malignant lymphoma.

The possible influence of phenobarbital and phenytoin treatment on cancer risk was investigated in a case-control study nested in a cohort of 8004 epileptic patients in Denmark. Information on anticonvulsive treatments was abstracted for 95% of 60 patients with cancers of the liver and biliary tract or malignant lymphoma and for 94% of 171 cancer-free control patients. Use of anticonvulsive drugs was correlated with angiographic procedures that used Thorotrast, a well-known human liver carcinogen. After exclusion of study subjects exposed to Thorotrast, no association was seen between treatment with phenobarbital and cancer of the liver (odds ratio, 1.0; 95% confidence interval, 0.1-8.0) or biliary tract (odds ratio, 0.8; 95% confidence interval, 0.1-4.2). Furthermore, a histopathological evaluation of slides from 7 of 9 liver cancer patients not treated with Thorotrast revealed that 3 of the 4 cases of hepatocellular carcinoma involved cirrhosis of the liver, which suggested an etiological role for alcohol or viral hepatitis. A possible link was observed between use of phenytoin and risk for non-Hodgkin's lymphoma (1.8; 0.5-6.6), with a rising trend in risk with increasing dose. Our results suggest that the increased risk for cancers of the liver and biliary tract among Danish epileptic patients is likely to be due to Thorotrast administration and factors associated with cirrhosis of the liver rather than to anticonvulsive treatment.

Aged↗
PubMed1994

Primary liver tumors among Danish patients exposed to Thorotrast.

The potential carcinogenic effects of internally deposited alpha-particle-emitting nuclides, notably plutonium, in the liver in humans are unknown but are of concern in relation to exposures from the nuclear industry. However, patients injected with the radiographic contrast medium Thorotrast are chronically exposed to alpha-particle radiation from 232ThO2 in the liver. Among 1003 patients injected with Thorotrast, 584 of whom were alive 15 years after the injection and 40 at the end of follow-up, a total of 127 liver cancers were diagnosed, 45 of which were hepatocellular carcinomas, 41 cholangiocarcinomas and 33 hemangiosarcomas. The median time from injection to diagnosis was 35 years (range 18-48) and the cumulative frequency was 55.4% after 48 years. In univariate and multivariate analyses, the cumulative frequency of liver cancer was best described as a function of the estimated mean cumulative alpha-particle radiation dose to the liver 15 years ago, being independent of age, gender and volume of injected Thorotrast. This may be interpreted to mean that the liver cancer rate is not related to the dose rate and that the period from malignant transformation to diagnosis of cancer is 15 years. The risk of liver carcinogenesis induced by alpha-particle radiation, assuming 15 years from induction to diagnosis, was estimated to be 712 cases/10(4) persons per gray. This value is considerably higher than estimated earlier.

Adolescent↗
PubMed1994

Translocation of Thorotrast in the body.

To investigate whether there is a permanent translocation of Thorotrast in the body, the liver of male Lewis rats was removed 4 weeks after injection of Thorotrast (300 microliters) and replaced by a donor liver. In half of the animals the spleen was removed as well. Measuring the 232Th content in the donor liver at different times after implantation demonstrated a permanent transport of 232Th into the surrogate organ. After 231 days a 232Th depot of about 1.1 mg was found, representing about 3% of the total body burden. The additional removal of the spleen resulted in a significantly lower transport of 232Th into the implanted liver. Histological examinations of the donated livers revealed increasing local concentration of Thorotrast granules, leading to the development of conglomerates. A comparable translocation of Thorotrast was verified in two humans who required liver transplantation more than 40 years after Thorotrast injection.

Animals↗
PubMedDate not supplied

Phenobarbital, drug metabolism, and human cancer.

To investigate the possible influence of anticonvulsant treatment on cancer risk, a nested case-control study of 104 lung cancers, 18 bladder cancers, and 322 cancer-free controls was conducted. The background for the study was previous observations among 8004 epileptics in Denmark with a significantly high risk for lung cancer and a significantly low risk for bladder cancer. Cigarette smoking appears to explain the lung cancer excess but not the low risk for bladder cancer, another tobacco-related disease. Information was abstracted on 94 and 95% of the cases and controls, respectively. Lung cancer was not associated with any anticonvulsant drug, but bladder cancer was inversely related to use of phenobarbital (PB). The apparent protective effect of PB was further evaluated in a study of rats given 4-aminobiphenyl (ABP), a bladder carcinogen. The levels of 4-aminobiphenyl adducts in hemoglobin and in bladder and liver DNA were significantly lower in rats given PB prior to 4-aminobiphenyl, compared to controls. These studies suggest that PB may induce drug-metabolizing enzymes of the liver that deactivate bladder carcinogens found in cigarette smoke and provide clues to the role of activation and detoxification of carcinogens in humans.

Animals↗
PubMed1993

Systemic deposits of thorium in thorotrast patients with particular reference to sites of minor storage.

It is well established that injected Thorotrast is deposited in the liver, spleen, bone marrow, and lymph nodes, but accumulations in organs with lower macrophage activity have previously been given little attention. In this work, neutron activation analysis has been used to investigate concentrations of thorium in autopsy samples taken at sites of major and minor deposition in 24 Thorotrast patients. In the latter category, the highest values were found in the testis [40 x 10(-6) g/g(wet)], followed by those in the adrenal gland, gallbladder, lung, and pancreas. The resulting alpha-particle dose rates (mGy/year) are tentatively estimated to be 8.5 to the testis, 5.5 to the gallbladder, and 5.3 to the lung. These results may be relevant to the residual excess mortality among Thorotrast patients after diseases of the principal organs of deposition have been excluded; they also support previous indications that thorium deposited in pulmonary tissues is responsible for an important component of the total dose to the lung. In another context, our data may bear on the connection, postulated elsewhere, between exposure to alpha-particle emitters and elevated incidence of leukemia in the children of workers engaged in the reprocessing of nuclear fuel.

Adult↗
PubMed1993

[Thorotrast-related hepatosis].

The clinical, pathological and laparoscopic data of five patients with liver disease due to Thorotrast are presented. Laparoscopy showed various degrees of fibrosis and nodularity. One patient developed cholangiocarcinoma and two showed dysplasia at biopsy. The laparoscopic appearance is practically diagnostic.

Adenoma, Bile Duct↗
PubMed1993

[CT appearance of thorotrast-related and non-thorotrast-related peripheral cholangiocarcinoma].

To assess the differences in CT findings among patients with peripheral cholangiocarcinoma with and without a history of Thorotrast administration, CT studies from 13 Thorotrast patients and eight non-Thorotrast patients were reviewed. Diagnostic and prognostic differences were evaluated between the two groups. Despite periodic imaging surveillance, eight of the 13 (62%) lesions discovered by CT were larger than 6 cm. The prognosis for Thorotrast patients was unfavourable due to difficulties in early detection and complications from associated hepatic fibrosis. The main problem with early detection was that a background of uneven Thorotrast deposits visualized in the liver disguised the tumor as Thorotrast granulations. Although non-Thorotrast patients were not monitored regularly, they had a better chance of undergoing curative resection for the following three reasons: 1) it was easy to detect the tumor (detection rate, 100%); 2) this group rarely had associated liver cirrhosis in noncancerous areas, and 3) non-Thorotrast patients were younger than Thorotrast patients. Early detection of cancer by CA19-9 assay and imaging in asymptomatic subjects without any history of liver disease could be important steps toward the early and radical resection of cancer to achieve a better prognosis.

Adenoma, Bile Duct↗
PubMedDate not supplied

MRI appearance of thorotrast-induced cholangiocarcinoma in a case of thorotrastosis.

The case of a 71-year-old man with thorotrastosis and a cholangiocarcinoma detected by MRI is presented, and the radiographic appearance of the cholangiocarcinoma is discussed. We concluded that MR is more useful for detecting Thorotrast-induced liver tumors than US and CT, but CT is more useful for the detection of Thorotrast deposits.

Adenoma, Bile Duct↗