History note: tragedy of Thorotrast
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KeywordsEsophageal Varix Angiosarcoma Japanese Adult Thorotrast Thorium Dioxide
Learning from the history is something that we should continue over the generations. 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. Although we will not see this type of case any more, we believe we should document historically important issues that may help shape our future practice.
After autopsy, liver, pancreas and spleen were inspected and radiographed. The liver weighed 3000 g, and was spongy. The average weight of the liver in Japanese adults is 1262 g in men and 1147 g in women. Therefore, the patient’s liver weighed much more than normal, because the liver harbored a tumor.
There were esophageal varices. Ascites, 600 ml, was hemorrhagic. The spleen weighed 12 g, and was fibrosed and atrophic. The average weight of the spleen in Japanese adults is 131.5 g in men and 122.4 g in women. Therefore, the spleen was much smaller than normal.
Thorotrast is a trade name of radioactive thorium dioxide suspension, widely used in the 1930s and 1940s. It was considered to be an ideal arteriographic contrast medium due to its high radiodensity and relatively low acute and subacute complication rates. 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 × 1010 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].
The case presented developed angiosarcoma of the liver, 49 years after Thorotrast injection. 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  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 %). Angiosarcoma of the liver, rare in the general population, is a relatively specific tumor after Thorotrast deposition.
Weber et al.  reported in 1995 about their experience of seeing a female patient with sudden right-sided abdominal pain. Subsequently, hepatic carcinoma induced by Thorotrast exposure was found in her body. The patient did not remember that she had received an injection of a contrast medium like Thorotrast. They concluded in saying, “This case leads us to remind recently trained clinicians of this historical pathology, which obviously will disappear with time, but must kept in mind for at least two decades, when confronted with atypical abdominal pain in elderly patients.”
This is a lesson in the necessity of long-term follow-ups for a specific study or treatment, learned from an article on Thorotrast.
Thorotrast seemed to be an ideal contrast medium at the beginning, but keen research followed and studied the effects of long-standing radiation from Thorotrast.
What we learn from old cases like the one we presented in this paper would be that we should continue to follow and study the sequences and results of drugs, contrast medium and techniques.
The authors thank Choichiro Kido, M.D., then Vice President of Aichi Cancer Center Hospital, for his help in performing autoradiography for alpha tracks and the measurement of concentration of Thorotrast. A part of this case was presented at the 22nd Autumn Assembly of Japan Radiological Society in 1987. The authors also would like to acknowledge editorial assistance by Dr. Shigeru Ehara, Professor of Radiology, Iwate Medical University.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
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