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Thorium dioxide (Thorotrast) was used extensively in the United States from the 1930s through the 1950s for contrast radiography, including cerebral angiography. Its use was discontinued after the pathologic consequences of tumor formation and local fibrotic reaction (thorium dioxide granuloma) were recognized. The latency period for the development of these consequences is 20 to 30 years and, thus, has not expired. Radical surgical excision in an attempt to remove cervical thorium dioxide granulomas and their ionizing radiation has been advocated previously. A case prompted reconsideration of this management. Total surgical removal does not seem possible and is extremely hazardous in those cases with a patent carotid artery adjacent to the cervical granuloma. More cases should be expected, and each case should be approached individually as to benefits and risks of attempted surgical removal of the granuloma. Radical surgery is not always the treatment of choice.
The ultrastructual localization of thorium dioxide was examined in liver biopsy specimens from two patients injected more than 30 years before with thorotrast. An energy dispersive X-ray microanalysis spectrometer (Kevex 5100) was used to identify thorium in the liver tissue. By electron microscopy, most of the thorium particles were found in the cells of the reticuloendothelial system, such as macrophages of the portal triad and Kupffer cells in the hepatic sinusoid. Thorium dioxide particles were mainly located within the phagosomes, but larger aggregates existed in the cytoplasma with no visible limiting membrane. In addition, the deposition of thorium granules in a few hepatocytes was also confirmed by electron microscopy. This fact indicates that two main pathways of elimination are still functioning in the late period, but the hepatocytic pathway appears to be less effective than the reticuloendothelial system.
Thorium dioxide, a producer of alpha particle radiation, was used in the United States from 1930 to 1950 for carotid and cerebral angiography. Cervical thorium dioxide granuloma is a well-recognized sequela of extravasation of this material near the carotid bifurcation. Radical neck dissection to remove the granuloma for aesthetic and functional reasons may lead to massive postoperative hemorrhage if a patent, but radiation-weakened, carotid artery is present. Additionally, hemorrhage may occur spontaneously because of pharyngeal necrosis or following infection of a pharyngeal biopsy site. The case described illustrates that life-threatening, thorium-dioxide--induced pharyngeal hemorrhage may occur even with an occluded carotid system. The bleeding site may go unrecognized, and laryngopharyngectomy with radical neck debridement may be required for hemostasis. Extension of an infection into the retroesophageal space and thoracic inlet requires exteriorization of the entire neck wound to prevent placing the great vessels of the superior mediastinum at risk for rupture. Spontaneous rupture of the aorta may occur due to thorium-dioxide--induced necrosis of its wall.
The late effects of thorium dioxide (Thorotrast) in the perivascular space of the neck are reviewed. The roentgenographic analysis of the problem consists of both plain films (to detect the residual density of extravasated thorium dioxide) and computed tomography (to help define any involvement of the carotid artery).
A case of hepatoma induced by thorium dioxide (Thorotrast) is reported. The literature concerning neoplasia associated with this agent is reviewed, with emphasis on the long latent period before the development of these tumours and the equally long latent period which preceded the recognition of their iatrogenic nature.In particular, this report is intended to illustrate the diagnosis of such tumours on radiological and histological findings, provided that one is aware of their existence and familiar with the distribution and appearance of thorium dioxide deposits in the tissues. Such a diagnosis can be made without a history of thorium dioxide administration, which often may not be available.
At a metallurgical facility using thorium dioxide feed materials, a number of conventional direct- and indirect-bioassay methods were potentially suitable monitoring methodologies when industry-standard dose assessment methodologies were based upon ICRP recommendations issued in 1959. When the ICRP recommended a different dose assessment methodology in 1977, the intake limits for thorium dropped significantly, and conventional bioassay methods for routine monitoring were rendered ineffective. While determining the technical basis for its air monitoring program, the facility noted that the radioactive materials used as feed to the process were highly insoluble. Therefore, their solubility in simulated lung fluids was determined. The results of this determination indicated that the facility's materials, if inhaled, dissolve in the lung at a half-time that is significantly longer than that contained in international consensus standards for Y-class compounds. They also indicated that the secondary dose limits, if adjusted to eliminate the dose contribution from translocated radionuclides, should be higher, and that a derived air concentration based upon more recent international recommendations is more appropriate for use in the facility's routine monitoring program.
Patients who have received thorium dioxide (Thorotrast) are at risk for hepatic and other malignancies. Because of the need to identify and carefully follow up these patients, we have presented three cases with the characteristic radiologic findings on plain films so that physicians unfamiliar with this appearance will now be aware of it.
The case of a 56 years old patient is reported who died of a malignant hepatic angiosarcoma 38 years after administration of thorium dioxide. Although the incidence of thorium dioxide-induced late effects is declining still today in the differential-diagnosis of liver cancers thorium dioxide associated tumors have to be considered. The progress of the disease is described and the radiological findings are discussed.
A 10-year-old girl, with congenital heart disease, harboring a brain stem abscess, was recently treated at the UCLA Hospital. Needle aspirations of the abscess was performed through a posterior occipital craniectomy, and thorium dioxide (Thorotrast) was placed within the abscess cavity as a marker. Postoperatively, the patient improved temporarily but died 18 days later. Autopsy examination included radioactive analysis of brain and liver tissue. Radioautographs were superimposed on H&E preparations of the abscess wall to localize the extent of activity of the thorium dioxide. The unusual occurrence of this abscess in a young patient, clinically diagnosed and treated by operation, provided a rare opportunity to assess the problem of the surgical accessibility of brain stem abscess as well as to reevaluate a role for thorium dioxide as a marker for intracranial purulent collections.
Vascular complications occurring late after exposure to thorium dioxide (thorotrast) are described in two patients. One patient had both cerebral andmyocardial infarcts and died at age 25 years. Necropsy disclosed both adventitial and intimal fibrosis of the left carotid artery and greater than 75 per cent cross-sectional area luminal narrowing of both the left main and left anterior descending coronary arteries. The other patient, a 33 year old man, had no cerebral symptoms in life but total obstruction of the right carotid artery secondary to a thorotrastoma was found at necropsy. Vascular complications due to thorotrast appear to represent consequences of chronic alpha irradiation.
Hodgkin's disease occurred in a 53-year-old man who, 25 years previously, had undergone cerebral angiography, for which thorium dioxide suspension (Thorotrast) was used. Deposits of throium dioxide were noted in reticuloendothelial cells in various locations. An association between thorium dioxide administration and the subsequent development of malignant tumours and neoplastic hematologic disorders has previously been reported.
Summary--Thorotrast (thorium dioxide) is a contrast material which was first used for angiography about 40 years ago. Its use was discontinued because of the reported incidences of malignancy following injection. Its long-term effects are related to its long half-life and slow excretion rate. Following extravasation into the soft tissues of the neck, the prolonged radiation effect results in tissue breakdown with formation of granulomas. There can also be cranial nerve palsies, occlusion of the major blood channels, laryngeal edema, pharyngeal and esophageal ulceration, and fistula formation. To avoid these late consequences, it is suggested that Thorotrast granuloma in the neck be excised radically. Partial or limited resections are inadequate.
An elderly woman had an expanding cervical mass that entrapped and compressed the adjacent cranial nerves, blood vessels, and muscles. The mass was dense on radiographs, extended from the skull base to low neck in the prevertebral and parapharyngeal tissues, and showed mixed intensity on MR. A previous direct carotid arteriogram with thorium dioxide as the contrast agent suggested the histologically proved diagnosis of a cervical thorium dioxide granuloma ("thorotrastoma").
The distribution of thorium dioxide (Thorotrast) in the liver from a Thorotrast-administered autopsy case was examined stereographically by analytical scanning electron microscopy. Thorium particles were detected in the macrophages of the portal triad and hepatic sinusoid. These macrophages were irregularly shaped and tended to be aggregated. In the sinusoid, accumulation of the macrophages formed a thrombus-like structure. Furthermore, observed in the sinusoid were free Thorotrast particles that appeared to have been released into the sinusoid as a result of breakdown of the macrophages (Kupffer cells).
The aim of this work was to investigate the biokinetics of thorium dioxide in animals for the purpose of assessing intakes of the compound by workers and the resulting doses. The results imply that measurements of the decay products in the chest or extrapolations from urine analysis data are unlikely to be of value for doses below 20 mSv. Even higher doses should be interpreted with caution as a consequence of uncertainties in particle size distribution and variations in dietary excretion.
Since the recognition of the development of certain malignant neoplasms in association with thorium dioxide (Thorotrast), its presence has been documented by light microscopic appearance and time-consuming autoradiography. Energy dispersive x-ray microanalysis can be used in the rapid documentation of thorium in paraffin-embedded tissues and it is confirmed that thorium is the principal component of the granular deposits described by light microscopy.
The ability of the mouse mast cell to phagocytize colloidal thorium dioxide, Thorotrast, was investigated employing the mouse connective tissue air pouch. The connective tissue mast cell of mouse was found to have limited capability to ingest the particulate Thorotrast in comparison to the rat peritoneal mast cell which ingested this material readily. Fibroblasts and macrophages in the connective tissue removed injected Thorotrast very rapidly in contrast to mast cells that demonstrated limited phagocytic capabilities. The tissue mast cell of the mouse, therefore, should not be considered a part of the reticuloendothelial system.