The incidence of thyroid cancer was evaluated in 35,074 patients examined for suspected thyroid disorders between 1951 and 1969 with an average of 1.92 megabecquerel [(MBq) 52 microCi] of 131I. The radiation dose to the thyroid gland was, on the average, approximately 0.5 Gy. The mean age at the time of examination was 44 years; 5% were under age 20. Patients were followed for an average of 20 years. Record linkage with the Swedish Cancer Register identified 50 thyroid cancers occurring 5 years or more after the initial 131I examination, in contrast to 39.4 expected based on general population rates [standardized incidence ratio (SIR) = 1.27, 95% confidence interval = 0.94-1.67]. Risk was highest among males (SIR = 2.70, n = 10), patients followed 5-9 years (SIR = 2.22, n = 23), and patients receiving more than 74 microCi or 2.74 MBq of 131I (SIR = 2.04, n = 17). However, these observations were confounded by the fact that patients examined for a suspected thyroid tumor received the highest 131I exposures and were at highest overall risk (SIR = 2.77, n = 34). Patients given 131I for reasons other than a suspected tumor were not at increased risk (SIR = 0.62, n = 16). Patients anticipated to be at highest risk, i.e., women (SIR = 1.12, n = 40) and those observed for 10 years or more (SIR = 0.93, n = 27), showed no evidence of a dose response. Overall, these data provide little proof that 131I is carcinogenic in humans and support the notion that the carcinogenic potential of internal 131I beta particles might be as low as four times less than external x rays or gamma rays.

Hepatitis E virus (HEV) is an enteric virus that usually causes a self-resolving hepatitis; although, it may be fatal, especially in pregnant women. Although HEV is endemic in Israel, there have been no recent local outbreaks. We report the case of a 70-year-old man who presented with painless jaundice. Ultrasound and abdominal computed tomography scan revealed gallstones, with no evidence of cholecystitis and no dilatation of the intra-or extrahepatic bile ducts. An open cholecystectomy was performed with intraoperative cholangiography. There was no evidence of choledocholithiasis. A subsequent endoscopic retrograde cholangiopancreatography was normal. His bilirubin level subsequently increased to a maximum of 25 mg/dL, and his gamma-glutamyl-transferase level reached 1,400 U/L. There was no evidence of any autoimmune or metabolic disease, and routine viral serology was normal except for immunoglobulin G to hepatitis A virus. A liver biopsy revealed an acute cholestatic picture. The jaundice resolved slowly after a period of 6 months. Hepatitis E virus RNA was isolated from the acute-phase serum and was not detectable in the convalescent serum. This case is a unique example of chronic cholestatic jaundice that we think is caused by acute HEV infection.

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Previously, we conducted a study of 35,074 patients receiving diagnostic doses of 131I for suspected thyroid disorders between 1951 and 1969. We reported that, between 1958 and 1984, the incidence of thyroid cancers in these patients was insignificantly greater than the incidence expected in the general population. This increase was attributed to the underlying condition that prompted the examination and not to the administration of 131I. The purpose of the present study was to analyze the total cancer risk in the same cohort of patients examined with diagnostic doses of 131I. To further evaluate the underlying risk of disease in these patients, we compared the incidence of all cancers with that expected in the general population. The average radiation dose was approximately 500 mGy to the thyroid and less than 10 mGy to other organs. In the 35,074 patients, 3,746 cancers occurred following the first 5 years after examination, and the resulting standardized incidence rate (SIR) was 1.01 (95% confidence interval = 0.98-1.04). SIRs were significantly increased for endocrine tumors other than thyroid cancer (1.93) and for lymphomas (1.24), leukemias (1.34), and nervous system tumors (1.19). The risk of leukemia was similar for chronic lymphocytic leukemia (CLL) (SIR = 1.30) and non-CLL (SIR = 1.34). SIR was significantly decreased for cancers of the female genital organs (0.86). The risk for cancer of all sites and types combined was highest 5-9 years after examination (SIR = 1.07) and did not differ from unity thereafter. With greater than or equal to 10 years of follow-up, risk was not statistically associated with the dose of 131I. Overall, the data exclude cancer risk increments greater than 5% (SIR = 1.05) with 95% confidence. The significant increase in the risk of non-CLL, a prominent radiogenic malignancy, however, warrants special attention. We are continuing our study to determine the possible factors involved in the significant increase in the risk of leukemia.

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