Iodine-131 metaiodobenzylguanidine (131I-MIBG), a radiopharmaceutical agent used for scintigraphic localization of pheochromocytomas, has been employed to treat malignant pheochromocytomas since 1983 in a few specialized centers around the world. We review our clinical experience together with the published experience of 23 other centers in 10 countries, regarding the use of 1311-MIBG for treating patients with malignant adrenal pheochromocytomas or extra-adrenal paragangliomas. There were a total of 116 evaluable patients: 3 were from our current report and another 113 were reported in the literature from 1983 to 1996. A majority of the patients were selected for treatment based upon positive tracer uptake studies. The cumulative dose of 131I-MIBG administered ranged from 96 to 2,322 mCi (3.6 to 85.9 GBq), with a mean (+/-SD) of 490+/-350 mCi (18.1+/-13.0 GBq). The subjects received a mean single therapy dose of 158 mCi (5.8 GBq) and the number of doses administered ranged from 1 to 11, with a mean of 3.3+/-2.2 doses. Initial symptomatic improvement was achieved in 76% of patients, tumor responses in 30%, and hormonal responses in 45%. Five patients had complete tumor and hormonal responses, ranging from 16 to 58 months, which were sustained at the time of reporting. Patients with metastases to soft tissue had more favorable responses to treatment than those with metastases to bone. No difference was noted in the age between the responders and non-responders. Adverse effects, recorded in 41% of the treated patients, were generally mild except for one fatality from bone marrow aplasia. Among 89 patients with follow-up data, 45% of the responders had relapsed with recurrent or progressive disease after a mean interval of 29.3+/-31.1 months (median 19 months). Of patients with an initial response to 1311-MIBG, death was reported in 33% after a mean of 23.2+/-8.1 months (median 22 months) following treatment. Of non-responders, death was reported in 45% after a mean of 14.3+/-8.3 months (median 13 months). In conclusion, this review suggests that 131I-MIBG therapy may be a useful palliative adjunct in selected patients with malignant pheochromocytoma or paraganglioma. Although controlled studies are lacking, our review raises the hope that this therapeutic modality may prolong survival with an occasional sustained complete remission or possible cure.
Three patients who developed symptomatic, autoimmune-mediated thyroid dysfunction during treatment with interferon-alpha (IFN-alpha) for chronic active hepatitis C with liver cirrhosis, age-related macular degeneration with foveal involvement, and chronic myelogenous leukemia, respectively, are described. The first two patients developed autoimmune hypothyroidism that required thyroxine replacement, and the third developed autoimmune thyroiditis with transient thyrotoxicosis. The clinical manifestations were protean, and required a high index of suspicion for diagnosis, the failure of which led to significant morbidity. A literature review revealed that the mean incidence of IFN-alpha induced thyroid dysfunction was 6%. Spontaneous resolution occurred in more than half with discontinuation of IFN-alpha treatment. Hypothyroidism was induced more frequently than hyperthyroidism. At least one positive thyroid autoantibody titer was found in 17% of patients receiving IFN-alpha. Risk factors for developing thyroid dysfunction with IFN-alpha treatment were female sex, underlying malignancy or hepatitis C, higher doses of IFN-alpha for longer durations, combination immunotherapy (especially with interleukin-2), and the presence of thyroid autoantibodies prior to or during treatment.
Both the association between lymphocytic thyroiditis (LT) and papillary thyroid carcinoma (PTC), and the prognostic significance of lymphocytic infiltrate in patients with thyroid malignancy, remain controversial. We examine the above relationships by retrospectively reviewing our series of patients treated for differentiated nonmedullary thyroid carcinoma at University of California-San Francisco over a 25-yr period (1970-1995). Of the 631 patients with complete data for analysis, 128 patients (20.3%) showed concomitant histologic evidence of LT and 503 patients (79.7%) had no evidence of LT. Prognostic outcome was assessed using Kaplan-Meier survival plots and analysis of risk factors by Cox's proportional-hazard modeling. The cohort with LT revealed a higher frequency of PTC (97.7% vs. 87.3%) and female patients (85.2% vs. 66.8%), a lower frequency of extrathyroidal invasion (7.8% vs. 23.3%) and nodal metastases (25.8% vs. 43.3%), and absence of distant metastases (0% vs. 4.8%), respectively, compared with those without LT. At initial surgery, a significantly greater proportion of patients with LT belonged to lower pathological tumor-node-metastasis stages, compared with those without LT (stage 1, 86.7% vs. 73%; stage 2, 4.7% vs. 8.3%; stage 3, 8.6% vs. 15.3%; and stage 4, 0% vs. 3.4%). Over a mean +/- SE follow-up period of 11.1 +/- 0.4 yr, patients with LT had significantly lower cancer recurrence rate (6.3% vs. 24.1%; P < 0.0001) and cancer mortality rate (0.8% vs. 8.0%; P = 0.001), respectively, compared with those without LT. In summary, our series showed a relatively common occurrence of LT in patients with PTC, and we believed that lymphocytic infiltration developed mainly in response to the tumor itself. We also found a more favorable course of PTC in the presence of LT; this supports the hypothesis that lymphocytic infiltration represents a form of immune reaction to control tumor growth and proliferation.
Study objective-The aim ofthe study was to examine cardiovascular risk factors to see how these might explain differences in cardiovascular disease mortality among Chinese, Malays, and Indians in the Republic of Singapore. Comparisons were made between the respondents, the sample, and the sampling frame, and no major discrepancies were found by age, sex, and ethnic group; the youngest age group had slightly lower response rates than the older ones. PROCEDURESAll clinics were held on Saturday mornings between 0900 and 1200 hours and the subjects were asked to fast from 2100 hours the previous evening. A questionnaire was administered by a field investigator (a nurse trained in interview techniques) and personal details including ethnic group (derivation previously described),' present and past occupations, medical history, drug usage, diet, and family medical history were obtained. Questions were asked on alcohol intake (including frequency, type and quantity, similar to those used in the British Regional Heart Study2 based on the UK General Household Survey 1972-73),3 smoking (same questionnaire as used in MONICA project of WHO),4 and chest pain.
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