Lack of association between obesity and aggressiveness of differentiated thyroid cancer.

PURPOSE: Aim of this study was to evaluate the association between body mass index (BMI) and aggressive features of differentiated thyroid cancer (DTC) in a prospective cohort. METHODS: Patients with DTC were prospectively enrolled at a tertiary referral center and grouped according to their BMI. Aggressive clinic-pathological features were analyzed following the American Thyroid Association Initial Risk Stratification System score. RESULTS: The cohort was composed of 432 patients: 5 (1.2%) were underweight, 187 (43.3%) normal weight, 154 (35.6%) overweight, 68 (15.7%) grade 1 obese, 11 (2.5%) grade 2 obese and 7 (1.6%) grade 3 obese. No single feature of advanced thyroid cancer was more frequent in obese patients than in others. No significant correlation was found between BMI, primary tumor size (Spearman's ρ - 0.02; p = 0.71) and ATA Initial Risk Stratification System score (ρ 0.03; p = 0.49), after adjustment for age. According to the multivariate logistic regression analysis, male gender and pre-surgical diagnosis of cancer were significant predictors of cancer with high or intermediate-high recurrence risk according to the ATA system (OR 2.06 and 2.51, respectively), while older age at diagnosis was a protective factor (OR 0.98), and BMI was not a predictor. BMI was a predictor of microscopic extrathyroidal extension only (OR 1.06). CONCLUSIONS: Obesity was not associated with aggressive features in this prospective, European cohort of patients with DTC.

131I therapy and Graves' disease in a long term observation: euthyroidism is a suitable goal. Our experience.

OBJECTIVE: The aim of the study was to verify early and definitive outcome of radioiodine therapy in patients with Graves' disease, administering 131I calculated dose to pursue euthyroidism. PATIENTS AND METHODS: We retrospectively analyzed 639 patients affected by Graves' disease and treated by one or more 131I calculated doses. Results dose by dose are reported. As to the first administration, outcome is related to parameters used to calculate dose and to patients' available features. Failures and hypothyroidism onset are evaluated. RESULTS: A mean dose of 10 mCi shows great effectiveness: 75% of patients were cured after one administration, 88% after two. Of the failures, 84.1% occurred in a mean time of 0.34±0.23 years and were more frequent for larger glands, accelerated intra-gland radioiodine turnover, ophtalmopathy, administration of antithyroid drugs until 131I therapy. Of hypothyroid patients, 39.8% were diagnosed within the first year. After a sharp initial rise, hypothyroidism occurred at a slower rate, with estimated yearly increases of 3.8% until 10 years and of 1.8% later. In still followed up patients, euthyroidism was observed in about half the population after 10 years and in a third after 25 years. CONCLUSIONS: 131I can be the first line treatment for Graves' disease in small-medium thyroids. Calculated doses can achieve a high amount of long term euthyroid patients. Similar results could be expected by fixed doses of 10 mCi.

Lymph node metastases from differentiated thyroid carcinoma: does radioiodine still play a role?

OBJECTIVES: Ultrasonography and surgery have now become the elective diagnostic and therapeutic tools for neck lymph node (LN) metastases from differentiated thyroid carcinoma (DTC), reserving radioiodine therapy (RAI) for surgery failures. Aim of the present retrospective study was to evaluate results of RAI in cases of LN metastases displaying (131)I uptake over a long-term observation period and its possible role today. MATERIALS AND METHODS: From a series of 1276 patients who had undergone surgery for DTC, 130 cases were selected showing (131)I uptaking LN metastases, detected during follow-up scans and who were then submitted to surgery and/or RAI. Patients were divided into groups according both to extent of surgery, with/without lymphectomy, and to following treatment and outcome. RESULTS: The initial surgical approach does not seem to significantly influence the outcome. (131)I therapy alone, sometimes at low doses, can be very effective in the management of LN metastases detected at Whole Body Scan, but multiple doses are often needed. The age at diagnosis is confirmed as a negative prognostic factor. CONCLUSIONS: Considered radioprotection questions, RAI may solve (131)I uptaking LN metastases, above all if < 10 mm. For larger LN metastases and in the case of failure of RAI surgical excision is mandatory, while a subsequent therapeutic dose of (131)I could be useful to reveal incomplete excision.

Our experience on pain palliation of bone metastasis with Sr-89 or Sm-153 in cancer patients resistant to a conventional analgesic therapy. A retrospective study.

OBJECTIVES: These retrospective study is aimed to evaluate the efficacy of therapy with Stronthium-chloride 89 (89SrCl) and Samarium 153 conjugated with ethylenediaminetetramethylene phosphonic acid (153Sm-EDTMP) in the palliation of bone pain due to metastatic malignancy. MATERIALS AND METHODS: The study refers to a presentation sample of 27 patients with bone metastases caused by different cancers (16 prostate, 5 breast, 6 lung) who were enrolled and followed-up for 11.5 +/- 6.3 months. 89SrCl (150MBq) was administered in 17 pts, 153Sm-EDTMP (37 MBq/Kg) in 10 pts. All patients showed multiple metastatic sites of 99Tc-HDP uptake documented by a standard bone scintigraphy. Effectiveness of treatment was evaluated by questionnaires about pain and quality of life, Karnofsky index, specific cancer markers, a post-treatment bone scintigraphy. Presence of flare reaction and haematological toxicity were evaluated too. RESULTS: Questionnaire scores decreased both in patients treated with 89SrCl and in those given 153Sm-EDTM, without significant difference. Karnofsky index significantly increased only in patients with prostate cancer. After therapy, there were no significant changes of tumor marker levels, neither in bone scintigraphic pattern. Flare reaction occurred in 44% of the cases within 2 weeks from the therapy. Remarkable variations of platelets and leukocytes occurred in 33.3% and 18.5% of patients, respectively, independently of the radiopharmaceutical used, but reversed within 6 weeks after therapy. CONCLUSIONS: Radionuclide therapy with bone-seeker agents 89Sr and 153Sm in the palliation of painful bone metastases allows a partial/total relief of pain with an improvement of quality of life. No tumoricid effect was found. Haematological toxicity was limited and reversible. Patients with prostate cancer seem to have a higher response rate.

Thyroid stunning in clinical practice: is it a real problem?

Stunning is a phenomenon of reducing (131)I uptaking activity by residual or metastatic tissue during the follow-up of patients after total thyroidectomy for differentiated thyroid carcinoma. It was observed at whole body scintigraphy performed after therapeutic dose, administered for remnant ablation, in patients who were previously given a (131)I dose for diagnostic purpose. This phenomenon could influence the efficacy of radioisotopic therapy, making it unsuccessful. Stunning was observed also in case of hyperthyroidism treated by fractionated doses of (131)I. After a careful revision of literature, Authors report their last 10 years-experience about very few cases of supposed stunning, observed in oncological and hyperthyroidal patients who underwent diagnostic scan and radioiodine therapy. In case of differentiated thyroid carcinoma, we recommended a careful selection of patients who will be given ablative therapy using very low diagnostic doses and administering further therapeutic dose in a short time. In case of hyperthyroidism treatment, it is confirmed the opportunity of a single therapeutic dose with TSH value within the normal range. Because it was found out a very small number of cases in our wide population, we conclude that stunning is not influent in clinical practice, above all if ''well-practice'' diagnostic-therapeutical procedures are strictly observed.

A finding of myocardial uptake at a bone scintigraphy with Tc-99m HDP.

We present a patient admitted to our Department for a Tc-99m HDP three-phase bone scintigraphy to evaluate a hip prosthesis. Delayed images showed diffuse myocardial uptake at whole body scan. In such cases, several diseases should be considered in the differential diagnosis.

Sensitivity of [99mTc]methoxyisobutylisonitrile scan in patients with metastatic differentiated thyroid cancer.

AIM: The aim of the present study was to evaluate the diagnostic sensitivity of [(99m)Tc]methoxyisobutylisonitrile ([(99m)Tc]MIBI) in a large series of patients with metastatic differentiated thyroid carcinoma (DTC), as compared with (131)I-whole body scan (WBS) and other diagnostic imaging techniques. METHODS: Eighty-four patients with known metastases from DTC where recruited during the course of replacement thyroxine therapy and undergone [(99m)Tc]MIBI scan. All patients previously performed a (131)I-WBS with thyroglobulin (Tg) measurement and neck ultrasound or computerized tomography, or magnetic resonance imaging, or bone scan or positron emission tomography (PET) scan. RESULTS: Patients were divided in two groups: group A (n=50) with known metastases and positive at a previous (131)I-WBS and group B (n=34) with known metastases, but negative at (131)I-WBS. All patients had elevated serum Tg level in absence of replacement therapy. Technetium-99m-MIBI scan showed 76.2% sensitivity in detecting metastases, Tg during opotherapy 64.3%, and the other imaging techniques combined 86.9%. Sensitivity of [(99m)Tc]MIBI was greater in metastases without (131)I uptake than in metastases with (131)I uptake, although the difference was not statistically significant. CONCLUSION: Technetium-99m-MIBI scan improves sensitivity of Tg measurement in patients with suspected metastases from DTC during the course of opotherapy and is a useful alternative to fluorodeoxyglucose-PET or other imaging techniques in patients with elevated serum Tg and negative (131)I-WBS.

[Hyperthyroidism in the elderly]. / L'ipertiroidismo nell'anziano.

UNLABELLED: Hyperthyroidism in elderly patients is not to be under-evaluated, since it is characterized in such age range by particular clinical and prognostic features. Based upon literature survey and their clinical experience, the authors discuss in the present paper clinical, diagnostic and therapeutic problems of hyperthyroidism in geriatric patients. MATERIAL AND METHOD: In the period between 1978-2003 out of 1804 patients surgically treated for thyroid disease (non neoplastic in 1470 pts.), 180 subjects presented hyperthyroidism (17%). 36 were in geriatric age-range (mean age 76 yr.; 29 females and 7 males). 26 presented a Multinodular Toxic Goiter (72.2%), whereas 9 patients complained of Plummer Adenoma (25%); only 1 patient showed Basedow disease (2.7%). RESULTS: As far as ASA classification, there were 7 ASA I, 27 ASA II and 2 ASA III. Compression of digestive tract and/or respiratory airway represented a surgical indication in 15 patients (41.6%). 12 (33.4%) were operated due to predominant cardiac symptoms (tachycardia, atrial fibrillation). The remaining 9 patients (25%) were treated for the concomitance of atypical symptoms of hyperthyroidism. We performed 15 total thyroidectomy, 7 "near totally", 8 sub-total, 6 hemithyroidectomy in case of Plummer adenoma. Postoperative mortality was nihil; p.o. morbidity was 5.5% for medical conditions (pneumonia) and surgery-related (1 laryngeal recurrent paralysis and 1 hypoparathyroidism) in 5.5%. Post-operative follow-up, conducted at 6 and 12 months from the operation, showed regression of hyperthyroidism and regression or improvement of all clinical symptoms complained by the patient. CONCLUSION: Surgical treatment seems to be the only immediate and definitive cure for hyperthyroidism. Geriatric age does not seem to be a surgical contraindication.

Lung metastases from differentiated thyroid carcinoma. A 40 years' experience.

AIM: Retrospective studies have been carried out to estimate the survival of 96 patients with lung metastases from differentiated thyroid carcinoma, observed from 1958 to 2000. METHODS: All patients had undergone total thyroidectomy. Case histories were analysed with respect to age at diagnosis, sex, histology, local lymph node involvement, size of lung metastases and 131I uptake by metastases. Survival functions were calculated. Cox regression was performed. RESULTS: There was no statistically significant difference in histological type and lymph node involvement, whereas a significantly longer survival time was observed in patients under 45 years of age at diagnosis (p= or <0.0001), in those with metastases concentrating 131I (p= or <0.0001) and in those with fine miliaric metastases (p=0.0037). Multi-variate analysis revealed that the risk of death increases about 5.4-fold in patients over 45 years old, whereas 131I treatment is likely to reduce this risk to nearly 1/6. Conclusion. In conclusion, in patients with lung metastases from differentiated thyroid carcinoma, young age at diagnosis and 131I uptake by metastases are the most important factors positively affecting survival time. Radioiodine therapy, also with high cumulative 131I activity, can lead to longer survival time or complete recovery.

Sodium iodide symporter expression and radioiodine distribution in extrathyroidal tissues.

The functional role of the sodium iodide symporter (NIS) in extrathyroidal tissues was investigated by examining its mRNA and protein expression, together with the evidence of radioiodine (131)I uptake in 302 patients who underwent (131)I total body scanning, following the administration of high doses of (131)I for a papillary or follicular thyroid carcinoma. By using a real-time kinetic quantitative RT-PCR and immunohistochemistry, the expression of NIS protein was detected mainly in secretory tissues. In parallel, 1311 uptake was evidenced in the majority of patients in the salivary glands (in 39%) and stomach (in 78%), but was found in breast in only 4 young female patients. These data demonstrate a strong correlation between the organ radioactivity distribution, as observed in vivo, and NIS protein expression. Interestingly, (131)I is rarely concentrated by mammary glands, even when large doses are administered. Moreover, a (131)I transfer in secretion fluids may represent a potential source of contamination responsible for false positive images and diagnostic pitfalls.

Physiological characterization of 'stay green' mutants in durum wheat.

Four mutants with delayed leaf senescence were selected from seed of durum wheat mutagenized with ethylmethane sulphonate. Changes in net photosynthetic rate, efficiency of photosystem II and chlorophyll concentration during the maturation and senescence of the flag leaves of both mutant and parental plants were determined under glasshouse conditions. The four mutant lines maintained photosynthetic competence for longer than the parental line and are therefore functionally 'stay green'. The mutant lines also had higher seed weights and grain yields per plant than the parental line.

Micronucleus yield and colorimetric test as indicators of damage in patients' lymphocytes after 131I therapy.

UNLABELLED: To estimate the absorbed dose received by patients who underwent 131I therapy, a modified compartmental model of the International Commission on Radiological Protection (ICRP) was used. The activity in plasma and micronucleus (MN) frequency (MN test) were measured before and after therapy. To evaluate whether a correlation exists between lymphocytes and absorbed dose, a colorimetric test, based on the tetrazolium salt 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT test), was used. METHODS: Twenty patients who underwent 131I therapy were studied. Activity was measured in plasma, and isolated lymphocytes were collected to perform the MN and MTT tests. RESULTS: The mean MN frequency observed in unexposed patient lymphocytes was comparable with that of healthy subjects. 131I therapy induces a small increase in MN, and a good correlation with the bone marrow absorbed dose was obtained (P = 0.040). A consistent decrease in phytostimulation observed after therapy (MTT test) correlated significantly with bone marrow absorbed dose (P = 0.0085). CONCLUSION: The MTT test appears to be more reliable than the MN test for evaluating lymphocyte damage induced by 131I therapy.

Imaging active lymphocytic infiltration in coeliac disease with iodine-123-interleukin-2 and the response to diet.

Coeliac disease is diagnosed by the presence of specific antibodies and a jejunal biopsy showing mucosal atrophy and mononuclear cell infiltration. Mucosal cell-mediated immune response is considered the central event in the pathogenesis of coeliac disease, and untreated coeliac patients show specific features of T-cell activation in the small intestine. Here we describe the use of iodine-123-interleukin-2 scintigraphy in coeliac patients as a non-invasive tool for detection of lymphocytic infiltration in the small bowel and its use for therapy follow-up, and we demonstrate the specificity of binding of labelled-IL2 to activated lymphocytes by ex-vivo autoradiography of jejunal biopsies. 123I-IL2 was administered i.v. [74 MBq (2 mCi)], and gamma camera images were acquired after 1 h. Ten patients were studied with 123I-IL2 scintigraphy at diagnosis and seven were also investigated after 12-19 months of gluten-free diet. Results were expressed as target-to-background radioactivity ratios in six different bowel regions before and after the diet. At the time of diagnosis all patients showed a significantly higher bowel uptake of 123I-IL2 than normal subjects (P < 0.003 in all regions). A significant correlation was found between jejunal radioactivity and the number of IL2R + ve lymphocytes per millimetre of jejunal mucosa as detected by immunostaining of jejunal biopsy (r2 = 0.66; P = 0.008). Autoradiography of jejunal biopsies confirmed that labelled-IL2 only binds to activated T-lymphocytes infiltrating the gut mucosa. After 1 year of the diet, bowel uptake of 123I-IL2 significantly decreased in five out of six regions (P < 0.03), although two patients still had a positive IL2 scintigraphy in one region. We conclude that 123I-IL2 scintigraphy is a sensitive non-invasive technique for assessing in vivo the presence of activated mononuclear cells in the bowel of patients affected by coeliac disease. Unlike jejunal biopsy, this method provides information from the whole intestine and gives a non-invasive measure of the effectiveness of the gluten-free diet.

Value of the first serum thyroglobulin level after total thyroidectomy for the diagnosis of metastases from differentiated thyroid carcinoma.

The aim of this study was to evaluate the diagnostic significance of the first serum thyroglobulin (Tg) measurement, performed 40 days after total thyroidectomy for differentiated thyroid carcinoma and prior to the ablation of residual thyroid tissue by means of iodine-131 therapy. In a retrospective study we examined 334 consecutive patients followed up for 4-16 years by means of regular Tg measurements, (131)I whole-body scans (WBS) and other diagnostic techniques, if necessary. In 79 patients metastases were discovered (32 lymph node and 47 distant metastases) within 18 months following thyroidectomy. Mean values of first Tg were significantly higher in patients with than in patients without metastases (258.9+/-310.6 vs 15.9+/-19.6 ng/ml; P<0.0001). Receiver operating characteristic (ROC) curve analysis of data revealed that for first Tg values higher than 69.7 ng/ml, the positive predictive value for the presence of metastases exceeded 90%. No statistically significant correlation was found between first Tg value and either thyroid-stimulating hormone (TSH) value or percentage of (131)I uptake by residual thyroid tissue. No other parameter (age, histological type, site of metastases, (131)I uptake by metastases) was significantly related to the first Tg value. We conclude that the first Tg measurement after total thyroidectomy provides a useful early diagnostic indication of metastatic disease in spite of the presence of a post-surgical thyroid remnant, and that this holds true regardless of the TSH value and WBS result. This early information is of clinical relevance for patient follow-up.

[Restoration of digestive continuity after subtotal gastrectomy: comparison of the methods of Billroth I, Billroth II and roux en Y. Randomized prospective study]. / Ripristino della continuità digestiva dopo gastrectomia subtotale: confronto tra la Billroth I, la Billroth II e l'ansa ad Y. Studio prospettico randomizzato.

UNLABELLED: The aim of this study was to evaluate functional results after Billroth I, Billroth II and Roux en Y reconstruction in subtotal gastrectomy. MATERIAL AND METHODS: 45 patients were randomised between 1990 and 1995 and stratified in 3 different groups: 15 BI, 15 BII and 15 Roux. They were investigated by EGDS with multiple biopsies and upper gastro-intestinal scintiscanning, to evaluate gastro-esophageal reflux (GER) and dynamics of gastric emptying. Besides they answered a questionnaire: "Gastrointestinal Quality of Life Index" (GIQLI). RESULTS: A reflux esophagitis was found in 5 BI, in 7 BII and in 2 Roux (p < 0.001). No gastric lesions were found in 6 BI, in 5 BII and in 12 Roux, (BI vs. Y, p < 0.05; BII vs. Y, p < 0.001). Chronic superficial gastritis was present in 9 BI, in 4 BII and in 3 Roux (BI vs. Y, p < 0.05). Dynamic scintiscan demonstrated the presence of GER in 5 BI and gastric emptying was fast (37' < T 1/2 < 86'), but incomplete (60' residual activity: 49-62%). GER was evident in 7 BII with slow (28' < T 1/2 < 143') and incomplete (60' residual activity: 48-72%) gastric emptying. GER was detected in 2 Roux and radioactive bolus progression in the Roux limb was fast (24' < T 1/2 < 53') and complete (60 residual activity: 42-52%) (BI vs. Y; BII vs. Y, p < 0,001). There was not statistical significance between GIQLI score in the 3 groups. CONCLUSION: The authors affirm the Roux en Y is the technique of choice in subtotal gastrectomy, if compared with BI and BII.

Role of initial iodine-131 whole-body scan and serum thyroglobulin in differentiated thyroid carcinoma metastases.

UNLABELLED: We evaluated the role of first (131)I-whole-body scan and of first serum thyroglobulin (Tg) measurement after surgery in the early diagnosis of metastases from differentiated thyroid carcinoma (DTC). METHODS: In 269 patients with metastases from DTC, we retrospectively evaluated the results of first whole-body scan (performed 40 days after surgery with diagnostic or therapeutic (131)I dose) and in 69 of them we also evaluated the result of first Tg measurement (performed the day before the first whole-body scan) in relation to the presence, localization and type of metastases. RESULTS: In all patients, the first whole-body scan was positive for the thyroid remnant, and in 54.3% of patients it was also positive for metastases. In the remaining 45.7% of patients, metastases were detected during the follow-up. First Tg levels were >60 ng/ml in 66.7% of patients with metastases. First whole-body scan detected metastases in 47.8% of patients with Tg values <60 ng/ml, while Tg values were >60 ng/ml in 61.3% of patients with first whole-body scan negative for metastases. The combined results of both first whole-body scan and first Tg measurement allowed the early detection of metastases in 82.6% of patients. Whole-body scan detected distant metastases more frequently than local lymph node metastases (p < 0.01). CONCLUSION: In more than 80% of patients, metastases were suspected or diagnosed as early as 40 days after surgery in the presence of residual thyroid tissue by combined evaluation of results of first whole-body scan and Tg measurement.

Prognostic relevance of pancreatic uptake of technetium-99m labelled human polyclonal immunoglobulins in patients with type 1 diabetes.

Insulin-dependent type 1 diabetes (IDDM) is caused by the autoimmune destruction of insulin-producing beta cells. Approximately 10%-20% of patients may benefit from adjuvant immunotherapy upon diagnosis of the disease in order to protect residual beta-cell function. It has been suggested that this subgroup of patients differs from others by virtue of the presence of residual pancreatic inflammation and beta-cell function. In this study we have investigated to what extent technetium-99m-labelled human polyclonal immunoglobulins (99mTc-HIG) accumulate in the pancreas of IDDM patients at the time of diagnosis and 1 year thereafter, with a view to ascertaining whether HIG scintigraphy is useful for the identification of IDDM patients with residual pancreatic inflammation. Patients with recent-onset IDDM (n=15) were investigated at the time of diagnosis and 1 year later, and ten age- and sex-matched normal subjects were also studied. Gamma camera imaging and target to background ratio, analysed blind by three independent readers, were used to quantify the radioactivity in the pancreatic region and findings were correlated with metabolic, immunological and clinical parameters. Seven out of 15 newly diagnosed IDDM patients showed a significant accumulation of radiolabelled HIG in the pancreas (pancreas/bone ratio higher than the mean +2SD of normal subjects). One year after diagnosis, pancreatic accumulation of HIG was still detectable in most IDDM patients who were positive at the time of diagnosis. Six out of seven patients with positive scintigraphy had a partial clinical remission. These results indicate that HIG scintigraphy at the time of onset of diabetes identifies a subset of patients with residual beta-cell function who may benefit from adjuvant immunotherapy.

Post-Chernobyl thyroid carcinoma in Belarus children and adolescents: comparison with naturally occurring thyroid carcinoma in Italy and France.

After the Chernobyl nuclear accident (April 26, 1986), childhood thyroid carcinoma had a great increase in Belarus and Ukraine, as a consequence of the exposure to iodine radioactive fallout. The epidemiological and clinical features of the disease were studied in 472 patients less than 21 yr old at diagnosis, with differentiated thyroid carcinoma, representing 97.7% of all thyroid carcinomas diagnosed in Belarus between May, 1986, and December, 1995. The results were compared with those of 369 subjects of the same age group, with naturally occurring thyroid carcinoma, observed in Italy and France. Between 1986 and 1989, the number of thyroid cancer cases per year ranged from 3-8 and increased to 31 in 1990, to 66 in 1991, to 72 in 1992, to 93 in 1993, to 96 in 1994, and to 90 in 1995. The age at diagnosis was 14 yr or less in 78.8% (children group) and more than 14, but less than 21, yr in the remaining subjects (adolescents group). Mean (+/- SD) age at the time of the accident was 4.4 +/- 3.4 yr (3.2 +/- 2.3 in children and 8.9 +/- 2.7 in adolescents), the majority of the patients (62.9%) being 5 yr old or less. The time interval between the accident and the diagnosis (latency period) decreased progressively from 7.5 +/- 1.6 yr in children 0-2 yr old at the time of the accident to 6.0 +/- 1.6 yr in those 9-11 yr old. Since 1993, the yearly distribution of new cases showed a decrease in the subjects 9 yr old or more at the time of the accident but not in those 5 yr old or less. This could not be accounted for by a shift of exposed subjects to an age group at diagnosis not included in this study, because only subjects less than 12 yr of age at the time of the accident were considered in this analysis. Mean age at diagnosis in Belarus patients was 11.3 +/- 3.1 yr (10.1 +/- 2.3 in children and 15.7 +/- 1.4 in adolescents), whereas, among patients with naturally-occurring thyroid carcinomas from Italy and France, the majority of cases were diagnosed after 14 yr of age (mean age at diagnosis: 14.6 +/- 4.2 yr). The female-to-male ratio was significantly higher in Italy and France (2.5/1), compared with the ratio of patients from Belarus (1.6/1). Most of the tumors were papillary in both series, but a relatively high proportion of follicular carcinomas (P = 0.0001) was found in Italy/France (15.2%), as opposed to 5.3% in Belarus. Extrathyroidal extension and lymph node metastases were more frequent in Belarus (49.1%, P = 0.0001; and 64.6%, P = 0.002, respectively) with respect to Italy/France (24.9% and 53.9%, respectively). Thyroid lymphocytic infiltration and circulating antithyroperoxidase antibody were more frequent in Belarus patients. Our analysis of Belarus thyroid cancer patients less than 21 yr old showed that the post-Chernobyl increase in thyroid carcinomas involved both children and, to a much lesser extent, adolescents. Subjects 5 yr old or less at the time of the accident accounted for the majority of the patients. No evidence of a decrease in the number of new cases was observed in this age group, as opposed to older subjects. These data support the concept that subjects who were younger at the time of radiation exposure had, and continue to have, a greater risk of developing thyroid carcinoma and strongly suggest that this age group should be carefully monitored in the future. When compared with naturally occurring thyroid carcinoma of the same age group observed in Italy and France, the post-Chernobyl Belarus thyroid carcinomas affected younger subjects, were less influenced by gender, were virtually always papillary, had a greater aggressiveness at presentation, and were more frequently associated with thyroid autoimmunity.