Influence of nitrate in drinking water on the prevalence of thyroid cancer and other diseases (literature review and experience in post-chernobyl period in Belarus).

In the last 60 years dramatically increased the content of nitrates in groundwater due to intensive use of nitrogen fertilizers in agriculture. Research in post-Chernobyl period has shown that a sharp increase in the incidence of thyroid cancer depends not only on the level of thyroid dose, but also on the level of nitrates in groundwater.

Improved follow-up of patients with differentiated thyroid carcinoma. The quantitative detection limit of 131I uptake in diagnostic scans.

AIM: Physicians typically are unaware of the radioiodine uptake (RIU) detection limit (LoD) on scintigrams of differentiated thyroid carcinoma (DTC) patients. We evaluated a novel method to determine LoD as a quantitative upper limit for RIU in negative scans and as a value to contextualize faint visible uptake. PATIENTS, METHODS: To test whether LoD is related to physicians' ratings, RIU and LoD were calculated from scintigraphic count statistics for 120 static planar neck scans and were compared with the ratings of five nuclear medicine specialists blinded to patient/scan characteristics regarding visible cervical uptake. Scans were acquired on days 1 (d1) and 2 (d2) post-administration of 298 ± 30 MBq iodine-131 in 60 consecutive DTC patients after recombinant human thyrotropin (rhTSH) or thyroid hormone withdrawal (THW) (n = 30 each). RESULTS: Indicating good inter-observer agreement, ≥ 4 readers concurred regarding 56 (93.3%) [54 (90.0%)] d1[d2] scans. Seventeen scans from 12 patients received ≥ 3 positive votes; in 15 (88.2%), RIU exceeded LoD. RIU assessed from regions-of-interest over former thyroid beds in scans with ≤ 2 positive votes was typically below the LoD (99/103 scans, 96.1%). In 48 patients with ≤ 2 positive votes in both scans, LoD was a median 0.0094% (0.0050%) in d1(d2) images and was significantly lower (p < 0.01) on early or late scans in 22 euthyroid rhTSH patients versus 26 hypothyroid THW patients. CONCLUSION: LoD data obtained by the proposed method closely reflect nuclear medicine specialists' scan ratings and provide comparators in serial scintigrams, improving diagnostic 131I imaging accuracy in differentiated thyroid carcinoma.

Thyroid cancer in infants and adolescents after Chernobyl.

Studies in children medically exposed to external irradiation more than 50 years ago revealed a considerably increased risk for thyroid cancer. Similarly, a strongly age-dependent risk for thyroid cancer was observed in the Japanese population after the atomic bomb explosions with the highest risk in the group of children below age of 10. After the Chernobyl accident, children from Belarus living in highly exposed regions received mean thyroid doses by radioactive fallout higher by a factor of approximately 2 as compared to the survivors of the atomic bomb explosions. This lead to a radiation related increase of thyroid cancer incidence in children and adolescents with the highest incidence in age group 0-4 years up to now totally amounting to approximately 5 000 cases. For screening of thyroid cancer in children, high resolution ultrasound is the method of choice which has to be complemented by fine-needle aspiration biopsy in suspicious cases. Diagnostic criteria for malignancy in childhood thyroid cancer by ultrasound are hypoechogenicity and irregularity of the outline, subcapsular location of lesions and increased peri-intranodular vascularisation. The treatment strategy for thyroid cancer in children does not differ substantially from the approach used in adults. Primary treatment consists of thyroidectomy and lymph node dissection. Careful and complete removal of the lymph nodes is of great clinical relevance in children because of very frequent node involvement (between 40% and 90%). Because of the high prevalence of lymph node metastases, ablation of thyroid remnants is mostly indicated in children with thyroid cancer. Distant metastases which need higher activities of radioiodine are less frequent with 10-20%. Even in advanced cases of childhood thyroid cancer, long-lasting remissions can be achieved. A specific finding in children is disseminated, milliary lung metastases with intense radioiodine uptake. In this situation, pulmonary fibrosis may be a severe side-effect so that the indication for repeated courses of radioiodine therapy has to be decided thoroughly. With respect to side-effects of radioiodine therapy, the risk of developing breast cancer has to be taken into account seriously since especially the female breast is exposed to a relatively high radiation dose. Generally, young patients treated with high activities of radioiodine should be carefully followed up during their whole lifespan.

Impact of parathyroid status and Ca and vitamin-D supplementation on bone mass and muscle-bone relationships in 208 Belarussian children after thyroidectomy because of thyroid carcinoma.

This observational study analyzes Ca-P metabolism and its impact on bone mass accrual and density and the muscle-bone mass/mass relationships in male and female children and adolescents who were parathyroidectomized because of thyroid carcinoma. Two hundred and eight children and adolescents (119 girls and 89 boys) from Gomel city (Belarus) and its rural surroundings were referred to our institution after having undergone total thyroidectomy for the treatment of advanced papillary thyroid cancer. A subgroup of children with demonstrated primary hypoparathyroidism received dihydrotachysterol (AT-10) and/or Ca supplementation. Among routine procedures over a maximum follow-up period of 5 years (average 3.7 years, maximum 8 visits), whole-body scans were taken using dual energy X-ray absorptiometry (DXA) at each visit in order to determine whole-body bone mineral content (TBMC), projected "areal" bone mineral density (TBMD), total lean mass (TLM) and total fat mass (TFM). The average serum Ca, P and AP concentrations over the whole observation period were significantly different between the groups; however, TBMC z-scores for all studied children were statistically similar in all visits. In girls, no between-group differences in height- and weight-controlled TBMC and TBMD or the TBMC/TLM ratio were observed (ANCOVA) and supplementation exerted no effect on these data, suggesting that the total bone mass accrual was not impaired by PTH deficiency in the studied conditions. However, non-supplemented boys showed lower values of the TBMC/TLM ratio than girls, and supplementation normalized these values in direct correlation with the induced improvement in serum P availability to bone. Results indicate that the primary impairment in parathyroid function and bone metabolism indicators in the thyroidectomized children was unrelated to any measurable change in crude bone mass values. However, in boys this condition impaired the TBMC/TLM ratio in such a way that the administered supplementation could normalize it as a function of improved P availability. Girls' skeleton seemed to have been naturally protected against the negative metabolic effect of the studied condition. An estrogen-induced enhancement of the biomechanical impact of muscle contractions on bone mass and structure could not be excluded in this group.

Micronucleus formation in lymphocytes of children from the vicinity of Chernobyl after (131)I therapy.

After the Chernobyl accident a statistically significant increase in the number of children with thyroid tumours was observed. In this study 166 children with and 75 without thyroid tumours were analysed for micronucleus formation in peripheral blood lymphocytes using the cytochalasin B approach. The following factors did not significantly affect micronucleus formation: gender, age at the time of the first (131)I treatment, tumour stage, tumour type, or metastases; a statistically significant increase in the number of micronuclei, however, was observed for the residents of Gomel compared to other locations, such as Brest, Grodno, and Minsk. The children with tumours received (131)I treatment after surgical resection of the tumours. This gave us the opportunity to systematically follow the effect of (131)I on micronucleus formation. A marked increase was observed 5 days after the (131)I treatment followed by a decrease within a 4-7 months interval up to the next application, but the pre-treatment levels were not achieved. Up to 10 therapy cycles were followed each including an analysis of micronucleus formation before and 5 days after (131)I application. The response of the children was characterised by clear individual differences and the increase/decrease pattern of micronucleus frequencies induced by iodine-131 was correlated with a decrease/increase pattern in the number of lymphocytes.

Inverse association between age at the time of radiation exposure and extent of disease in cases of radiation-induced childhood thyroid carcinoma in Belarus.

BACKGROUND: Increased incidence of childhood thyroid carcinoma, particularly in the youngest children, has been reported from Belarus since the nuclear reactor accident at Chernobyl in 1986. The relation between disease severity and age at the time of the accident, not previously established in this cohort, was analyzed in this study. METHODS: The authors studied the association between disease severity, expressed by TNM classification, and age at radiation exposure in a cohort of 483 patients younger than 8 years at the time of the Chernobyl accident who have been diagnosed with differentiated thyroid carcinoma since 1986 at the Center for Thyroid Cancer in Minsk. The associations between age at radiation exposure and TNM categories were compared among 4 groups of patients who were ages <2, 2.1-4, 4.1-6, and 6.1-8 years at the time of the accident. Multivariate discriminant analysis was performed to examine the effects of age at the time of the accident, gender, histology, tumor stage, and N classification on the frequency of distant metastasis. RESULTS: Younger age at the time of the Chernobyl accident was associated with greater extrathyroidal tumor extension (P<0.01) and more lymph node involvement (P<0.0001) and tended to be associated with more distant metastases (P = 0.09). Compared with patients who were ages 6.1-8 years at the time of the accident, patients who were younger than 2 years had significantly more extrathyroidal tumor invasion (P = 0.004), lymph node involvement (P = 0.004), and distant metastases (P = 0.05). The age at diagnosis increased with older age at the time of radiation exposure (linear regression analysis; correlation coefficient = 0. 67; P<0.001). Multivariate analysis revealed that younger age at the time of the accident (P = 0.001) and advanced locoregional tumor extension (P<0.001) were the only powerful factors influencing the risk for distant metastasis of this malignancy. CONCLUSIONS: The severity of disease was associated inversely with age at the time of radiation exposure in these cases of radiation-induced childhood thyroid carcinoma.

Comparison of total and regional body composition in adolescent patients with anorexia nervosa and pair-matched controls.

Body composition in 31 adolescent girls suffering from anorexia nervosa (AN) was measured at the time of hospitalization in order to assess the muscle/bone relationship as a potential source of the development of osteopenia. Differences in lean tissue, fat and bone mass in total body, weight bearing and non weight bearing limbs were estimated in AN and pair-matched controls aged 14.2 +/- 1.8 years (range: 9-17 years). Further, it was investigated if bone mineral density (BMD) better reflects the muscle/bone relationship than bone mineral content (BMC). At the distal radius parameters measured by peripheral quantitative computed tomography (pQCT) were used to estimate the association of volumetric bone density to bone strength and lean body mass. The correspondence to the same and different body regions was assessed. Total lean mass in the controls was closely related to total body bone mineral content (TBBMC), as was lean tissue and bone mass of the limb subregions (r = 0.82 to 0.93). In contrast, the correlation was significantly lower in AN (r = 0.33 to 0.77). In the controls, the pQCT-derived bone strength was correlated with muscle mass of the forearm (r = 0.78, p < 0.001), but only moderately in AN (r = 0.47, n.s.). Regional lean tissue was 11-20% and fat mass was 56-66% lower in AN (p < 0.01). After adjustment for height, TBBMC was different at p = 0.01. Within the limbs subregions, BMC (but not BMD) was different in both groups only in the upper arm and the thigh. BMC reflected the bone/muscle relationship better than BMD. Intra- and between group regressions gave no significant differences between weight bearing and non weight bearing limbs. In conclusion, the assessment of musculoskeletal factors may be a useful tool to develop individual preventive measures for therapy after recovery of our patients.

Effect of specific activity on cardiac uptake of iodine-123-MIBG.

UNLABELLED: Radioiodinated meta-iodobenzylguanidine (MIBG), an analog of norepinephrine, has been used to assess myocardial sympathetic innervation. Recent in vivo studies predict enhanced cardiac uptake of this radiopharmaceutical with high specific activity. METHODS: To clarify the effect of specific activity on cardiac uptake of radioiodinated MIBG, the distribution and kinetics of no-carrier-added [123I]MIBG (> or = 7.4 TBq/mumol) were compared with those of commercial [123I]MIBG (approximately 74 MBq/mumol) in three healthy volunteers by serial imaging and blood sampling. RESULTS: Higher specific activity result in higher uptake of radioiodinated MIBG in all volunteers in the heart (p < 0.05) and liver (p < 0.05) but not in the lung (p = 0.26). Due to rapid deiodination, a more pronounced accumulation of radioactivity was present in plasma after no-carrier-added MIBG than commercial [123I]MIBG, resulting in higher background and thyroid activity after administration of the former. Calculated heart-to-liver (p = 0.96) and heart-to-lung (p = 0.42) count ratios in all volunteers revealed no significant improvement in cardiac imaging with no-carrier-added [123I]MIBG compared to commercial [123I]MIBG. CONCLUSION: This study highlights the appreciably higher in vivo deiodination of no-carrier-added [123I]MIBG compared to commercial preparation of [123I]MIBG in humans. Cardiac images acquired with no-carrier-added [123I]MIBG do not seem to be superior to those obtained with commercial MIBG.

Effect of specific activity on organ uptake of iodine-123-meta-iodobenzylguanidine in humans.

Radioiodinated meta-iodobenzylguanidine (MIBG), an analogue of norepinephrine, has been used in management of neuroendocrine tumors. Recent studies reveal that distribution of radioiodinated MIBG in animals depends on the specific activity of this radiopharmaceutical. In order to clarify the effect of specific activity on organ uptake of radioiodinated MIBG. the kinetics of no-carrier-added (n.c.a.) [I-123]MIBG (greater than or equal to 7.4 TBq/mu mol) were compared with those of commercial (com.) [I-123]MIBG (similar to 74 MBq/mu mol) in 3 healthy volunteers by serial imaging and blood sampling. The organ uptake of radioiodinated MIBG did not remarkably differ between the two specific activities. Due to rapid degradation a more pronounced accumulation of radioactivity was present in plasma alter n.c.a. than after com. [I-123]MIBG resulting in a higher background and thyroid activity. In addition due to a prolonged residence time of the radioactivity, the radiation exposure to organs was in general slightly higher with n.c.a. [I-123]MIBG as compared to com. [I-123]MIBG. This finding highlights the higher in vivo deiodination of n.c.a. [I-123]MIBG than of com. [I-123]MIBG in humans. In the treatment of children suffering from neuroblastoma, therefore, degradation of n.c.a. [I-123]MIBG may decrease the concentration of radioiodinated MIBG available for binding at tumor sites and result in higher radiation exposure of non-tumor tissue.

Polymorphisms in the p53 gene in thyroid tumours and blood samples of children from areas in Belarus.

We present changes in the p53 gene in a group of 70 thyroid tumours and 40 blood samples obtained from children from Belarus. Three thyroid tumours show a polymorphism in exon 6 (codon 213) and 5 tumours show a polymorphism in intron 6, 37 bp upstream to the 5'-end of exon 7. Only one patient has a mutation in exon 7 (codon 258) resulting in an amino acid substitution in the protein p53. The distribution of polymorphisms in the 40 blood samples was as follows: three patients had a polymorphism in exon 6 and two persons had a polymorphism in intron 6. One polymorphism in intron 6 was also found in the group of 30 healthy children from Belarus. The fact that the differences in the sequence in p53 found in the tumours was also seen in the blood of these patients demonstrates that they are polymorphisms not induced by radiation exposure. It is difficult to conclude, if the polymorphisms found by us could be associated with the predisposition to radiation-induced cancer.

Micronuclei in lymphocytes of children from the vicinity of Chernobyl before and after 131I therapy for thyroid cancer.

The present study addresses the monitoring of children from the Belorussian and Ukrainian Republics exposed to the fall-out of the Chernobyl accident. Micronucleus analysis has been performed on 56 children from different areas. The micronucleus frequencies in individuals as well as in regional groups were comparable with controls, except for three donors. Such results had to be expected, taking into account that at least 7 years have passed since the accident. Most of the children whose micronucleus frequencies were determined are suffering from thyroid cancer and were treated by radioiodine (131I) therapy. We studied the effect of in vitro exposure with 131I on micronucleus induction and that proliferative ability of lymphocytes. The present investigation indicates that micronuclei can be usefully employed to detect individual exposures to the incorporated radionuclide within several days after the intake of the radionuclide in a dose range of around 65-390 mGy (effective dose).