The common genetic variant rs944289 on chromosome 14q13.3 associates with risk of both malignant and benign thyroid tumors in the Japanese population.

BACKGROUND: Several single nucleotide polymorphisms (SNP) have been identified to be associated with the risk for differentiated thyroid cancer in populations of distinct ethnic background. The relationship of these genetic markers to a benign tumor of the thyroid, follicular adenoma (FA), is not well established. METHODS: In a multicenter retrospective case-control study, five thyroid cancer-related SNPs-rs966513 (9q22.33, FOXE1), rs944289 (14q13.3, PTCSC3), rs2439302 (8p12, NRG1), rs1867277 (9q22.23, FOXE1), and rs6983267 (8q24, POU5F1B)-were genotyped in 959 cases of histologically verified FA, 535 papillary thyroid carcinomas (PTC), and 2766 population controls. RESULTS: A significant association was found between FA and rs944289 (p=0.002; OR 1.176 [CI 1.064-1.316]), and suggestively with rs2439302 (p=0.033; OR 1.149 [CI 1.010-1.315]). In PTC, significant associations were confirmed for rs965513 (p=4.21E-04; OR 1.587 [CI 1.235-2.000]) and rs944289 (p=0.003; OR 1.234 [CI 1.075-1.408]), newly found for rs2439302 (p=0.003; OR 1.266 [CI 1.087-1.493]) and rs1867277 (p=1.17E-04; OR 1.492 [CI 1.235-1.818]), and was not replicated for rs6983267 (p=0.082; OR 1.136 [CI 0.980-1.316]) in this series. A significant correlation between rs2439302 genotype and relative expression of NRG1 was detected in normal and tumor counterparts of PTC (about 10% decrease per each risk allele). NRG1 expression also significantly correlated with that of PTCSC3. CONCLUSIONS: Association of rs944289, which was previously known to confer risk for thyroid cancer, with FA, and the correlation between PTCSC3 and NRG1 expression demonstrates that predisposing genetic factors are partly common for benign and malignant thyroid tumors, and imply broader roles of the pathways they underlie in thyroid tumorigenesis, not limited to carcinogenesis.

Thyroid blockade during a radiation emergency in iodine-rich areas: effect of a stable-iodine dosage.

We examined the effect of stable iodine on thyroid gland blockade in patients with hyperthyroidism in order to make a preliminary evaluation of the appropriate dose of iodine prophylaxis in the event of a radiation emergency in Japan in which radioiodine is released to the environment. Eight patients were orally given single doses of 50 mg or 100 mg of potassium iodide, which contained 38 mg and 76 mg of iodide, respectively. Both doses significantly suppressed a thyroid uptake of (123)I for 24 h (p = 0.03). The protective effects at 24 h were 73.3% and 79.5%, respectively. No side effects were observed during the trial. The present study demonstrates that a single oral administration of 38 mg of iodide produces a thyroid-blocking effect equivalent to that of 76 mg of iodide, suggesting that a reevaluation of the stable iodine dosage during radiation emergencies in iodine-rich areas such as Japan is warranted.

Correlation of cytoplasmic beta-catenin and cyclin D1 overexpression during thyroid carcinogenesis around Semipalatinsk nuclear test site.

The Semipalatinsk nuclear test site (SNTS), the Republic of Kazakhstan, has been contaminated by radioactive fallout. The alteration of oncogenic molecules in thyroid cancer around the SNTS was considered worthy of analysis because it presented the potential to elucidate the relationship between radiation exposure and thyroid cancer. This study aimed to analyze both beta-catenin and cyclin D1 expressions in thyroid carcinomas around the SNTS. We examined nine cases of chronic thyroiditis, eight cases of follicular adenomas, and 23 cases of papillary carcinomas. Immunohistochemically, all carcinomas displayed a strong cytosolic beta-catenin expression, while both chronic thyroiditis and follicular adenomas showed a significantly lower cytoplasmic beta-catenin (22.2% and 37.5%, respectively). No cyclin D1 immunoreactivity was evident in chronic thyroiditis. In contrast, 62.5% of follicular adenomas and 87.0% of papillary carcinoma showed cyclin D1 overexpression. Additionally, a strong correlation between cytoplasmic beta-catenin and cyclin D1 expression was suggested in thyroid tumors. This study revealed a higher prevalence of both aberrant beta-catenin expression and cyclin D1 overexpression in papillary thyroid cancers around the SNTS than sporadic cases. The analysis of the alteration of the Wnt signaling-related molecules in thyroid cancer around the SNTS may be important to gain an insight into radiation-induced thyroid tumorigenesis.

A granulomatous liver abscess which developed after a toothpick penetrated the gastrointestinal tract: report of a case.

An unusual case of a toothpick perforating the stomach, then penetrating the liver, and thereafter forming a liver abscess is reported. A 48-year-old woman who had ingested a toothpick 1 month earlier was admitted to our hospital because of severe epigastralgia which had progressively worsened. A laparotomy was performed because a granulomatous abscess in the liver due to this ingested foreign body was suspected. We found a granulomatous abscess in the liver due to the penetration of the toothpick through the stomach. The toothpick had become completely embedded about 2 cm deep in the left lobe of the liver. When dissecting the tumor, a 5.5-cm toothpick was removed, and a partial lateral resection of the liver was performed. The histological diagnosis was a hepatic abscess with granulomatous change. This was a rare case of a migration of an ingested toothpick into the liver through the stomach.

Video-assisted neck surgery for thyroid and parathyroid diseases.

BACKGROUND: Endoscopic surgery has now become a well-established modality for the treatment of various organ diseases. In the present study, we analyzed the surgical results achieved by video-assisted neck surgery (VANS) in thyroid and parathyroid diseases. METHODS: From January 2000 to April 2002, 87 patients (eight males and 79 females) with a mean age of 49 years underwent VANS. The preoperative diagnoses of these patients included 37 benign thyroid tumors, 30 Graves' diseases, 17 parathyroid adenomas and three thyroid cancers. RESULTS: The mean operative time of VANS was 165 min for a hemithyroidectomy, 287 min for a subtotal thyroidectomy, and 157 min for a parathyroidectomy. The mean intraoperative blood loss was 60, 183 and 23 g for a hemithyroidectomy, subtotal thyroidectomy and parathyroidectomy, respectively. No conversion from VANS to conventional surgery was experienced. Three patients (3.4%) had temporary palsy of the recurrent laryngeal nerve. Otherwise, the postoperative courses were uneventful. CONCLUSIONS: VANS for thyroid and parathyroid diseases was found to be safe and effective. From a cosmetic point of view, a high degree of patient satisfaction was obtained. VANS is thus considered to be an excellent option for selected patients with thyroid and parathyroid diseases.

Aberrant localization of beta-catenin correlates with overexpression of its target gene in human papillary thyroid cancer.

Alterations of the Wnt/beta-catenin signaling pathway are known to occur in mutations of the component genes such as APC, Axin, and beta-catenin, and play a pathogenetic role in tumorigenesis. Activated Wnt signaling stabilizes beta-catenin, which associates with T cell factor, resulting in transactivation of the downstream target genes including c-myc and cyclin D1. To investigate the involvement of Wnt/beta-catenin signaling pathway in thyroid tumorigenesis, we analyzed its activation and localization in 5 human thyroid cancer cell lines and 132 thyroid tumor tissue samples. Dislocalization of beta-catenin was observed in all cell lines. Constitutive activation of T cell factor in two of four thyroid cancer cell lines was observed using reporter gene assay. Furthermore, high expression levels of c-Myc and cyclin D1 were observed in cell lines that showed cytoplasmic or nuclear accumulation of beta-catenin. In 132 paraffin-embedded thyroid carcinoma tissue samples, cytoplasmic beta-catenin was immunohistochemically observed in 52 out of 78 (67%) papillary thyroid cancers, but only in 3 of 34 (9%) follicular adenomas and 5 of 20 (25%) follicular cancers. Cytoplasmic localization of beta-catenin significantly correlated with overexpression of cyclin D1 in papillary carcinomas. Our results suggest that aberrant activation of Wnt/beta-catenin signaling is strongly involved in thyroid tumorigenesis.