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Zivaljevic V.,Center for Endocrine Surgery | Tausanovic K.,Center for Endocrine Surgery | Sipetic S.,Institute of Epidemiology | Paunovic I.,Center for Endocrine Surgery | And 6 more authors.
European Journal of Cancer Prevention

Thyroid carcinomas in children and adolescents are rare tumors and the most common among them is papillary thyroid cancer (PTC). Its etiology is still under research and has not been clearly defined thus far, especially in young individuals. The aim of this case-control study was to determine potential risk factors for the development of PTC in children and adolescents. This type of study has not been carried out previously in this age group. A case-control study was carried out during a 15-year period, between 1995 and 2009. The case group included 75 patients with PTC younger than 20 years of age, with the youngest patient being 6.5 years old; 45 patients were female and 30 were male. The control group included the same number of participants, and the cases were individually matched by sex, age, and place of residence. Conditional univariate and multivariate logistic regression methods were applied in data analysis. According to univariate logistic regression analysis, PTC in children and adolescents was significantly related to the following factors: family history of thyroid cancer, family history of residence in an endemic-goiter area, family history of benign thyroid disease, and family history of nonthyroid malignant tumors. According to the multivariate logistic regression method, PTC in children and adolescents was independently related to a family history of thyroid cancer (odds ratio=4.5, 95% confidence interval=1.2-19.8) and a family history of nonthyroid malignant tumors (odds ratio=3.8, 95% confidence interval=1.4-8.7). In conclusion, all of the factors associated with the development of PTC in children and adolescents were related to their family history. © 2013 Wolters Kluwer Health Lippincott Williams & Wilkins. Source

Sabljak V.,Center for Endocrine Surgery
Acta chirurgica Iugoslavica

Preoperative evaluation of patients with thyroid land disease, in any kind of surgery, should include the possibility of difficult intubation caused by thyromegaly, the hormonal status (its disbalance), as well as the screening, and therapy of consequences of thyroid imbalance on specific organ systems, especially cardiovascular. It is necessary to select the adequate anesthetics and other pharmacological agents, according to current hormonal status. It is also necessary to select the adequate medications and other therapeutic measures for prevention and treatment of possible complications in perioperative period, some of which are life-threatening (thyroid storm and mixedema coma). Source

Isic Dencic T.,University of Belgrade | Cvejic D.,University of Belgrade | Paunovic I.,Center for Endocrine Surgery | Tatic S.,University of Belgrade | And 2 more authors.
Medical Oncology

Cytokeratin19 (CK19) has been reported as a useful marker of thyroid tumors. We evaluated its value for differential diagnosis of thyroid neoplastic lesions and assessed its usefulness for predicting aggressive behavior of papillary thyroid carcinomas by correlating immunohistochemical results with clinicopathological features of the patients. A total of 351 thyroid tissue samples included 27 follicular adenomas (FTA), 18 follicular carcinomas (FTC), 147 papillary carcinomas (71 of follicular type-PTCfv and 76 of classical type-PTCcl) and 33 cases of anaplastic carcinoma with 126 adjacent thyroid tissues. Diagnostic usefulness of CK19 was determined by ROC analysis, while its value as a predictive marker of PTC was tested by univariate and multivariate analysis. According to ROC analysis, CK19 can discriminate both types of PTC from other neoplasias of the thyroid gland (p < 0.05). Although greatest accuracy was gained for the identification of PTCcl (91.07 %), this marker was also helpful for distinguishing PTCfv from FTA and FTC (accuracy 71.43 and 65.17 %, respectively). Regarding the univariate set of tests, high expression of CK19 correlated significantly with age, multifocality, extrathyroidal extension, pT status and pTNM stage of PTC (p < 0.05 for all). Multivariate analyses confirmed the significant association of high CK19 expression with extrathyroidal extension of PTC as well as with pTNM stage (p < 0.05 and p < 0.01, respectively). CK19 is a useful marker for the identification of both types of PTC. High expression of this protein predicts the aggressive behavior of PTC and can help in the identification of a particular subgroup of PTC patients with a potentially worse prognosis. © 2012 Springer Science+Business Media New York. Source

Selemetjev S.,University of Belgrade | Dencic T.I.,University of Belgrade | Marecko I.,University of Belgrade | Jankovic J.,University of Belgrade | And 3 more authors.
Pathology Research and Practice

Overexpression of survivin, an inhibitor of apoptosis protein, has been found in a variety of human cancers, and is associated with tumor aggressiveness. In this study, we analyzed the expression of survivin in papillary thyroid carcinoma (PTC) and evaluated its clinical significance for predicting an aggressive course of disease at the time of diagnosis. Survivin expression was determined by immunohistochemistry in 104 tissue specimens of PTC, confirmed by Western blot and correlated with clinicopathological parameters. Of the tumors examined, 74 (71.15%) showed high cytoplasmic survivin expression. There was no association between high survivin expression and age, gender or tumor size. On the other hand, it was closely correlated with the presence of lymph node metastasis (P= 0.009), and there was a tendency for correlation with extrathyroidal invasion (P= 0.062). The high risk PTC group (TNM stage III-IV) was associated with high levels of survivin (P= 0.027). These results indicate that survivin is an unfavorable molecule for PTC prognosis, and that its high expression may indicate a subset of PTC patients with a more aggressive disease course. Evaluation of its expression in fine needle aspiration samples could be a useful tool for the identification of those PTC patients who require more extensive surgery, careful follow-up and therapeutic strategy. © 2013 Elsevier GmbH. Source

Marecko I.,University of Belgrade | Cvejic D.,University of Belgrade | Tatic S.,University of Belgrade | Dragutinovic V.,University of Belgrade | And 3 more authors.
Cancer Biomarkers

Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) have roles in physiological and pathological processes. We evaluated immunohistochemical expression of MMP-2 and TIMP-2 in paraffin sections of 12 human fetal thyroids at mid-term gestation and 79 thyroid tumors of follicular origin. Besides evaluating expression of these proteins during fetal development and neoplastic transformation, we determined whether expression of MMP-2 and TIMP-2 may help to differentiate papillary thyroid carcinoma (PTC) from follicular thyroid adenoma (FTA) and/or peritumoral tissue (PT). We also investigated their relationship with prognostically important clinicopathological parameters of PTC. Immunoreactive MMP-2 and TIMP-2 were found in all fetal thyroid tissues examined. Tumor tissues contained variable amounts of MMP-2 and TIMP-2, with overexpression of these proteins in PTC compared to FTA and PT tissue. According to the statistical analysis, MMP-2 distinguished follicular variant of PTC from FTA and overall PTC from total nonmalignant lesions. In PTC, high MMP-2 expression correlated with lymph node metastasis (P=0.022), while high TIMP-2 expression was positively correlated with tumor size (P=0.049) and extrathyroid invasion (P=0.017). Overall, these results indicate a role for MMP-2 and TIMP-2 in both thyroid development and malignant transformation and suggest that positive immunohistochemistry for MMP-2 and TIMP-2 might support diagnosis of PTC and predict unfavorable biological behavior. © 2011/2012 IOS Press and the authors. All rights reserved. Source

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