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1.
Antioxidant defence-related genetic variants are not associated with higher risk of secondary thyroid cancer after treatment of malignancy in childhood or adolescence
Ana Lina Vodušek, Katja Goričar, Barbara Gazić, Vita Dolžan, Janez Jazbec, 2016, original scientific article

Abstract: Background. Thyroid cancer is one of the most common secondary cancers after treatment of malignancy in childhood or adolescence. Thyroid gland is very sensitive to the carcinogenic effect of ionizing radiation, especially in children. Imbalance between pro- and anti-oxidant factors may play a role in thyroid carcinogenesis. Our study aimed to assess the relationship between genetic variability of antioxidant defence-related genes and the risk of secondary thyroid cancer after treatment of malignancy in childhood or adolescence. Patients and methods. In a retrospective study, we compared patients with childhood or adolescence primary malignancy between 1960 and 2006 that developed a secondary thyroid cancer (cases) with patients (controls), with the same primary malignancy but did not develop any secondary cancer. They were matched for age, gender, primary diagnosis and treatment (especially radiotherapy) of primary malignancy. They were all genotyped for SOD2 p.Ala16Val, CAT c.-262C>T, GPX1 p.Pro200Leu, GSTP1 p.Ile105Val, GSTP1 p.Ala114Val and GSTM1 and GSTT1 deletions. The influence of polymorphisms on occurrence of secondary cancer was examined by McNemar test and Cox proportional hazards model. Results. Between 1960 and 2006 a total of 2641 patients were diagnosed with primary malignancy before the age of 21 years in Slovenia. Among them 155 developed a secondary cancer, 28 of which were secondary thyroid cancers. No significant differences in the genotype frequency distribution were observed between cases and controls. Additionally we observed no significant influence of investigated polymorphisms on time to the development of secondary thyroid cancer. Conclusions. We observed no association of polymorphisms in antioxidant genes with the risk for secondary thyroid cancer after treatment of malignancy in childhood or adolescence. However, thyroid cancer is one of the most common secondary cancers in patients treated for malignancy in childhood or adolescence and the lifelong follow up of these patients is of utmost importance.
Keywords: secondary thyroid cancer, antioxidant genes, genetic polymorphism
Published in DiRROS: 09.05.2024; Views: 72; Downloads: 47
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2.
Functional polymorphisms in antioxidant genes in Hurthle cell thyroid neoplasm - an association of GPX1 polymorphism and recurrent Hurthle cell thyroid carcinoma
Blaž Krhin, Katja Goričar, Barbara Gazić, Vita Dolžan, Nikola Bešić, 2016, original scientific article

Abstract: Hurthle cells of the thyroid gland are very rich in mitochondria and oxidative enzymes. As a high level oxidative metabolism may lead to higher level of oxidative stress and can be associated with an increased risk for cancer, we investigated whether common functional polymorphisms in antioxidant genes (SOD2, CAT, GPX, GSTP1, GSTM1 and GSTT1) are associated with the development or clinical course of Hurthle cell thyroid carcinoma (HCTC). Methods. A retrospective study was performed in 139 patients treated by thyroid surgery for a Hurthle cell neoplasm. HCTC, Hurthle cell thyroid adenoma (HCTA) or Hurthle cell thyroid nodule (HCTN) were diagnosed by pathomorphology. DNA was extracted from cores of histologically confirmed normal tissue obtained from formalin-fixed paraffinembedded specimens and genotyped for investigated polymorphisms. Logistic regression was used to compare genotype distributions between patient groups. Results. HCTC, HCTA and HCTN were diagnosed in 53, 47 and 21 patients, respectively. Metastatic disease and recurrence of HCTC were diagnosed in 20 and 16 HCTC patients, respectively. Genotypes and allele frequencies of investigated polymorphisms did not deviate from Hardy-Weinberg equilibrium in patients with HCTC, HCTA and HCTN. Under the dominant genetic model we observed no differences in the genotype frequency distribution of the investigated polymorphisms when the HCTA and HCTN group was compared to the HCTC group for diagnosis of HCTC or for the presence of metastatic disease. However, GPX1 polymorphism was associated with the occurrence of recurrent disease (p = 0.040). Conclusions. GPX1 polymorphism may influence the risk for recurrent disease in HCTC.
Keywords: Hurthle cell thyroid carcinoma, Hurthle cell neoplasm, thyroid, oxidative stress
Published in DiRROS: 30.04.2024; Views: 101; Downloads: 24
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3.
Recurrence rate in regional lymph nodes in 737 patients with follicular or Hürthle cell neoplasms
Andrej Vogrin, Hana Bešič, Nikola Bešić, Maja Marolt-Mušič, 2016, original scientific article

Abstract: . Preoperative ultrasound (US) evaluation of central and lateral neck compartments is recommended for all patients undergoing a thyroidectomy for malignant or suspicious for malignancy cytologic or molecular findings. Our aim was to find out how frequent was recurrence in regional lymph nodes in patients with follicular or Hürthle cell neoplasm and usefulness of preoperative neck US investigation in patients with neoplasm. Patients and Methods. Altogether 737 patients were surgically treated because of follicular or Hürthle cell neoplasms from 1995 to 2014 at our cancer comprehensive center. Altogether 207 patients (163 females, 44 males; mean age 52 years) had thyroid carcinoma. Results. Carcinoma was diagnosed in follicular and Hürthle cell neoplasm in 143/428 and 64/309 of cases, respectively. A recurrence in regional lymph nodes occurred in 12/207 patients (6%) during a median follow-up of 55 months. Among patients with carcinoma a recurrence in regional lymph nodes was diagnosed in follicular and Hürthle cell neoplasms in 2% and 14%, respectively (p=0.002). Recurrence in regional lymph nodes was diagnosed in 3/428 (0.7%) of all patients with follicular neoplasm and 9/309 (3%) of all patients with Hürthle cell neoplasm. Recurrence in lymph nodes was diagnosed in 0.7% of patients with a preoperative diagnosis of follicular neoplasm and 3% of patients with a Hürthle cell neoplasm. A recurrence in regional lymph nodes is rare in patients with carcinoma and preoperative diagnosis of follicular neoplasm.
Keywords: ultrasonography, thyroid neoplasms, diagnosis, pathology
Published in DiRROS: 30.04.2024; Views: 88; Downloads: 50
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4.
Thyroid lesions incidentally detected by [sup] 18F-FDG PET-CT : a two centre retrospective study
Jan Jamšek, Ivana Žagar, Simona Gaberšček, Marko Grmek, 2015, original scientific article

Abstract: Incidental 18F-FDG uptake in the thyroid on PET-CT examinations represents a diagnostic challenge. The maximal standardized uptake value (SUVmax) is one possible parameter that can help in distinguishing between benign and malignant thyroid PET lesions. We retrospectively evaluated 18F-FDG PET-CT examinations of 5,911 patients performed at two different medical centres from 2010 to 2011. If pathologically increased activity was accidentally detected in the thyroid, the SUVmax of the thyroid lesion was calculated. Patients with incidental 18F-FDG uptake in the thyroid were instructed to visit a thyroidologist, who performed further investigation including fine needle aspiration cytology (FNAC) if needed. Lesions deemed suspicious after FNAC were referred for surgery. Incidental 18F-FDG uptake in the thyroid was found in 3.89% - in 230 out of 5,911 patients investigated on PET-CT. Malignant thyroid lesions (represented with focal thyroid uptake) were detected in 10 of 66 patients (in 15.2%). In the first medical centre the SUVmax of 36 benign lesions was 5.6 +- 2.8 compared to 15.8 +- 9.2 of 5 malignant lesions (p < 0.001). In the second centre the SUVmax of 20 benign lesions was 3.7 +- 2.2 compared to 5.1 +- 2.3 of 5 malignant lesions (p = 0.217). All 29 further investigated diffuse thyroid lesions were benign. Incidental 18F-FDG uptake in the thyroid was found in 3.89% of patients who had a PET-CT examination. Only focal thyroid uptake represented a malignant lesion in our study - in 15.2% of all focal thyroid lesions. SUVmax should only serve as one of several parameters that alert the clinician on the possibility of thyroid malignancy.
Keywords: thyroid cancer, PET incidentaloma, PET-CT
Published in DiRROS: 22.04.2024; Views: 64; Downloads: 24
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5.
Neoadjuvant chemotherapy in 13 patients with locally advanced poorly differentiated thyroid carcinoma based on Turin proposal : a single institution experience
Nikola Bešić, Marta Dremelj, Andreja A. Schwarzbartl-Pevec, Barbara Gazić, 2015, original scientific article

Abstract: There is a paradigm that chemotherapy is ineffective in thyroid carcinoma. The aim of our study was to find out whether neoadjuvant chemotherapy before thyroid surgery had an effect on the size of primary tumour in patients with poorly differentiated thyroid carcinoma (PDTC) based on Turin proposal. Patients and methods. Altogether, 13 patients (8 women, 5 men; median age 61 years) with PDTC based on Turin proposal were treated with neoadjuvant chemotherapy between 1986 and 2005. Tumour diameter was from 4.5 to 18 cm (median 9 cm). Regional and distant metastases were detected in 6 and 9 patients, respectively. Eight patients had pT4 tumour. Results. Altogether, 29 (range 1%5) cycles of chemotherapy were given. Tumour diameter decreased in all the patients and by more than 30% in 5 patients (= 38%). Two of these five patients had also preoperative external beam irradiation (EBRT). Total thyroidectomy, lobectomy and neck dissection were performed in 10, 3 and 5 cases, respectively. R0 and R1 resection was done in 5 and 8 cases, respectively. Eight patients had postoperative EBRT of the neck and upper mediastinum. The 5-year and 10-year cause-specific survival rates of patients were 66% and 20%, respectively. Conclusions. After neoadjuvant chemotherapy a partial tumour regression was observed in 38% of patients with PDTC based on Turin proposal.
Keywords: poorly differentiated thyroid carcinoma, neoadjuvant, chemotherapy, survival
Published in DiRROS: 22.04.2024; Views: 207; Downloads: 276
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6.
Incidental uptake of 18F-fluorocholine (FCH) in the head or in the neck of patients with prostate cancer
Marina Hodolič, Jurij Fettich, 2014, original scientific article

Abstract: Background. Positron emission tomography-computed tomography (PET/CT) with 18F-fluorocholine (FCH) is routinely performed in patients with prostate cancer. In this clinical context, foci of FCH uptake in the head or in the neck were considered as incidentalomas, except for those suggestive of multiple bone metastases. Case reports. In 8 patients the incidental focus corresponded to a benign tumour. The standard of truth was histologyin two cases, correlative imaging with MRI in four cases, 99mTc-SestaMIBI scintigraphy, ultrasonography and biochemistry in one case and biochemistry including PTH assay in one case. The final diagnosis of benign tumoursconsisted in 3 pituitary adenomas, 2 meningiomas, 2 hyperfunctioning parathyroid glands and 1 thyroid adenoma. Malignancy was proven histologically in 2 other patients: 1 papillary carcinoma of the thyroid and 1 cerebellar metastasis.Conclusions. To the best of our knowledge, FCH uptake by pituitary adenomas or hyperfunctioning parathyroidglands has never been described previously. We thus discuss whether there might be a future indication for FCH PET/CT when one such tumour is already known or suspected: to detect a residual or recurrent pituitary adenoma aftersurgery, to guide surgery or radiotherapy of a meningioma or to localise a hyperfunctioning parathyroid gland. Inthese potential indications, comparative studies with reference PET tracers or with 99mTc-sestaMIBI in case of hyperparathyroidism could be undertaken.
Keywords: FCH, PET/CT, incidentaloma, meningioma, pituitary adenoma, hyperparathyroidism, thyroid adenoma
Published in DiRROS: 10.04.2024; Views: 121; Downloads: 27
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7.
Medullary thyroid carcinoma and associated endocrinopathies in Slovenia from 1995 to 2021
Sara Milićević, Mateja Krajc, Ana Blatnik, Barbara Perić, 2022, original scientific article

Abstract: Background: Medullary thyroid cancer (MTC) is a rare endocrine tumour that is sporadic in 75% of cases and occurs as a part of inherited cancer syndromes in approximately 25% of cases. The aim of this study was to determine the frequency and type of RET pathogenic variants (PVs) in the Slovenian MTC patient population diagnosed between 1995 and 2021 and to elucidate the full range of associated endocrinopathies. Methods: A retrospective analysis of medical records of 266 MTC patients and their relatives seen in a tertiary centre between 1995 and 2021 was performed. Sequence analysis of exons 10, 11, 13, 14, 15, and 16 of the RET gene was analysed in most patients using Sanger sequencing. From 2017, the entire sequence of RET gene was analysed in most patients using targeted next-generation sequencing. Results: Germline PVs in the RET proto-oncogene were identified in 21.6% probands from 21 different MTC families. Of their tested relatives, 65% (67/103) were RET-positive and 35% (36/103) were RET-negative. PVs were detected in codon 618 and codon 634 in 28.6%, and in codon 790 in 23.8%. The RET-positive group consisted of 52 MTC patients, 13 patients with C cell hyperplasia and 2 individuals with neither. Associated endocrinopathies were diagnosed in 8/21 families: primary hyperparathyroidism (PHPT) in six families and pheochromocytoma (PHEO) in five families. In 62% of RET-positive families (13/21), no associated endocrinopathies were diagnosed. PHEO was most commonly associated with C634R (6/13) and PHPT with C634R (4/7). Hirschsprung’s disease appeared in one patient with RET PV in codon 618. Based on data from the Cancer Registry of Republic of Slovenia, only individual cases of common cancers with well understood environmental risk factors were discovered; lung cancer in 2/21 of families, papillary thyroid cancer in 3/21 of families, cutaneous melanoma in 2/21 of families, cervical cancer in 1/21 families, and lymphoma in 1/21 families. Conclusions: Analysis of prospectively collected MTC cases during a 27-year period revealed that 21.6% of Slovenian patients are RET PV carriers. Sixty-two percent of families had none of the associated endocrinopathies, confirming the thesis that FMTC is the most common presentation. This could suggest using risk-stratified management approaches when screening for PHEO and PHPT in RET PV carriers. However, more studies are needed to evaluate potential genetic risk modifiers as well as safety, improved quality of life, and medical cost reduction in the case of a patient-oriented approach.
Keywords: medullary thyroid carcinoma, multiple endocrine neoplasia, primary hyperparathyroidism
Published in DiRROS: 23.09.2022; Views: 557; Downloads: 258
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