Accuracy of the European Thyroid Imaging Reporting and Data System (EU-TIRADS) in the valuation of thyroid nodule malignancy in reference to the post-surgery histological results.

PURPOSE: To assess the clinical usefulness of the European Thyroid Imaging and Reporting Data System (EU-TIRADS) in the valuation of thyroid nodules malignancy in reference to post-surgery histological results. MATERIAL AND METHODS: Pre-operative ultrasound was performed in consecutive patients admitted for thyroid surgery between June 2017 and January 2018. Thyroid nodules were classified according to EU-TIRADS to five groups: 1-5. At least one fine-needle aspiration biopsy (FNAB)/patient (dominant or suspected nodule) was performed in an outpatient clinic. The final diagnosis was based on the histological result. The percentage of cancers in each EU-TIRADS group was evaluated. Finally, sensitivity, specificity, accuracy, as well as positive and negative predictive values for malignancy were assessed. RESULTS: Fifty-two patients with a total of 140 thyroid nodules (median: 3 nodules/thyroid [minimum-maximum: 1-6]) were enrolled in the study. Thyroid cancer was diagnosed in 0% (0/6) in EU-TIRADS 2; 0% (0/92) in EU-TIRADS 3; 5.9% (2/34) in EU-TIRADS 4, and 75% (6/8) in EU-TIRADS 5. In nodules assessed as EU-TIRADS ≥ 4 sensitivity, specificity, positive and negative predictive values for malignancy were, respectively: 75% (CI 95%: 40.7-93.5), 94.1% (CI 95%: 86.0-98.5), 75% (CI 95%: 40.7-93.5), and 94.1% (CI 95%: 86.0-98.5). CONCLUSIONS: EU-TIRADS is a valuable and simple tool for assessment of the risk of malignancy of thyroid nodules and demonstrates a high ultrasound correlation with histological post-surgery results. FNAB should be performed in all nodules assessed as EU-TIRADS ≥ 4, due to higher risk of malignancy.

[Prevalence and difficulties in chronic obstructive pulmonary disease diagnosis in patients suffering from severe peripheral arterial disease]. / Czestosc wystepowania oraz trudnosci w diagnozowaniu POChP u chorych na zaawansowana miazdzyce zarostowa tetnic konczyn dolnych.

UNLABELLED: Cigarette smoking is the most prominent risk factor for chronic obstructive pulmonary disease (COPD) and peripheral arterial disease (PAD). Prevalence of COPD among cigarette smokers is about 23% in Poland. Effort dyspnea which develops in advanced stage of COPD is the leading cause of seeking medical advice. Physical activity among patients with PAD is reduced due to intermittent claudication. It may cause delayed COPD diagnosis in this group of patients. THE AIM OF THE STUDY: To estimate the prevalence of COPD among patients suffering from severe PAD who were hospitalized in surgery department due to critical limb ischemia and to evaluate difficulties during COPD diagnosis in this group of patients. MATERIAL AND METHODS: We examined 64 patients suffering from severe PAD (at least IIb stage according to Fontaine's scale). Patients were asked about the typical symptoms of COPD: chronic cough, regular sputum production and dyspnea. To evaluate the intensity of dyspnea we used British Medical Research Council scale. Spirometry was performed to every patient. Patients with airways obstruction underwent spirometry after the administration of inhaled bronchodilator. Every patient who had the post-bronchodilator value of FEV,/FVC ratio below the lower limit of normal values was diagnosed with COPD. RESULTS: It was not possible to evaluate the dyspnea intensity using MRC scale in 44% of 34 patients who reported dyspnea. During the study we diagnosed 16 patients with COPD (9 pts had 1st stage of COPD according to GOLD classification, 7 pts--2nd). 9 patients had been formerly diagnosed with COPD (2 pts--1st stage, 5 pts--2nd, and 2 pts--3rd). Spirometry-defined COPD was present in 39% of study group. The analysis of data from patients with PAD coexistent COPD revealed that 60% of them were current cigarette smokers and 28% of them declared passive smoking exposure. The other known negative prognostic factors in patients with COPD such as BMI lower than 21 kg/mr2, FEV1% of predicted value below 65% and X-rays photograph visible emphysema were observed in 40%, 32% and 12% of patients with PAD and coexistent COPD respectively. Hypertension was present in 52% of patients with PAD and coexistent COPD, cardiac arterial disease in 52% and chronic heart failure due to cardiac arterial disease in 36%. Further analysis of laboratory tests revealed dyslipidemia and chronic kidney disease in 52% and 60% of these patients respectively. CONCLUSIONS: COPD diagnosis among patients suffering from severe PAD involves several difficulties such as uselessness of MRC dyspnea scale and frequent heart diseases which delay the COPD diagnosis being considered as primary dyspnea reason. Many factors which have been proven to be responsible for worse prognosis due to COPD were observed in patients with PAD and coexistent COPD. High prevalence of COPD among patients suffering from PAD suggests the spirometry as a COPD screening would be justified in that group.

Resection of liver metastases from differentiated thyroid cancer: who might benefit? A report of 2 cases with review of literature.

BACKGROUND: Liver metastases of differentiated thyroid cancers (DTC) are uncommon. Surgery has proven to be effective in patients with 131I-negative hepatic lesions. Here, we present two patients who underwent liver resection for metastatic DTC. CASE PRESENTATION: The first patient is a 36-year-old woman who reported with 70-mm hepatic metastases of papillary thyroid cancer. After primary treatment of cancer, she was disease-free for 8 years when the elevation of TSH levels resulted for the need to search for metastasis. Notably, the 131I SPECT did not show any lesions. The CT scan revealed an 80mm diameter mass in the liver. Histology confirmed metastasis of thyroid cancer. Lack of iodine uptake and the size of lesion excluded treatment with radioactive iodine. Radical resection of the metastasis was performed with good short- and long-term postoperative result. The second patient is a 65-year-old man previously treated for follicular thyroid cancer. When a iodine-negative 70mm diameter metastasis was detected within the liver, he was referred for surgery. Extended right hepatectomy was performed. In a 12-months follow-up, he remained stable, with no signs of recurrence. CONCLUSIONS: These two cases show that resection of hepatic metastases of DTC is an option even in the case of large lesions. Given the effectiveness and safety of liver surgery, we reckon that it should be the treatment of choice when possible. The decision to perform surgical treatment should be based on analysis of the ability to perform radical and safe resection.

Family of microRNA-146 Regulates RARß in Papillary Thyroid Carcinoma.

Retinoic acid is a promising tool in adjuvant cancer therapies, including refractory thyroid cancer, and its biological role is mediated by the retinoic acid receptor beta (RARß). However, expression of RARß is lowered in papillary thyroid carcinoma (PTC), contributing to promotion of tumor growth and inefficiency of retinoic acid and radioactive iodine treatment. The causes of aberrant RARB expression are largely unknown. We hypothesized that the culpable mechanisms include the action of microRNAs from the miR-146 family, previously identified as significantly upregulated in PTC tumors. To test this hypothesis, we assessed the expression of RARB as well as miR-146a-5p and miR-146b-5p in 48 PTC tumor/normal tissue pairs by Taqman assay to reveal that the expression of RARB was 3.28-fold decreased, and miR-146b-5p was 28.9-fold increased in PTC tumors. Direct interaction between miRs and RARB was determined in the luciferase assay and further confirmed in cell lines, where overexpression of miR-146a-5p and miR-146b-5p caused a 31% and 33% decrease in endogenous RARB mRNA levels. Inhibition of miR-146a and miR-146b resulted in 62.5% and 45.4% increase of RARB, respectively, and a concomitant decrease in proliferation rates of thyroid cancer cell lines, analyzed in xCELLigence system.We showed that two microRNAs of the miR-146 family directly regulate RARB. Inhibition of miRs resulted in restoration of RARB expression and decreased rates of proliferation of thyroid cancer cells. By restoring RARB levels, microRNA inhibitors may become part of an adjuvant therapy in thyroid cancer patients.

Association between GWAS-Derived rs966423 Genetic Variant and Overall Mortality in Patients with Differentiated Thyroid Cancer.

PURPOSE: Five germline genetic variants (rs116909374, rs965513, rs944289, rs966423, and rs2439302) have been associated in genome-wide association studies (GWAS) with increased risk of differentiated thyroid cancer (DTC), but their role in mortality of patients has not been established. Also, no preoperative marker of the clinical outcome of thyroid cancer had yet been identified. The aim of the study was to investigate the relationship between the variants and overall mortality in patients with DTC. EXPERIMENTAL DESIGN: Retrospective study of 1,836 patients (1,643 women, 193 men) with median age at diagnosis of 49 years and overall median follow-up time of 8.7 years after initial treatment at a single comprehensive cancer center between 1990 and 2013. RESULTS: Among 5 variants, rs966423 was associated with increased mortality, which was 6.4% (33 of 518) versus 3.7% (47 of 1,259) in TT carriers versus CC/CT carriers (P = 0.017). The HR of TT versus TC/CC carriers was 1.6 [95% confidence interval (CI), 1.02-2.49; P = 0.038] after adjustment for age at diagnosis and sex. Importantly, the association of rs966423 with mortality remained valid when clinicopathologic risk factors were included in the model (HR, 1.89; 95% CI, 1.14-3.13; P = 0.014). Higher rs966423-associated patient mortality of TT versus CC/CT carriers was also observed in interaction with angioinvasion (adjusted HR, 3.48; 95% CI, 1.67-7.22; P < 0.001), lymph node metastasis (adjusted HR, 3.47; 95% CI, 1.16-10.4; P = 0.018), extrathyroidal invasion (adjusted HR, 2.07; 95% CI, 1.15-3.73; P = 0.013). CONCLUSIONS: The presence of the rs966423-TT genotype was associated with a significant increase in overall mortality of patients with DTC. Contrary to BRAF mutation and other somatic changes, the status of germline rs966423 is known before the treatment and might be used in the management of mortality risk by means of modification of therapy.

Thyroid sialyltransferase mRNA level and activity are increased in Graves' disease.

Sialylation of cell components is an important immunomodulating mechanism affecting cell response to hormones and adhesion molecules. To study alterations in sialic acid metabolism in Graves' disease (GD) we measured the following parameters in various human thyroid tissues: lipid-bound sialic acid (LBSA) content, ganglioside profile, total sialyltransferase activity, and the two major sialyltransferase mRNAs for sialyltransferase-1 (ST6Gal I) and for sialyltransferase-4A (ST3Gal I). Fragments of toxic thyroid nodules (TN), nontoxic thyroid nodules (NN) and nontumorous tissue from patients with nodular goiter or thyroid cancer were used as a control (C). The LBSA content and sialyltransferase activity were the highest in the GD group (164 +/- 4.44 versus 120 +/- 2.00 nmoL/g, p = 0.005 and 1625 +/- 283.5 versus 324 +/- 54.2 cpm/mg of protein, p < 0.005 compared to control group C). Ganglioside profile in the GD group was similar to that in control tissues. Sialyltransferase- 1 mRNA and sialyltransferase-4A mRNA levels were significantly higher in the GD group than in the control group (12.52 +/- 6.90 versus 2.54 +/- 1.24 arbitrary units, p < 0.005 and 2,49 +/- 1.16 versus 1.23 +/- 0.46 arbitrary units, p < 0.05, respectively). There was a positive correlation between the increased sialyltransferase-1 mRNA level and the TSH-receptor antibody titer determined by the TRAK test. These results indicate that sialyltransferases expression and activity are increased in GD. Exact mechanism of this upregulation remains unknown, though one of possible explanations is the activation of the thyrotropin (TSH) receptor.

Pax-8 expression correlates with type II 5' deiodinase expression in thyroids from patients with Graves' disease.

Transcription factors TTF-1 and Pax-8 control the expression of thyroid-specific genes crucial for thyroid function. It has been postulated that they may play a role in thyrotropin (TSH)-mediated augmentation of gene expression observed in some thyroid diseases including Grave's hyperthyroidism. Recently, we and others described the expression of two genes participating in thyroid hormone metabolism type I and type II deiodinase (D1 and D2, respectively) that are upregulated by TSH, although the mechanisms responsible for this effect are likely to be different. The aim of this study was to investigate whether there is a correlation between TTF-1 and Pax-8 mRNA levels and type I or type II 5' deiodinases expression in Graves' disease. D1 activity and mRNA level, as well as D2 activity and mRNA level, were significantly increased in Graves' disease in comparison to control tissues. D1, but not D2, activity correlated with its mRNA level in Graves' disease and toxic multinodular goitre. The TTF-1 mRNA level was not different between Graves' disease and control thyroids and no correlation between TTF-1 mRNA level and either D1 or D2 mRNA levels were found. The Pax-8 mRNA level was significantly increased in Graves' disease in comparison to control tissues and correlated with D2, but not D1, mRNA levels among all investigated groups of tissues. Our data suggest that transcription factor Pax-8 could be involved in the upregulation of D2 expression in the thyroid of Graves' patients.

In-depth characterization of the microRNA transcriptome in normal thyroid and papillary thyroid carcinoma.

CONTEXT: A single microRNA gene may give rise to several mature products that differ in length, called isomiRs. IsomiRs are known to be tissue specific and functionally relevant. The microRNA sequence heterogeneity of the thyroid gland has yet to be determined. OBJECTIVE: The objective of the study was to provide a comprehensive view of the microRNA transcriptome in normal thyroid and papillary thyroid carcinoma (PTC). DESIGN: We used next-generation deep sequencing to analyze microRNA length heterogeneity and expression profiles of PTC tumors (n = 14), unaffected tissue adjacent to tumors (n = 14), and control, noncancerous thyroid tissue (n = 14). The results were validated with a microarray on an additional set of 9 PTC tumor/normal tissue pairs. RESULTS: Eighty-nine microRNAs were significantly deregulated in PTC compared with normal thyroid tissue (false discovery rate < 0.05, fold change 0.13-20.7). Top deregulated miRNAs included miR-146b-5p, miR-221-3p, miR-7-3p, miR-551b-3p, miR-486-3p, and miR-144-3p, confirming previous microarray profiling. The expression of miRNAs did not depend on the BRAF mutation status. Interestingly, 85% of the most abundant microRNAs consisted of isoforms that differed from the standard reference sequence deposited in miRBase. Moreover, the reference microRNAs were completely absent in 42.4% and 35.9% of the microRNAs expressed in normal thyroid and PTC tumors, respectively. Numerous isomiRs had altered seed sequences, which led to a different set of target genes. For highly deregulated miR-146b-5p, we detected 6 isoforms (tumor/normal fold change 14.4-28.7, false discovery rate < 0.002) that varied at their 5' ends with a 1-nt difference that created 2 alternative seeds. The target genes for those 2 seeds overlapped in only 13.1% of genes. CONCLUSIONS: Almost all microRNAs exhibit isoforms of variable length and potentially distinct function in thyroid tumorigenesis.

Systemic inflammation in peripheral arterial disease with or without coexistent chronic obstructive pulmonary disease: analysis of selected markers.

INTRODUCTION: Low-grade systemic inflammation plays an important role in the pathogenesis and natural history of chronic obstructive pulmonary disease (COPD) and peripheral arterial disease (PAD). The aim of the study was to analyze plasma concentrations of selected markers of inflammation in patients suffering from PAD with or without coexistent COPD. MATERIAL AND METHODS: Thirty patients (6 women) with advanced PAD (at least IIb stage according to Fontaine scale) hospitalized due to critical limb ischemia were examined. In all patients spirometry was performed to confirm or exclude COPD. Plasma concentration of IL-6, IL-8 and TNF-α was measured using ELISA method. Statistical analysis was performed according to COPD status and according to smoking status independently. RESULTS: In the whole group of patients with PAD, COPD was recognized in 14 cases (for the first time in 10 cases). All patients were smokers (46.7% current, 53.3% ex-smokers). We found a significant correlation between FEV1%N (percent of norm of first second expiratory volume) and the number of years of smoking (r = -0.39; p < 0.05). We found similar concentrations of IL-6 (2.54 pg/ml vs. 2.31 pg/ml), IL-8 (8.55 pg/ml vs. 8.14 pg/ml, TNF-α (0.72 pg/ml vs. 1.75 pg/ml) in the COPD(+) group in comparison to the COPD(-) group (differences were not significant). We observed significant positive correlations (p < 0.05) between concentrations of measured markers and significant negative correlations between pain free walking distance and these markers. CONCLUSIONS: Our study confirmed coexistence of PAD with COPD. The character of inflammation is similar in these smoking-related diseases.