RET fusion genes in pediatric and adult thyroid carcinomas: cohort characteristics and prognosis.

Thyroid cancer is associated with a broad range of different mutations, including RET (rearranged during transfection) fusion genes. The importance of characterizing RET fusion-positive tumors has recently increased due to the possibility of targeted treatment. The aim of this study was to identify RET fusion-positive thyroid tumors, correlate them with clinicopathological features, compare them with other mutated carcinomas, and evaluate long-term follow-up of patients. The cohort consisted of 1564 different thyroid tissue samples (including 1164 thyroid carcinoma samples) from pediatric and adult patients. Samples were analyzed for known driver mutations occurring in thyroid cancer. Negative samples were subjected to extensive RET fusion gene analyses using next-generation sequencing and real-time PCR. RET fusion genes were not detected in any low-risk neoplasm or benign thyroid tissue and were detected only in papillary thyroid carcinomas (PTCs), in 113/993 (11.4%) patients, three times more frequently in pediatric and adolescent patients (29.8%) than in adult patients (8.7%). A total of 20 types of RET fusions were identified. RET fusion-positive carcinomas were associated with aggressive tumor behavior, including high rates of lymph node (75.2%) and distant metastases (18.6%), significantly higher than in NTRK fusion, BRAF V600E and RAS-positive carcinomas. Local and distant metastases were also frequently found in patients with microcarcinomas positive for the RET fusions. 'True recurrences' occurred rarely (2.4%) and only in adult patients. The 2-, 5-, 10-year disease-specific survival rates were 99%, 96%, and 95%, respectively. RET fusion-positive carcinomas were associated with high invasiveness and metastatic activity, but probably due to intensive treatment with low patient mortality.

Disulfiram increases the efficacy of 5-fluorouracil in organotypic cultures of colorectal carcinoma.

Drug efficacy determined in preclinical research is difficult to transfer to clinical practice. This is mainly due to the use of oversimplified models omitting the effect of the tumor microenvironment and the presence of various cell types participating in the formation of tumors in vivo. In this study, we used robust three-dimensional models including spheroids grown from colon cancer cell lines and organotypic cultures prepared from the colorectal carcinoma tissue to test novel therapeutic strategies. We developed a multi-modal approach combining brightfield and fluorescence microscopy for evaluating drug effects on organotypic cultures. Combined treatment with 5-fluorouracil and disulfiram/copper efficiently eliminated cancer cells in these 3D models. Moreover, disulfiram/copper down-regulated the expression of markers associated with 5-fluorouracil resistance, such as thymidylate synthase and CD133/CD44. Thus, we propose combined therapy of 5-fluorouracil and disulfiram/copper for further testing as a treatment for colorectal carcinoma. In addition, we show that organotypic cultures are suitable models for anti-cancer drug testing.

Ischemic Colitis in a Patient with Severe COVID-19 Pneumonia.

At the time of the current COVID-19 pandemic, on a daily basis, we encountered patients suffering from various manifestations of this infection. The most common are respiratory symptoms. Many of the patients require acute hospital care, and a smaller group of them are hospitalized in intensive care units. A subset of these critically ill patients demonstrates clinically remarkable hypercoagulability and thus a predisposition to venous and arterial thromboembolism, manifested by thrombotic events ranging from acute pulmonary embolism and splanchnic vascular ischemia to extremity ischemia. The article describes a case of a patient with COVID-19 pneumonia complicated by massive bleeding into the gastrointestinal tract due to ischemic enterocolitis in connection with COVID-19 infection.

Metal Oxide Laser Ionization Mass Spectrometry Imaging of Fatty Acids and Their Double Bond Positional Isomers.

We present a novel combination of a metal oxide laser ionization mass spectrometry imaging (MOLI MSI) technique with off-line lipid derivatization by ozone for the detection of fatty acids (FA) and their carbon-carbon double bond (C═C) positional isomers in biological tissues. MOLI MSI experiments were realized with CeO2 and TiO2 nanopowders using a vacuum matrix-assisted laser desorption/ionization time-of-flight (MALDI TOF) mass spectrometer in the negative mode. The catalytic properties of these metal oxides allow FA cleavage from phospholipids under UV laser irradiation. At the same time, fragile ozonides produced at the sites of unsaturation decomposed, yielding four diagnostic ions specific for the C═C positions. Advantageously, two MOLI MSI runs from a single tissue sprayed with the metal oxide suspension were performed. The first run prior to ozone derivatization revealed the distribution of FAs, while the second run after the reaction with ozone offered additional information about FA C═C isomers. The developed procedure was demonstrated on MSI of a normal mouse brain and human colorectal cancer tissues uncovering the differential distribution of FAs down to the isomer level. Compared to the histological analysis, MOLI MSI showed the distinct distribution of specific FAs in different functional parts of the brain and in healthy and cancer tissues pointing toward its biological relevance. The developed technique can be directly adopted by laboratories with MALDI TOF analyzers and help in the understanding of the local FA metabolism in tissues.

Basic Motor Competencies of 6- to 8-Year-Old Primary School Children in 10 European Countries: A Cross-Sectional Study on Associations With Age, Sex, Body Mass Index, and Physical Activity.

Basic motor competencies (BMC) are a prerequisite for children to be physically active, participate in sports and thus develop a healthy, active lifestyle. The present study provides a broad screening of BMC and associations with age, sex, body mass index (BMI) and extracurricular physical activity (PA) in 10 different European countries. The different country and regional contexts within Europe will offer a novel view on already established BMC associations. The cross-sectional study was conducted in 11 regions in 10 European countries in 2018. The motor competence areas, object movement (OM) and self-movement (SM), were assessed using the MOBAK-1-2 test instrument in 3758 first and second graders (age: M = 6.86 ± 0.60 years; 50% girls) during Physical Education classes. Children were questioned about their extracurricular PA and age. Their body weight and height were measured in order to calculate BMI. Statistical analyses included variances and correlations. The results showed significant differences in BMC levels between countries (OM: F = 18.74, p < 0.001, η2 = 0.048; SM: F = 73.10, p < 0.001, η2 = 0.163) whereas associations between BMC and correlates were similar. Boys performed significantly better in OM while girls performed better in SM. Age was consistently positively related to OM and SM with older children reaching higher levels of BMC than younger ones. While participation rates for extracurricular PA differed widely, participation in ball sports was correlated with OM and SM. Participation in individual sports showed a significant association with SM. In summary, BMC levels of children seem to depend on where they live and are strongly related to their participation in extracurricular PA. Therefore, education and health policies, in order to enhance motor competence development and PA participation, are recommended. Further research on country-specific Physical Education frameworks and their influence on BMC will provide more insights into structural factors and cultural characteristics of BMC development. On a school level, support tools and educational materials for teachers about BMC may enable children to achieve a basic level of motor competencies through Physical Education, contributing to lifelong participation in PA.

A selective p53 activator and anticancer agent to improve colorectal cancer therapy.

Impairment of the p53 pathway is a critical event in cancer. Therefore, reestablishing p53 activity has become one of the most appealing anticancer therapeutic strategies. Here, we disclose the p53-activating anticancer drug (3S)-6,7-bis(hydroxymethyl)-5-methyl-3-phenyl-1H,3H-pyrrolo[1,2-c]thiazole (MANIO). MANIO demonstrates a notable selectivity to the p53 pathway, activating wild-type (WT)p53 and restoring WT-like function to mutant (mut)p53 in human cancer cells. MANIO directly binds to the WT/mutp53 DNA-binding domain, enhancing the protein thermal stability, DNA-binding ability, and transcriptional activity. The high efficacy of MANIO as an anticancer agent toward cancers harboring WT/mutp53 is further demonstrated in patient-derived cells and xenograft mouse models of colorectal cancer (CRC), with no signs of undesirable side effects. MANIO synergizes with conventional chemotherapeutic drugs, and in vitro and in vivo studies predict its adequate drug-likeness and pharmacokinetic properties for a clinical candidate. As a single agent or in combination, MANIO will advance anticancer-targeted therapy, particularly benefiting CRC patients harboring distinct p53 status.

NTRK Fusion Genes in Thyroid Carcinomas: Clinicopathological Characteristics and Their Impacts on Prognosis.

Chromosomal rearrangements of NTRK genes are oncogenic driver mutations in thyroid cancer (TC). This study aimed to identify NTRK fusion-positive thyroid tumors and to correlate them with clinical and pathological data and determine their prognostic significance. The cohort consisted of 989 different TC samples. Based on the detected mutation, samples were triaged, and those that were positive for a BRAF, HRAS, KRAS, NRAS, RET, RET/PTC or PAX8/PPARγ mutation were excluded from further analyses. NTRK fusion gene testing was performed in 259 cases, including 126 cases using next-generation sequencing. NTRK fusion genes were detected in 57 of 846 (6.7%) papillary thyroid carcinomas and in 2 of 10 (20.0%) poorly differentiated thyroid carcinomas. A total of eight types of NTRK fusions were found, including ETV6/NTRK3, EML4/NTRK3, RBPMS/NTRK3, SQSTM1/NTRK3, TPM3/NTRK1, IRF2BP2/NTRK1, SQSTM1/NTRK1 and TPR/NTRK1.NTRK fusion-positive carcinomas were associated with the follicular growth pattern, chronic lymphocytic thyroiditis and lymph node metastases. NTRK1-rearranged carcinomas showed a higher frequency of multifocality and aggressivity than NTRK3-rearranged carcinomas. Tumor size, presence of metastases, positivity for the NTRK3 or NTRK1 fusion gene and a late mutation event (TERT or TP53 mutation) were determined as factors affecting patient prognosis. NTRK fusion genes are valuable diagnostic and prognostic markers.

ERCP in patients after choledochodenoanastomosis.

The aim of this retrospective study is to evaluate our experience with diagnostic and therapeutic endoscopic retrograde cholangiopancreaticography (ERCP) in patients after choledochoduodenoanastomosis. METHODS: The study took 20 years (November 1994 - December 2014). Three patients after choledochoduodenoanastomosis who had symptoms of biliary obstruction were retrospectively evaluated. In all cases, a standard therapeutic videolateroscope was used to perform ERCP. PATIENTS AND RESULTS: We achieved ERCP in these 3 patients with choledochoduodenoanastomosis 100% cannulation success rate - 3 out of 3 patients. This was 100% success rate of diagnostic ERCP. In all of these patients, ERCP was found - both stenosis of the natural mouth of the Vater papilla, stenosis of choledochoduodenoanastomosis, and suprastenotic distal choledocholithiasis. In all patients with the above-described ERCP pathology, endoscopic treatment was initiated immediately after diagnostic ERCP, consisting of standard endoscopic papillotomy of the stenotic Vater papilla, balloon dilatation of choledochoduodenoanastomosis stenosis, and endoscopic extraction of suprastenotic distal choledocholithiasis. In total, therapeutic ERCP was completely successful in all 3 patients out of 3 (100%) who had initially started endoscopic treatment. There were no complications in our group of 3 patients. CONCLUSION: In ERCP in patients after choledochoduodenoanastomosis, we achieved 100% success of both diagnostic and therapeutic ERCP in all of our 3 patients.

RET, NTRK, ALK, BRAF, and MET Fusions in a Large Cohort of Pediatric Papillary Thyroid Carcinomas.

Background: Pediatric papillary thyroid carcinoma (PTC) is a rare malignancy, but with increasing incidence. Pediatric PTCs have distinct clinical and pathological features and even the molecular profile differs from adult PTCs. Somatic point mutations in pediatric PTCs have been previously described and studied, but complex information about fusion genes is lacking. The aim of this study was to identify different fusion genes in a large cohort of pediatric PTCs and to correlate them with clinical and pathological data of patients. Methods: The cohort consisted of 93 pediatric PTC patients (6-20 years old). DNA and RNA were extracted from fresh frozen tissue samples, followed by DNA and RNA-targeted next-generation sequencing analyses. Fusion gene-positive samples were verified by real-time polymerase chain reaction. Results: A genetic alteration was found in 72/93 (77.4%) pediatric PTC cases. In 52/93 (55.9%) pediatric PTC patients, a fusion gene was detected. Twenty different types of RET, NTRK3, ALK, NTRK1, BRAF, and MET fusions were found, of which five novel, TPR/RET, IKBKG/RET, BBIP1/RET, OPTN/BRAF, and EML4/MET, rearrangements were identified and a CUL1/BRAF rearrangement that has not been previously described in thyroid cancer. Fusion gene-positive PTCs were significantly associated with the mixture of classical and follicular variants of PTC, extrathyroidal extension, higher T classification, lymph node and distant metastases, chronic lymphocytic thyroiditis, and frequent occurrence of psammoma bodies compared with fusion gene-negative PTCs. Fusion-positive patients also received more doses of radioiodine therapy. The most common fusion genes were the RET fusions, followed by NTRK3 fusions. RET fusions were associated with more frequent lymph node and distant metastases and psammoma bodies, and NTRK3 fusions were associated with the follicular variant of PTC. Conclusions: Fusion genes were the most common genetic alterations in pediatric PTCs. Fusion gene-positive PTCs were associated with more aggressive disease than fusion gene-negative PTCs.

Comparison of Pheochromocytoma-Specific Morbidity and Mortality Among Adults With Bilateral Pheochromocytomas Undergoing Total Adrenalectomy vs Cortical-Sparing Adrenalectomy.

Importance: Large studies investigating long-term outcomes of patients with bilateral pheochromocytomas treated with either total or cortical-sparing adrenalectomies are needed to inform clinical management. Objective: To determine the association of total vs cortical-sparing adrenalectomy with pheochromocytoma-specific mortality, the burden of primary adrenal insufficiency after bilateral adrenalectomy, and the risk of pheochromocytoma recurrence. Design, Setting, and Participants: This cohort study used data from a multicenter consortium-based registry for 625 patients treated for bilateral pheochromocytomas between 1950 and 2018. Data were analyzed from September 1, 2018, to June 1, 2019. Exposures: Total or cortical-sparing adrenalectomy. Main Outcomes and Measures: Primary adrenal insufficiency, recurrent pheochromocytoma, and mortality. Results: Of 625 patients (300 [48%] female) with a median (interquartile range [IQR]) age of 30 (22-40) years at diagnosis, 401 (64%) were diagnosed with synchronous bilateral pheochromocytomas and 224 (36%) were diagnosed with metachronous pheochromocytomas (median [IQR] interval to second adrenalectomy, 6 [1-13] years). In 505 of 526 tested patients (96%), germline mutations were detected in the genes RET (282 patients [54%]), VHL (184 patients [35%]), and other genes (39 patients [7%]). Of 849 adrenalectomies performed in 625 patients, 324 (52%) were planned as cortical sparing and were successful in 248 of 324 patients (76.5%). Primary adrenal insufficiency occurred in all patients treated with total adrenalectomy but only in 23.5% of patients treated with attempted cortical-sparing adrenalectomy. A third of patients with adrenal insufficiency developed complications, such as adrenal crisis or iatrogenic Cushing syndrome. Of 377 patients who became steroid dependent, 67 (18%) developed at least 1 adrenal crisis and 50 (13%) developed iatrogenic Cushing syndrome during median (IQR) follow-up of 8 (3-25) years. Two patients developed recurrent pheochromocytoma in the adrenal bed despite total adrenalectomy. In contrast, 33 patients (13%) treated with successful cortical-sparing adrenalectomy developed another pheochromocytoma within the remnant adrenal after a median (IQR) of 8 (4-13) years, all of which were successfully treated with another surgery. Cortical-sparing surgery was not associated with survival. Overall survival was associated with comorbidities unrelated to pheochromocytoma: of 63 patients who died, only 3 (5%) died of metastatic pheochromocytoma. Conclusions and Relevance: Patients undergoing cortical-sparing adrenalectomy did not demonstrate decreased survival, despite development of recurrent pheochromocytoma in 13%. Cortical-sparing adrenalectomy should be considered in all patients with hereditary pheochromocytoma.

Somatic genetic alterations in a large cohort of pediatric thyroid nodules.

There is a rise in the incidence of thyroid nodules in pediatric patients. Most of them are benign tissues, but part of them can cause papillary thyroid cancer (PTC). The aim of this study was to detect the mutations in commonly investigated genes as well as in novel PTC-causing genes in thyroid nodules and to correlate the found mutations with clinical and pathological data. The cohort of 113 pediatric samples consisted of 30 benign lesions and 83 PTCs. DNA from samples was used for next-generation sequencing to identify mutations in the following genes: HRAS, KRAS, NRAS, BRAF, IDH1, CHEK2, PPM1D, EIF1AX, EZH1 and for capillary sequencing in case of the TERT promoter. RNA was used for real-time PCR to detect RET/PTC1 and RET/PTC3 rearrangements. Total detection rate of mutations was 5/30 in benign tissues and 35/83 in PTCs. Mutations in RAS genes (HRAS G13R, KRAS G12D, KRAS Q61R, NRAS Q61R) were detected in benign lesions and HRAS Q61R and NRAS Q61K mutations in PTCs. The RET/PTC rearrangement was identified in 18/83 of PTCs and was significantly associated with higher frequency of local and distant metastases. The BRAF V600E mutation was identified in 15/83 of PTCs and significantly correlated with higher age of patients and classical variant of PTC. Germline variants in the genes IDH1, CHEK2 and PPM1D were found. In conclusion, RET/PTC rearrangements and BRAF mutations were associated with different clinical and histopathological features of pediatric PTC. RAS mutations were detected with high frequency in patients with benign nodules; thus, our results suggest that these patients should be followed up intensively.

Chromogranin A in the Laboratory Diagnosis of Pheochromocytoma and Paraganglioma.

This work discusses the clinical performance of chromogranin A (CGA), a commonly measured marker in neuroendocrine neoplasms, for the diagnosis of pheochromocytoma/paraganglioma (PPGL). Plasma CGA (cut-off value 150 µg/L) was determined by an immunoradiometric assay. Free metanephrine (cut-off value 100 ng/L) and normetanephrine (cut-off value 170 ng/L) were determined by radioimmunoassay. Blood samples were collected from PPGL patients preoperatively, one week, six months, one year and two years after adrenal gland surgery. The control patients not diagnosed with PPGL suffered from adrenal problems or from MEN2 and thyroid carcinoma. The clinical sensitivity in the PPGL group of patients (n = 71) based on CGA is 90% and is below the clinical sensitivity determined by metanephrines (97%). The clinical specificity based on all plasma CGA values after surgery (n = 98) is 99% and is the same for metanephrines assays. The clinical specificity of CGA in the control group (n = 85) was 92% or 99% using metanephrines tests. We can conclude that plasma CGA can serve as an appropriate complement to metanephrines assays in laboratory diagnosis of PPGL patients. CGA is elevated in PPGLs, as well as in other neuroendocrine or non-neuroendocrine neoplasia and under clinical conditions increasing adrenergic activity.

High c-Myb Expression Associates with Good Prognosis in Colorectal Carcinoma.

Colorectal cancer (CRC) represents a serious challenge for oncologists due to high incidence and large heterogeneity. Prognostic factors are needed to stratify patients according to risk of disease progression. In this study, we report that high expression of c-Myb protein, determined by immunohistochemistry (IHC), associates with better overall and disease-free survival (OS, DFS) in a cohort of 103 patients. Although MYB has been previously considered to act as oncogene in CRC, our further analysis of datasets deposited in PrognoScan and SurvExpress databases confirmed that high MYB expression largely associates with good prognosis in CRC. As therapies targeting c-Myb have been developed and tested in preclinical studies, we believe that further studies are needed for detailed understanding of c-Myb function in CRC, before the c-Myb-targeted therapy enters clinical trials.

Natural history, treatment, and long-term follow up of patients with multiple endocrine neoplasia type 2B: an international, multicentre, retrospective study.

BACKGROUND: Multiple endocrine neoplasia type 2B is a rare syndrome caused mainly by Met918Thr germline RET mutation, and characterised by medullary thyroid carcinoma, phaeochromocytoma, and extra-endocrine features. Data are scarce on the natural history of multiple endocrine neoplasia type 2B. We aimed to advance understanding of the phenotype and natural history of multiple endocrine neoplasia type 2B, to increase awareness and improve detection. METHODS: This study was a retrospective, multicentre, international study in patients carrying the Met918Thr RET variant with no age restrictions. The study was done with registry data from 48 centres globally. Data from patients followed-up from 1970 to 2016 were retrieved from May 1, 2016, to May 31, 2018. Our primary objectives were to determine overall survival, and medullary thyroid carcinoma-specific survival based on whether the patient had undergone early thyroidectomy before the age of 1 year. We also assessed remission of medullary thyroid carcinoma, incidence and treatment of phaeochromocytoma, and the penetrance of extra-endocrine features. FINDINGS: 345 patients were included, of whom 338 (98%) had a thyroidectomy. 71 patients (21%) of the total cohort died at a median age of 25 years (range <1-59). Thyroidectomy was done before the age of 1 year in 20 patients, which led to long-term remission (ie, undetectable calcitonin level) in 15 (83%) of 18 individuals (2 patients died of causes unrelated to medullary thyroid carcinoma). Medullary thyroid carcinoma-specific survival curves did not show any significant difference between patients who had thyroidectomy before or after 1 year (comparison of survival curves by log-rank test: p=0·2; hazard ratio 0·35; 95% CI 0.07-1.74). However, there was a significant difference in remission status between patients who underwent thyroidectomy before and after the age of 1 year (p<0·0001). There was a significant difference in remission status between patients who underwent thyroidectomy before and after the age of 1 year (p<0·0001). In the other 318 patients who underwent thyroidectomy after 1 year of age, biochemical and structural remission was obtained in 47 (15%) of 318 individuals. Bilateral phaeochromocytoma was diagnosed in 156 (50%) of 313 patients by 28 years of age. Adrenal-sparing surgery was done in 31 patients: three (10%) of 31 patients had long-term recurrence, while normal adrenal function was obtained in 16 (62%) patients. All patients with available data (n=287) had at least one extra-endocrine feature, including 106 (56%) of 190 patients showing marfanoid body habitus, mucosal neuromas, and gastrointestinal signs. INTERPRETATION: Thyroidectomy done at no later than 1 year of age is associated with a high probability of cure. The reality is that the majority of children with the syndrome will be diagnosed after this recommended age. Adrenal-sparing surgery is feasible in multiple endocrine neoplasia type 2B and affords a good chance for normal adrenal function. To improve the prognosis of such patients, it is imperative that every health-care provider be aware of the extra-endocrine signs and the natural history of this rare syndrome. The implications of this research include increasing awareness of the extra-endocrine symptoms and also recommendations for thyroidectomy before the age of 1 year. FUNDING: None.

Neovascularization after ischemic conditioning of the stomach and the influence of follow-up neoadjuvant chemotherapy thereon.

INTRODUCTION: Esophagectomy and reconstruction remain the optimal treatment for patients with resectable esophageal cancer. Neovascularization after ischemic conditioning of the stomach before esophagectomy is a laparoscopic procedure which may potentially reduce gastric conduit ischemia. AIM: To investigate the influence of ischemic conditioning on neovascularization along the greater curvature of the stomach and to explore the effect of neoadjuvant chemotherapy on neovascularization after ischemic conditioning. MATERIAL AND METHODS: Staging laparoscopy was performed before the main resection procedure; during this procedure ischemic conditioning was performed. Samples taken from the human stomach were divided into 3 groups: group A - patients after ischemic conditioning with a delay of 30-45 days after left gastric artery (LGA) ligation (n = 4); group B - patients who were undergoing neoadjuvant chemotherapy with a delay of 90-140 days after left gastric artery ligation (n = 4); and control group C - patients without ischemic conditioning (n = 7). RESULTS: After ischemic conditioning with a delay of 30-45 days, the count of neovessels along the greater curvature of the stomach increased from 5.4 ±0.7 in the control group to 17.5 ±0.9 in a low-power field of view (LPF) in group A and increased still further on average to 19.8 ±10.4 in group B. CONCLUSIONS: Left gastric artery ligation only is a sufficient procedure for ischemic conditioning of the stomach. Neovascularization along the greater curvature is a continuous process that depends on delay time. Neoadjuvant therapy has no influence on the effect of neovascularization.

[Thyroid carcinomas: the present view on diagnostics and therapy]. / Karcinomy stítné zlázy: soucasný pohled na diagnostiku a lécbu.

Thyroid carcinoma (TC) represents 1-2 % of all human tumors, and is the seventh most common tumor. Women are in large majority among new patients. For women, this is the fifth most common tumor. In the Czech Republic, 1 143 new cases of TC were diagnosed in 2015. It is the tumor with the highest increase in incidence. Among newly diagnosed tumors, most of those are differentiated thyroid gland carcinomas (DTCs) originating from follicular thyroid cells. These tumors are follicular and papillary carcinomas and Hurthle carcinoma, accounting for 95 % of new cases. Due to the great progress in treatment, the prognosis is most commonly good for these tumors. Treatment is more difficult for other types of tumors. Anaplastic thyroid cancer (representing less than 1 % of thyroid tumors) is a rare form of thyroid cancer that is very malignant. Also found in the thyroid gland is Euro-C-cell tumor, which originates in C cells. This is the so-called medullary thyroid carcinoma, which is less common (5 % of all thyroid carcinomas). It emerges from the parapolyclic neuroendocrine cells of the thyroid gland. This tumor often metastasizes to the cervical lymph nodes, and frequently occurs in distant bone, liver and lung metastases. In 2015, in this publication we published an article: Thyroid gland carcinomas, current therapeutic procedures. This article was devoted to the diagnosis of thyroid carcinoma and individual treatment procedures. In this article, we look at differentiated thyroid carcinomas (DTCs), especially current opinions on the treatment of low-risk carcinomas.Key words: differentiated thyroid cancer - radioidine - targeted therapy.

[Thyroid cancer in children and adolescents and its molecular genetic background]. / Nádory stítné zlázy u detí a dospívajících a jejich molekulárne genetická podstata.

Thyroid cancer is the main endocrine malignancy. Its incidence is steadily growing and what is alarming is its increase in children and adolescent population. Pediatric thyroid carcinomas differ from the adult ones in phenotype as well as in genetics. These carcinomas tend to be clinically more aggressive, with more frequent local and distant metastases. However, their long-term prognosis is better in comparison with the adult thyroid cancers. Due to the rarity of the disease, there is lack of data on genetic changes in this age group. Knowledge on the genetic background of thyroid cancer in children will help to precise diagnosis and prognosis of the disease and to personalized treatment.Key words: adolescents - carcinoma - gene - genetics - children - mutation - next generation sequencing - thyroid.

[Thyroid carcinomas - current therapeutic procedures]. / Karcinomy stítné zlázy - soucasné lécebné postupy.

Incidence of differentiated thyroid carcinomas, especially papillary carcinomas, in recent decades worldwide increase. This is especially the detection of small tumor sizes up to two centimeters. Causes of the increase of these cancers are either increased number of thyroid investigations, but also the actual increase of this disease. The subject of expert discussion on this topic is mainly assessment of the severity of newly diagnosed tumors, the choice of treatment strategy and choice of follow-up of patients. Given that a large part of tumor detected in an early stage and due to the success of the current treatment options for the prognosis of thyroid cancer is usually good. Despite the large increase of the incidence, mortality for this type of cancer, in countries with good individualized treatment, decreases. We present a review of literature on the topic.Key words: thyroid carcinoma - post-operation monitoring - radioiodine - stratification of the risk of relapse.

Polymorphisms in selected DNA repair genes and cell cycle regulating genes involved in the risk of papillary thyroid carcinoma.

BACKGROUND: Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer. In addition to causal somatic mutations in the BRAF gene and RET/PTC rearrangements, the contribution of single nucleotide polymorphisms (SNPs) in low-penetrance genes in the development of PTC has been proposed. METHODS: Four SNPs in the XRCC1 (Arg399Gln, Arg280His, Arg194Trp and T-77C) and one SNP from each of three other genes participating in DNA repair pathways and/or cell cycle regulation (ATM Asp1853Asn, TP53 Arg72Pro, CDKN1B Val109Gly) were selected. The allelic and genotypic distributions of these variants as well as haplotypes of the XRCC1 were examined in 583 individuals comprising well-characterized cohorts of 209 PTC patients and 374 healthy volunteers. Correlations of polymorphism with clinical-pathological data and mutation status were performed. RESULTS: XRCC1 T-77C polymorphism affects the genetic susceptibility for PTC development in men, the specific combination of XRCC1 haplotypes correlates with RET/PTC incidence, CDKN1B Val109Gly significantly influences the risk of developing PTC regardless of gender and in PTC cases, selected genotypes of TP53 Arg72Pro and ATM Asp1853Asn were significantly associated with monitored tumour characteristics. CONCLUSION: It seems that SNPs in studied regulating genes contribute to the development of PTC and modify the tumour behaviour or characteristics.