Clinical and molecular genetic analysis of cytologically uncertain thyroid nodules in patients with thyroid disease.

BACKGROUND: The current requirement is to establish the preoperative diagnosis accurately as possible and to achieve an adequate extent of surgery. The aim of this study was to define the preoperative clinical and molecular genetic risks of malignancy in indeterminate thyroid nodules (Bethesda III and IV) and to determine their impact on the surgical strategy. METHODS: Prospectively retrospective analysis of 287 patients provided the basis of preoperative laboratory examination, sonographic stratification of malignancy risks and cytological findings. Molecular tests focused on pathogenic variants of genes associated with thyroid oncogenesis in cytologically indeterminate nodules (Bethesda III and IV). The evaluation included clinical risk factors: positive family history, radiation exposure and growth in size and/or number of nodules. RESULTS: Preoperative FNAB detected 52 cytologically indeterminate nodules (28.7%) out of 181 patients. Postoperative histopathological examination revealed malignancy in 12 cases (23.7%) and there was no significant difference between Bethesda III and IV categories (P=0.517). Clinical risk factors for malignancy were found in 32 patients (61.5%) and the presence of at least one of them resulted in a clearly higher incidence of malignancy than their absence (31.3% vs. 10.0%, respectively). Pathogenic variants of genes were detected in 12/49 patients in Bethesda III and IV, and in 4 cases (33.3%) thyroid carcinoma was revealed. The rate of malignancies was substantially higher in patients with pathogenic variants than in those without (33.3% vs. 16.2%, respectively). CONCLUSIONS: Our experience implies that molecular genetic testing is one of several decision factors. We will continue to monitor and enlarge our patient cohort to obtain long-term follow-up data.

Total thyroidectomy can still remain the method of choice in some Bethesda III cases.

BACKGROUND: The latest WHO classification of tumours of endocrine organs defines new units of borderline thyroid tumours (BTT). The aim of our study was to evaluate ultrasonographic and cytological features, mutation profile and surgery treatment in rare thyroid tumours. METHODS: An analysis of 8 BTT out of 487 patients, who underwent thyroid surgery between June 2016 and June 2020. The definitive diagnosis was made postoperatively by extensive histopathological examination. Molecular genetic analysis of genes associated with thyroid oncology (BRAF, HRAS, KRAS, NRAS, TERT, TP53, fused genes) were performed from one FNAB, and 7 formalin-fixed paraffin-embedded (FFPE) samples. RESULTS: BTT were found in a total of 8 patients (1.6%), with a predominance of men with respect to other operated patients. FNAB samples were classified in the Bethesda system as Bethesda I, Bethesda II and Bethesda III in one, four and three cases, respectively. Hemithyroidectomy and total thyroidectomy were performed equally in four patients. The histopathological diagnosis revealed non-invasive encapsulated follicular neoplasm with papillary-like nuclear features (NIFTP) in three patients, follicular tumour of uncertain malignant potential (FT-UMP) in three patients, well differentiated tumour of uncertain malignant potential (WDT-UMP) in one patient, and hyalinizing trabecular tumour (HTT) in one case. In NIFTP cases mutation in HRAS gene in one patient together with probable pathogenic variant in TP53 gene and in NRAS gene in two patients were detected. In HTT patient PAX8/GLIS3 fusion gene was detected. CONCLUSION: The surgical treatment of BTT is necessarily individual influenced by preoperative clinical, ultrasonographic, cytological and molecular genetic findings, and the presence of other comorbidities.

Positive Antithyroid Antibodies and Nonsuppressed TSH Are Associated with Thyroid Cancer: A Retrospective Cross-Sectional Study.

The relationship between Hashimoto's thyroiditis (HT) and thyroid cancer (TC) is a controversial topic; it remains unclear if HT acts as a risk factor of TC. The aim of our study was to compare the presence of HT and thyroid function in patients with TC and benign nodules. We analyzed 2571 patients after fine needle aspiration biopsy of thyroid nodule. Totally, 91 patients with primary TC and 182 sex- and age-matched controls were included. Positive antithyroid peroxidase (anti-TPO) and antithyroglobulin (anti-Tg) antibodies were associated with TC (anti-TPO 44% in TC vs. 27% in controls, P = 0.005, anti-TG 35% in TC group vs. 21% in controls, P = 0.018), and the TC group had significantly higher TSH (median 1.88 mIU/l vs. 1.21 mIU/l, P < 0.001). Using multiple logistic regression, positive anti-TPO was identified as an independent risk factor (OR 2.21, P = 0.018), while spontaneously suppressed TSH < 0.5 mIU/l was a protective factor (OR 0.3, P = 0.01) against TC. In conclusion, nodules in subjects with positive antithyroid antibodies could be considered to have a higher risk of malignancy. However, based on our results, it is not possible to declare that TC is triggered by HT.

[Draft of the best medical treatment in patients with low-risk thyroid cancer]. / Návrh optimálního lécebného postupu v lécbe nízkorizikového karcinomu stítné zlázy.

INTRODUCTION: The incidence of well-differentiated low-risk thyroid cancer have increased globally over the last three decades. Thyroid cancer treatment relates to a suitable surgical procedure and the use of adjuvant radio-iodine therapy in selected patients. Evaluation of prognostic factors and risk stratification are critical for determining appropriate treatment. Survival of patients with low-risk thyroid cancer is excellent. Appropriate choice of medical treatment resulted in full recovery in most patients. Relapse risk increases with the size of the primary tumor, along with the findings of the risk factors in men. METHODS AND RESULTS: Our study included a total of 1 980 patients in whom were diagnosed T1a and T1b tumors between the years 2003 to 2012. The population included 1 675 women (84.6 %) of average age of 45.22 years and 305 men (15.4 %) of average age of 50.0 years. The bulk of the file represented papillary carcinomas (1 868; 94.4 %), and smaller group of follicular carcinomas (112; 5.6 %). Patients were divided into four groups according to tumor size. Patients were evaluated according to risk factors: unifocality no other risk factors, multifocality - more bearings in thyroid tumor, metastases in regional lymph nodes, distant metastases or combination of risk factors. Group A: In the monitored set of 678 patients with papillary and follicular microcarcinoma up to 5 mm, during histological input, the findings revealed one bearing (unifocal type of cancer) in 566 patients. Multifocality was found in 112 patients, local nodal metastasis were demonstrated in 24 cases and pulmonary metastasis was discove-red in 1 case. Group B: In this group there were 576 study patients with papillary and follicular microcarcinoma size of 5-10 mm. Histological findings were captured input one bearing carcinoma in 434 patients, 142 patients with multifocality, in 53 cases of local nodal metastasis, and 1 case of bone metastases. Group C: In this group there were 467 study patients with papillary and follicular microcarcinoma size 10-15 mm. The histological initial finding captured unifocal type of cancer in 344 patients, multifocality in 123 patients, in 45 cases local metastases and in 3 cases of pulmonary metastases. Group D: 259 patients were monitored in this group with breast size 16-20 mm. At the initial finding was captured one bearing cancer in 188 patients, multifocality in 71 patients, in 24 cases evidence of local metastases and 2 patients had a case of distant lung metastases. In patients in whom risk factors were found, radioiodine treatment was indicated. This included 744 patients. In this group of patients after a year or more, relapse was observed in 74 patients (9.94 %). In 1 236 patients who did not undergo radioiodine treatment, there was a relapse in 49 patients (3.96 %). CONCLUSION: Based on our analysis, it is necessary to stratify the risk of relapse according to risk factors. In case of missed radioiodine therapy in patients with low-risk cancer without confirmed risk factors, it is also necessary to have regular clinical, laboratory and ultrasound examination. It is important to distinguish patients with risk factors that may contribute to disease recurrence. Only in this way, on one hand we prevent excessive treatment of patients with low-risk thyroid cancer which leads to increased cost of health care, and on the other hand prevent reduced level of care for patients with an increase in relapses.

Secondary or second primary malignancy in the thyroid? metastatic tumors suggested clinically: a differential diagnostic task.

OBJECTIVE: To describe the algorithms employed to explore the suggestion or consideration of metastatic malignancy in the thyroid. STUDY DESIGN: Thirty-seven cases with a history of malignancy (n = 21) and/or uncommon fine-needle aspiration biopsy (FNAB) findings (n = 37) were reviewed and reclassified according to The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC). RESULTS: The group was heterogeneous in terms of the final histopathology results: the suggested metastasis was confirmed in only half of the cases (11/21; 52.4%). Primary thyroid malignancies were mostly nondifferentiated, medullary, or rare. However, 3 papillary carcinomas (the less common variants) were also found. Finally, 5 out of 37 cases were surprisingly benign upon histopathological investigation (uncommon repair and fibrotizing Hashimoto thyroiditis). CONCLUSIONS: The metastatic nature of thyroid gland nodule(s) must be considered in cases of generalization of malignancy and/or uncommon FNAB findings. We must be as open-minded as possible from the outset. Additional techniques are helpful if available - cytoblock and immunocytochemistry can contribute substantially. Morphological comparisons with the previous malignancy are recommended whenever possible. To avoid overtreatment, cases without precise typing should not be classified as TBSRTC diagnostic category VI - malignant, but should remain in TBSRTC diagnostic category V - suspicious for malignancy. Repeated FNAB to enable additional techniques may be suggested.

Mild iodine deficiency in women after spontaneous abortions living in an iodine-sufficient area of Czech Republic: prevalence and impact on reproductive health.

OBJECTIVE: Iodine deficiency is associated with thyroid dysfunction and adverse pregnancy outcomes. The aim of our study was to investigate the status of iodine saturation in women after spontaneous abortion (SpA) residing in an iodine-sufficient area and to evaluate their subsequent reproductive health. DESIGN: Nonrandomized prospective follow-up study. PATIENTS AND METHODS: We compared urinary iodine concentration (UIC) in 171 women 2-8 weeks (median 4) after an early SpA with age-matched controls. Women with known thyroid diseases were excluded. We also analysed a relationship of UIC to serum thyroid-stimulating hormone, free thyroxine, antibodies against thyroid peroxidase and thyroid ultrasound. Afterwards, we followed the women for a median of 38 months (range 12-47). We used a multivariate regression analysis to assess the influence of iodine status and other thyroid biochemical and ultrasound parameters on their subsequent reproductive health. RESULTS: Women after SpA were almost twice as likely to suffer from mild iodine deficiency and had lower median UIC as compared to age-matched controls [rate 105/181 (58·0%) vs 57/181 (31·5%), P < 0·001, medians UIC 92·00 vs 117·80 mcg/l, P < 0·001]. UIC was not influenced by the use of iodine supplements in the previous pregnancy. We did not find any association neither between UIC and thyroid dysfunction and/or thyroid antibodies, nor between UIC and rates of subsequent successful pregnancies or obstetric complications. CONCLUSIONS: More than half of women after SpA residing in an iodine-sufficient area are suffering from mild iodine deficiency. However, it does not seem to have a negative impact on their subsequent reproductive health.

The epidemiology of thyroid cancer in the Czech Republic in comparison with other countries.

BACKGROUND: Thyroid cancer includes a broad spectrum of tumours with different prognoses. The global incidence has been increasing in recent years. Variables affecting its etiology are dietary, especially iodine intake and to a lesser extent selenium, environmental, like - ionizing radiation and, increased TSH level. These factors interplay with epigenetic and genetic changes within the cell. This review article presents thyroid cancer epidemiology, describes its main characteristics and the influence of environmental and lifestyle risk factors in the Czech Republic in comparison with other countries. METHODS AND RESULTS: An epidemiological study of Czech patients with malignant thyroid carcinoma was made on the basis of the National Oncologic Registry (NOR) and Czech Statistical Office data summarized on the web portal SVOD. The data were compared with international data from the project GLOBOCAN 2008 Cancer Incidence and Mortality Worldwide. Apart from risk factors, prognostic factors with effect on patient survival were also analyzed. The survey showed that the incidence of thyroid cancer has been steadily growing in the Czech Republic. Since the beginning of the 1980s, it has increased 4 fold. It has a higher incidence than most other European countries but it is ranked with countries with an average and decreasing mortality. Obviously, the improved detection methods do not explain the growing incidence. The highest incidence is found for papillary carcinoma (PTC), now over 80% of cases. For follicular and medullar cancers, the incidence has not increased and for anaplastic carcinoma there is a slight decrease. Women over 40 years of age constitute the highest risk group. CONCLUSIONS: There are a number of reasons for these trends, such as improved diagnostic techniques using ultrasound and FNAB and more radical surgery. There are also dietary/environmental factors (iodine deficiency and to a lesser extent selenium), nitrates, polychlorinated biphenyls, increased ionizing radiation, and prolonged increase in TSH. The prognosis of patients with DTC depends on the age at the time of diagnosis. A favorable prognosis also depends on timely detection.

Laryngotracheal stenosis in critically ill patients.

CONCLUSIONS: Prolonged artificial pulmonary ventilation by tracheostomy tube (>30 days) doubled the risk of stenosis (relative risk, RR = 2.04, p = 0.002). Critically ill patients with repeated tracheotomies were more than six times likely to experience stenosis (RR = 6.44, p< 0.001) than other critically ill patients. OBJECTIVE: In this retrospective study, we describe the occurrence of laryngotracheal stenosis (LTS) in critically ill patients after elective tracheostomy who had undergone treatment for LTS at the Na Homolce Hospital in Prague, Czech Republic. METHODS: We studied 28 patients who were diagnosed with symptomatic LTS. Basic major demographic data, duration of mechanical ventilation, onset of tracheal stenosis after decannulation, and tracheostomy type (percutaneous dilatational or surgical tracheostomy) were recorded. The number of patients requiring repeated tracheostomies was also recorded. RESULTS: Neither the demographic data nor the type of tracheostomy represented statistically significant risk factors. The risk factors for LTS were prolonged artificial pulmonary ventilation using the tracheostomy tube (p = 0.005) and repeated tracheostomy (p< 0.001). The mean onset of stenosis symptoms was 53.7 days (range 2-300 days), with a median of 58 days. Stenosis involved the trachea in 20 patients, subglottis in five cases, and glottis and subglottis in three cases. Seven patients (25%) underwent a tracheal resection and primary end-to-end reconstruction. One patient underwent laryngotracheoplasty with dilatation. The procedure was endoscopic in 18 patients (64.3%). Two patients (7.1%) received permanent tracheostomies.

Therapy of the osteoarthritis of the temporomandibular joint.

Osteoarthritis is a common condition of the mandible. The treatment of osteoarthritis primarily consists of rest therapy (restricting jaw movements), the use of pharmaceuticals (analgesics, antiinflammatories), splint therapy, thermotherapy or mini-invasive therapy. Our study investigated the effectiveness of the various therapeutic options in the treatment of osteoarthritis. We compared the effectiveness of rest therapy (restricting mouth opening, analgesic therapy), splints, arthrocentesis of the upper joint space, and arthrocentesis in combination with splint therapy. We looked at 80 patients diagnosed with osteoarthritis of the temporomandibular joint. We only included patients with symptoms in one temporomandibular joint (TMJ). This 3 months long-term study shows that arthrocentesis combined with the use of a splint is an effective first-stage treatment method for patients with osteoarthritis of the TMJ (80% patients with good outcome 3 months after commencement of therapy).

[The occurrence of microcarcinomas in the patients after thyroidectomy--retrospective analysis]. / Výskyt mikrokarcinomu stítné zlázy u operovaných pacientu--retrospektivní analýza.

BACKGROUND: Microcarcinomas, minimum carcinomas, are tumours, which are in clinical practice defined as tumours < or = 1 cm in size. WHO defines thyroid microcarcinomas as tumours < or = 2 cm in size, which have different biological behaviour. The aim of the study was to analyze the occurrence of MC in post-operative patients. METHODS: Using retrospective analysis we evaluated the occurrence of thyroid microcarcinoma in post-operative patients. Except for basic demographic data, carcinoma size and histological variance, the occurrence of bilateral impairment, presence of multi-focuses and occurrence of regional throat metastases were considerd. RESULTS: From 2004 to 2008 thyroid surgeries were performed in 400 patients. Microcarcinoma was diagnosed in 34 patients (8.5%), 5 men and 29 women. The average age of patients with microcarcinoma was 52 years, similarly to other patients undergoing surgery. Histologically, 32 cases (94%) were papillary carcinoma, from which 4 cases were papillary follicular and 2 were follicular carcinomas. There were multifocal findings of microcarcinomas in 5 patients (15%), and 4 patients (12%) had bilateral involvement. The average size of the tumours was 5 mm, sd 2.6. Two patients (6%) had metastases in the lymph nodes of the neck. Total thyroidectomies were carried out in 32 patients (94%) and hemithyroidectomies in 2 patients (6%). Five patients (15%), i. e. both patients with metastases in the lymph nodes of the neck and three patients with bilateral multifocal carcinomas underwent postoperative adjuvant radioiodine 131I ablation therapy. CONCLUSIONS: Due to the possibility of the future growth, metastasizing andreoccurrence, microcarcinomas cannot be considered harmless or almost insignificant findings. The increased risk of the MC occurrence was found in chronic lymphoplasmocellular thyroiditis (17%).

Standard surgical versus percutaneous dilatational tracheostomy in intensive care patients.

OBJECTIVE: The present prospective randomized trial compared surgical tracheostomy (ST) and percutaneous dilatational tracheostomy (PDT) in intensive care unit (ICU) patients in terms of outcomes and complications. METHODS: Between January 2003 and December 2005 tracheostomies were performed on critically ill ICU patients in Medical Faculty Hospital in Prague, with a random allocation of 105 patients for ST and 100 for PDT. RESULTS: The 2 groups did not differ significantly in terms of basic demographic characteristics or length of endotracheal intubation prior to the procedure. Following the procedures, the 2 groups did not differ significantly in terms of the time required for decannulation, decannulated patients or mortalities. Post-mortem examination showed that both groups were similar in terms of placement of the tracheostomy tube. Surgical tracheostomy was found to take longer time to perform than PDT (p<0.001). In terms of early postoperative complications, PDT was associated with a higher rate of postoperative bleeding compared to ST (p=0.0302). CONCLUSION: Percutaneous dilatational tracheostomy is a simpler and faster technique to perform, but is associated with a higher occurrence of early complications, particularly postoperative bleeding.