Neuromonitoring of recurrent laryngeal nerves in thyroid surgery comparative study of visualisation and electrophysiology methods.

Úvod: Poranění zvratného nervu je jedna z nejzávažnějších komplikací chirurgie štítné žlázy, chirurgie příštítných tělísek a chirurgie krčních obratlů. V literatuře se popisuje poranění zevní větve hrtanových nervů jako méně časté. Tato komplikace je natolik vážná, že může vést k invalidizaci hlasových profesionálů (učitelů, herců, zpěváků, profesionálních řečníků a manažerů). Současná klinická praxe je spojena se zvýšeným úsilím o peroperační ochranu funkce zvratných nervů využíváním elektrofyziologické monitorace funkce inervace hrtanu a současné vizualizace zvratných nervů. Metody: Design studie je prospektivní observační. Ze souboru 100 po sobě jdoucích operací byly chirurgy náhodně vytvořeny dvě skupiny: Skupina A - s použitím neuromonitoringu (IONM) a skupina B - identifikace a vizualizace zvratného nervu (NLR) bez IONM. Jeden tým chirurgů byl složen z experta (více než 1000 provedených operací) a začínajícího chirurga (méně než 100 operací) a druhý ze dvou zkušených chirurgů (jeden více než 150 operací a druhý více než 500 operací). Každý tým byl zapojen do operací několikrát v týdnu. Porovnání bylo provedeno statistickými metodami a pomocí indexu poranění zvratného nervu (recurrent nerve injury - IRI). Cílem studie je porovnat incidenci parézy zvratných nervů při využití neuromonitorace (IONM) a využití peroperační vizualizace anatomicky neporaněného nervu dvěma týmy chirurgů. Výsledky: Bylo analyzováno 100 operací, respektive 50 operací ve skupině A a 50 ve skupině B. Skupina A zahrnovala 43 totálních thyreoidektomií a 7 hemithyreoidektomií a byly zjištěny dvě dočasné jednostranné parézy. Skupina A měla IRI=1,075. Skupina B zahrnovala 48 totálních thyreoidektomií a 2 hemithyreoidektomie. V této skupině byly zjištěna také dvě jednostranné dočasné parézy zvratného nervu. Skupina B měla IRI=1,02. Uvedené hodnoty IRI tak charakterizují asymetrické soubory, i tato drobná asymetrie je ve výsledku hodnoty patrna. Celková incidence poranění zvratných nervů v celém souboru operovaných sledovaného roku, ve kterém byl výběr pacientů dle metodiky této práce, byla 1,3 %. V souboru bylo 16 dočasných a 4 permanentní parézy zvratného nervu ve všech případech na jedné straně. Ve sledovaném období nebyla zjištěna ani jediná oboustranná paréza trvalá ani dočasná. Index IRI pro operace štítné žlázy v uvedeném období byl 2,26. Tento soubor byl srovnáván se soubory skupiny A a skupiny B a výsledky nevykazují statisticky významné rozdíly na hladině významnosti 1 % (p=0,01). Závěr: Studie neprokázala statisticky významné rozdíly incidence poranění zvratného nervu (trvalá jednostranná paréza) v závislosti na chirurgické technice bez využití IONM a s využitím IONM prováděných chirurgem s rozdílnou zkušeností v chirurgii štítné žlázy. Studie prokázala, že IONM může pomoci vyrovnat handicap u začínajících a méně zkušených chirurgů a omezit incidenci morbidity zvratného nervu v chirurgii štítné žlázy.

Morbidity and mortality associated with thyroid surgery - retrospective analysis 19912010.

INTRODUCTION: The incidence of thyroid disorders has been rising worldwide. Unlike the incidence, mortality associated with malignant thyroid cancer shows only a modest increase. Between 1979 and 2009, mortality in Czech women increased from 1.21 to 1.31 and in Czech men from 0.54 to 0.74 cases per 100,000 individuals.  Methods: A retrospective statistical analysis was performed in patients undergoing thyroid surgery at the Department of Otorhinolaryngology and Head and Neck Surgery of the 1st Faculty of Medicine, Charles University and University Hospital Motol, and at the Department of Otorhinolaryngology of the Institute for Postgraduate Medical Education in Prague from 1991 to 2010 (twenty years). In this period, 11,005 procedures were done for thyroid disease. The study analysed the incidence, morbidity, mortality, surgical complications and lethality. RESULTS: The study group included surgeries in 1588 male and 9417 female patients. The male/female ratio was 1:5.93. Benign thyroid tumours - mean patient age is 54.7 years; recurrent nerve morbidity is 1.37% (calculated from exposed nerves). Hypocalcaemia incidence is low, 5.4% of permanent hypocalcaemia or hypoparathyroidism, respectively, based on decreased serum parathyroid hormone (PTH) levels. Temporary hypocalcaemia is much more frequent, occurring in almost 15% cases depending on age, season of the year, and nutritional status. Hypoparathyroidism was demonstrated based on laboratory serum PTH levels only in 0.3% patients. In total, 442 patients were operated for the mechanic syndrome (a large goitre). The mean thyroid volume was 493 ml±136 ml; however, the maximum volume was 980 ml and weight 1115 g. The incidence of recurrent nerve injury occurs in 4.5%, i.e. the morbidity is 2 times higher compared to surgeries for other diagnoses. The incidence of hypoparathyroidism is not higher compared to other surgeries. Revision surgeries were indicated more commonly in malignant thyroid diseases, particularly in papillary and follicular carcinomas. Cervical lymph nodes procedures comprise another large segment in tumour treatment. Our analysis supports selective neck dissections while preserving non-lymphatic structures. As a rule, mortality associated with thyroid surgery is divided as mortality in the perioperative period (within 24 hours after the procedure) and early postoperative mortality (within 120 hours after the procedure). Surgery-related mortality was never classified as perioperative or within 24 hours after the procedure. Despite that, we believe that perioperative mortality within 120 hours after the procedure, which occurred in 7 cases, is very important. Mortality of the group was 0.007%. CONCLUSIONS: Each surgery procedure is associated with complications, morbidity and mortality. Experience of endocrine surgeons of all disciplines leads to a very low incidence of recurrent nerve and parathyroid gland injuries while at the same time achieving sufficient radicality. This, in cooperation with other medical fields such as endocrinologists, nuclear medicine specialists and oncologists, supports a safe and effective management of all thyroid disorders, including a good prognosis of patients with most types of cancer. Key word: thyroid surgery - complications recurrent nerve - hypoparathyroidism lethality.

Morbidity and mortality of parathyroid surgery - a retrospective analysis.

INTRODUCTION: The incidence of parathyroid - glandula parathyreoideae (PTG) diseases has been increasing worldwide. Unlike benign tumours, the incidence of malignant PTG tumours is rather a rare diagnosis. The morbidity of parathyroid surgery is associated with surgical removal of one or more pathologically altered parathyroid glands, particularly parathyroid adenoma associated with primary hyperparathyroidism (HPPT), but also hyperplasia associated with secondary or tertiary HPPT, and last but not least, HPPT due to parathyroid cancer. METHODS: A retrospective statistical analysis was performed in the set of patients undergoing surgery for a parathyroid disorder at the Department of Otorhinolaryngology and Maxillofacial Surgery, 3rd Faculty of Medicine, Charles University and Military University Hospital in Prague in 2013-2019 (7-year period). In this period, 127 procedures were performed. The incidences of morbidity, mortality, complications and lethality were analysed. RESULTS: Parathyroid surgery was performed in 20 male and 107 female patients. The mean age was 54.7 years, and the morbidity expressing recurrent laryngeal nerve (RLN) palsy was 0.7% of the nerves exposed during the procedure. The incidence of permanent normal postoperative calcaemia was 98.43%, demonstrated by a decrease in serum parathyroid hormone (PTH) levels. In 12 cases, this state was achieved only after a surgical revision (primary procedure for primary HPPT in 2 cases; 10 patients came for surgical revision with secondary or tertiary HPPT from other centres). Decreased PTH levels were demonstrated intraoperatively in 12.6% patients using the so-called PTH assay (a rapid serum PTH assay). Surgery for secondary or tertiary hyperparathyroidism was done in 33 patients (26% procedures). PTG surgery lethality (mortality) was divided into perioperative mortality within 24 hours from the procedure and early mortality within 120 hours. Lethality related to PTG surgery was 0.0% including patients undergoing the surgery while being in a dialysis programme and those with kidney transplant. CONCLUSIONS: Surgery is always associated with complications, with morbidity and mortality. Experience of endocrinology surgeons of all specialties is reflected in a very low incidence of RLN injuries and in sufficient oncological, or respectively, surgical radicality. This, in connection with other medical fields of endocrinology, nephrology, transplantology, nuclear medicine and oncology, allows a safe and effective treatment of all PTG disorders with a good prognosis for the patients. In those with secondary or tertiary HPPT, it not only improves their quality of life, which was not explored in our study, but in many cases it is an essential step for listing the patient for the transplant surgery. The current level of experience in the field of parathyroid carcinoma does not enable us to formulate any conclusions in terms of prognosis which should be considered as very serious in all cases.

Nonfunctional parathyroid cancer a case report.

INTRODUCTION: Parathyroid cancer is a rare endocrine malignancy. These tumors are typically functional, causing severe hypercalcemia due to primary hyperparathyroidism. Nonfunctional parathyroid cancer with normal serum calcium and parathyroid hormone levels is extremely rare. The disease is usually indolent but progressive with a tendency to metastasize. It is very difficult to diagnose this malignancy. The definitive diagnosis is made by histopathological examination. Radical surgery with ipsilateral lobectomy and en bloc neck dissection is considered to be the most appropriate therapeutic approach. There is no evidence of efficiency of adjuvant cancer therapy and its indication has not been defined. Disease recurrence is common. CASE REPORT: We report the case of a 26-year-old female patient who underwent left hemithyroidectomy for growth progression of a hypoechoic lesion behind the left thyroid lobe detected by ultrasonography. Preoperative cytology and imaging assessments were not suspicious for malignancy. Serum parathyroid hormone and calcium levels were normal. The diagnosis of nonfunctional parathyroid carcinoma was determined based on histopathological examination. No further surgery or adjuvant therapy was indicated. No signs of recurrence or generalization have been observed at 36 months after the surgery. CONCLUSION: Nonfunctional parathyroid cancer is extremely rare. In many cases, the diagnosis is made in advanced stages of the disease. No formal classification or treatment protocol has been established so far. A new staging system has been proposed in the 8th edition of AJCC/UICC. Early detection, radical surgery and close follow-up are crucial aspects to affect the mortality and morbidity of patients with this type of malignancy.

A systematic review on the genetic analysis of paragangliomas: primarily focused on head and neck paragangliomas.

Head and neck paragangliomas Paragangliomas and pheochromocytomas are rare, mostly benign neuroendocrine tumors, which are embryologically derived from neural crest cells of the autonomic nervous system. Paragangliomas are essentially the extra-adrenal counterparts of pheochromocytomas. As such this family of tumors can be subdivided into head and neck paragangliomas, pheochromocytomas and thoracic and abdominal extra-adrenal paragangliomas. Ten out of fifteen genes that contribute to the development of paragangliomas are more susceptible to the development of head and neck paragangliomas when mutated. Gene expression profiling revealed that pheochromocytomas and paragangliomas can be classified into two main clusters (C1 and C2) based on transcriptomes. These groups were defined according to their mutational status and as such strongly associated with specific tumorigenic pathways. The influence of the main genetic drivers on the somatic molecular phenotype was shown by DNA methylation and miRNA profiling. Certain subunits of succinate dehydrogenase (SDHx), von Hippel-Lindau (VHL) and transmembrane protein 127 (TMEM127) still have the highest impact on development of head and neck paragangliomas. The link between RAS proteins and the formation of pheochromocytoma and paragangliomas is clear due to the effect of receptor tyrosine-protein kinase (RET) and neurofibromatosis type 1 (NF1) in RAS signaling and recent discovery of the role of HRAS. The functions of MYC-associated factor X (MAX) and prolyl hydroxylase 2 (PHD2) mutations in the contribution to the pathogenesis of paragangliomas still remain unclear. Ongoing studies give us insight into the incidence of germline and somatic mutations, thus offering guidelines to early detection. Furthermore, these also show the risk of mistakenly assuming sporadic cases in the absence of definitive family history in head and neck paragangliomas.

[Current treatment strategies for papillary thyroid microcarcinoma]. / Aktuelle Behandlungskonzepte des papillären Schilddrüsenmikrokarzinoms.

The increase in the incidence of thyroid cancer is accompanied by a mortality rate that is stable or perhaps even slightly decreasing. This phenomenon is due to the increased frequency of papillary microcarcinomas (thyroid tumors with a diameter of less than 1 cm), which is presumably attributable to the improved diagnosis enabled by high resolution ultrasound and fine needle aspiration cytology. The American and European Thyroid Associations have recently published new guidelines for the diagnosis and therapy of differentiated thyroid tumors. These guidelines are aimed at minimizing the diagnostic and therapeutic procedures without reducing their effectiveness. This goal is particularly important for papillary thyroid microcarcinoma patients, who have an excellent prognosis and almost normal life expectancy. This article summarizes the history of thyroid surgery and introduces papillary thyroid microcarcinoma--an important topic in modern thyroid oncology. Current methods for diagnosis, treatment and follow-up care of this disease are discussed.

Comparison of Helicobacter pylori genotypes obtained from the oropharynx and stomach of the same individuals - a pilot study.

Helicobacter pylori has been recently detected in the oral cavity and oropharynx. However, the role it plays in oral and oropharyngeal pathogenesis remains unclear. The virulence of H. pylori strains can be distinguished according to the virulence factors genes carried. Our research has been focused on realtime PCR analysis of cagA and vacA genes of H. pylori strains in tonsils and tonsillar squamous cell cancer and their comparison with H. pylori strains obtained from the gastric mucosa of the same patients. Urea breath test (UBT) test was used to detect a gastric H. pylori infection in 20 patients with previously proven H. pylori in the oropharynx. Genotyping of H. pylori in gastric biopsies was performed in patients with positive gastric infection. Out of 20 patients positive for oropharyngeal H. pylori, 8 were positive for concurrent gastric H. pylori infection. In 6 of them gastric biopsies were obtained. Comparison of oropharyngeal and stomach H. pylori genotypes showed important differences. Four of 6 patients had different H. pylori strains in the oropharynx and stomach. The differences were found in cagA gene as well as in vacA gene. The finding of oral presence of H. pylori without concurrent stomach infection was confirmed using UBT. The results show that more than one H. pylori strain can be present in oropharynx and stomach in the same patient. The oropharyngeal infection seems to be independent to the gastric infection.

[PIMS-a new pediatric challenge]. / PIMS ­ eine neue pädiatrische Herausforderung: 9-Jahre alter Knabe mit SARS-CoV-2 assoziiertem hyperinflammatorischem Schocksyndrom.

The boy of Egyptian origin was previously healthy. After a history of fever for 7 days, abdominal pain, vomiting and dry cough resistant to treatment with oral antibiotics, he was admitted to hospital. The clinical examination showed a slightly red throat, a tense abdomen and erythema. The blood tests revealed leukocytosis and significantly increased inflammatory parameters. The abdominal ultrasound showed thickened intestinal loops in the left lower abdomen and the echocardiography showed minimal mitral regurgitation, a narrow pericardial effusion lamella over both ventricles and normal coronary arteries. Accordingly, cardiac enzymes were elevated. The day after admission, the boy developed an increasing rash and was transferred to the PICU because of septic shock refractory to high volume resuscitation, requiring hemodynamic support with noradrenaline and noninvasive respiratory assistance. The initial testing for SARS-CoV­2 on nasopharyngeal aspirates was negative twice; however, serum IgG antibodies were positive. Other viral and bacterial infections were excluded as the cause of the symptoms.The patient received IVIG, ASS, furosemide and methylprednisolone and the antibiotic treatment was continued. The dosage of the catecholamine could be reduced according to the patient's condition and the serially performed echocardiographic findings. The patient recovered in his general condition and was discharged from the PICU after 8 days. With the help of a detailed family history, we were able to figure out that the whole family, including the patient himself, had symptoms of a cold about 1 month earlier. Hence, SARS-CoV­2 antibody tests carried out showed a positive result for all of them.Pediatric inflammatory multisystem syndrome (PIMS) can quickly lead to manifest shock symptoms, necessitating close monitoring. A PICU background is crucial to treat possibly occurring symptoms and complications. High-dose steroids are used therapeutically alongside supportive therapies.

BRAFV600E mutation in the pathogenesis of a large series of papillary thyroid carcinoma in Czech Republic.

BACKGROUND: Activating point mutation of the BRAF gene, the most common genetic alteration reported in papillary thyroid carcinomas (PTC), has been associated with poor prognostic characteristics. AIM: Our objective was to determine the frequency of BRAFV600E mutation in PTC tumor tissues from the period 1960-2007 and to correlate it with clinicopathological parameters. SUBJECTS AND METHODS: DNAs were extracted from 242 PTCs, 23 sporadic medullary carcinomas, one anaplastic carcinoma and 6 poorly differentiated carcinomas. The presence of BRAFV600E mutation was determined using single strand conformation polymorphism method and verified by direct sequencing. RESULTS: BRAFV600E mutation was detected in 81 of 242 PTCs (33.5%), in one of 6 poorly differentiated carcinomas (16.7%) and in anaplastic carcinoma. BRAFV600E mutation was much less frequent in the follicular variant compared to classical variant and mixed follicular- classical variant of PTCs (p=0.001). BRAFV600E mutation was significantly associated with presence of nodal metastasis (p=0.029), more advanced TNM stage (p=0.014) and recurrence of disease (p=0.008). The mutation correlated with a higher age at diagnosis (p=0.049) and with a greater tumor size (p=0.041). Multivariate analysis confirmed these findings. The prevalence of BRAFV600E mutation before 1986 was significantly lower than after it (p=0.008). CONCLUSIONS: Our data suggest that BRAFV600E mutation is associated with high-risk clinicopathological characteristics of PTC and worse prognosis of patients. The frequency of the mutation significantly varied during the observed period but rather because of the different age distribution of patients in particular periods than as a consequence of Chernobyl accident.

Somatic mutations in the RET proto-oncogene in sporadic medullary thyroid carcinomas.

The frequency and prognostic relevance of RET proto-oncogene somatic mutations in sporadic medullary thyroid carcinoma (MTC) remain controversial. In order to study somatic mutations in the RET proto-oncogene in sporadic MTCs found in the Czech population and to correlate these mutations with clinical and pathological characteristics, we investigated 48 truly sporadic MTCs by sequencing classical risk exons 10, 11, 13, 14, 15 and 16. From the 48 tumors studied, 23 (48%) had somatic mutation in the RET proto-oncogene in exons 10, 11, 15 or 16. The classical somatic mutation Met918Thr in exon 16 was only found in 13 tumors (27%). In five cases, multiple somatic mutations and deletions were detected. A statistically significant correlation between the presence of somatic mutation with more advanced pathological TNM stages was observed. Other clinical and pathological characteristics did not show any statistical significant association with the presence or absence of somatic mutation.

Expression of endothelial and inducible nitric oxide synthase and caspase-3 in tonsillar cancer, chronic tonsillitis and healthy tonsils.

Neoangiogenesis and inhibition of apoptosis are two factors considered as major leading causes of tumorigenesis. NO, synthesized by NOS, plays an important role in tumour growth, dissemination and vascularization. Caspase-3 is an executive enzyme of apoptosis. The presented research work has been focused on the comparative evaluation of localization of the angiogenic and proapoptotic cytokines expressed in tonsillar diseases. The immunohistochemical reaction of eNOS, iNOS and caspase-3 in tonsillar cancer (N = 17), chronic tonsillitis (N = 11) and clinically healthy tonsils (N = 8) was detected. High eNOS occurrence in endothelial cells of highly vascularized regions in tonsillar cancer, variable eNOS expression in the vessels of lamina propria in chronic tonsillitis and high expression in the cytoplasm of endothelial cells of small veins in healthy tonsillar tissue was ascertained. Increased iNOS expression was found in cancer tissue in comparison with the healthy tonsils. Nevertheless, the highest expression of iNOS was found in chronic tonsillitis. Higher expression of caspase-3 was discovered in germinal centres of lymphoid follicles of the chronic tonsillitis tissue. However, the positivity in the interfollicular zone and surface squamous epithelium was weak only. Merely isolated caspase-3-positive cells were found in tonsillar cancer. Very low expression of caspase-3 was detected in the lymphatic follicles of the healthy tonsils. Research results showed high expression of eNOS in the carcinomatous tissue. The eNOS expression in chronic tonsillitis confirms its role in regulating the lymphocyte circulation. Low expression of caspase-3 in malignant epithelial cells of tonsillar cancer shows decreased capability of apoptosis compared to chronic tonsillitis tissue, where apoptosis seems to be rather frequent and concentrated in the germinal centres of lymphatic follicles. The differences in localization of eNOS and caspase-3 expression between benign and malignant processes may be a promising tool for precise morphological distinction of chronic inflammation and tumours.

Helicobacter pylori in tonsillar and adenoid tissue and its possible role in oropharyngeal carcinogenesis.

Helicobacter pylori is a well-known gastric pathogen. It plays a major role in the pathogenesis of chronic gastritis, duodenal and gastric ulcers, adenocarcinoma and gastric lymphoma. HP infection is one of the most common bacterial infections worldwide. Recently, the oral cavity was proposed as an extragastric reservoir of HP infection. HP was detected by culture and PCR in both dental plaque and saliva. It is supposed that HP infection can cause the same immunological changes in the oropharyngeal mucosa as in gastric mucosa and can also contribute to the progression of oropharyngeal diseases. HP can induce production of different cytokines and regulatory molecules, which are suggested to play a role in carcinogenesis of the oropharynx. Only a few studies have explored the presence of HP in tonsillar and adenoid tissue, where MALT is present similar to the gastric mucosa. The results of these studies were inconsistent. The question of persistence of HP in tonsillar and adenoid tissue and its role in the pathogenesis of oropharyngeal diseases still remains unclear. In this review, recent findings about oral HP are considered. Possibilities of diagnostics of HP in oral specimens are discussed.

Ectopic parathyroid adenoma in child.

A 10-year old girl presented with fatigue, hypercalcemia, and subperiosteal phalangeal osteolytic lesions. Ultrasonography and MIBI scintigraphy showed a structure near the lower pole of thyroid gland. The structure macroscopically appeared as adenoma, histologically it was thymic tissue. Bilateral neck exploration together with exploration of cervical thymic extensions was performed; adenoma was not found. During next two years, the level of calcium and parathormone raised, bone mineral density decreased. Ultrasonography, MRI, CT and PET/CT were negative. Adenoma was located by MIBI-SPECT/CT near the left border of jugulum. It was found dorsolateral to left common carotid artery and removed.

Helicobacter pylori isolated from patients with tonsillar cancer or tonsillitis chronica could be of different genotype compared to isolates from gastrointestinal tract.

Helicobacter pylori from patients with different diseases, including so-called autoimmune thyroiditis, chronic tonsillitis and tonsillar cancer, was isolated and cultured. It was identified according to the genotype using labeled hybridization probes complementary to six sequences of cagA and vacA genes. Different types of strains were found in isolates from gastrointestinal tract and patients suffering from thyroiditis. Six out of seven genotyped isolates from patients in our Department of Otorhinolaryngology and Head and Neck Surgery exhibited the same genotype, differing from isolates obtained from other patients; the 7th isolate originated from a patient who had undergone surgery for deviatio septi nasi, at the same time suffering from autoimmune thyroiditis, having confirmed gastric infection by H. pylori from biopsy. This data made it possible to formulate the hypothesis on probable association of specific H. pylori genotype with chronic tonsillitis and tonsillar cancer. We assessed commercial transport media and improved nucleic acid isolation techniques and the RT-PCR-based tests, which allowed us to skip a culture step and to test directly the patients' samples; however, for full confirmation of our hypothesis and explanation of possible mechanisms of the contribution of Helicobacter sp. to the pathogenesis of the disease further data are to be collected and evaluated.

Activation of Helicobacter pylori causes either autoimmune thyroid diseases or carcinogenesis in the digestive tract.

Helicobacter pylori has been implicated in stimulation of immune system, development of autoimmune endocrinopathies as autoimmune thyroiditis (AT) and on other hand induction of immunosupresion activates gastric and extra-gastric diseases such as gastric ulcer or cancer. It causes persistent lifelong infection despite local and systemic immune response. Our results indicate that Helicobacter pylori might cause inhibition of the specific cellular immune response in Helicobacter pylori-infected patients with or without autoimmune diseases such as AT. We cannot also declare the carcinogenic effect in oropharynx. However the association of any infection agents and cancerogenesis exists. The adherence of Helicobacter pylori expression and enlargement of benign lymphatic tissue and the high incidence of the DNA of Helicobacter pylori in laryngopharyngeal and oropharyngeal cancer is reality. LTT appears to be a good tool for detection of immune memory cellular response in patients with Helicobacter pylori infection and AT. All these complications of Helicobacter pylori infection can be abrogated by successful eradication of Helicobacter pylori.

Serum levels of IGF-I, HGF, TGFbeta1, bFGF and VEGF in thyroid gland tumors.

IGF-I, HGF, TGFbeta1, bFGF and VEGF are involved in the pathogenesis of thyroid gland tumors and their growth. We decided to find whether changes in the production of these cytokines by thyroid tumor cells are reflected by changes of their peripheral blood. Using ELISA kits, we measured the concentrations of growth factors in the peripheral blood serum in 28 patients with thyroid gland tumors (14 adenomas, 14 papillary carcinomas) and compared these concentrations with those in healthy people. We found significantly lower serum levels of IGF-I in patients with thyroid adenoma compared to the healthy population. Serum levels of HGF and bFGF were significantly higher in patients with thyroid adenoma and papillary carcinoma compared with those in healthy subjects. Serum concentrations of TGFbeta1 and VEGF were not significantly different in any groups of investigated subjects. Changes in the production of these cytokines by thyroid gland tumor cells are reflected in their peripheral blood levels, but these levels also depend on a number of other physiological and pathological processes in the organism. However, significant differences of HGF and bFGF serum levels can be explained by their very high production by thyroid tumor cells and by their strong effect on the follicular and endothelial cell proliferation.

Heterotopy of thyroid tissue--a modified therapeutical approach.

OBJECTIVES: The authors describe the classification of heterotopic thyroid tissue. A survey of more than 600 literature cases is provided. Different therapy approaches for these anomalies are discussed. Data from seven subsequent cases have been added to the existing literature data. The authors present an alternative approach to the therapy of heterotopic thyroid tissue. MATERIALS AND METHODS: The records of seven patients treated for a heterotopy of the thyroid tissue as the Department of ENT and Head and Neck Surgery of First Medical school of the Charles University of Prague since 1.1.1991 to 1.1.2001 have been analyzed. RESULTS: The first group: No surgery. This approach was used for children. In these patients the heterotopic thyroid tissue is the only thyroid tissue they have, but its function is not damaged and there are no mechanical symptoms (no airway obstruction and dysphagia). TSH substitution-suppression therapy is necessary for this group. Cooperation and follow up by the endocrinology, otolaryngology and pediatric departments is necessary. At a later age these patients can be treated as in the second group. The second group: Surgery. All patients in this group had heterotopic thyroid tissue. The total removal of thyroid tissue has been preferred. Carcinomatous change or the development of mechanical syndrome, dysphagia or airway obstruction is possible. Total removal is the best surgical approach. Various surgical methods are described in the literature (CO2 laser, intraoral, mandibulotomy, middle hyotomy etc.). These patients are treated as after total thyroidectomy and substitution therapy with synthetic thyroid hormones is necessary. The authors describe and add seven cases to the literature data. The authors describe radical removal of aberrant and accessory tissue [corrected].

[Plasma and tissue levels of cytokines and adhesive molecules in patients before strumectomy]. / Plazmatické a tkánové koncentrace cytokinu a adhezivních molekul u pacientu pred strumektomií.

From a group of 134 patients with complete documentation before goitrectomy the authors selected 10 histologically defined cases of (A) simple colloid nodular goitre, (B) toxic parenchymatous goitre type GB and (C) autoimmune thyroiditis. Marked hormonal suppression was achieved in group B by thyrostatic therapy, as compared with A and C, the autoantibody titres (TGAb and TMAb) differentiated the groups. The authors examined the interleukin 6 concentrations and those of its soluble receptor (IL-6, IL-6R), of the tumour necrotizing factor alpha (TNF-alpha) interferon gamma (IFN-gamma) and of adhesion molecules ICAM-1 and VCAM-1. Plasma values were, except for not very significant differences, similar in all groups and ruled out a marked effect on tissue levels. The most remarkable finding in the homogenate of a peroperative excision were low IL-6, IL-6R and adhesion molecule values in group A, as compared with B and C and the absence of differences in TNF-alpha values between groups and in particular markedly higher IFN-gamma values in group B which supports theories on the etiopathogenetic role of this cytokine in GB disease. The pilot study is part of the preparation of in situ hybridization of mRNA for diagnostically usable cytokines.

Pilot study: Association between Helicobacter pylori in adenoid hyperplasia and reflux episodes detected by multiple intraluminal impedance in children.

OBJECTIVES: The aim of this pilot study was to investigate an association between laryngopharyngeal reflux detected by combined multiple intraluminal impedance and pH monitoring and Helicobacter pylori in adenoid hyperplasia detected with real time polymerase chain reaction (PCR). METHODS: The study group consisted of 30 children (median age 5.34 years) with extraesophageal symptoms of gastroesophageal reflux disease with adenoid hyperplasia. All children underwent adenoidectomy with subsequent PCR detection of H. pylori DNA in the tissue and multiple intraluminal impedance and pH monitoring. The most proximal impedance sensor was located 1cm caudal to the entrance of the oesophagus. RESULTS: We found significant differences in the number of reflux episodes among patients with PCR positivity (median 35) and negativity (median 0) of H. pylori (p-value of Mann-Whitney U-test 0.0056). Patients with PCR positivity of H. pylori had significantly more reflux episodes reaching the upper oesophageal sphincter (p-value of Mann-Whitney U-test 0.023). The absence of reflux episode was the only independent factor for PCR negativity of H. pylori in the multiple logistic regression model. CONCLUSIONS: These results support the hypothesis that reflux episodes reaching the upper oesophageal sphincter may play an important role in the transmission of H. pylori into lymphoid tissue of the nasopharynx and thus may contribute to adenoid hyperplasia in children.

The pathogenesis of chronic inflammation and malignant transformation in the human upper airways: the role of beta-defensins, eNOS, cell proliferation and apoptosis.

The surrounding environment contains plenty of pathogens, which represent a danger of infection. The simplest way for the pathological microorganism to enter the organism is the upper airways. Inflammation of the upper airways is among the most common and frequent diseases. This category includes nasal polyposis and chronic tonsillitis. In many cases it is associated with disorders in relation to the immune response. An inflammatory infiltration of mononuclears, eosinophils, plasma and mast cells can be found in the histological structure of the polypous as well as tonsillar mucosa. One aim of this study was to determine the expression of beta-defensins and various proteins, with a possible potential role in relation to the rise and development of those changes. Another aim was to determine the relationship between the inflammatory and malignant processes in the tonsils. The samples of nasal polyps were obtained during clinically indicated endonasal surgery from patients diagnosed with nasal polyposis (n=50). The samples of tonsils were collected during surgery from patients suffering from chronic tonsillitis (n=11) or tonsillar carcinoma (n=17). Immunohistochemical procedures for the detection of human beta-defensin 1, 2, 3 (HBD-1, 2, 3), Ki- 67, endothelial nitric oxide synthase (eNOS) and cleaved caspase 3 were performed on cryostate and paraffin sections. It was proven that HBD are secreted in fairly large amounts in cases of chronic inflammation. Their secretion during the malignant transformation is limited. This is a very probable fact that plays a role in malignant transformation in tonsillar tissue. The crucial role in the development of chronic inflammation, and maybe that of malignant transformation, is played by eNOS and its product NO molecule. eNOS and the NO molecule are involved in cell cycle regulation, in the apoptotic processes and cell proliferation, as well as in the angiogenesis and vasculogenesis. Our result confirmed that eNOS is presented in the tissues of the upper airways in both chronic inflammation and carcinomatous processes. Ki-67 and cleaved caspase 3 were used as markers of cell proliferation and apoptosis.