Prediktori zbrinjavanja otežanog dišnog puta u kirurgiji štitnjače: petogodišnja opservacijska prospektivna studija u jednom centru

Difficult tracheal intubation (DI) is more common in thyroid than in other surgical branches due to thyromegaly. Proper preoperative airway evaluation is necessary in order to reduce the potential numerous complications. The study examined the incidence of DI in thyroid surgery and the influence of tracheal dislocation and other risk factors on DI. A prospective study was conducted on 2379 patients who underwent thyroidectomy at the Center for Endocrine Surgery, Clinical Center of Serbia, from 2007 to 2012. Patients were divided into groups with (n=162) and without DI (n=2217). Besides tracheal dislocation, another 13 risk factors contained in 13 screening tests and three additional factors of gender, age and diagnosis were defined. The incidence of DI in our study was 6.81%. The presence of tracheal dislocation was statistically significant, but not an independent predictor of DI. The diagnosis, large circumference and small neck length, previous DI, recessive mandible, tooth characteristics and oral anomalies were the most significant and independent predictors of DI. Neck circumference and small neck length had highest sensitivity. Previous DI had highest specificity. Thyromegaly, if causing tracheal dislocation and/or stenosis, represents a significant DI predictor, not individually, but in combination with other factors.Otežana intubacija (OI) traheje je češća u kirurgiji štitnjače nego u drugim kirurškim granama zbog tireomegalije. Pravilna prijeoperacijska evaluacija dišnoga puta je neophodna za smanjenje brojnih potencijalnih komplikacija. Ispitivali smo učestalost OI u kirurgiji štitnjače, utjecaj dislokacije traheje i drugih čimbenika na OI. Provedena je prospektivna studija na 2379 bolesnika podvrgnutih operacijama štitne žlijezde u Centru za endokrinu kirurgiju Kliničkog centra Srbije u Beogradu u razdoblju od 2007. do 2012. godine. Bolesnici su bili podijeljeni u skupine s OI (n=162) i bez OI (n=2217). Uz dislokaciju i/ili stenozu traheje definirano je još 13 čimbenika rizika sadržanih u 13 probirnih testova i 3 dodatna čimbenika – spol, životna dob i dijagnoza. Učestalost OI u našoj studiji iznosila je 6,81%. Prisutnost dislokacije traheje bila je statistički značajan, ali ne i nezavisni prediktor OI. Kao najznačajniji i nezavisni prediktori OI izdvojili su se: dijagnoza, veliki obim i mala dužina vrata, prethodna OI, recesivna mandibula, karakteristike zuba i oralne anomalije. Najveću osjetljivost imali su obim i dužina vrata, a najveću specifičnost prethodna OI. Ako dovodi do dislokacije i/ili stenoze traheje, tireomegalija je značajan prediktor OI, ne samostalno, nego u kombinaciji s drugim čimbenicima

Small bowel adenocarcinoma mimicking a large adrenal tumor

Introduction. Adenocarcinoma of the small bowel is a rare gastrointestinal neoplasm usually affecting the distal duodenum and proximal jejunum. Because of their rarity and poorly defined abdominal symptoms, a correct diagnosis is often delayed. Case Outline. We present a 43-year-old woman admitted at the Clinic for Endocrinology due to a large tumor (over 7 cm) of the left adrenal gland. The tumor was detected by ultrasound and confirmed by CT scan. The patient complained of abdominal pain in the left upper quadrant, fatigue and septic fever. Normal urinary catecholamines excluded pheochromocytoma. The endocrine evaluations revealed laboratory signs of subclinical hypercorticism: midnight cortisol 235 nmol/L, post 1 mg - overnight Dexamethasone suppression test for cortisol 95.5 nmol/L and basal ACTH 4.2 pg/mL. Plasma rennin activity and aldosterone were within the normal range. Surgery was performed. Intraoperative findings showed signs of acute peritonitis and a small ulceration of the jejunum below at 70 cm on the anal side from the Treitz’s ligament. Adrenal glands were not enlarged. Patohistology and immunochemistry identified adenocarcinoma of the jejunum without infiltration of the lymphatic nodules. The extensive jejunal resection and lavage of the peritoneum were performed. Due to complications of massive peritonitis, the patient died seven days after surgery. Conclusion. Poorly defined symptoms and a low incidence make the diagnosis of small bowel carcinoma, particularly of the jejunal region, very difficult in spite of the new endoscopic techniques

Interleukin-6, a potential plasma biomarker for diagnosis and prognosis of thyroid neoplasms

Background: Thyroid neoplasms include benign tumors – thyroid adenoma (TA), and malignant tumors of various histological types: papillary thyroid carcinoma (PTC) – the most common and usually indolent, anaplasƟ c thyroid carcinoma (ATC) – the most aggressive, and several other types such as follicular, medullary and poorly diff erenƟ ated. Despite the progress in understanding the epidemiology and geneƟ c landscape of thyroid tumors, the diagnosis, prognosis and treatment approach require further improvement. Interleukin-6 (IL-6) is a pro-infl ammatory cytokine with a central role in the regulaƟ on of immune and infl ammatory responses including autoimmune thyroid diseases. Studies have revealed a potenƟ al impact of IL-6 in the development, progression and control of thyroid cancer. The aim of this study was to provide novel aspects for the preoperaƟ ve diff erenƟ al diagnosis and/or prognosis of thyroid cancer. To achieve this, we assessed the circulaƟ ng levels of IL-6 in paƟ ents with benign and malignant thyroid tumors of various histotypes, compared them with healthy volunteers, and correlated the results with clinicopathological parameters. PaƟ ents and Methods: The study included 43 paƟ ents with benign or malignant thyroid tumors, surgically treated at the Center for Endocrine Surgery, Clinical Center of Serbia. IL-6 protein levels were determined in plasma samples by quanƟ taƟ ve ELISA. Parametric and nonparametric staƟ sƟ cal tests were used for data analysis. Results: IL-6 concentraƟ ons in paƟ ents with either TA or carcinoma (PTC, ATC) were signifi cantly higher compared to the healthy volunteers (Mann Whitney test). The highest concentraƟ ons were detected in ATC paƟ ents (Median±SD 15.97±0.71 pg/mL), being signifi cantly higher compared to TA and PTC (2.14±1.34 pg/mL and 1.96±2.12 pg/mL, respecƟ vely). In PTC microcarcinoma, IL-6 was higher compared to controls, but there was no signifi cant diff erence compared to other PTC or TA (Mann Whitney test). The correlaƟ on analysis with clinicopathological parameters in PTC paƟ ents revealed a trend towards the associaƟ on of increased IL-6 plasma levels with the presence of nodal and distant metastases. No other signifi cant associaƟ ons were found. Conclusion: PaƟ ents with thyroid adenoma or carcinoma have increased plasma IL-6 levels that are in proporƟ on with the aggressiveness of the thyroid tumor, suggesƟ ng that IL-6 might be a candidate biomarker for diagnosis and prognosis of thyroid neoplasms.The first number of Oncology Insights includes Proceedings book of The Sixth Congress of the Serbian Association for Cancer Research with international participation (Oct 2-4, 2023, Belgrade

Faktori rizika za pojavu intraoperativnih varijacija vrednosti krvnog pritiska i srčanih disritmija tokom tireoidne hirurgije

Introduction/Objective Intraoperative variations in blood pressure and/or cardiac dysrhythmias (IOVBP/CD) represent one of the most common causes of morbidity and mortality in surgical patients. The aim of the study was to determine the incidence and risk factors for IOVBP/CD in thyroid surgery patients with comorbidities. Methods The study included 1,252 euthyroid patients with ASA 2 and ASA 3 status (American Society of Anesthesiologists - physical status classification) who underwent thyroid surgery. The following risk factors were examined: sex, age, body mass index (BMI), ASA status, admission diagnoses, type of operation, duration of surgery, time under general anesthesia, difficult intubation of trachea, and coexisting diseases - hypertension, cardiomyopathy, cardiac arrhythmias, angina pectoris, diabetes mellitus, kidney disease. The following intraoperative events were recorded: hypertension, severe hypertension, hypotension, and cardiac arrhythmias. We used Pearson χ2 square test, univariate, and multivariate logistic regression for statistical analysis. Results The majority of patients were female (86.3%). In 903 (72.1%) patients IOVBP/CD were detected. The most common problem was intraoperative hypertension (61.4%). Eight risk factors for IOVBP/CD were registered by univariate analysis: advanced age, ASA 3 status, BMI > 25 kg/m2, duration of surgery, time under general anesthesia, hypertension, and cardiomyopathy as a coexisting disease. The multivariate regression model identified three independent predictors for IOVBP/CD: age, hypertension, and cardiomyopathy. Conclusion IOVBP/CD are common in thyroid surgery. The most common is intraoperative hypertension. Older age, hypertension, and cardiomyopathy as a coexisting disease are independent risk factors for IOVBP/CD.Uvod/Cilj Intraoperativne varijacije krvnog pritiska i/ ili srčane disritmije (IVKP/SD) jedan su od najčešćih uzročnika morbiditeta i mortaliteta hirurških bolesnika. Cilj studije je bio da ispita učestalost i faktore rizika za pojavu IVKP/SD u tireoidnoj hirurgiji kod bolesnika sa komorbiditetima. Metode Ispitivanje je obuhvatilo 1252 eutireoidna bolesnika ASA 2 i ASA 3 statusa podvrgnutih tireoidnoj hirurgiji. Ispitivan je uticaj sledećih faktora rizika: pol, starost, indeks telesne mase (ITM), ASA status, prijemna dijagnoza, tip operacije, trajanje operacije, trajanje anestezije, otežana intubacija traheje, kao i komorbiditeti: hipertenzija, kardiomiopatija, srčane aritmije, angina pektoris, dijabetes melitus, bolesti bubrega. Registrovani su intraoperativno: hipertenzija, hipertenzivna kriza, hipotenzija i srčane aritmije. Korišćen je Pirsonov χ2-test, univarijantna i multivarijantna regresiona analiza za statističku obradu podataka. Rezultati Većinu bolesnika su činile žene (86,3%). IVKP/ SD su registrovani kod 903 (72,1%) bolesnika. Najčešći poremećaj je bila intraoperativna hipertenzija - 61,4%. Univarijantnom analizom je registrovano sedam faktora rizika za pojavu IVKP/SD: godine života, ASA 3 status, ITM > 25 kg/m2, trajanje hirurgije, trajanje anestezije, hipertenzija i kardiomiopatija kao komorbiditet. Multivarijantnom regresionom analizom izdvojila su se tri nezavisna prediktora pojave IVKP/SD: godine starosti, hipertenzija i kardiomiopatija. Zaključak IVKP/SD su česte u tireoidnoj hirurgiji. Najčešća je intraoperativna hipertenzija. Starije životno doba, hipertenzija i kardiomiopatija kao koegzistirajuće bolesti su nezavisni faktori rizika za pojavu IVKP/SD

Altered expression of microRNA-30a-3p in papillary thyroid cancer and its association with clinicopathological characteristics

A growing number of studies suggest a tumor suppressive role and potential prognostic significance of miR- 30a-3p in different types of cancer. However, relatively few studies have focused on this microRNA in neoplastic thyroid lesions, including papillary thyroid cancer (PTC). The aim of our study was to shed more light on the potential involvement and clinical relevance of miR-30a-3p in this type of cancer. We examined the expression levels of this microRNA in 42 pairs of PTCs and matched non-tumor thyroid tissues using quantitative RT-PCR. We analyzed their association with clinical and histopathological parameters. The results revealed that miR-30a-3p was significantly downregulated in the majority of PTC tissues compared to corresponding non-tumor tissues. Moreover, decreased expression of miR-30a-3p was associated with advanced clinical stage, presence of multiple tumor foci and capsular invasion, suggesting a role in aggressive disease. Although the role of this microRNA and its prognostic utility remain to be elucidated, the presented data suggest that downregulated expression of miR-30a-3p indicates poorer prognosis in PTC patients, warranting further investigations

Validation of diagnostic and prognostic potential of PINK1, DLGAP5 and BUB1B expression patterns in adrenocortical tumors

Adrenocortical tumors (ACTs) are heterogeneous neoplasms with incompletely understood pathogenesis. Correct differential diagnosis between adrenocortical adenoma (ACA) and localized adrenocortical carcinoma (ACC), as well as improved prognostic stratification of ACC patients, are of great clinical importance. Alterations in gene expression patterns have been found in adrenocortical neoplasms compared to normal tissue. In addition to having a role in tumorigenesis, distinct gene expression signatures may help to distinguish different ACT types. The combined expression patterns of PINK1, DLGAP5 and BUB1B have been suggested as malignancy and outcome predictors in previous studies. In order to validate their diagnostic/prognostic potential, we investigated the expression levels of these three genes and their association with clinico-pathological parameters in a cohort of 47 ACC and 15 ACA patients from Serbia. In addition, we analyzed the association of their expression levels with survival data in an independent ACC cohort of 79 patients from The Cancer Genome Atlas (TCGA) database. The results showed that high expression levels of BUB1B and DLGAP5, and low expression levels of PINK1 significantly associated with ACC. Moreover, combined expression of both DLGAP5 and BUB1B with PINK1 were significantly higher in localized ACC compared with ACA. The results from the TCGA cohort showed that expression alterations of these genes were strong predictors of disease-free and overall survival in ACC patients. These results are consistent with the previously reported results and confirm that the expression patterns of PINK1, DLGAP5 and BUB1B might have value as molecular predictors of malignancy and/or survival in ACC patients.The 21st ENS@T and 1st COST-HARMONIS@TION meeting; September 28-30, Warsaw, Poland, 2022

Correction to: Redox Status and Antioxidative Cofactor Metals Influence Clinical and Pathological Characteristics of Papillary Thyroid Carcinoma and Colloid Goiter (Biological Trace Element Research, (2020), 197, 2, (349-359), 10.1007/s12011-019-01995-x)

Papillary thyroid carcinoma (PTC) is the endocrine neoplasm that occurs the most often worldwide, and its molecular pathophysiology is still not well characterized. Redox status is recognized as an important factor of carcinogenesis, but its influence on the PTC's clinical course needs to be better elucidated. The aim of this research was to determine the tissue redox status of 65 PTC and 45 colloid goiter (CG) patients together with antioxidative cofactor metal profiling. The malondialdehyde (MDA) concentration was used to access the prooxidation level, while antioxidant mechanisms were estimated by assaying the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione reductase (GR). The antioxidative cofactor metals included quantification of Se, Cu, Zn, and Mn concentration. PTC tissues had normal prooxidation levels and increased GPx and GR activity. The activity of SOD has been significantly reduced in multicentric PTC dissemination and increased in smokers. SOD activity was directly dependent on MDA levels in CG tissues. CG patients with retrosternal goiter had reduced MDA concentration and SOD activity. Numerous correlations between redox parameters in PTC tissues reveal good co-activation of antioxidative mechanisms and cooperative response on prooxidation. PTC tissues had decreased Se levels and increased concentration of Cu and Mn in comparison to other tissues. MDA concentration and SOD activity were significant predictors of PTC's multicentric dissemination and for the existence of lymph node metastases, respectively. Particularly, the concentration of Cu predicted the retrosternal localization in CG patients. Significant findings presented in this study provide a possibility for development of novel prognostic molecular biomarkers of PTC and CG.The contribution corrects an equation from the paper: Rovcanin, B.; Stojsavljevic, A.; Kekic, D.; Gopcevic, K.; Manojlovic, D.; Jovanovic, M.; Knezevic, S.; Zivaljevic, V.; Diklic, A.; Paunovic, I. Redox Status and Antioxidative Cofactor Metals Influence Clinical and Pathological Characteristics of Papillary Thyroid Carcinoma and Colloid Goiter. Biol Trace Elem Res 2020, 197 (2), 349–359. [https://doi.org/10.1007/s12011-019-01995-x

Supplementary data for the article: Jagodić, J.; Rovčanin, B.; Krstić, Đ.; Paunović, I.; Živaljević, V.; Manojlović, D.; Stojsavljević, A. Elemental Profiling of Adrenal Adenomas in Solid Tissue and Blood Samples by ICP-MS and ICP-OES. Microchemical Journal 2021, 165, 106194. https://doi.org/10.1016/j.microc.2021.106194.

Supplementary material for: [https://doi.org/10.1016/j.microc.2021.106194]Related to published version: [https://cherry.chem.bg.ac.rs/handle/123456789/4530

Methylation status of p16INK4a tumor-suppressor gene in adrenocortical carcinoma: preliminary study

Adrenocortical carcinoma (ACC) is a rare cancer with poor prognosis. Identifying novel molecular parameters with prognostic value is of great clinical importance for a personalized therapeutic approach. Epigenetic changes have been proven to play an important role in cancer pathogenesis. Hypermethylation of the promoter region of p16INK4a gene has been shown to be a significant event in a number of cancer types. Several studies suggested that it might have a prognostic impact in ACC as well, however the data are relatively ambiguous. According to the dataset from The Cancer Genome Atlas (TCGA) database, in cohort of 79 ACC patients, the analysis of the p16INK4a gene methylation showed that higher methylation was associated with shorter progression-free and overall survival. We evaluate the methylation status of p16INK4a in a preliminary cohort of 30 ACC patients by using the methylation-specific polymerase chain reaction (MSP) and aberrant methylation of p16INK4a was present in 66.7% (20/30) of cases. Our results indicate that epigenetic alteration of this gene is common event in ACC and may be important for pathogenesis of this tumor type. Although, we did not observed significant association between p16INK4a methylation status and clinico-pathological characteristics (age and gender, tumor size and weight, regional lymph node and distant metastasis), we will evaluate methylation status of this gene in another 30 ACC cases and compare it with methylation profile of adrenocortical adenoma patients, since inactivation of p16INK4a gene by promoter hypermethylation has been frequently reported as an early event in premalignant lesions in many tumor types.The 21st ENS@T and 1st COST-HARMONIS@TION meeting; September 28-30, Warsaw, Poland, 2022

Supplementary material for the article: Stojsavljević, A.; Rovčanin, B.; Krstić; Jagodić, J.; Borković-Mitić, S.; Paunović, I.; Živaljević, V.; Mitić, B.; Gavrović-Jankulović, M.; Manojlović, D. Cadmium as Main Endocrine Disruptor in Papillary Thyroid Carcinoma and the Significance of Cd/Se Ratio for Thyroid Tissue Pathophysiology. Journal of Trace Elements in Medicine and Biology 2019, 55, 190–195. https://doi.org/10.1016/j.jtemb.2019.06.009

Supplementary material for: [https://doi.org/10.1016/j.jtemb.2019.06.009]Related to published version: [http://cherry.chem.bg.ac.rs/handle/123456789/3293