Establishing the European diagnostic reference levels for interventional cardiology.

Interventional cardiac procedures may be associated with high patient doses and therefore require special attention to protect the patients from radiation injuries such as skin erythema, cardiovascular tissue reactions or radiation-induced cancer. In this study, patient exposure data is collected from 13 countries (37 clinics and nearly 50 interventional rooms) and for 10 different procedures. Dose data was collected from a total of 14,922 interventional cardiology procedures. Based on these data European diagnostic reference levels (DRL) for air kerma-area product are suggested for coronary angiography (CA, DRL = 35 Gy cm2), percutaneous coronary intervention (PCI, 85 Gy cm2), transcatheter aortic valve implantation (TAVI, 130 Gy cm2), electrophysiological procedures (12 Gy cm2) and pacemaker implantations. Pacemaker implantations were further divided into single-chamber (2.5 Gy cm2) and dual chamber (3.5 Gy cm2) procedures and implantations of cardiac resynchronization therapy pacemaker (18 Gy cm2). Results show that relatively new techniques such as TAVI and treatment of chronic total occlusion (CTO) often produce relatively high doses, and thus emphasises the need for use of an optimization tool such as DRL to assist in reducing patient exposure. The generic DRL presented here facilitate comparison of patient exposure in interventional cardiology.

Rising incidence of thyroid cancer in Serbia.

BACKGROUND: In the past decade, the incidence of thyroid cancer (TC) has shown a stable increase, for both sexes, in many parts of the world at a rate faster than for any other type of malignancy. The aim of our study was to analyze and report changes in TC incidence in Serbia, as well as to evaluate potential reasons for these changes. So far, the incidence of TC in Serbia has not been reported. MATERIAL AND METHODS: This is a retrospective descriptive epidemiological study of TC data from the Cancer Register for Serbia for a ten year period, from 1999 to 2008. Crude rates (CR), age-specific rates (ASR), age-adjusted rates (AAR), linear trends and average annual percentage changes (AAPC) were calculated and analyzed. RESULTS: TC incidence increased substantially for both genders with the highest increase in 2007 for the age group 50-59 (females 14.2, males 10.3). TC was three times more common in females (CR 4.7:1.5). The AAR for females ranged 1.9-4.8 (3.3, 95% CI 2.6-4.0), for males 1.0-2.6 (1.0, 95% CI 0.8-1.2) and for both sexes combined 1.4-3.2 (2.2, 95% CI 1.7-2.6). The incidence trend for males showed an increase (y =0.05x + 0.70, p =0.058). It was highly statistically significant for females (y =0.31x + 1.61, p <0.001) and both genders combined (y =0.18x + 1.18, p <0.001). AAPC was highest for ages 20-29 and 30-39, for females (+25.2%) and males (+17.3%), respectively. CONCLUSIONS: We found a substantial increase in TC incidence in Serbia for both genders. The highest increase in TC incidence was found in females aged 20 to 29 years while the highest incidence was found in the age group 50 to 59.

The results of molecular genetic testing for RET proto-oncogene mutations in patients with medullary thyroid carcinoma in a referral center after the two decade period.

BACKGROUND: Medullary thyroid carcinoma (MTC) is a type of thyroid neoplasm which originates from parafollicular cells, and it is commonly diagnosed by calcitonin screening. Besides the sporadic form, the heritable form of MTC is characterized by constitutive activation of the RET (REarranged during Transfection) proto-oncogene caused by different mutations. METHOD: We collected data regarding RET genetic screening performed in the Center for Endocrine Surgery in Belgrade during a 20-year-period. The study group included 249 MTC patients who were genetically tested for RET mutations by Sanger's sequencing method. RESULTS: Genetic screening of the study population revealed nine different mutations of the RET gene in 42 carriers. The most common mutation was C634F, and it has been detected in 31 % (13/42) of individuals, while C618R, L790F, and S904S were present in only 2 % (1/42) each in the study group. Detected mutations were unequally distributed in different RET gene exons. Among MTC patients, 67 % (28/42) had mutation harbored in exon 11, while the rarest mutation was located in exons 10 and 15, each present in only 2 % (1/42) of patients. CONCLUSIONS: The RET gene mutation profile has a unique distribution in this study population when compared with the other European populations. The mutations in codon 634 are most common; therefore the cost-reducing genetic screening should primarily target this codon, and if the negative outcome appears, then other codons should be examined in the order that depends on their occurrence. Hippokratia 2016, 20(3): 187-191.

Survival and prognostic factors of anaplastic thyroid carcinoma.

BACKGROUND: Anaplastic thyroid carcinoma (ATC) is relatively rare and represents one of the most aggressive tumours with poor prognosis, despite therapy. The aim of the study was to analyse demographic and clinical characteristics of ATC patients, and to identify survival rates and prognostic factors. METHODS: In a retrospective study (1995-2005) ATC was found in 150 patients treated at our institution. Survival was calculated by Kaplan-Meier curve and log-rank test. Potential prognostic factors affecting survival were compared by Cox univariate and multivariate analyses. RESULTS: Mean survival time was 56 weeks; median survival time was 16 weeks and 1 and 5-year survival were 17% and 8%. More than 10% died during the first month and 50% died up to the fourth month. Multivariate analysis showed that age, goitre and surgery were independent prognostic factors of survival in all ATC patients. Among operated patients, the extent of tumour resection, distant metastasis and multicentricity were independent prognostic risk factors of survival. Postoperative radiotherapy was a protective factor. CONCLUSIONS: There is still no successful treatment of ATC that can guarantee long term survival. Younger patients with pre-existing goitre, who undergo complete resection of unilocular early stage ATC without distant metastasis and with postoperative external radiotherapy, stand a better chance of long-term survival.

Survival and Prognostic Factors of Anaplastic Thyroid Carcinoma.

BACKGROUND: Anaplastic thyroid carcinoma (ATC) is relatively rare and represents one of the most aggressive tumours with poor prognosis, despite therapy. The aim of the study was to analyse demographic and clinical characteristics of ATC patients, and to identify survival rates and prognostic factors. METHODS: In a retrospective study (1995-2005) ATC was found in 150 patients treated at our institution. Survival was calculated by Kaplan-Meier curve and log-rank test. Potential prognostic factors affecting survival were compared by Cox univariate and multivariate analyses. RESULTS: Mean survival time was 56 weeks; median survival time was 16 weeks and 1 and 5-year survival were 17% and 8%. More than 10% died during the first month and 50% died up to the fourth month. Multivariate analysis showed that age, goitre and surgery were independent prognostic factors of survival in all ATC patients. Among operated patients, the extent of tumour resection, distant metastasis and multicentricity were independent prognostic risk factors of survival. Postoperative radiotherapy was a protective factor. CONCLUSIONS: There is still no successful treatment of ATC that can guarantee long term survival. Younger patients with pre-existing goitre, who undergo complete resection of unilocular early stage ATC without distant metastasis and with postoperative external radiotherapy, stand a better chance of long-term survival.

Prognostic parameters after surgery for adrenal metastases: a single institution experience.

BACKGROUND: Clinically isolated adrenal metastases are rare and therefore present a therapeutic challenge. We report our experience with surgery of adrenal metastases and analyze factors that may influence postoperative survival. METHODS: A consecutive series of 31 patients (16 male, 15 female) underwent adrenal surgery for metastases at a single institution over 10-year period (1999-2008). The Kaplan-Meier method and log-rank test were used to determine overall survival. Potential prognostic factors were identified by univariate and multivariate Cox regression analysis. RESULTS: The primary tumor diagnoses were non-small-cell lung carcinoma (NSCLC) 20, colorectal carcinoma 5, renal cell carcinoma (RCC) 2, malignant melanoma and breast carcinoma, one each. The median survival was 12 months, with one year and five year survival of 21% and 3.4% respectively. According to multivariate analysis independent prognostic factors of favorable survival were disease free interval (DFI) longer than 12 months (Hazard ratio (HR) = 0.28, 95% CI = 0.09-0.90), potentially curative resection (Hazard ratio (HR) = 0.35, 95% CI = 0.12-1.00) and postoperative radiotherapy of adrenal bed (Hazard ratio (HR) = 0.33, 95% CI = 0.12-0.91). CONCLUSIONS: Overall survival after surgery for adrenal metastases is poor. In multivariate analyses, survival is influenced by DFI, curative resection, and postoperative radiotherapy.

Risk factors for anaplastic thyroid cancer.

Background. Anaplastic thyroid cancer (ATC) is a form of thyroid cancer with very poor prognosis, but is fortunately quite rare. Its aetiology is unknown and not well researched. Aim. The aim of this study was to identify potential risk factors for ATC. Material and Method. Case-control study of 126 ATC patients (77 females and 49 males) and 252 controls individually matched by gender, age, and place of abode. In statistical analysis we used a Cox regression model. Results. Univariate logistic regression showed that the risk factors for ATC are low education level, type B blood group, goitre, other nonthyroid malignancies, diabetes, late menarche, and an early first pregnancy. Multivariate logistic regression analysis showed that independent risk factors for ATC are low education level (OR = 1.42, 95% CI = 1.09-1.86), type B blood group (OR = 2.41, 95% CI = 1.03-5.66), and goitre (OR = 25-33, 95% CI = 5.66-126.65). Conclusion. Independent risk factors for ATC are: low education level, type B blood group, and goitre.

Primary hyperparathyroidism in children and young adults:--a single institution experience.

BACKGROUND: Primary hyperparathyroidism (PHPT) is an extremely rare disorder in children and young adults. In the literature, only small case series or case reports can be found. The aim of this study was to show our experience in the management of PHPT patients under the age of 20. METHODS: We performed a retrospective study of PHPT patients who underwent surgery in our institution. From 2004 to 2010, 522 patients underwent surgery (74, male; 478, female). Of these, 7 patients were under the age of 19 (4 [5%], male, 3 [0.6%], female). The following was analyzed demographic characteristics, length of the disease, clinical presentation, and preoperative and postoperative parathyroid hormone (PTH) and serum calcium levels. Ultrasonography, scintigraphy, and computerized tomography were performed for preoperative localization, and the types of operations and histopathological findings were assessed. RESULTS: The average age of the patients was 15.7 years. Average duration of disease was 4.8 months. Only 2 patients (28%) were asymptomatic. The mean serum calcium level was 3.06 mmol/l, and the mean PTH level was 620.6 pg/ml. Both parameters showed significant reduction after surgery. One patient was positive for multiple endocrine neoplasia type I syndrome, while the other patients were sporadic. Five parathyroidectomies (72%), 1 double parathyroidectomy (14%), and 1 subtotal parathyroidectomy (14%) were performed. CONCLUSION: PHPT in children and young adults is rare. It occurs more frequently in young adults than in children, with slight predominance in males. Most of the patients are symptomatic at diagnosis. Surgery is a successful method of treatment.

Changing trends in mortality of thyroid cancer in Belgrade population.

PURPOSE: Thyroid cancer patients have favorable prognosis. The aim of this study was to analyze changing trends in mortality of thyroid cancer in Belgrade, during the period between 1987 and 2006. METHODS: Mortality data were obtained from the Belgrade Office of Statistics. Mortality rates per 100,000 inhabitants were standardized according to the Segi's world population. Regression analysis was used to estimate the thyroid cancer mortality trend for the period 1987-2006. RESULTS: The average percent of deaths due to thyroid cancer among all deaths was almost 2-fold higher in females (0.11%) than in males (0.6%), as well as among deaths due to all malignancies (females 0.54% and males 0.27%). During this 20-year period, the average standardized mortality rate was 1.5 times higher in females (0.74 per 100.000) than in males (0.51 per 100.000). In the observed period, the mortality rates for thyroid cancer were increased (+0.40%) in women and decreased (-0.42%) in men. In particular, in the 60-69 years age group in males, a significant trend for mortality decrease of 3.5%/year was detected. CONCLUSION: Belgrade is classified in the regions with low risk of dying due to thyroid malignancies. The increasing trend of thyroid cancer mortality in females during the examined period calls for improvement of methods for early detection of disease and differential diagnosis of thyroid nodules, so that surgical treatment of thyroid cancer could be performed at a stage when it is not life threatening.

[Solitary hyperfunctioning thyroid gland carcinomas]. / Unifokale hyperfunktionelle Karzinome der Schilddrüse.

BACKGROUND: Thyroid gland carcinomas usually appear as afunctional and hypofunctional lesions on thyroid scintigrams, but some rare cases of thyroid carcinoma with scintigraphic hyperfunctional lesions have also been reported. The aim of our retrospective study was to elucidate the frequency of carcinomas in patients operated for solitary hyperfunctional thyroid nodules and to represent their demographic and clinical features. PATIENTS AND METHODS: During one decade (1997/2006), 308 patients were operated for solitary hyperfunctional thyroid nodules in the Centre for Endocrine Surgery in Belgrade. RESULTS: Malignancy was revealed in 9 cases (about 3 %) by histopathological examination. In 6 cases papillary microcarcinomas were found adjacent to dominant hyperfunctional adenomas, while in 3 cases (about 1 %) real hyperfunctional carcinomas were confirmed. Follicular carcinoma was diagnosed in 2 cases and papillary carcinoma in one. All 3 patients were preoperatively hyperthyroid. In both patients with follicular carcinoma we performed lobectomies. In the third case we carried out a total thyroidectomy considering the intraoperative frozen section finding of a papillary carcinoma. CONCLUSIONS: According to our results the frequency of solitary hyperfunctioning thyroid carcinomas is about 1 %, so that the possibility that a hyperfunctional nodule is malignant should be considered in the treatment of such lesions.

Acute suppurative klebsiella thyroiditis: a case report.

Acute suppurative thyroiditis and thyroid abscess are extremely rare disorders. The most common pathogens causing acute suppurative thyroiditis are Gram-positive bacteria, including staphylococcal and streptococcal species. Thyroid abscess is mostly located in the left thyroid lobe. We report the case of a 75-year-old female patient with acute suppurative thyroiditis and right lobe thyroid abscess caused by Klebsiella spp. The patient had a firm, livid, hardly mobile cervical swelling. Axial computed tomography image showed soft-tissue swelling, an abscess in the right thyroid lobe and swelling of the thyroid gland. The diagnosis was established on a smear culture result. The patient was diabetic and had been operated on for goitre fifty years before. On indirect laryngoscopic examination, the patient was found to have right vocal cord paralysis. Infection and abscess resolved following surgical drainage and treatment with intravenous antibiotics, while the vocal cord paralysis persisted. Diabetes mellitus and previous thyroid surgery, in which sutures were used with unresorptive material, might have been the precipitating factors for the patient to acquire this unusual infection.

The incidence of familial nonmedullary thyroid cancer in a large case series.

PURPOSES OF THE STUDY: In contrast to familial medullary carcinoma, familial nonmedullary thyroid carcinoma (FNMTC) is less frequent and has been less investigated. The aim of this study was to determine the frequency of FNMTC and analyse the main demographic and clinical characteristics of the patients. MATERIAL AND METHODS: Data on 1411 patients surgically treated for nonmedullary thyroid carcinoma, in the Center for Endocrine Surgery in Belgrade, from 1995 to 2006 were analysed. The possible presence of malignant tumours of the thyroid gland was investigated in their closest relatives in order to identify cases of FNMTC. Only data on first-degree relatives (parents and children) and second-degree relatives (grandparents, grandchildren and siblings) were taken into account in the analysis. RESULTS: Thirteen patients (11 females and 2 males) (0.92% of those with nonmedullary carcinoma of the thyroid gland) had a familial form of the disease. In five families two members had a tumour, and in one family three members. In five out of six families it was a papillary carcinoma and in one family a follicular carcinoma. Patient age varied from 20 to 79 years, with a mean age of 40 years. The tumour size ranged from 5 to 60 mm (mean 25 mm). In two of the thirteen cases the tumour penetrated the capsule of the thyroid gland. In four cases the tumour was multicentric and bilateral, and in a further two metastases were present in regional lymph nodes. During the follow-up period, which lasted from 2 to 12 years (mean 8.5 years), two relapses were detected. CONCLUSION: Familial nonmedullary carcinoma of the thyroid gland occurs very rarely.

[The incidence rate of thyroid microcarcinoma during surgery benign disease].

Thyroid microcarcinoma are well-differentiated tumors less than 1 cm in diameter. A retrospective analysis was performed on patients operated of benign thyroid disease at the Center for endocrine surgery, Institute of endocrinology, Clical Center of Serbia in Belgrade, from January 1st to December 31st 2004, in order to establish the incidence of microcarcinoma. Indications for surgery were euthyroid multinodular goiter in 201 patients, thyroiditis in 31, thyroid adenoma in 178, Graves disease in 89 and Plummers disease in 79 patients. The results of this study, demonstrate that in 13.4% of the patients operated for goiter, 6.4% operated for thyroiditis, 5.6% for thyroid adenomas, 9.0% for Graves disease and 7.0% of the patients operated for Plumers disease, the presence of a microcarcinoma was noticed in the definitive histopathologic examination. The results obtained are in line with the current knowledge of high incidence of thyroid microcarcinoma.

Tuberculosis of the thyroid gland: a case report.

Thyroid tuberculosis is a very rare condition even if the incidence of extrapulmonary forms of tuberculosis has increased. We report the case of a 56-year old female patient with tuberculosis of the thyroid gland and tubercular lymphadenitis of the neck mimicking thyroid malignancy. The diagnosis was established on histological examination after surgery in August 2002. Total thyroidectomy and central neck dissection were performed for very hard euthyroid multinodular goiter and paratracheal bilateral lymphadenopathy. There were no evidence of tubercular involvement of the other organs. The patient underwent combination treatment with antitubercular drugs for 6 months. During the three years follow-up period there was no evidence of disease recurrence.

Surgery for thyroid Hürthle cell tumours--a single institution experience.

AIMS: The objective of the study was to report a series of patients with Hürthle cell tumours. METHODS: We reviewed medical records of single institution from January 1982 to December 2002, including follow-up information. RESULTS: We identified 199 patients with Hürthle cell tumours (HCT), 88 patients with Hürthle cell carcinoma (HCC) and 111 patients with Hürthle cell adenoma (HCA). The HCC group had significantly longer duration of the disease and larger tumours (4.8 vs 3.8 cm) compared with HCA group. Gender appeared to play significant role in patients with HCT (women outnumbered man by 7:1; p < 0.01). Surgical management for 80% of patients with HCA consisted of hemithyroidectomy and total thyroidectomy in 87% patients in the HCC group. Temporary laryngeal nerve palsy and temporary hypoparathyroidismus were not seen in HCA group, in HCC group were confirmed in 2.27 and 3.41%, respectively. Four patients with HCC relapsed and two died of HCC. CONCLUSIONS: HCC has outlook for favorable outcome when treated radically with total thyroidectomy.

[Endoscopic ultrasonography (EUS) in preoperative localization of neuroendocrine tumors (NET) of the pancreas].

BACKGROUND: Preoperative localization of pancreatic neuroendocrine tumours (NET) is usually very difficult. Noninvasive, imaging tests, such as abdominal ultrasound, CT or MRI are not sensitive enough as well as selective angiography. The aim of the study was to clarify the usefulness of the EUS in preoperative localization of the pancreatic NET. METHODS: From September 1998 March 2005, EUS was performed in 1600 patients. Among them, in 10 (0.7%), this examination was carried out due to previous biochemical tests, which diagnosed the pancreatic NET. We studied the location, the size and echo-pattern of the neoplasm. The results were compared with operation and histology or EUS- FNA guided pancreatic biopsy in 9/10 patients. All EUS examinations were performed using Olympus GIF-130 videoecho-endoscope with 7,5 /12MHz switchable radial probe. RESULTS: EUS correctly localized the pancreatic NET in 7/8 cases, (sensitivity:87.5%). In 2 patients, EUS accurately exclouded pancreatic NET. There were no false positive findings (specificity 100%). Six tumours were benign (75%), and two were malign (25%). We localized 6 insulinomas and single pancreatic carcinoid tumour. The median tumour size detected by EUS was 21mm. CONCLUSION: EUS is highly accurate in preoperative localization of the pancreatic NET-s and We confirmed it in our study. EUS presents the method of choice for preoperative localization of the pancreatic NET.

Case-control study of female thyroid cancer--menstrual, reproductive and hormonal factors.

A case-control study including 204 histologically verified female thyroid cancer patients and an equal number of hospital controls individually matched with cases by sex, age (+/- 2 years), place of residence and time of hospitalization was performed during the period 1996-2000. In the analysis of data, univariate and multivariate conditional logistic regression, methods were applied. According to multivariate analysis, out of hormonal, menstrual and reproductive characteristics, risk factors for thyroid cancer were spontaneous abortions (odds ratio: OR = 1.89, 95% confidence interval (CI) = 1.03-3.50), oral contraceptives use (OR = 2.34, 95% CI = 1.31-4.18) and thyroid enlargement during pregnancy (OR = 16.44, 95% CI = 3.81-70.80). However, none of these three factors remained independently related to thyroid cancer after adjustment for other factors, which were significantly associated with thyroid cancer in the present study (history of residence in endemic goitre area, history of goitre or thyroid nodule, history of other endocrine diseases, radioactive iodine therapy, occupational exposure to various chemicals, family history of thyroid gland diseases and malignant tumours as well as intake of cruciferous vegetables and other vegetables, and consumption of smoked meat and cheese).

[Rational diagnosis and surgical treatment of solitary thyroid nodules]. / Racionalna dijagnoza i hirursko lecenje solitarnog nodusa stitaste zlezde.

Few subjects in endocrine surgery have generated as much controversy as the management of thyroid nodule. The controversial issues include evaluation of laboratory findings and imaging diagnostic procedures in the patient with solitary thyroid nodule. The major issue in relation to controversies is choice of optimal diagnostic workup.

[Cytologic evaluation of solitary thyroid nodules]. / Citoloska evaluacija solitarnog nodusa stitaste zlezde.

Fine-needle aspiration is a low-cost diagnostic tool with principal value in determining which patients with thyroid nodules should undergo surgery. Team work and close cooperation among endocrinologists, surgeons, and pathologists are essential for success. Cytologic criteria for diagnosis of the most frequent conditions (benign cystic lesions), Hashimoto thyroiditis and malignancies found in thyroid aspirates have been provided. The unsolved problem of the so-called "follicular" or oxyphilic lesion or neoplasia will be investigated by immunocytochemistry.

[Classification, staging, prognostic factors and risk factors in thyroid carcinoma]. / Klasifikacija, stepenovanje, prognosticki faktori i faktori rizika kod karcinoma stitaste zlezde.

Thyroid carcinomas arise from follicular cells (papillary, follicular, Hurthle, anaplastic), parafollicular cells (medullary) and stroma (lymphoma, sarcoma). Gradation and prognostic factors are different for every one of histological type. Most patients with papillary and follicular thyroid cancer have an excellent prognosis. At the other extreme is anaplastic thyroid cancer whose usual mean survival can be measured in months. Exposure to external radiation and living in endemic goiter area increase the frequency of thyroid cancer. Medullary thyroid carcinoma is often familial and may occur in associations with the multiple endocrine neoplasia syndromes.