The Current State of Nuclear Nephrology in Modern Medicine.

Glomerular filtration rate (GFR) is the most reliable parameter of renal function. Regarding the complexity of the gold standard inulin clearance, different estimating equations have been developed with CKD-EPI creatinine equation recommended as the most reliable one. In some clinical situations where creatinine based equations might not be valid, alternative methods are needed. Nuclear medicine methods for measuring GFR with 51Cr EDTA and 99mTc DTPA have been widely used for decades. There are different methodologies for the measurement of kidney function with radiopharmaceuticals: urinary clearance, plasma clearance, multiple plasma sampling, slope intercept, single sample plasma equation, slope only, and the gamma camera-based method. Greater precision of measuring GFR is needed in certain clinical situations. The most common are diagnosis and follow up of chronic kidney disease and definition of the beginning of replacement therapy. The assessment of renal function is also important for potential kidney donors. In recent years, with the introduction of new chemotherapeutic drugs and targeted therapy, oncologic patients treated with nephrotoxic drugs have become more commonly referred for measuring GFR. The monitoring of renal function is important during treatment in order to detect the transformation from reversible acute kidney injury to irreversible chronic kidney disease as well as in the cases of renal insufficiency reduce the dosage and prevent accumulation of the drug and avoid dosage related toxic effects. Assessment of kidney function using measured mGFR will be an important milestone in the creation of more accurate and expanding personalized medicine principle in current onconephrology practice.

Polyostotic Fibrous Dysplasia in a Six-year-Old Boy.

Fibrous dysplasia (FD) is a rare congenital benign bone disease that manifests as a defect in the bone remodeling process, affecting the function, differentiation, and maturation of osteoblasts. This process is located in the bone marrow, where the normal marrow tissue is replaced with immature bone islands and fibrous stroma. The etiology is unclear so far, but it is known to be connected with a point mutation of the gene that encodes Gs α protein at the time of embryogenesis, and because of that, all of the affected somatic cells become dysplastic. It is important to determine whether the mutation occurred earlier in the process of embryogenesis so that there will be more mutant cells and the disease will appear in a more severe form. The clinical presentation of FD is variable, so there are plenty of potential differential diagnoses. The most common include Paget disease, non-ossifying fibroma, osteofibrous dysplasia, aneurysmal bone cyst, adamantinoma, giant cell tumor, fracture callus, and low-grade central osteosarcoma.

The usefulness of [99mTc]MIBI scintigraphy in the diagnostic algorithm of ultrasonographical suspected thyroid nodules by using EU-TIRADS criteria.

BACKGROUND: Although not yet involved in the algorithm of thyroid nodules, 99mTc-methoxy-isobutyl-isonitrile ([99mTc]MIBI) scintigraphy may help in the individual diagnostic workup of a thyroid patient, especially where indeterminate fine needle aspiration biopsy (FNAB) is present. The aim of this study was to evaluate the usefulness of [99mTc]MIBI thyroid scintigraphy in the diagnostic algorithm of thyroid nodules, particularly in ultrasound EU-TIRADS 4 or 5 lesions, that cytologically were either indeterminate or benign. MATERIAL AND M: ETHODS: A retrospective randomized study, including 42 thyroid patients, with mean age 47 ± 17 years, was conducted. [99mTc]MIBI scan was compared with ultrasound (US) EU-TIRADS criteria, pertechnetate scan, FNAB and histopathological findings for the differentiation of malignant thyroid nodules from benign lesions. RESULTS: The US mainly detected hypoechoic inhomogeneous presentation of the thyroid nodules (35/42, 83.33%), 4 cases with isoechoic nodules and 2 cases presented with hyperechoic thyroid nodules. Histopathology revealed malignancy in 15/42 (35.71%), while all other patients 27/42 (64.29%) were benign. Visual analysis score showed that patients scored with 1+ and 2+ were statistically significant to be benign, while 13 vs. 10 pts that were visual score 3+ were malignant vs. benign (p > 0.05). Sensitivity was 100%, while specificity was very low 22.22%, PPV was 41.67%. CONCLUSIONS: Even [99mTc]MIBI scan is not routinely used as a daily practice diagnostic tool of thyroid nodules, we will further apply it on a larger group of patients and try to quantify the uptake of the radiotracer to see whether it will help in the diagnostic algorithm of thyroid nodules.

Ultrasound features and preoperative accuracy of the fine needle aspiration biopsy in detection of thyroid carcinomas.

OBJECTIVE: To analyze the ultrasound (US) characteristics and fine needle biopsy (FNAB) of thyroid carcinomas (TCs) prior to surgery and compare with postoperative histopathology and to determine FNAB sensitivity and specificity. MATERIAL AND METHODS: Retrospective analysis of the US data during 1999-2015 was performed, as well as analysis of FNAB results and using histopathology report as "gold standard" the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of this method was evaluated. RESULTS: Data revealed that tumors >51 mm were declining by 50% in the period 2011-2015 compared to 2005-2010 or by 18% 2011-2015 compared to 1999-2004 and significant increase was detected in diagnosis of multicentric tumors. The analysis revealed that FNAB has sensitivity = 65.7% CI (0.59% - 0.71%) and specificity = 50% CI (0.43%-0.56%), PPV = 56.9% and NPV = 59.2%. CONCLUSION: We found increasing detection of smaller TCs, as well as more frequent detection of multicentricity of the neoplastic foci. FNAB results in our study revealed low sensitivity and specificity. Major limitation of the study was inability to exactly separate US guided from non US guided FNAB in evaluation of the sensitivity and specificity, due to retrospective nature of the analysis. Further studies evaluating only US guided FNAB should be performed.

Solitary metastatic deposit in the mandible from follicular thyroid carcinoma.

Follicular thyroid carcinoma (FTC) is the second most common cancer of the thyroid, after papillary carcinoma. Oral metastasis arising from FTC is very rare. Mandible is more commonly affected than maxilla, with the premolar-molar region being the most frequent site of metastasis. We present the case of a 68yearold female, with swelling in the region of the parotid gland, complaining of periodic rightsided pain in the temporomandibular joint, which occurred most often in the morning with numbness and pain, and difficulty in opening the mouth. After ultrasound and X-ray, the patient was operated and the pathohistological finding was in favor of metastasis of FTC. After 3 months, a total thyroidectomy was performed, and FTC was detected in the right thyroid lobe. Laboratory results were as follows: FT4 = 9.92 pmol/L, thyroid-stimulating hormone = 9.9 mIU/L, and hTG >300 µg/L. Bone scan showed no bone metastasis. Radioablation with 131I of 150 mCi was given to the patient, followed by substitutional therapy with levothyroxine. Mandible metastasis as a single skeletal deposit from follicular thyroid carcinomas is a rare clinical finding. Maxillofacial surgeons should consider and rule out thyroid pathology before performing operation of tumor formation in the mandible region. If feasible, surgical-based treatment options offer the best survival outcomes.

Prognostic factors in thyroid carcinomas: a 17-year outcome study

ABSTRACT Objectives The aim of our study was to evaluate the survival rate of all thyroid carcinomas (TCs) diagnosed in the 1999-2015 period in the Republic of North Macedonia and to analyze the prognostic influence of several characteristics on development of distant metastases, as well as to analyze the prognostic effect of seven clinical and constitutional features on mortality. Material and methods A retrospective analysis of medical data from all TCs diagnosed in 1999-2015 was performed. The survival rate of all types of TCs was estimated using the Kaplan Meier method. Univariate and multivariate logistic regression analysis was applied for evaluation of the predictive role of seven clinical and constitutional characteristics for development of distant metastases, and the univariate Cox-proportional model was applied for evaluation of the predictors for mortality. Results A total of 422 TC cases were diagnosed in the 17-year period, with an average survival time of 212.99 months. Results of the univariate regression analysis showed that dimension at initial ultrasound and histopathological type of tumor were significantly predictive variables for distant metastases. Multifocal tumors vs. unifocal tumors < 15 mm significantly increased the probability of distant metastases by 7.401 (p = 0.005, 95% CI = 1.817-30.190) times. Age, initial lymph node involvement, number of radioiodine therapies, and histopathology of the tumor were selected as independent significant predictors for mortality. Conclusion Our results showed an excellent overall prognosis of thyroid tumors in the Macedonian population. The dimension of the tumor, multifocality, and histopathological type were the most relevant prognostic predictive features for development of distant metastases.

Prognostic factors in thyroid carcinomas: a 17-year outcome study.

Objectives The aim of our study was to evaluate the survival rate of all thyroid carcinomas (TCs) diagnosed in the 1999-2015 period in the Republic of North Macedonia and to analyze the prognostic influence of several characteristics on development of distant metastases, as well as to analyze the prognostic effect of seven clinical and constitutional features on mortality. Material and methods A retrospective analysis of medical data from all TCs diagnosed in 1999-2015 was performed. The survival rate of all types of TCs was estimated using the Kaplan Meier method. Univariate and multivariate logistic regression analysis was applied for evaluation of the predictive role of seven clinical and constitutional characteristics for development of distant metastases, and the univariate Cox-proportional model was applied for evaluation of the predictors for mortality. Results A total of 422 TC cases were diagnosed in the 17-year period, with an average survival time of 212.99 months. Results of the univariate regression analysis showed that dimension at initial ultrasound and histopathological type of tumor were significantly predictive variables for distant metastases. Multifocal tumors vs. unifocal tumors < 15 mm significantly increased the probability of distant metastases by 7.401 (p = 0.005, 95% CI = 1.817-30.190) times. Age, initial lymph node involvement, number of radioiodine therapies, and histopathology of the tumor were selected as independent significant predictors for mortality. Conclusion Our results showed an excellent overall prognosis of thyroid tumors in the Macedonian population. The dimension of the tumor, multifocality, and histopathological type were the most relevant prognostic predictive features for development of distant metastases.

FALSE POSITIVE RADIOIODINE POST-ABLATION SCAN IN SCALP REGION IN A WOMAN WHO USED HAIR COLORING REVEALED BY SPECT/CT.

OBJECTIVE: Radioiodine ablation with iodine-131 is a standard therapeutic procedure for patients diagnosed with differentiated thyroid carcinoma (DTC). We present a contamination artifact on whole-body scan (WBS), after radioiodine ablation due to papillary thyroid carcinoma. The hybrid imaging resolved the question of metastasis versus contamination. METHODS: In the case of 35-year-old female patient we used a General Electric hybrid gamma camera with a high-energy-general-purpose collimator for performing WBS, and single photon emission computed tomography combined with low dose computed tomography (SPECT/CT) for the detection of any residual thyroid tissue or meta-static disease and at the same time ablation and treatment of any confirmed metastasis. RESULTS: A thyroid scan showed activity in the remnant thyroid tissue of the right lobe, but also laterally in the calvaria (left temporal region). The patient's neck ultra-sound and thyroglobulin level were not in favor of metastasis. A false positive finding due to hair coloring was concluded with SPECT/CT hybrid imaging. CONCLUSION: SPECT/CT scan can contribute to establishing a final diagnosis in patients being evaluated for atypical locations of radioactive iodine accumulation after ablative doses of radioactive iodine, distinguishing between metastases from DTC and false positive accumulations or artifacts.

Demographic and Clinical Features of Thyroid Carcinomas in Republic of Macedonia (1999-2010).

BACKGROUND: Thyroid carcinomas (TC) are the most common endocrine malignancies. In some parts of the world, the incidence of TCs has increased over the past few decades, especially in females according to some studies. AIM: We have set as the objective for our study to analyse the demographic, ultrasound features, thyroid hormonal status and frequency of thyroid carcinomas in the Republic of Macedonia according to histopathological type. MATERIALS AND METHODS: Retrospective analysis of medical data from all diagnosed and treated patients with TC at the Institute of Pathophysiology and Nuclear Medicine for the period 1999-2010 was performed. Demographic characteristics: age at diagnosis, gender, histopathological type of TC and from clinical features: US findings and thyroid hormonal state at initial examination and their distribution in eight state regions were evaluated. RESULTS: Total number of 204 patients with TC in the Republic of Macedonia was registered. Papillary thyroid carcinoma (PTC) was the most frequent with 131 pts (64.21%), follicular (FTC) with 13 pts (6.37%) was second thyroid malignoma, followed by medullary (MTC) with 12 pts (5.88%), anaplastic (ATC) 11 pts (5.39%) and the rarest types were Hurtle cell carcinoma and intrathyroid sarcoma with only 1 diagnosed case. Age varied widely from 7 yrs to 88 yrs age (average 47.9 ± 16.6 yrs). PTC was more prevalent in younger age groups, while ATC was diagnosed in elderly patients. In all of the eight-country regions, the prevalence rate was higher for females than males (3:1) or 15.21/105 female to 5.03/105 male prevalence rate. According to US appearance mostly TC was unilateral in 42.65% and multifocal in 7.84% with dimensions from 15 to 50 mm. CONCLUSION: There is an increase in incidence and prevalence rate of TCs in our country, mostly PTC, while reduction exists in the number of diagnosed cases of ATC and FTC, comparing with previous studies before iodine prophylaxis program. Different from described in the literature is female: male (4:1) ratio for ATC. According to US features, we can conclude that introduction of more detailed reporting system may improve diagnostic accuracy.

Etiopathogenesis of Differentiated Thyroid Carcinomas.

INTRODUCTION: Thyroid malignomas are a heterogeneous group of neoplasm consisting of most frequent differentiated encountered carcinomas, papillary and follicular thyroid carcinoma, then medullary thyroid carcinoma originating from neuroendocrine calcitonin-producing C-cells and rare forms of thyroid lymphomas arising from intrathyroidal lymphatic tissue, thyroid sarcomas and poorly differentiated anaplastic thyroid carcinoma. There are increasing numbers of epidemiological studies and publications that have suggested increased incidence rate of thyroid carcinomas. We have read, analysed and compare available reviews and original articles investigating different etiological factors in the development of thyroid carcinomas through Google Scholar and PubMed Database. DISCUSSION: Aetiology involved in the development of thyroid carcinomas is multifactorial and includes external influences, as well as constitutional predispositions and genetic etiological factors. The actual effect of environmental and constitutional factors is on promoting genetic and epigenetic alterations which result in cell proliferation and oncogenesis. Until now are identified numerous genetic alterations, assumed to have an important role in oncogenesis, with MAPK and PI3K-AKT as crucial signalling networks regulating growth, proliferation, differentiation and cell survival/apoptosis. CONCLUSION: This new molecular insight could have a crucial impact on diagnosis and also on improving and selecting an appropriate treatment to the patients with thyroid malignancies.