Nuclear medicine training and practice in Turkey.

Nuclear medicine applications in Turkey started in the early 1950s, grew as an independent medical discipline and finally were recognized by the Ministry of Health in 1973. Later on, the professional organization of nuclear medicine physicians and other related professionals including radiopharmacists and technologists under the Turkish Society of Nuclear Medicine were established in 1975. Recently after completing more than a half century in Turkey, nuclear medicine has proved to be a strong and evolving medical field with more than 600 physicians serving for the changing needs of clinical practice throughout these years. This article describes past and present facts in this field and attempts to provide insights into the future which hopefully will be brighter than before.

Lack of α8 integrin leads to morphological changes in renal mesangial cells, but not in vascular smooth muscle cells.

BACKGROUND: Extracellular matrix receptors of the integrin family are known to regulate cell adhesion, shape and functions. The α8 integrin chain is expressed in glomerular mesangial cells and in vascular smooth muscle cells. Mice deficient for α8 integrin have structural alterations in glomeruli but not in renal arteries. For this reason we hypothesized that mesangial cells and vascular smooth muscle cells differ in their respective capacity to compensate for the lack of α8 integrin. RESULTS: Wild type and α8 integrin-deficient mesangial cells varied markedly in cell morphology and expression or localization of cytoskeletal molecules. In α8 integrin-deficient mesangial cells α-smooth muscle actin and CTGF were downregulated. In contrast, there were no comparable differences between α8 integrin-deficient and wild type vascular smooth muscle cells. Expression patterns of integrins were altered in α8 integrin-deficient mesangial cells compared to wild type mesangial cells, displaying a prominent overexpression of α2 and α6 integrins, while expression patterns of the these integrins were not different between wild type and α8 integrin-deficient vascular smooth muscle cells, respectively. Cell proliferation was augmented in α8 integrin-deficient mesangial cells, but not in vascular smooth muscle cells, compared to wild type cells. CONCLUSIONS: Our findings suggest that α8 integrin deficiency has differential effects in mesangial cells and vascular smooth muscle cells. While the phenotype of vascular smooth muscle cells lacking α8 integrin is not altered, mesangial cells lacking α8 integrin differ considerably from wild type mesangial cells which might be a consequence of compensatory changes in the expression patterns of other integrins. This could result in glomerular changes in α8 integrin-deficient mice, while the vasculature is not affected in these mice.

The Correlation of Clinicopathological Findings and Neutrophil-to-Lymphocyte and Platelet-to-Lymphocyte Ratios in Papillary Thyroid Carcinoma

Objectives: Inflammatory markers such as neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) have been recently introduced as potential biomarkers for tumor pathogenesis, development and prognosis in solid tumors. Our aim was to assess the correlation of clinicopathological features and NLR and PLR in patients with papillary thyroid carcinoma (PTC). Methods: A total of 201 papillary thyroid carcinoma patients were divided into groups with a cut-off preoperative median NLR and PLR value of 1,92 and 123.9, respectively. The correlation of NLR and PLR and clinicopathological features including age, tumor size, extra-thyroidal extension, thyroid capsule invasion, surgical margin positivity, multifocality, bilaterality of the patients were analyzed. Results: The mean NLR and PLR were 2.11±0.94, 129.69±42.81, respectively. Larger tumor size and higher positivity of extra-thyroidal spread were correlated with higher NLR values. No significant relationship was found between NLR and age, presence of thyroid capsule invasion, surgical margin positivity, multifocality, bilaterality, and lymph node metastasis. Also no significant association was observed between the clinicopathological features and PLR. Conclusion: High NLR was found to correlate with tumor size and extra-thyroidal extension. NLR may be used as a marker to determine the clinical behavior of disease in patients with papillary thyroid carcinoma (PTC).

Multiple primary tumors in differentiated thyroid carcinoma and relationship to thyroid cancer outcome.

AIM: Patients with differentiated thyroid carcinoma (DTC) have long-life expectancy and are at risk for developing a second primary cancer. Aim of this study was to assess the occurrence of DTC in conjunction with other primary neoplasms. It was also aimed to explore the possibility of synchronous or metachronous other malignancies having an impact on clinical course of thyroid carcinoma. MATERIAL & METHODS: Clinical records of 1680 DTC patients treated and followed in our institution over last twenty years were reviewed. Forty-five second primary tumors were found in 42 patients. These patients were classified into 3 groups as antecedent (group I), synchronous (group II) or subsequent (group III) according to the timing of occurrence of non-thyroidal malignancy. The initial characteristics of thyroid neoplasm were compared between patients with DTC plus another tumor and DTC only. Kaplan-Meier Survival Analysis was used to estimate the survival probability for patients with DTC alone and DTC plus another primary tumor. RESULTS: There were 15 synchronous and 30 metachronous tumors in 42 patients. Three of them had triple tumors. The most common second primary was lympho-haematological and upper aero digestive system tumors in group I and II respectively, whereas a variety of tumors were noted in group III. Despite the more common occurrence of unfavourable prognostic factors in patients with multiple cancers than thyroid cancer alone, complete response to radioiodine therapy and recurrence free survival rate was similar in both groups (p>0.05). CONCLUSION: The results of the current series imply that the occurrence of multiple primary tumors is not uncommon in patients with DTC. Close medical surveillance and the use of advanced screening modalities might lead to the detection of second primary tumors in DTC. However, the presence of second primary seems not to affect the clinical course of DTC.

Surgical approaches for papillary microcarcinomas: Turkey's perspective.

OBJECTIVES: The incidence of papillary microcarcinomas, which are defined as thyroid cancers of <10mm in size, has been increasing in the last decade. Herein, we present internet-based questionnaire results performed by the Turkish Association of Endocrine Surgery with the aim to evaluate the perspective of the management of papillary microcarcinomas in Turkey. MATERIAL AND METHODS: The user-friendly questionnaire consisted of 13 questions in total. These questions mainly addressed the surgical management of nodules and cancer of <1 cm in size. Patient management before, during, and after surgical intervention was also included; additionally, the "active surveillance approach" was questioned. RESULTS: There were 420 responders in total who were of multidisciplinary origin (endocrinologists, surgeons, nuclear medicine specialists, pathologists, and oncologists). Total thyroidectomy was the predominant treatment approach (65%) for the classical type of microcarcinoma limited in one lobe, whereas in cases of microcarcinomas incidentally diagnosed during hemithyroidectomy, complementary surgery approach was advised by 40% of the responders. The responders found capsule invasion (86%) and patient based management (94%) of high importance. The percentage of the responders who recommended radioactive iodine ablation in incidental cancers having no aggressive criteria was 51%. The survey participants that were against routine central dissection in these cases accounted for 73% of the responders. The recommendation of active surveillance (follow-up without any interventional therapy) was limited with 9% responders. CONCLUSION: The results of the questionnaire demonstrated that there have been various choices in Turkey for the surgical treatment of the papillary microcarcinomas.

False-positive I-131 accumulation in a hepatic hydatid cyst.

In this report, a case of differentiated thyroid carcinoma having false-positive I-131 accumulation due to a large hydatid cyst in the liver is presented. Abdominal sonographic examination of a 37-year-old patient with differentiated thyroid carcinoma demonstrated an ovoid, complex cystic mass containing cystic parts as well as solid-appearing components in the right lobe of liver, which is concordant with a type CE-3 hydatid cyst. The postablative whole-body scan obtained 10 days after 100 mCi I-131 therapy displayed intense and homogeneous uptake of radioiodine in the liver. Hepatic cystic mass was removed, and postoperative histologic evaluation confirmed hydatid disease. Some cystic lesions of the kidney and liver have been previously reported as causes of false-positive radioiodine accumulation.

Risk factors for persistent disease in papillary thyroid carcinoma with lymph node metastasis.

PURPOSE: It is known that the presence of neck lymph node (LN) metastasis is correlated with persistent disease in papillary thyroid carcinoma (PTC) patients. After appropriate therapy, most patients become disease free, whereas some may still have persistent disease. The present study aimed to determine the potential variables affecting the clinical course of the disease and persistent disease patterns in PTC patients with LN metastasis. MATERIALS AND METHODS: The study group included consecutive PTC patients with LN metastasis. Clinicopathological characteristics and persistent disease pattern during the follow-up period were examined to identify risk factors for persistent disease using univariate and multivariate analyses. RESULTS: At the end of a median follow-up of 84 months, 90 (69%) patients became disease free and 40 (31%) patients had persistent disease. Univariate analysis showed that male sex, older age at initial diagnose (≥45 years), larger tumor size (>4 cm), presence of lateral cervical LN metastasis, extrathyroidal invasion, and higher number of metastatic LN (≥10) were significant predictors for persistent disease. Multivariate analysis showed that extrathyroidal involvement, presence of lateral cervical LN metastasis, and older age at initial diagnosis (≥45 years) were independent predictors for persistent disease. CONCLUSION: Despite the presence of LN involvement, most patients may become disease free with therapy. Patients with extrathyroidal invasion, lateral cervical LN involvement, and those at least 45 years old at initial diagnosis are more likely to have persistent disease. However, disease control can be achieved with close clinical follow-up and therapy.

Scintigraphic diagnosis of protein-losing enteropathy secondary to amyloidosis.

Protein-losing enteropathy is an uncommon syndrome of excessive loss of protein via the gastrointestinal mucosa. 99mTc-dextran scintigraphy was performed on a 42-year-old woman with protein-losing enteropathy. She had secondary amyloidosis due to rheumatoid arthritis. Abnormal leakage of the radiotracer was observed in the mid-abdominal region suggesting the site of protein loss. It is concluded that 99mTc-dextran scintigraphy is useful as a noninvasive and simple test for the imaging and confirmation of diagnosis in protein-losing enteropathy.

The role of Tc-99m sestamibi imaging in predicting clinical response to chemotherapy in lung cancer.

Multidrug resistance (MDR) is a major problem in lung cancer. Tc-99m methoxyisobutyl isonitrile (MIBI) has been demonstrated to be a non-invasive marker to diagnose MDRI related P-glycoprotein (Pgp) and multidrug resistance-associated protein (MRP) expression in various solid tumors. The aim of this study was to evaluate the relationship between the degree of Tc-99m MIBI uptake and its retention on delayed images and the response to chemotherapy in lung cancer. Twenty-three patients (1 woman and 22 men, age range 40-67 years) with lung cancer (9 small cell and 14 non-small cell) were examined with Tc-99m MIBI imaging before chemotherapy. After i.v. administration of 740 MBq Tc-99m MIBI, planar and SPECT imaging at 30 minutes and 2 hours was performed. Tumor to normal lung uptake ratio (T/N) and percent retention were measured. Response to chemotherapy was evaluated according to follow-up CT and grouped as complete responders (CR), partial responders (PR) and non-responders (NR). Clinical follow-up and CT evaluation revealed that 12 patients had partial remission, 4 patients had complete remission and 7 patients had no-remission after chemotherapy. Statistically, there was no significant correlation between early (30 min), delayed (2 hr) T/N ratios and percent retention of Tc-99m MIBI with chemotherapeutic response of the lung cancer among the three groups (p > 0.05). Results of the current study imply that Tc-99m MIBI uptake and the retention index may not correlate with chemotherapy response in lung cancer, so that the accuracy of this method needs to be verified in a larger series with additional investigation at the molecular level.

Technetium-99m-DTPA aerosol scintigraphy in amiodarone induced pulmonary toxicity in comparison with Ga-67 scintigraphy.

Amiodarone hydrochloride, which is used in life-threatening cardiac tachyarrhythmia, has been known to cause amiodarone induced pulmonary toxicity (AIPT) as a complication. In this study we aimed to investigate the clinical value of technetium-99m diethylene triamine penta-acetic acid (DTPA) aerosol lung scintigraphy in patients with AIPT in comparison with gallium-67 (Ga-67) scan. The study group included 26 cases, 7 patients with diagnosis of AIPT (Group A), 8 patients receiving amiodarone therapy but without AIPT (Group B) and 11 healthy subjects as a control group (Group C). All patients underwent Ga-67 and Tc-99m-DTPA aerosol scintigraphy in addition to various laboratory tests, Ga-67 scintigraphy was positive in 4 of 7 AIPT patients but quite normal in Group B. A positive correlation was found (r = 0.52, p < 0.05) between kep values determined by Tc-99m-DTPA aerosol scintigraphy and the cumulative dose of amiodarone. The mean kep values were 2.04% +/- 0.85%/min, 1.30% +/- 0.42%/min and 0.86% +/- 0.19%/min for groups A, B and C, respectively. The mean clearance rate of group A was significantly faster than that of normals (p < 0.0005) and group B (p = 0.028). In addition, there was a significant difference between groups B and C (p = 0.015). In conclusion, Ga-67 lung scintigraphy is a useful method for the detection of AIPT but Tc-99m-DTPA aerosol scintigraphy offers better results than Ga-67 scintigraphy. Early changes in Tc-99m-DTPA clearance may be observed in patients receiving amiodarone. The kep value in patients with AIPT is noticeably increased with respect to the control group. With its favorable physical properties, low cost, lower radiation burden and its ability to be used as an objective measure for the pulmonary clearance rate, Tc-99m-DTPA aerosol scintigraphy appears to be promising in patients receiving amiodarone therapy.

Radiosynovectomy in hemophilic synovitis.

UNLABELLED: Radisosynovectomy (RS) is a local form of radionuclide therapy used in various forms of arthritis characterized by synovitis. In hemophilic arthropathy, RS provides removal of inflamed synovium and prevents further joint damage. This review focuses on the practical aspects of radionuclide synovectomy in hemophilic patients and describes the issues both related to the methodology and post-therapeutic follow-up. CONFLICT OF INTEREST: None declared.

Clinical implications of diffuse hepatic uptake observed in postablative and post-therapeutic I-131 scans.

Diffuse hepatic uptake of I-131 either on diagnostic or post-therapeutic scans is a usual finding in patients with differentiated thyroid carcinoma. The aim of this study was to evaluate the frequency and clinical significance of diffuse hepatic uptake of radioiodine on post-therapeutic (PT) and postablative (PA) whole-body scans.A total of 720 PA and 172 PT I-131 scans in a total of 732 patients with differentiated thyroid carcinoma were retrospectively reviewed. Residual thyroid tissue and diffuse liver uptake of I-131 were classified from 0 to 4. The correlation between the liver and thyroid remnant uptake score, dose of radioiodine, serum thyroglobuline (Tg), liver function test levels (ALT, AST), liver ultrasonography, presence of metastatic foci, and recurrent disease were examined.Diffuse hepatic uptake was observed in 701 of 722 (94.2%) PA and 162 of 172 (97%) PT whole body I-131 scans. Hepatic radioiodine uptake was positively correlated with the dose of administered I-131 and increased levels of serum AST and ALT. Liver uptake scores of patients with hepatosteatosis were significantly higher than all study groups. However, no evidence of a relationship between diffuse visualization of liver and serum thyroglobulin levels, uptake score of thyroid remnants, presence of local or distant metastatic foci on I-131 scan, and recurrence rate could be demonstrated.The lack of correlation between hepatic radioactive iodine (RAI) uptake and Tg levels, functioning metastatic tissue or thyroid remnants suggests that this finding may be related to factors other than thyroid tissue. The positive correlation between administered RAI dose, hepatic enzymes and hepatosteatosis support the conclusion that diffuse hepatic RAI uptake may be related to different mechanisms as well.