Current approach to pediatric differentiated thyroid cancer.

Differentiated thyroid cancers (DTC) is a rare cancer in children and adolescents, having features of different clinical presentation, biological behavior, and treatment from adult population. Most of the patient management guidelines are based on literature on adult population and the literature on children and adolescents still limited. There are still unsettled issues regarding both patient management and the therapy. However, the current approach for treatment of DTC includes thyroidectomy, lymph node dissection in patients with nodal metastases and possible use of Iodine-131 radiotherapy. The incidence of DTC is low in pediatric population, and the characteristics of the disease vary among different age groups within this population. Therefore, the literature depends on small cohorts and heterogeneous retrospective studies. This paper aims to review the current literature and give an overview to the approach in the management of DTC in pediatric population. DTC in pediatric population, has an aggressive nature, however the patient's overall survival is excellent. A multidisciplinary approach in the management of pediatric DTC patients would yield fewer side effects and a better life quality.

Factors affecting the response to Y-90 microsphere therapy in the cholangiocarcinoma patients.

OBJECTIVE: The aim of this study was to assess the early therapy response in patients with unresectable CCA who received Y-90 microsphere therapy for CCA and define the factors related to therapy response. MATERIALS AND METHODS: Data of 19 patients [extrahepatic (n: 6) and intrahepatic (n: 13)] who received 24 sessions of Y-90 microsphere therapy [glass (n: 13) and resin (n: 11)] were retrospectively evaluated. Tumor load, tumor size, therapy response evaluation by RECIST1.1 criteria (n: 13), tumor lesion glycolysis (TLG), metabolic tumor volume (MTV), and metabolic therapy responses were evaluated (n: 8) using PERCIST1.0 criteria. RESULTS: No significant relation was found between therapy response and tumor localization, treated liver lobe, type of Y90 microspheres, the presence of previous therapies, perfusion pattern on hepatic artery perfusion scintigraphy, or patient demographics. The mean overall survival (OS) was 11.9 ± 2.3 months and was similar after both resin and glass Y90 microspheres; however, it was longer RECIST responders (p: 0.005). MTV and TLG values significantly decreased after therapy, and ΔMTV (- 45.4% ± 12.1) was found to be positively correlated with OS. No statistical difference was found between iCCA and eCCA, in terms of OS and response to therapy. Although not quantitatively displayed, better-perfused areas on HAPS images had a better metabolic response and less perfused areas were prone to local recurrences. CONCLUSIONS: Both resin and glass microsphere therapy can be applied safely to iCCA and eCCA patients. Early therapy response can be evaluated with both RECIST and PERCIST criteria. Both anatomical and metabolic therapy response evaluations give complementary information.

Ictal Coprolalia: Three Cases with Nondominat Frontal Lobe Involvement and Review of the Literature.

Objective: Coprolalia is defined as the involuntary use of obscene, socially unacceptable, and derogatory words. Ictal coprolalia is a rare presentation of epilepsy. This study aimed to determine the localizing and lateralizing value and frequency of ictal coprolalia in epilepsy patients. Methods: Medical files, discharge summaries, and electroencephalography (EEG) reports of 2238 patients were reviewed retrospectively. We identified patients who suffered from ictal coprolalia. Electroencephalography reports, neuroimaging [brain magnetic resonance imaging (MRI), fluorodeoxyglucose positron emission tomography (FDG-PET), single-photon emission computerized tomography (SPECT)] records, F-18 FDG fused on MRI images, and ictal SPECT fused on MRI images were evaluated. Also, original and review articles were identified through a systematic search of Pubmed, Scopus, and Clarivate Analytics. Results: Ictal coprolalia was detected in 3 male (0.15%) patients. In all patients, ictal semiology was extratemporal-frontal type, and potential/proven epileptic focus was non-dominant hemisphere frontal lobe. Topectomy was done in one of the patients, including the suspected dysplastic area plus the area where the electroencephalographic ictal and interictal changes occur, on the left frontal lobe, and the patient had an Engel's classification class IIA. The data depending on the published cases showed that ictal coprolalia was dominant in the male gender and the responsible epileptic area tended to be located in the non-dominant hemisphere frontotemporal region. Conclusion: The rate of ictal coprolalia in the Turkish population is lower compared to other series. Our results are consistent with previous studies in which reported that male preponderance for ictal coprolalia and involvement of non-dominant frontal lobe.

Thyroid cancer in pediatric age group: an institutional experience and review of the literature.

Very few have been reported on children with differentiated thyroid cancer (DTC), although 15% of them are diagnosed below 20 years of age. Children with DTC present with more advanced disease; however, they have a more favorable outcome. In this paper, we aimed to present the data in our institution on pediatric DTC patients, making an emphasis on the risk factors of metastasis and recurrence, as well as to the outcome of treatment. Clinical data of 50 pediatric patients referred to our institution for radioiodine treatment (RAI) between 1976 and 2010 were obtained. Papillary carcinoma was the most common histopathologic diagnosis (36 patients) followed by papillary carcinoma with follicular variant (10 patients). Multifocality was reported in 66% of the pathology reports. At the time of diagnosis 35 patients had regional lymph node metastasis, 18 had local invasion, and 11 had distant metastasis. No distant metastasis was present in patients with unifocal disease (P=0.018). The mean duration of follow-up was 77.6±62.7 months. Patients with local disease had longer disease-free survival than patients with distant metastasis (P=0.033). Despite the small number of patients, the follow-up was relatively long and the presented results confirmed overall good prognosis in children with DTC.

Diuretic Renal Scintigraphy in Adults: Practical Aspects and Reporting.

Diuretic renal scintigraphy (DRS) is used worldwide for evaluation of kidney functions, diagnosis of pelvic or ureteric obstruction and documentation of the effectiveness of surgical interventions. Although it is a basic imaging procedure of nuclear medicine, there is a wide range of variability in acquisition procedures. Nuclear medicine physicians have the opportunity to modify DRS imaging protocols according to specific clinical problem or question. This plasticity requires readers experience. Interpretation of dynamic images and the quantitative parameters entails knowledge of physiology and pathophysiology of kidneys and collective system. Standardization of patient preparation, imaging protocols and reporting not only would increase the readers' confidence but also would increase the reliability of DRS.

Imaging in Renal Transplants: An Update.

Renal transplantation has become the best treatment for the patients with chronic renal insufficiency. The surgical procedures, immunosuppressive regiments and patient follow-up have evolved especially in the last 10 years. However, the diagnosis for renal transplantation dysfunction remained the same in these years. Serum creatinine levels and estimated glomerular filtration rate calculated by serum creatinine based equations are used in routine patient follow-up. Pelvic ultrasonography and color Doppler ultrasonography are used as a first-line imaging method. Assessment of allograft functions both qualitatively and quantitatively are possible using nuclear medicine procedures. Surgical complications, acute tubular necrosis, subacute and/or acute rejection, infections, toxicity due to immunosuppressive medications, complications relating the collecting system, chronic rejection are the main causes for renal function impairment. The imaging procedures can diagnose the worsening of renal transplant function; however, they still lack the ability to differentiate types of rejection as histopathology or differentiate rejection from other causes of allograft dysfunction. The transplant biopsy gives detailed diagnosis for allograft dysfunction, guide the treatment and therefore it is the preferred diagnostic choice in recent years. On recent years, literature on radionuclide imaging is focused on perfusion analysis for the early diagnosis of renal transplant dysfunction and prognostic use of perfusion parameters, and then this article will focus on these studies and their outcome.

Cerebral blood flow and cognitive function in obstructive sleep apnea syndrome.

Neuropsychological deficits are among the main symptoms of obstructive sleep apnea syndrome (OSAS), which could be related to impaired cerebral blood flow (CBF). We conducted a study in 20 subjects tested in our Sleep Laboratory, to assess regional CBF and cognitive function in OSAS. Our measurements included technetium-99m hexamethylamino propylenamine oxime brain perfusion scintigraphy in wakeful state, i.e. in the morning after polysomnography and also cognitive function tests after polysomnography, in 20 patients, 16 male and 4 female, aging between 30 and 60 years. We found that apnea-hypopnea index was greater than or equal to 5 in 16 (85%) subjects, consistent with OSAS. Mean arterial oxygen saturation during sleep was correlated with CBF in all regions. Cognitive function test scores in verbal memory were positively correlated with percentage of sleep duration with less than 90% of oxygen saturation during sleep. Cerebral blood flow was not uniform in OSAS patients, and was significantly lower in the left frontal and left temporal regions as compared to that of these regions on the right hemisphere. In conclusion, our findings indicated association of CBF and verbal memory with hypoxemia during sleep and decreased perfusion after apneic episodes in the left frontal and temporal lobes in OSAS patients, which could also indicate impairment of upper airway motor control.

Evaluation of SISCOM in routine regional cerebral blood flow alterations after clozapine, in schizophrenia.

Subtraction ictal single photon emission tomography (SPET) co-registered to magnetic resonance imaging (SISCOM) is an ictal-interictal brain perfusion SPET subtraction method, developed for evaluation of brain perfusion changes applied for the identification of epileptic foci. The aim of this study was to test whether regional cerebral blood flow (rCBF) alterations due to clozapine in schizophrenic patients could also be detected with SISCOM. We have studied the brain perfusion SPET data obtained both before (pre-SPET) and 8 weeks after (post-SPET) clozapine treatment, in 20 patients with schizophrenia. These data were used for SISCOM processing. In order to identify any alterations in the perfusion pattern using SISCOM, pre- and post-SPET data were subtracted from each other. Activation maps were created and merged on either pre- or post-SPET images. Visual interpretation of brain perfusion SPET studies were performed and compared with SISCOM findings. We found that final SISCOM images and visual evaluation of pre- and post-SPET studies were well concordant in 17/20 patients. Discordance was observed in 3 patients. In 1 of these 3 patients alterations observed with SISCOM were confirmed as subtle changes on visual re-evaluation of the images. In the remaining 2 of these 3 patients, SISCOM did not confirm the changes observed by visual analysis. Additionally, SISCOM depicted perfusion alteration in occipital cortex in 5 patients. In conclusion, the algorithm of SISCOM seemed to be useful and complementary to visual evaluation, to assess rCBF changes due to clopazine in outpatient schizophrenic patients who had treatment refractoriness or intolerance of previous antipsychotics and to provide additional information when both pre- and post-SPET data were subtracted from each other.

The Complementary Role of 68Ga-DOTATATE PET/CT in Neuroblastoma.

A girl diagnosed with neuroblastoma at 33 months underwent I-MIBG scan after surgery and chemoradiotherapy. Although MIBG scan showed complete response, the bone marrow biopsy showed refractory disease. Therefore, she underwent Ga-DOTATATE PET/CT, which revealed bone marrow involvement and Ga-DOTATATE-avid brain metastasis. Rare physiological pineal gland uptake was also depicted. Ga-DOTATATE PET/CT showed active progressive disease earlier, before it was detectable with MIBG scan. For patients with MIBG-negative relapsed/refractory disease, Ga-DOTATATE may have an important role in restaging, detecting unsuspected metastasis, therapy planning.

The effect of clozapine on regional cerebral blood flow and brain metabolite ratios in schizophrenia: relationship with treatment response.

The purpose of this study was to investigate the effect of clozapine on regional cerebral blood flow (rCBF) and its relationship with response to treatment. In addition, we aimed to study the influence of clozapine on proton magnetic resonance spectroscopy ((1)H-MRS) findings in the dorsolateral prefrontal cortex (DLPFC) in a subgroup of patients. Psychopathology, neurocognitive functioning, and SPECT imaging of 22 patients were assessed at the baseline and 8 weeks after the initiation of clozapine treatment. In 10 of these patients intermediate-echo (TE: 135 ms) single-voxel (1)H-MRS was also performed at the baseline and after 8 weeks. Clozapine treatment increased the right frontal (superior and medial)/caudate perfusion ratio in the whole group, while it increased bilateral frontal (superior and medial)/caudate perfusion ratios in treatment responders. In addition, percentage changes in left and right frontal (superior and medial)/caudate perfusion ratios compared to the baseline were higher in treatment responders than in non-responders. The improvement in attention was related to the increase in percentage change in the right frontal (superior and medial)/caudate perfusion ratio, while the improvement in verbal fluency was related to the increase in percentage changes in both right and left frontal (superior and medial)/caudate perfusion ratios and to right frontal (superior and medial)/thalamus perfusion. Baseline frontal (superior and medial)/thalamus perfusion could explain 32% of the variability of percentage improvements in psychopathology. (1)H-MRS showed that the baseline PANSS general psychopathology score was inversely correlated with the baseline NAA/Cre ratio. An increased NAA/Cre ratio in DLPFC after 8 weeks of clozapine treatment was also revealed by (1)H-MRS. Our SPECT imaging results suggest the presence of an imbalance in fronto-striato-thalamic circuitry that changes with clozapine, especially in the responders, while (1)H-MRS results indicate a supportive effect of clozapine on neuronal integrity.

Impact of renin-angiotensin system polymorphisms on renal haemodynamic responsiveness to acute angiotensin-converting enzyme inhibition in type 2 diabetes mellitus.

INTRODUCTION: The aim of this study was to document the impact of renin-angiotensin system (RAS) polymorphisms on renal haemodynamics and renal hormones in type 2 diabetes mellitus. MATERIALS AND METHODS: Fifty-nine adult patients were studied. Renal haemodynamics were evaluated using 99mTc-MAG3 clearance (MAG3( Cle)) using Bubeck's method and captopril renogram. RAS hormones and angiotensin-converting enzyme (ACE) levels were measured before and after captopril.ACE, angiotensin II type 1 receptor and angiotensinogen gene polymorphisms were analysed. RESULTS: Post-captopril MAG3(Cle) values were significantly lower in patients with microalbuminuria compared to nonproteinuric patients. Statistically significant negative correlation was found between clearance percentage change values and HbA(1c) levels (r: -0.42, p=0.009). MAG3(Cle) was relatively lower following captopril administration in DD patients, while a relative increment was observed in I allele carriers (p=0.02).TheAC-CC group had significantly higher mean post-captopril clearance value compared to the AA genotype (480.9+/-56.1 ml/min/1.73 m(2) vs. 428.4+/-74.8 ml/min/1.73 m(2), p=0.022). CONCLUSIONS: Our data indicate that the heterogeneity of patients' response to ACE inhibition is, at least partly, genetically determined, and the genetic polymorphisms in RAS might predict the acute responsiveness to ACE inhibitors.

Nuclear Medicine in Thyroid Diseases in Pediatric and Adolescent Patients.

Both benign and malignant diseases of the thyroid are rare in the pediatric and adolescent population, except congenital hypothyroidism. Nuclear medicine plays a major role, both in the diagnosis and therapy of thyroid pathologies. Use of radioactivity in pediatric population is strictly controlled due to possible side effects such as secondary cancers; therefore, management of pediatric patients requires detailed literature knowledge. This article aims to overview current algorithms in the management of thyroid diseases and use of radionuclide therapy in pediatric and adolescent population.

Etiological yield of SNP microarrays in idiopathic intellectual disability.

Intellectual disability (ID) has a prevalence of 3% and is classified according to its severity. An underlying etiology cannot be determined in 75-80% in mild ID, and in 20-50% of severe ID. After it has been shown that copy number variations involving short DNA segments may cause ID, genome-wide SNP microarrays are being used as a tool for detecting submicroscopic copy number changes and uniparental disomy. This study was performed to investigate the presence of copy number changes in patients with ID of unidentified etiology. Affymetrix(®) 6.0 SNP microarray platform was used for analysis of 100 patients and their healthy parents, and data were evaluated using various databases and literature. Etiological diagnoses were made in 12 patients (12%). Homozygous deletion in NRXN1 gene and duplication in IL1RAPL1 gene were detected for the first time. Two separate patients had deletions in FOXP2 and UBE2A genes, respectively, for which only few patients have recently been reported. Interstitial and subtelomeric copy number changes were described in 6 patients, in whom routine cytogenetic tools revealed normal results. In one patient uniparental disomy type of Angelman syndrome was diagnosed. SNP microarrays constitute a screening test able to detect very small genomic changes, with a high etiological yield even in patients already evaluated using traditional cytogenetic tools, offer analysis for uniparental disomy and homozygosity, and thereby are helpful in finding novel disease-causing genes: for these reasons they should be considered as a first-tier genetic screening test in the evaluation of patients with ID and autism.

The relation between perfusion pattern of hepatic artery perfusion scintigraphy and response to y-90 microsphere therapy.

OBJECTIVE: Hepatic artery perfusion scintigraphy is a routine procedure for patient evaluation before Y-90 radiomicrosphere therapy and mostly used for prediction of extrahepatic leakage. Moreover, it also displays perfusion pattern of tumours, which is an important parameter on success of the therapy. The aim of this study is to assess the relation between the perfusion pattern on hepatic artery perfusion scintigraphy and radiomicrosphere therapy response. METHODS: A total of 99 radiomicrosphere therapy applications were carried out in 80 patients (M/F: 55/25). RESULTS: Heterogeneous and diffuse perfusion patterns were observed in 47 patients and 52 patients, respectively. The patients with diffuse perfusion pattern had better therapy response both on FDG PET/CT (p= 0.04) and CT (p=0.008) when compared to those with heterogenous perfusion pattern. CONCLUSION: Perfusion pattern observed on hepatic artery perfusion scintigraphy may be a successful predictor of early response to radiomicrosphere therapy. CONFLICT OF INTEREST: None declared.

Experience with nuclear medicine information system.

OBJECTIVE: Radiology information system (RIS) is basically evolved for the need of radiologists and ignores the vital steps needed for a proper work flow of Nuclear Medicine Department. Moreover, CT/MRI oriented classical PACS systems are far from satisfying Nuclear Physicians like storing dynamic data for reprocessing and quantitative analysis of colored images. Our purpose was to develop a workflow based Nuclear Medicine Information System (NMIS) that fulfills the needs of Nuclear Medicine Department and its integration to hospital PACS system. MATERIAL AND METHODS: Workflow in NMIS uses HL7 (health level seven) and steps include, patient scheduling and retrieving information from HIS (hospital information system), radiopharmacy, acquisition, digital reporting and approval of the reports using Nuclear Medicine specific diagnostic codes. Images and dynamic data from cameras of are sent to and retrieved from PACS system (Corttex©) for reprocessing and quantitative analysis. RESULTS: NMIS has additional functions to the RIS such as radiopharmaceutical management program which includes stock recording of both radioactive and non-radioactive substances, calculation of the radiopharmaceutical dose for individual patient according to body weight and maximum permissible activity, and calculation of radioactivity left per unit volume for each radionuclide according their half lives. Patient scheduling and gamma camera patient work list settings were arranged according to specific Nuclear Medicine procedures. Nuclear Medicine images and reports can be retrieved and viewed from HIS. CONCLUSION: NMIS provides functionality to standard RIS and PACS system according to the needs of Nuclear Medicine. CONFLICT OF INTEREST: None declared.

Serum PON-1 activity but not Q192R polymorphism is related to the extent of atherosclerosis.

AIM: Paraoxonase-1 (PON1) is an antioxidant enzyme located in high density lipoprotein (HDL). PON1 was defined as a protective factor against atherosclerosis. The aim of this study was to investigate the possible relationship between serum paraoxonase (PONase), homocysteine thiolactonase (HTase) activities and PON1 Q192R polymorphism, and the extent and severity of atherosclerosis. METHODS: Blood specimens were collected from 142 individuals who had no coronary artery lesions angiographically (control group) and 128 individuals who had angiographically documented coronary artery disease of several degrees (patient group). The extent and severity of arterial lesions were evaluated by the Gensini scoring system. PONase and HTase activities were measured in serum using a spectrophotometric method. PON1 Q192R polymorphism was evaluated using PCR-RFLP after DNA isolation from blood. RESULTS: Serum PONase and HTase activities were significantly lower in the patient group than in healthy controls (135.7±56.0U/mL vs 153.8±62.0U/mL, p< 0.05; 36.0±6.1 U/mL vs 43.0±4.04 U/mL, p< 0.01; respectively). In the patient group, there was a negative correlation between PONase, HTase activities and the Gensini score (r=-0.168, p= 0.039; r=-0.164, p= 0.006, respectively). In both groups, there was no significant difference in the distribution of PON1 Q192R polymorphism. In the patient group, the distribution of Gensini scores according to genotypes was not significant. CONCLUSION: It has been concluded that serum PONase and HTase activities might be a more relevant marker than PON1 genotype in evaluating the extent and severity of atherosclerosis.

The relationship between changes in functional cardiac parameters following anthracycline therapy and carbonyl reductase 3 and glutathione S transferase Pi polymorphisms.

The aim of this prospective clinical study is to evaluate the relationship between changes in functional cardiac parameters following anthracycline therapy and carbonyl reductase 3 (CBR3p.V244M) and glutathione S transferase Pi (GSTP1p.I105V) polymorphisms. Seventy patients with normal cardiac function and no history of cardiac disease scheduled to undergo anthracycline chemotherapy were included in the study. The patients' cardiac function was evaluated by gated blood pool scintigraphy and echocardiography before and after chemotherapy, as well as 1 year following therapy. Gene polymorphisms were genotyped in 70 patients using TaqMan probes, validated by DNA sequencing. A deteriorating trend was observed in both systolic and diastolic parameters from GG to AA in CBR3p.V244M polymorphism. Patients with G-allele carriers of GSTP1p.I105V polymorphism were common (60%), with significantly decreased PFR compared to patiens with AA genotype. Variants of CBR3 and GSTP1 enzymes may be associated with changes in short-term functional cardiac parameters.

A new autosomal dominant Peters' anomaly phenotype expanding the anterior segment dysgenesis spectrum.

PURPOSE: To test the association of genes involved in anterior segment development in a family with autosomal dominantly inherited Peters' anomaly (PA) with a unique ocular phenotype. METHODS: Six members of a five-generation family with PA were extensively phenotyped and linkage analysis of candidate genes, namely, PAX6, PITX2, FOXC1, CYP1B1 and MAF, was performed. RESULTS: The complete pedigree consisted of 38 members, 19 of whom were affected. The six probands examined had bilateral microcornea, corneal opacity, iridocorneal adhesions, nystagmus and strabismus, but cataract, keratolenticular adhesions, glaucoma and posterior embryotoxon were absent. PAX6 gene mutations had been previously excluded in one of the affected members. DNA markers for candidate genes CYP1B1 on 2p22, PITX2 on 4q25, PAX6 on 11p13, MAF on 16q23 and FOXC1 on 6p25 were genotyped. Highly negative lod scores were obtained for all markers. CONCLUSIONS: The exclusion of these genes as likely candidates supports the hypothesis that the ocular phenotype associated with PA segregating in this family is a distinct, new, autosomal dominant entity in the anterior segment dysgenesis spectrum.