Indolent B-cell non-Hodgkin lymphomas in children: high association with inborn errors of immunity.

Indolent lymphomas are rare in children and mostly consist of pediatric type follicular (PTFL) and pediatric marginal zone lymphomas (PMZL) and extranodal marginal zone lymphoma (ENMZL). Twenty children with indolent lymphoma (10 PTFL, 6 PMZL, 3 ENMZL, 1 mixed type) among 307 Non-Hodgkin Lymphoma (NHL) were retrospectively evaluated. The mean age of the entire group was 10.4 ± 4.4 and was significantly lower in PTFL than in PMZL. Seven patients (35%) had an associated inborn error of immunity (IEI) which was higher than that seen in aggressive lymphomas (5.9%) (p < 0.0001). Seventeen patients (85%) had stage I/II disease. Two patients received no treatment after surgery. Eleven patients were treated only with 3-6 courses of rituximab. Four patients received 3-6 courses of R-CHOP protocol. The prognosis was excellent Five years overall and event-free survivals were 100% and 85%, respectively.

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.

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.

Albuminuria is associated with 24-hour and night-time diastolic blood pressure in urinary tract infection with renal scarring.

BACKGROUND: We aimed to detect complications and associated risk factors in patients with renal scarring (RS) secondary to recurrent urinary tract infections (UTI). METHODS: Fifty patients with RS were compared with 25 patients without RS by means of, serum creatinine, 24- hour urinary creatinine clearance, and 24-hour urinary albumin levels. Office blood pressure (BP) examination and ambulatory BP monitoring (ABPM) were also performed. RESULTS: Vesicoureteral reflux was detected in 50 patients. Glomerular filtration rate (GFR) < 90 ml/min/1.73 m2 was observed in 5 patients with RS but in no patient without RS. Albuminuria was significantly higher in patients with bilateral RS and severe RS. Patients with albuminuria had a significantly lower GFR than those without. All patients with ambulatory hypertension (HT) were in the RS group, and 60% of those had isolated nocturnal HT. Compared to those without RS, patients with RS had significantly higher SDS values for all BP readings, 24-hour and nighttime systolic and diastolic BP loads with significantly lower systolic dipping. GFR was negatively correlated with diastolic BP SDS and diastolic BP load in patients with RS. Daytime diastolic BP load was significantly higher in those with severe RS than in those with mild RS. CONCLUSIONS: Isolated nocturnal HT could be an early sign of complications in RS of UTI. Albuminuria is related to increased BP and impaired renal function. Therefore, ABPM and assessing albuminuria should be a routine part of the follow-up. Diastolic BP elevations could be associated with worse outcomes in these patients.

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.

Role of FDG PET/CT in the Evaluation of Therapy Response in Systemic Juvenile Xanthogranuloma.

ABSTRACT: Juvenile xanthogranuloma, a rare type of non-Langerhans cell histiocytosis, is mostly seen in childhood and adolescence and generally manifests as widespread skin lesions. It rarely shows systemic involvement. Although the cutaneous form is often self-limited, systemic form is quite aggressive. Here we report the findings of FDG PET/CT scans during the course of cladribine therapy in a 6-year-old girl with systemic juvenile xanthogranuloma.

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.

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.

Utility of 'dual phase' cone beam computed tomography during radioembolisation in patients with hepatocellular carcinoma: what is really changing in flow dynamics before and after 90Y delivery?

PURPOSE: The aims of the study were: 1) to compare two phases of dual-phase cone beam computed tomography (DP-CBCT) achieved before and after Yttrium-90 (90Y) administration and to evaluate additional benefits during radioembolisation (RE) procedures; and 2) to compare DP-CBCT with pre-procedure contrast enhanced cross-sectional images in terms of tumour detection. MATERIAL AND METHODS: Twenty-three hepatocellular carcinoma patients undergoing RE treatment were scanned with DP-CBCT consisting of early arterial (EA) and late arterial (LA) phases before and after 90Y administration. The CT-like datasets were compared according to embolisation effect, enhancement patterns, lesion detectability, image quality, and artifacts by two interventional radiologists blinded to each other. The compatibility of the two radiologists was evaluated with kappa statistical analysis, and the difference between EA and LA phases was evaluated with marginal homogeneity test. Also, DP-CBCT images were compared with preprocedural cross-sectional images (CT/MRI). RESULTS: For 23 patients 92 data were acquired. Thirteen patients showed a decrease on post-embolisation images both visually and on Hounsfield unit (HU) measurements. No statistical difference was found for tumour detection between EA and LA phases (p = 1.0). Tumour enhancement was visually superior at LA phases whereas EA phases were better for arterial mapping for selective catheterisation. DP-CBCT images were not inferior to preprocedural cross-sectional imaging findings. CONCLUSIONS: DP-CBCT is a promising tool for predicting tumour response to therapy and is not inferior to preprocedural cross-sectional imaging in terms of tumour detection. It allows better assessment during RE procedures because early phases provide good mapping for superselective catheterisation whereas late phases are better for visualisation of tumour enhancement.

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.

Outcomes of Radioembolization in Patients with Chemorefractory Colorectal Cancer Liver Metastasis: a Single-Center Experience.

PURPOSE: We aimed to evaluate the efficacy and outcomes of radioembolization with Yttrium-90 (Y-90) microspheres in patients with unresectable and chemorefractory colorectal cancer liver metastasis (CRCLM). METHODS: This single-center study included 43 patients (34 male, 9 female) who underwent radioembolization with Y-90 for unresectable, chemorefractory CRCLM between September 2008 and July 2014. Overall survival (OS), liver progression-free survival (LPFS), overall response rate (ORR), local disease control rate (LDCR), and relations of these parameters with patient disease characteristics were evaluated. OS and LPFS rates were compared according to microspheres. Survival rates were calculated with Kaplan-Meier method, and potential prognostic variables were evaluated on univariate analyses. RESULTS: Post-procedural median OS was 12.8 months. LPFS was 5.6 months. ORR was 33%, LDCR was 67% on 3rd month follow-up. Low tumor burden (< 25%) was associated with higher median OS after radioembolization (< 25 vs > 25-50% p < 0.0001 and < 25 vs > 50% p = 0.005). Patients with left colon tumors exhibited significantly longer median OS after metastasis than right colon tumors (p = 0.046). Extrahepatic disease and synchronicity showed poorer survival parameters; however, the difference was not significant (p = 0.1 and p = 0.3, respectively). In subgroup analyses, the distribution of patient number and characteristics showed heterogeneity as number of patients with low tumor burden was higher in resin Y-90 group. Resin Y-90 group exhibited significantly higher median OS and LPFS compared to glass Y-90 group (16.5 vs. 7 months, p = 0.001; 6.73 vs. 3.38 months, p = 0.023, respectively). CONCLUSION: Radioembolization is a safe local-regional treatment option in chemorefractory, inoperable CRCLM. Radioembolization at earlier stages may lead to more favorable results especially with lower tumor burden patients.

Intra-Arterial Radionuclide Therapies for Liver Tumors.

Intra-arterial radionuclide therapies serve essentially as internal radiation treatment options for both primary and metastatic liver tumors, which imply delivering implantable radioactive microspheres into branches of hepatic arteries that feed liver tumors to provide a high dose of targeted radiation to tumor tissue, while sparing the healthy liver tissue from hazardous effects of radiation. The principle of this therapeutic option depends on the unique preferential arterial supply of malignant liver tumors in contrast with mostly portal venous supply of normal hepatocytes as well as excess amount of arterial neovascularization in the tumor bed. Therefore, intra-arterial radionuclide therapy can provide very high radiation exposure to tumor tissue, which is impossible to reach with external radiation therapy due to serious side effects and moreover, radiation can be targeted to tumor tissue selectively with less side effects. Yttrium-90 (Y-90), a high-energetic beta emitter is the most preferred radionuclide, which is used to label microspheres. Two types of Y-90 microspheres are commercially available that are made of resin and glass. Many studies in the literature have demonstrated that Y-90 microsphere therapy is an efficient and safe locoregional therapeutic option for unresectable primary and metastatic liver tumors such as hepatocellular carcinoma and liver metastases from colorectal cancer and breast cancer as well as neuroendocrine tumors. Furthermore, limited number of studies has reported its use in some relatively uncommon metastatic liver tumors from melanoma, pancreatic, renal, and lung cancer. Besides Y-90 microspheres, Iodine-131 lipiodol, Rhenium-188 lipiodol, Rhenium-188 microspheres, Holmium-166 chitosan, and Holmium-166 microspheres have been introduced as alternative radiopharmaceuticals for intra-arterial therapy for liver tumors.

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.

A homozygous deletion in GRID2 causes a human phenotype with cerebellar ataxia and atrophy.

GRID2 is a member of the ionotropic glutamate receptor family of excitatory neurotransmitter receptors. GRID2 encodes the glutamate receptor subunit delta-2, selectively expressed in cerebellar Purkinje cells. The phenotype associated with loss of GRID2 function was described only in mice until now, characterized by different degrees of cerebellar ataxia and usually relatively mild abnormalities of the cerebellum. This work describes for the first time the human phenotype associated with homozygous partial deletion of GRID2 in 3 children in one large consanguineous Turkish family. Homozygous deletion of exons 3 and 4 of GRID2 (94 153 589-94 298 037 bp) in the proband and similarly affected cousins, and heterozygous deletions in parental DNA were shown using Affymetrix® 6.0 single-nucleotide polymorphism array, confirmed by real-time polymerase chain reaction. The phenotype includes nystagmus, hypotonia with marked developmental delay in gross motor skills in early infancy followed by a static encephalopathy course with development of cerebellar ataxia, oculomotor apraxia, and pyramidal tract involvement.

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.

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.

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.

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.