Clinical and genetic characteristics of retinoblastoma patients in a single center with four novel RB1 variants.

AIM: To assess the clinical and genetic characteristics of children diagnosed with retinoblastoma (RB) at Gazi University Faculty of Medicine's Department of Pediatric Oncology. METHODS: All cases diagnosed with RB and received treatment and follow-up in the Ophthalmology and Pediatric Oncology Department, October 2016 to May 2021 were evaluated retrospectively. The RB1 gene was analyzed by next-generation sequencing (NGS) technique in DNAs obtained from peripheral blood samples of the patients. RESULTS: This study included 53 cases with 67 RB-affected eyes during the study period. The mean age was 24.6 (median: 18.5, range: 3-151)mo. There were 15 (22.3%) Group D eyes and 39 (58.2%) Group E eyes. The RB1 gene was sequenced by the NGS method in 19 patients. Heterozygous RB1:NM_000321.3: c.54_76del (p.Glu19AlafsTer4) variant was detected in a 15-month-old female with bilateral RB. Heterozygous RB1:NM_000321.3: c.1814+3A>T variant was detected in a 5.5-month-old male with bilateral RB. The intronic RB1:NM_000321.3: c.1332+4A>G variant was detected in patient 14, a 13-month-old male with unilateral RB. The RB1:NM_000321.3: c.575_576del (p.Lys192SerfsTer10) variant was found in an 18-month-old female with an allele frequency of 37%. These variants have not been reported in the literature and mutation databases. CONCLUSION: Four novel variants are described and one of them is found in two different patients. This data is crucial for assessing prognosis. It serves as a guide for estimating the long-term risk of secondary malignancy as well as the short-term risk of developing additional malignancies in the same eye and the other eye.

Quantitative and visual analyses of the effect of activity reduction on image metrics and quality in 18F-FDG PET/MRI in pediatric oncology.

BACKGROUND: : The aim of our study was to evaluate the effect of reduced injected tracer activities on the quantitative image metrics and the visual image quality in whole-body 18F-FDG PET/MRI with TOF capability in pediatric oncology. METHODS: Seventy-seven PET/MRI examinations of 54 patients were analyzed (standard injected activity: 1.9 MBq/kg, standard PET scan duration: 5 min per bed position). Lower activity PET images (1.2 MBq/kg and 0.9 MBq/kg) were retrospectively simulated from the originally acquired list-mode data sets. Quantitative parameters were assessed by measuring the SUV metrics, signal-to-noise ratio (SNR), contrast-to-noise ratios (CNR), and textural features in each PET data set. PET images were also evaluated visually for image quality by using a scoring system. RESULTS: SNRs were found as significantly different among PET data sets (p < 0.001) and showed increasing image noise with decreasing activities. CNR values did not show significant differences among PET data sets. The mean relative percentage changes in SUV metrics were found to be lower in 1.2 MBq/kg data set compared to 0.9 MBq/kg data set. Lesion SUVmax, SUVmean, SULpeak, and textural features were significantly different in 0.9 MBq/kg data set compared to the original data set (p < 0.05 for all). However, SUV metrics and textural features did not show a significant difference between the original and 1.2 MBq/kg data sets. While, the mean visual scores in 0.9 MBq/kg data set were significantly different compared to the original data set (p < 0.001), there was no significant difference between the original and 1.2 MBq/kg data sets in terms of general image quality and image sharpness. DISCUSSION: Our analyses showed that the reduction of injected activity to 1.2 MBq/kg may be feasible in pediatric oncological PET/ MRI, with a smaller relative percentage change in quantitative parameters and with similar image quality to the original data set.

Prognostic value of fluorodeoxyglucose positron emission tomography derived metabolic parameters and textural features in pediatric sarcoma.

PURPOSE: The aim of this study was to evaluate the prognostic value of PET-derived metabolic features and textural parameters of primary tumors in pediatric sarcoma patients. METHODS: The imaging findings of 43 patients (14 girls and 29 boys; age 11.4 ± 4.4 years) who underwent 18-fluorodeoxyglucose positron emission tomography (PET)/computed tomography for primary staging prior to therapy between 2005 and 2020 were retrospectively evaluated. The diagnoses were osteosarcoma in 10, rhabdomyosarcoma in 10, and Ewing sarcoma in 23 patients. PET metabolic data and textural features of primary tumors were obtained. Cox proportional hazards regression models were used to identify predictors for progression-free survival and overall survival. Survival curves were estimated by using the Kaplan-Meier method. RESULTS: Distant metastases were detected in primary staging in 13 patients (30.2%). The median follow-up duration after diagnosis was 28 months (range: 10-171 months). In multivariate Cox regression analysis, the presence of distant metastasis and neighborhood grey-level difference matrix_Contrast (ngldm_Contrast) were found as independent predictors for both progression-free survival and overall survival. Grey-level zone length matrix_Zone-length nonuniformity (glzlm_ZLNU) was also found as an independent predictor for overall survival. The Kaplan-Meier survival analysis showed that higher ngldm_Contrast and glzlm_ZLNU values of primary tumors were significantly associated with shorter progression-free survival and overall survival. CONCLUSION: In addition to the presence of distant metastasis at initial diagnosis, textural features of primary tumors may be used as prognostic biomarkers to identify patients with worse prognosis in pediatric sarcoma. Higher tumor heterogeneity is significantly associated with shorter progression-free survival and OS.

Assessment of PD-L1 expression in patients with neuroblastoma and renal tumors.

BACKGROUND: Programmed death 1 (PD-1) is a co-receptor which is located at the surface of cells like natural killer, monocytes, T and B cells. It has two ligands including programmed death ligand-1 (PD-L1) and ligand-2 (PD-L2). T cell functions are inhibited by activation of PD-1/PD-L1 pathway and this pathway is used by viruses and some tumor cells in order to escape from immune eradication. In our study we evaluated PD-L1 expression in the tissue specimens of patients with Wilms tumor, neuroblastoma and other renal tumors. METHODS: Totally 60 patients who were followed up at Gazi University Hospital with the diagnosis of neuroblastoma, Wilms tumor and other renal tumors were included. PD-L1 expression was examined in tumor samples of the patients. RESULTS: Positive staining with PD-L1 was detected only in two male patients. Both of them had neuroblastoma and advanced stage disease. None of the patients with Wilms tumor and other renal tumors had positive PD-L1 staining. CONCLUSIONS: Unlike adult tumors, PD-L1 expression is not common in childhood tumors due to differences in immune system between children and adults. Further studies are needed to establish the importance and effects of PD-1/PD-L1 pathway in pediatric tumors.

Comparison of FDG PET/MRI and FDG PET/CT in Pediatric Oncology in Terms of Anatomic Correlation of FDG-positive Lesions.

The aims of our study were to compare F-18 fluorodeoxyglucose (FDG) positron-emission tomography/magnetic resonance imaging (PET/MRI) and PET/computed tomography (CT) in pediatric oncology patients in terms of anatomic correlation of FDG-positive lesions, and also to compare diffusion-weighted imaging (DWI) with PET to assess the correlation between apparent diffusion coefficient (ADC) values and standardized uptake value (SUV). Sequential PET/CT and PET/MRI images and/or whole-body DWI and ADC mapping in 34 pediatric patients were retrospectively analyzed. FDG-positive lesions were visually scored for CT, T1-weighted, T2-weighted, and DWI images separately in terms of anatomic correlation of FDG-avid lesions. Correlation analysis was performed for SUV parameters and ADC values. Among 47 FDG-positive lesions identified concurrently on PET/CT and PET/MRI, 37 were positive on CT and 46 were positive on at least one MRI sequence (P=0.012). Among 32 FDG-positive lesions for which DWI were available, 31 could be clearly depicted on DWI, resulting in significant difference compared with CT alone in the detection of FDG-positive lesions. No correlation was found between ADC and SUV. FDG PET/MRI exhibits better performance than PET/CT in terms of anatomic correlation of FDG-avid lesions. Therefore, PET/MRI may be more advantageous than PET/CT, not only due to reduced ionizing radiation dose but also for a better depiction of FDG-avid lesions in pediatric PET imaging.

Oral and dental alterations and growth disruption following chemotherapy in long-term survivors of childhood malignancies.

PURPOSE: More attention has been focused on the long-term side effects of treatment protocols since impressive advances in childhood cancer treatment have resulted in a growing population of patients. The purpose of this study was to investigate the disturbances of dento-facial development in children who were long-term survivors of childhood malignancies. METHODS: Fifty-three children (mean age, 10 years + 4 months) in long-term remission underwent oral/dental and radiographic examinations after completion of therapy. Crown and root malformations, gingival/periodontal status, enamel defects, discolorations, decayed and unerupted teeth, premature apexifications, agenesis, maximal interincisal opening and lateral movement of jaws, and soft tissue abnormalities were noted. Caries were evaluated by the decayed-missing-filled teeth (DMFT) index. Forty healthy children (mean age, 12 years + 4 months) belonging to the same age group and socioeconomic community were served as controls. All participants in the study were evaluated in terms of craniofacial development. RESULTS: The data of the study showed that higher prevalence of root malformation, unerupted teeth, and enamel hypoplasia were detected as a consequence of childhood cancer and/or antineoplastic therapy. Although no differences of craniofacial growth and development were observed between groups (P > 0.05), plaque and gingival index scores were statistically higher in the study group (P < 0.05). CONCLUSION: A range of variations in dental structures is recognized as a side effect of childhood cancer therapy in long-term survivors of pediatric malignancies that may affect their quality of life.

Epigenetic silencing of the tumor suppressor genes SPI1, PRDX2, KLF4, DLEC1, and DAPK1 in childhood and adolescent lymphomas.

The aim of the study was to investigate the expression and methylation status of seven distinctive genes with tumor suppressing properties in childhood and adolescent lymphomas. A total of 96 patients with Hodgkin Lymphoma (HL, n = 41), Non-Hodgkin Lymphoma (NHL, n = 15), and reactive lymphoid hyperplasia (RLH, n = 40, as controls) are included in the research. The expression status of CDKN2A, SPI1, PRDX2, DLEC1, FOXO1, KLF4 and DAPK1 genes were measured with QPCR method after the RNA isolation from paraffin blocks of tumor tissue and cDNA conversion. DNA isolation was performed from samples with low gene expression followed by methylation PCR study specific to promoter regions of these genes. We found that SPI1, PRDX2, DLEC1, KLF4, and DAPK1 genes are significantly less expressed in patient than the control group (p = 0.0001). However, expression of CDKNA2 and FOXO1 genes in the patient and control groups were not statistically different. The methylation ratios of all genes excluding the CDKN2A and FOXO1 were significantly higher in the HL and NHL groups than the controls (p = 0.0001). We showed that SPI1, PRDX2, DLEC1, KLF4 and DAPK1 genes are epigenetically silenced via hypermethylation in the tumor tissues of children with HL and NHL. As CDKN2A gene was not expressed in both patient and control groups, we conclude that it is not specific to malignancy. As FOXO1 gene was similarly expressed in both groups, its relationship with malignancy could not be established. The epigenetically silenced genes may be candidates for biomarkers or therapeutic targets in childhood and adolescent lymphomas.

Association of CYP3A5 Expression and Vincristine Neurotoxicity in Pediatric Malignancies in Turkish Population.

Vincristine is a widely used chemotherapeutic agent in the treatment of childhood malignancies. Neuropathy is the most common adverse effect. CYP3A4 and CYP3A5 enzymes of cytochrome p450 enzyme system are responsible in vincristine metabolism. Genetic polymorphism may alter the vincristine metabolism and the neurotoxicity rate. In this study, distribution of CYP3A5 alleles among Turkish children with malignancies, relation between CYP3A5 genotype and neurotoxicity rates, as well as severity and duration of neuropathy and total vincristine doses were investigated. Patient group consisted of 115 patients (age, 1 to 17 y) with acute lymphoblastic leukemia and solid tumors, who were treated with vincristine consisting chemotherapy protocols. Control group consisted of 50 children without any neurological symptom or disorders. All patient files were reviewed for presence and severeness of neurotoxicity symptoms. Blood samples were obtained and CYP3A5 genotypes were analyzed. Neurotoxicity occurred in 20.8% of patients. Although it was found to occur more frequently after 4 doses of vincristine, and rates were higher in the low-dose vincristine group suggesting other contributing factors. Although neurotoxicity rate in the CYP3A5*1/*3 genotype was 17.6%, it was 21.6% in the CYP3A5*3/*3 genotype and the difference was not statistically significant (P<0.05). This study suggested that vincristine-related neurotoxicity is dose-independent and genotype is not the only causative factor in the occurrence of neurotoxicity in these patients.

Treatment of high-risk neuroblastoma: National protocol results of the Turkish Pediatric Oncology Group.

BACKGROUND: The national protocol aimed to improve the outcome of the high risk neuroblastoma patients by high-dose chemotherapy and stem cell rescue with intensive multimodal therapy. MATERIALS AND METHODS: After the 6 induction chemotherapy cycles, patients without disease progression were nonrandomly (by physicians' and/or parent's choices) allocated into two treatment arms, which were designed to continue the conventional chemotherapy (CCT), or myeloablative therapy with autologous stem cell rescue (ASCR). RESULTS: Fifty-six percent (272 patients) of patients was evaluated as high risk. Response rate to induction chemotherapy was 71%. Overall event-free survival (EFS) and overall survival (OS) at 5 years were 28% and 36%, respectively. "As treated" analysis documented postinduction EFS of 41% in CCT arm (n = 138) and 29% in ASCR group (n = 47) (P = 0.042); whereas, OS was 45% and 39%, respectively (P = 0.05). Thirty-one patients (11%) died of treatment-related complications. CONCLUSION: Survival rates of high-risk neuroblastoma have improved in Turkey. Myeloablative chemotherapy with ASCR has not augmented the therapeutic end point in our country's circumstances. The adequate supportive care and the higher patients' compliance are attained, the better survival rates might be obtained in high-risk neuroblastoma patients received myeloablative chemotherapy and ASCR.

Assessment of brachial artery reactivity, carotid intima-media thickness, and adhesion molecules in pediatric solid tumor patients treated with anthracyclines.

The aim of this study was to determine subclinical atherosclerosis and endothelial functional disturbance with measurement of carotid intima-media thickness (IMT), brachial artery reactivity (BAR), and levels of serum adhesion molecules in children with solid tumors who were treated with anthracyclines and are actually in complete remission. Fifty patients who were in remission and 30 healthy children were included in the study. Mean ages of patient and control groups were 13.5 ± 4.7 years (range: 3-23 years) and 12.00 ± 4.3 years (range: 4-21 years), respectively. The patients were divided into 3 groups according to cumulative doxorubicin dose: Group 1, ≤100 mg/m(2); Group 2, 101-299 mg/m(2); Group 3, ≥300 mg/m(2). The BAR and carotid IMT were measured in order to determine the endothelial function. The serum adhesion molecule levels in our patients and controls were also measured. The BAR of the patients with cumulative anthracycline dose ≥300 mg/m(2) was significantly lower than the patients with cumulative anthracycline dose ≤100 mg/m(2) and healthy controls (P =.005 and P =.003, respectively). Also, there was a negative correlation between brachial artery reactivity and increasing cumulative anthracycline dose (r = -.287, P =.044). We also found significant difference between the mean carotid IMT of the patients and the healthy children (P =.041). No statistically significant difference was detected between the serum levels of sICAM-1 (soluble intercellular adhesion molecule-1), sVCAM-1 (soluble vascular cell adhesion molecule-1), sE-selectin of the patients and controls. The use of anthracyclines in pediatric patients with cancer could result in increase of the carotid IMT and endothelial dysfunction.

Multisystem langerhans cell histiocytosis with thymic involvement diagnosed with anterior mediastinal mass in a 2-month-old boy.

Thymus gland involvement in Langerhans cell histiocytosis (LCH) is usually part of multi-system disease and may be more common than previously recognized. However, thymic involvement causing an anterior mediastinal mass is an extremely rare presentation of multisystem LCH. Here we report a 2-month-old-boy admitted to hospital with a giant anterior mediastinal mass with multisystem LCH involving the thymus, lungs, liver and skin. The differential diagnosis of mediastinal mass in children should also include LCH, especially multisystem disease. LCH should also be kept in mind in the differential diagnosis of skin lesions in infants, even if spontaneous regression occurs.

Breastfeeding and Childhood Cancer: Is Breastfeeding Preventative to Childhood Cancer?

Breastfeeding is well-known to have a protective effect against infection in infants. It has been suggested that breast milk may play a role in the prevention of certain childhood cancer. We investigated this issue in a case-control study comprising 300 patients with childhood cancer. There was 73 patients (24.3%) with leukemia, 82 patients (27.3%) with lymphoma, and 146 patients (48.4%) with solid tumors (brain tumors, neuroblastoma, soft tissue sarcomas, germ cell tumors, renal tumor, bone tumor, retinoblastoma, hepatoblastoma, and others) and 316 controls matched for age and sex. Breastfeeding duration of the control group was found to be significantly longer than the patient group (X(2) = 57.774; P < .001). In conclusion, breastfeeding was found to be inversely associated with pediatric cancer in our study.

Risk factors for cisplatin-induced long-term nephrotoxicity in pediatric cancer survivors.

BACKGROUND: The aim of this study was to compare the nephrotoxicity risk of cisplatin (CPL) and ifosfamide (IFO) combination treatment (CT) with that of CPL alone and to evaluate the prevalence of CPL-induced long-term nephrotoxicity in pediatric cancer survivors (CS). METHODS: A total of 33 patients with pediatric solid tumors who have been cured of their disease were included in the study. They were divided into two groups based on the type of chemotherapeutics, either CPL (n = 21) or CT (n = 12), given during cancer treatment and were evaluated for glomerular and tubular function using the Skinner grading system. RESULTS: Nephrotoxicity was found in 15 CS (45.4%): seven (21.3%) of those had moderate, six (18.2%) had mild, and two (6.1%) had severe nephrotoxicity. Neither the rates of overall nephrotoxicity, glomerular toxicity and tubular toxicity, nor the mean overall, glomerular and tubular toxicity scores differed significantly among the CPL and CT groups (P > 0.05 for all parameters). Cumulative IFO dose and age at treatment were found to be independent risk factors for both development and severity of CPL-induced nephrotoxicity (P = 0.025 and P = 0.036 for development of nephrotoxicity; P = 0.004 and P = 0.050 for severity of nephrotoxicity, respectively). CONCLUSIONS: Although CPL-induced long-term nephrotoxicity was found in half of the pediatric CS of solid tumors, clinically significant nephrotoxicity was detected only in a minority of them. Both higher cumulative IFO dose and younger age at treatment were found to be independent risk factors for both development and severity of CPL-induced nephrotoxicity.

Thyroid abnormalities in survivors of childhood cancer.

OBJECTIVE: To investigate the late side effects of childhood cancer therapy on the thyroid gland and to determine the risk factors for development of thyroid disorder among childhood cancer survivors. METHODS: One hundred and twenty relapse-free survivors of childhood cancer (aged 6-30 years) were included in this study. The diagnoses of patients were lymphoma, leukemia, brain tumor, rhabdomyosarcoma and nasopharyngeal carcinoma (NPC). The patients were divided into two groups depending on the treatment: group 1-chemotherapy (ChT) only (n=52) and group 2-combination therapy of ChT + radiotherapy (RT) (head/neck/thorax) (n=68). Thyroid function tests, urinary iodine levels, and thyroid gland ultrasound examinations were evaluated in both groups. RESULTS: Incidence of thyroid disease was 66% (n=79) in the survivors. The thyroid abnormalities were: hypothyroidism (HT) (n=32, 27%), thyroid nodules (n=27, 22%), thyroid parenchymal heterogeneity (n=40, 33%), autoimmune thyroiditis (n=36, 30%), and thyroid malignancy (n=3, 2%). While the incidence of HT and thyroid nodules in group 2 was significantly higher than in group 1, the incidence of thyroid parenchymal heterogeneity and autoimmune thyroiditis was similar in the two patient groups. HT and thyroid malignancy were seen only in group 2. In multivariate logistic regression analysis, a history of Hodgkin lymphoma (HL), brain tumor and NPC, as well as cervical irradiation and 5000-5999 cGy doses of radiation were found to constitute risk factors for HT. History of HL and 4000-5999 cGy doses of radiation were risk factors for thyroid nodules. Head/neck irradiation and treatment with platinum derivatives were risk factors for autoimmune thyroiditis. In univariate analysis, a history of NPC, cervical + nasopharyngeal irradiation, and treatment with platinum derivatives were risk factors for thyroid parenchymal heterogeneity. CONCLUSION: Our results indicate that there is especially an increased risk of HT and thyroid nodules in patients treated with combination therapy of ChT with head/neck/thorax RT. Although chemotherapeutic agents per se do not seem to cause HT, longer follow-up is needed to assess whether or not there is an increased risk for autoimmune thyroiditis and thyroid parenchymal heterogeneity after antineoplastic therapy.

Successful multimodal treatment for aggressive metastatic and recurrent fibrolamellar hepatocellular carcinoma in a child.

Fibrolamellar variant of hepatocellular carcinoma (FLHCC) does not have a favorable prognosis than conventional HCC, and there is no difference regarding the response to chemotherapy and the degree of surgical resectability. FLHCC commonly recurs after complete surgical resection, and there is a high rate of lymph node metastases. Herein, we report a 12-year-old girl with metastatic FLHCC with multiple recurrences aggressively treated with surgery, chemotherapy, and antiangiogenic agents. She is in complete remission after 4 years and 2 months after the diagnosis of metastatic FLHCC. The standard treatment of FLHCC is excision of the primary tumor and its metastases. Chemotherapy for FLHCC is controversial, and it has been suggested that cytoreductive chemotherapy was ineffective and adjuvant chemotherapy did not improve survival. Our patient with multiple recurrences was successfully treated with surgery, first-line chemotherapy with cisplatin and doxorubicin, second-line chemotherapy with 5-fluorouracil/interferon-α combination, and adjuvant antiangiogenic agents like cyclophosphamide and thalidomide. As FLHCC patients have no underlying liver disease, they can tolerate higher doses of chemotherapy compared with conventional HCC patients. We support the use of repeated aggressive surgery with adjuvant chemotherapy and antiangiogenic therapy, which provided complete remission in our patient with metastatic and recurrent FLHCC.

Resveratrol and adipose-derived mesenchymal stem cells are effective in the prevention and treatment of doxorubicin cardiotoxicity in rats.

Anthracyclines can cause severe cardiac toxicity leading to heart failure. The aim of this study was to determine the effects of cardioprotective polyphenolic compound resveratrol (RES) and adipose-derived mesenchymal stem cells (ADMSCs) on cardiac tissue of rats treated with doxorubicin (DOX). Forty-two female and three male Wistar-Albino rats were included in the study. The study groups and the control groups were as follows: Group I: DOX; Group II: DOX + RES; Group III: DOX + ADMSCs; Group IV: DOX + RES + ADMSCs; Group V: Sham operation; and Group VI: normal saline. ADMSCs obtained from male rats were defined with stem cell markers [CD11b/c(-), CD45(-), CD90(+), CD44(+), and CD49(+)]. DOX 12 mg/kg intraperitoneally (i.p.) was injected as a single dose in female rats. Resveratrol 100 mg/kg was injected three times i.p. in Groups II and IV. ADMSCs 2 × 10(6) cells/kg/dose were labeled with bromodeoxyuridine (BrdU) and injected i.p. for a total of three times in Groups III and IV. When the study was terminated after 4 weeks, the beating hearts were connected to a Langendorff setup and records were obtained for 30 minutes. Histopathological, immunhistochemical, and immunofluorescent examination with H&E, Troponin I, and BrdU stains were also performed. Also, ADMSCs were demonstrated in the myocardium of transplanted rats. Left ventricle functions and myocardial histology demonstrated significant impairment in DOX only group compared to groups with ADMSCs (P < .05). We suggest that RES and ADMSCs were successful in the prevention and treatment of the doxorubicin cardiomyopathy in rats. The hypothetical mechanisms of regeneration are multiple, including cell differentiation and autocrine/paracrine effects of ADMSCs.

High-risk ALK negative anaplastic large-cell lymphoma presenting with hypereosinophilic syndrome in a 2.5-year-old child.

The hypereosinophilic syndromes (HES) are characterized by prolonged nonreactive peripheral blood hypereosinophilia with tissue damage. The lymphocytic HES variant can precede malignant clonal T-cell disease in adults but it is extremely rare to be the presenting feature of lymphomas in children. Here we present a 2.5-year-old boy with HES and mediastinal T-cell anaplastic lymphoma kinase (ALK) negative systemic anaplastic large-cell lymphoma. Mature and immature eosinophils without blasts were shown on bone marrow aspiration while biopsy revealed malignant infiltration. The patient responded well to initial corticosteroid therapy, but high-risk features make a challenge of finding the cure in this extremely rare case.

High-risk CD117-positive gastrointestinal stromal tumor of the colon in a 12-year-old girl: adjuvant treatment with imatinib mesylate.

Gastrointestinal stromal tumors (GISTs) are mesenchymal tumors of the alimentary tract rarely observed in children. The treatment of choice for GIST is surgical resection. Although the prognosis of GISTs with low malignant potential is excellent, high-malignant-potential GISTs have a high rate of recurrence. Prognostic factors such as tumor size, mitotic rate and presence of metastases may provide an indication for adjuvant imatinib mesylate (IM) treatment. Here we present a young patient with a large GIST with high-risk features who is in complete remission after surgical excision and adjuvant IM treatment. This patient is the only colon-located CD117-positive case where IM was administered. The exact indications as well as the optimal dose and duration of IM need to be clarified with the contribution of new cases and the growing experience of this rare disease.

Familial synchronous bilateral teratoid Wilms tumor with elevated alpha-fetoprotein level.

Familial Wilms tumor is a rare entity that accounts for only 1-2% of all Wilms tumor cases, with an earlier age of onset and an increased frequency of bilateral tumors. Teratoid Wilms tumor is a variant of nephroblastoma with a predominance of heterologous tissues comprising more than 50% of the tumor volume. Wilms tumor does not usually secrete any specific tumor marker and all teratoid Wilms tumor cases previously reported were sporadic non-secreting neoplasms. Here we describe an infant with familial synchronous bilateral teratoid Wilms tumor whose serum alpha-fetoprotein level was elevated. To our knowledge, this extremely rare type of case is reported for the first time in the literature.

Institutional experience of paediatric high-grade central nervous system tumours: an analysis of 74 patients and review of the literature.

AIM OF THE STUDY: Although the survival for children with certain central nervous system (CNS) tumour types has improved through current surgical and adjuvant treatment modalities, the prognosis of many high-grade tumours remains poor despite aggressive treatment. The aim of this study is to analyse patients with high-grade brain tumours in our institution to determine the histopathology, clinical characteristics, treatment modalities, and survival. MATERIAL AND METHODS: A total of 74 patients with a diagnosis of high-grade brain tumour were analysed. There were a total of 31 patients with embryonal tumours, 27 patients with high-grade glial tumours, 12 patients with brain stem gliomas and 4 patients with other high-grade brain tumours. RESULTS: There were 48 (65%) boys and 26 (35%) girls (ratio: 1.85) with a median age of 99.7 months (range = 2-204 months). The median follow-up period was 19 months (range = 1-204 months). Tumour recurrence was observed in 38 patients (51.4%). The overall survival rate and event-free survival rate of our patients were 27% and 19.5%, respectively. CONCLUSIONS: Pediatric high-grade CNS tumours have a very aggressive behaviour and a significant number of children eventually succumb to disease despite multimodal treatment. There is a need of more effective therapeutic approaches for these tumours with poor prognosis. The future improvement in childhood high-grade brain tumour management depends on a better understanding of the molecular genetics and biology of brain tumours.