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  • 1
    Language: English
    In: International Journal of Radiation Oncology, Biology, Physics, 01 March 2012, Vol.82(3), pp.1135-1141
    Description: Therapy and tumor-related effects such as hypoperfusion, internal hydrocephalus, chemotherapy, and irradiation lead to significant motor and cognitive sequelae in pediatric posterior fossa tumor survivors. A distinct proportion of those factors related to the resulting late effects is hitherto poorly understood. This study aimed at separating the effects of neurotoxic factors on central nervous system metabolism by using H-1 MR spectroscopy to quantify cerebral metabolite concentrations in these patients in comparison to those in age-matched healthy peers. Fifteen patients with World Health Organization (WHO) I pilocytic astrocytoma (PA) treated by resection only, 24 patients with WHO IV medulloblastoma (MB), who additionally received chemotherapy and craniospinal irradiation, and 43 healthy peers were investigated using single-volume H-1 MR spectroscopy of parietal white matter and gray matter. Concentrations of -acetylaspartate (NAA) were significantly decreased in white matter ( 0.0001) and gray matter ( 0.0001) of MB patients and in gray matter ( 0.005) of PA patients, compared to healthy peers. Decreased creatine concentrations in parietal gray matter correlated significantly with older age at diagnosis in both patient groups (MB patients, 0.009, 0.52; PA patients, 0.006, 0.7). Longer time periods since diagnosis were associated with lower NAA levels in white matter of PA patients ( 0.008, 0.66). Differently decreased NAA concentrations were observed in both PA and MB groups of posterior fossa tumor patients. We conclude that this reflects a disturbance of the neurometabolic steady state of normal-appearing brain tissue due to the tumor itself and to the impact of surgery in both patient groups. Further incremental decreases of metabolite concentrations in MB patients may point to additional harm caused by irradiation and chemotherapy. The stronger decrease of NAA in MB patients may correspond to the additional damage of combined irradiation and chemotherapy on neuroaxonal cell viability and number.
    Keywords: Medulloblastoma ; Mr Proton Spectroscopy ; Neurometabolism ; Pilocytic Astrocytoma ; Sequelae ; Medicine
    ISSN: 0360-3016
    E-ISSN: 1879-355X
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  • 2
    Language: English
    In: International Journal of Radiation Oncology, Biology, Physics, 2010, Vol.76(3), pp.859-866
    Description: To elucidate morphologic correlates of brain dysfunction in pediatric survivors of posterior fossa tumors by using magnetic resonance diffusion tensor imaging (DTI) to examine neuroaxonal integrity in white matter. Seventeen medulloblastoma (MB) patients who had received surgery and adjuvant treatment, 13 pilocytic astrocytoma (PA) patients who had been treated only with surgery, and age-matched healthy control subjects underwent magnetic resonance imaging on a 3-Tesla system. High-resolution conventional T1- and T2-weighted magnetic resonance imaging and DTI data sets were obtained. Fractional anisotropy (FA) maps were analyzed using tract-based spatial statistics, a part of the Functional MRI of the Brain Software Library. Compared with control subjects, FA values of MB patients were significantly decreased in the cerebellar midline structures, in the frontal lobes, and in the callosal body. Fractional anisotropy values of the PA patients were not only decreased in cerebellar hemispheric structures as expected, but also in supratentorial parts of the brain, with a distribution similar to that in MB patients. However, the amount of significantly decreased FA was greater in MB than in PA patients, underscoring the aggravating neurotoxic effect of the adjuvant treatment. Neurotoxic mechanisms that are present in PA patients ( , internal hydrocephalus and damaged cerebellar structures affecting neuronal circuits) contribute significantly to the alteration of supratentorial white matter in pediatric posterior fossa tumor patients.
    Keywords: Diffusion Tensor Imaging ; Medulloblastoma ; Pilocytic Astrocytoma ; White Matter ; Sequelae ; Medicine
    ISSN: 0360-3016
    E-ISSN: 1879-355X
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  • 3
    Language: English
    In: Child's Nervous System, May, 2013, Vol.29(5), p.717(2)
    Description: Byline: Ulrich-Wilhelm Thomale (1), Pablo Hernaiz Driever (2) Author Affiliation: (1) Arbeitsbereich Padiatrische Neurochirurgie, Charite-Universitatsmedizin Berlin, Campus Virchow Klinik, Berlin, Germany (2) Klinik fur Padiatrie mit Schwerpunkt Onkologie und Hamatologie, Charite-Universitatsmedizin Berlin, Campus Virchow Klinik, Berlin, Germany Article History: Registration Date: 01/03/2013 Received Date: 25/02/2013 Accepted Date: 28/02/2013 Online Date: 16/03/2013
    ISSN: 0256-7040
    Source: Cengage Learning, Inc.
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  • 4
    Language: English
    In: Cancer, 01 February 2010, Vol.116(3), pp.705-712
    Description: BACKGROUND: The authors hypothesized that intensified chemotherapy in protocol HIT-GBM-C would increase survival of pediatric patients with high-grade glioma (HGG) and diffuse intrinsic pontine glioma (DIPG). METHODS: Pediatric patients with newly diagnosed HGG and DIPG were treated with standard fractionated radiation and simultaneous chemotherapy (cisplatin 20 mg/m2 X 5 days, etoposide 100 mg/m2 X 3 days, and vincristine, and 1 cycle of cisplatin + etoposide + ifosfamide 1.5 g/m X 5 days [PEI] during the last week of radiation). Subsequent maintenance chemotherapy included further cycles of PEI in Weeks 10, 14, 18, 22, 26, and 30, followed by oral valproic acid. RESULTS: Ninety-seven (pons, 37; nonpons, 60) patients (median age, 10 years; grade IV histology, 35) were treated. Resection was complete in 21 patients, partial in 29, biopsy only in 26, and not performed in 21. Overall survival rates were 91% (standard error of the mean [SE] ? 3%), 56%, and 19% at 6, 12, and 60 months after diagnosis, respectively. When compared with previous protocols, there was no significant benefit for patients with residual tumor, but the 5-year overall survival rate for patients with complete resection treated on HIT-GBM-C was 63% ? 12% SE, compared with 17% ? 10% SE for the historical control group (P = .003, log-rank test). CONCLUSIONS: HIT-GBM-C chemotherapy after complete tumor resection was superior to previous protocols. Cancer 2010.
    Keywords: Glioblastoma ; Diffuse Intrinsic Pontine Glioma ; Chemotherapy ; Resection ; Children
    ISSN: 0008-543X
    E-ISSN: 1097-0142
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  • 5
    Language: English
    In: Medical Microbiology and Immunology, 2011, Vol.200(1), pp.1-5
    Description: The question whether human cytomegalovirus may affect cancer diseases has been discussed (very controversially) for decades. There are convinced believers and strict opponents of the idea that HCMV might be able to play a role in the course of cancer diseases. In parallel, the number of published reports on the topic is growing. Recently published and presented (Ranganathan P, Clark P, Kuo JS, Salamat S, Kalejta RF. A Survey of Human Cytomegalovirus Genomic Loci Present in Glioblastoma Multiforme Tissue Samples. 35th Annual International Herpes Workshop, Salt Lake City, 2010) data on HCMV detection in glioblastoma tissues and colocalisation of HCMV proteins with cellular proteins known to be relevant for glioblastoma progression motivated us to recapitulate the current state of evidence.
    Keywords: Cytomegalovirus ; Cancer ; Oncomodulation ; Tumour virus ; Glioblastoma ; Neuroblastoma
    ISSN: 0300-8584
    E-ISSN: 1432-1831
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  • 6
    Language: English
    In: Child's Nervous System, 2013, Vol.29(5), pp.717-718
    Keywords: Medicine & Public Health ; Neurosurgery ; Neurosciences ; Medicine;
    ISSN: 0256-7040
    E-ISSN: 1433-0350
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  • 7
    Language: English
    In: European Journal of Cancer, August 2017, Vol.81, pp.1-8
    Description: Temozolomide (TMZ) is widely used in high-grade glioma (HGG). There is a major concern of treatment-induced secondary haematological malignancies (SHMs). Due to the poor overall survival of HGG patients, the true incidence is yet elusive. Thus, the aim of this study was to determine the risk of SHMs following TMZ in paediatric HGG. We analysed 487 patients from the HIT-HGG database of the German-speaking Society of Pediatric Oncology and Hematology with follow up beyond 1 year. The incidence of SHM was 7.7 ± 3.2% at 10 years. No SHM occurred in 194 patients after first-line TMZ therapy, but four out of 131 patients treated with TMZ for relapse following first-line multiagent chemotherapy experienced SHM (20% at 10 years;  = 0.041). SHMs occurred in two out of 162 patients who underwent multiagent chemotherapy without TMZ (4.1% at 10 years). Gender, patient age and acute haematological toxicity during treatment did not affect the incidence of SHMs. Data of our cohort do not indicate an increased risk of SHM following TMZ treatment when compared to previous chemotherapy regimen. However, if TMZ is administered as a second-line treatment following conventional chemotherapy regimen, the risk might be disproportionately increasing.
    Keywords: Children ; Glioblastoma ; High-Grade Glioma ; Secondary Haematological Malignancies ; Medicine
    ISSN: 0959-8049
    E-ISSN: 1879-0852
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  • 8
    In: Journal of Pediatric Hematology/Oncology, 2012, Vol.34(2), pp.e66-e68
    Description: We report on the first pediatric patient with a localized primary peripheral T-cell lymphoma, not otherwise specified, of the central nervous system (CNS). The solid lesion that was enhanced in magnetic resonance images of the left precentral region was totally resected. The histopathology revealed a peripheral T-cell lymphoma, not otherwise specified. Staging procedures showed that the lesion was confined to the CNS. Without any further therapy, the patient still remains in complete remission 6 years after diagnosis. Thus, we conclude that a peripheral T-cell lymphoma, not otherwise specified, of the CNS can occur in children. In the case presented here, complete resection sufficed.
    Keywords: Brain Neoplasms -- Pathology ; Lymphoma, T-Cell, Peripheral -- Pathology;
    ISSN: 1077-4114
    E-ISSN: 15363678
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  • 9
    Language: English
    In: European Journal of Paediatric Neurology, January 2015, Vol.19(1), pp.75-77
    Description: Levetiracetam is increasingly used as antiepileptic drug (AED) of choice in children as well as in adults with complex diseases due to its lack of interactions and a large spectrum of action. Secondary graft failure, i.e. loss of donor cells after initial engraftment, is a relatively uncommon but serious and life-theatening complication after pediatric hematopoietic stem cell transplantation. We report a case of secondary graft failure after hematopoietic stem cell transplantation for treatment-related myelodysplastic syndrome during antiepileptic treatment with levetiracetam. Exclusion of all other possible etiologies left levetiracetam as the most likely cause of the imminent complete secondary graft failure after hematopoietic stem cell transplantation. Furthermore, the blood cell count improved just a few days after cessation of levetiracetam medication. Thus, we recommend that in case of secondary graft failure after hematopoietic stem cell transplantation, all possible causes should carefully be excluded, including adverse events through new generation AED agents. Switching to different AEDs with less harming effect on bone marrow function should strongly be considered.
    Keywords: Levetiracetam ; Allogenic Hematopoietic Stem Cell Transplantation ; Myelosuppression ; Secondary Graft Failure ; Medicine
    ISSN: 1090-3798
    E-ISSN: 1532-2130
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  • 10
    In: Pediatrics International, February 2010, Vol.52(1), pp.75-79
    Description: Midkine (MK), a heparin‐binding growth factor, is a secreted protein and can be detected in a patient's sera. MK was studied in the sera of 215 children and adolescents without malignant disease using an enzyme‐linked immunosorbent assay in order to determine the distribution of concentrations in a control population for pediatric oncology patients. Tested subjects either underwent surgical procedures or suffered from endocrinological diseases. Elevated MK levels were found in patients with short stature, diabetes mellitus, obesity, and cleft lip and palate. These patients were subsequently excluded from the “non‐cancer” group. MK serum levels did neither correlate with sex, age, weight or height nor showed a normal distribution (= 152, range: 0.0–5.58 ng/ml, median: 0.0 ng/ml, mean: 0.26 ng/ml, SD: ±0.61). MK serum values in children and adolescents are widely spread and not normally distributed. The present results indicate that the MK expression is influenced by many factors apart from cancer, which have not yet been identified.
    Keywords: Elisa ; Midkine ; Non‐Cancer Value ; Pediatric Population
    ISSN: 1328-8067
    E-ISSN: 1442-200X
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