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1.
Front Pediatr ; 9: 734181, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-35004533

RESUMEN

Introduction: Specialized palliative home care (SPHC) enables children and adolescents with life-limiting illnesses and complex needs to receive care at home. In addition to controlling symptoms and stabilizing the psychosocial situation, crisis anticipation is a component of SPHC. Since the establishment of the reporting SPHC team, parents have called for additional help from emergency medical services (EMS) in emergency situations with unexpected frequency. Children with life limiting diseases could undergo invasive procedures and unhelpful treatments with uncertain consequences. The questions arose as to which factors led to the involvement of the EMS in a palliative situation, what therapy was performed and what outcome could be reached. Methods: Records of the pediatric SPHC patients and EMS call-outs in these children of the reporting SPHC-team in the central region of Hesse, Germany (population: 1.1 million) were retrospectively analyzed from 01.11.2014 to 01.05.2021. The causes of the call-outs, the existence of an emergency agreement, the National Advisory Committee for Aeronautics (NACA) score, EMS therapy and outcome were examined. Patient data included age, palliative-justifying diagnosis, duration and intensity of care, place of death and median overall survival (MOS) and palliative SHPC treatment. Results: In total, 172 patients were analyzed during the study period. There were 27 EMS calls for a total of 20 patients/families (= EMS group). Palliative illness or a complication was the most frequent cause of call-outs. The patients in the EMS group were significantly less likely to have a DNR order, required more home visits and telephone calls and were under SPHC care for longer. There was a significantly higher proportion of crisis interventions at home visits. The children in the EMS group died less often from the underlying disease. Of the remaining 152 patients (= non-EMS group), a significantly higher proportion had a European home country. Conclusions: Despite the introduction of the SPHC, parents still call the EMS. Good cooperation and joint training should be sought to prepare all those involved for future call-outs.

2.
Am J Pathol ; 175(4): 1631-7, 2009 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-19717644

RESUMEN

Choroid plexus tumors are intraventricular neoplasms predominantly affecting young children. In contrast to choroid plexus papillomas, choroid plexus carcinomas progress frequently, necessitating the development of adjuvant treatment concepts. Platelet derived growth factor (PDGF) signaling has been shown to support growth in a variety of tumors. The finding of PDGF receptor expression in choroid plexus tumors prompted us to elucidate PDGF receptor activation state using a novel method, in situ proximity ligation assay, on formalin-fixed, paraffin-embedded, archival samples of 19 choroid plexus tumors. As assessed by in situ proximity ligation assay, the proportion of phosphorylated PDGF receptor alpha was low in choroid plexus papillomas and choroid plexus carcinomas, whereas phosphorylated PDGF receptor beta was found to be significantly higher in choroid plexus carcinomas. In the immortalized choroid plexus epithelial cell line Z310 expressing PDGF receptor beta, PDGF-BB exhibited a time- and dose-dependent proliferative response, which was significantly attenuated by imatinib (gleevec). In conclusion, our findings suggest that PDGF receptor beta is functionally involved in the biology of choroid plexus tumors and may represent a molecular target for therapy. In addition, this study demonstrates the feasibility and usefulness of in situ proximity ligation assay for monitoring receptor tyrosine kinase activation in formalin-fixed, paraffin-embedded, archival tissues.


Asunto(s)
Neoplasias del Plexo Coroideo/metabolismo , Receptor alfa de Factor de Crecimiento Derivado de Plaquetas/metabolismo , Receptor beta de Factor de Crecimiento Derivado de Plaquetas/metabolismo , Animales , Línea Celular , Línea Celular Transformada , Proliferación Celular/efectos de los fármacos , Neoplasias del Plexo Coroideo/patología , Células Epiteliales/efectos de los fármacos , Células Epiteliales/metabolismo , Células Epiteliales/patología , Femenino , Humanos , Inmunohistoquímica , Lactante , Masculino , Papiloma/metabolismo , Papiloma/patología , Fosforilación/efectos de los fármacos , Factor de Crecimiento Derivado de Plaquetas/farmacología , Ratas
4.
J Neurooncol ; 97(2): 257-65, 2010 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-19806321

RESUMEN

Gliosarcoma (GS) is a glioblastoma with a sarcomatous component that is presumed to be a metaplastic differentiation of glioma cells. We studied the clinical relevance of this histological glioblastoma subentity within the pediatric population. We obtained patient data from the German HIT-GBM database, which contains clinical data for more than 600 pediatric patients with centrally reviewed high-grade gliomas. By applying defined inclusion criteria (diagnosis of GS proven by central neuropathological review; patient age 0 to 21 years), four patients were identified. In addition, after a review of the English medical scientific literature, 19 additional cases were found. The relative frequency of GS in the German HIT-GBM database was only 1.9%. In the whole series of 23 pediatric GS patients, including previously reported cases, the male-to-female-ratio was 1.2:1. GS was found in all pediatric age groups with a median age of 11 years, but there was an unexpectedly high accumulation in infants (6 of 23 <3 years of age, 26%). GS showed a strong predilection of the cerebral hemispheres (22 out of 23 cases). Increased intracranial pressure was the leading symptom of a short clinical history with a median duration of 0.7 month. Interestingly, six patients (26%) were reported with a history of cranial radiotherapy prior to GS diagnosis. In 60% of the GS patients in our series, gross total resection was achieved. Median overall (OS) and event-free survivals (EFS) of the total cohort were 12.1 and 9.8 months, respectively. In conclusion, GS is a very rare tumor entity in children. Literature review suggests a relatively higher incidence in infants and in patients with a previous history of radiotherapy.


Asunto(s)
Neoplasias Encefálicas/epidemiología , Neoplasias Encefálicas/patología , Gliosarcoma/epidemiología , Gliosarcoma/patología , Adolescente , Neoplasias Encefálicas/terapia , Niño , Preescolar , Femenino , Gliosarcoma/terapia , Humanos , Lactante , Recién Nacido , Estimación de Kaplan-Meier , Masculino , Adulto Joven
5.
Pediatr Blood Cancer ; 55(3): 520-4, 2010 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-20658624

RESUMEN

BACKGROUND: Measuring the quality of life or performance status in pediatric neurooncology has proven a challenge. Here, we report in a treatment protocol for pediatric patients with high-grade glioma and diffuse intrinsic pontine glioma. PROCEDURE: The Fertigkeitenskala Münster-Heidelberg (FMH) is a 56-item quantitative measure of health status. The number of yes answers is transformed to age-dependent percentiles. Physicians were also asked the patients' health status by their own judgment on a 1-5 scale: normal, mild handicap, age-normal activity severely reduced but patient not in bed, in bed, and in ICU. RESULTS: Assessments were available from 50 of 97 eligible patients. For 22 patients both questionnaire and the physicians score obtained. At the beginning of the treatment, only 5 patients scored over 40 FMH%, and 4 of these survived. Of 16 patients who initially scored less than 40 FMH%, 15 died. During later assessments, most FMH measures became gradually worse. FMH scores improved in three patients. The physician's judgment was documented at diagnosis and during treatment (n = 50). Per physician, 22% of the patients were normal before chemotherapy, decreasing to 16% in the middle of the protocol. At diagnosis only 16% of patients had severely reduced activity, which increased to 30.6% in the middle of the protocol. The FMH% correlated well with the physicians' judgments (P < 0.005). CONCLUSION: The FMH scale is easily obtained and provides a valid assessment of health status. Patients with poor performance at diagnosis had a poorer prognosis.


Asunto(s)
Actividades Cotidianas , Neoplasias Encefálicas/fisiopatología , Glioma/fisiopatología , Estado de Salud , Calidad de Vida , Encuestas y Cuestionarios , Adolescente , Neoplasias del Tronco Encefálico/fisiopatología , Niño , Preescolar , Femenino , Humanos , Masculino
6.
Pediatr Blood Cancer ; 54(2): 228-37, 2010 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-19856394

RESUMEN

BACKGROUND: Studies in adults with malignant glioma suggest MGMT methylation as a stratification marker. Similar data for children are sparse. We investigated the impact of MGMT methylation and expression on survival of children with high-grade glioma (HGG) registered into the German HIT-GBM database receiving temozolomide (TMZ) as part of their treatment (n = 21 relapsed, n = 4 primary). PROCEDURE: Twenty-four patients were included retrospectively. Methylation specific PCR (MSP), calibrated combined bisulfite restriction analysis (COBRA), and immunohistochemistry (IHC) were applied. Survival analyses were performed by Kaplan-Meier and Cox proportional-hazards models. RESULTS: MSP demonstrated DNA methylation in 77%. Patients with a methylated MGMT promoter had a sixfold longer median EFS (P = 0.015; 5.5 months vs. 0.9 months). Considering the results of calibrated COBRA, MGMT methylation was again associated with an elevated EFS (P = 0.05; 10.2 months vs. 2.6 months) and OS (P = 0.06; 18.7 months vs. 7.2 months) only if methylation was >14%. No difference in EFS and OS at all was noted between unmethylated and tumors methylated at low level (n = 9). Twenty-two tumors were positive by IHC, 10 showed low MGMT expression (IHC score 0-4). We did not detect any difference in EFS and OS between moderate/high-expressing tumors (IHC score 6-12) and those with low or no expression (IHC score 0-4). CONCLUSION: DNA methylation, but not protein expression of MGMT was associated with an increased median EFS and OS of children with relapsed HGG. MGMT methylation status warrants prospective evaluation as a stratification marker for children with HGG.


Asunto(s)
Biomarcadores de Tumor/genética , Metilación de ADN , Metilasas de Modificación del ADN/genética , Enzimas Reparadoras del ADN/genética , Glioma/diagnóstico , Proteínas Supresoras de Tumor/genética , Adolescente , Biomarcadores de Tumor/metabolismo , Niño , Preescolar , Metilasas de Modificación del ADN/metabolismo , Enzimas Reparadoras del ADN/metabolismo , Femenino , Glioma/patología , Humanos , Masculino , Análisis Multivariante , Pronóstico , Modelos de Riesgos Proporcionales , Recurrencia , Estudios Retrospectivos , Análisis de Supervivencia , Proteínas Supresoras de Tumor/metabolismo , Adulto Joven
7.
Pediatr Blood Cancer ; 54(4): 519-25, 2010 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-19852061

RESUMEN

BACKGROUND: A large experience with dendritic cell (DC)-based vaccination for malignant brain tumours has been gained in adults. Here we focus on the results obtained in children with relapsed malignant brain tumours. PROCEDURE: In total 45 children were vaccinated: 33 high grade glioma (HGG), 5 medulloblastoma (MB)/primitive neuro-ectodermal tumour (PNET), 4 ependymoma and 3 atypical teratoid-rhabdoid tumour (ATRT). Autologous, monocyte-derived DC were generated and loaded with tumour lysate, which was used as source of tumour-associated antigens. RESULTS: In 38 patients peripheral blood mononuclear cells (PBMC) were obtained from leukapheresis and in 7 patients from fresh blood samples. 7 HGG patients are still alive with median follow-up (FU) of 35.7 months (range: 12.1-85.6). Median overall survival (OS) was 13.5 months (range: 1.4-85.6). All patients with MB/PNET died (median OS 5.7 months; range 4.3-51.2). One patient with ependymoma is still alive at 22.3 months FU. The other three patients died at, respectively, 7.7, 30.1 and 31.5 months. Two patients with ATRT are still alive at, respectively, 34.1 and 52.6 months FU. The third patient died at 50.5 months. No severe adverse events were noticed. CONCLUSIONS: In this exploratory study, HGG and ATRT seem to respond more favourably to vaccination than MB/PNET and ependymoma. Although preliminary, our results are promising and support further testing of DC-based immunotherapy in new treatment protocols for HGG and ATRT.


Asunto(s)
Neoplasias Encefálicas/terapia , Vacunas contra el Cáncer/uso terapéutico , Células Dendríticas/trasplante , Antineoplásicos/uso terapéutico , Niño , Terapia Combinada , Femenino , Humanos , Masculino , Calidad de Vida , Vacunación/métodos
8.
J Pediatr Hematol Oncol ; 32(2): 160-2, 2010 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-20168252

RESUMEN

Choroid plexus tumors are rare brain tumors which account for 0.4% to 0.6% among brain tumors. Tumor resection is known to be of large prognostic impact, and re-resection of residual tumors is a part of standard care. However, after multiple resections it can become difficult to differentiate tumor from reactive tissue. 99mTC-sestamibi scans may assist in differentiating neoplastic (99mTC-sestamibi positive) from non-neoplastic tissue (99mTC-sestamibi negative). Previous literature showed sestamibi to be helpful in detecting residual choroid plexus tumors resulting in further resection. Here, we report the first case to show that sestamibi scans can also help with the opposite decision.


Asunto(s)
Neoplasias del Plexo Coroideo/diagnóstico por imagen , Radiofármacos , Tecnecio Tc 99m Sestamibi , Tomografía Computarizada de Emisión , Barrera Hematoencefálica , Neoplasias del Plexo Coroideo/patología , Neoplasias del Plexo Coroideo/cirugía , Femenino , Humanos , Lactante , Tecnecio Tc 99m Sestamibi/farmacocinética
9.
Neuro Oncol ; 11(3): 323-9, 2009 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-19050301

RESUMEN

Little is known about giant cell glioblastoma (GCG) in pediatric patients. The present study identified 18 pediatric patients with centrally reviewed GCG from the HIT-GBM database of the Gesellschaft für Paediatrische Onkologie und Haematologie in Germany, Austria, and Switzerland. Clinical and epidemiological data were compared with those of 178 pediatric patients with centrally reviewed glioblastoma multiforme (GBM) from the same database. In this unique series, median age, male preference, and median clinical history did not differ significantly between pediatric GCG and GBM patients. GCG showed a stronger predilection for cerebral hemispheres than did GBM, which may only partly explain the higher percentage of gross total tumor resections in GCG patients. Most surprising, the widely distributed hypothesis that GCG may imply a better prognosis than GBM could not be substantiated for our pediatric series. Future studies with larger patient numbers and molecular pathological analyses are still needed to corroborate the present findings and further elucidate the biology of GCG in children.


Asunto(s)
Neoplasias Encefálicas/mortalidad , Neoplasias Encefálicas/patología , Glioblastoma/mortalidad , Glioblastoma/patología , Adolescente , Edad de Inicio , Neoplasias Encefálicas/terapia , Quimioterapia Adyuvante , Niño , Preescolar , Femenino , Glioblastoma/terapia , Humanos , Lactante , Recién Nacido , Estimación de Kaplan-Meier , Masculino , Procedimientos Neuroquirúrgicos , Pronóstico , Radioterapia Adyuvante , Estudios Retrospectivos
10.
Neuro Oncol ; 11(2): 201-10, 2009 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-18818397

RESUMEN

To investigate the utility of postoperative chemotherapy in delaying radiotherapy and to identify prognostic factors in early childhood medulloblastoma, we studied children younger than 3 years of age registered to the HIT-SKK'87 (Therapieprotokoll für Säuglinge und Kleinkinder mit Hirntumoren [Brain Tumor Radiotherapy for Infants and Toddlers with Medulloblastoma] 1987) trial who received systemic interval chemotherapy until craniospinal radiotherapy was applied at 3 years of age or at relapse, from 1987 to 1993. Children with postoperative residual tumor or metastatic disease received systemic induction chemotherapy prior to interval chemotherapy. Twenty-nine children were eligible for analyses (median age, 1.7 years; median follow-up, 12.6 years). In children without macroscopic metastases, rates (+/-SEM) for 10-year progression-free survival (PFS) and overall survival (OS) were 52.9% +/- 12.1% and 58.8% +/- 11.9% (complete resection), and 55.6% +/- 16.6% and 66.7% +/- 15.7% (incomplete resection), compared with 0% and 0% in children with macroscopic metastases. Survival was superior in nine children with desmoplastic or extensive nodular histology compared with 20 children with classic medulloblastoma (10-year PFS, 88.9% +/- 10.5% and 30.0% +/- 10.3%, p = 0.003; OS, 88.9% +/- 10.5% and 40.0% +/- 11.0%, p = 0.006). Eleven of 12 children with tumor progression during chemotherapy had classic medulloblastoma. After treatment, IQ scores were inferior compared with nonirradiated children from the subsequent study, HIT-SKK'92. Classic histology, metastatic disease, and male gender were independent adverse risk factors for PFS and OS in 72 children from HIT-SKK'87 and HIT-SKK'92 combined. In terms of survival, craniospinal radiotherapy was successfully delayed especially in young children with medulloblastoma of desmoplastic/extensive nodular histology, which was a strong independent favorable prognostic factor. Because of the neurocognitive deficits of survivors, the emerging concepts to avoid craniospinal radiotherapy should rely on the histological medulloblastoma subtype.


Asunto(s)
Antineoplásicos/uso terapéutico , Neoplasias Cerebelosas/tratamiento farmacológico , Neoplasias Cerebelosas/radioterapia , Irradiación Craneana , Meduloblastoma/tratamiento farmacológico , Meduloblastoma/radioterapia , Recurrencia Local de Neoplasia/terapia , Neoplasias Cerebelosas/cirugía , Preescolar , Terapia Combinada , Supervivencia sin Enfermedad , Femenino , Humanos , Lactante , Masculino , Meduloblastoma/cirugía , Recurrencia Local de Neoplasia/diagnóstico , Proyectos Piloto , Pronóstico , Tasa de Supervivencia , Resultado del Tratamiento
11.
J Neurooncol ; 91(3): 279-86, 2009 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-18853233

RESUMEN

Choroid plexus carcinomas are rare tumors that typically occur in young children. Prognosis is poor, and very little information is available to optimize treatment protocols. We used a cell culture model to evaluate whether combining chemotherapeutic agents such as methotrexate with histone deacetylase inhibitors (HDACI) such as valproic acid and MS-275 could improve efficacy. Valproic acid increased the cytotoxicity of radiation and of all the chemotherapeutic agents in Z310 and SV11 mouse choroid plexus cell lines, with the exception of methotrexate. Both HDACIs made choroid plexus cells resistant to this folate antagonist. Searching for a molecular explanation, we found that thymidylate synthase was up regulated when the cells were incubated with HDACI. We also confirmed this finding in human choroid plexus carcinoma cells. Methotrexate should not be combined with HDACI in the treatment of choroid plexus carcinoma.


Asunto(s)
Plexo Coroideo/citología , Inhibidores Enzimáticos/farmacología , Inhibidores de Histona Desacetilasas , Histonas/metabolismo , Ácido Valproico/farmacología , Acetilación/efectos de los fármacos , Animales , Antígenos Virales de Tumores/genética , Antígenos Virales de Tumores/metabolismo , Apoptosis/efectos de los fármacos , Benzamidas/farmacología , Carcinoma , Línea Celular Transformada , Línea Celular Tumoral , Plexo Coroideo/efectos de los fármacos , Plexo Coroideo/efectos de la radiación , Relación Dosis-Respuesta a Droga , Relación Dosis-Respuesta en la Radiación , Rayos gamma , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Concentración 50 Inhibidora , Metotrexato , Ratones , Piridinas/farmacología , Sales de Tetrazolio , Tiazoles
12.
J Neurooncol ; 92(2): 157-63, 2009 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-19043777

RESUMEN

PURPOSE: Anaplastic gangliogliomas (AGG) are gangliogliomas with areas of pronounced hypercellularity, vascular proliferation, necrosis, and many mitotic figures. As very few pediatric patients have been studied, we analyzed the cases registered in the HIT-GBM database. PATIENTS AND METHODS: Patient data were obtained from the German HIT-GBM database. Inclusion criteria were diagnosis of AGG proven by a central neuropathological review and patient age 0 to 17 years. Eight patients (five male and three female) were identified. RESULTS: Patients' median age was 10 years. The median history of disease was 9 months (range, 1.0-43.0 months). Initial symptoms included signs of raised intracranial pressure, seizures, and, in the case of spinal cord tumor, bladder dysfunction. In five cases, AGGs were localized supratentorially with three patients having multiple lobes involved. The tumors affected the frontal (n = 3 cases), parietal (n = 2), temporal (n = 2), and occipital lobes (n = 1), as well as the brainstem (n = 1) and the spinal cord (n = 2). Gross total tumor resection was achieved in six patients. The estimated 5-year overall survival rate +/- standard error was 88 +/- 12%, and the event-free survival rate was 63 +/- 17%. While gender and tumor location did not affect survival rates, gross total tumor resection provided a better overall survival than non-total resection. CONCLUSION: The prognosis of pediatric patients with AGG is good, especially for those who undergo gross total tumor resection.


Asunto(s)
Neoplasias Encefálicas/patología , Ganglioglioma/patología , Adolescente , Neoplasias Encefálicas/fisiopatología , Neoplasias Encefálicas/cirugía , Niño , Preescolar , Femenino , Ganglioglioma/fisiopatología , Ganglioglioma/cirugía , Humanos , Lactante , Recién Nacido , Estimación de Kaplan-Meier , Masculino , Pronóstico
13.
J Neurooncol ; 95(3): 383-392, 2009 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-19543851

RESUMEN

Atypical choroid plexus papilloma (APP) represents a novel intermediate-grade subtype of choroid plexus tumor (CPT), the clinical outcome of which has not been described yet. We present the first analysis of a group of APP patients enrolled in the ongoing CPT-SIOP-2000 study of CPTs. A worldwide registration and a randomized trial for those patients who require chemotherapy started in 2000. For APP, maximal surgical resection was recommended. After surgery, patients who had undergone complete resection were observed, whereas patients with incompletely resected or metastasized APP were treated with six chemotherapy courses (etoposide and vincristine, combined with either carboplatin or cyclophosphamide). Risk-adapted radiotherapy was given only to patients older than 3 years of age. Of the 106 patients with a centrally confirmed CPT histology, 30 had APP, 42 CPP and 34 CPC. APP patients were significantly younger (median = 0.7 years) than patients with CPP or CPC (both medians = 2.3 years). Complete resection was achieved in 68 (64%) patients (79% in CPP, 63% in APP, and 47% in CPC). Metastases were present at diagnosis in 17% of APP patients, 5% of CPP patients, and 21% of CPC patients. All nine APP patients who received postoperative chemotherapy showed an early response after two cycles: two had complete remission, four had partial response, and three had stable disease. In the observation group of 15 patients, one event was seen, and all patients were alive. In the treatment group, one patient with a metastasized tumor and incompletely resected APP died. While APP was defined histologically, median percentages of both the Ki-67/MIB-1 proliferation marker and the p53 tumor suppressor protein increased across the three histological subtypes (from CPP to APP and then CPC), suggesting that the subtypes comprise an ordinal categorization of increasingly severe CPT tumors. This ordering was reiterated by clinical outcome in the 92 patients treated per the study protocol, with 5-year EFS rates of 92% in 39 CPP patients, 83% in 24 APP patients, and 28% in 29 CPC patients. A similar ordering was seen when all 106 patients were evaluated for EFS. APP responded favorably to chemotherapy. The intermediate position of APP between CPP and CPC was supported by the clinical data.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Neoplasias del Plexo Coroideo/tratamiento farmacológico , Neoplasias del Plexo Coroideo/mortalidad , Papiloma del Plexo Coroideo/tratamiento farmacológico , Papiloma del Plexo Coroideo/mortalidad , Adolescente , Adulto , Carboplatino/administración & dosificación , Preescolar , Neoplasias del Plexo Coroideo/patología , Terapia Combinada , Ciclofosfamida/administración & dosificación , Etopósido/administración & dosificación , Femenino , Gadolinio , Humanos , Lactante , Estimación de Kaplan-Meier , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Papiloma del Plexo Coroideo/patología , Sistema de Registros , Vincristina/administración & dosificación , Adulto Joven
14.
Pediatr Blood Cancer ; 53(4): 672-4, 2009 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-19544396

RESUMEN

Meningioangiomatosis (MA) is an uncommon brain tumor. The role of imaging techniques is underscored in cases where the tumor location makes resection (or even biopsy) dangerous. We report the case of a child with an MA tumor located deep in the right sylvian fissure. A computed tomography (CT) scan showed calcifications in a highly vascular lesion with surrounding edema. Magnetic resonance spectroscopy (MRS) showed a distinct choline (Cho) peak, which usually suggests a proliferating tumor. Fluorodeoxyglucose positron emission tomography (FDG-PET) showed the lesion lacked hypermetabolic features. These radiological features should put MA in the differential diagnosis.


Asunto(s)
Angiomatosis/diagnóstico , Neoplasias Meníngeas/diagnóstico , Meningioma/diagnóstico , Angiomatosis/metabolismo , Angiomatosis/patología , Niño , Femenino , Fluorodesoxiglucosa F18 , Humanos , Imagen por Resonancia Magnética , Espectroscopía de Resonancia Magnética , Neoplasias Meníngeas/metabolismo , Neoplasias Meníngeas/patología , Meningioma/metabolismo , Meningioma/patología , Tomografía de Emisión de Positrones , Tomografía Computarizada por Rayos X
15.
Pediatr Blood Cancer ; 53(7): 1349-51, 2009 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-19653292

RESUMEN

Frasier syndrome is characterized by a 46 XY disorder of sex development, nephropathy, and increased risk for gonadoblastoma due to Wilms tumor 1(WT1) mutation in the donor splice site of intron-9, resulting in the splice form +KTS. Germ cell tumors and gonadoblastomas have been reported previously in Frasier syndrome. We present the clinical, radiological, and genetic (WT1 mutation analysis) of a 46 XY phenotypic female with Frasier syndrome with bilateral gonadoblastoma with dysgerminoma who developed pilocytic astrocytoma.


Asunto(s)
Astrocitoma/genética , Disgerminoma/genética , Síndrome de Frasier/genética , Genes del Tumor de Wilms , Gonadoblastoma/genética , Neoplasias Hipotalámicas/genética , Síndromes Neoplásicos Hereditarios/genética , Mutación Puntual , Sitios de Empalme de ARN/genética , Astrocitoma/complicaciones , Astrocitoma/patología , Astrocitoma/cirugía , Niño , Disgerminoma/patología , Disgerminoma/cirugía , Femenino , Disgenesia Gonadal 46 XY/genética , Gonadoblastoma/patología , Gonadoblastoma/cirugía , Hemianopsia/etiología , Humanos , Neoplasias Hipotalámicas/complicaciones , Neoplasias Hipotalámicas/patología , Neoplasias Hipotalámicas/cirugía , Masculino , Neoplasias Primarias Múltiples/genética , Neoplasias Primarias Múltiples/patología , Neoplasias Primarias Múltiples/cirugía , Fenotipo , Proteinuria/genética , Trastornos del Habla/etiología
16.
Clin Cancer Res ; 14(10): 3098-104, 2008 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-18483377

RESUMEN

PURPOSE: To investigate the therapeutic role of adjuvant vaccination with autologous mature dendritic cells (DC) loaded with tumor lysates derived from autologous, resected glioblastoma multiforme (GBM) at time of relapse. EXPERIMENTAL DESIGN: Fifty-six patients with relapsed GBM (WHO grade IV) were treated with at least three vaccinations. Children and adults were treated similarly in three consecutive cohorts, with progressively shorter vaccination intervals per cohort. Feasibility and toxicity were assessed as well as effect of age, extent of resection, Karnofsky Performance Score, and treatment cohort on the progression-free (PFS) and overall survival (OS) using univariable and multivariable analysis. RESULTS: Since the prevaccine reoperation, the median PFS and OS of the total group was 3 and 9.6 months, respectively, with a 2-year OS of 14.8%. Total resection was a predictor for better PFS both in univariable analysis and after correction for the other covariates. For OS, younger age and total resection were predictors of a better outcome in univariable analysis but not in multivariable analysis. A trend to improved PFS was observed in favor of the faster DC vaccination schedule with tumor lysate boosting. Vaccine-related edema in one patient with gross residual disease before vaccination was the only serious adverse event. CONCLUSION: Adjuvant DC-based immunotherapy for patients with relapsed GBM is safe and can induce long-term survival. A trend to PFS improvement was shown in the faster vaccination schedule. The importance of age and a minimal residual disease status at the start of the vaccination is underscored.


Asunto(s)
Antígenos de Neoplasias/uso terapéutico , Neoplasias Encefálicas/terapia , Vacunas contra el Cáncer/uso terapéutico , Células Dendríticas/inmunología , Glioblastoma/terapia , Recurrencia Local de Neoplasia/terapia , Adolescente , Adulto , Anciano , Antígenos de Neoplasias/inmunología , Vacunas contra el Cáncer/inmunología , Niño , Supervivencia sin Enfermedad , Femenino , Glioblastoma/mortalidad , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/mortalidad , Periodo Posoperatorio
17.
N Engl J Med ; 352(10): 978-86, 2005 Mar 10.
Artículo en Inglés | MEDLINE | ID: mdl-15758008

RESUMEN

BACKGROUND: The prognosis for young children with medulloblastoma is poor, and survivors are at high risk for cognitive deficits. We conducted a trial of the treatment of this brain tumor by intensive postoperative chemotherapy alone. METHODS: After surgery, children received three cycles of intravenous chemotherapy (cyclophosphamide, vincristine, methotrexate, carboplatin, and etoposide) and intraventricular methotrexate. Treatment was terminated if a complete remission was achieved. Leukoencephalopathy and cognitive deficits were evaluated. RESULTS: Forty-three children were treated according to protocol. In children who had complete resection (17 patients), residual tumor (14), and macroscopic metastases (12), the five-year progression-free and overall survival rates (+/-SE) were 82+/-9 percent and 93+/-6 percent, 50+/-13 percent and 56+/-14 percent, and 33+/-14 percent and 38+/-15 percent, respectively. The rates in 31 patients without macroscopic metastases were 68+/-8 percent and 77+/-8 percent. Desmoplastic histology, metastatic disease, and an age younger than two years were independent prognostic factors for tumor relapse and survival. Treatment strategies at relapse were successful in 8 of 16 patients. There were no major instances of unexpected toxicity. In 19 of 23 children, asymptomatic leukoencephalopathy was detected by magnetic resonance imaging. After treatment, the mean IQ was significantly lower than that of healthy controls within the same age group but higher than that of patients in a previous trial who had received radiotherapy. CONCLUSIONS: Postoperative chemotherapy alone is a promising treatment for medulloblastoma in young children without metastases.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Cerebelosas/tratamiento farmacológico , Meduloblastoma/tratamiento farmacológico , Análisis de Varianza , Carboplatino/administración & dosificación , Neoplasias Cerebelosas/psicología , Neoplasias Cerebelosas/cirugía , Quimioterapia Adyuvante , Preescolar , Ciclofosfamida/administración & dosificación , Etopósido/administración & dosificación , Estudios de Seguimiento , Humanos , Lactante , Inteligencia/efectos de los fármacos , Meduloblastoma/psicología , Meduloblastoma/secundario , Meduloblastoma/cirugía , Metotrexato/administración & dosificación , Recurrencia Local de Neoplasia/tratamiento farmacológico , Pruebas Neuropsicológicas , Cuidados Posoperatorios , Modelos de Riesgos Proporcionales , Inducción de Remisión , Análisis de Supervivencia , Vincristina/administración & dosificación
18.
Pediatr Blood Cancer ; 51(1): 137-40, 2008 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-18338396

RESUMEN

A 5-year-old male presented with spinal cord drop metastasis from a recurrent neurocytoma. Topotecan (0.5 mg/m(2)) and carboplatin (250 mg/m(2)) were administered on days 1-3 and ifosfamide (1,800 mg/m(2)) on days 1-5, every 21 days, for three cycles and resulted in complete response without severe complications. A literature review yielded 20 patients with central neurocytoma but no complete responses. The complete response of central neurocytoma to chemotherapy only reported here should be helpful to those caring for patients with this rare tumor.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neurocitoma/tratamiento farmacológico , Carboplatino , Preescolar , Supervivencia sin Enfermedad , Humanos , Ifosfamida , Imagen por Resonancia Magnética , Masculino , Neurocitoma/diagnóstico , Inducción de Remisión , Topotecan
19.
Anticancer Res ; 28(4C): 2437-42, 2008.
Artículo en Inglés | MEDLINE | ID: mdl-18751431

RESUMEN

BACKGROUND: Chemotherapy has limited effects in the treatment of high-grade gliomas (HGGs). Valproic acid (VPA), a histone deacetylase (HDAC) inhibitor, may sensitize HGGs to radiochemotherapy. As the drug has been given frequently as an antiepileptic drug, a retrospective analysis was conducted to ensure relevant information was not missed before a prospective study was launched. MATERIALS AND METHODS: An analysis of 66 pediatric patients (range, 1-19 years of age) with glioblastoma multiforme (GBM) (n=40) or anaplastic astrocytoma (AA) (n=26) was retrospectively conducted for predictors of survival and response and for effects of VPA on outcome or toxicity. RESULTS: The overall survival (OS) was better for AA (p=0.0114) and complete resection (p<0.00005) and event-free survival (EFS) was better for complete resection (p=0.0049). Nine patients received VPA (for seizure) plus further oncological treatment. The most severe adverse effect was a pulmonary embolism (n=1); no other severe side-effects were noted. The response to nonsurgical treatment after 8 weeks was: complete response (CR): 0, partial response (PR): 3, stable disease (SD): 4, progressive disease (PD): 2. Some of the patients with SD responded later resulting in best response: CR:0, PR:5, SD:2, PD:2. CONCLUSION: Treatment with VPA plus radiochemotherapy is well tolerated with an encouraging response rate.


Asunto(s)
Astrocitoma/tratamiento farmacológico , Glioblastoma/tratamiento farmacológico , Ácido Valproico/uso terapéutico , Adolescente , Adulto , Astrocitoma/cirugía , Niño , Preescolar , Supervivencia sin Enfermedad , Femenino , Glioblastoma/cirugía , Humanos , Lactante , Masculino , Estudios Retrospectivos , Ácido Valproico/efectos adversos
20.
Anticancer Res ; 27(1B): 523-9, 2007.
Artículo en Inglés | MEDLINE | ID: mdl-17348436

RESUMEN

BACKGROUND: Comprehensive, efficient health status assessment tools are needed for multi-center studies examining childhood brain tumor treatment outcomes. The Fertigkeitenskala Münster Heidelberg (FMH) is presented as a quantitative measure of health status. PATIENTS AND METHODS: The FMH was compared with the medical assessments, intelligence scores, and behavioral/emotional adjustment scores of 21 survivors of medulloblastoma to examine the instrument's feasibility and discriminate validity. The subjects, aged from 3 to 38 years, represented a broad range of health functioning, from asymptomatic to severely handicapped. The median age at diagnosis was 10.5 years. The median time of assessment was 1.5 years from diagnosis. RESULTS: Correlations calculated between the physicians' assessments and the other measures showed a very close relationship between the physicians' ratings and the FMH scores (rho =0. 784, p < 0. 0005) and physicians' ratings and Performance IQ (rho=0.679, p=0.005). Additionally, a correlation between the FMH and Full Scale IQ was demonstrated (r=0.627, p=0.012). The Child Behavior Checklist (CBCL) did not correlate with any other tests. Of the three assessment methods, the FMH showed the highest correlation with degree of handicap (p <0.0005). The FMH took less than 10 minutes to administer and was the only test feasible in all patients. CONCLUSION: The FMH is useful as an objective, easily administered measure of health status in brain tumor patients. The FMH offers health status information that is correlated with physicians' assessments and FSIQ, but not behavioral/emotional adjustment as assessed by the CBCL.


Asunto(s)
Neoplasias Cerebelosas/terapia , Estado de Salud , Meduloblastoma/terapia , Evaluación de Resultado en la Atención de Salud/métodos , Encuestas y Cuestionarios , Adolescente , Adulto , Neoplasias Cerebelosas/psicología , Niño , Preescolar , Humanos , Lactante , Meduloblastoma/psicología , Evaluación de Resultado en la Atención de Salud/estadística & datos numéricos , Reproducibilidad de los Resultados
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