Treatment of Children and Adolescents With Metastatic Medulloblastoma and Prognostic Relevance of Clinical and Biologic Parameters.

Purpose To assess an intensified treatment in the context of clinical and biologic risk factors in metastatic medulloblastoma. Patients and Methods Patients (4 to 21 years old, diagnosed between 2001 and 2007) received induction chemotherapy, dose-escalated hyperfractionated craniospinal radiotherapy, and maintenance chemotherapy. Subgroup status and other biologic parameters were assessed.

Cost-utility analysis of a telerehabilitation program: a case study of COPD patients.

Objective: The present study seeks to conduct cost-utility analysis (CUA) of the Danish TELEKAT (Telehomecare, Chronic Patients and the Integrated Healthcare System) project. The TELEKAT project seeks to test and develop a preventive home monitoring concept across sectors for chronic obstructive pulmonary disease (COPD) patients. The concept of the TELEKAT project is to reduce admissions by enabling the COPD patients to conduct self-monitoring and maintain rehabilitation activities in their own home.

Long-term follow-up of the multicenter, multidisciplinary treatment study HIT-LGG-1996 for low-grade glioma in children and adolescents of the German Speaking Society of Pediatric Oncology and Hematology.

The Hirntumorstudien (HIT)-LGG-1996 protocol offered a comprehensive treatment strategy for pediatric patients with low-grade glioma (LGG), ie, observation, surgery, adjuvant radiotherapy, and chemotherapy to defer the start of irradiation in young children. In this current study, we sought to determine clinical factors for progression and survival. Between October 1, 1996 and March 31, 2004, 1031 patients were prospectively recruited into an observation arm (n = 668) and a nonsurgical arm stratifying 12 months of vincristine-carboplatin chemotherapy (n = 216) and conventional radiotherapy/brachytherapy (n = 147) in an age-dependent manner.

Using preventive home monitoring to reduce hospital admission rates and reduce costs: a case study of telehealth among chronic obstructive pulmonary disease patients.

We studied whether preventive home monitoring of patients with chronic obstructive pulmonary disease (COPD) could reduce the frequency of hospital admissions and lower the cost of hospitalization. Patients were recruited from a health centre, general practitioner (GP) or the pulmonary hospital ward. They were randomized to usual care or tele-rehabilitation with a telehealth monitoring device installed in their home for four months.

A long duration of the prediagnostic symptomatic interval is not associated with an unfavourable prognosis in childhood medulloblastoma.

Background: Due to the lacking specificity of symptoms making a correct diagnosis can be a challenge in children with medulloblastoma. This can lead to prediagnostic symptomatic intervals (PSIs) of several weeks to months. It is unknown whether the length of the PSI is associated with an inferior survival outcome in this population.

Frequency, risk-factors and survival of children with atypical teratoid rhabdoid tumors (AT/RT) of the CNS diagnosed between 1988 and 2004, and registered to the German HIT database.

Purpose: To analyze the frequency, prognostic factors, and outcome of children with atypical teratoid/rhabdoid tumors (AT/RT), a rare and highly malignant embryonal brain tumor.

Materials And Methods: Clinical data of patients diagnosed between 1988 and 2004 with AT/RT who were registered to the German HIT trial center, were correlated with outcome. Patient numbers for AT/RT were compared to numbers for primitive neuroectodermal tumors and medulloblastomas (PNET/MB) registered to the population-based HIT trials.

Impact of chemotherapy on disseminated low-grade glioma in children and adolescents: report from the HIT-LGG 1996 trial.

Background: We describe demographic data of disseminated childhood low-grade glioma (DLGG) prospectively recruited in the HIT-LGG 1996 study and evaluate the impact of primary chemotherapy (CT) on the outcome of these tumors, which have previously only been described in small and retrospective series.

Patients And Methods: The multicenter study HIT-LGG 1996 accrued 1181 children and adolescents with low-grade glioma. 61 patients (5.

Outcome of 11 children with ependymoblastoma treated within the prospective HIT-trials between 1991 and 2006.

Ependymoblastoma is a rare malignant brain tumor of early childhood. Data on clinical behavior and optimal treatment strategies are scarce. We report on 11 consecutively treated children with centrally confirmed diagnosis of CNS ependymoblastoma, registered between February 1994 and October 2006 to the prospective GPOH-HIT multicenter brain tumor trials, and treated by multimodal regimens.

Aberrant methylation and reduced expression of LHX9 in malignant gliomas of childhood.

High-grade gliomas (HGGs) of childhood represent approximately 7% of pediatric brain tumors. They are highly invasive tumors and respond poorly to conventional treatments in contrast to pilocytic astrocytomas, which usually are well demarcated and frequently can be cured by surgery. The molecular events for this clinical relevant finding are only partially understood.

Long-term outcome and clinical prognostic factors in children with medulloblastoma treated in the prospective randomised multicentre trial HIT'91.

Purpose: To analyse long-term outcome and clinical prognostic factors in medulloblastoma.

Methods: We analysed 280 patients with medulloblastoma (3-18 years) included from 1991 to 1997 in the randomised multicentre trial HIT'91 comparing pre-('sandwich') and postradiation ('maintenance') chemotherapy (median follow-up of survivors for 10 years).

Results: In 187 patients with complete staging, overall survival (OS) was higher after maintenance compared to sandwich treatment for M0 (10-year OS 91% and 62%, p=0.

Treatment of early childhood medulloblastoma by postoperative chemotherapy and deferred radiotherapy.

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.

Postoperative adjuvant dendritic cell-based immunotherapy in patients with relapsed glioblastoma multiforme.

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.

Low level of microsatellite instability in paediatric malignant astrocytomas.

Aim: Microsatellite instability (MSI) has been proposed as a possible mechanism in the development of cancer. The aim of the current study was to determine whether MSI is involved in the pathogenesis of paediatric malignant astrocytomas.

Methods: We screened a cohort of 126 high-grade astrocytoma samples for MSI using a sensitive and precise method of DNA analysis including a panel of five mononucleotide repeats, in combination with immunohistochemistry for DNA mismatch repair (MMR) proteins.

Prognostic relevance of clinical and biological risk factors in childhood medulloblastoma: results of patients treated in the prospective multicenter trial HIT'91.

Purpose: To identify better risk stratification systems in childhood medulloblastoma based on clinical factors and analysis of routinely processed formalin-fixed tumor material.

Experimental Design: Formalin-fixed paraffin-embedded tumor samples from well-documented patients treated within the prospective randomized multicenter trial HIT'91 were analyzed for DNA amplification of c-myc and N-myc (n=133) and mRNA expression of c-myc and trkC (n=104; compared with human cerebellum) using validated methods of quantitative PCR and reverse transcription-PCR. Results were related to clinical data and outcome.

Spinal deformity after multilevel osteoplastic laminotomy.

Multilevel laminectomy in children has a significant rate of postoperative spinal deformity. To decrease the incidence of this complication, the use of osteoplastic laminotomy is advocated to minimise the risk of spinal deformity by preserving the normal architecture of the spine. In this retrospective study, a 10-year series of a paediatric population undergoing multilevel osteoplastic laminotomy is reviewed to determine the incidence, especially in contrast to laminectomies, and to identify factors that affect the occurrence of spinal column deformity.

Childhood pineoblastoma: experiences from the prospective multicenter trials HIT-SKK87, HIT-SKK92 and HIT91.

Objective: To analyze the outcome of children with pineoblastoma (PB), treated within the prospective multicenter trials HIT-SKK87, HIT-SKK92 and HIT91 of German-speaking countries.

Patients: We report on 11 children suffering from PB. Five children younger than 3 years of age received chemotherapy after surgery until eligible for radiotherapy (HIT-SKK87 and HIT-SKK92).

Biological activity of paediatric cerebral cavernomas: an immunohistochemical study of 28 patients.

Objective: According to the hypothesis that paediatric cerebral cavernomas may have different biological activity compared to adult cavernomas, immunohistochemical analysis was used to elucidate the biological nature of paediatric cavernomas.

Patients And Methods: We examined the histological features and the proliferative and angiogenic capacity of the tissue specimens acquired from 28 paediatric patients. Normal paediatric brain tissues obtained from paediatric autopsy cases were used as a control group.

Treatment of early childhood medulloblastoma by postoperative chemotherapy alone.

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.

Three-dimensional intraoperative ultrasound of vascular malformations and supratentorial tumors.

The benefits and limits of a magnetic sensor-based 3-dimensional (3D) intraoperative ultrasound technique during surgery of vascular malformations and supratentorial tumors were evaluated. Twenty patients with 11 vascular malformations and 9 supratentorial tumors undergoing microsurgical resection or clipping were investigated with an interactive magnetic sensor data acquisition system allowing freehand scanning. An ultrasound probe with a mounted sensor was used after craniotomies to localize lesions, outline tumors or malformation margins, and identify supplying vessels.

Ultrasound-guided neuronavigation of deep-seated cavernous haemangiomas: clinical results and navigation techniques.

The aim of this study was to evaluate guidance techniques and patient outcomes of ultrasound-guided neuronavigation of deep-seated intracerebral cavernous hemangiomas (CAs). Thirty-five patients with deep-seated intracerebral CAs with sizes ranging between 7 and 45 mm were operated upon only with ultrasound-guidance. Twenty-seven were located in or near eloquent regions.

New ultrasound techniques and their application in neurosurgical intra-operative sonography.

We describe a variety of new ultrasound techniques by their physical background, potentials and applications regarding usefulness during intra-operative neurosurgical procedures. Transducers like high-frequency and small rotating probes fitting into neuroendoscopes, imaging techniques as extended field-of-view technique, harmonic imaging, echo-enhancers, 3-D imaging and the real-time integration of neurosonography with pre-operative CT- or MR-data are mentioned. The technical or physical principles are explained, followed by a discussion of these techniques from available literature dealing with their intra-operative neurosurgical applications and the experience of the authors with the techniques.

Different vascular patterns of medulloblastoma and supratentorial primitive neuroectodermal tumors.

Astrocytoma vasculature patterns differ according to histological grade of malignancy with glioblastoma multiforme (WHO grade IV) showing most extensive endothelial proliferation. Here, we determined whether the vascular patterns of medulloblastoma and supratentorial primitive neuroectodermal tumors (PNETs), which can be hardly distinguished histopathologically, differ. We evaluated the spatial organization of vessels in medulloblastomas and PNETs using antibodies to von Willebrand factor (vWF) and CD34.

Localization and characterization of intracerebral cavernous angiomas by intra-operative high-resolution colour-duplex-sonography.

The aim of this prospective study was to evaluate the reliability of high-resolution Colour-Duplex-Sonography (= CDS) in intra-operative localization, guiding and characterization of intracerebral cavernous angiomas (= CA). During a time period from 5/93 to 12/96 a total of 26 patients with 21 supratentorial and 5 infratentorial CA (15 of them deep-seated) were examined intra-operatively by CDS. The study focussed on 1.

Intra-operative colour-duplex-sonography in the surgical management of cerebral AV-malformations.

In this prospective study the role of intra-operative Colour-Duplex-Sonography (= CDS) during surgery of arteriovenous malformations (= AVM) is evaluated. During the last three years 20 consecutive patients with supratentorial AVMs were examined by intra-operative CDS in order to evaluate the potential of CDS to 1) localize the AVM, 2) differentiate between embolized and perfused parts, 3) identify feeding and draining vessels and 4) control the complete excision of the AVM. All AVMs were localized supratentorially, 9 were grade I and II (according to Spetzler and Martin [31]), 8 grade III and 3 grade IV.