7 research outputs found

    Safe surgery for glioblastoma: recent advances and modern challenges

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    One of the major challenges during glioblastoma surgery is balancing between maximizing extent of resection and preventing neurological deficits. Several surgical techniques and adjuncts have been developed to help identify eloquent areas both preoperatively (fMRI, nTMS, MEG, DTI) and intraoperatively (imaging (ultrasound, iMRI), electrostimulation (mapping), cerebral perfusion measurements (fUS)), and visualization (5-ALA, fluoresceine)). In this review, we give an update of the state-of-the-art management of both primary and recurrent glioblastomas. We will review the latest surgical advances, challenges, and approaches that define the onco-neurosurgical practice in a contemporary setting and give an overview of the current prospective scientific efforts

    Global comparison of awake and asleep mapping procedures in glioma surgery: an international multicenter survey

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    Background Mapping techniques are frequently used to preserve neurological function during glioma surgery. There is, however, no consensus regarding the use of many variables of these techniques. Currently, there are almost no objective data available about potential heterogeneity between surgeons and centers. The goal of this survey is therefore to globally identify, evaluate and analyze the local mapping procedures in glioma surgery. Methods The survey was distributed to members of the neurosurgical societies of the Netherlands (Nederlandse Vereniging voor Neurochirurgie-NVVN), Europe (European Association of Neurosurgical Societies-EANS), and the United States (Congress of Neurological Surgeons-CNS) between December 2020 and January 2021 with questions about awake mapping, asleep mapping, assessment of neurological morbidity, and decision making. Results Survey responses were obtained from 212 neurosurgeons from 42 countries. Overall, significant differences were observed for equipment and its settings that are used for both awake and asleep mapping, intraoperative assessment of eloquent areas, the use of surgical adjuncts and monitoring, anesthesia management, assessment of neurological morbidity, and perioperative decision making. Academic practices performed awake and asleep mapping procedures more often and employed a clinical neurophysiologist with telemetric monitoring more frequently. European neurosurgeons differed from US neurosurgeons regarding the modality for cortical/subcortical mapping and awake/asleep mapping, the use of surgical adjuncts, and anesthesia management during awake mapping. Discussion This survey demonstrates the heterogeneity among surgeons and centers with respect to their procedures for awake mapping, asleep mapping, assessing neurological morbidity, and decision making in glioma patients. These data invite further evaluations for key variables that can be optimized and may therefore benefit from consensus

    Decoupling genetics, lineages, and microenvironment in IDH-mutant gliomas by single-cell RNA-seq.

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    Tumor subclasses differ according to the genotypes and phenotypes of malignant cells as well as the composition of the tumor microenvironment (TME). We dissected these influences in isocitrate dehydrogenase (IDH)-mutant gliomas by combining 14,226 single-cell RNA sequencing (RNA-seq) profiles from 16 patient samples with bulk RNA-seq profiles from 165 patient samples. Differences in bulk profiles between IDH-mutant astrocytoma and oligodendroglioma can be primarily explained by distinct TME and signature genetic events, whereas both tumor types share similar developmental hierarchies and lineages of glial differentiation. As tumor grade increases, we find enhanced proliferation of malignant cells, larger pools of undifferentiated glioma cells, and an increase in macrophage over microglia expression programs in TME. Our work provides a unifying model for IDH-mutant gliomas and a general framework for dissecting the differences among human tumor subclasses

    An Integrative Model of Cellular States, Plasticity, and Genetics for Glioblastoma.

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    Diverse genetic, epigenetic, and developmental programs drive glioblastoma, an incurable and poorly understood tumor, but their precise characterization remains challenging. Here, we use an integrative approach spanning single-cell RNA-sequencing of 28 tumors, bulk genetic and expression analysis of 401 specimens from the The Cancer Genome Atlas (TCGA), functional approaches, and single-cell lineage tracing to derive a unified model of cellular states and genetic diversity in glioblastoma. We find that malignant cells in glioblastoma exist in four main cellular states that recapitulate distinct neural cell types, are influenced by the tumor microenvironment, and exhibit plasticity. The relative frequency of cells in each state varies between glioblastoma samples and is influenced by copy number amplifications of the CDK4, EGFR, and PDGFRA loci and by mutations in the NF1 locus, which each favor a defined state. Our work provides a blueprint for glioblastoma, integrating the malignant cell programs, their plasticity, and their modulation by genetic drivers
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