BACKGROUND Several studies have proven the benefit of a greater extent of resection on progression-free survival and overall survival in glioblastoma (GBM). Possible reasons for incomplete tumor resection might be wrong interpretation of fading fluorescence or overseen fluorescent tumor tissue by a lacking line of sight between tumor tissue and the microscope. OBJECTIVE To evaluate if an endoscope being capable of inducing fluorescence might overcome some limitations of microscopic fluorescence-guided (FG) resection. METHODS 5-Aminolevulinic acid (20 mg/kg) was given 4 h before surgery. Microsurgical resection of all fluorescent tissue was performed. Then, the resection cavity was scanned with the endoscope. Fluorescent tissue, not being visualized by the microscope, was additionally removed and histopathologically examined separately. Neuronavigation was used for defining the sites of additional tumor resection. All patients underwent magnetic resonance imaging within 48 h after surgery. RESULTS Twenty patients with GBM were operated using microscopic and endoscopic FG resection. In all patients, additional fluorescent tissue was detected with the endoscope. This tissue was completely resected in 19 patients (95%). Eloquent localization precluded complete resection in the remaining patient. In 19 patients (95%), histopathological examination confirmed tumor in the additionally resected tissue. In 19 patients (95%), complete resection was confirmed. In all patients, endoscopic FG resection reached beyond the borders of contrast-enhancing tumor. CONCLUSION Endoscopic FG resection of GBM allows increasing the complete resection rate substantially and therefore is a useful adjunct to microscopic FG resection.

Background Adult-type diffuse gliomas, CNS WHO grade 4 are the most aggressive primary brain tumors and represent a particular challenge of therapeutic intervention. Methods In a single-center retrospective study of matched pairs of initial and post-therapeutic glioma cases with a recurrence period greater than one year, we performed whole exome sequencing combined with mRNA and microRNA expression profiling to identify processes that are altered in recurrent gliomas. Results Mutational analysis of recurrent gliomas revealed early branching evolution in seventy-five percent of patients. High plasticity was confirmed at the mRNA and miRNA levels. SBS1 signature was reduced and SBS11 was elevated, demonstrating the effect of alkylating agent therapy on the mutational landscape. There was no evidence for secondary genomic alterations driving therapy resistance. ALK7/ACVR1C and LTBP1 were upregulated, whereas LEFTY2 was downregulated, pointing towards enhanced Tumor Growth Factor β (TGF-β) signaling in recurrent gliomas. Consistently, altered microRNA expression profiles pointed towards enhanced Nuclear Factor Kappa B and Wnt signaling that, cooperatively with TGF-β, induces epithelial to mesenchymal transition (EMT), migration and stemness. TGF-β-induced expression of pro-apoptotic proteins and repression of anti-apoptotic proteins were uncoupled in the recurrent tumor. Conclusions Our results suggest an important role of TGF-β signaling in recurrent gliomas. This may have clinical implication, since TGF-β inhibitors have entered clinical phase studies and may potentially be used in combination therapy to interfere with chemoradiation resistance. Recurrent gliomas show high incidence of early branching evolution. High tumor plasticity is confirmed at the level of microRNA and mRNA expression profiles.

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Background A methylation-based classification of ependymoma has recently found broad application. However, the diagnostic advantage and implications for treatment decisions remain unclear. Here, we retrospectively evaluate the impact of surgery and radiotherapy on outcome after molecular reclassification of adult intracranial ependymomas. Methods Tumors diagnosed as intracranial ependymomas from 170 adult patients collected from eight diagnostic institutions were subjected to DNA methylation profiling. Molecular classes, patient characteristics, and treatment were correlated with progression-free survival (PFS). Results The classifier indicated an ependymal tumor in 73.5%, a different tumor entity in 10.6% and non-classifiable tumors in 15.9% of cases, respectively. The most prevalent molecular classes were posterior fossa ependymoma group B (EPN-PFB, 32.9%), posterior fossa subependymoma (PF-SE, 25.9%), and supratentorial ZFTA fusion-positive ependymoma (EPN-ZFTA, 11.2%). With a median follow-up of 60.0 months, the 5- and 10-year-PFS rates were 64.5% and 41.8% for EPN-PFB, 67.4% and 45.2% for PF-SE and 60.3% and 60.3% for EPN-ZFTA. In EPN-PFB, but not in other molecular classes, gross total resection (p=0.009) and postoperative radiotherapy (p=0.007) were significantly associated with improved PFS in multivariable analysis. Histological tumor grading (WHO 2 vs. 3) was not a predictor of prognosis within molecularly defined ependymoma classes. Conclusions DNA methylation profiling improves diagnostic accuracy and risk stratification in adult intracranial ependymoma. The molecular class of PF-SE is unexpectedly prevalent among adult tumors with ependymoma histology and relapsed as frequently as EPN-PFB, despite the supposed benign nature. Gross total resection and radiotherapy may represent key factors in determining the outcome of EPN-PFB patients.