The Prognostic Value of the Prognostic Nutritional Index in Operable High-Grade Glioma Patients and the Establishment of a Nomogram

BackgroundStudies confirmed the predictive value of the prognostic nutrition index (PNI) in many malignant tumors. However, it did not reach a consensus in glioma. Therefore, this study investigated the prognostic value of preoperative PNI in operable high-grade glioma and established a nomogram.MethodsClinical data of high-grade glioma patients were retrospectively analyzed. The primary endpoint was overall survival (OS). Survival analysis was conducted by the Kaplan–Meier method, log-rank test, and Cox regression analysis. A nomogram was established. The prediction effect of the nomogram covering PNI was verified by area under the curve (AUC).ResultsA total of 91 operable high-grade glioma patients were included. Kaplan–Meier analysis showed that among grade IV gliomas (n = 55), patients with higher PNI (>44) showed a trend of OS benefit (p = 0.138). In grade III glioma (n = 36), patients with higher PNI (>47) had longer OS (p = 0.023). However, the intersecting Kaplan–Meier curve suggested that there may be some confounding factors. Cox regression analysis showed that higher PNI was an independent prognostic factor for grade IV glioma (HR = 0.388, p = 0.040). In grade III glioma, there was no statistically relationship between PNI levels and prognosis. When evaluating the prognostic ability of PNI alone by ROC, the AUC in grade III and IV gliomas was low, indicating that PNI alone had poor predictive power for OS. Interestingly, we found that the nomogram including preoperative PNI, age, extent of resection, number of gliomas, and MGMT methylation status could predict the prognosis of patients with grade IV glioma well.ConclusionThe PNI level before surgery was an independent prognostic factor for patients with grade IV glioma. The nomogram covering PNI in patients with grade IV glioma also proved the value of PNI. However, the value of PNI in grade III glioma needs to be further evaluated. More prospective studies are needed to verify this conclusion.

Local detection of microvessels in IDH-wildtype glioblastoma using relative cerebral blood volume: an imaging marker useful for astrocytoma grade 4 classification

Background The microvessels area (MVA), derived from microvascular proliferation, is a biomarker useful for high-grade glioma classification. Nevertheless, its measurement is costly, labor-intense, and invasive. Finding radiologic correlations with MVA could provide a complementary non-invasive approach without an extra cost and labor intensity and from the first stage. This study aims to correlate imaging markers, such as relative cerebral blood volume (rCBV), and local MVA in IDH-wildtype glioblastoma, and to propose this imaging marker as useful for astrocytoma grade 4 classification. Methods Data from 73 tissue blocks belonging to 17 IDH-wildtype glioblastomas and 7 blocks from 2 IDH-mutant astrocytomas were compiled from the Ivy GAP database. MRI processing and rCBV quantification were carried out using ONCOhabitats methodology. Histologic and MRI co-registration was done manually with experts’ supervision, achieving an accuracy of 88.8% of overlay. Spearman’s correlation was used to analyze the association between rCBV and microvessel area. Mann-Whitney test was used to study differences of rCBV between blocks with presence or absence of microvessels in IDH-wildtype glioblastoma, as well as to find differences with IDH-mutant astrocytoma samples. Results Significant positive correlations were found between rCBV and microvessel area in the IDH-wildtype blocks (p < 0.001), as well as significant differences in rCBV were found between blocks with microvascular proliferation and blocks without it (p < 0.0001). In addition, significant differences in rCBV were found between IDH-wildtype glioblastoma and IDH-mutant astrocytoma samples, being 2–2.5 times higher rCBV values in IDH-wildtype glioblastoma samples. Conclusions The proposed rCBV marker, calculated from diagnostic MRIs, can detect in IDH-wildtype glioblastoma those regions with microvessels from those without it, and it is significantly correlated with local microvessels area. In addition, the proposed rCBV marker can differentiate the IDH mutation status, providing a complementary non-invasive method for high-grade glioma classification.

H3.3K27M Mutation Promotes The Migration and Invasion of Glioma Cells By Activating β-Catenin/USP1 Signaling

H3.3K27M is a newly identified molecular pathology marker in glioma and is especially correlated with the malignancy of diffuse intrinsic pontine glioma (DIPG). In recent years, accumulating research has revealed that other types of glioma also contain the H3.3K27M mutation. However, the role of H3.3K27M in high-grade adult glioma, which is the most malignant glioma, has not been investigated. In this study, we focused on exploring the expression and function of H3.3K27M in high-grade adult glioma patients. We found that H3.3K27M is partly highly expressed in high-grade glioma tissues. Then, we introduced H3.3K27M into H3.3 wild-type glioma cells, U87 cells and LN229 cells. We found that H3.3K27M did not regulate the growth of glioma in vitro and in vivo; however, the survival of mice with transplanted tumors was significantly reduced. Further investigation revealed that H3.3K27M expression mainly promoted the migration and invasion of glioma cells. Moreover, we certified that H3.3K27M overexpression enhanced the protein levels of ꞵ-catenin and p-ꞵ-catenin, the protein and mRNA levels of ubiquitin-specific protease 1 (USP1), and the protein level of enhancer of zeste homolog 2 (EZH2). Importantly, the ꞵ-catenin inhibitor XAV-939 significantly attenuated the upregulation of the aforementioned proteins. Overall, the H3.3K27M mutation is present in a certain proportion of high-grade glioma patients and facilitates a poor prognosis by promoting the metastasis of glioma by regulating the ꞵ-catenin/USP1/EZH2 pathway.

Contemporary intraoperative visualization for GBM with use of exoscope, 5-ALA fluorescence-guided surgery and tractography

Maximal safe resection is the primary goal of glioma surgery. By incorporating improved intraoperative visualization with the 3D exoscope combined with 5-ALA fluorescence, in addition to neuronavigation and diffusion tensor imaging (DTI) fiber tracking, the safety of resection of tumors in eloquent brain regions can be maximized. This video highlights some of the various intraoperative adjuncts used in brain tumor surgery for high-grade glioma. In this case, the authors highlight the resection of a left posterior temporal lobe high-grade glioma in a 33-year-old patient, who initially presented with seizures, word-finding difficulty, and right-sided weakness. They demonstrate the multiple surgical adjuncts used both before and during surgical resection, and how multiple adjuncts can be effectively orchestrated to make surgery in eloquent brain areas safer for patients. Patient consent was obtained for publication. The video can be found here: https://stream.cadmore.media/r10.3171/2021.10.FOCVID21174

Microscope-based augmented reality with diffusion tensor imaging and fluorescein in insular glioma resection

Maximal safe resection is the goal of insular glioma surgery. The combination of intraoperative augmented reality (AR) diffusion tensor imaging (DTI) fiber tracking with fluorescein dye (F) helps achieve this goal throughout a microscope-based visualization of the tumor and white matter fiber tracts. The aim of the present video article was to show the technical key aspects of DTI-F microscope-based AR-assisted surgery during the gross-total resection of an insular Berger-Sanai type I+IV high-grade glioma in a 63-year-old patient, performed through a pterional transsylvian approach. The video can be found here: https://stream.cadmore.media/r10.3171/2021.10.FOCVID2157