Correlation of LLT-1 and NLRC4 inflammasome and its effect on glioblastoma prognosis.

PURPOSE: LLT-1 is a well-known ligand for the natural killer (NK) cell inhibitory receptor NKRP1A. Here, we examined NLRC4 inflammasome components and LLT-1 expression in glioblastoma (GBM) tissues to elucidate potential associations and interactions between these factors. METHODS: GBM tissues were collected for RNA sequencing (RNA-seq) and Immunofluorescent experiments. Colocalization of LLT-1 and other proteins was assessed by immunofluorescence. Computational analyses utilized RNA-seq data from 296 to 52 patients from the Chinese Glioma Genome Atlas and CHA medical records, respectively. These data were subjected to survival, non-negative matrix factorization clustering, Gene Ontology enrichment, and protein-protein interaction analyses. Receptor-ligand interactions between tumor and immune cells were confirmed by single-cell RNA-seq analysis. RESULTS: In GBM tissues, LLT-1 was predominantly colocalized with glial fibrillary acidic protein (GFAP)-expressing astrocytes, but not with microglial markers like Iba-1. Additionally, LLT-1 and activated NLRC4 inflammasomes were mainly co-expressed in intratumoral astrocytes, suggesting an association between LLT-1, NLRC4, and glioma malignancy. High LLT-1 expression correlates with poor prognosis, particularly in the mesenchymal subtype, and is associated with TNF and NOD-like receptor signaling pathway enrichment, indicating a potential role in tumor inflammation and progression. At the single-cell level, mesenchymal-like malignant cells showed high NF, NLR, and IL-1 signaling pathway enrichment compared to other malignant cell types. CONCLUSION: We revealed an association between NLRC4 inflammasome activity and LLT-1 expression, suggesting a novel regulatory pathway involving TNF, inflammasomes, and IL-1, potentially offering new NK-cell-mediated anti-glioma approaches.

Rethinking extent of resection of contrast-enhancing and non-enhancing tumor: different survival impacts on adult-type diffuse gliomas in 2021 World Health Organization classification.

OBJECTIVES: Extent of resection (EOR) of contrast-enhancing (CE) and non-enhancing (NE) tumors may have different impacts on survival according to types of adult-type diffuse gliomas in the molecular era. This study aimed to evaluate the impact of EOR of CE and NE tumors in glioma according to the 2021 World Health Organization classification. METHODS: This retrospective study included 1193 adult-type diffuse glioma patients diagnosed between 2001 and 2021 (183 oligodendroglioma, 211 isocitrate dehydrogenase [IDH]-mutant astrocytoma, and 799 IDH-wildtype glioblastoma patients) from a single institution. Patients had complete information on IDH mutation, 1p/19q codeletion, and O6-methylguanine-methyltransferase (MGMT) status. Cox survival analyses were performed within each glioma type to assess predictors of overall survival, including clinical, imaging data, histological grade, MGMT status, adjuvant treatment, and EOR of CE and NE tumors. Subgroup analyses were performed in patients with CE tumor. RESULTS: Among 1193 patients, 935 (78.4%) patients had CE tumors. In entire oligodendrogliomas, gross total resection (GTR) of NE tumor was not associated with survival (HR = 0.56, p = 0.223). In 86 (47.0%) oligodendroglioma patients with CE tumor, GTR of CE tumor was the only independent predictor of survival (HR = 0.16, p = 0.004) in multivariable analysis. GTR of CE and NE tumors was independently associated with better survival in IDH-mutant astrocytoma and IDH-wildtype glioblastoma (all ps < 0.05). CONCLUSIONS: GTR of both CE and NE tumors may significantly improve survival within IDH-mutant astrocytomas and IDH-wildtype glioblastomas. In oligodendrogliomas, the EOR of CE tumor may be crucial in survival; aggressive GTR of NE tumor may be unnecessary, whereas GTR of the CE tumor is recommended. CLINICAL RELEVANCE STATEMENT: Surgical strategies on contrast-enhancing (CE) and non-enhancing (NE) tumors should be reassessed considering the different survival outcomes after gross total resection depending on CE and NE tumors in the 2021 World Health Organization classification of adult-type diffuse gliomas. KEY POINTS: The survival impact of extent of resection of contrast-enhancing (CE) and non-enhancing (NE) tumors was evaluated in adult-type diffuse gliomas. Gross total resection of both CE and NE tumors may improve survival in isocitrate dehydrogenase (IDH)-mutant astrocytomas and IDH-wildtype glioblastomas, while only gross total resection of the CE tumor improves survival in oligodendrogliomas. Surgical strategies should be reconsidered according to types in adult-type diffuse gliomas.

Classification of IDH wild-type glioblastoma tumorspheres into low- and high-invasion groups based on their transcriptional program.

BACKGROUND: Glioblastoma (GBM), one of the most lethal tumors, exhibits a highly infiltrative phenotype. Here, we identified transcription factors (TFs) that collectively modulate invasion-related genes in GBM. METHODS: The invasiveness of tumorspheres (TSs) were quantified using collagen-based 3D invasion assays. TF activities were quantified by enrichment analysis using GBM transcriptome, and confirmed by cell-magnified analysis of proteome imaging. Invasion-associated TFs were knocked down using siRNA or shRNA, and TSs were orthotopically implanted into mice. RESULTS: After classifying 23 patient-derived GBM TSs into low- and high-invasion groups, we identified active TFs in each group-PCBP1 for low invasion, and STAT3 and SRF for high invasion. Knockdown of these TFs reversed the phenotype and invasion-associated-marker expression of GBM TSs. Notably, MRI revealed consistent patterns of invasiveness between TSs and the originating tumors, with an association between high invasiveness and poor prognosis. Compared to controls, mice implanted with STAT3- or SRF-downregulated GBM TSs showed reduced normal tissue infiltration and tumor growth, and prolonged survival, indicating a therapeutic response. CONCLUSIONS: Our integrative transcriptome analysis revealed three invasion-associated TFs in GBM. Based on the relationship among the transcriptional program, invasive phenotype, and prognosis, we suggest these TFs as potential targets for GBM therapy.

Revisiting prognostic factors in glioma with leptomeningeal metastases: a comprehensive analysis of clinical and molecular factors and treatment modalities.

PURPOSE: To comprehensively investigate prognostic factors, including clinical and molecular factors and treatment modalities, in adult glioma patients with leptomeningeal metastases (LM). METHODS: Total 226 patients with LM (from 2001 to 2021 among 1495 grade 2 to 4 glioma patients, 88.5% of LM patients being IDH-wildtype) with complete information on IDH mutation, 1p/19q codeletion, and MGMT promoter methylation status were enrolled. Predictors of overall survival (OS) of entire patients were determined by time-dependent Cox analysis, including clinical, molecular, and treatment data. Subgroup analyses were performed for patients with LM at initial diagnosis and LM diagnosed at recurrence (herein, initial and recurrent LM). Identical analyses were performed in IDH-wildtype glioblastoma patients. RESULTS: Median OS was 17.0 (IQR 9.7-67.1) months, with shorter median OS in initial LM than recurrent LM patients (12.2 vs 20.6 months, P < 0.001). In entire patients, chemotherapy and antiangiogenic therapy were predictors of longer OS, while male sex and initial LM were predictors of shorter OS. In initial LM, higher KPS, chemotherapy, and antiangiogenic therapy were predictors of longer OS, while male sex was a predictor of shorter OS. In recurrent LM, chemotherapy and longer interval between initial glioma and LM diagnoses were predictors of longer OS, while male sex was a predictor of shorter OS. A similar trend was observed in IDH-wildtype glioblastoma. CONCLUSION: Active chemotherapy and antiangiogenic therapy demonstrated survival benefit in glioma patients with LM. There is consistent female survival advantage, whereas longer interval between initial glioma diagnosis and LM development suggests longer OS in recurrent LM.

Impact of boost sequence in concurrent chemo-radiotherapy on newly diagnosed IDH-wildtype glioblastoma multiforme.

BACKGROUND: The standard of care for glioblastoma multiforme (GBM) is maximal surgical resection followed by conventional fractionated concurrent chemoradiotherapy (CCRT) with a total dose of 60 Gy. However, there is currently no consensus on the optimal boost technique for CCRT in GBM. METHODS: We conducted a retrospective review of 398 patients treated with CCRT between 2016 and 2021, using data from two institutional databases. Patients were divided into two groups: those receiving sequential boost (SEB, N = 119) and those receiving simultaneous integrated boost (SIB, N = 279). The primary endpoint was overall survival (OS). To minimize differences between the SIB and SEB groups, we conducted propensity score matching (PSM) analysis. RESULTS: The median follow-up period was 18.6 months. Before PSM, SEB showed better OS compared to SIB (2-year, 55.6% vs. 44.5%, p = 0.014). However, after PSM, there was no significant difference between two groups (2-year, 55.6% vs. 51.5%, p = 0.300). The boost sequence was not associated with inferior OS before and after PSM (all p-values > 0.05). Additionally, the rates of symptomatic pseudo-progression were similar between the two groups (odds ratio: 1.75, p = 0.055). CONCLUSIONS: This study found no significant difference in OS between SEB and SIB for GBM patients treated with CCRT. Further research is needed to validate these findings and to determine the optimal boost techniques for this patient population.

Non-canonical NLRC4 inflammasomes in astrocytes contribute to glioma malignancy.

BACKGROUND: The present study was designed to explore the pathological role of non-canonical NLRC4 inflammasome in glioma. METHODS: This retrospective study included bioinformatical analysis, including survival, gene ontology, ssGSEA, cox regression, IPA and drug repositioning with TCGA and DepMap database. Experimental validations were conducted in glioma patient's sample and evaluated with histological or cellular functional analysis. RESULT: Clinical dataset analysis revealed that non-canonical NLRC4 inflammasomes significantly contribute to glioma progression and poor survival rates. Experimental validation was revealed that the expression of non-canonical NLRC4 inflammasomes were co-localized with astrocytes in malignant gliomas, with a sustained clinical correlation observed between astrocytes and inflammasome signatures. Indeed, the formation of an inflammatory microenvironment increased in malignant gliomas, leading to pyroptosis, known as inflammatory cell death. Molecular interaction analysis revealed that NF-κB pathways potentially serve as the connecting point between the canonical and noncanonical pathways of the NLRC4 inflammasome. Finally, drug repositioning analysis of non-canonical NLRC4 inflammasome-associated molecules revealed that MK-5108, PF4981517, and CTEP may represent effective options for glioma therapy. CONCLUSION: The findings of this study suggest that non-canonical NLRC4 inflammasomes contribute to poor prognosis in patients with glioma and induce an inflammatory microenvironment. We propose the pathological phenomenon of non-canonical NLRC4 inflammasomes and several therapeutic strategies based on the modulation of the inflammatory tumor microenvironment.

Etomoxir, a carnitine palmitoyltransferase 1 inhibitor, combined with temozolomide reduces stemness and invasiveness in patient-derived glioblastoma tumorspheres.

INTRODUCTION: The importance of fatty acid oxidation (FAO) in the bioenergetics of glioblastoma (GBM) is being realized. Etomoxir (ETO), a carnitine palmitoyltransferase 1 (CPT1) inhibitor exerts cytotoxic effects in GBM, which involve interrupting the FAO pathway. We hypothesized that FAO inhibition could affect the outcomes of current standard temozolomide (TMZ) chemotherapy against GBM. METHODS: The FAO-related gene expression was compared between GBM and the tumor-free cortex. Using four different GBM tumorspheres (TSs), the effects of ETO and/or TMZ was analyzed on cell viability, tricarboxylate (TCA) cycle intermediates and adenosine triphosphate (ATP) production to assess metabolic changes. Alterations in tumor stemness, invasiveness, and associated transcriptional changes were also measured. Mouse orthotopic xenograft model was used to elucidate the combinatory effect of TMZ and ETO. RESULTS: GBM tissues exhibited overexpression of FAO-related genes, especially CPT1A, compared to the tumor-free cortex. The combined use of ETO and TMZ further inhibited TCA cycle and ATP production than single uses. This combination treatment showed superior suppression effects compared to treatment with individual agents on the viability, stemness, and invasiveness of GBM TSs, as well as better downregulation of FAO-related gene expression. The results of in vivo study showed prolonged survival outcomes in the combination treatment group. CONCLUSION: ETO, an FAO inhibitor, causes a lethal energy reduction in the GBM TSs. When used in combination with TMZ, ETO effectively reduces GBM cell stemness and invasiveness and further improves survival. These results suggest a potential novel treatment option for GBM.

Sex as a prognostic factor in adult-type diffuse gliomas: an integrated clinical and molecular analysis according to the 2021 WHO classification.

PURPOSE: To investigate whether type-specific sex differences in survival exist independently of clinical and molecular factors in adult-type diffuse gliomas according to the 2021 World Health Organization (WHO) classification. METHODS: A retrospective chart and imaging review of 1325 patients (mean age, 54 ± 15 years; 569 females) with adult-type diffuse gliomas (oligodendroglioma, IDH-mutant, and 1p/19q-codeleted, n = 183; astrocytoma, IDH-mutant, n = 211; glioblastoma, IDH-wildtype, n = 800; IDH-wildtype diffuse glioma, NOS, n = 131) was performed. The demographic information, extent of resection, imaging data, and molecular data including O6-methylguanine-methyltransferase promoter methylation (MGMT) promotor methylation were collected. Sex differences in survival were analyzed using Cox analysis. RESULTS: In patients with glioblastoma, IDH-wildtype, female sex remained as an independent predictor of better overall survival (hazard ratio = 0.91, P = 0.031), along with age, histological grade 4, MGMT promoter methylation status, and gross total resection. Female sex showed a higher prevalence of MGMT promoter methylation (40.2% vs 32.0%, P = 0.017) but there was no interaction effect between female sex and MGMT promoter methylation status (P-interaction = 0.194), indicating independent role of female sex. The median OS for females were 19.2 months (12.3-35.0) and 16.2 months (10.5-30.6) for males. No sex difference in survival was seen in other types of adult-type diffuse gliomas. CONCLUSION: There was a female survival advantage in glioblastoma, IDH-wildtype, independently of clinical data or MGMT promoter methylation status. There was no sex difference in survival in other types of adult-type diffuse gliomas, suggesting type-specific sex effects solely in glioblastoma, IDH-wildtype.

Dual inhibition of CPT1A and G6PD suppresses glioblastoma tumorspheres.

PURPOSE: Limited treatment options are currently available for glioblastoma (GBM), an extremely lethal type of brain cancer. For a variety of tumor types, bioenergetic deprivation through inhibition of cancer-specific metabolic pathways has proven to be an effective therapeutic strategy. Here, we evaluated the therapeutic effects and underlying mechanisms of dual inhibition of carnitine palmitoyltransferase 1A (CPT1A) and glucose-6-phosphate dehydrogenase (G6PD) critical for fatty acid oxidation (FAO) and the pentose phosphate pathway (PPP), respectively, against GBM tumorspheres (TSs). METHODS: Therapeutic efficacy against GBM TSs was determined by assessing cell viability, neurosphere formation, and 3D invasion. Liquid chromatography-mass spectrometry (LC-MS) and RNA sequencing were employed for metabolite and gene expression profiling, respectively. Anticancer efficacy in vivo was examined using an orthotopic xenograft model. RESULTS: CPT1A and G6PD were highly expressed in GBM tumor tissues. Notably, siRNA-mediated knockdown of both genes led to reduced viability, ATP levels, and expression of genes associated with stemness and invasiveness. Similar results were obtained upon combined treatment with etomoxir and dehydroepiandrosterone (DHEA). Transcriptome analyses further confirmed these results. Data from LC-MS analysis showed that this treatment regimen induced a considerable reduction in the levels of metabolites associated with the TCA cycle and PPP. Additionally, the combination of etomoxir and DHEA inhibited tumor growth and extended survival in orthotopic xenograft model mice. CONCLUSION: Our collective findings support the utility of dual suppression of CPT1A and G6PD with selective inhibitors, etomoxir and DHEA, as an efficacious therapeutic approach for GBM.

Pedicled frontal periosteal rescue flap via eyebrow incision for skull base reconstruction (SevEN-002).

PURPOSE: Cerebrospinal fluid (CSF) leakage is one of the major complications after endoscopic endonasal surgery. The reconstructive nasoseptal flap is widely used to repair CSF leakage. However, it could not be utilized in all cases; thus, there was a need for an alternative. We developed a pericranial rescue flap that could cover both sellar and anterior skull base defects via the endonasal approach. A modified surgical technique that did not violate the frontal sinus and cause cosmetic problems was designed using the pericranial rescue flap. METHODS: We performed 12 cadaveric dissections to investigate the applicability of the lateral pericranial rescue flap. An incision was made, extending from the middle to the lateral part of the eyebrow. The pericranium layer was dissected away from the galea layer, from the supraorbital region towards the frontoparietal region. With endoscopic assistance, the periosteal flap was raised, the flap base was the pericranium layer at the eyebrow incision. After a burr-hole was made in the supraorbital bone, the pericranial flap was inserted via the intradural or extradural pathway. RESULTS: The mean size of the pericranial flap was 11.5 cm × 3.2 cm. It was large enough to cross the midline and cover the dural defects of the anterior skull base, including the sellar region. CONCLUSION: We demonstrated a modified endoscopic technique to repair the anterior skull base defects. This minimally invasive pericranial flap may resolve neurosurgical complications, such as CSF leakage.

Dynamic contrast-enhanced MRI may be helpful to predict response and prognosis after bevacizumab treatment in patients with recurrent high-grade glioma: comparison with diffusion tensor and dynamic susceptibility contrast imaging.

PURPOSE: We aimed to evaluate the utility of diffusion tensor imaging (DTI), dynamic contrast-enhanced (DCE), and dynamic susceptibility contrast (DSC) imaging for stratifying bevacizumab treatment outcomes in patients with recurrent high-grade glioma. METHODS: Fifty-three patients with recurrent high-grade glioma who underwent baseline magnetic resonance imaging including DTI, DCE, and DSC before bevacizumab treatment were included. The mean apparent diffusion coefficient, fractional anisotropy, normalized cerebral blood volume, normalized cerebral blood flow, volume transfer constant, rate transfer coefficient (Kep), extravascular extracellular volume fraction, and plasma volume fraction were assessed. Predictors of response status, progression-free survival (PFS), and overall survival (OS) were determined using logistic regression and Cox proportional hazard modeling. RESULTS: Responders (n = 16) showed significantly longer PFS and OS (P < 0.001) compared with nonresponders (n = 37). Multivariable analysis revealed that lower mean Kep (odds ratio = 0.01, P = 0.008) was the only independent predictor of favorable response after adjustment for age, isocitrate dehydrogenase (IDH) mutation status, and O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status. Multivariable Cox proportional hazard modeling showed that a higher mean Kep was the only variable associated with shorter PFS (hazard ratio [HR] = 7.90, P = 0.006) and OS (HR = 9.71, P = 0.020) after adjustment for age, IDH mutation status, and MGMT promoter methylation status. CONCLUSION: Baseline mean Kep may be a useful biomarker for predicting response and stratifying patient outcomes following bevacizumab treatment in patients with recurrent high-grade glioma.

Optimization of orbital retraction during endoscopic transorbital approach via quantitative measurement of the intraocular pressure - [SevEN 006].

BACKGROUND: Increased use of the transorbital approach (TOA) warrants greater understanding of the risk of increased intraocular pressure (IOP) and intraorbital pressure (IORP) due to orbital compression. We aimed to investigate the changes in IOP and IORP in response to orbital retraction in TOA and establish a method for the continuous measurement of intraoperative IORP. METHODS: We assessed nine patients who underwent TOA surgery from January 2017 to December 2019, in addition to five cadavers. IORP and IOP were measured using a cannula needle monitor, tonometer, cuff manometer, and micro strain gauge monitor. RESULTS: In all nine clinical cases and five cadavers, increased physical compression of the orbit increased the IOP and IORP in a curvilinear pattern. In clinical cases, when the orbit was compressed 1.5 cm from the lateral margin in the sagittal plane, the mean IOP and IORP were 25.4 ± 5.2 mmHg and 14 ± 9.2 mmH2O, respectively. The IORP satisfactorily reflected the IOP (Pearson correlation coefficient = 0.824, p < 0.001). CONCLUSION: We measured IOP and IORP simultaneously during orbital compression to gain basic information on pressure changes. In clinical cases, the change in the IOP could be conveniently and noninvasively monitored using continuous IORP measurements.

Combinatorial Therapeutic Effect of Inhibitors of Aldehyde Dehydrogenase and Mitochondrial Complex I, and the Chemotherapeutic Drug, Temozolomide against Glioblastoma Tumorspheres.

Resident cancer cells with stem cell-like features induce drug tolerance, facilitating survival of glioblastoma (GBM). We previously showed that strategies targeting tumor bioenergetics present a novel emerging avenue for treatment of GBM. The objective of this study was to enhance the therapeutic effects of dual inhibition of tumor bioenergetics by combination of gossypol, an aldehyde dehydrogenase inhibitor, and phenformin, a biguanide compound that depletes oxidative phosphorylation, with the chemotherapeutic drug, temozolomide (TMZ), to block proliferation, stemness, and invasiveness of GBM tumorspheres (TSs). Combination therapy with gossypol, phenformin, and TMZ induced a significant reduction in ATP levels, cell viability, stemness, and invasiveness compared to TMZ monotherapy and dual therapy with gossypol and phenformin. Analysis of differentially expressed genes revealed up-regulation of genes involved in programmed cell death, autophagy, and protein metabolism and down-regulation of those associated with cell metabolism, cycle, and adhesion. Combination of TMZ with dual inhibitors of tumor bioenergetics may, therefore, present an effective strategy against GBM by enhancing therapeutic effects through multiple mechanisms of action.

Co-expression of cancer driver genes: IDH-wildtype glioblastoma-derived tumorspheres.

BACKGROUND: Driver genes of GBM may be crucial for the onset of isocitrate dehydrogenase (IDH)-wildtype (WT) glioblastoma (GBM). However, it is still unknown whether the genes are expressed in the identical cluster of cells. Here, we have examined the gene expression patterns of GBM tissues and patient-derived tumorspheres (TSs) and aimed to find a progression-related gene. METHODS: We retrospectively collected primary IDH-WT GBM tissue samples (n = 58) and tumor-free cortical tissue samples (control, n = 20). TSs are isolated from the IDH-WT GBM tissue with B27 neurobasal medium. Associations among the driver genes were explored in the bulk tissue, bulk cell, and a single cell RNAsequencing techniques (scRNAseq) considering the alteration status of TP53, PTEN, EGFR, and TERT promoter as well as MGMT promoter methylation. Transcriptomic perturbation by temozolomide (TMZ) was examined in the two TSs. RESULTS: We comprehensively compared the gene expression of the known driver genes as well as MGMT, PTPRZ1, or IDH1. Bulk RNAseq databases of the primary GBM tissue revealed a significant association between TERT and TP53 (p < 0.001, R = 0.28) and its association increased in the recurrent tumor (p < 0.001, R = 0.86). TSs reflected the tissue-level patterns of association between the two genes (p < 0.01, R = 0.59, n = 20). A scRNAseq data of a TS revealed the TERT and TP53 expressing cells are in a same single cell cluster. The driver-enriched cluster dominantly expressed the glioma-associated long noncoding RNAs. Most of the driver-associated genes were downregulated after TMZ except IGFBP5. CONCLUSIONS: GBM tissue level expression patterns of EGFR, TERT, PTEN, IDH1, PTPRZ1, and MGMT are observed in the GBM TSs. The driver gene-associated cluster of the GBM single cells were enriched with the glioma-associated long noncoding RNAs.

Lateral supraorbital versus pterional approach for parachiasmal meningiomas: surgical indications and esthetic benefits.

The lateral supraorbital (LSO) approach is a minimally invasive modification of the pterional approach. The authors assess the surgical indications and esthetic benefits of the LSO approach in comparison with the pterional approach for parachiasmal meningiomas. From April 2013 to May 2017, a total of 64 patients underwent surgery for parachiasmal meningiomas. Among them, tumor resection was performed with the LSO approach for 34 patients and pterional approach for 30 patients. A retrospective analysis was done on tumor characteristics, surgical outcome, approach-related morbidity, and esthetic outcome between the two approaches. Gross total resection was achieved in 33 of 34 patients (97.1%) with the LSO approach. There were no differences in tumor size, origin, consistency, internal carotid artery encasement, cranial nerve adhesion, and optic canal invasion between the two approaches. The most common tumor origin was the tuberculum sellae for both the LSO and pterional approaches. For tumors with preoperative visual compromise, immediate visual outcome improved or remained stable in 76% and 80.9% with the LSO and pterional approaches, respectively. Surgery time, surgical bleeding, hospital length of stay, and esthetic outcome were significantly shorter and superior with the LSO approach. There were no differences in surgical morbidity and brain retraction injury between the two approaches. The LSO approach can provide a safe, rapid, and minimally invasive exposure for parachiasmal meningiomas compared with the pterional approach. Surgeons must consider tumor size, origin, and extent in determining the resectability of the tumor rather than the extent of exposure.

Biportal endoscopic transorbital approach: a quantitative anatomical study and clinical application.

BACKGROUND: We devised a biportal endoscopic transorbital approach (BiETOA) to gain surgical freedom by making a port for the endoscope and investigated the benefits and limitations of BiETOA. METHODS: A cylindrical port was designed and 3-D printed using biocompatible material. The port was inserted through a keyhole between the superolateral side of the orbital rim and the temporal muscle. An endoscope was inserted through the port, and other instruments were inserted through the conventional transorbital route. BiETOA was used to dissect eight cadaveric heads, and the angle of attack and surgical freedom were assessed. RESULTS: The mean maximal angle of attack was significantly different in BiETOA and endoscopic transorbital approach (ETOA) (P < 0.01) but not in BiETOA and ETOA lateral orbital rim (LOR) osteotomy (P = 0.207, P = 0.21). The mean surgical freedom was significantly different in BiETOA and ETOA (P < 0.01) and in BiETOA and ETOA LOR osteotomy (P < 0.01). In the clinical cases, tumors were removed successfully without any complications. CONCLUSIONS: BiETOA provided increased surgical freedom and better visibility of deep target lesion and resulted in good surgical and cosmetic outcomes.

Re-evaluation of the diagnostic performance of 11C-methionine PET/CT according to the 2016 WHO classification of cerebral gliomas.

PURPOSE: We evaluated the usefulness of 11C-methionine (MET) positron emission tomography/computed tomography (PET/CT) for grading cerebral gliomas according to the 2016 WHO classification with special emphasis on the presence of the isocitrate dehydrogenase 1 (IDH1) gene mutation and 1p/19q codeletion. METHODS: In total, 144 patients underwent MET PET/CT before surgery. The ratios of the maximum standardized uptake value (SUV) of the gliomas to the mean SUV of the contralateral cortex on MET PET/CT (MET TNR) were calculated. RESULTS: The median MET TNRs in IDH1-mutant and IDH1-wildtype tumours were 1.95 and 3.35, respectively. From among 74 IDH1-mutant tumours, the oligodendrogliomas showed a higher median MET TNR than the astrocytic tumours (2.90 vs. 1.40, P < 0.001). In grade II, III and IV IDH1-mutant astrocytic tumours, the median MET TNRs were 1.20, 2.05 and 2.20, respectively (grade II vs. grade III, P < 0.0001; grade II vs. grade IV, P = 0.023). In oligodendrogliomas, the MET TNR was lower fin grade II tumours than in grade III tumours (2.30 vs. 3.30 P = 0.008). In differentiating low-grade (grade II) from high-grade (grade III and IV) gliomas, receiver operating characteristic analysis showed a higher area under the curve for wildtype tumours (0.976) than for all tumours (0.852; P < 0.001) and IDH1-mutant tumours (0.817; P = 0.004). CONCLUSION: IDH1-mutant tumours showed lower MET uptake than IDH1-wildtype tumours. Regardless of IDH1 mutation status, oligodendrogliomas with 1p/19q codeletion showed MET uptake as high as that in high-grade IDH1-wildtype tumours. Therefore, MET uptake for glioma grading was more consistent for IDH1-wildtype tumours than for IDH1-mutant tumours.

Effectiveness of navigation-guided cyst aspiration before resection of large cystic brain tumors: a proof of concept for more radical surgery.

BACKGROUND: Resection of tumors close to the corticospinal tract (CST) carries a high risk of damage to the CST. For cystic tumors, aspirating the cyst before resection may reduce the risk of damage to vital structures. This study evaluated the effectiveness of cyst aspiration, by comparing the results before and after aspiration of diffusion tensor image (DTI) tractography. METHODS: This study enrolled 23 patients with large cystic brain tumors (>20 cm3) between 2012 and 2016. All underwent magnetic resonance imaging (MRI), including DTI tractography, followed by navigation-guided aspiration of the cyst and subsequent tumor resection via craniotomy. Distances between the tumor margin and CST before and after cyst aspiration, volume reduction, and postoperative outcomes were assessed. RESULTS: Median tumor volume decreased from 88 cm3 (range, 25-153) to 29 cm3 (range, 20-80) and distances between tumor margins and the CST increased from 5.7 mm (range, 0.6-22.0) to 14.8 mm (range, 0.6-41.4) after aspiration. Neurological symptoms of patients immediately improved after cyst aspiration. All patients, except for one with a secondary glioblastoma, underwent gross total resection of the tumor. No neurological deterioration was observed after tumor resection. CONCLUSIONS: Navigation-guided cyst aspiration followed by resection is a useful and safe procedure for brain tumors with large cystic components. Cyst aspiration resulted in expansion of the compressed brain tissue between the tumor margins and vital structures, making maximal safe resection possible.

Success of tumorsphere isolation from WHO grade IV gliomas does not correlate with the weight of fresh tumor specimens: an immunohistochemical characterization of tumorsphere differentiation.

BACKGROUND: A trend of stage-by-stage increase in tumorsphere (TS) formation from glioma samples has been reported. Despite this trend, not all surgical specimens give rise to TSs, even World Health Organization (WHO) grade IV gliomas. Furthermore, it has been reported that differences in overall survival of primary glioblastoma patients depends on the propensity of their tumors to form TSs. However, the weights of fresh specimens vary from one surgical isolate to the next. METHODS: Accordingly, we evaluated the relationship between the weights of surgical specimens in WHO grade IV gliomas with the capacity to isolate TSs. Thirty-five fresh WHO grade IV glioma specimens were separated into two groups, based on whether they were positive or negative for TS isolation, and the relationship between TS isolation and weight of surgical specimens was assessed. RESULTS: We observed no significant difference in the weights of surgical samples in the two groups, and found that the optimal weight of specimens for TSs isolation was 500 mg. CONCLUSION: Thus, contrary to our expectations, the ability to isolate TSs from WHO grade IV glioma specimens was not related to the weight of fresh specimens.