Drug-resistant F V600E-mutant recurrent pleomorphic xanthoastrocytoma, CNS WHO Grade 3 successfully resolved with incidental discontinuation of combined BRAF and MEK inhibitor therapy.

Background: Combination therapy with BRAF and MEK inhibitor holds promise for treating gliomas harboring the V600E mutation; however, the development of acquired resistance remains a challenge.

Case Description: We describe a case of repeated recurrent mutant pleomorphic xanthoastrocytoma (central nervous system World Health Organization grade 3) treated with combination therapy with BRAF and MEK inhibitor. The patient received dabrafenib (BRAF inhibitor) and trametinib (MEK inhibitor); however, she developed resistance to the combination therapy.

A case of a pilocytic astrocytoma with histological features of anaplasia and unprecedent genetic alterations.

We report a case of pediatric glioma with uncommon imaging, morphological, and genetic features. A one-year-old boy incidentally presented with a tumor in the fourth ventricle. The tumor was completely resected surgically and investigated pathologically.

Intratumoral thrombosis as a histological biomarker for predicting epidermal growth factor receptor alteration and poor prognosis in patients with glioblastomas.

Purpose: Intratumoral thrombosis is a specific finding in glioblastomas and considered the origin of palisading necrosis. Its distribution and contribution to the glioblastoma pathophysiology and systemic thrombosis are obscure, although deep vein thrombosis is a common complication in glioblastoma cases.

Methods: Clinicopathological and genetic analyses were performed on 97 glioblastoma tissue specimens to elucidate the role of thrombotic events and associated molecular abnormalities.

Visual Outcomes and Surgical Approach Selection Focusing on Active Optic Canal Decompression and Maximum Safe Resection for Suprasellar Meningiomas.

The goal of treating patients with suprasellar meningioma is improving or preserving visual function while achieving long-term tumor control. We retrospectively examined patient and tumor characteristics and surgical and visual outcomes in 30 patients with a suprasellar meningioma who underwent resection via an endoscopic endonasal (15 patients), sub-frontal (8 patients), or anterior interhemispheric (7 patients) approach. Approach selection was based on the presence of optic canal invasion, vascular encasement, and tumor extension.

Effects of Microvascular Decompression on Pain Relief and Quality of Life in Late Elderly Patients with Trigeminal Neuralgia.

Pharmacotherapy is frequently selected over surgical interventions for late elderly patients with trigeminal neuralgia (TN). However, medication may affect these patients' activities of daily living (ADL). Hence, we investigated the effect of the surgical treatment of TN on ADL in older patients.

A multicenter, randomized, placebo-controlled phase IIb trial of an autologous formalin-fixed tumor vaccine for newly diagnosed glioblastomas.

Objective: An autologous formalin-fixed tumor vaccine (AFTV) derived from resected glioblastoma (GBM) tissue can be used against unidentified tumor antigens. Thus, the authors conducted a multicenter double-blind phase IIb trial to investigate the efficacy of an AFTV.

Methods: Eligible patients were adults with supratentorial GBMs, 16-75 years of age, with Karnofsky Performance Scale (KPS) scores ≥ 60%, and no long-term steroid administration.

Endoscopic aqueductal membrane fenestration was effective for intractable hydrocephalus after removal of a nongerminomatous germ cell tumor exhibiting growing teratoma syndrome: a case report.

Background: Primary central nervous system (CNS) germ cell tumors (GCTs) are rare neoplasms predominantly observed in the pediatric and young adult populations. A mixed GCT including immature teratoma exhibiting growing teratoma syndrome is presented. The pathogenesis of growing teratoma syndrome remains unclear, and its treatment strategy has not been established.

Systemic inflammation caused by an intracranial mesenchymal tumor with a EWSR1::CREM fusion presenting associated with IL-6/STAT3 signaling.

Pediatric neoplastic diseases account for about 10% of cases of fever of unknown origin (FUO), and most neoplastic disease cases are leukemia, lymphoma, and neuroblastoma. Brain tumors are rarely reported as the cause of FUO, although craniopharyngioma, metastatic brain tumor, and Castleman's disease have been reported. We report a case of intracranial mesenchymal tumor (IMT) with a FET:CREB fusion gene, which had inflammatory phenotype without neurological signs.

The first-in-human phase I study of a brain-penetrant mutant IDH1 inhibitor DS-1001 in patients with recurrent or progressive IDH1-mutant gliomas.

Background: Approximately 70% of lower-grade gliomas harbor isocitrate dehydrogenase 1 (IDH1) mutations, resulting in the accumulation of oncometabolite D-2-hydroxyglutarate (D-2-HG); this leads to epigenetic dysregulation, oncogenesis, and subsequent clonal expansion. DS-1001 is an oral brain-penetrant mutant IDH1 selective inhibitor. This first-in-human study investigated the safety, pharmacokinetics, pharmacodynamics, and efficacy of DS-1001.

Low tumor cell content predicts favorable prognosis in germinoma patients.

Background: Germinoma preferentially occurs in pediatric and young adult age groups. Although they are responsive to treatment with chemotherapy and radiation, the treatment may cause long-term sequelae in their later lives. Here, we searched for clinical and histopathological features to predict the prognosis of germinoma and affect treatment response.

Primary Nondural Central Nervous System Marginal ZoneB-Cell Lymphoma of the Mucosa-Associated Lymphoid Tissue Type Mimicking CNS Inflammatory Diseases.

Marginal zone B-cell lymphomas (MZBCLs) are non-Hodgkin lymphomas arising from postgerminal center marginal zone B cells. MZBCLs are subclassified into extranodal, nodal, and splenic MZBCLs. Primary nondural central nervous system (CNS) MZBCLs of the mucosa-associated lymphoid tissue (MALT) type are among the extranodal examples.

Mathematical Modeling and Mutational Analysis Reveal Optimal Therapy to Prevent Malignant Transformation in Grade II IDH-Mutant Gliomas.

Isocitrate dehydrogenase-mutant low-grade gliomas (IDHmut-LGG) grow slowly but frequently undergo malignant transformation, which eventually leads to premature death. Chemotherapy and radiotherapy treatments prolong survival, but can also induce genetic (or epigenetic) alterations involved in transformation. Here, we developed a mathematical model of tumor progression based on serial tumor volume data and treatment history of 276 IDHmut-LGGs classified by chromosome 1p/19q codeletion (IDH/1p19q and IDH/1p19q) and performed genome-wide mutational analyses, including targeted sequencing and longitudinal whole-exome sequencing data.

Effectiveness of four doses of pertussis vaccine during infancy diminished in elementary school age: A test-negative case-control study in Japan.

Objective: The Japanese national immunization program recommends that children receive 4 doses of acellular pertussis vaccine between 3 months and 2 years of age. Nevertheless, the number of pertussis cases is increasing in elementary school children aged 6-12 years. Therefore, a test-negative case-control study was conducted to assess the effectiveness of the pertussis vaccine program.

Central nervous system neuroblastic tumor with FOXR2 activation presenting both neuronal and glial differentiation: a case report.

A subset of central nervous system neuroblastomas (CNS NB), rare primary embryonal CNS tumors, has been encompassed in CNS NB with FOXR2 activation (CNS NB-FOXR2) and usually shows the primitive neuronal architecture and occasional neurocytic differentiation. Here, we report a rare case of 3-year-old female with uncommon morphology of CNS embryonal tumor with FOXR2 activation presenting bidirectional differentiation to neurocytic small primitive cells and astrocytic spindle cells both of which are positive for synaptophysin and GFAP. Ultrastructural study also showed that there were presynaptic structure and intermediate filament in the tumor cells, suggesting glioneuronal differentiation.

Pitfall of heart rate variability analyses for autonomic nervous system activity with photoplethysmography.

The purpose of this study is to measure the temporary intervals between R peak with ECG and pulse peak with photoplethysmography (PPG) and then to compare their precisions of two types of heart rate variability (HRV) analyses, power spectral analysis and Tone-Entropy analysis. A lot of papers used to measure cardiac autonomic nervous system (CANS) activity with HRV from PPI without awareness of the issue on another variability except CANS activity. Fifteen young male subjects were participated in this study.

Integrated clinical, histopathological, and molecular data analysis of 190 central nervous system germ cell tumors from the iGCT Consortium.

Background: We integrated clinical, histopathological, and molecular data of central nervous system germ cell tumors to provide insights into their management.

Methods: Data from the Intracranial Germ Cell Tumor Genome Analysis (iGCT) Consortium were reviewed. A total of 190 cases were classified as primary germ cell tumors (GCTs) based on central pathological reviews.

A C19MC-LIN28A-MYCN Oncogenic Circuit Driven by Hijacked Super-enhancers Is a Distinct Therapeutic Vulnerability in ETMRs: A Lethal Brain Tumor.

Embryonal tumors with multilayered rosettes (ETMRs) are highly lethal infant brain cancers with characteristic amplification of Chr19q13.41 miRNA cluster (C19MC) and enrichment of pluripotency factor LIN28A. Here we investigated C19MC oncogenic mechanisms and discovered a C19MC-LIN28A-MYCN circuit fueled by multiple complex regulatory loops including an MYCN core transcriptional network and super-enhancers resulting from long-range MYCN DNA interactions and C19MC gene fusions.

Expression of GLUT1 in Pseudopalisaded and Perivascular Tumor Cells Is an Independent Prognostic Factor for Patients With Glioblastomas.

Glioblastomas are highly aggressive brain tumors with a particularly poor prognosis. Glucose transporter-1 (GLUT1/SLC2A1), a uniporter that is expressed by various carcinomas and may be involved in malignant neoplasm glycometabolism, may also be related to prognosis in glioblastomas. GLUT1 is essential to central nervous system glycometabolism.

CSF TACI and BAFF levels in patients with primary CNS lymphoma as novel diagnostic biomarkers.

We used an enzyme-linked immunosorbent assay to measure pretreatment B cell-activating factor belonging to the tumour necrosis factor family (BAFF) and transmembrane activator and CAML-interactor (TACI) levels in CSF and serum collected from patients with primary central nervous system lymphoma (PCNSL) and control groups. The decision tree analysis of CSF TACI and BAFF levels for patients with a PCNSL diagnosis showed 100% sensitivity and 100% specificity when we attempted to differentiate PCNSL from glioblastoma and CNS inflammatory diseases. The combination of CSF TACI and BAFF levels may thus be a novel and useful diagnostic biomarker of PCNSL.