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Purpose Leptomeningeal metastasis (LM) is a complication of surgery for brain metastasis and is a risk factor of poor prognosis. The risk of LM is particularly high after surgery for a breast cancer metastasis to the brain. If the risk of LM after surgical resection for a brain metastasis were predictable, appropriate adjuvant therapy could be administered to individual patients to improve their prognosis. The present study aimed to reveal the genetic characteristics of brain metastases as means of predicting LM in breast cancer patients. Methods Ten patients with brain metastases of breast cancer presented LM after surgical resection were analyzed by whole-exome sequencing. Results A chromodomain-helicase-DNA-binding protein 5 (CHD5) gene alteration was detected in nine cases (90%), including a nonsynonymous variant in four cases and copy number deletion in five cases. CHD5 protein expression was lost in nine cases and had decreased in one case. The frequency of CHD5 gene alteration in brain metastases with LM was significantly higher than in primary breast cancer (2.3%) or in brain metastases of breast cancer (0%) (p < 0.0001). Conclusions These results suggested that the CHD5 gene alteration was associated with LM after surgical resection of breast cancer brain metastases. Searching for the gene alteration might predict the LM risk after surgical resection.

Background Hearing preservation in patients with vestibular schwannomas remains difficult by microsurgery or radiosurgery. Method In this study, awake surgery via the retrosigmoid approach was performed for vestibular schwannomas (volume, 11.6 ± 11.2 ml; range, 1.3–26.4 ml) in eight consecutive patients with preoperative quartering of pure tone audiometry (PTA) of 53 ± 27 dB. Results After surgery, hearing was preserved in seven patients and improved in one patient. The postoperative quartering PTA was 51 ± 21 dB. Serviceable hearing (class A + B + C) using the American Association of Otolaryngology-Head and Neck Surgery (AAO-HNS) classification was preserved in all patients. Preoperative useful hearing (AAO-HNS class A + B) was observed in three patients, and useful hearing was preserved in all three of these patients after surgery. In addition, useful facial nerve function (House-Blackmann Grade 1) was preserved in all patients. Conclusions These results suggest that awake surgery for vestibular schwannomas is associated with low patient morbidity, including with respect to hearing and facial nerve function.

Background Little is known concerning the risk of hospitalization and the risk of death before receiving dialysis by the stage of chronic kidney disease (CKD) in Japan. Methods The subjects comprised a total of 13,911 Japanese men (mean age 49.2 ± 9.9 years). Based on the results of a health checkup performed in 2006, they were divided into 5 groups according to their estimated glomerular filtration rate (GFR) levels and dialysis status: GFR ≥60, 45–59, 30–44, <30 mL/min/1.73 m 2 , and undergoing dialysis. From 2006 through to 2013, we investigated their hospitalization, dialysis initiation, and cause-specific death. The adjusted hazard ratios (HRs) for each end point were calculated compared with the GFR ≥60 mL/min/1.73 m 2 group using a Cox proportional hazard model. Results A lower GFR was independently associated with higher risks of overall hospitalization, dialysis initiation, and all-cause death. In particular, the HRs for long-term hospitalization (≥1 month a year), dialysis, and cardiovascular disease (CVD) death markedly increased along with a decreased GFR. The rate ratios of dialysis to all-cause death (calculated based on the incidences of dialysis and death per 1000 person-years) were 0.03 (0.11 vs. 3.19), 0.08 (0.29 vs. 3.62), 0.51 (12.5 vs. 24.7), and 4.50 (179.8 vs. 40.0) for GFR ≥60, 45–59, 30–44, and <30 mL/min/1.73 m 2 , respectively. Conclusion In Japanese men, although the risk of CVD death before dialysis initiation can never be ignored, CKD patients aged <60 years with a GFR of <30 mL/min/1.73 m 2 are more likely to undergo dialysis prior to death.

Epithelioid glioblastomas (E-GBMs) are rare, highly aggressive tumors consisting of closely packed tumor cells with smooth, round cell borders and abundant eosinophilic cytoplasm. They tend to affect younger patients compared with conventional GBM. BRAF V600E mutation is characteristically found in approximately 50 % of all E-GBMs, compared with a low frequency of this mutation in conventional GBM. Here, we report an unusual case of glioma involving the right frontal lobe, basal ganglia and thalamus in an HIV-positive 30-year-old man on antiretroviral therapy. The lesion was composed of abundant discohesive, monotonous epithelioid cells with extensive necrosis, spindle and polyhedral cells, low-grade oligoastrocytoma-like areas, sarcomatous components, and numerous osteoclast-like giant cells (OLGCs) intermingled with epithelioid tumor cells. As the epithelioid cells accounted for more than one-third of the tumor, a pathological diagnosis of E-GBM was made. BRAF V600E mutation was detected in both oligoastrocytoma-like and epithelioid cell components. Similar to previously reported findings on E-GBM associated with low-grade glioma, this case suggested that low-grade astrocytic glioma with BRAF V600E mutation progressed to E-GBM. OLGCs are rarely observed in gliomas, and this is the first case report of E-GBM associated with abundant OLGC infiltration.

•To safely undergo an awake craniotomy, a patient must cooperate the surgery.•Sleepiness is one of the causes of failure of an awake craniotomy.•We assess the preoperative cognitive factors related to sleepiness.•Perioperative sleepiness was correlated with the preoperative cognitive abilities. An awake craniotomy is a safe neurological surgical technique that minimizes the risk of brain damage. During the course of this surgery, the patient is asked to perform motor or cognitive tasks, but some patients exhibit severe sleepiness. Thus, the present study investigated the predictive value of a patient's preoperative neuropsychological background in terms of sleepiness during an awake craniotomy. Thirty-seven patients with brain tumor who underwent awake craniotomy were included in this study. Prior to craniotomy, the patient evaluated cognitive status, and during the surgery, each patient's performance and attitude toward cognitive tasks were recorded by neuropsychologists. The present findings showed that the construction and calculation abilities of the patients were moderately correlated with their sleepiness. These results indicate that the preoperative cognitive functioning of patients was related to their sleepiness during the awake craniotomy procedure and that the patients who exhibited sleepiness during an awake craniotomy had previously experienced reduced functioning in the parietal lobe.

Diffuse midline glioma, H3 K27M mutant, is newly recognized as a distinct category, which usually arises in the brain stem, thalamus or spinal cord of children, and young adults. The oncogenic H3 K27M mutation involves H3.3 (encoded by H3F3A ) or H3.1 (encoded by HIST1H3B / HIST1H3C ), and the incidence of each mutation differs among the primary sites. Recently, several papers have reported that cerebellar high-grade gliomas in both children and adults also harbor H3 K27 mutation. With the exception of one pediatric case, all of the cases carried the mutation in H3.3. We herein present the case of an adult cerebellar high-grade astrocytic tumor with H3.1 K27M mutation in a 45-year-old man, which also involved TP53 mutation and was immunonegative for ATRX. Some groups have reported that H3.3 and H3.1 K27M mutations define subgroups of diffuse intrinsic pontine gliomas (DIPGs) with different phenotypes as well as genetic alterations. On comparing the findings of the present case, particularly TP53 mutation status and ATRX expression, to the findings of the previous studies on DIPGs, our case seems unusual among the H3.1 K27M mutant subgroup. Further studies are needed to clarify the exact frequency, clinicopathological characteristics, and genomic alterations of cerebellar gliomas harboring H3 K27M mutation.

Abstract A 46-year-old female patient with glioblastoma multiforme (GBM), IDH wild type developed severe pancytopenia 5 months after postoperative chemoradiotherapy. Bone marrow aspirate showed normocellular marrow with 70.0% abnormal cells, which suggested the possibility of acute myeloid leukemia. Immunophenotypic analysis did not show any hematological lineage markers, except for cluster of differentiation 56. The results of immunohistochemical staining of glial fibrillary acidic protein and oligodendrocyte transcription Factor 2 were positive. Based on these findings, the patient was diagnosed with bone marrow metastasis from GBM. Bone marrow metastasis from GBM is rare and little is known about the morphological characteristics of bone marrow aspiration smear findings. We experienced a rare case with marrow metastasis from GBM mimicking acute myeloid leukemia.

Purpose Diffusion tensor tractography provides useful information regarding the surgical strategy for brain tumors. The goal of the present study was to analyze relationships between visual field deficits and the locations of brain tumors compared with optic tracts as visualized by tractography, and compared with the calcarine fissure. Methods Subjects comprised 11 patients with brain tumor in the occipital lobe or atrium of the lateral ventricle who underwent surgery between October 2006 and February 2009. Tumors were categorized as Type A, with almost all the optic tract in the occipital lobe or atrium of the lateral ventricle running close to and stretched by the brain tumor; and Type B, with the optic tract running at least partially distant to the brain tumor and remaining unstretched. Results Those type A optic tracts that were laterally compressed by brain tumors (Cases 1–3) displayed hemianopsia after surgery. When the brain tumor was located rostro-medial to the calcarine fissure and optic tracts were compressed caudally by the tumor, lower quadrant hemianopsia remained after surgery (Cases 4, 5). In other cases, the visual field remained or improved to normal after surgery. Conclusion The relationship between optic tracts or the calcarine fissure, and brain tumors in the occipital lobe or atrium of the lateral ventricle is related to visual field deficits after surgery. In particular, those Type A optic tracts that are compressed laterally show hemianopsia of the visual field after surgery.

Purpose Glioblastoma (GBM) is the most common type of primary malignant brain tumor and has a poor prognosis. Identifying novel targets and stratification strategies is urgently needed to improve patient survival. The present study aimed to identify clinically relevant genomic alterations in IDH -wildtype GBM using data from comprehensive genomic profiling (CGP) assays performed nationwide in Japan. Methods The CGP assay results of 392 IDH -wildtype GBM cases performed between October 2019 and February 2023 obtained from the Center for Cancer Genomics and Advanced Therapeutics were retrospectively analyzed. Results The median patient age was 52.5 years, and 207 patients (53%) were male. In the 286 patients for whom survival information was available, a protein-tyrosine phosphatase non-receptor type 11 (PTPN11) variant detected in 20 patients (6.8%) was extracted as the gene associated with significantly shorter overall survival (p = 0.002). Multivariate analysis demonstrated that the PTPN11 variant and poor performance status were independent prognostic indicators. In contrast, no prognostic impact was observed in the cohort in The Cancer Genome Atlas data. The discrepancy in the prognostic impact of the PTPN11 variant from these two pools might have resulted from differences in the biases affecting the survival of patients who underwent a CGP assay, including left-truncation and right-censored bias. However, survival simulation done to adjust for these biases showed that the prognostic impact of the PTPN11 variant was also significant. Conclusions The PTPN11 variant was a negative prognostic indicator of IDH -wildtype GBM in the patient cohort with the CGP assay.

Abstract Adrenocorticotropic hormone (ACTH) and another pro-opiomelanocortin-derived neuropeptide, β-endorphin (β-End), are stimulated by corticotropin-releasing hormone (CRH) at the anterior pituitary. CRH and β-End have predominantly proinflammatory effects in peripheral inflammatory sites. We have supposed that inflammatory stimuli develop ACTH as well as β-End. In this study, we investigated the expression of ACTH in inflamed synovial tissue from patients with rheumatoid arthritis (RA) and osteoarthritis (OA), and at inflammatory joints with adjuvant-induced arthritis (AA) in female Lewis (LEW/N) rats. The expression of ACTH immunostaining was significantly greater in synovium of RA patients than in that of OA patients (P < 0.0001), and correlated with the extent of inflammatory mononuclear cell infiltration. Extensive and intense intracellular ACTH immunostaining, which correlated with the advance in arthritis score, was observed in the synovial lining layer, inflammatory mononuclear cells, and fibroblast-like cells of synovium and chondrocytes in LEW/N rats with AA. In addition, we performed double immunostaining of the same sections from arthritic joints in rats with anti-ACTH and anti-CRH antibodies. ACTH and CRH colocalized in inflammatory mononuclear cells and fibroblast-like cells. ACTH may play a role in the pathogenesis of RA as well as CRH.