Language：Japanese   Publisher：日本脳腫瘍病理学会  

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Language：English   Publishing type：Research paper (scientific journal)  

OBJECTIVE: The utility of the tubular retractor for deep-seated tumors, including intraventricular tumors, has recently been reported. However, the surgical field's depth and narrowness can lead to blind spots, and it is crucial to prevent damage to the cortex and white matter fibers in eloquent areas. Therefore, preoperative simulation is critical for tubular retractor surgery. In this study, we investigated the benefits of threedimensional (3D)-printed intraventricular tumor models for tubular retractor surgery. METHODS: Nine patients with intraventricular central neurocytoma who underwent tubular retractor surgery at our institution between March 2013 and August 2023 were retrospectively reviewed. Fusion images and 3D-printed intraventricular tumor models were developed from preoperative computed tomography (CT) and magnetic resonance imaging (MRI). The puncture points of the tubular retractor were simulated using fusion images and 3D-printed intraventricular tumor models by 11 neurosurgeons (3 experts in brain tumors, 2 experts in areas other than brain tumors, and 6 residents). The dispersion of puncture points among 8 neurosurgeons (excluding brain tumor experts) was compared in each simulation model. RESULTS: These cases were categorized into two groups based on the dispersion of puncture points simulated by fusion images. Puncture point dispersion was markedly smaller in all cases when using 3D-printed intraventricular tumor models compared to simulations solely based on fusion images. CONCLUSIONS: In intraventricular tumor surgery using a tubular retractor, 3D-printed intraventricular tumor models proved more beneficial in preoperative simulation compared to fusion images.

DOI： 10.1016/j.wneu.2025.123743

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Language：English   Publishing type：Research paper (scientific journal)  

PURPOSE: Craniopharyngiomas are histologically benign tumors, but their proximity to vital neurovascular structures can significantly deteriorate functional prognoses and severely restrict patients' social interaction and activity. We retrospectively identified risk factors related to the functional prognoses in patients with craniopharyngioma treated at our center. METHODS: A retrospective analysis was conducted on 40 patients who underwent surgery for craniopharyngioma and follow-up at our institution between 2003 and 2022. Functional prognoses were evaluated in terms of obesity (body mass index [BMI] ≥ 25 for adults, BMI-Z ≥ 1.65 for children), visual function, endocrine function, and social participation. We investigated whether patient characteristics, tumor size, tumor location, hypothalamic involvement, surgical hypothalamic damage, extent of resection, and recurrence rate correlated with these functional prognostic factors. RESULTS: The median age at diagnosis was 28.0 years, with a median follow-up of 80.5 months. Postoperative obesity was present in 22 patients, and those with postoperative obesity had a significantly higher preoperative BMI or BMI-Z (preoperative BMI for adults: p = 0.074; preoperative BMI-Z for children: p = 0.020) and were significantly correlated with preoperative hypothalamic involvement grade 2 (p = 0.012) and surgical hypothalamic damage grade II (p = 0.0001). Deterioration in social participation was significantly associated with a larger tumor size (p = 0.023) and tumor recurrence (p = 0.0047). CONCLUSIONS: Patients with higher preoperative BMI or BMI-Z and hypothalamic involvement have a greater risk of postoperative obesity, and larger tumor size and recurrence can significantly deteriorate the rate of patients' social participation.

DOI： 10.1007/s11060-024-04925-7

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Language：English   Publishing type：Research paper (scientific journal)  

OBJECTIVE: The extent of resection (EOR) is an important prognostic factor for both low- and high-grade gliomas. Intraoperative MRI (iMRI) has been used to increase the EOR in glioma surgery. While a recent study reported differences between iMRI and early postoperative MRI (epMRI), their specific relationship to postoperative clinical symptoms remains unclear. This study aims to compare the differences between iMRI and epMRI in glioma surgery. METHODS: A retrospective assessment was conducted on 43 patients with glioma who underwent surgery with iMRI and for whom no additional resection was performed after iMRI. The study evaluated the discrepancies in EOR, surgically induced contrast enhancement (SICE), and diffusion-weighted imaging (DWI) abnormality between iMRI and epMRI. EOR was defined as gross-total resection (GTR), near-total resection, subtotal resection (STR), or partial resection (PR) for enhancing lesions, and GTR, STR, or PR for nonenhancing lesions. In addition, the relationship between postoperative neurological findings and iMRI findings was evaluated. RESULTS: Discrepancies in EOR were observed in 2 (11.1%) of 18 cases with nonenhanced lesions and 1 (4.0%) of 25 cases with enhanced lesions. The positive rate of SICE was 25.0% on iMRI and 67.9% on epMRI. Enhancement at the resection cavity was the most frequent pattern in both iMRI and epMRI. The positive rate of enhancement of the resection cavity was strongly increased on epMRI compared with iMRI, potentially mimicking residual tumor. The positive rate of DWI abnormality was 73% on iMRI and 89.2% on epMRI. Among the 10 patients who showed no DWI abnormality on iMRI, 6 exhibited DWI abnormality on epMRI (the late-developing group). Two patients developed new neurological deficits postoperatively, and both showed DWI abnormality on both iMRI and epMRI. No patient in the late-developing group developed postoperative neurological deficits. CONCLUSIONS: Overall, iMRI demonstrated more accurate EOR and less SICE compared with epMRI. Although the positive rate of DWI abnormality was lower on iMRI than on epMRI, the late-developing group showed no postoperative neurological deficits. Therefore, iMRI is more useful in assessing accurate EOR and detecting postoperative neurological deficits than epMRI.

DOI： 10.3171/2024.7.JNS24784

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Publishing type：Research paper (scientific journal)   Publisher：Oxford University Press (OUP)  

Abstract

Reduced expression in immortalized cells/Dickkopf-3 (REIC/Dkk-3) is a tumor suppressor gene and its overexpression has been shown to exert anti-tumor effects as a therapeutic target gene in many human cancers. Recently, we revealed the anti-glioma effects of an adenoviral vector carrying REIC/Dkk-3 with the super gene expression system (Ad-SGE-REIC) and conducted the phase Ⅰ/Ⅱ a clinical trial for recurrent malignant glioma (jRCT2063190013). Anti-vascular endothelial growth factor treatments such as bevacizumab have demonstrated convincing therapeutic efficacy in patients with glioma. In this study, we examined the effects of Ad-SGE-REIC on glioma treated with bevacizumab in vitro and in vivo. Ad-SGE-REIC treatment resulted in a significant reduction in the number of invasion cells treated with bevacizumab. Western blot analyses revealed the increased expression of several endoplasmic reticulum stress markers in cells treated with both bevacizumab and Ad-SGE-REIC, as well as decreased β-catenin protein levels. In glioma-bearing mouse models, survival was extended in the combination therapy group. These results suggest that the combination therapy of Ad-SGE-REIC and bevacizumab showed anti-glioma effects by suppressing the angiogenesis and invasion of tumor cells. Combined Ad-SGE-REIC and bevacizumab might be a promising strategy for the treatment of malignant glioma.

DOI： 10.1093/neuonc/noae165.0935

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Publishing type：Research paper (scientific journal)   Publisher：Oxford University Press (OUP)  

Abstract

BACKGROUND

Although vestibular schwannoma is a benign tumor, 10% of the tumor regrow after primary tumor resection. The factors associated with tumor progression from several reports remain controversial, and the role of the tumor microenvironment in vestibular schwannoma is still unclear. In this study, we analyzed the prognostic factors associated with the tumor progression after primary resection.

METHODS

We retrospectively reviewed the medical records of patients who underwent surgical resection and were diagnosed with vestibular schwannoma between January 2005 and June 2020. We performed RNA sequencing to identify the prognostic factors and immunohistochemistry to assess the tumor microenvironment, including analysis of the CD80 and CD206 expression of macrophages. We compared the progressed group whose tumor size got larger than 2mm after primary resection or who underwent additional treatment because of regrowth with the stable group.

RESULTS

Fifty-five patients underwent surgical resection for newly diagnosed vestibular schwannoma, and 12 of them had tumor regrowth. RNA sequencing revealed that the significantly upregulated pathways in the stable group was related to immune systems, while that of the progressed group was related to cell cycle. In addition, there were more myeloid cells, especially M2 macrophage infiltration in the stable group. Immunohistochemistry also showed higher M2 macrophages in the stable group.

CONCLUSION

In this study, multiomic analysis revealed the upregulation of immune-related pathways in the stable group and the cell cycle pathway in the progressed group. Altering the tumor microenvironment may offer a therapeutic strategy in vestibular schwannoma after primary resection.

DOI： 10.1093/neuonc/noae165.1209

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Language：English   Publishing type：Research paper (scientific journal)  

Tectal glioma (TG) is a rare lower grade glioma (LrGG) that occurs in the tectum, mainly affecting children. TG shares pathological similarities with pilocytic astrocytoma (PA), but recent genetic analyses have revealed distinct features, such as alterations in KRAS and BRAF. We conducted a retrospective review of cases clinically diagnosed as TG and treated at our institute between January 2005 and March 2023. Six cases were identified and the median age was 30.5 years. Four patients underwent biopsy and two patients underwent tumor resection. Histological diagnoses included three cases of PA, one case of astrocytoma, and two cases of high-grade glioma. The integrated diagnosis, according to the fifth edition of the World Health Organization Classification of Tumours of the central nervous system, included two cases of PA and one case each of diffuse high-grade glioma; diffuse midline glioma H3 K27-altered; glioblastoma; and circumscribed astrocytic glioma. Among the three patients who underwent molecular evaluation, two had KRAS mutation and one had H3-3A K27M mutation. Our results demonstrate the diverse histological and molecular characteristics of TG distinct from other LrGGs. Given the heterogeneous pathological background and the risk of pathological progression in TG, we emphasize the importance of comprehensive diagnosis, including molecular evaluation.

DOI： 10.1007/s10014-024-00494-9

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Language：English   Publisher：(一社)日本癌治療学会  

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Language：English   Publisher：(一社)日本癌治療学会  

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Language：English   Publisher：(一社)日本癌学会  

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Language：English   Publishing type：Research paper (scientific journal)  

Organized chronic subdural hematoma (OCSDH) is a relatively rare condition that forms over a longer period of time compared to chronic subdural hematoma and is sometimes difficult to diagnose with preoperative imaging. We resected an intracranial lesion in a 37-year-old Japanese man; the lesion had been increasing in size for >17 years. The preoperative diagnosis based on imaging findings was meningioma; however, pathological findings revealed OCSDH. Clinicians should be aware that OCSDH mimics other tumors and consider surgical strategies for this disease.

DOI： 10.18926/AMO/67204

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Language：Japanese   Publisher：日本脳腫瘍病理学会  

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Language：Japanese   Publisher：日本脳腫瘍病理学会  

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Language：Japanese   Publisher：日本脳腫瘍病理学会  

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Language：Japanese   Publisher：(一社)日本小児神経外科学会  

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Language：Japanese   Publisher：(一社)日本小児神経外科学会  

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Language：Japanese   Publisher：(一社)日本内分泌学会  

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Language：Japanese   Publisher：(一社)日本小児神経外科学会  

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Language：Japanese   Publisher：(一社)日本内分泌学会  

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Language：English  

In the current World Health Organization classification of central nervous system tumors, comprehensive genetic and epigenetic analyses are considered essential for precise diagnosis. A 14-year-old male patient who presented with a cerebellar tumor was initially diagnosed with glioblastoma and treated with radiation and concomitant temozolomide chemotherapy after resection. During maintenance temozolomide therapy, a new contrast-enhanced lesion developed in the bottom of the cavity formed by the resection. A second surgery was performed, but the histological findings in specimens from the second surgery were different from those of the first surgery. Although genome-wide DNA methylation profiling was conducted using frozen tissue for a precise diagnosis, the proportion of tumor cells was insufficient and only normal cerebellum was observed. We then performed comprehensive genetic analysis using formalin-fixed paraffin-embedded sections, which revealed MYCN amplification without alteration of IDH1, IDH2, or Histone H3. Finally, the patient was diagnosed with pediatric-type diffuse high-grade glioma, H3-wildtype and IDH-wildtype. In conclusion, comprehensive genetic and epigenetic analysis should be considered in pediatric brain tumor cases.

DOI： 10.18926/AMO/65502

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Language：English  

An 85-year-old woman presented with aphasia due to an occupying lesion in the left frontal lobe near the language area. Complete resection of the contrast-enhancing lesion was performed under awake conditions. The pathological diagnosis was anaplastic astrocytoma, and postoperative radiochemotherapy was administered. Awake surgery is a useful technique to reduce postoperative neurological sequelae and to maximize surgical resection. Although the patient was elderly, which is generally considered high risk, she did not have any severe neurological deficits and had a good outcome. Even in the extreme elderly, awake surgery can be useful for gliomas in language cortices.

DOI： 10.18926/AMO/65504

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Language：English   Publishing type：Research paper (scientific journal)  

PURPOSE: Pilocytic astrocytoma (PA) is a circumscribed low-grade astrocytic glioma, generally considered to be associated with a good prognosis. However, a subset of PA patients shows unfavorable outcomes. In this study, we retrospectively reviewed PA patients and performed further molecular analysis, such as DNA methylation profiling, to identify prognostic factors. METHODS: We analyzed 29 histologically-confirmed PA patients from a single center from 2002 to 2021 and conducted integrated molecular analyses among elderly PA patients since age was an independent prognostic factor for poor outcomes. RESULTS: The median age at diagnosis was 14 years (range 3-82 years) and 4 patients (14%) were elderly (patients ≥ 60 years old). Age over 60 was associated with poor progression-free survival and overall survival. We performed DNA methylation analysis on 2 of the 4 elderly patients. Both cases were histologically diagnosed as PA, but DNA methylation profiling revealed one as high-grade astrocytoma with piloid features (all methylation class scores were below 0.3 in both v11b4 and v12.5) and the other as glioblastoma, IDH-wildtype (score was over 0.5 in both v11b4 and v12.5), using the German Cancer Research Center methylation profiling classifiers and t-SNE analysis. CONCLUSIONS: Elderly patients with PA morphology showed unfavorable outcomes in this cohort. In those patients, further molecular analysis and DNA methylation profiling revealed the possibility of high-grade astrocytic tumors, including newly defined entities.

DOI： 10.1007/s11060-022-04131-3

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Language：English   Publishing type：Research paper (scientific journal)  

Reduced expression in immortalized cells/Dickkopf-3 (REIC/Dkk-3) is a tumor suppressor and its overexpression has been shown to exert anti-tumor effects as a therapeutic target gene in many human cancers. Recently, we demonstrated the anti-glioma effects of an adenoviral vector carrying REIC/Dkk-3 with the super gene expression system (Ad-SGE-REIC). Anti-vascular endothelial growth factor treatments such as bevacizumab have demonstrated convincing therapeutic advantage in patients with glioblastoma. However, bevacizumab did not improve overall survival in patients with newly diagnosed glioblastoma. In this study, we examined the effects of Ad-SGE-REIC on glioma treated with bevacizumab. Ad-SGE-REIC treatment resulted in a significant reduction in the number of invasion cells treated with bevacizumab. Western blot analyses revealed the increased expression of several endoplasmic reticulum stress markers in cells treated with both bevacizumab and Ad-SGE-REIC, as well as decreased β-catenin protein levels. In malignant glioma mouse models, overall survival was extended in the combination therapy group. These results suggest that the combination therapy of Ad-SGE-REIC and bevacizumab exerts anti-glioma effects by suppressing the angiogenesis and invasion of tumors. Combined Ad-SGE-REIC and bevacizumab might be a promising strategy for the treatment of malignant glioma.

DOI： 10.1371/journal.pone.0273242

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Language：English   Publishing type：Research paper (scientific journal)  

Glioblastoma (GBM) is the most lethal primary brain tumor characterized by significant cellular heterogeneity, namely tumor cells, including GBM stem-like cells (GSCs) and differentiated GBM cells (DGCs), and non-tumor cells such as endothelial cells, vascular pericytes, macrophages, and other types of immune cells. GSCs are essential to drive tumor progression, whereas the biological roles of DGCs are largely unknown. In this study, we focused on the roles of DGCs in the tumor microenvironment. To this end, we extracted DGC-specific signature genes from transcriptomic profiles of matched pairs of in vitro GSC and DGC models. By evaluating the DGC signature using single cell data, we confirmed the presence of cell subpopulations emulated by in vitro culture models within a primary tumor. The DGC signature was correlated with the mesenchymal subtype and a poor prognosis in large GBM cohorts such as The Cancer Genome Atlas and Ivy Glioblastoma Atlas Project. In silico signaling pathway analysis suggested a role of DGCs in macrophage infiltration. Consistent with in silico findings, in vitro DGC models promoted macrophage migration. In vivo, coimplantation of DGCs and GSCs reduced the survival of tumor xenograft-bearing mice and increased macrophage infiltration into tumor tissue compared with transplantation of GSCs alone. DGCs exhibited a significant increase in YAP/TAZ/TEAD activity compared with GSCs. CCN1, a transcriptional target of YAP/TAZ, was selected from the DGC signature as a candidate secreted protein involved in macrophage recruitment. In fact, CCN1 was secreted abundantly from DGCs, but not GSCs. DGCs promoted macrophage migration in vitro and macrophage infiltration into tumor tissue in vivo through secretion of CCN1. Collectively, these results demonstrate that DGCs contribute to GSC-dependent tumor progression by shaping a mesenchymal microenvironment via CCN1-mediated macrophage infiltration. This study provides new insight into the complex GBM microenvironment consisting of heterogeneous cells.

DOI： 10.1186/s40478-021-01124-7

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Language：Japanese   Publisher：金原出版(株)  

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2018&ichushi_jid=J01266&link_issn=&doc_id=20180719160010&doc_link_id=10.18888%2Fhi.0000000860&url=https%3A%2F%2Fdoi.org%2F10.18888%2Fhi.0000000860&type=%E5%8C%BB%E6%9B%B8.jp_%E3%82%AA%E3%83%BC%E3%83%AB%E3%82%A2%E3%82%AF%E3%82%BB%E3%82%B9&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

Language：English  

DOI： 10.1111/1346-8138.13967

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Language：Japanese   Publisher：日本脳腫瘍病理学会  

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