Faculty Profiles - OOISHI Makoto

Papers - OOISHI Makoto

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Improved health-related quality of life after rehabilitation in patients with brain tumors is not affected by tumor type

Takahiro WATANABE, Shinichi NOTO, Manabu NATSUMEDA, Shinji KIMURA, Fumie IKARASHI, Satoshi TABATA, Mayuko TAKANO, Yoshihiro TSUKAMOTO, Makoto OISHI

European Journal of Physical and Rehabilitation Medicine 2025.2

Diagnosis of Leptomeningeal Disease in Diffuse Midline Gliomas by Detection of H3F3A K27M Mutation in Circulating Tumor DNA of Cerebrospinal Fluid. International journal

Satoshi Shibuma, Jotaro On, Manabu Natsumeda, Akihide Koyama, Haruhiko Takahashi, Jun Watanabe, Masaki Mitobe, Satoshi Nakata, Yuki Tanaka, Yoshihiro Tsukamoto, Masayasu Okada, Junichi Yoshimura, Mari Tada, Hiroshi Shimizu, Soichi Oya, Junko Murai, Kouichirou Okamoto, Hiroyuki Kawashima, Akiyoshi Kakita, Makoto Oishi

Pediatric blood & cancer e31535 2025.1

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

INTRODUCTION: Leptomeningeal disease (LMD) in diffuse midline gliomas (DMGs) can lead to devastating symptoms such as severe pain, urinary incontinence, and tetraparesis, with limited treatment options. We determined whether detecting H3F3A K27M-mutant droplets in cerebrospinal fluid (CSF) circulating tumor deoxyribonucleic acid (ctDNA) could be a biomarker for detecting LMD in DMGs. METHODS: Twenty-five CSF samples were obtained from 22 DMG patients. Histological confirmation of H3F3A K27M mutation was obtained in 10 (45.5%) cases. ctDNA was extracted from CSF, and H3F3A K27M-mutant and wildtype droplets were detected using digital droplet polymerase chain reaction (ddPCR). LMD was diagnosed by CSF cytology and pre- and post-contrast head and spine magnetic resonance (MR) imaging. RESULTS: The number of H3F3A K27M-mutant droplets (median 27 [range: 1-379] vs. median 0 [range: 0-1]; p < 0.0001) and variant allele frequency (VAF) (median 48.9% [range: 7.5%-87.5%] vs. median 0.0% [range: 0.0%-50.0%]; p < 0.0001) were significantly higher in the LMD/early-LMD group compared to no-LMD group. In two cases (Cases 4 and 11) without clinical evidence of LMD, multiple H3F3A K27M-mutant droplets were detected in CSF ctDNA. In those cases, extensive spinal dissemination was detected 6 months after the initial liquid biopsy. One case (Case 15) with high Schlafen11 (SLFN11) expression responded well to treatment for LMD and survived for 532 days after the diagnosis of LMD. CONCLUSION: This study provides evidence that detecting H3F3A K27M-mutant droplets in CSF ctDNA is diagnostic for LMD and is more sensitive than traditional methods such as CSF cytology and MR imaging.

DOI： 10.1002/pbc.31535

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Improvements in activities of daily living among patients with brain tumors are associated with age, baseline physical function, duration of rehabilitation, and tumor recurrence but not type. International journal

Takahiro Watanabe, Shinichi Noto, Manabu Natsumeda, Shinji Kimura, Fumie Ikarashi, Satoshi Tabata, Mayuko Takano, Yoshihiro Tsukamoto, Makoto Oishi

International journal of rehabilitation research. Internationale Zeitschrift fur Rehabilitationsforschung. Revue internationale de recherches de readaptation 2024.8

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

Genetic testing has improved the accuracy of diagnosis of brain tumors, and treatment is now tailored to the type of brain tumor. In contrast, the factors that influence the improvement in independence in activities of daily living (ADLs) following rehabilitation have not been clarified, particularly the role of tumor type. In this retrospective cohort study of 358 participants, we analyzed changes in the Functional Independence Measure (FIM) from pre-rehabilitation to post-rehabilitation provided in an acute care hospital. Multiple regression was used to determine whether FIM gain is associated with age, gender, preadmission Karnofsky Performance Status (KPS), number of rehabilitation days, average duration of daily therapy (min/day), and tumor recurrence and type (WHO grade 1, 2, 3, and 4 gliomas; primary central nervous system lymphomas; and metastatic brain tumors). The results showed that older age (β -0.183), tumor recurrence (β -0.137), preadmission KPS < 80 (β -0.180), and higher baseline total FIM score (β -0.470) were associated with lower FIM gain whereas the average duration of daily therapy (β 0.153) was associated with higher FIM gain. Brain tumor type was not associated with FIM gain. Improved independence in ADLs is more influenced by demographic, functional status, and treatment factors than differences in brain tumor type.

DOI： 10.1097/MRR.0000000000000641

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難治性てんかんとしての海馬硬化症における神経成長関連タンパク質のリン酸化解析

岡田正康, 北浦弘樹, 柿田明美, 大石誠, 五十嵐道弘

JSBMS Letters 49 ( Suppl. ) 112 - 112 2024.8

Primary spinal cord gliomas: Pathologic features associated with prognosis. International journal

Yuki Tanaka, Manabu Natsumeda, Masayuki Ohashi, Rie Saito, Nayuta Higa, Toshiaki Akahane, Hideki Hashidate, Junko Ito, Satoshi Fujii, Atsushi Sasaki, Akihide Tanimoto, Ryosuke Hanaya, Kei Watanabe, Makoto Oishi, Hiroyuki Kawashima, Akiyoshi Kakita

Journal of neuropathology and experimental neurology 2024.7

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

Primary spinal cord gliomas are rare and are associated with high mortality. Unlike brain tumors, the clinicopathological features of spinal cord gliomas are not well defined. We analyzed clinical, histopathology, and immunohistochemical features and overall survival (OS) of 25 patients with primary spinal cord gliomas treated between 1994 and 2023 at 4 institutions. IDH1 R132H, H3K27M, and p53 were assessed by immunohistochemistry (IHC). Four (16%), 5 (20%), 2 (8%), and 13 (52%) patients were diagnosed as having grades 1, 2, 3, and 4 gliomas according to the World Health Organization (WHO) 2021 classification, respectively. One case (4%), with a circumscribed diffuse midline glioma, H3K27-altered, had a rare molecular profile and could not be graded. IHC demonstrated H3K27M positivity, indicative of H3F3A K27M or HIST1H3B K27M mutation, in 9 (36%) patients. H3K27me3-loss was evident in 13 (52%) patients. In one patient with a grade 1 tumor that showed negative staining for H3K27M and H3K27me3 loss, numbers of EZHIP-positive cells were increased, suggesting diffuse midline glioma, H3K27-altered (WHO grade 4). H3K27me3 loss, frequency of p53 positive cells (≥10%), MIB-1 index (≥10%), and high histopathological grades significantly correlated with poor OS. These results indicate the pathological and immunohistochemical characteristics of primary spinal cord gliomas that impact prognosis.

DOI： 10.1093/jnen/nlae084

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A patient with neuronal intranuclear inclusion disease developed encephalitis‐like symptoms after cerebral angiography

Shin Koide, Shintaro Tsuboguchi, Shingo Koide, Itaru Ninomiya, Taiki Saito, Takanobu Ishiguro, Etsuji Saji, Yo Higuchi, Takeshi Ikeuchi, Makoto Oishi, Masato Kanazawa, Osamu Onodera

Neurology and Clinical Neuroscience 2024.6

Publishing type：Research paper (scientific journal) Publisher：Wiley

Abstract

Patients with neuronal intranuclear inclusion disease (NIID) can present with encephalitis‐like symptoms such as recurrent paroxysmal fever and unconsciousness. To date, no specific triggers for these symptoms have been reported. In our case, an 78‐year‐old woman became unconscious and developed fever after cerebral angiography. The patient had experienced four episodes of unconsciousness and fever in the past 7 years. Postangiography, she immediately became unconscious and developed fever. No vascular abnormalities were found and magnetic resonance imaging of the brain revealed expanding white matter lesions and hyperintense lesions along the corticomedullary junction. Genetic analysis revealed an abnormal GGC repeat expansion in NOTCH2NLC. Thus, we diagnosed the patient with NIID. We suggest that cerebral angiography is a possible trigger for encephalitis‐like symptoms in NIID.

DOI： 10.1111/ncn3.12839

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Clinical and Hemodynamic Features of Aneurysm Rupture in Coil Embolization of Intracranial Aneurysms. International journal

Tomoaki Suzuki, Hitoshi Hasegawa, Kohei Shibuya, Hidemoto Fujiwara, Makoto Oishi

Diagnostics (Basel, Switzerland) 14 ( 11 ) 2024.6

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

Intraprocedural rupture (IPR) during coil embolization (CE) of an intracranial aneurysm is a significant clinical concern that necessitates a comprehensive understanding of its clinical and hemodynamic predictors. Between January 2012 and December 2023, 435 saccular cerebral aneurysms were treated with CE at our institution. The inclusion criterion was extravasation or coil protrusion during CE. Postoperative data were used to confirm rupture points, and computational fluid dynamics (CFD) analysis was performed to assess hemodynamic characteristics, focusing on maximum pressure (Pmax) and wall shear stress (WSS). IPR occurred in six aneurysms (1.3%; three ruptured and three unruptured), with a dome size of 4.7 ± 1.8 mm and a D/N ratio of 1.5 ± 0.5. There were four aneurysms in the internal carotid artery (ICA), one in the anterior cerebral artery, and one in the middle cerebral artery. ICA aneurysms were treated using adjunctive techniques (three balloon-assisted, one stent-assisted). Two aneurysms (M1M2 and A1) were treated simply, yet had relatively small and misaligned domes. CFD analysis identified the rupture point as a flow impingement zone with Pmax in five aneurysms (83.3%). Time-averaged WSS was locally reduced around this area (1.3 ± 0.7 [Pa]), significantly lower than the aneurysmal dome (p < 0.01). Hemodynamically unstable areas have fragile, thin walls with rupture risk. A microcatheter was inserted along the inflow zone, directed towards the caution area. These findings underscore the importance of identifying hemodynamically unstable areas during CE. Adjunctive techniques should be applied with caution, especially in small aneurysms with axial misalignment, to minimize the rupture risk.

DOI： 10.3390/diagnostics14111203

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頭蓋骨転移した胸部SMARCA4欠損未分化腫瘍の1例

渋間啓, 西田京香, 小倉良介, 岡田正康, 棗田学, 加藤卓, 梅津哉, 大石誠, 柿田明美

Brain Tumor Pathology 41 ( Suppl. ) 159 - 159 2024.5

間脳下垂体腫瘍病理診断の現状と治療:PitNETを含め機能性PitNETの治療中に転移を来たし,下垂体転写因子の有無で鑑別した2症例の経験

岡田正康, 棗田学, 塚本佳広, 梅津哉, 柿田明美, 大石誠

Brain Tumor Pathology 41 ( Suppl. ) 079 - 079 2024.5

Recent advances in liquid biopsy of central nervous system lymphomas: case presentations and review of the literature

Manabu Natsumeda, Satoshi Shibuma, Haruhiko Takahashi, Jotaro On, Yoshihiro Mouri, Kaoru Tomikawa, Hidemoto Fujiwara, Jun Watanabe, Yoshihiro Tsukamoto, Masayasu Okada, Rui Takeda, Hiroshi Shimizu, Jun Takizawa, Akiyoshi Kakita, Makoto Oishi

Brain Tumor Pathology 41 ( 2 ) 85 - 91 2024.4

Preoperative interactive virtual simulation applying three-dimensional multifusion images using a haptic device for lumbosacral lipoma. International journal

Ryosuke Ogura, Hidemoto Fujiwara, Manabu Natsumeda, Tetsuya Hiraishi, Masakazu Sano, Makoto Oishi

Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery 40 ( 4 ) 1129 - 1136 2024.4

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

PURPOSE: Untethering surgery for lumbosacral lipoma is a preventive procedure, and avoidance of complications and good long-term outcomes are required. We introduced presurgical interactive virtual simulation (IVS) applying three-dimensional multifusion images using a haptic device aimed at improving operative outcomes. METHODS: Fourteen patients with newly diagnosed lumbosacral lipoma were recruited and underwent preoperative IVS. The median age at surgery was 8 months. A three-dimensional image analysis system was used to extract and fuse structures necessary for surgery, such as the lipoma, spinal cord and skin, from CT and MRI, and create three-dimensional multifusion images. The created images were individually converted to standard triangulated language format and loaded onto a workstation (Geomagic freeform™) that could be freely transformed, and the laminectomy range and lipoma extraction procedure were examined. Presurgical IVS was performed, and the actual surgery was performed. RESULTS: The disease types were dorsal, caudal, lipomyelomeningocele, transitional, and filum in 5, 5, 2, 1, and 1 patients, respectively. The surgical procedure and extent of the laminectomy were as planned for all patients. Resection of the lipomas tended to be less than expected preoperatively because of positive reactions on intraoperative monitoring. No postoperative complications were observed. The median postoperative follow-up period was 29 months, and there were no reoperations during the observation period. CONCLUSIONS: Although there are various types of lumbosacral lipoma, surgery can be safely performed by performing presurgical IVS. The short-term course is good; however, long-term follow-up is necessary for the appearance of neurological symptoms associated with growth and re-tethering.

DOI： 10.1007/s00381-023-06234-2

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脳腫瘍1 Diffuse midline gliomaにおける髄液中H3K27M変異検出は髄膜播種を予測する

棗田学, 温城太郎, 渋間聡, 高橋陽彦, 渡邉潤, 塚本佳広, 小倉良介, 岡田正康, 大石誠

小児の脳神経 49 ( 2 ) 128 - 128 2024.4

画像診断小児神経外科手術における外視鏡と三次元融合画像の有用性

小倉良介, 吉田至誠, 藤原秀元, 棗田学, 平石哲也, 大石誠

小児の脳神経 49 ( 2 ) 167 - 167 2024.4

毛様細胞性星細胞腫(Non-NF1)の治療と現状

大石誠, 棗田学, 塚本佳広, 小倉良介, 三橋大樹, 平石哲也

小児の脳神経 49 ( 2 ) 207 - 207 2024.4

脳腫瘍1 Diffuse midline gliomaにおける髄液中H3K27M変異検出は髄膜播種を予測する

棗田学, 温城太郎, 渋間聡, 高橋陽彦, 渡邉潤, 塚本佳広, 小倉良介, 岡田正康, 大石誠

小児の脳神経 49 ( 2 ) 128 - 128 2024.4

神経皮膚黒色症剖検例における多領域ゲノム解析

高橋陽彦, 棗田学, 塚本佳広, 岡田正康, 原範和, 小山哲秀, 宮下哲典, 結城明彦, 清水宏, 柿田明美, 池内健, 大石誠

小児の脳神経 49 ( 2 ) 228 - 228 2024.4

[Interactive Virtual Simulation with Haptics for Neurosurgery].

Makoto Oishi, Ryosuke Ogura

No shinkei geka. Neurological surgery 52 ( 2 ) 279 - 288 2024.3

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

We established a unique pre-surgical simulation method by applying interactive virtual simulation(IVS)using multi-fusion three-dimensional imaging data, presenting high-quality visualization of microsurgical anatomies. Our IVS provided a realistic environment for imitating surgical manipulations, such as dissecting bones, retracting brain tissues, and removing tumors, with tactile and kinesthetic sensations delivered through a specific haptic device. The great advantage of our IVS was in deciding the most appropriate craniotomy and bone resection to create the optimal surgical window and obtain the best working space with a thorough understanding of the lesion-bone relationship. Particularly for skull-base tumors, tailoring the procedures to individual patients for craniotomy and bone resection was sufficiently achieved using our IVS. In cases of large skull base meningiomas, our IVS was also helpful preoperatively regarding tumors, as several compartments were achievable in every potentially usable surgical direction. Additionally, the non-risky realistic microsurgical environments of the IVS provided improvement in the microsurgical senses and skills of young trainees through the repetition of surgical tasks. Finally, our presurgical IVS simulation method provided a realistic environment for practicing microsurgical procedures virtually and enabled us to ascertain the complex microsurgical anatomy, determine optimal surgical strategies, and efficiently educate neurosurgical trainees.

DOI： 10.11477/mf.1436204912

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Reliable detection of genetic alterations in cyst fluid DNA for the diagnosis of brain tumors. International journal

Jotaro On, Manabu Natsumeda, Haruhiko Takahashi, Akihide Koyama, Satoshi Shibuma, Nao Shibata, Jun Watanabe, Shoji Saito, Yu Kanemaru, Yoshihiro Tsukamoto, Masayasu Okada, Ryosuke Ogura, Takeyoshi Eda, Mari Tada, Hiroshi Shimizu, Jun-Ichi Adachi, Kazuhiko Mishima, Ryo Nishikawa, Akiyoshi Kakita, Makoto Oishi

Journal of neuro-oncology 2024.1

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

PURPOSE: Liquid biopsy of cyst fluid in brain tumors has not been extensively studied to date. The present study was performed to see whether diagnostic genetic alterations found in brain tumor tissue DNA could also be detected in cell-free DNA (cfDNA) of cyst fluid in cystic brain tumors. METHODS: Cyst fluid was obtained from 22 patients undergoing surgery for a cystic brain tumor with confirmed genetic alterations in tumor DNA. Pathological diagnoses based on WHO 2021 classification and diagnostic alterations in the tumor DNA, such as IDH1 R132H and TERT promoter mutation for oligodendrogliomas, were detected by Sanger sequencing. The same alterations were analyzed by both droplet digital PCR (ddPCR) and Sanger sequencing in cyst fluid cfDNA. Additionally, multiplex ligation-dependent probe amplification (MLPA) assays were performed to assess 1p/19q status, presence of CDKN2A loss, PTEN loss and EGFR amplification, to assess whether differentiating between astrocytomas and oligodendrogliomas and grading is possible from cyst fluid cfDNA. RESULTS: Twenty-five genetic alterations were found in 22 tumor samples. All (100%) alterations were detected in cyst fluid cfDNA by ddPCR. Twenty of the 25 (80%) alterations were also detected by Sanger sequencing of cyst fluid cfDNA. Variant allele frequency (VAF) in cyst fluid cfDNA was comparable to that of tumor DNA (R = 0.62, Pearson's correlation). MLPA was feasible in 11 out of 17 (65%) diffuse gliomas, with close correlation of results between tumor DNA and cyst fluid cfDNA. CONCLUSION: Cell-free DNA obtained from cyst fluid in cystic brain tumors is a reliable alternative to tumor DNA when diagnosing brain tumors.

DOI： 10.1007/s11060-023-04555-5

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Multi-omics analyses of choroid plexus carcinoma cell lines reveal potential targetable pathways and alterations. International journal

Dina Hesham, Jotaro On, Nouran Alshahaby, Nada Amer, Sameh Magdeldin, Masayasu Okada, Yoshihiro Tsukamoto, Tetsuya Hiraishi, Chihaya Imai, Shujiro Okuda, Toshifumi Wakai, Akiyoshi Kakita, Makoto Oishi, Shahenda El-Naggar, Manabu Natsumeda

Journal of neuro-oncology 166 ( 1 ) 27 - 38 2024.1

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

PURPOSE: Choroid plexus carcinomas (CPCs) are extremely rare brain tumors and carry a dismal prognosis. Treatment options are limited and there is an urgent need to develop models to further research. In the present study, we established two CPC cell lines and performed multi-omics analyses. These cell lines serve as valuable models to propose new treatments in these rare but deadly brain tumors. METHODS: Multi-omic profiling including, (i) methylation array (EPIC 850 K), (ii) whole genome sequencing (WGS), (iii) CANCERPLEX cancer genome panel testing, (iv) RNA sequencing (RNA-seq), and (v) proteomics analyses were performed in CCHE-45 and NGT131 cell lines. RESULTS: Both cell lines were classified as methylation class B. Both harbored pathogenic TP53 point mutations; CCHE-45 additionally displayed TP53 loss. Furthermore, alterations of the NOTCH and WNT pathways were also detected in both cell lines. Two protein-coding gene fusions, BZW2-URGCP, and CTTNBP2-ERBB4, mutations of two oncodrivers, GBP-4 and KRTAP-12-2, and several copy number alterations were observed in CCHE-45, but not NGT131. Transcriptome and proteome analysis identified shared and unique signatures, suggesting that variability in choroid plexus carcinoma tumors may exist. The discovered difference's importance and implications highlight the possible diversity of choroid plexus carcinoma and call for additional research to fully understand disease pathogenesis. CONCLUSION: Multi-omics analyses revealed that the two choroid plexus carcinoma cell lines shared TP53 mutations and other common pathway alterations and activation of NOTCH and WNT pathways. Noticeable differences were also observed. These cell lines can serve as valuable models to propose new treatments in these rare but deadly brain tumors.

DOI： 10.1007/s11060-023-04484-3

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Case report: Progressive multifocal leukoencephalopathy co-occurring with neurosarcoidosis: early brain biopsy and appropriate therapy for PML resulted in a favorable prognosis. International journal

Qiannan Wang, Shintaro Tsuboguchi, Kouichirou Okamoto, Mari Tada, Akiyoshi Kakita, Kazuo Nakamichi, Makoto Oishi, Masato Kanazawa, Osamu Onodera

Frontiers in immunology 15 1447992 - 1447992 2024

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

Progressive multifocal leukoencephalopathy (PML) is a rare central nervous system disease caused by JC virus (JCV) infection. Human immunodeficiency virus (HIV) infection is the greatest risk factor for PML. Other immunological diseases, including systemic sarcoidosis, have also been reported as risk factors for PML. Herein, we report a case of PML co-occurring with neurosarcoidosis. Early diagnosis using brain biopsy and appropriate therapeutic interventions achieved favorable outcomes. PML in patients with active intracranial neurosarcoidosis is extremely rare. We believe that it is important to perform brain biopsy at an early stage to allow diagnosis, even for central nervous system involvement with a progressive parenchymal lesion in patients with sarcoidosis, if PML is possible.

DOI： 10.3389/fimmu.2024.1447992

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Papers - OOISHI Makoto