2024/12/21 更新

写真a

オグラ リヨウスケ
小倉 良介
OGURA Ryosuke
所属
脳研究所 臨床神経科学部門 脳神経外科学 助教
職名
助教
外部リンク

学位

  • 博士(医学) ( 2015年3月   新潟大学 )

研究分野

  • ライフサイエンス / 脳神経外科学

経歴

  • 新潟大学   脳研究所 臨床神経科学部門 脳神経外科学   助教

    2023年12月 - 現在

  • 新潟大学   医歯学総合病院 脳神経外科   特任助教

    2022年11月 - 2023年11月

  • 新潟大学   医歯学総合病院 脳神経外科   助教

    2022年4月 - 2022年10月

  • 新潟大学   医歯学総合病院 高次救命災害治療センター   特任助教

    2019年4月 - 2022年3月

 

論文

  • Preoperative interactive virtual simulation applying three-dimensional multifusion images using a haptic device for lumbosacral lipoma. 国際誌

    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年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    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年4月

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    記述言語:日本語   出版者・発行元:(一社)日本小児神経外科学会  

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  • [Interactive Virtual Simulation with Haptics for Neurosurgery].

    Makoto Oishi, Ryosuke Ogura

    No shinkei geka. Neurological surgery   52 ( 2 )   279 - 288   2024年3月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

    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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  • Missense mutation of NRAS is associated with malignant progression in neurocutaneous melanosis. 国際誌

    Haruhiko Takahashi, Manabu Natsumeda, Norikazu Hara, Akihide Koyama, Hiroshi Shimizu, Akinori Miyashita, Daiken Satake, Yoshihiro Mouri, Jun Tsukano, Keita Kawabe, Yoshihiro Tsukamoto, Masayasu Okada, Ryosuke Ogura, Akihiko Yuki, Hajime Umezu, Akiyoshi Kakita, Takeshi Ikeuchi, Makoto Oishi

    Acta neuropathologica communications   12 ( 1 )   14 - 14   2024年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Neurocutaneous melanosis (NCM) is a rare congenital neurocutaneous syndrome characterized by congenital melanocytic nevus of skin and abnormal proliferation of leptomeningeal melanocytes. Early acquisition of post-zygotic somatic mutations has been postulated to underlie the pathogenesis of NCM. The pathogenesis of NCM remains to be fully elucidated, and treatment options have not been established. Here, we report for the first time, multiregional genomic analyses in a 3-year-old autopsied girl with leptomeningeal melanomatosis associated with NCM, in which a ventriculo-peritoneal (VP) shunt was inserted for the treatment of hydrocephalus. The patient expired six months after the onset due to respiratory failure caused by abdominal dissemination via VP shunt. We performed multiregional exome sequencing to identify genomic differences among brain and abdominal tumors, nevus, and normal tissues. A total of 87 somatic mutations were found in 71 genes, with a significantly large number of gene mutations found in the tumor site. The genetic alterations detected in the nevus were only few and not shared with other sites. Three mutations, namely GNAQ R183Q, S1PR3 G89S and NRAS G12V, considered pathogenic, were found, although S1PR3 mutations have not been previously reported in melanocytic tumors. GNAQ and S1PR3 mutations were shared in both tumor and normal sites. Moreover, the mutant allele frequencies of the two mutations were markedly higher in tumor sites than in normal sites, with copy-neutral loss-of-heterozygosity (CN-LOH) occurring in tumor. NRAS mutation was found only in the abdominal tumor and was thought to be responsible for malignant progression in the present case. Multiregional comprehensive genetic analysis may lead to discovering novel driver mutations associated with tumorigenesis and targeted therapy.

    DOI: 10.1186/s40478-024-01723-0

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  • Reliable detection of genetic alterations in cyst fluid DNA for the diagnosis of brain tumors. 国際誌

    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   166 ( 2 )   273 - 282   2024年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    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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  • 嚢胞形成PRL産生PitNETの治療成績

    岡田 正康, 小倉 良介, 平石 哲也, 米岡 有一郎, 大石 誠

    新潟医学会雑誌   137 ( 12 )   447 - 447   2023年12月

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    記述言語:日本語   出版者・発行元:新潟医学会  

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  • 【「脳神経外科領域におけるPDTの現状と問題点」】当科における光線力学療法の経験および次世代への挑戦

    棗田 学, 温 城太郎, 渡邉 潤, 塚本 佳広, 岡田 正康, 小倉 良介, 平石 哲也, 大石 誠, 藤井 幸彦

    日本レーザー医学会誌   44 ( 2 )   95 - 101   2023年7月

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    記述言語:日本語   出版者・発行元:(NPO)日本レーザー医学会  

    2018年7月に当科に光線力学療法(photodynamic therapy:PDT)を導入してから2021年6月まで,当科でPDTを施行した悪性脳腫瘍症例の臨床的特徴および無増悪生存期間(progression free survival:PFS),全生存期間(overall survival:OS),主な合併症について検討した.初発膠芽腫9例におけるPFSの中央値は14ヵ月,OS中央値は未達であった.死亡例は早期に遠隔再発を来した1例のみであった.主な合併症は光過敏症が1例,脳表に可逆性のFLAIR高信号が3例,術後うつ状態が5例に認め,いずれも一過性であった.術後の長期間遮光管理が原因と思われるうつ症状には,早期遮光解除などの工夫が必要と思われた.実際の症例を提示し我々のPDT初期治療経験を紹介し,また,次世代治療と考える近赤外光線免疫療法(near-infrared photoimmunotherapy:NIR-PIT)の研究に関しても紹介する.NIR-PITは,癌細胞の表面抗原を標識とし,近赤外線照射により生じた熱エネルギーにより腫瘍細胞の細胞膜を破壊する画期的な治療法である.今回,我々は膠芽腫細胞株に特異的な表面抗原Xに対する抗体を用いたNIR-PITを行い,殺細胞効果を確認した.(著者抄録)

    DOI: 10.2530/jslsm.jslsm-44_0024

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    その他リンク: https://search.jamas.or.jp/default/link?pub_year=2023&ichushi_jid=J01213&link_issn=&doc_id=20230803380003&doc_link_id=10.2530%2Fjslsm.jslsm-44_0024&url=https%3A%2F%2Fdoi.org%2F10.2530%2Fjslsm.jslsm-44_0024&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_2.gif

  • Preoperative three-dimensional multifusion imaging aiding successful microvascular decompression of a cerebellopontine angle lipoma: associated hemifacial spasm. Illustrative case. 国際誌

    Hiroki Seto, Ryosuke Ogura, Tetsuya Hiraishi, Yoshihiro Tsukamoto, Taiki Saito, Satoshi Shibuma, Kohei Shibuya, Kouichirou Okamoto, Makoto Oishi, Yukihiko Fujii

    Journal of neurosurgery. Case lessons   5 ( 12 )   2023年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Cerebellopontine angle (CPA) lipoma-associated hemifacial spasm (HFS) is rare. As the removal of CPA lipomas has a high risk of worsening the neurological symptoms, surgical exploration is warranted only in selected patients. Preoperative identification of the lipoma affected site of the facial nerve, and offending artery are crucial for patient selection and successful microvascular decompression (MVD). OBSERVATIONS: Presurgical simulation using three-dimensional (3D) multifusion imaging showed a tiny CPA lipoma wedged between the facial and auditory nerves, as well as an affected facial nerve by the anterior inferior cerebellar artery (AICA) at the cisternal segment. Although a recurrent perforating artery from the AICA anchored the AICA to the lipoma, successful MVD was achieved without lipoma removal. LESSONS: The presurgical simulation using 3D multifusion imaging could identify the CPA lipoma, affected site of the facial nerve, and offending artery. It was helpful for patient selection and successful MVD.

    DOI: 10.3171/CASE2318

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  • Elucidating the multiple genetic alterations involved in the malignant transformation of a KRAS mutant neurenteric cyst. A case report. 国際誌

    Shoji Saito, Manabu Natsumeda, Makoto Sainouchi, Toru Takino, Kohei Shibuya, Jotaro On, Yu Kanemaru, Ryosuke Ogura, Masayasu Okada, Makoto Oishi, Yoshifumi Shimada, Toshifumi Wakai, Shujiro Okuda, Yoichi Ajioka, Akiyoshi Kakita, Yukihiko Fujii

    Neuropathology : official journal of the Japanese Society of Neuropathology   42 ( 6 )   519 - 525   2022年9月

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    記述言語:英語  

    Neurenteric cyst (NC) shows benign histopathology and rarely demonstrate malignant transformation. We herein describe a case of NC that exhibited malignant transformation. A 65-year-old female presented with gait disturbance due to compression by a cystic mass on the dorsal surface of the medulla oblongata. Partial resection was performed twice, leading to improvement of her symptoms. Two years after the second surgery, gadolinium-perfused T1-weighted magnetic resonance imaging revealed an invasive lesion with contrast enhancement at the trigone of the left lateral ventricle for which partial resection followed by radiotherapy was performed. However, mass regrowth was observed, with the patient eventually succumbing to her disease 11 months after her third surgery. Histopathological analyses of the first and second surgical specimens identified pseudostratified cuboidal epithelial cells, with no nuclear or cellular atypia resembling gastrointestinal mucosa, lining the inner surface of the cystic wall. Based on these findings the lesion was diagnosed as NC. The third surgical specimen exhibited apparent malignant features of the epithelial cells with elongated and hyperchromatic nuclei, several mitotic figures, small necrotic foci, and a patternless or sheet-like arrangement. Based on these findings, the lesion was diagnosed as NC with malignant transformation. Next-generation sequencing revealed KRAS p.G12D mutation in all specimens. Additionally, the third surgical specimen harbored the following 12 de novo gene alterations: ARID1A loss, BAP1 p.F170L, CDKN1B loss, CDKN2A loss, CDKN2B loss, FLCN loss, PTCH1 loss, PTEN loss, PTPRD loss, SUFU loss, TP53 loss, and TSC1 loss. The aforementioned results suggest that KRAS mutation is associated with the development of the NC, and that the additional gene alterations contribute to malignant transformation of the NC.

    DOI: 10.1111/neup.12822

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  • 小児・AYA世代のヒストン遺伝子変異びまん性神経膠腫症例の後方視的検討

    塚本 佳広, 高橋 陽彦, 温 城太郎, 小倉 良介, 棗田 学, 岡本 浩一郎, 大石 誠, 柿田 明美, 藤井 幸彦

    Brain Tumor Pathology   39 ( Suppl. )   100 - 100   2022年5月

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    記述言語:日本語   出版者・発行元:日本脳腫瘍病理学会  

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  • Novel Repositioning Therapy for Drug-Resistant Glioblastoma: In Vivo Validation Study of Clindamycin Treatment Targeting the mTOR Pathway and Combination Therapy with Temozolomide. 国際誌

    Takeyoshi Eda, Masayasu Okada, Ryosuke Ogura, Yoshihiro Tsukamoto, Yu Kanemaru, Jun Watanabe, Jotaro On, Hiroshi Aoki, Makoto Oishi, Nobuyuki Takei, Yukihiko Fujii, Manabu Natsumeda

    Cancers   14 ( 3 )   2022年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Multimodal therapy including surgery, radiation treatment, and temozolomide (TMZ) is performed on glioblastoma (GBM). However, the prognosis is still poor and there is an urgent need to develop effective treatments to improve survival. Molecular biological analysis was conducted to examine the signal activation patterns in GBM specimens and remains an open problem. Advanced macrolides, such as azithromycin, reduce the phosphorylation of p70 ribosomal protein S6 kinase (p70S6K), a downstream mammalian target of rapamycin (mTOR) effector, and suppress the proliferation of T-cells. We focused on its unique profile and screened for the antitumor activity of approved macrolide antibiotics. Clindamycin (CLD) reduced the viability of GBM cells in vitro. We assessed the effects of the candidate macrolide on the mTOR pathway through Western blotting. CLD attenuated p70S6K phosphorylation in a dose-dependent manner. These effects on GBM cells were enhanced by co-treatment with TMZ. Furthermore, CLD inhibited the expression of the O6-methylguanine-DNA methyltransferase (MGMT) protein in cultured cells. In the mouse xenograft model, CLD and TMZ co-administration significantly suppressed the tumor growth and markedly decreased the number of Ki-67 (clone MIB-1)-positive cells within the tumor. These results suggest that CLD suppressed GBM cell growth by inhibiting mTOR signaling. Moreover, CLD and TMZ showed promising synergistic antitumor activity.

    DOI: 10.3390/cancers14030770

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  • Detection of 2-Hydroxyglutarate by 3.0-Tesla Magnetic Resonance Spectroscopy in Gliomas with Rare IDH Mutations: Making Sense of "False-Positive" Cases. 国際誌

    Manabu Natsumeda, Hironaka Igarashi, Ramil Gabdulkhaev, Haruhiko Takahashi, Kunio Motohashi, Ryosuke Ogura, Jun Watanabe, Yoshihiro Tsukamoto, Kouichirou Okamoto, Akiyoshi Kakita, Tsutomu Nakada, Yukihiko Fujii

    Diagnostics (Basel, Switzerland)   11 ( 11 )   2021年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    We have previously published a study on the reliable detection of 2-hydroxyglutarate (2HG) in lower-grade gliomas by magnetic resonance spectroscopy (MRS). In this short article, we re-evaluated five glioma cases originally assessed as isocitrate dehydrogenase (IDH) wildtype, which showed a high accumulation of 2HG, and were thought to be false-positives. A new primer was used for the detection of IDH2 mutation by Sanger sequencing. Adequate tissue for DNA analysis was available in 4 out of 5 cases. We found rare IDH2 mutations in two cases, with IDH2 R172W mutation in one case and IDH2 R172K mutation in another case. Both cases had very small mutant peaks, suggesting that the tumor volume was low in the tumor samples. Thus, the specificity of MRS for detecting IDH1/2 mutations was higher (81.3%) than that originally reported (72.2%). The detection of 2HG by MRS can aid in the diagnosis of rare, non-IDH1-R132H IDH1 and IDH2 mutations in gliomas.

    DOI: 10.3390/diagnostics11112129

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  • High grade astrocytomaに準じて治療したprimary anaplastic pleomorphic xanthoastrocytomaの4症例の検討

    塚本 佳広, 棗田 学, 温 城太郎, 小倉 良介, 清水 宏, 岡本 浩一郎, 大石 誠, 藤井 幸彦, 柿田 明美

    Brain Tumor Pathology   38 ( Suppl. )   078 - 078   2021年5月

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    記述言語:日本語   出版者・発行元:日本脳腫瘍病理学会  

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  • 脳腫瘍遺伝子異常の画像診断 IDH変異型神経膠腫における3T-MRSを用いた2HGの検出

    棗田 学, 五十嵐 博中, 本橋 邦夫, 塚本 佳広, 小倉 良介, 岡本 浩一郎, 大石 誠, 柿田 明美, 藤井 幸彦

    Brain Tumor Pathology   38 ( Suppl. )   059 - 059   2021年5月

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    記述言語:日本語   出版者・発行元:日本脳腫瘍病理学会  

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  • Four-dimensional multifusion imaging for assessment of meningioma hemodynamics 査読

    Ryosuke Ogura, Makoto Oishi, Tetsuya Hiraishi, Haruhiko Takahashi, Kohei Shibuya, Tomoaki Suzuki, Manabu Natsumeda, Kouichirou Okamoto, Yukihiko Fujii

    Interdisciplinary Neurosurgery: Advanced Techniques and Case Management   2021年2月

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    担当区分:筆頭著者   掲載種別:研究論文(学術雑誌)  

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  • マイクロバルーンカテーテルによるflow reductionを併用したOnyx塞栓術

    高橋 陽彦, 安藤 和弘, 渋谷 航平, 齋藤 祥二, 小倉 良介, 鈴木 倫明, 長谷川 仁, 吉村 淳一, 藤井 幸彦

    脳血管内治療   5 ( Suppl. )   83 - 83   2020年11月

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    記述言語:日本語   出版者・発行元:(NPO)日本脳神経血管内治療学会  

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  • 症例 中村のⅠ型乳児急性硬膜下血腫の手術例-Big Black Brainと過灌流について

    吉村 淳一, 森川 愛美, 熊谷 駿介, 齋藤 太希, 髙橋 陽彦, 藤原 秀元, 小倉 良介, 土屋 尚人

    Neurological Surgery 脳神経外科   48 ( 9 )   841 - 847   2020年9月

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    記述言語:日本語   出版者・発行元:株式会社医学書院  

    DOI: 10.11477/mf.1436204281

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  • A Case of Curative Onyx Embolization for Tentorial dAVF via Low-flow Feeders with Temporary Balloon Occlusion of High-flow Feeders 査読

    Ryosuke Ogura, Hitoshi Hasegawa, Shunsuke Kumagai, Haruhiko Takahashi, Hidemoto Fujiwara, Junichi Yoshimura, Yukihiko Fujii

    Journal of Neuroendovascular Therapy   14 ( 3 )   112 - 117   2020年

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    担当区分:筆頭著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:The Japanese Society for Neuroendovascular Therapy  

    OBJECTIVE: For curative Onyx embolization of dural arteriovenous fistulas (dAVF) with multiple feeders, it is essential to select the optimal target artery as well as to control the blood flow at the fistula point. We report a case of tentorial dAVF (TdAVF) treated by Onyx embolization under flow control using balloon catheters. CASE PRESENTATION: A 66-year-old male was admitted to our hospital for treatment of TdAVF detected incidentally by MRI, which revealed a dilated and tortuous vein around the cerebellum. Cerebral angiography demonstrated a TdAVF, fed mainly by bilateral middle meningeal arteries (MMA) and bilateral occipital arteries (OA), with the fistula point at the torcular and venous drainage to the two superior vermian veins (SVVs). Onyx 18 was injected from the low-flow feeder of the MMA under flow control by occluding the high-flow feeder of the OA using balloon catheters, obliterating the arteriovenous shunt. CONCLUSION: In treatment of TdAVF involving low- and high-flow feeders, Onyx embolization via the low-flow feeder with temporary balloon occlusion of other high-flow feeders is a useful method. This technique makes it easier for Onyx to penetrate the fistula point.

    DOI: 10.5797/jnet.tn.2019-0053

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  • Main feederをバルーンで一時遮断し、細径の標的動脈より根治的ONYX塞栓術を施行し得た小脳テント部硬膜動静脈瘻の1例

    小倉 良介, 長谷川 仁, 熊谷 駿介, 高橋 陽彦, 藤原 秀元, 吉村 淳一, 藤井 幸彦

    脳血管内治療   4 ( Suppl. )   S294 - S294   2019年11月

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    記述言語:日本語   出版者・発行元:(NPO)日本脳神経血管内治療学会  

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  • Reliable diagnosis of IDH-mutant glioblastoma by 2-hydroxyglutarate detection: a study by 3-T magnetic resonance spectroscopy. 査読 国際誌

    Manabu Natsumeda, Kunio Motohashi, Hironaka Igarashi, Takanori Nozawa, Hideaki Abe, Yoshihiro Tsukamoto, Ryosuke Ogura, Masayasu Okada, Tsutomu Kobayashi, Hiroshi Aoki, Hitoshi Takahashi, Akiyoshi Kakita, Kouichirou Okamoto, Tsutomu Nakada, Yukihiko Fujii

    Neurosurgical review   41 ( 2 )   641 - 647   2018年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    We have previously reported that reliable detection of 2-hydroxyglutarate (2HG) in isocitrate dehydrogenase (IDH)-mutant WHO grade 2 and 3 gliomas is possible utilizing 3.0-T single-voxel magnetic resonance spectroscopy (SVMRS). We set out to determine whether the same method could be applied to detect 2HG in IDH-mutant glioblastoma. Forty-four patients harboring glioblastoma underwent pre-operative MRS evaluation to detect 2HG and other metabolites. Presence of IDH-mutations was determined by IDH1 R132H immunohistochemical analysis and DNA sequencing of surgically obtained tissues. Six out of 44 (13.6%) glioblastomas were IDH-mutant. IDH-mutant glioblastoma exhibited significantly higher accumulation of 2HG (median 3.191 vs. 0.000 mM, p < 0.0001, Mann-Whitney test). A cutoff of 2HG = 0.897 mM achieved high sensitivity (100.0%) and specificity (92.59%) in determining IDH-mutation in glioblastoma. Glioblastoma with high 2HG accumulation did not have significantly longer overall survival than glioblastoma with low 2HG accumulation (p = 0.107, log-rank test). Non-invasive and reliable detection of 2HG in IDH-mutant glioblastoma was possible by 3.0-T SVMRS.

    DOI: 10.1007/s10143-017-0908-y

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  • Cerebral venous sinus thrombosis due to oral contraceptive use: Postmortem 3 T-MRI and autopsy findings. 査読

    Masahiro Uemuraa, Yoshihiro Tsukamoto, Yasuhisa Akaiwa, Masaki Watanabe, Ayako Tazawa, Sou Kasahara, Minoru Endou, Ryosuke Ogura, Kouichirou Okamoto, Yukihiko Fujii, Tsutomu Nakada

    Human Pathology   6 ( 6 )   32 - 36   2016年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1016/j.ehpc.2016.01.002

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  • Chemical Screening Identifies EUrd as a Novel Inhibitor Against Temozolomide-Resistant Glioblastoma-Initiating Cells. 査読 国際誌

    Yoshihiro Tsukamoto, Naoki Ohtsu, Smile Echizenya, Satoko Otsuguro, Ryosuke Ogura, Manabu Natsumeda, Mizuho Isogawa, Hiroshi Aoki, Satoshi Ichikawa, Masahiro Sakaitani, Akira Matsuda, Katsumi Maenaka, Yukihiko Fujii, Toru Kondo

    Stem cells (Dayton, Ohio)   34 ( 8 )   2016 - 25   2016年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY  

    Glioblastoma (GBM), one of the most malignant human cancers, frequently recurs despite multimodal treatment with surgery and chemo/radiotherapies. GBM-initiating cells (GICs) are the likely cell-of-origin in recurrences, as they proliferate indefinitely, form tumors in vivo, and are resistant to chemo/radiotherapies. It is therefore crucial to find chemicals that specifically kill GICs. We established temozolomide (the standard medicine for GBM)-resistant GICs (GICRs) and used the cells for chemical screening. Here, we identified 1-(3-C-ethynyl-β-d-ribopentofuranosyl) uracil (EUrd) as a selective drug for targeting GICRs. EUrd induced the death in GICRs more effectively than their parental GICs, while it was less toxic to normal neural stem cells. We demonstrate that the cytotoxic effect of EUrd on GICRs partly depended on the increased expression of uridine-cytidine kinase-like 1 (UCKL1) and the decreased one of 5'-nucleotidase cytosolic III (NT5C3), which regulate uridine-monophosphate synthesis positively and negatively respectively. Together, these findings suggest that EUrd can be used as a new therapeutic drug for GBM with the expression of surrogate markers UCKL1 and NT5C3. Stem Cells 2016;34:2016-2025.

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  • 当科で経験した成人テント上PNETの2例 症例報告

    塚本 佳広, 小倉 良介, 五十川 瑞穂, 青木 洋, 平石 哲也, 高尾 哲郎, 吉村 淳一, 藤井 幸彦, 高橋 均, 柿田 明美

    Brain Tumor Pathology   33 ( Suppl. )   149 - 149   2016年5月

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    記述言語:日本語   出版者・発行元:日本脳腫瘍病理学会  

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  • 術中脳表NIRSを用いた言語野のcortico-cortical activityの検討

    佐藤 圭輔, 福多 真史, 平石 哲也, 高尾 哲郎, 小倉 良介, 青木 洋, 藤井 幸彦

    新潟医学会雑誌   130 ( 3 )   210 - 211   2016年3月

  • Immunohistochemical profiles of IDH1, MGMT and P53: practical significance for prognostication of patients with diffuse gliomas. 査読 国際誌

    Ryosuke Ogura, Yoshihiro Tsukamoto, Manabu Natsumeda, Mizuho Isogawa, Hiroshi Aoki, Tsutomu Kobayashi, Seiichi Yoshida, Kouichiro Okamoto, Hitoshi Takahashi, Yukihiko Fujii, Akiyoshi Kakita

    Neuropathology : official journal of the Japanese Society of Neuropathology   35 ( 4 )   324 - 35   2015年8月

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    担当区分:筆頭著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL  

    Genetic and epigenetic status, including mutations of isocitrate dehydrogenase (IDH) and TP53 and methylation of O(6) -methylguanine-DNA methyltransferase (MGMT), are associated with the development of various types of glioma and are useful for prognostication. Here, using routinely available histology sections from 312 patients with diffuse gliomas, we performed immunohistochemistry using antibodies specific for IDH1 mutation, MGMT methylation status, and aberrant p53 expression to evaluate the possible prognostic significance of these features. With regard to overall survival (OS), univariate analysis indicated that an IDH1-positive profile in patients with glioblastoma (GBM), anaplastic astrocytoma (AA), anaplastic oligoastrocytoma and oligodendroglioma, or a MGMT-negative profile in patients with GBM and AA were significantly associated with a favorable outcome. Multivariate analysis revealed that both profiles were independent factors influencing prognosis. The OS of patients with IDH1-positive/MGMT-negative profiles was significantly longer than that of patients with negative/negative and negative/positive profiles. A p53 profile was not an independent prognostic factor. However, for GBM/AA patients with IDH1-negative/MGMT-negative profiles, p53 overexpression was significantly associated with an unfavorable outcome. Thus, the immunohistochemical profiles of IDH1 and MGMT are of considerable significance in gliomas, and a combination of IDH1, MGMT and p53 profiles may be useful for prognostication of GBM/AA.

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  • Cortico-cortical activity between the primary and supplementary motor cortex: An intraoperative near-infrared spectroscopy study. 査読 国際誌

    Masafumi Fukuda, Tetsuro Takao, Tetsuya Hiraishi, Hiroshi Aoki, Ryosuke Ogura, Yosuke Sato, Yukihiko Fujii

    Surgical neurology international   6   44 - 44   2015年

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    記述言語:英語  

    BACKGROUND: The supplementary motor area (SMA) makes multiple reciprocal connections to many areas of the cerebral cortices, such as the primary motor cortex (PMC), anterior cingulate cortex, and various regions in the parietal somatosensory cortex. In patients with SMA seizures, epileptic discharges from the SMA rapidly propagate to the PMC. We sought to determine whether near-infrared spectroscopy (NIRS) is able to intraoperatively display hemodynamic changes in epileptic network activities between the SMA and the PMC. CASE DESCRIPTIONS: In a 60-year-old male with SMA seizures, we intraoperatively delivered a 500 Hz, 5-train stimulation to the medial cortical surface and measured the resulting hemodynamic changes in the PMC by calculating the oxyhemoglobin (HbO2) and deoxyhemoglobin (HbR) concentration changes during stimulation. No hemodynamic changes in the lateral cortex were observed during stimulation of the medial surface corresponding to the foot motor areas. In contrast, both HbO2 and HbR increased in the lateral cortex corresponding to the hand motor areas when the seizure onset zone was stimulated. In the premotor cortex and the lateral cortex corresponding to the trunk motor areas, hemodynamic changes showed a pattern of increased HbO2 with decreased HbR. CONCLUSIONS: This is the first reported study using intraoperative NIRS to characterize the epileptic network activities between the SMA and PMC. Our intraoperative NIRS procedure may thus be useful in monitoring the activities of cortico-cortical neural pathways such as the language system.

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  • Accumulation of 2-hydroxyglutarate in gliomas correlates with survival: a study by 3.0-tesla magnetic resonance spectroscopy. 査読 国際誌

    Manabu Natsumeda, Hironaka Igarashi, Toshiharu Nomura, Ryosuke Ogura, Yoshihiro Tsukamoto, Tsutomu Kobayashi, Hiroshi Aoki, Kouichirou Okamoto, Akiyoshi Kakita, Hitoshi Takahashi, Tsutomu Nakada, Yukihiko Fujii

    Acta neuropathologica communications   2   158 - 158   2014年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BIOMED CENTRAL LTD  

    INTRODUCTION: Previous magnetic resonance spectroscopy (MRS) and mass spectroscopy studies have shown accumulation of 2-hydroxyglutarate (2HG) in mutant isocitrate dehydrogenase (IDH) gliomas. IDH mutation is known to be a powerful positive prognostic marker in malignant gliomas. Hence, 2HG accumulation in gliomas was assumed to be a positive prognostic factor in gliomas, but this has not yet been proven. Here, we analyzed 52 patients harboring World Health Organization (WHO) grade II and III gliomas utilizing 3.0-tesla MRS. RESULTS: Mutant IDH gliomas showed significantly higher accumulation of 2HG (median 5.077 vs. 0.000, p =0.0002, Mann-Whitney test). 2HG was detectable in all mutant IDH gliomas, whereas in 10 out of 27 (37.0%) wild-type IDH gliomas, 2HG was below the detectable range (2HG =0) (p =0.0003, chi-squared test). Screening for IDH mutation by 2HG analysis was highly sensitive (cutoff 2HG =1.489 mM, sensitivity 100.0%, specificity 72.2%). Gliomas with high 2HG accumulation had better overall survival than gliomas with low 2HG accumulation (p =0.0401, Kaplan-Meier analysis). DISCUSSION: 2HG accumulation detected by 3.0-tesla MRS not only correlates well with IDH status, but also positively correlates with survival in WHO grade II and III gliomas.

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  • Cerebral amyloid angiopathy-related leukoencephalopathy: successful steroid treatment for neurological deficits and subcortical white matter lesions partly involving the cortical gray matter 査読

    Neurology and Clinical Neuroscience   2 ( 4 )   119 - 121   2014年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

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  • "Gliomatosis encephali" as a novel category of brain tumors by the first autopsy case report of gliomatosis cerebelli. 査読 国際誌

    Asa Nakahara, Toshikazu Yoshida, Masanobu Yazawa, Takashi Ehara, Jun Nakayama, Akiyoshi Kakita, Ryosuke Ogura, Mika Asakawa, Emi Suzuki-Kouyama, Kiyomitsu Oyanagi

    Neuropathology : official journal of the Japanese Society of Neuropathology   34 ( 3 )   295 - 303   2014年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL  

    Gliomatosis cerebri is a rare diffuse glioma that is neither mass-forming nor necrotic, and does not disrupt existing structures. Gliomatosis occurring in the cerebellum is known as gliomatosis cerebelli, and only three such cases examined by biopsy have been reported. Here we describe the first autopsy findings of a patient who was diagnosed as having gliomatosis in the cerebellum. Neuropathological examination identified the tumor cells as being positive for glial fibrillary acidic protein, vimentin and nestin, with atypical nuclei that were cashew-nut- or dishcloth-gourd-shaped. These tumor cells were dense in the right cerebellum, but also spread broadly throughout the brain including the left cerebrum and optic nerve. Mitotic figures were frequently seen in the cerebellum, brain stem and cerebrum. Scherer's secondary structures were evident not only in the cerebellum but also the cerebrum. No necrosis, microvascular proliferation or destruction of anatomical structures was detected in the whole brain. Differences in the origin of the tumors of the gliomatoses cerbri and cerebelli suggests these tumors are different types of brain tumors. Thus the findings support that the gliomatosis cerebelli is a novel type of brain tumor classification. Furthermore, by the similarities of the histological features among the tumors, it appears appropriate to establish a novel category of "gliomatosis encephali" which includes both gliomatosis cerebri and gliomatosis cerebelli.

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  • Entrapment of the inferior horns of the lateral ventricle with enlargement of the bilateral choroid plexus. 査読 国際誌

    Ryosuke Ogura, Junichi Yoshimura, Masakazu Sano, Shouichi Kawasaki, Kenichi Nishiyama, Kouichirou Okamoto, Hitoshi Takahashi, Yukihiko Fujii, Akiyoshi Kakita

    Neuropathology : official journal of the Japanese Society of Neuropathology   34 ( 2 )   210 - 3   2014年4月

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    担当区分:筆頭著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL  

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  • Neuronal differentiation associated with Gli3 expression predicts favorable outcome for patients with medulloblastoma. 査読 国際誌

    Hiroaki Miyahara, Manabu Natsumeda, Junichi Yoshimura, Ryosuke Ogura, Kenichi Okazaki, Yasuko Toyoshima, Yukihiko Fujii, Hitoshi Takahashi, Akiyoshi Kakita

    Neuropathology : official journal of the Japanese Society of Neuropathology   34 ( 1 )   1 - 10   2014年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL  

    Medulloblastoma (MB) is a malignant cerebellar tumor arising in children, and its ontogenesis is regulated by Sonic Hedgehog (Shh) signaling. No data are available regarding the correlation between expression of Gli3, a protein lying downstream of Shh, and neuronal differentiation of MB cells, or the prognostic significance of these features. We re-evaluated the histopathological features of surgical specimens of MB taken from 32 patients, and defined 15 of them as MB with neuronal differentiation (ND), three as MB with both glial and neuronal differentiation (GD), and 14 as differentiation-free (DF) MB. Gli3-immunoreactivity (IR) was evident as a clear circular stain outlining the nuclei of the tumor cells. The difference in the frequency of IR between the ND+GD (94.4%) and DF (0%) groups was significant (P < 0.001). The tumor cells with ND showed IR for both Gli3 and neuronal nuclei. Ultrastructurally, Gli3-IR was observed at the nuclear membrane. The overall survival and event-free survival rates of the patients in the ND group were significantly higher than those in the other groups. The expression profile of Gli3 is of considerable significance, and the association of ND with this feature may be prognostically favorable in patients with MB.

    DOI: 10.1111/neup.12052

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  • Malignant peripheral nerve sheath tumor of the trigeminal nerve: clinicopathologic features in a young adult patient. 査読 国際誌

    Yoko Nakayama, Masatoshi Watanabe, Kenji Suzuki, Hiroyuki Usuda, Iwao Emura, Ryosuke Ogura, Atsushi Shiga, Yasuko Toyoshima, Hitoshi Takahashi, Tadashi Kawaguchi, Akiyoshi Kakita

    Neuropathology : official journal of the Japanese Society of Neuropathology   33 ( 5 )   541 - 6   2013年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Malignant peripheral nerve sheath tumors (MPNSTs) arising from cranial nerves are rare and usually affect adults. Here we report the clinicopathologic features of a young adult patient with a trigeminal nerve MPNST, in whom another tumor involving the oculomotor nerve on the contralateral side was evident. The patient, an 18-year-old woman, had suffered recurrent paroxysmal sharp stabbing pain over her cheek and forehead on the right side for 1 month. A brain MRI study disclosed a mass, 35 mm in diameter, in the right Meckel's cave, and another mass, 10 mm in diameter, involving the intracranial portion of the left oculomotor nerve. Following gadolinium administration, the former and latter tumors exhibited strong and weak enhancement, respectively. The patient had no clinical stigmata characteristic of neurofibromatosis type 1. Following a tentative diagnosis of schwannoma, total resection of the trigeminal nerve tumor was performed. Histologically, the tumor consisted of highly cellular, spindle-shaped cells arranged in a fascicular pattern, with occasional mitotic figures, nuclear pleomorphism and necrosis. Immunohistochemically, the tumor cells showed variable intensities and frequencies of reactivity for S-100 protein, myelin basic protein, CD34, podoplanin and p53, but no reactivity for Smarcb1. Thus, the tumor exhibited features of MPNST. This case appears to provide information that is useful for accurate diagnosis and surgical planning in patients with bilateral or multiple cranial nerve tumors.

    DOI: 10.1111/neup.12004

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  • Epstein-Barr virus-associated primary central nervous system cytotoxic T-cell lymphoma. 査読 国際誌

    Ryosuke Ogura, Hiroshi Aoki, Manabu Natsumeda, Hiroshi Shimizu, Tsutomu Kobayashi, Tomohisa Saito, Jun Takizawa, Kouichirou Okamoto, Go Hasegawa, Hajime Umezu, Kouichi Ohshima, Hitoshi Takahashi, Yukihiko Fujii, Akiyoshi Kakita

    Neuropathology : official journal of the Japanese Society of Neuropathology   33 ( 4 )   436 - 41   2013年8月

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    担当区分:筆頭著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL  

    Primary central nervous system lymphoma (PCNSL) expressing T-cell markers is rare, among which nasal-type extranodal NK/T-cell lymphoma is an extremely rare subtype associated with Epstein-Barr virus (EBV) infection. Here we report the clinicopathologic features of a case of EBV-associated PCNSL showing a cytotoxic T-cell phenotype. The patient, a 73-year-old woman, presented with rapidly progressive mental deterioration. Brain MRI revealed multiple lesions with swelling in the bilateral cerebral hemispheres, which were hypointense on T1-weighted images, hyperintense on T2-weighted and fluid-attenuated inversion recovery images, and slightly hyperintense on diffusion-weighted images. Biopsy specimens from the temporal region showed many medium-sized anaplastic lymphocytic cells with perivascular and angio-invasive patterns in the cortex. Immunohistochemically, the cells were positive for CD3, CD8, T-cell-restricted intracellular antigen-1 (TIA-1), granzyme B and perforin, but negative for CD56 and CD20. In situ hybridization revealed EBV-encoded RNAs in the tumor cell nuclei. A rearrangement study showed T-cell receptor γ-chain gene rearrangement with a clonal appearance. The patient died 6 months after surgery, and a general autopsy revealed no lymphoma cells outside the brain. These cellular profiles are inconsistent with those of extranodal NK/T-cell lymphoma, and have not been previously described. This case appears to represent an unusual CNS manifestation of EBV-associated T-cell lymphoma.

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  • [Intraoperative monitoring of motor evoked potentials during glioma removal]. 査読

    Masafumi Fukuda, Makoto Oishi, Tetsuro Takao, Tetsuya Hiraishi, Tsutomu Kobayashi, Hiroshi Aoki, Ryosuke Ogura, Akihiko Saito, Yukihiko Fujii

    No shinkei geka. Neurological surgery   41 ( 3 )   219 - 27   2013年3月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

    OBJECTIVE: To determine whether motor evoked potentials(MEPs)provide reliable monitoring of the motor system during resection of gliomas in or adjacent to the motor cortex or pyramidal tract. MATERIALS AND METHODS: MEP recording was performed during 64 operations in 55 patients harboring gliomas. Intraoperative MEP findings were classified into 3 groups:Group A was defined as having no significant MEP changes, Group B as having reversible MEP changes(?50% amplitude decrease or loss), and Group C as having irreversible changes. Postoperative motor function was evaluated according to the presence/absence of deterioration immediately after surgery and 1 month later, as compared to preoperative motor status RESULTS: Immediately after surgery, 13 of 39(33%)patients in Group A, 6 of 17(35%)in Group B, and 7 of 8(88%)in Group C experienced deterioration of motor function. One month after surgery, 4 of 39(10%)patients in Group A, 3 of 17(18%)in Group B, and 4 of 8(50%)showed deterioration of motor function. Both immediately(χ2=8.3, p<0.05)and 1 month(χ2=6.9, p<0.05)after surgery, MEP alterations correlated significantly with postoperative deterioration of motor function. Despite MEPs being stable throughout surgery(Group A), there were some patients with deterioration of motor function initially appearing to represent false negative monitoring. However, these deteriorations were confirmed to have been caused by secondary hemorrhage, venous return dysfunction, postoperative convulsion, or resection of the supplementary motor area. CONCLUSIONS: MEP monitoring provides reliable information on the motor system during glioma surgery. Although false negative MEP results may exist in some patients, most data were not influenced by intraoperative manipulation but rather were attributable to secondary postoperative events.

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  • グリオーマ摘出術中の運動誘発電位モニタリングの有用性と限界

    福多 真史, 大石 誠, 高尾 哲郎, 平石 哲也, 小林 勉, 青木 洋, 小倉 良介, 斉藤 明彦, 藤井 幸彦

    Neurological Surgery   41 ( 3 )   219 - 227   2013年3月

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    記述言語:日本語   出版者・発行元:(株)医学書院  

    運動野および錐体路近傍のグリオーマ摘出術55例64回(男34例、女21例、平均43.5歳)を対象に、術中皮質刺激による運動誘発電位(MEP)モニタリングの有用性について検討した。術中MEPの振幅低下を認めなかったのは39例(A群)、一時的に振幅低下や反応消失を認め、最終的に回復したのは17例(B群)、回復なしが8例(C群)であった。術翌日に上肢の運動機能が術前に比較して悪化していたのはA群13例(33%)、B群6例(35%)、C群7例(88%)で、3群間に有意差が認められた。A群悪化例のうち、補足運動野症候群を呈したのが6例、術直後のけいれん発作、静脈灌流障害、術直後の出血による悪化が各1例であった。C群で悪化を認めなかった1例は、MEPが最終的に50%以下となった症例であった。術後1ヵ月目の悪化はA群4例、B群3例、C群4例と減少し、A群の内訳は補足運動野症候群の回復過程、術後の頻回なけいれん発作、腫瘍の再増大、照射中の浮腫増強であった。

    DOI: 10.11477/mf.1436101949

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  • Occurrence of metachronous pure germinomas long after treatment of a mixed germ cell tumor containing yolk sac tumor and germinoma. 査読 国際誌

    Shinya Jinguji, Kouichirou Okamoto, Junichi Yoshimura, Yuichiro Yoneoka, Ryousuke Ogura, Akihiko Saito, Yukihiko Fujii

    Journal of neurosurgery. Pediatrics   11 ( 1 )   68 - 73   2013年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The authors report a rare case involving the occurrence of metachronous pure germinomas long after treatment of a mixed germ cell tumor (GCT) categorized as having a poor prognosis. A neurohypophysial germinoma occurred 4 years and 6 months after the initial treatment of a mixed pineal GCT containing a yolk sac tumor and a germinoma. Furthermore, intramedullary germinomas occurred 21 years after the initial treatment of the mixed GCT and 15 years after the second treatment of the neurohypophysial germinoma. The neurohypophysial germinoma was not confirmed histopathologically, but the intramedullary germinoma was histopathologically diagnosed as a pure germinoma. Serum α-fetoprotein levels at the second neurohypophysial and third intramedullary occurrences of the germinomas were less than 10 ng/ml. Therefore, no yolk sac components seemed to be contained in the tumors. The second neurohypophysial and third intramedullary germinomas might be recurrences of the germinoma component of the pineal mixed GCT, which consisted of a yolk sac tumor and a germinoma. However, it seems very unlikely that only the germinoma, categorized in the good prognosis group, would be the only one to recur. Hence, it seems plausible that both the second and the third occurrences of pure germinoma were de novo metachronous GCTs arising after the pineal mixed GCT was cured. The authors' case indicates the possibility of multicentric GCTs in the CNS.

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  • Advantages of dose-dense methotrexate protocol for primary central nervous system lymphoma: comparison of two different protocols at a single institution. 査読

    Hiroshi Aoki, Ryosuke Ogura, Yoshihiro Tsukamoto, Masayasu Okada, Manabu Natsumeda, Mizuho Isogawa, Seiichi Yoshida, Yukihiko Fujii

    Neurologia medico-chirurgica   53 ( 11 )   797 - 804   2013年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The efficacy and toxicity of high-dose methotrexate (HD-MTX)-based chemotherapy were retrospectively reviewed in patients with primary central nervous system lymphoma (PCNSL). All immunocompetent patients with histologically or radiographically diagnosed PCNSL treated between 2006 and 2012 at Niigata University Hospital were enrolled. Thirty-eight patients with a diagnosis of PCNSL were treated with one of two regimens during different time periods. During the first period, from 2006 to 2009, three 3-week cycles of MPV (MTX + procarbazine + vincristine) were administered (MPV3 group). In the second period, from 2010 to 2012, five 2-week cycles of MTX were administered (MTX5 group). High-dose cytarabine was used in both groups following HD-MTX-based chemotherapy. Whole-brain radiotherapy was used for patients who did not attain a complete response (CR) based on magnetic resonance images. In the MPV3 group, 20 out of 23 patients (87%) completed the planned treatment. The CR rate after chemotherapy was 30%, and 57% after radiation therapy. Thirteen out of 15 patients (87%) in the MTX5 group completed the planned treatment. The CR rates after chemotherapy and radiation therapy were 53% and 93%, respectively. Renal dysfunction was assessed by measuring creatinine clearance rates, which were very similar in both groups. In terms of hematologic toxicity and other adverse reactions, there was no significant difference between the two groups. In conclusion, dose-dense MTX chemotherapy improved outcome with acceptable toxicity compared with the treatment schedule for three cycles of MPV treatment.

    DOI: 10.2176/nmc.oa2013-0195

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  • Identification of a gene expression signature that predicts outcome in primary central nervous system lymphoma patients 査読

    18 ( 20 )   2012年

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    記述言語:英語  

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共同研究・競争的資金等の研究

  • 難治性髄膜腫に対するSSTR2aを標的とした近赤外光線免疫療法の開発

    研究課題/領域番号:22K16652

    2022年4月 - 2025年3月

    制度名:科学研究費助成事業

    研究種目:若手研究

    提供機関:日本学術振興会

    小倉 良介

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    配分額:4550000円 ( 直接経費:3500000円 、 間接経費:1050000円 )

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  • ボリノスタットによるオートファジー誘導とMGMT抑制効果に関する研究

    研究課題/領域番号:26861141

    2014年4月 - 2016年3月

    制度名:科学研究費助成事業 若手研究(B)

    研究種目:若手研究(B)

    提供機関:日本学術振興会

    小倉 良介

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    配分額:3510000円 ( 直接経費:2700000円 、 間接経費:810000円 )

    ヒストン脱アセチル化酵素阻害剤であるボリノスタットには、悪性神経膠腫の薬剤耐性のひとつであるMGMT活性を抑制する作用を有するが、その機序は不明な点が多い。本研究では、オートファジーとの関係に注目し、ボリノスタットによるMGMT活性を抑制する機序について検討した。MGMTがテモゾロミド耐性を発揮するためには、核内に局在している必要がある可能性が示唆された。さらに核外で過剰に発現したMGMT蛋白は、シャペロン介在性オートファジーで分解される可能性が示唆された。本研究を通して、MGMT蛋白をはじめとする薬剤耐性酵素の局在を変化させることは、薬剤耐性克服の新たな治療戦略である可能性が示唆された。

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