Yamaguchi Shigeru

Faculty of Medicine Specialized Medicine Neurological DisorderLecturer
Hokkaido University HospitalLecturer
Last Updated :2025/06/07

■Researcher basic information

Researchmap personal page

Research Field

  • Life sciences, Neurosurgery, Brain tumor

Educational Organization

■Career

Career

  • Apr. 2021
    Department of Neurosurgery, Faculty of Medicine, Hokkaido University, 講師, Japan
  • Jan. 2019 - Mar. 2021
    Hokkaido University Hospital, Department of Neurosurgery, Lecturer, Japan
  • Apr. 2017 - Dec. 2018
    Hokkaido University Hospital, Department of Neurosurgery, Assistant Professor
  • Aug. 2014 - Mar. 2017
    ,Graduate School of Medicine, Hokkaido University, Department of Nuclear Medicine, Assistant Professor
  • Sep. 2013 - Jul. 2014
    Hokkaido University, Hokkaido University Hospital, 医員
  • Nov. 2011 - Aug. 2013
    Baylor College of Medicine, Department of Pediatric Neuro-oncology, Post-doctoral researcher
  • Apr. 2010 - Oct. 2011
    札幌麻生脳神経外科病院, 脳神経外科
  • Apr. 2009 - Mar. 2010
    Hokkaido University, Hokkaido University Hospital, 医員
  • Dec. 2007 - Mar. 2008
    函館中央病院, 脳神経外科
  • Oct. 2006 - Nov. 2007
    Hokkaido University, Hokkaido University Hospital
  • Oct. 2005 - Sep. 2006
    北海道脳神経外科記念病院, 脳神経外科
  • Apr. 2005 - Sep. 2005
    Hokkaido University, Hokkaido University Hospital
  • Oct. 2003 - Mar. 2005
    函館中央病院, 脳神経外科
  • Apr. 2003 - Sep. 2003
    Hokkaido University, School of Medicine

Educational Background

  • Apr. 2008 - Mar. 2011, Hokkaido University, Graduate School of Medicine, Department of Neurosurgery
  • Apr. 1997 - Mar. 2003, Hokkaido University, School of Medicine, 医学科

■Research activity information

Papers

  • Phase II trial of pathology-based tripartite treatment stratification for patients with CNS germ cell tumors: A long-term follow-up study.
    Hirokazu Takami, Masao Matsutani, Tomonari Suzuki, Kazuhiko Takabatake, Takamitsu Fujimaki, Michinari Okamoto, Shigeru Yamaguchi, Masayuki Kanamori, Kenichiro Matsuda, Yukihiko Sonoda, Manabu Natsumeda, Toshiya Ichinose, Mitsutoshi Nakada, Ai Muroi, Eiichi Ishikawa, Masamichi Takahashi, Yoshitaka Narita, Shota Tanaka, Nobuhito Saito, Fumi Higuchi, Masahiro Shin, Yohei Mineharu, Yoshiki Arakawa, Naoki Kagawa, Shinji Kawabata, Masahiko Wanibuchi, Takeshi Takayasu, Fumiyuki Yamasaki, Kentaro Fujii, Joji Ishida, Isao Date, Keisuke Miyake, Yutaka Fujioka, Daisuke Kuga, Shinji Yamashita, Hideo Takeshima, Naoki Shinojima, Akitake Mukasa, Akio Asai, Ryo Nishikawa
    Neuro-oncology, 27, 3, 828, 840, 07 Mar. 2025, [International Magazine]
    English, Scientific journal, BACKGROUND: A previous Phase II clinical trial, conducted from 1995 to 2003, evaluated CNS germ cell tumors (GCTs) using a three-group treatment stratification based on histopathology. The primary objective of the study was to assess the long-term efficacy of standardized treatment regimens, while the secondary objective focused on identifying associated long-term complications. METHODS: A total of 228 patients were classified into 3 groups for treatment: germinoma (n = 161), intermediate prognosis (n = 38), and poor prognosis (n = 28), excluding one mature teratoma case. Treatment involved stratified chemotherapy regimens and varied radiation doses/coverage. Clinical data was retrospectively analyzed at a median follow-up of 18.5 years. RESULTS: The treatment outcomes for germinoma, with or without syncytiotrophoblastic giant cells, were similar. The 10- and 20-year event-free survival rates for the germinoma, intermediate, and poor prognosis groups were 82/76/49% and 73/66/49%, respectively. Overall survival (OS) rates were 97/87/61% at 10 years and 92/70/53% at 20 years. Germinomas in the basal ganglia, treated without whole-brain radiation therapy (WBRT), frequently relapsed but were effectively managed with subsequent WBRT. Deaths in germinoma cases had varied causes, whereas deaths in the poor prognosis group were predominantly disease-related. Nineteen treatment-related complications were identified in 16 patients, with cumulative event rates of 1.9% at 10 years and 11.3% at 20 years. OS rates at 1 and 2 years post-relapse for tumors initially classified as germinoma, intermediate, and poor prognosis were 94/88/18% and 91/50/9%, respectively. CONCLUSIONS: Initial treatment intensity is crucial for managing non-germinomatous GCTs, while long-term follow-up for relapse and complications is imperative in germinomas. Irradiation extending beyond the immediate tumor site is essential for basal ganglia germinomas. Addressing relapse in non-germinomatous GCT remains a significant challenge.
  • Long-term outcome and social-intellectual ability of patients with basal ganglia germinoma
    Michinari Okamoto, Shigeru Yamaguchi, Ryosuke Sawaya, Yukitomo Ishi, Hiroaki Motegi, Yukayo Terashita, Minako Sugiyama, Yuko Cho, Kentaro Nishioka, Takashi Mori, Takayuki Hashimoto, Hidefumi Aoyama, Atsushi Manabe, Miki Fujimura
    Pediatric Neurology, Elsevier BV, Jan. 2025
    Scientific journal
  • Pretreatment pathology study in anti-LGI1 encephalitis.
    Kazuki Yamada, Hiroaki Yaguchi, Kaede Ishikawa, Daiki Tanaka, Yuki Oshima, Keiichi Mizushima, Shintaro Fujii, Taichi Nomura, Akihiko Kudo, Hisashi Uwatoko, Shinichi Shirai, Ikuko Takahashi-Iwata, Masaaki Matsushima, Riku Miyaishi, Noriyuki Otsuka, Zen-Ichi Tanei, Shigeru Yamaguchi, Keiko Tanaka, Koji Taniguchi, Shinya Tanaka, Ichiro Yabe
    Journal of the neurological sciences, 466, 123258, 123258, 27 Sep. 2024, [International Magazine]
    English
  • Cost of medical care for malignant brain tumors at hospitals in the Japan Clinical Oncology Group brain-tumor study group.
    Kazuya Motomura, Keita Sasaki, Narushi Sugii, Shigeru Yamaguchi, Hirotaka Inoue, Akito Oshima, Kazuhiro Tanaka, Yoshihiro Otani, Mitsuaki Shirahata, Ichiyo Shibahara, Motoo Nagane, Shunsuke Tsuzuki, Tomoo Matsutani, Yoshihiro Tsukamoto, Noriyuki Kijima, Kenichiro Asano, Makoto Ohno, Akihiro Inoue, Yohei Mineharu, Keisuke Miyake, Yuta Mitobe, Mitsuto Hanihara, Yu Kawanishi, Shoichi Deguchi, Masato Saito, Ryosuke Matsuda, Kenta Ujifuku, Hideyuki Arita, Yuichi Sato, Shinji Yamashita, Ushio Yonezawa, Junya Yamaguchi, Yasutomo Momii, Takahiro Ogawa, Atsushi Kambe, Shigeo Ohba, Junya Fukai, Norihiko Saito, Masashi Kinoshita, Koichiro Sumi, Ryohei Otani, Takeo Uzuka, Noriyoshi Takebe, Shinichiro Koizumi, Ryuta Saito, Yoshiki Arakawa, Yoshitaka Narita
    Japanese journal of clinical oncology, 54, 10, 1123, 1131, 02 Sep. 2024, [International Magazine]
    English, Scientific journal, BACKGROUND: This study aimed to investigate what treatment are selected for malignant brain tumors, particularly glioblastoma (GBM) and primary central nervous system lymphoma (PCNSL), in real-world Japan and the costs involved. METHODS: We conducted a questionnaire survey regarding treatment selections for newly diagnosed GBM and PCNSL treated between July 2021 and June 2022 among 47 institutions in the Japan Clinical Oncology Group-Brain Tumor Study Group. We calculated the total cost and cost per month of the initial therapy for newly diagnosed GBM or PCNSL. RESULTS: The most used regimen (46.8%) for GBM in patients aged ≤74 years was 'Surgery + radiotherapy concomitant with temozolomide'. This regimen's total cost was 7.50 million JPY (Japanese yen). Adding carmustine wafer implantation (used in 15.0%), TTFields (used in 14.1%), and bevacizumab (BEV) (used in 14.5%) to the standard treatment of GBM increased the cost by 1.24 million JPY for initial treatment, and 1.44 and 0.22 million JPY per month, respectively. Regarding PCNSL, 'Surgery (biopsy) + rituximab, methotrexate, procarbazine, and vincristine (R-MPV) therapy' was the most used regimen (42.5%) for patients of all ages. This regimen incurred 1.07 million JPY per month. The three PCNSL regimens based on R-MPV therapy were in ultra-high-cost medical care (exceeding 1 million JPY per month). CONCLUSIONS: Treatment of malignant brain tumors is generally expensive, and cost-ineffective treatments such as BEV are frequently used. We believe that the results of this study can be used to design future economic health studies examining the cost-effectiveness of malignant brain tumors.
  • Moyamoya syndrome after proton beam therapy in a pediatric patient with a pineal germ cell tumor and a germline polymorphism in RNF213.
    Ting-Chun Lin, Haruto Uchino, Masaki Ito, Shigeru Yamaguchi, Yukitomo Ishi, Miki Fujimura
    Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery, 21 Aug. 2024, [International Magazine]
    English, Scientific journal, The effects of RNF213, which leads to moyamoya disease susceptibility, on radiation-induced moyamoya syndrome (MMS) remain unknown. We report a case of MMS after proton beam therapy (PBT) was deployed to treat a brain tumor in a patient with an RNF213 polymorphism. An 8-year-old boy underwent whole ventricular and local PBT for a pineal germ cell tumor and was diagnosed with radiation-induced MMS 9 months later. He underwent right and left revascularization surgeries for cerebral hemodynamic compromise at 17- and 18-years of age, respectively. Genetic analysis revealed a heterozygous germline polymorphism RNF213 p.R4810K. This is the first report to suggest an association between RNF213 polymorphism and radiation-induced MMS.
  • Clinical outcome, radiological findings, and genetic features of IDH-mutant brainstem glioma in adults.
    Sogo Oki, Yukitomo Ishi, Ryosuke Sawaya, Michinari Okamoto, Hiroaki Motegi, Zen-Ichi Tanei, Masumi Tsuda, Takashi Mori, Kentaro Nishioka, Hiromi Kanno-Okada, Hidefumi Aoyama, Shinya Tanaka, Shigeru Yamaguchi, Miki Fujimura
    Acta neurochirurgica, 166, 1, 263, 263, 12 Jun. 2024, [International Magazine]
    English, Scientific journal, BACKGROUND: With the recent advent of genetic testing, IDH-mutant glioma has been found among adult brainstem gliomas. However, the clinical outcome and prognosis of IDH-mutant brainstem gliomas in adults have not been elucidated. This study aimed to investigate the clinical outcome, radiological findings, and genetic features of adult patients with IDH-mutant diffuse brainstem gliomas. METHODS: Data from adult patients with brainstem glioma at Hokkaido University Hospital between 2006 and 2022 were retrospectively analyzed. Patient characteristics, treatment methods, genetic features, and prognosis were evaluated. RESULTS: Of 12 patients with brainstem glioma with proven histopathology, 4 were identified with IDH mutation. All patients underwent local radiotherapy with 54 Gray in 27 fractions combined with chemotherapy with temozolomide. Three patients had IDH1 R132H mutation and one had IDH2 R172G mutation. The median progression-free survival and overall survival were 68.4 months and 85.2 months, respectively, longer than that for IDH-wildtype gliomas (5.6 months and 12.0 months, respectively). At the time of initial onset, contrast-enhanced lesions were observed in two of the four cases in magnetic resonance imaging. CONCLUSION: As some adult brainstem gliomas have IDH mutations, and a clearly different prognosis from those with IDH-wildtype, biopsies are proactively considered to confirm the genotype.
  • 今月の症例 腎移植30年後に発症した中枢神経原発移植後リンパ増殖性疾患の1例               
    石川 楓, 白井 慎一, 上床 尚, 岩田 育子, 松島 理明, 松川 敏大, 山口 秀, 矢口 裕章, 外丸 詩野, 矢部 一郎
    日本内科学会雑誌, 113, 6, 980, 985, (一社)日本内科学会, Jun. 2024
    Japanese
  • Pre- and post-operative semicircular canal function evaluated by video head impulse test in patients with vestibular schwannoma.
    Keishi Fujiwara, Shinya Morita, Hiroaki Motegi, Shigeru Yamaguchi, Yukitomo Ishi, Kimiko Hoshino, Atsushi Fukuda, Makoto Kobayashi, Yuji Nakamaru, Miki Fujimura, Akihiro Homma
    Auris, nasus, larynx, 51, 3, 542, 547, Jun. 2024, [International Magazine]
    English, Scientific journal, OBJECTIVES: To evaluate pre- and post-operative semicircular canal function in patients with vestibular schwannoma (VS) by the video Head Impulse Test (vHIT). METHODS: Nineteen patients with VS who underwent surgery were enrolled in this study. The gain in vestibulo-ocular reflex (VOR) and the degree of scatter in catch-up saccades were examined pre- and post-operatively for the semicircular canals in VS patients. RESULTS: Ten of 19 cases (52.6 %) with VS were defined as demonstrating both superior vestibular nerve (SVN) and inferior vestibular nerve (IVN) impairment from the results of pre-operative vHIT. Hearing level and subjective vestibular symptoms showed significant correlations with pre-operative semicircular canal function. Compared to pre-operative vHIT results, VOR gains within 1 month after surgery were significantly reduced in all three canals; however, significant differences had disappeared in the anterior and posterior semicircular canals at 6 months after surgery. Cases of unknown origin had a significantly greater reduction in posterior semicircular canal function after surgery compared with those with disease of IVN origin. CONCLUSIONS: As vHIT could evaluate pre-operative vestibular nerve impairment, post-operative VOR gain reduction and the degree of vestibular compensation, semicircular canal function evaluated by vHIT provides a good deal of useful information regarding VS patients undergoing surgery compared to caloric testing, and vHIT should be performed pre- and post-operatively for patients with VS.
  • Increased CD44 expression in primary meningioma: its clinical significance and association with peritumoral brain edema.
    Ryosuke Sawaya, Shigeru Yamaguchi, Yukitomo Ishi, Michinari Okamoto, Sumire Echizenya, Hiroaki Motegi, Noriyuki Fujima, Miki Fujimura
    Journal of neurosurgery, 141, 1, 1, 8, 09 Feb. 2024, [International Magazine]
    English, Scientific journal, OBJECTIVE: CD44 is a major cell surface receptor involved in cell adhesion and migration. The overexpression of CD44 is a poor prognostic factor in many neoplasms, including meningiomas. The aim of this study was to investigate the association between CD44 gene expression and clinical signatures of primary meningiomas. METHODS: CD44 gene expression was quantitatively evaluated by snap freezing tumor tissues obtained from 106 patients with primary meningioma. The relationships between CD44 expression and clinical signatures of meningiomas, including histological malignancy, tumor volume, and peritumoral brain edema (PTBE), were analyzed. PTBE was assessed using the Steinhoff classification (SC) system (from SC 0 to SC III). RESULTS: CD44 gene expression in WHO grade 2 and 3 meningiomas was significantly higher than that in grade 1 meningiomas. In addition, CD44 expression increased with the severity of PTBE. Particularly, among the grade 1 meningiomas or small-sized tumors (maximum tumor diameter < 43 mm), CD44 expression in tumors with severe PTBE (SC II or III) was significantly higher than that in tumors without or with mild PTBE (SC 0 or I). Multivariate logistic regression analysis also revealed that overexpression of CD44 was an independent significant factor of severe PTBE development in primary meningiomas. CONCLUSIONS: In addition to tumor cell aggressiveness, CD44 expression promotes the development of PTBE in meningioma. Since PTBE is a strong factor of tumor-related epilepsy or cognitive dysfunction in patients with meningioma, CD44 is thus a potential therapeutic target in meningioma with PTBE.
  • 当院における転移性脳腫瘍への術後定位照射症例の検討               
    高橋 周平, 森 崇, 打浪 雄介, 西岡 健太郎, 青山 英史, 茂木 洋晃, 山口 秀
    Japanese Journal of Radiology, 42, Suppl., 10, 10, (公社)日本医学放射線学会, Feb. 2024
    Japanese
  • Impact of tumor-treating fields on the survival of Japanese patients with newly diagnosed glioblastoma: A multicenter, retrospective cohort study
    Masayuki Kanamori, Shunsuke Tsuzuki, Ichiyo Shibahara, Kuniaki Saito, Yoshiteru Shimoda, Kazuhiro Tanaka, Shigeru Yamaguchi, Manabu Natsumeda, Tomoo Matsutani, Mitsuto Hanihara, Mitsutoshi Nakada, Jun-Ichiro Kuroda, Masahide Matsuda, Koji Yoshimoto, Ushio Yonezawa, Yukihiko Sonoda, Koji Takano, Hajime Yonezawa, Yoshihiro Otani, Yukiko Nakahara, Masashi Uchida, Masahiro Nonaka, Yohei Mineharu, Yohei Kitamura, Shinji Yamashita, Takahiro Yamauchi, Yohei Miyake, Shoichi Deguchi, Takaaki Beppu, Kaoru Tamura, Shinichiro Koizumi, Yuichi Hirose, Kenichiro Asano, Ryo Hiruta, Manabu Kinoshita, Keisuke Miyake, Noriyuki Nakayama, Akihiro Inoue, Takahiro Ono, Takahiro Sasaki, Yukinori Akiyama, Shinjiro Fukami, Atsuo Yoshino, Yu Kawanishi, Taku Asanome, Takuhiro Yamaguchi, Masamichi Takahashi, Fumiyuki Yamasaki, Yoshiki Arakawa, Yoshitaka Narita
    Neuro-Oncology Advances, 6, 1, Oxford University Press (OUP), 01 Jan. 2024
    Scientific journal, Abstract

    Background

    The EF-14 clinical trial demonstrated the safety and efficacy of tumor-treating fields (TTFields) for newly diagnosed glioblastoma. This study aimed to clarify the current status, safety, and efficacy of TTFields in Japanese patients who meet the EF-14 inclusion criteria.

    Methods

    This was a multicenter retrospective cohort study. Background, treatment, and outcome data of patients who satisfied the inclusion criteria of the EF-14 trial were collected from 45 institutions across Japan. The rate, determinants, and current status of TTField use, including its safety and efficacy in terms of progression and survival, were retrospectively investigated. This study was conducted in accordance with the STROBE checklist.

    Results

    Among the 607 patients enrolled, 70 were excluded due to progressive disease during radiation and temozolomide therapy, age &gt; 80 years old, and Karnofsky Performance Status score of &lt;70. Among the remaining 537 patients, 210 (39%) underwent TTField treatment. Multivariate analysis revealed younger age and spouse as a caregiver as significant factors for TTField use. The compliance rate of TTField use exceeded 75% in 60% of patients, with a median TTField usage duration of 11 months. Skin disorders requiring medical treatment occurred in 56% of patients. Multivariate Cox proportional hazards analysis in the whole series and propensity score-matched analysis revealed that TTField use was not a prognostic factor for progression-free survival (PFS) or overall survival (OS).

    Conclusions

    TTField use did not have a substantial effect on either PFS or OS in Japanese patients with glioblastoma, despite compliance rates comparable to those observed in the EF-14.
  • Identifying G6PC3 as a Potential Key Molecule in Hypoxic Glucose Metabolism of Glioblastoma Derived from the Depiction of 18F-Fluoromisonidazole and 18F-Fluorodeoxyglucose Positron Emission Tomography.
    Michinari Okamoto, Shigeru Yamaguchi, Ryosuke Sawaya, Sumire Echizenya, Yukitomo Ishi, Sadahiro Kaneko, Hiroaki Motegi, Takuya Toyonaga, Kenji Hirata, Miki Fujimura
    BioMed research international, 2024, 2973407, 2973407, 2024, [International Magazine]
    English, Scientific journal, PURPOSE: Glioblastoma is the most aggressive primary brain tumor, characterized by its distinctive intratumoral hypoxia. Sequential preoperative examinations using fluorine-18-fluoromisonidazole (18F-FMISO) and fluorine-18-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) could depict the degree of glucose metabolism with hypoxic condition. However, molecular mechanism of glucose metabolism under hypoxia in glioblastoma has been unclear. The aim of this study was to identify the key molecules of hypoxic glucose metabolism. METHODS: Using surgically obtained specimens, gene expressions associated with glucose metabolism were analyzed in patients with glioblastoma (n = 33) who underwent preoperative 18F-FMISO and 18F-FDG PET to identify affected molecules according to hypoxic condition. Tumor in vivo metabolic activities were semiquantitatively evaluated by lesion-normal tissue ratio (LNR). Protein expression was confirmed by immunofluorescence staining. To evaluate prognostic value, relationship between gene expression and overall survival was explored in another independent nonoverlapping clinical cohort (n = 17) and validated by The Cancer Genome Atlas (TCGA) database (n = 167). RESULTS: Among the genes involving glucose metabolic pathway, mRNA expression of glucose-6-phosphatase 3 (G6PC3) correlated with 18F-FDG LNR (P = 0.03). In addition, G6PC3 mRNA expression in 18F-FMISO high-accumulated glioblastomas was significantly higher than that in 18F-FMISO low-accumulated glioblastomas (P < 0.01). Protein expression of G6PC3 was consistent with mRNA expression, which was confirmed by immunofluorescence analysis. These findings indicated that the G6PC3 expression might be facilitated by hypoxic condition in glioblastomas. Next, we investigated the clinical relevance of G6PC3 in terms of prognosis. Among the glioblastoma patients who received gross total resection, mRNA expressions of G6PC3 in the patients with poor prognosis (less than 1-year survival) were significantly higher than that in the patients who survive more than 3 years. Moreover, high mRNA expression of G6PC3 was associated with poor overall survival in glioblastoma, as validated by TCGA database. CONCLUSION: G6PC3 was affluently expressed in glioblastoma tissues with coincidentally high 18F-FDG and 18F-FMISO accumulation. Further, it might work as a prognostic biomarker of glioblastoma. Therefore, G6PC3 is a potential key molecule of glucose metabolism under hypoxia in glioblastoma.
  • Clinical outcomes for olfactory neuroblastoma.
    Akira Nakazono, Hiroaki Motegi, Masanobu Suzuki, Yuji Nakamaru, Shigeru Yamaguchi, Yukitomo Ishi, Satoshi Kano, Nayuta Tsushima, Aya Honma, Takayoshi Suzuki, Shogo Kimura, Seijiro Hamada, Jun Taguchi, Yasushi Shimizu, Takashi Mori, Koichi Yasuda, Hidefumi Aoyama, Ichiro Kinoshita, Miki Fujimura, Akihiro Homma
    Frontiers in oncology, 14, 1329572, 1329572, 2024, [International Magazine]
    English, Scientific journal, BACKGROUND: Olfactory neuroblastoma (ONB) is a rare malignant tumor arising from the olfactory neuroepithelium. The standard of care for ONB is surgical resection; however, detailed treatment protocols vary by institution. Our treatment protocol consists of endoscopic skull base surgery (ESBS) for endoscopically resectable cases and induction chemotherapy followed by craniotomy combined with ESBS for locally advanced cases, with postoperative radiotherapy performed for all cases. Chemoradiotherapy (CRT) is performed in unresectable cases. In this study, we evaluate our treatment protocol and outcomes for ONB. METHODS: A retrospective review of patients with ONB was conducted. Outcomes included survival outcomes and perioperative data. RESULTS: Fifteen patients (53.6%) underwent ESBS, 12 (42.9%) underwent craniotomy combined with ESBS, and 1 (3.6%) received CRT. The 5- and 10-year overall survival rates for all patients were 92.9% and 82.5%, respectively, with a median follow-up period of 81 months. The 5- and 10-year disease-free survival rates were 77.3% and 70.3%, respectively, and the 5- and 10-year local control rates were 88.2% and 80.2%, respectively. Patients undergoing ESBS demonstrated a significantly shorter operating time, period from operation to ambulation, hospitalization period, and less blood loss than those undergoing craniotomy combined with ESBS. CONCLUSION: Our treatment protocol was found to afford favorable outcomes. Patients who underwent endoscopic resection showed lower complication rates and better perioperative data than those who underwent craniotomy combined with ESBS. With appropriate case selection, ESBS is considered a useful approach for ONB.
  • [Medulloblastoma].
    Shigeru Yamaguchi, Miki Fujimura
    No shinkei geka. Neurological surgery, 51, 5, 858, 866, Sep. 2023, [Domestic magazines]
    Japanese, Scientific journal, In the 5th edition of the WHO classification, medulloblastomas, which are representative pediatric brain tumors, are categorized into four groups: WNT, SHH-TP53 wild, SHH-TP53 mutant, and non-WNT/non-SHH, based on their molecular background. While the histopathological findings still hold importance in predicting prognosis, the histopathological classification is no longer utilized in this edition. SHH medulloblastomas are further subdivided into two groups based on the presence or absence of TP53 mutation, as their clinical characteristics and prognosis differ. Group 3 and Group 4 medulloblastomas, recognized as distinct molecular groups in clinical practice, are combined into a single group called "non-WNT/non-SHH", because they lack specific molecular pathway activation. Furthermore, based on methylation profiling, dividing SHH medulloblastoma into four subgroups and non-WNT/non-SHH medulloblastoma into eight subgroups was proposed. Understanding the unique clinical characteristics and prognosis associated with each group is crucial. However, it is important to acknowledge that our current understanding of prognosis is based on treatment approaches guided by clinical risk factors such as postoperative residual tumor volume and the presence of metastatic disease. This molecular-based classification holds promise in guiding the development of optimal treatment strategies for patients with medulloblastoma.
  • Slow-growing WNT medulloblastoma with atypical magnetic resonance imaging findings: illustrative case.
    Makoto Mizushima, Michinari Okamoto, Shigeru Yamaguchi, Sogo Oki, Hiroaki Motegi, Minako Sugiyama, Atsushi Manabe, Ai Shimizu, Kentaro Nishioka, Takayuki Hashimoto, Junko Hirato, Yonehiro Kanemura, Miki Fujimura
    Journal of neurosurgery. Case lessons, 6, 7, 14 Aug. 2023, [International Magazine]
    English, Scientific journal, BACKGROUND: Medulloblastomas, with four molecular subgroups, are generally rapid-growing tumors with significant contrast enhancement and well-defined margins. However, each subgroup's clinical features, including disease time course and imaging characteristics, are not well defined. OBSERVATIONS: The authors describe the case of a 15-year-old female who presented with a 7-month history of impaired left-hand movement and was found to have a lesion on the dorsal side of the fourth ventricle. T2-weighted magnetic resonance imaging (MRI) at the patient's first presentation showed diffuse hyperintense signal without apparent mass, and gadolinium-enhanced T1-weighted imaging showed very slight contrast enhancement. In 1 month, her symptoms progressed, and follow-up MRI revealed an increase in the size of the lesion, showing greater diffusion restriction and contrast enhancement. She underwent gross-total resection, and pathology was consistent with classic medulloblastoma. Genetic analysis of the tumor confirmed the wingless (WNT) molecular subgroup. Adjuvant chemotherapy and proton beam therapy were performed. At the 18-month follow-up, MRI showed no recurrence of disease. LESSONS: Slow-growing medulloblastoma is very rare and not known to be associated with a specific molecular subgroup. Here, the authors report a case of slow-growing WNT medulloblastoma, indicating that slow growth may be a feature of this subgroup.
  • AT/RTのEZH2およびBRD4を標的とした新規治療               
    伊師 雪友, ツァン・ヨンザン, ツァン・アリ, 佐々木 貴浩, 渡邊 潤, 阿部 幸喜, 棗田 学, 山口 秀, 藤村 幹, 橋詰 倫太郎
    Brain Tumor Pathology, 40, Suppl., 109, 109, 日本脳腫瘍病理学会, May 2023
    Japanese
  • The need of radiotherapy optimization for glioblastomas considering immune responses.
    Kentaro Nishioka, Shuhei Takahashi, Takashi Mori, Yusuke Uchinami, Shigeru Yamaguchi, Manabu Kinoshita, Masaaki Yamashina, Hajime Higaki, Katsuya Maebayashi, Hidefumi Aoyama
    Japanese journal of radiology, 41, 10, 1062, 1071, 18 Apr. 2023, [Domestic magazines]
    English, Scientific journal, Glioblastoma is the most common of malignant primary brain tumors and one of the tumors with the poorest prognosis for which the overall survival rate has not significantly improved despite recent advances in treatment techniques and therapeutic drugs. Since the emergence of immune checkpoint inhibitors, the immune response to tumors has attracted increasing attention. Treatments affecting the immune system have been attempted for various tumors, including glioblastomas, but little has been shown to be effective. It has been found that the reason for this is that glioblastomas have a high ability to evade attacks from the immune system, and that the lymphocyte depletion associated with treatment can reduce its immune function. Currently, research to elucidate the resistance of glioblastomas to the immune system and development of new immunotherapies are being vigorously carried out. Targeting of radiation therapy for glioblastomas varies among guidelines and clinical trials. Based on early reports, target definitions with wide margins are common, but there are also reports that narrowing the margins does not make a significant difference in treatment outcome. It has also been suggested that a large number of lymphocytes in the blood are irradiated by the irradiation treatment to a wide area in a large number of fractionations, which may reduce the immune function, and the blood is being recognized as an organ at risk. Recently, a randomized phase II trial comparing two types of target definition in radiotherapy for glioblastomas was conducted, and it was reported that the overall survival and progression-free survival were significantly better in a small irradiation field group. We review recent findings on the immune response and the immunotherapy to glioblastomas and the novel role of radiotherapy and propose the need to develop an optimal radiotherapy that takes radiation effects on the immune function into account.
  • Supratentorial multifocal gliomas associated with Ollier disease harboring IDH1 R132H mutation: A case report.
    Hiroshi Ikeda, Shigeru Yamaguchi, Yukitomo Ishi, Kento Wakabayashi, Ai Shimizu, Hiromi Kanno-Okada, Takeshi Endo, Mitsutoshi Ota, Michinari Okamoto, Hiroaki Motegi, Norimasa Iwasaki, Miki Fujimura
    Neuropathology : official journal of the Japanese Society of Neuropathology, 43, 5, 413, 420, 20 Mar. 2023, [International Magazine]
    English, Somatic mosaicism of isocitrate dehydrogenase 1/2 (IDH1/2) mutation is a cause of Ollier disease (OD), characterized by multiple enchondromatosis. A 35-year-old woman who was diagnosed with OD at age 24 underwent resection surgery for multifocal tumors located at the right and left frontal lobes that were discovered incidentally. No apparent spatial connection was observed on preoperative magnetic resonance imaging. Pathological examinations revealed tumor cells with a perinuclear halo in the left frontal lobe tumor, whereas astrocytic tumor cells were observed in the right frontal lobe tumor. Based on positive IDH1 R132H immunostaining and the result of 1p/19q fluorescent in situ hybridization, pathological diagnoses were IDH mutant and 1p/19q-codeleted oligodendroglioma in the right frontal lobe tumor and IDH mutant astrocytoma in the left frontal lobe tumor, respectively. The DNA sequencing revealed IDH1 R132H mutation in the peripheral blood sample and frontal lobe tumors. This case suggested that in patients with OD, astrocytoma and oligodendroglioma can co-occur within the same individual simultaneously, and IDH1 R132H mutation was associated with supratentorial development of gliomas.
  • Sunburst appearanceを呈する頭蓋骨腫瘤を契機に発見された神経芽腫の1例               
    北川 悠, 竹中 淳規, 渡邊 史郎, 平田 健司, 内山 裕子, 木村 理奈, 中川 純一, 池辺 洋平, 長谷河 昌孝, 澤井 彩織, 寺下 友佳代, 杉山 未奈子, 平林 真介, 長 祐子, 山口 秀, 真部 淳, 工藤 與亮
    北海道放射線医学雑誌, 3, 33, 36, (NPO)メディカルイメージラボ, Mar. 2023
    Japanese
  • 鞍上部に生じた毛様細胞性星細胞腫により続発性副腎皮質機能低下症を呈した1例
    関 萌花, 亀田 啓, 宮本 麻唯子, 小野 翼, 宮 愛香, 野本 博司, 曹 圭龍, 中村 昭伸, 山口 秀, 田中 伸哉, 三好 秀明, 渥美 達也
    日本内分泌学会雑誌, 98, 4, 718, 718, (一社)日本内分泌学会, Feb. 2023
    Japanese
  • Safety and efficacy of tumour-treating fields (TTFields) therapy for newly diagnosed glioblastoma in Japanese patients using the Novo-TTF System: a prospective post-approval study.
    Ryo Nishikawa, Fumiyuki Yamasaki, Yoshiki Arakawa, Yoshihiro Muragaki, Yoshitaka Narita, Shota Tanaka, Shigeru Yamaguchi, Akitake Mukasa, Masayuki Kanamori
    Japanese journal of clinical oncology, 53, 5, 371, 377, 16 Jan. 2023, [International Magazine]
    English, Scientific journal, BACKGROUND: Tumour-treating fields therapy is a locoregional, anti-cancer treatment. Efficacy and safety of tumour-treating fields therapy in adults with newly diagnosed glioblastoma were demonstrated in the pivotal phase 3 EF-14 study (NCT00916409). Here, we report post-approval data of tumour-treating fields therapy in Japanese patients with newly diagnosed glioblastoma. METHODS: Unsolicited post-marketing surveillance data from Japanese patients with newly diagnosed glioblastoma treated with tumour-treating fields therapy (December 2016-June 2020) were retrospectively analysed. The primary endpoints were skin, neurological and psychiatric adverse events. The secondary endpoints were 1- and 2-year overall survival rates, and the 6-month progression-free survival. adverse events were analysed using MedDRA v24.0. The overall survival and progression-free survival were assessed using the Kaplan-Meier survival analysis (log-rank testing). The Cox proportional hazard regression analyses were also performed. RESULTS: Forty patients with newly diagnosed glioblastoma were enrolled (62.5% male; median age 59 years; median baseline Karnofsky Performance Scale score 90). The most common tumour-treating-fields-therapy-related adverse event was beneath-array local skin reaction (60% of patients). The adverse events were mostly mild to moderate in severity. Neurological disorders were observed in 2.5% patients (one patient reported dysesthesia). No psychiatric disorders were reported. The 1- and 2-year overall survival rates were 77.9% (95% CI 60.6-88.3) and 53.6% (35.5-68.7%), respectively. The 6-month progression-free survival was 77.5% (61.2-87.6%). These survival rates compare favourably with those in the EF-14 trial (1- and 2-year overall survival rates: 73% [69-77%] and 43% [39-48%], respectively; 6-month progression-free survival rate: 56% (51-61%). CONCLUSION: This post-approval, real-world evidence study revealed no new safety signals and suggests the safety and efficacy of tumour-treating fields therapy in Japanese patients with newly diagnosed glioblastoma.
  • A common deletion at BAK1 reduces enhancer activity and confers risk of intracranial germ cell tumors
    Kyuto Sonehara, Yui Kimura, Yoshiko Nakano, Tatsuya Ozawa, Meiko Takahashi, Ken Suzuki, Takashi Fujii, Yuko Matsushita, Arata Tomiyama, Toshihiro Kishikawa, Kenichi Yamamoto, Tatsuhiko Naito, Tomonari Suzuki, Shigeru Yamaguchi, Tomoru Miwa, Hikaru Sasaki, Masashi Kitagawa, Naoyuki Ohe, Junya Fukai, Hideki Ogiwara, Atsufumi Kawamura, Satoru Miyawaki, Fumihiko Matsuda, Nobutaka Kiyokawa, Koichi Ichimura, Ryo Nishikawa, Yukinori Okada, Keita Terashima
    Nature Communications, 13, 1, 4478, 4478, Springer Science and Business Media LLC, Dec. 2022, [International Magazine]
    English, Scientific journal, Abstract

    Intracranial germ cell tumors (IGCTs) are rare brain neoplasms that mainly occur in children and adolescents with a particularly high incidence in East Asian populations. Here, we conduct a genome-wide association study (GWAS) of 133 patients with IGCTs and 762 controls of Japanese ancestry. A common 4-bp deletion polymorphism in an enhancer adjacent to BAK1 is significantly associated with the disease risk (rs3831846; P = 2.4 × 10−9, odds ratio = 2.46 [95% CI: 1.83–3.31], minor allele frequency = 0.43). Rs3831846 is in strong linkage disequilibrium with a testicular GCTs susceptibility variant rs210138. In-vitro reporter assays reveal rs3831846 to be a functional variant attenuating the enhancer activity, suggesting its contribution to IGCTs predisposition through altering BAK1 expression. Risk alleles of testicular GCTs derived from the European GWAS show significant positive correlations in the effect sizes with the Japanese IGCTs GWAS (P = 1.3 × 10−4, Spearman’s ρ = 0.48). These results suggest the shared genetic susceptibility of GCTs beyond ethnicity and primary sites.
  • vHIT,VEMPを用いて手術による前庭機能改善を評価し得た小脳橋角部を占拠する錐体斜台部巨大軟骨肉腫の1例
    藤原 圭志, 山口 秀, 茂木 洋晃, 藤原 由有希, 本間 明宏
    日本耳鼻咽喉科頭頸部外科学会会報, 125, 11, 1593, 1598, (一社)日本耳鼻咽喉科頭頸部外科学会, Nov. 2022
    Japanese
  • Long-term consequences of residual lesions after chemoradiotherapy in patients with germinoma at onset.
    Shigeru Yamaguchi, Michinari Okamoto, Yukitomo Ishi, Ryosuke Sawaya, Hiroaki Motegi, Minako Sugiyama, Taisuke Harada, Noriyuki Fujima, Takashi Mori, Takayuki Hashimoto, Emi Takakuwa, Atsushi Manabe, Kohsuke Kudo, Hidefumi Aoyama, Miki Fujimura
    Journal of neurosurgery. Pediatrics, 30, 5, 1, 8, 09 Sep. 2022, [International Magazine]
    English, Scientific journal, OBJECTIVE: In patients with intracranial germ cell tumors, residual lesions are sometimes observed after completion of primary chemoradiotherapy. Although salvage resection of these end-of-treatment residual lesions is recommended for patients with nongerminomatous germ cell tumors, the necessity of early salvage resection for those with germinoma is not clear. The aim of this study was to investigate the frequency of residual germinoma lesions after primary chemoradiotherapy, as well as their management, long-term consequences, and prognosis. METHODS: The authors retrospectively reviewed patients who were primarily treated for germinoma between 2002 and 2021. Residual lesions were evaluated with MRI with and without contrast enhancement within 2 weeks after chemoradiotherapy. The decision to perform salvage resection of residual lesions was at the discretion of the treating physicians. The change in appearance of residual lesions was assessed with serial MRI. Overall survival (OS), progression-free survival (PFS), and recurrence pattern were also investigated. RESULTS: Sixty-nine patients were treated with chemoradiotherapy for germinoma, with a mean follow-up period of 108 months. Residual lesions were radiologically observed in 30 patients (43.5%). Among these, 5 patients (3 with pineal lesions and 2 with basal ganglia lesions) underwent salvage resection. Pathological examination revealed teratomatous components in 3 patients, whereas no tumoral components were identified in 2 patients. One patient with a basal ganglia lesion showed worsening of hemiparesis postoperatively. The remaining 25 patients received watchful observation without surgical intervention. Chronological periodic radiological change in residual lesions was evaluated in 21 patients. One year after primary treatment, the size of the residual lesions was stable and had decreased in 10 and 11 patients, respectively. None of the lesions increased in size. The 10-year PFS and OS rates were 96.7% and 97.3% in patients without residual lesions (n = 39), and 87.1% and 100% in patients with residual lesions (n = 30), respectively. Presence of residual lesions had no significant effect on PFS or OS. All recurrences occurred at distant sites or via dissemination without progression of the primary tumor site, regardless of the presence of residual lesion. CONCLUSIONS: End-of-treatment residual lesions are not rare in patients with germinoma, and these residual lesions seldom show progression. Because of the potential risk of surgical complications, the indication for early salvage surgery for residual lesions should be carefully determined. Watchful observation is recommended for the majority of these cases.
  • 放射線治療を中心としたがん治療について-最近の変化と将来- 膠芽腫に対する免疫反応を考慮した照射野最適化の必要性               
    西岡 健太郎, 高橋 周平, 森 崇, 打浪 雄介, 山口 秀, 木下 学, 山品 将祥, 前林 勝也, 青山 英史
    日本医学放射線学会秋季臨床大会抄録集, 58回, S345, S345, (公社)日本医学放射線学会, Aug. 2022
    Japanese
  • 放射線治療を中心としたがん治療について-最近の変化と将来- 膠芽腫に対する免疫反応を考慮した照射野最適化の必要性               
    西岡 健太郎, 高橋 周平, 森 崇, 打浪 雄介, 山口 秀, 木下 学, 山品 将祥, 前林 勝也, 青山 英史
    日本医学放射線学会秋季臨床大会抄録集, 58回, S345, S345, (公社)日本医学放射線学会, Aug. 2022
    Japanese
  • 【脳腫瘍の放射線治療と画像診断:画像診断医が伝えたいこと】脳腫瘍に対する核医学の役割 再発・壊死の鑑別や核医学治療の可能性
    平田 健司, 竹中 淳規, 山口 秀, 志賀 哲, 豊永 拓哉, 工藤 與亮
    臨床放射線, 67, 7, 683, 692, 金原出版(株), Jul. 2022
    Japanese
  • Clinical and radiological findings of glioblastomas harboring a BRAF V600E mutation.
    Yukitomo Ishi, Shigeru Yamaguchi, Michinari Okamoto, Ryosuke Sawaya, Shogo Endo, Hiroaki Motegi, Shunsuke Terasaka, Zen-Ichi Tanei, Kanako C Hatanaka, Shinya Tanaka, Miki Fujimura
    Brain tumor pathology, 39, 3, 162, 170, 01 Apr. 2022, [Domestic magazines]
    English, Scientific journal, The aim of this study was to analyze the clinical and radiological characteristics of glioblastomas (GBMs) harboring a BRAF mutation. Sequencing analysis of BRAF, IDH1/2, and TERT promoters was performed on GBM samples of patients older than 15 years. The clinical, pathological, and radiological data of patients were retrospectively reviewed. Patients were classified into three groups according to their BRAF and IDH1/2 status: BRAF group, IDH group, and BRAF/IDH-wild-type (WT) group. Among 179 GBM cases, we identified nine cases with a BRAF mutation and nine with IDH mutation. The WT group had 161 cases. Age at onset in the BRAF group was significantly lower compared to the WT group and was similar to the IDH group. In cases with negative IDH1-R132H staining and age < 55 years, 15.2% were BRAF-mutant cases. Similar to the IDH group, overall survival of the BRAF group was significantly longer compared with the WT group. Among nine cases in the BRAF group, three cases had hemorrhagic onset and prior lesions were observed in two cases. In conclusion, age < 55 years, being IDH1-R132H negative, with hemorrhagic onset or the presence of prior lesions are factors that signal recommendation of BRAF analysis for adult GBM patients.
  • Analysis of induced pluripotent stem cell clones derived from a patient with mosaic neurofibromatosis type 2.
    Yukitomo Ishi, Takumi Era, Sayaka Yuzawa, Michinari Okamoto, Ryosuke Sawaya, Hiroaki Motegi, Shigeru Yamaguchi, Shunsuke Terasaka, Kiyohiro Houkin, Miki Fujimura
    American journal of medical genetics. Part A, 188, 6, 1863, 1867, 18 Feb. 2022, [International Magazine]
    English, The diagnosis of mosaicism is challenging in patients with neurofibromatosis type 2 (NF2) subset due to low variant allele frequency. In this study, we generated induced pluripotent stem cells (iPSCs) were generated from a patient clinically diagnosed with NF2 based on multiple schwannomas, including bilateral vestibular schwannomas and meningiomas. Genetic analysis of the patient's mononuclear cells (MNCs) from peripheral blood failed to detect NF2 alteration but successfully found p.Q65X (c.193C>T) mutation in all separate tumors with three intracranial meningiomas and one intraorbital schwannoma, and confirming mosaicism diagnosis in NF2 alteration using deep sequencing. Five different clones with patient-derived iPSCs were established from MNCs in peripheral blood, which showed sufficient expression of pluripotent markers. Genetic analysis showed that one of five generated iPSC lines from MNCs had the same p.Q65X mutation as that found in NF2. There was no significant difference in the expression of genes related to NF2 between iPSC clones with the wild-type and mutant NF2. In this case, clonal expansion of mononuclear bone marrow-derived stem cells recapitulated mosaicism's genetic alteration in NF2. Patient-derived iPSCs from mosaic NF2 would contribute to further functional research of NF2 alteration.
  • Variations and natural history of primary intraparenchymal lesions associated with neurofibromatosis type 2.
    Yukitomo Ishi, Taisuke Harada, Hiroyuki Kameda, Hiromi Okada, Isao Yokota, Michinari Okamoto, Ryosuke Sawaya, Hiroaki Motegi, Shigeru Yamaguchi, Shunsuke Terasaka, Kohsuke Kudo, Miki Fujimura
    Neuroradiology, 64, 2, 393, 396, Feb. 2022, [International Magazine]
    English, Scientific journal, The study aimed to investigate the clinical implications and natural history of primary intraparenchymal lesions in patients with neurofibromatosis type 2. Radiological findings of 15 neurofibromatosis type 2 cases were retrospectively collected. Twenty-seven primary intraparenchymal lesions were observed in 7 out of 15 patients (47%). Cortical/subcortical T2 hyperintense lesions and enlarged Virchow-Robin spaces were the most common findings in five and four patients, respectively. During the follow-up period (median 84 months), one new primary intraparenchymal lesion was identified and increased lesions were observed in two cases on contrast-enhanced MRI. Surgical resection was performed in one case pathologically diagnosed with atypical meningioma. Twenty-five other lesions without contrast enhancement presented no apparent growth during follow-up. Although most primary intraparenchymal lesions are benign, a subset of cases would present newly developed or increased lesions on contrast-enhanced MRI. Careful monitoring is necessary for such cases, and pathological confirmation should be considered.
  • Cystic Intracranial Recurrence of Olfactory Neuroblastoma without Accumulation on Fluorine-18-fluorodeoxyglucose Positron Emission Tomography.
    Yukitomo Ishi, Shigeru Yamaguchi, Kanako C Hatanaka, Emi Takakuwa, Hiroaki Motegi, Taishi Honda, Hiroyuki Kobayashi, Shunsuke Terasaka, Akihiro Homma, Miki Fujimura, Kiyohiro Houkin
    Acta medica Okayama, 76, 1, 93, 98, Feb. 2022, [Domestic magazines]
    English, A 66-year-old man underwent multimodal treatment for olfactory neuroblastoma (ONB). When he was 72 years old, a cystic intracranial lesion without accumulation on fluorine-18-fluorodeoxyglucose positron emission tomography was detected. Surgical resection was performed when the patient was 73 years old. The pathological examination revealed recurrence of ONB, and the patient underwent focal irradiation. At age 81, he presented with a second recurrence in the right occipital lobe with radiological and pathological findings similar to the prior recurrence. This case suggests that pathological confirmation should be considered in cases with atypical radiological findings following the treatment of ONB.
  • [The Potential of Personalized/Precision Medicine for Meningiomas].
    Shigeru Yamaguchi, Miki Fujimura
    No shinkei geka. Neurological surgery, 50, 1, 132, 140, Jan. 2022, [Domestic magazines]
    Japanese, Scientific journal, Meningiomas are one of the most common primary brain tumors. The majority of patients with meningiomas can undergo curative resection or remain asymptomatic for a lifetime, but a minority of them have tumors with cumbersome clinicopathological features causing life-threatening disease. Although several cytotoxic agents and hormonal therapies have been tried for refractory and unresectable meningiomas, there are no effective drugs available for meningiomas so far. In the last decade, due to the rapid progress in comprehensive genomic research for individual tumors, novel somatic and recurrent mutations were discovered in meningiomas. The discovered somatic mutations were mostly mutually exclusive with NF2 gene alterations, and importantly, several of these mutations, such as AKT1 and SMO, are potentially actionable mutations for precision/personalized medicine. In addition, immunotherapy is another attractive treatment option for refractory meningiomas due to the development of immune checkpoint inhibitors. Herein, we describe the possibility of precision medicine for meningiomas according to each molecular aberrancy and present the currently ongoing clinical trials including hormonal therapy, targeted kinase inhibitors, and immunotherapy.
  • Detection of the Moment of Nerve Decompression Using Continuous Monitoring of Evoked Facial Nerve Electromyograms in a Patient with Facial Nerve Schwannoma: Case Report.
    Asuka Nakazaki, Shigeru Yamaguchi, Hiroaki Motegi, Yukitomo Ishi, Michinari Okamoto, Miki Fujimura
    NMC case report journal, 9, 213, 216, 2022, [Domestic magazines]
    English, Facial nerve function improvement is a challenging goal in facial nerve schwannoma (FNS) surgery. Intraoperative continuous monitoring of evoked facial nerve electromyograms (CFN-EMGs) is performed in acoustic neuroma surgery to preserve facial nerve function. CFN-EMGs were applied in decompression surgery for FNS with severe facial paresis. A 39-year-old woman presented with a sudden onset of vertigo, left hearing disturbance, and severe left facial palsy with House-Brackmann (HB) grade 5. FNS was strongly suspected based on the patient's clinical course and magnetic resonance imaging findings, and the patient underwent surgical decompression of the internal auditory canal (IAC) to improve facial nerve function 9 weeks after onset. CFN-EMG responses suddenly improved after removing the posterior wall of the IAC and incising its dura matter. Since the patient's facial nerve paresis improved to HB grade 2 after surgery, CFN-EMGs could detect the moment of facial nerve decompression. This would be the first report to show that CFN-EMGs applied in decompression surgery for FNS could detect the effects of decompression during surgery in real-time. Thus, CFN-EMGs may be an effective monitoring method in decompression surgery for FNS.
  • Successful Treatment of Intracranial Methotrexate-associated Lymphoproliferative Disorder without Epstein-Barr Virus Infection Using Rituximab, Methotrexate, Procarbazine, and Vincristine: A Case Report.
    Makoto Mizushima, Yukitomo Ishi, Hiroshi Ikeda, Ikuma Echizenya, Takuya Otsuka, Tomoko Mitsuhashi, Shigeru Yamaguchi, Miki Fujimura
    NMC case report journal, 9, 237, 242, 2022, [Domestic magazines]
    English, Methotrexate-associated lymphoproliferative disorder (MTX-LPD) occurs in patients with rheumatoid arthritis (RA) treated with methotrexate (MTX). MTX-LPD is typically associated with Epstein-Barr virus (EBV) infection and regresses with MTX discontinuation. On the other hand, EBV-negative MTX-LPDs are less common and are more likely to show partial or no regression after MTX discontinuation. There were no standard chemotherapeutic options for refractory MTX-LPD. We present a case of EBV-negative MTX-LPD in the central nervous system (CNS) that was successfully treated with rituximab, methotrexate, procarbazine, and vincristine (R-MPV), followed by reduced-dose whole-brain radiotherapy (rdWBRT), following the same treatment protocol as primary CNS lymphoma. A 59-year-old woman with RA treated with MTX presented with gradually developing staggered gait, memory deficit, and disorientation. Multiple lesions with heterogeneous contrast enhancement were discovered using brain magnetic resonance imaging. The patient was suspected of having MTX-LPD, but discontinuing MTX did not result in regression of the brain lesions. She underwent a biopsy from the left parietal lesion. The tissue was pathologically diagnosed as diffuse large B-cell lymphoma. Furthermore, pathological examination through EBV-encoded ribonucleic acid in situ hybridization demonstrated a lack of EBV infection. She was ultimately diagnosed with EBV-negative CNS MTX-LPD. We applied chemotherapy with R-MPV and rdWBRT. The patient achieved a complete response. In the case of CNS MTX-LPD without EBV infection, chemotherapy with R-MPV followed by rdWBRT may be considered.
  • The prognostic improvement of add-on bevacizumab for progressive disease during concomitant temozolomide and radiation therapy in patients with glioblastoma and anaplastic astrocytoma
    Shigeru Yamaguchi, Yukitomo Ishi, Hiroaki Motegi, Michinari Okamoto, Hiroyuki Kobayashi, Kenji Hirata, Yoshitaka Oda, Shinya Tanaka, Shunsuke Terasaka, Kiyohiro Houkin
    Journal of Neurosurgical Sciences, 64, 6, 502, 508, Edizioni Minerva Medica, 01 Dec. 2021
    English, Scientific journal
  • Notable therapeutic response in a patient with systemic juvenile xanthogranuloma with KIF5B-ALK fusion.
    Minako Sugiyama, Shinsuke Hirabayashi, Yukitomo Ishi, Junko Kikuchi, Ayako Ishikura, Hiroaki Motegi, Yuki Ueda, Saori Sawai, Kazuya Hara, Yukayo Terashita, Yuko Cho, Emi Takakuwa, Shohei Honda, Shigeru Yamaguchi, Ichiro Kinoshita, Atsushi Manabe
    Pediatric blood & cancer, 68, 11, e29227, Nov. 2021, [International Magazine]
    English
  • Determination of brain tumor recurrence using 11 C-methionine positron emission tomography after radiotherapy.
    Shigeru Yamaguchi, Kenji Hirata, Michinari Okamoto, Eku Shimosegawa, Jun Hatazawa, Ryuichi Hirayama, Naoki Kagawa, Haruhiko Kishima, Noboru Oriuchi, Masazumi Fujii, Kentaro Kobayashi, Hiroyuki Kobayashi, Shunsuke Terasaka, Ken-Ichi Nishijima, Yuji Kuge, Yoichi M Ito, Hiroshi Nishihara, Nagara Tamaki, Tohru Shiga
    Cancer science, 112, 10, 4246, 4256, Oct. 2021, [International Magazine]
    English, Scientific journal, We conducted a prospective multicenter trial to compare the usefulness of 11 C-methionine (MET) and 18 F-fluorodeoxyglucose (FDG) positron emission tomography (PET) for identifying tumor recurrence. Patients with clinically suspected tumor recurrence after radiotherapy underwent both 11 C-MET and 18 F-FDG PET. When a lesion showed a visually detected uptake of either tracer, it was surgically resected for histopathological analysis. Patients with a lesion negative to both tracers were revaluated by magnetic resonance imaging (MRI) at 3 months after the PET studies. The primary outcome measure was the sensitivity of each tracer in cases with histopathologically confirmed recurrence, as determined by the McNemar test. Sixty-one cases were enrolled, and 56 cases could be evaluated. The 38 cases where the lesions showed uptake of either 11 C-MET or 18 F-FDG underwent surgery; 32 of these cases were confirmed to be subject to recurrence. Eighteen cases where the lesions showed uptake of neither tracer received follow-up MRI; the lesion size increased in one of these cases. Among the cases with histologically confirmed recurrence, the sensitivities of 11 C-MET PET and 18 F-FDG PET were 0.97 (32/33, 95% confidence interval [CI]: 0.85-0.99) and 0.48 (16/33, 95% CI: 0.33-0.65), respectively, and the difference was statistically significant (P < .0001). The diagnostic accuracy of 11 C-MET PET was significantly better than that of 18 F-FDG PET (87.5% vs. 69.6%, P = .033). No examination-related adverse events were observed. The results of the study demonstrated that 11 C-MET PET was superior to 18 F-FDG PET for discriminating between tumor recurrence and radiation-induced necrosis.
  • Efficacy and safety of nivolumab in Japanese patients with first recurrence of glioblastoma: an open-label, non-comparative study.
    Tomokazu Aoki, Naoki Kagawa, Kazuhiko Sugiyama, Toshihiko Wakabayashi, Yoshiki Arakawa, Shigeru Yamaguchi, Shota Tanaka, Eiichi Ishikawa, Yoshihiro Muragaki, Motoo Nagane, Mitsutoshi Nakada, Satoshi Suehiro, Nobuhiro Hata, Junichiro Kuroda, Yoshitaka Narita, Yukihiko Sonoda, Yasuo Iwadate, Manabu Natsumeda, Yoichi Nakazato, Hironobu Minami, Yuki Hirata, Shunsuke Hagihara, Ryo Nishikawa
    International journal of clinical oncology, 26, 12, 2205, 2215, 29 Sep. 2021, [Domestic magazines]
    English, Scientific journal, BACKGROUND: An open-label, non-comparative study assessed the efficacy and safety of nivolumab in Japanese patients with first recurrence glioblastoma. METHODS: Patients with first recurrence of histologically confirmed World Health Organization Grade IV glioma, after treatment with temozolomide and radiotherapy, received nivolumab 3 mg/kg every 2 weeks until confirmed disease progression (Response Assessment in Neuro-Oncology criteria) or toxicity. Primary endpoint was 1-year overall survival rate assessed by Bayesian approach. The prespecified efficacy criterion was that the Bayesian posterior probability threshold for exceeding the 1-year overall survival of bevacizumab (34.5%) from the Japanese phase 2 study (JO22506) would be 93%. RESULTS: Of the 50 enrolled patients, 44 (88.0%) had recurrent malignant glioma (glioblastoma, gliosarcoma), and of these, 26 (59.1%) had at least one measurable lesion at baseline. The Bayesian posterior mean 1-year overall survival (90% Bayesian credible intervals) with nivolumab was 54.4% (42.27-66.21), and the Bayesian posterior probability of exceeding the threshold of the 1-year overall survival rate of bevacizumab (34.5%) was 99.7%. Median (90% confidence interval) overall and progression-free survival was 13.1 (10.4-17.7) and 1.5 (1.4-1.5) months, respectively. One partial response was observed (objective response rate 1/26 evaluable patients [3.8%]). Treatment-related adverse event rates were 14.0% for Grade 3-4 and 2.0% for Grade 5; most adverse events resolved and were manageable. CONCLUSIONS: The 1-year overall survival with nivolumab monotherapy in Japanese patients with glioblastoma met the prespecified efficacy criterion. The safety profile of nivolumab was consistent with that observed in other tumor types. CLINICAL TRIAL REGISTRATION: JapicCTI-152967.
  • Distinct TERT promoter C228T and C250T mutations in a patient with an oligodendroglioma: A case report.
    Yukitomo Ishi, Hiromi Okada, Michinari Okamoto, Hiroaki Motegi, Shinya Tanaka, Tomoko Mitsuhashi, Shigeru Yamaguchi
    Neuropathology : official journal of the Japanese Society of Neuropathology, 41, 3, 236, 242, Jun. 2021, [International Magazine]
    English, Scientific journal, The majority of oligodendroglial tumors harbor mutations in the telomerase reverse transcriptase (TERT) gene (TERT) promoter and the isocitrate dehydrogenase 1/2 (IDH1/2) gene (IDH1/2), as well as 1p/19q codeletion. Generally, TERT promoter mutations, C250T and C228T, are mutually exclusive. We present a case of oligodendroglioma harboring both C250T and C228T mutations in TERT promoter. A 38-year-old man presented with grand mal seizures and underwent a resection surgery for a left frontal lobe tumor. He was pathologically diagnosed as having oligodendroglioma and was carefully observed. At 48 years of age, he underwent another resection surgery due to tumor regrowth, with the pathological diagnosis of anaplastic oligodendroglioma. Genetic analysis of the initial tumor specimen revealed IDH1 R132H mutation and both C250T and C228T mutations in TERT promoter. Using mutation-specific primers, two mutations were considered to be distributed in different alleles. In the tumor specimen obtained during the second surgery, IDH1 R132H mutation was detected to be similar to that of the initial specimen; however, only C228T mutation was detected in TERT promoter. The 1p/19q codeletion was detected in both the initial and recurrent tumor specimens. According to the sequencing data from the two tumor specimens, although TERT promoter mutation has been considered to be an early genetic event in the tumorigenesis of oligodendroglial tumors, it is likely that the C250T and C228T mutations in TERT promoter are subclonally distributed in the same tumor specimen of the present case.
  • Ollier病に合併した多発神経膠腫の一例               
    池田 寛, 山口 秀, 伊師 雪友, 若林 健人, 清水 亜衣, 岡本 迪成, 茂木 洋晃, 藤村 幹
    Brain Tumor Pathology, 38, Suppl., 079, 079, 日本脳腫瘍病理学会, May 2021
    Japanese
  • High-grade neuroepithelial tumor with BCL6 corepressor-alteration presenting pathological and radiological calcification: A case report.
    Yukitomo Ishi, Ai Shimizu, Emi Takakuwa, Minako Sugiyama, Michinari Okamoto, Hiroaki Motegi, Shinsuke Hirabayashi, Yuko Cho, Akihiro Iguchi, Atsushi Manabe, Sumihito Nobusawa, Shinya Tanaka, Shigeru Yamaguchi
    Pathology international, 71, 5, 348, 354, May 2021, [International Magazine]
    English, A 5-year-old girl presented with headache and vomiting. Head computed tomography and magnetic resonance imaging showed a right frontal lobe tumor with marked calcification. The patient underwent resection surgery with suspicion of anaplastic ependymoma, and the tumor was gross totally removed. Pathological examination revealed areas of dense tumor cells with a high nucleocytoplasmic ratio and myxoid areas consisting of tumor cells with a round-shaped nucleus and eosinophilic cytoplasm. Perivascular pseudorosette, necrosis, circumscribed growth, and microcalcification were also observed. Immunohistochemistry demonstrated negative staining for glial fibrillary protein and epithelial membrane antigen. Diagnosis of a high-grade neuroepithelial tumor (HGNET) with BCL6 corepressor (BCOR) alteration was made based on pathological findings and internal tandem duplication in the exon 15 of BCOR. Although calcification on radiological and pathological examination is not typical, it would be essential to recognize that calcification could appear in HGNET-BCOR.
  • Clinical Outcome of Cytoreductive Surgery Prior to Bevacizumab for Patients with Recurrent Glioblastoma: A Single-center Retrospective Analysis.
    Shigeru Yamaguchi, Hiroaki Motegi, Yukitomo Ishi, Michinari Okamoto, Ryosuke Sawaya, Hiroyuki Kobayashi, Shunsuke Terasaka, Kiyohiro Houkin
    Neurologia medico-chirurgica, 61, 4, 245, 252, 15 Apr. 2021, [Domestic magazines]
    English, Scientific journal, Bevacizumab (BEV) is a key anti-angiogenic agent used in the treatment for recurrent glioblastoma multiforme (GBM). The aim of this study was to investigate whether cytoreductive surgery prior to treatment with BEV contributes to prolongation of survival for patients with recurrent GBM. We retrospectively analyzed the treatment outcomes of 124 patients with recurrent GBM who were initially treated with the Stupp protocol between 2006 and 2019. Given that BEV has only been available in Japan since 2013, we grouped the patients into two groups according to the time of first recurrence: the pre-BEV group (N = 51) included patients who had recurrence before BEV approval, and the BEV group (N = 73) included patients with recurrence after BEV approval. The overall survival after first recurrence (OS-R) was analyzed according to the treatment strategy. Among 124 patients, 27 patients (19.4%) received cytoreductive surgery. There were nine cases in the pre-BEV group and 18 cases in the BEV group. Although the mean extent of resection for both groups was almost equal, OS-R was significantly different. The median OS-R was 8.1 m in the pre-BEV group and 16.3 m in the BEV group (P = 0.007). Multivariate analysis revealed that the unavailability of BEV postoperatively (P = 0.03) and decreasing performance status by surgery (P = 0.01) were significant poor prognostic factors for survival after surgery. With the advent of BEV, cytoreductive surgery might provide superior survival benefit at the time of GBM recurrence, especially in cases where surgery can be performed without deteriorating the patient's condition.
  • Novel risk factors and management of brain sag after brain tumor surgery
    Hiroaki Motegi, Shigeru Yamaguchi, Michinari Okamoto, Yukitomo Ishi, Shogo Endo, Sadahiro Kaneko, Hiroyuki Kobayashi, Shunsuke Terasaka, Kiyohiro Houkin
    INTERDISCIPLINARY NEUROSURGERY-ADVANCED TECHNIQUES AND CASE MANAGEMENT, 23, Mar. 2021, [Peer-reviewed]
    English, Scientific journal
  • So-called bifocal tumors with diabetes insipidus and negative tumor markers: are they all germinoma?
    Masayuki Kanamori, Hirokazu Takami, Shigeru Yamaguchi, Takashi Sasayama, Koji Yoshimoto, Teiji Tominaga, Akihiro Inoue, Naokado Ikeda, Atsushi Kambe, Toshihiro Kumabe, Masahide Matsuda, Shota Tanaka, Manabu Natsumeda, Ken-Ichiro Matsuda, Masahiro Nonaka, Jun Kurihara, Masayoshi Yamaoka, Naoki Kagawa, Naoki Shinojima, Tetsuya Negoto, Yukiko Nakahara, Yoshiki Arakawa, Seiji Hatazaki, Hiroaki Shimizu, Atsuo Yoshino, Hiroshi Abe, Jiro Akimoto, Yu Kawanishi, Tomonari Suzuki, Atsushi Natsume, Motoo Nagane, Yukinori Akiyama, Dai Keino, Tadateru Fukami, Takahiro Tomita, Kohei Kanaya, Tsutomu Tokuyama, Shuichi Izumoto, Mitsutoshi Nakada, Daisuke Kuga, Shohei Yamamoto, Ryogo Anei, Takeo Uzuka, Junya Fukai, Noriyuki Kijima, Keita Terashima, Koichi Ichimura, Ryo Nishikawa
    Neuro-oncology, 23, 2, 295, 303, Oxford University Press (OUP), 25 Feb. 2021, [International Magazine]
    English, Scientific journal, Abstract

    Background
    The Delphi consensus statements on the management of germ cell tumors (GCTs) failed to reach agreements on the statement that the cases with (i) pineal and neurohypophyseal bifocal lesion, (ii) with diabetes insipidus, and (iii) with negative tumor markers can be diagnosed as germinoma without histological verification. To answer this, multicenter retrospective analysis was performed.




    Methods
    A questionnaire on clinical findings, histological diagnosis, and details of surgical procedures was sent to 86 neurosurgical and 35 pediatrics departments in Japan.




    Results
    Fifty-one institutes reported 132 cases that fulfilled the 3 criteria. Tissue sampling was performed in 91 cases from pineal (n = 44), neurohypophyseal (n = 32), both (n = 6), and distant (n = 9) lesions. Histological diagnosis was established in 89 cases: pure germinoma or germinoma with syncytiotrophoblastic giant cells in 82 (92.1%) cases, germinoma and mature teratoma in 2 cases, and granulomatous inflammation in 2 cases. Histological diagnosis was not established in 2 cases. Although no tumors other than GCTs were identified, 3 (3.4%) patients had non-germinomatous GCTs (NGGCTs). None of the patients developed permanent complications after endoscopic or stereotactic biopsy. Thirty-nine patients underwent simultaneous procedure for acute hydrocephalus without permanent complications, and hydrocephalus was controlled in 94.9% of them.




    Conclusion
    All patients who fulfilled the 3 criteria had GCTs or granulomatous inflammation, but not other types of tumors. However, no fewer than 3.4% of the patients had NGGCTs. Considering the safety and the effects of simultaneous procedures for acute hydrocephalus, biopsy was recommended in such patients.


  • Rationale and Design of BeatNF2 Trial: A Clinical Trial to Assess the Efficacy and Safety of Bevacizumab in Patients with Neurofibromatosis Type 2 Related Vestibular Schwannoma.
    Masazumi Fujii, Masao Kobayakawa, Kiyoshi Saito, Akihiro Inano, Akio Morita, Mitsuhiro Hasegawa, Akitake Mukasa, Takafumi Mitsuhara, Takeo Goto, Shigeru Yamaguchi, Takashi Tamiya, Hirofumi Nakatomi, Soichi Oya, Fumiaki Takahashi, Taku Sato, Mudathir Bakhit, On Behalf Of The BeatNF Trial Investigators
    Current oncology (Toronto, Ont.), 28, 1, 726, 739, 31 Jan. 2021, [International Magazine]
    English, Scientific journal, Neurofibromatosis type 2 (NF2) causes bilateral vestibular schwannomas (VSs), leading to deafness. VS is treated by surgery or radiation, but neither treatments prevent hearing loss. Bevacizumab was found to be effective in suppressing the tumor's growth and may help to improve hearing. We are conducting a randomized, double-blind, multicenter clinical trial to verify the efficacy and safety of bevacizumab in NF2-related VS. The primary objective is to evaluate the efficacy of bevacizumab in improving hearing in the affected ear. One of the secondary objectives is to evaluate bevacizumab's efficacy in rechallenge treatment in relapsed cases. Sixty patients will randomly receive either bevacizumab or a placebo and will be clinically observed for 48 weeks in the initial intervention phase. In the first half (24 weeks), they will receive either 5 mg/kg of bevacizumab or a placebo drug. In the second half, all patients will receive 5 mg/kg of bevacizumab. If hearing function deteriorated in a patient who had shown improvement during the first phase, a rechallenge dose with bevacizumab would be offered.
  • Preoperative Texture Analysis Using 11C-Methionine Positron Emission Tomography Predicts Survival after Surgery for Glioma.
    Osamu Manabe, Shigeru Yamaguchi, Kenji Hirata, Kentaro Kobayashi, Hiroyuki Kobayashi, Shunsuke Terasaka, Takuya Toyonaga, Keiichi Magota, Yuji Kuge, Nagara Tamaki, Tohru Shiga, Kohsuke Kudo
    Diagnostics (Basel, Switzerland), 11, 2, 28 Jan. 2021, [International Magazine]
    English, Scientific journal, BACKGROUND: Positron emission tomography with 11C-methionine (MET) is well established in the diagnostic work-up of malignant brain tumors. Texture analysis is a novel technique for extracting information regarding relationships among surrounding voxels, in order to quantify their inhomogeneity. This study evaluated whether the texture analysis of MET uptake has prognostic value for patients with glioma. METHODS: We retrospectively analyzed adults with glioma who had undergone preoperative metabolic imaging at a single center. Tumors were delineated using a threshold of 1.3-fold of the mean standardized uptake value for the contralateral cortex, and then processed to calculate the texture features in glioma. RESULTS: The study included 42 patients (median age: 56 years). The World Health Organization classifications were grade II (7 patients), grade III (17 patients), and grade IV (18 patients). Sixteen (16.1%) all-cause deaths were recorded during the median follow-up of 18.8 months. The univariate analyses revealed that overall survival (OS) was associated with age (hazard ratio (HR) 1.04, 95% confidence interval (CI) 1.01-1.08, p = 0.0093), tumor grade (HR 3.64, 95% CI 1.63-9.63, p = 0.0010), genetic status (p < 0.0001), low gray-level run emphasis (LGRE, calculated from the gray-level run-length matrix) (HR 2.30 × 1011, 95% CI 737.11-4.23 × 1019, p = 0.0096), and correlation (calculated from the gray-level co-occurrence matrix) (HR 5.17, 95% CI 1.07-20.93, p = 0.041). The multivariate analyses revealed OS was independently associated with LGRE and correlation. The survival curves were also significantly different (both log-rank p < 0.05). CONCLUSION: Textural features obtained using preoperative MET positron emission tomography may compliment the semi-quantitative assessment for prognostication in glioma cases.
  • Diagnostic Capability of Cerebrospinal Fluid-Placental Alkaline Phosphatase Value in Intracranial Germ Cell Tumor.
    Michinari Okamoto, Shigeru Yamaguchi, Yukitomo Ishi, Hiroaki Motegi, Takashi Mori, Takayuki Hashimoto, Yukayo Terashita, Shinsuke Hirabayashi, Minako Sugiyama, Akihiro Iguchi, Yuko Cho, Atsushi Manabe, Kiyohiro Houkin
    Oncology, 99, 1, 23, 31, 2021, [International Magazine]
    English, Scientific journal, OBJECTIVE: Most types of intracranial germ cell tumors (IGCTs) are sensitive to chemoradiation. However, biopsy specimens are usually small and thus cannot be used for obtaining an accurate pathological diagnosis. Recently, the cerebrospinal fluid (CSF) placental alkaline phosphatase (PLAP) value has been considered a new biomarker of IGCTs. The present study aimed to evaluate the discriminatory characteristics of the CSF-PLAP value upon diagnosis and at the time of recurrence in patients with IGCTs. METHODS: Between 2015 and 2019, this study included 37 patients with tumors located in the intraventricular and/or periventricular region. The CSF-PLAP level was assessed before the patients received any treatment. The PLAP level was evaluated during and after first-line chemoradiotherapy in 7 patients with IGCTs. The CSF-PLAP values were compared according to histological diagnosis, and the correlation between these values and radiographical features was assessed. The CSF-PLAP values of 6 patients with IGCTs with suspected recurrence were evaluated based on neuroimaging findings. RESULTS: The CSF-PLAP values were significantly higher in patients with IGCTs than in those with other types of brain tumor (n = 19 vs. 18; median: 359.0 vs. <8.0 pg/mL). The specificity and sensitivity were 88 and 95%, respectively, with a cutoff value of 8.0 pg/mL. In patients with IGCT, the CSF-PLAP value was higher in patients with germinoma than in those with nongerminomatous germ cell tumors (n = 12 vs. 7; median: 415.0 vs. 359.0 pg/mL). Regarding the time course, the CSF-PLAP value decreased to below the detection limit after the reception of first-line chemoradiotherapy in all 7 patients. A significant correlation was observed between the initial CSF-PLAP value and the tumor reduction volume after receiving first-line chemoradiotherapy (p < 0.0003, R2 = 0.6165, logY = 1.202logX - 1.727). Among the patients with suspected IGCT recurrence (n = 6), the CSF-PLAP value was high in patients with recurrence (n = 3; median: 259.0 pg/mL), and that in patients (n = 3) without recurrence was below the lower detection limit. CONCLUSIONS: The CSF-PLAP level is a useful biomarker during the initial diagnosis of IGCTs and at the time of recurrence. It may be associated with the volume of germinomatous components of tumors.
  • INITIAL MANAGEMENT OF HYDROCEPHALUS IN THE PEDIATRIC AND YOUNG-ADULT PATIENTS WITH BRAIN TUMORS; THE EFFICACY OF LONG-TERM INDWELLING EXTERNAL VENTRICULAR DRAINAGE
    Shigeru Yamaguchi, Hiroaki Motegi, Yukitomo Ishi, Michinari Okamoto, Akihiro Iguchi, Yuko Cho, Minako Sugiyama, Atushi Manabe, Kiyohiro Houkin
    NEURO-ONCOLOGY, 22, 461, 461, Dec. 2020, [Peer-reviewed]
    English
  • DIAGNOSTIC CAPABILITY OF CSF-PLAP ON INTRACRANIAL GERM CELL TUMOR
    Michinari Okamoto, Shigeru Yamaguchi, Yukitomo Ishi, Hiroaki Motegi, Yukayo Terashita, Shinsuke Hirabayashi, Minako Sugiyama, Yuko Cho, Akihiro Iguchi, Atushi Manabe, Kiyohiro Houkin
    NEURO-ONCOLOGY, 22, 334, 334, Dec. 2020, [Peer-reviewed]
    English
  • CAN HIGH LEVEL SERUM HCG-B BE CONSIDERED EQUIVALENT TO A DIAGNOSIS OF CHORIOCARCINOMA IN PRIMARY CENTRAL NERVOUS SYSTEM GERM-CELL TUMOR?
    Hiroaki Motegi, Shigeru Yamaguchi, Yukitomo Ishi, Michinari Okamoto, Akihiro Iguchi, Yuko Cho, Minako Sugiyama, Atsushi Manabe, Kiyohiro Houkin
    NEURO-ONCOLOGY, 22, 329, 330, Dec. 2020, [Peer-reviewed]
    English
  • TERT promoter mutation confers favorable prognosis regardless of 1p/19q status in adult diffuse gliomas with IDH1/2 mutations.
    Hideyuki Arita, Yuko Matsushita, Ryunosuke Machida, Kai Yamasaki, Nobuhiro Hata, Makoto Ohno, Shigeru Yamaguchi, Takashi Sasayama, Shota Tanaka, Fumi Higuchi, Toshihiko Iuchi, Kuniaki Saito, Masayuki Kanamori, Ken-Ichiro Matsuda, Yohei Miyake, Kaoru Tamura, Sho Tamai, Taishi Nakamura, Takehiro Uda, Yoshiko Okita, Junya Fukai, Daisuke Sakamoto, Yasuhiko Hattori, Eriel Sandika Pareira, Ryusuke Hatae, Yukitomo Ishi, Yasuji Miyakita, Kazuhiro Tanaka, Shunsaku Takayanagi, Ryohei Otani, Tsukasa Sakaida, Keiichi Kobayashi, Ryuta Saito, Kazuhiko Kurozumi, Tomoko Shofuda, Masahiro Nonaka, Hiroyoshi Suzuki, Makoto Shibuya, Takashi Komori, Hikaru Sasaki, Masahiro Mizoguchi, Haruhiko Kishima, Mitsutoshi Nakada, Yukihiko Sonoda, Teiji Tominaga, Motoo Nagane, Ryo Nishikawa, Yonehiro Kanemura, Aya Kuchiba, Yoshitaka Narita, Koichi Ichimura
    Acta neuropathologica communications, 8, 1, 201, 201, 23 Nov. 2020, [International Magazine]
    English, Scientific journal, TERT promoter mutations are commonly associated with 1p/19q codeletion in IDH-mutated gliomas. However, whether these mutations have an impact on patient survival independent of 1p/19q codeletion is unknown. In this study, we investigated the impact of TERT promoter mutations on survival in IDH-mutated glioma cases. Detailed clinical information and molecular status data were collected for a cohort of 560 adult patients with IDH-mutated gliomas. Among these patients, 279 had both TERT promoter mutation and 1p/19q codeletion, while 30 had either TERT promoter mutation (n = 24) or 1p/19q codeletion (n = 6) alone. A univariable Cox proportional hazard analysis for survival using clinical and genetic factors indicated that a Karnofsky performance status score (KPS) of 90 or 100, WHO grade II or III, TERT promoter mutation, 1p/19q codeletion, radiation therapy, and extent of resection (90-100%) were associated with favorable prognosis (p < 0.05). A multivariable Cox regression model revealed that TERT promoter mutation had a significantly favorable prognostic impact (hazard ratio = 0.421, p = 0.049), while 1p/19q codeletion did not have a significant impact (hazard ratio = 0.648, p = 0.349). Analyses incorporating patient clinical and genetic information were further conducted to identify subgroups showing the favorable prognostic impact of TERT promoter mutation. Among the grade II-III glioma patients with a KPS score of 90 or 100, those with IDH-TERT co-mutation and intact 1p/19q (n = 17) showed significantly longer survival than those with IDH mutation, wild-type TERT, and intact 1p/19q (n = 185) (5-year overall survival, 94% and 77%, respectively; p = 0.032). Our results demonstrate that TERT promoter mutation predicts favorable prognosis independent of 1p/19q codeletion in IDH-mutated gliomas. Combined with its adverse effect on survival among IDH-wild glioma cases, the bivalent prognostic impact of TERT promoter mutation may help further refine the molecular diagnosis and prognostication of diffuse gliomas.
  • 画像診断と病理 髄芽腫(desmoplastic/nodular type)
    竹中 淳規, 山口 晃典, 原田 太以佑, 工藤 與亮, 高桑 恵美, 山口 秀
    画像診断, 40, 14, 1394, 1395, (株)学研メディカル秀潤社, Nov. 2020
    Japanese
  • 下垂体単独ランゲルハンス細胞組織球症の一例               
    渡邊 敏史, 平林 真介, 原 和也, 杉山 未奈子, 長 祐子, 高桑 恵美, 茂木 洋晃, 山口 秀, 井口 晶裕, 真部 淳
    日本小児血液・がん学会雑誌, 57, 4, 306, 306, (一社)日本小児血液・がん学会, Oct. 2020
    Japanese
  • Prognostic role of H3K27M mutation, histone H3K27 methylation status, and EZH2 expression in diffuse spinal cord gliomas.
    Yukitomo Ishi, Soichiro Takamiya, Toshitaka Seki, Kazuyoshi Yamazaki, Kazutoshi Hida, Kanako C Hatanaka, Yusuke Ishida, Yoshitaka Oda, Shinya Tanaka, Shigeru Yamaguchi
    Brain tumor pathology, 37, 3, 81, 88, Jul. 2020, [Peer-reviewed], [Domestic magazines]
    English, Scientific journal, The objective of this study is to clarify clinical significance of the H3F3A K27M mutation (H3K27M) and analyze the correlation between H3K27M, H3K27me3 status, and EZH2 expression and prognosis in spinal cord gliomas. Patients with spinal cord diffuse glioma regardless of World Health Organization (WHO) grade underwent genetic analysis for H3F3A, HIST1H3B, TERT promoter, IDH1/2, and BRAF. H3K27me3 status and EZH2 expression were analyzed through immunohistochemistry. Thereafter, the association between H3K27M, H3K27me3 status, and EZH2 expression and prognosis was retrospectively analyzed using the log-rank test. A total of 26 cases, 5 with WHO grade 4, 9 with grade 3, and 12 with grade 2 glioma, were analyzed. Although WHO grade 2 cases tended to present favorable overall survival, the difference was not statistically significant. H3K27M, which was detected in four grade 4 cases (80%) and three grade 3 cases (33%), was not associated with prognosis among grade 3 and 4 cases. Among WHO grade 2-4 cases, the combination of retained H3K27me3 and negative EZH2 expression was correlated with favorable overall survival (p = 0.03). The combination of H3K27me3 status and EZH2 expression was considered as a potential prognostic marker in WHO grade 2-4 diffuse spinal cord gliomas.
  • Influence of the scan time point when assessing hypoxia in 18F-fluoromisonidazole PET: 2 vs. 4 h.
    Kentaro Kobayashi, Osamu Manabe, Kenji Hirata, Shigeru Yamaguchi, Hiroyuki Kobayashi, Shunsuke Terasaka, Takuya Toyonaga, Sho Furuya, Keiichi Magota, Yuji Kuge, Kohsuke Kudo, Tohru Shiga, Nagara Tamaki
    European journal of nuclear medicine and molecular imaging, 47, 8, 1833, 1842, Jul. 2020, [Peer-reviewed], [International Magazine]
    English, Scientific journal, PURPOSE: 18F-fluoromisonidazole (18F-FMISO) is the most widely used positron emission tomography (PET) tracer for imaging tumor hypoxia. Previous reports suggested that the time from injection to the scan may affect the assessment of 18F-FMISO uptake. Herein, we directly compared the images at 2 h and 4 h after a single injection of 18F-FMISO. METHODS: Twenty-three patients with or suspected of having a brain tumor were scanned twice at 2 and 4 h following an intravenous injection of 18F-FMISO. We estimated the mean standardized uptake value (SUV) of the gray matter and white matter and the gray-to-white matter ratio in the background brain tissue from the two scans. We also performed a semi-quantitative analysis using the SUVmax and maximum tumor-to-normal ratio (TNR) for the tumor. RESULTS: At 2 h, the SUVmean of gray matter was significantly higher than that of white matter (median 1.23, interquartile range (IQR) 1.10-1.32 vs. 1.04, IQR 0.95-1.16, p < 0.0001), whereas at 4 h, it significantly decreased to approach that of the white matter (1.10, IQR 1.00-1.23 vs. 1.02, IQR 0.93-1.13, p = NS). The gray-to-white matter ratio thus significantly declined from 1.17 (IQR 1.14-1.19) to 1.09 (IQR 1.07-1.10) (p < 0.0001). All 7 patients with glioblastoma showed significant increases in the SUVmax (2.20, IQR 1.67-3.32 at 2 h vs. 2.65, IQR 1.74-4.41 at 4 h, p = 0.016) and the TNR (1.75, IQR 1.40-2.38 at 2 h vs. 2.34, IQR 1.67-3.60 at 4 h, p = 0.016). CONCLUSION: In the assessment of hypoxic tumors, 18F-FMISO PET for hypoxia imaging should be obtained at 4 h rather than 2 h after the injection.
  • Spinal cord anaplastic astrocytoma with BRAF V600E mutation: A case report and review of literature.
    Soichiro Takamiya, Kanako C Hatanaka, Yukitomo Ishi, Toshitaka Seki, Shigeru Yamaguchi
    Neuropathology : official journal of the Japanese Society of Neuropathology, 40, 3, 275, 279, Jun. 2020, [Peer-reviewed], [International Magazine]
    English, Scientific journal, A 17-year-old female complained of lower extremity pain that progressed to low back pain accompanied by paraparesis. Magnetic resonance imaging revealed a mass in the conus medullaris of the spinal cord at the thoracic spine 11-12 level. The patient underwent resection of the mass. The pathological diagnosis was anaplastic astrocytoma based on the densely proliferating astrocytic tumor cells without necrosis or microvascular proliferation. The patient received chemoradiotherapy with oral temozolomide and a total of 54 Gy of local irradiation, followed by 24 courses of temozolomide as maintenance chemotherapy. The patient survived for 8 years without tumor recurrence following the initial treatment. Genetic analysis of the tumor revealed a BRAF V600E mutation that has not yet been reported in spinal cord high-grade gliomas (HGGs). In recent years, the molecular therapy targeting the BRAF V600E mutation has been applied in clinical practice for several cancer types. Although the frequency in spinal cord HGGs is uncertain, it is necessary to investigate BRAF V600E mutation as a potential therapeutic target in the future.
  • 化学療法導入直後に急激な嚢胞性増大を示した卵黄嚢腫瘍主体の頭蓋内胚細胞腫瘍の1例
    澤谷 亮佑, 山口 秀, 伊師 雪友, 茂木 洋晃, 小林 浩之, 杉山 未奈子, 長 祐子, 井口 晶裕, 大塚 拓也, 今本 鉄平, 高桑 恵美, 寳金 清博
    脳神経外科速報, 30, 3, 300, 305, (株)メディカ出版, Mar. 2020
    Japanese
  • 化学療法導入直後に急激な嚢胞性増大を示した卵黄嚢腫瘍主体の頭蓋内胚細胞腫瘍の1例               
    澤谷 亮佑, 山口 秀, 伊師 雪友, 茂木 洋晃, 小林 浩之, 杉山 未奈子, 長 祐子, 井口 晶裕, 大塚 拓也, 今本 鉄平, 高桑 恵美, 寳金 清博
    脳神経外科速報, 30, 3, 300, 305, (株)メディカ出版, Mar. 2020, [Peer-reviewed]
    Japanese
  • Association of the FGFR1 mutation with spontaneous hemorrhage in low-grade gliomas in pediatric and young adult patients.
    Yukitomo Ishi, Shigeru Yamaguchi, Kanako C Hatanaka, Michinari Okamoto, Hiroaki Motegi, Hiroyuki Kobayashi, Shunsuke Terasaka, Kiyohiro Houkin
    Journal of neurosurgery, 134, 3, 733, 741, 14 Feb. 2020, [Peer-reviewed], [International Magazine]
    English, Scientific journal, OBJECTIVE: The authors aimed to investigate genetic alterations in low-grade gliomas (LGGs) in pediatric and young adult patients presenting with spontaneous hemorrhage. METHODS: Patients younger than 30 years of age with a pathological diagnosis of World Health Organization (WHO) grade I or II glioma and who had undergone treatment at the authors' institution were retrospectively examined. BRAF V600E, FGFR1 N546/K656, IDH1 R132, IDH2 R172, and KIAA1549-BRAF (K-B) fusion genetic alterations were identified, and the presence of spontaneous tumoral hemorrhage was recorded. RESULTS: Among 66 patients (39 with WHO grade I and 27 with grade II tumors), genetic analysis revealed K-B fusion in 18 (27.3%), BRAF V600E mutation in 14 (21.2%), IDH1/2 mutation in 8 (12.1%), and FGFR1 mutation in 4 (6.1%). Spontaneous hemorrhage was observed in 5 patients (7.6%); 4 of them had an FGFR1 mutation and 1 had K-B fusion. Univariate analysis revealed a statistically significant association of an FGFR1 mutation and a diencephalic location with spontaneous hemorrhage. Among 19 diencephalic cases including the optic pathway, hypothalamus, and thalamus, an FGFR1 mutation was significantly associated with spontaneous hemorrhage (p < 0.001). Four FGFR1 mutation cases illustrated the following results: 1) a 2-year-old female with pilomyxoid astrocytoma (PMA) harboring the FGFR1 K656E mutation presented with intraventricular hemorrhage (IVH); 2) a 6-year-old male with PMA harboring FGFR1 K656E and D652G mutations presented with intratumoral hemorrhage (ITH); 3) a 4-year-old female with diffuse astrocytoma harboring FGFR1 K656M and D652G mutations presented with IVH; and 4) a young adult patient with pilocytic astrocytoma with the FGFR1 N546K mutation presented with delayed ITH and IVH after 7 years of observation. CONCLUSIONS: Although the mechanism remains unclear, the FGFR1 mutation is associated with spontaneous hemorrhage in pediatric and young adult LGG.
  • Somatic malignant transformationが疑われたgerm cell tumor再発の1例               
    高柳 歩, 原田 太以佑, 藤間 憲幸, 工藤 與亮, 岡田 宏美, 山口 秀, 小林 浩之
    Japanese Journal of Radiology, 38, Suppl., 7, 7, (公社)日本医学放射線学会, Feb. 2020
    Japanese
  • Sudden bilateral vision loss due to third ventricular cavernous angioma with intratumoral hemorrhage - case report.
    Kan Ishijima, Yasuhiro Shinmei, Mayo Nozaki, Shigeru Yamaguchi, Shinki Chin, Susumu Ishida
    BMC ophthalmology, 19, 1, 259, 259, 16 Dec. 2019, [Peer-reviewed], [International Magazine]
    English, Scientific journal, BACKGROUND: We report a rare case of sudden bilateral vision loss due to third ventricular cavernous angioma with intratumoral hemorrhage. CASE PRESENTATION: A 45-year-old woman presented decreased visual acuity in both eyes. Her best corrected visual acuity was 0.1 in the right eye and 0.15 in the left eye. Goldmann perimetry showed bilateral central scotomas and bitemporal visual field defects. MRI demonstrated a lesion with mixed hypo- and hyperintensity at the optic chiasm, which was thought to be an intratumoral hemorrhage. The patient underwent bifrontal craniotomy. The tumor was exposed via an anterior interhemispheric approach, and histological evaluation of the mass led to a diagnosis of cavernous angioma. Six months after the surgery, her best corrected visual acuity was 0.9 in the right eye and 0.9 in the left, with slight bitemporal visual field defects. CONCLUSION: Third ventricular cavernous angioma is considered in the differential diagnosis of chiasmal syndrome. Contrast-enhanced MRI and FDG-PET might be useful for differential diagnosis of cavernous angioma from other chiasmal tumors including glioblastoma.
  • Simplified Dural Reconstruction Procedure Using Biocompatible Polyglycolic Acid Felt with Autologous Abdominal Fat Grafts after a Transpetrosal Approach.
    Shigeru Yamaguchi, Shunsuke Terasaka, Michinari Okamoto, Yukitomo Ishi, Hiroaki Motegi, Hiroyuki Kobayashi, Kiyohiro Houkin
    World neurosurgery, 132, e710-e715, Dec. 2019, [Peer-reviewed], [International Magazine]
    English, Scientific journal, BACKGROUND: Dural reconstruction after transpetrosal approaches is complicated because complete primary closure of presigmoid dura mater is difficult to achieve. To address this problem, we use biocompatible polyglycolic acid (PGA) felt (Durawave) to reconstruct dural defects. To evaluate the use of PGA felt in dural reconstruction, we compared these results with those after conventional duraplasty using autologous fascia grafts. METHODS: We retrospectively surveyed all cases involving a transpetrosal approach reported since 2013. In the conventional procedure, autologous fascia was fixed over the dural defect using stay sutures; any remaining dead space was obliterated by placing abdominal fat grafts. Since April 2017, we have used PGA felt instead of fascia. RESULTS: Of the 37 cases identified, 27 were reconstructed according to the conventional procedure, and the remaining 10 cases were reconstructed using PGA felt. Among the 27 conventional cases, 8 involved cerebrospinal fluid (CSF)-related complications, including 3 cases of rhinorrhea and 5 cases of subcutaneous fluid collection, and 2 cases (7%) required repair surgery. Of the 10 cases involving PGA felt, 1 case (10%) involved subcutaneous fluid collection and required repair surgery, and whereas the remaining 9 cases had no evidence of CSF leakage. In addition, the median dural reconstruction time using PGA felt was 9 minutes, significantly shorter than that when autologous fascia was used (median, 44 minutes). CONCLUSIONS: Using PGA felt for presigmoid dura simplifies dural reconstruction because it obviates the need to suture in a deep field. PGA felt has the potential to prevent CSF-related complications after transpetrosal approaches.
  • 両側大脳半球に病変を呈したRasmussen脳炎の1例               
    岩見 昂亮, 水島 慶一, 工藤 彰彦, 高橋 育子, 大嶌 祐貴, 芳野 正修, 江口 克紀, 脇田 雅大, 白井 慎一, 松島 理明, 山口 秀, 越前谷 すみれ, 後藤 秀輔, 桑原 健, 高桑 恵美, 武井 英博, 矢部 一郎, 佐々木 秀直
    臨床神経学, 59, Suppl., S468, S468, (一社)日本神経学会, Nov. 2019
    Japanese
  • Overexpression of CD44 is associated with a poor prognosis in grade II/III gliomas.
    Chongxian Hou, Yukitomo Ishi, Hiroaki Motegi, Michinari Okamoto, Yafei Ou, Jiawei Chen, Shigeru Yamaguchi
    Journal of neuro-oncology, 145, 2, 201, 210, Nov. 2019, [Peer-reviewed], [International Magazine]
    English, Scientific journal, PURPOSE: Overexpression of CD44 has been detected in many types of tumor tissues. Moreover, CD44 is recognized as a cancer stem cell marker for many cancers. However, the prognostic value of CD44 for glioma patients has not yet been clarified. The authors tried to explore the impact of CD44 expression on grade II/III glioma patients. METHODS: To assess the RNA expression levels of CD44 in glioma tissues and normal brain tissues, meta-analyses were conducted in the online Oncomine database. The mRNA expression levels of CD44, CD44s, and CD44v2-v10 in 112 grade II/III glioma patients in Hokkaido University Hospital (HUH) were detected by qPCR. The RNA-seq data and clinical data of grade II/III glioma patients were obtained from The Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA) databases. RESULTS: Based on the Oncomine database, CD44 has significantly high expression in glioma tissues as compared with normal tissues. We explored the clinical relevance of CD44 mRNA expression based on the HUH cohorts, the TCGA cohorts, and the CGGA cohorts. In survival analysis, high mRNA expression of CD44 was correlated with poor overall survival and poor progression-free survival in grade II/III glioma patients. Multivariate Cox regression analyses confirmed CD44 as an independent prognostic factor for grade II/III glioma patients. CONCLUSIONS: The present study suggests that overexpression of CD44 is associated with a poor prognosis for grade II/III glioma patients. Moreover, our findings suggest that CD44 could serve as a prognostic biomarker in grade II/III glioma patients.
  • A Rare Case of Idiopathic Temporal Muscle Abscess in a Nine-month-old Infant.
    Sogo Oki, Masahito Kawabori, Hiroaki Motegi, Shigeru Yamaguchi, Hiroyuki Kobayashi, Shunsuke Terasaka, Kiyohiro Houkin
    Internal medicine (Tokyo, Japan), 58, 18, 2699, 2702, 15 Sep. 2019, [Peer-reviewed], [Domestic magazines]
    English, Scientific journal, Temporal muscle abscess in children usually occurs from acute otitis media, and rapid progression and concomitant infectious disease often make it easy to diagnose. We report a rare case of a nine-month-old infant who showed right temporal mass with no evidence of infection. Computed tomography showed an osteolytic round mass, and magnetic resonance imaging revealed heterogenous enhancement with a high apparent diffusion coefficient. Malignant tumor was first suspected, but an open biopsy revealed the swelling to be temporal muscle abscess. It should be noted that temporal abscess may mimic the features of a malignant tumor, and multiple examinations should be performed for an accurate diagnosis.
  • The Roles of Hypoxia Imaging Using 18F-Fluoromisonidazole Positron Emission Tomography in Glioma Treatment.
    Kenji Hirata, Shigeru Yamaguchi, Tohru Shiga, Yuji Kuge, Nagara Tamaki
    Journal of clinical medicine, 8, 8, 24 Jul. 2019, [Peer-reviewed], [International Magazine]
    English, Scientific journal, Glioma is the most common malignant brain tumor. Hypoxia is closely related to the malignancy of gliomas, and positron emission tomography (PET) can noninvasively visualize the degree and the expansion of hypoxia. Currently, 18F-fluoromisonidazole (FMISO) is the most common radiotracer for hypoxia imaging. The clinical usefulness of FMISO PET has been established; it can distinguish glioblastomas from lower-grade gliomas and can predict the microenvironment of a tumor, including necrosis, vascularization, and permeability. FMISO PET provides prognostic information, including survival and treatment response information. Because hypoxia decreases a tumor's sensitivity to radiation therapy, dose escalation to an FMISO-positive volume is an attractive strategy. Although this idea is not new, an insufficient amount of evidence has been obtained regarding this concept. New tracers for hypoxia imaging such as 18F-DiFA are being tested. In the future, hypoxia imaging will play an important role in glioma management.
  • Correlation between magnetic resonance imaging characteristics and BRAF alteration status in individuals with optic pathway/hypothalamic pilocytic astrocytomas.
    Yukitomo Ishi, Shigeru Yamaguchi, Michiharu Yoshida, Hiroaki Motegi, Hiroyuki Kobayashi, Shunsuke Terasaka, Kiyohiro Houkin
    Journal of neuroradiology = Journal de neuroradiologie, 48, 4, 266, 270, 20 Jun. 2019, [Peer-reviewed], [International Magazine]
    English, Scientific journal, BACKGROUND AND PURPOSE: Most individuals with optic pathway/hypothalamic pilocytic astrocytoma (OPHPA) harbor either the BRAF V600E mutation or KIAA1549-BRAF fusion (K-B). This study aimed to investigate the imaging characteristics of OPHPA in relation to BRAF alteration status. MATERIALS AND METHODS: Seven cases of OPHPA harboring either the BRAF V600E mutation or K-B fusion were included in the study. Preoperative magnetic resonance imaging (MRI) was assessed for degree of T2 hyperintensity on T2-weighted images (T2WI) and the ratio of nonenhancing T2 or fluid-attenuated inversion recovery (FLAIR) hyperintense area to the contrast enhanced area (CE) on gadolinium-enhanced-T1 weighted images (T2/FLAIR-CE mismatch). The T2 signal intensity was normalized to cerebrospinal fluid (T2/CSF) for both the V600E and K-B group and compared. T2/FLAIR-CE mismatch was assessed by calculating the proportion of the tumor volume of nonenhancing high T2 signal intensity to the whole lesion (nonenhancing and enhancing components). RESULTS: Four and three cases of OPHPA harboring the BRAF V600E mutation and K-B, respectively, were analyzed. The T2/CSF value was higher in the K-B group than in the V600E group. Moreover, the V600E group had a larger T2/FLAIR-CE mismatch than the K-B group. CONCLUSIONS: The BRAF alteration status in individuals with OPHPA was associated with preoperative MRI by focusing on T2 signal intensity and T2/FLAIR-CE mismatch. The BRAF V600E mutation was associated with a lower T2/CSF value and larger T2/FLAIR-CE mismatch, whereas K-B fusion was associated with a higher T2/CSF value and smaller T2/FLAIR-CE mismatch.
  • Identification of PEPT2 as an important candidate molecule in 5-ALA-mediated fluorescence-guided surgery in WHO grade II/III gliomas.
    Chongxian Hou, Shigeru Yamaguchi, Yukitomo Ishi, Shunsuke Terasaka, Hiroyuki Kobayashi, Hiroaki Motegi, Kanako C Hatanaka, Kiyohiro Houkin
    Journal of neuro-oncology, 143, 2, 197, 206, Jun. 2019, [Peer-reviewed], [International Magazine]
    English, Scientific journal, PURPOSE: 5-aminolevulinic acid (5-ALA) fluorescence-guided surgery (FGS) appears to be a promising treatment for glioma. However, 5-ALA-mediated fluorescence cannot always be detected in grade II/III gliomas. We hypothesized that gene expression patterns in the Protoporphyrin IX (PpIX) synthesis pathway may be associated with intraoperative fluorescence status of grade II/III gliomas, and then attempted to identify the key molecule of 5-ALA-mediated fluorescence. METHODS: Using 50 surgically obtained specimens, which were diagnosed as grade II and III gliomas, we analyzed gene expression within the PpIX synthesis pathway to identify candidate molecules according to intraoperative 5-ALA-mediated fluorescence status. The most likely candidate gene was selected and confirmed by protein expression analysis. To evaluate the biological function of the molecule in PpIX synthesis, functional analysis was performed using specific, small interference (si)RNA in the SW-1783 human grade III glioma cell line. RESULTS: Among the genes involved in the porphyrin synthesis pathway, the mRNA expression of Peptide transporter 2 (PEPT2) in FGS fluorescence-positive gliomas was significantly higher than that in fluorescence-negative gliomas. Protein expression of PEPT2 was also significantly higher in the fluorescence-positive gliomas, which was confirmed by western blot analysis and immunofluorescence analysis. The siRNA-mediated downregulation of the mRNA and protein expression of PEPT2 led to decreased PpIX fluorescence intensity, as confirmed by fluorescence spectrum analysis. CONCLUSIONS: The results suggest PEPT2 is an important candidate molecule in 5-ALA-mediated FGS in grade II/III gliomas. As the overexpression of PEPT2 was associated with higher PpIX fluorescence intensity, PEPT2 may improve fluorescence-guided resection in grade II/III gliomas.
  • Sonodynamic Therapy for Malignant Glioma Using 220-kHz Transcranial Magnetic Resonance Imaging-Guided Focused Ultrasound and 5-Aminolevulinic acid.
    Michiharu Yoshida, Hiroyuki Kobayashi, Shunsuke Terasaka, Shogo Endo, Shigeru Yamaguchi, Hiroaki Motegi, Rachmilevitch Itay, Shuji Suzuki, Omer Brokman, Yeruham Shapira, Kenji Moriyama, Yumiko Kawase, Toshiaki Akahane, Yasutaka Kato, Hajime Kamada, Kiyohiro Houkin
    Ultrasound in medicine & biology, 45, 2, 526, 538, Feb. 2019, [Peer-reviewed], [International Magazine]
    English, Scientific journal, Sonodynamic therapy (SDT) is used to treat various malignancies and can be applied to brain tumors using a transcranial magnetic resonance imaging-guided focused ultrasound (TcMRgFUS) device. This study investigated the efficacy of 220-kHz TcMRgFUS combined with 5-aminolevulinic acid (5-ALA) on malignant glioma in vitro and in vivo. F98 cells were irradiated with focused ultrasound (FUS) (4000 J, 20 W, 240 s, 100% duty cycle, target medium temperature <40°C) after treatment with 200 µg/mL 5-ALA, and cell viability and apoptosis were evaluated with the water-soluble tetrazolium-1 assay, triple fluorescent staining and Western blot analysis 20 h later. The anti-tumor effects of 5-ALA combined with FUS (500 J, 18 W, 30 s, 100% duty cycle, 10 repeats, target tissue temperature ≤42°C) were assessed on the basis of changes in tumor volume determined by MRI and histopathological analysis before and after treatment. The FUS/5-ALA combination reduced cell viability by inducing apoptosis and suppressed tumor proliferation and invasion as well as angiogenesis in vivo, while causing minimal damage to normal brain tissue. SDT with 220-kHz TcMRgFUS and 5-ALA can be safely used for the treatment of malignant glioma.
  • Long-Term Evaluation of Combination Treatment of Single Agent HD-MTX Chemotherapy up to Three Cycles and Moderate Dose Whole Brain Irradiation for Primary CNS Lymphoma.
    Hiroyuki Kobayashi, Shigeru Yamaguchi, Hiroaki Motegi, Sadahiro Kaneko, Shogo Endou, Rikiya Onimaru, Shunsuke Terasaka, Kiyohiro Houkin
    Journal of chemotherapy (Florence, Italy), 31, 1, 35, 41, Feb. 2019, [Peer-reviewed], [International Magazine]
    English, Scientific journal, High-dose methotrexate (HD-MTX)-based chemotherapy in combination with whole brain radiotherapy (WBRT) has been a common therapy for primary central nervous system lymphoma (PCNSL). The aim of this study was to evaluate the survival benefit of a minimized cycle of HD-MTX monotherapy prior to WBRT. A maximum of three cycles of HD-MTX was combined with a WBRT dose of 30 Gy and an additional localized boost was administered where remnant was observed. A total of 54 patients with newly diagnosed PCNSL were enrolled in this study. The objective response rate for HD-MTX was 80% and the median overall survival was 58.4 months. Responders to HD-MTX demonstrated better survival than patients with resistance. The concentration of MTX in serum and cerebrospinal fluid was not related the chemotherapeutic response. This study demonstrated the efficacy of HD-MTX prior to WBRT and indicated that three cycles of HD-MTX monotherapy may be sufficient in combination with radiotherapy.
  • Hashimoto's encephalopathy mimicking a brain tumor and its pathological findings: A case report.
    Hisashi Uwatoko, Ichiro Yabe, Shoki Sato, Megumi Abe, Shinichi Shirai, Ikuko Takahashi, Masaaki Matsushima, Takahiro Kano, Shigeru Yamaguchi, Kanako C Hatanaka, Makoto Yoneda, Hidenao Sasaki
    Journal of the neurological sciences, 394, 141, 143, 15 Nov. 2018, [Peer-reviewed], [International Magazine]
    English, Hashimoto's encephalopathy is characterized by the presence of anti-thyroid antibodies with no alternative cause. Patients with Hashimoto's encephalopathy present with various clinical symptoms and magnetic resonance imaging (MRI) findings. To our knowledge, this is the first documented report of Hashimoto's encephalopathy with MRI findings mimicking a brain tumor. The patient was a 41-year-old woman with a history of Hashimoto's disease. She experienced gradually worsening Parkinsonism and an MRI revealed a brain tumor-like lesion at the left caudate nucleus. She underwent a brain biopsy that revealed diffuse gliosis and perivascular lymphocyte infiltration with CD3+ T-cell predominance. No pathological signs of a brain tumor were found. Hashimoto's encephalopathy was suspected based on the patient's history and the presence of anti-thyroid antibodies. Her symptoms and the MRI findings improved with glucocorticoid treatment. Although there exist only a few studies on the pathology of Hashimoto's encephalopathy, our findings were consistent with those of previous reports. Our findings suggest cerebral vasculitis as an underlying etiology of Hashimoto's encephalopathy. We also emphasize the importance of considering Hashimoto's encephalopathy as a differential diagnosis of brain tumors.
  • The prognostic improvement of add-on bevacizumab for progressive disease during concomitant temozolomide and radiation therapy in the patients with glioblastoma and anaplastic astrocytoma.
    Shigeru Yamaguchi, Yukitomo Ishi, Hiroaki Motegi, Michinari Okamoto, Hiroyuki Kobayashi, Kenji Hirata, Yoshitaka Oda, Shinya Tanaka, Shunsuke Terasaka, Kiyohiro Houkin
    Journal of neurosurgical sciences, 64, 6, 502, 508, 09 Jul. 2018, [Peer-reviewed], [International Magazine]
    English, Scientific journal, BACKGROUND: Although newly diagnosed high-grade glioma patients in Japan can receive bevacizumab (BEV) as first-line chemotherapy, randomized clinical trials have not shown a survival benefit for BEV for these patients. In this study, we investigated whether selective add-on BEV for patients with newly diagnosed glioblastoma (GBM) and anaplastic astrocytoma (AA) improves prognosis, in cases where tumors were continuously growing during radiotherapy concomitant with temozolomide (TMZ). METHODS: We conducted a retrospective survey of the overall survival (OS) of patients with GBM/AAs who were treated in our institution between 2006 and 2016. Patients whose tumors were continuously growing regardless of radiotherapy were categorized as the "progressive" group; remaining patients were categorized as the "non-progressive" group. Since 2013, patients in the "progressive" group received add-on BEV therapy with the Stupp regimen during or just after radiotherapy. RESULTS: Of 151 GBM/AA patients, 34 (22.5%) were categorized in the "progressive" group. Median OSs of the "progressive" and "non-progressive" groups were 13.2 months and 25.3 months, respectively (P < 0.001). Twelve patients in the "progressive" group received add-on BEV therapy, and their median OS was 20.2 months; whereas for the remaining 22 patients in the "progressive" group who were treated before the BEV era, their median OS was 10.5 months. In the "progressive" group, add-on BEV significantly extended OS (P = 0.018) and was the lone clinical factor of better prognosis. CONCLUSIONS: We found that, for patients with GBM/AAs whose tumors were continuously growing during radiotherapy, add-on BEV treatment resulted in survival benefits.
  • 30年後の再発が疑われる脊髄Germinomaの1例               
    木野田 直也, 原田 太以佑, 吉田 篤司, 清水 幸衣, 藤間 憲幸, 工藤 興亮, Khin Khin Tha, 白土 博樹, 山口 秀, 小林 浩之, 寺坂 俊介, 岡田 宏美, 畑中 佳奈子
    Japanese Journal of Radiology, 36, Suppl., 3, 3, (公社)日本医学放射線学会, Feb. 2018
    Japanese
  • Noninvasive electrical conductivity measurement by MRI: a test of its validity and the electrical conductivity characteristics of glioma.
    Khin Khin Tha, Ulrich Katscher, Shigeru Yamaguchi, Christian Stehning, Shunsuke Terasaka, Noriyuki Fujima, Kohsuke Kudo, Ken Kazumata, Toru Yamamoto, Marc Van Cauteren, Hiroki Shirato
    European radiology, 28, 1, 348, 355, Jan. 2018, [Peer-reviewed], [International Magazine]
    English, Scientific journal, OBJECTIVES: This study noninvasively examined the electrical conductivity (σ) characteristics of diffuse gliomas using MRI and tested its validity. METHODS: MRI including a 3D steady-state free precession (3D SSFP) sequence was performed on 30 glioma patients. The σ maps were reconstructed from the phase images of the 3D SSFP sequence. The σ histogram metrics were extracted and compared among the contrast-enhanced (CET) and noncontrast-enhanced tumour components (NCET) and normal brain parenchyma (NP). Difference in tumour σ histogram metrics among tumour grades and correlation of σ metrics with tumour grades were tested. Validity of σ measurement using this technique was tested by correlating the mean tumour σ values measured using MRI with those measured ex vivo using a dielectric probe. RESULTS: Several σ histogram metrics of CET and NCET of diffuse gliomas were significantly higher than NP (Bonferroni-corrected p ≤ .045). The maximum σ of NCET showed a moderate positive correlation with tumour grade (r = .571, Bonferroni-corrected p = .018). The mean tumour σ measured using MRI showed a moderate positive correlation with the σ measured ex vivo (r = .518, p = .040). CONCLUSIONS: Tissue σ can be evaluated using MRI, incorporation of which may better characterise diffuse gliomas. KEY POINTS: • This study tested the validity of noninvasive electrical conductivity measurements by MRI. • This study also evaluated the electrical conductivity characteristics of diffuse glioma. • Gliomas have higher electrical conductivity values than the normal brain parenchyma. • Noninvasive electrical conductivity measurement can be helpful for better characterisation of glioma.
  • [Clinical Applications of Positron Emission Tomography for Neurosurgery(4)Applications of Positron Emission Tomography for Assessing Brain Tumors].
    Shigeru Yamaguchi
    No shinkei geka. Neurological surgery, 45, 11, 1015, 1024, Nov. 2017, [Peer-reviewed], [Domestic magazines]
    Japanese, Scientific journal
  • Diencephalic pediatric low-grade glioma harboring the BRAF V600E mutation presenting with various morphologies in sequential biopsy specimens.
    Yukitomo Ishi, Kanako C Hatanaka, Shigeru Yamaguchi, Hiromi Fujita, Hiroaki Motegi, Hiroyuki Kobayashi, Shunsuke Terasaka, Kiyohiro Houkin
    Brain tumor pathology, 34, 4, 165, 171, Oct. 2017, [Peer-reviewed], [Domestic magazines]
    English, Scientific journal, A 5-year-old boy underwent biopsy of an intra-axial calcified tumor in the hypothalamus, which was incidentally found. Based on the presence of ganglion-like cells combined with glial cell element, the pathological diagnosis was ganglioglioma. Because the tumor grew gradually in size over the next 2 years, he underwent chemotherapy with temozolomide. However, at 8 years of age, the boy developed hydrocephalus and the cystic lesion had re-grown. Endoscopic cyst fenestration and tumor biopsy was performed, and pathological diagnosis was tentatively oligodendroglioma based on the presence of tumor cells with a perinuclear halo. At 10 years of age, hydrocephalus recurred and the cystic lesion had re-grown. A second round of endoscopic cyst fenestration and tumor biopsy led to a pathological diagnosis of pilocytic astrocytoma due to a biphasic appearance with areas of dense tumor cells and microcystic areas, tumor cells with eosinophilic processes, and the presence of an eosinophilic granular body. Genetic analysis of the first biopsy successfully identified the BRAF V600E mutation. Because pathological diagnosis of diencephalic low-grade glioma harboring BRAF V600E would be sometimes difficult due to pathological variations, pathological diagnosis should be performed under the consideration of molecular diagnosis of BRAF V600E for optimal diagnosis and treatment.
  • 北海道大学病院の小児がん陽子線治療に対する取り組み
    橋本孝之, 井口晶裕, 寺坂俊介, 杉山美奈子, 大島淳二郎, 山口秀, 小林浩之, 長祐子, 清水伸一, 鬼丸力也, 白土博樹
    日本小児科学会雑誌, 121, 5, 914‐915, 915, (公社)日本小児科学会, 01 May 2017
    Japanese
  • Convolutional neural network (CNN) of MRI and FDG-PET images may predict hypoxia in glioblastoma.
    Takuya Toyonaga, Tohru Shiga, Kenji Hirata, Shigeru Yamaguchi, Wataru Takeuchi, Kohsuke Kudo, Keiichi Magota, Osamu Manabe, Kentaro Kobayashi, Shiro Watanabe, Yuji Kuge, Nagara Tamaki
    JOURNAL OF NUCLEAR MEDICINE, 58, May 2017, [Peer-reviewed]
    English
  • Hypoxic glucose metabolism in glioblastoma as a potential prognostic factor.
    Takuya Toyonaga, Shigeru Yamaguchi, Kenji Hirata, Kentaro Kobayashi, Osamu Manabe, Shiro Watanabe, Shunsuke Terasaka, Hiroyuki Kobayashi, Naoya Hattori, Tohru Shiga, Yuji Kuge, Shinya Tanaka, Yoichi M Ito, Nagara Tamaki
    European journal of nuclear medicine and molecular imaging, 44, 4, 611, 619, Apr. 2017, [Peer-reviewed], [International Magazine]
    English, Scientific journal, PURPOSE: Metabolic activity and hypoxia are both important factors characterizing tumor aggressiveness. Here, we used F-18 fluoromisonidazole (FMISO) and F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) to define metabolically active hypoxic volume, and investigate its clinical significance in relation to progression free survival (PFS) and overall survival (OS) in glioblastoma patients. EXPERIMENTAL DESIGN: Glioblastoma patients (n = 32) underwent FMISO PET, FDG PET, and magnetic resonance imaging (MRI) before surgical intervention. FDG and FMISO PET images were coregistered with gadolinium-enhanced T1-weighted MR images. Volume of interest (VOI) of gross tumor volume (GTV) was manually created to enclose the entire gadolinium-positive areas. The FMISO tumor-to-normal region ratio (TNR) and FDG TNR were calculated in a voxel-by-voxel manner. For calculating TNR, standardized uptake value (SUV) was divided by averaged SUV of normal references. Contralateral frontal and parietal cortices were used as the reference region for FDG, whereas the cerebellar cortex was used as the reference region for FMISO. FDG-positive was defined as the FDG TNR ≥1.0, and FMISO-positive was defined as FMISO TNR ≥1.3. Hypoxia volume (HV) was defined as the volume of FMISO-positive and metabolic tumor volume in hypoxia (hMTV) was the volume of FMISO/FDG double-positive. The total lesion glycolysis in hypoxia (hTLG) was hMTV × FDG SUVmean. The extent of resection (EOR) involving cytoreduction surgery was volumetric change based on planimetry methods using MRI. These factors were tested for correlation with patient prognosis. RESULTS: All tumor lesions were FMISO-positive and FDG-positive. Univariate analysis indicated that hMTV, hTLG, and EOR were significantly correlated with PFS (p = 0.007, p = 0.04, and p = 0.01, respectively) and that hMTV, hTLG, and EOR were also significantly correlated with OS (p = 0.0028, p = 0.037, and p = 0.014, respectively). In contrast, none of FDG TNR, FMISO TNR, GTV, HV, patients' age, or Karnofsky performance scale (KPS) was significantly correlated with PSF or OS. The hMTV and hTLG were found to be independent factors affecting PFS and OS on multivariate analysis. CONCLUSIONS: We introduced hMTV and hTLG using FDG and FMISO PET to define metabolically active hypoxic volume. Univariate and multivariate analyses demonstrated that both hMTV and hTLG are significant predictors for PFS and OS in glioblastoma patients.
  • Genomic Alterations of Adamantinomatous and Papillary Craniopharyngioma.
    Tobias Goschzik, Marco Gessi, Verena Dreschmann, Ursel Gebhardt, Linghua Wang, Shigeru Yamaguchi, David A Wheeler, Libero Lauriola, Ching C Lau, Hermann L Müller, Torsten Pietsch
    Journal of neuropathology and experimental neurology, 76, 2, 126, 134, 01 Feb. 2017, [Peer-reviewed], [International Magazine]
    English, Scientific journal, Craniopharyngiomas are rare histologically benign but clinically challenging neoplasms. To obtain further information on the molecular genetics and biology of craniopharyngiomas, we analyzed a cohort of 121 adamantinomatous and 16 papillary craniopharyngiomas (ACP, PCP). We extracted DNA from formalin-fixed paraffin-embedded tissue and determined mutational status of CTNNB1, BRAF, and DDX3X by Sanger sequencing, next generation panel sequencing, and pyrosequencing. Sixteen craniopharyngiomas were further analyzed by molecular inversion profiling (MIP); 76.1% of the ACP were mutated in exon 3 of CTNNB1 encoding for β-catenin and there was a trend towards a worse event-free survival in cases mutated at Thr41. Next generation panel sequencing of 26 ACP did not detect any recurrent mutations other than CTNNB1 mutations. BRAF V600E mutations were found in 94% of the PCP, but not in ACP. GISTIC analysis of MIP data showed no significant larger chromosomal aberrations but a fraction of ACP showed recurrent focal gains of chromosomal material, other cases showed loss in the chromosomal region Xq28, and a third group and the PCP had stable genomes. In conclusion, the crucial pathogenetic event appears to be WNT activation in ACP, whereas it appears to be activation of the Ras/Raf/MEK/ERK pathway by BRAF V600E mutations in PCP.
  • Diagnosis and surgical treatment of fourth ventricle tumors
    Shunsuke Terasaka, Shigeru Yamaguchi
    Japanese Journal of Neurosurgery, 26, 6, 436, 443, Japanese Congress of Neurological Surgeons, 2017, [Peer-reviewed]
    Japanese, Scientific journal
  • Change in F-18-Fluoromisonidazole PET Is an Early Predictor of the Prognosis in the Patients with Recurrent High-Grade Glioma Receiving Bevacizumab Treatment
    Shigeru Yamaguchi, Kenji Hirata, Takuya Toyonaga, Kentaro Kobayashi, Yukitomo Ishi, Hiroaki Motegi, Hiroyuki Kobayashi, Tohru Shiga, Nagara Tamaki, Shunsuke Terasaka, Kiyohiro Houkin
    PLOS ONE, 11, 12, e0167917, Dec. 2016, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • A significant correlation between delayed cure after microvascular decompression and positive response to preoperative anticonvulsant therapy in patients with hemifacial spasm
    Shunsuke Terasaka, Katsuyuki Asaoka, Shigeru Yamaguchi, Hiroyuki Kobayashi, Hiroaki Motegi, Kiyohiro Houkin
    NEUROSURGICAL REVIEW, 39, 4, 607, 612, Oct. 2016, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • Reliability of the Size Evaluation Method for Meningiomas: Maximum Diameter, ABC/2 Formula, and Planimetry Method
    Yukitomo Ishi, Shunsuke Terasaka, Shigeru Yamaguchi, Michiharu Yoshida, Shogo Endo, Hiroyuki Kobayashi, Kiyohiro Houkin
    WORLD NEUROSURGERY, 94, 80, 88, Oct. 2016, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • [Risk factor of brain tumor: General statement].
    Shigeru Yamaguchi
    Nihon rinsho. Japanese journal of clinical medicine, 74 Suppl 7, 70, 71, Sep. 2016, [Domestic magazines]
    Japanese, Scientific journal
  • Cellular Functions and Gene and Protein Expression Profiles in Endothelial Cells Derived from Moyamoya Disease-Specific iPS Cells
    Shuji Hamauchi, Hideo Shichinohe, Haruto Uchino, Shigeru Yamaguchi, Naoki Nakayama, Ken Kazumata, Toshiya Osanai, Takeo Abumiya, Kiyohiro Houkin, Takumi Era
    PLOS ONE, 11, 9, e0163561, Sep. 2016, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • 小児頭蓋内奇形腫の2例
    小林 聡, 山口 秀, 遠藤 将吾, 小林 浩之, 寺坂 俊介, 畑中 佳奈子, 宝金 清博
    日本小児血液・がん学会雑誌, 53, 2, 165, 165, (一社)日本小児血液・がん学会, Jul. 2016
    Japanese
  • (18)F-fluoromisonidazole positron emission tomography can predict pathological necrosis of brain tumors.
    Takuya Toyonaga, Kenji Hirata, Shigeru Yamaguchi, Kanako C Hatanaka, Sayaka Yuzawa, Osamu Manabe, Kentaro Kobayashi, Shiro Watanabe, Tohru Shiga, Shunsuke Terasaka, Hiroyuki Kobayashi, Yuji Kuge, Nagara Tamaki
    European journal of nuclear medicine and molecular imaging, 43, 8, 1469, 76, Jul. 2016, [Peer-reviewed], [International Magazine]
    English, Scientific journal, PURPOSE: Tumor necrosis is one of the indicators of tumor aggressiveness. (18)F-fluoromisonidazole (FMISO) is the most widely used positron emission tomography (PET) tracer to evaluate severe hypoxia in vivo. Because severe hypoxia causes necrosis, we hypothesized that intratumoral necrosis can be detected by FMISO PET in brain tumors regardless of their histopathology. We applied FMISO PET to various types of brain tumors before tumor resection and evaluated the correlation between histopathological necrosis and FMISO uptake. METHODS: This study included 59 brain tumor patients who underwent FMISO PET/computed tomography before any treatments. According to the pathological diagnosis, the brain tumors were divided into three groups: astrocytomas (group 1), neuroepithelial tumors except for astrocytomas (group 2), and others (group 3). Two experienced neuropathologists evaluated the presence of necrosis in consensus. FMISO uptake in the tumor was evaluated visually and semi-quantitatively using the tumor-to-normal cerebellum ratio (TNR). RESULTS: In visual analyses, 26/27 cases in the FMISO-positive group presented with necrosis, whereas 28/32 cases in the FMISO-negative group did not show necrosis. Mean TNRs with and without necrosis were 3.49 ± 0.97 and 1.43 ± 0.42 (p < 0.00001) in group 1, 2.91 ± 0.83 and 1.44 ± 0.20 (p < 0.005) in group 2, and 2.63 ± 1.16 and 1.35 ± 0.23 (p < 0.05) in group 3, respectively. Using a cut-off value of TNR = 1.67, which was calculated by normal reference regions of interest, we could predict necrosis with sensitivity, specificity, and accuracy of 96.7, 93.1, and 94.9 %, respectively. CONCLUSIONS: FMISO uptake within the lesion indicated the presence of histological micro-necrosis. When we used a TNR of 1.67 as the cut-off value, intratumoral micro-necrosis was sufficiently predictable. Because the presence of necrosis implies a poor prognosis, our results suggest that FMISO PET could provide important information for treatment decisions or surgical strategies of any type of brain tumor.
  • Primary pineal rhabdomyosarcoma successfully treated by high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation: case report
    Yukitomo Ishi, Shigeru Yamaguchi, Akihiro Iguchi, Yuko Cho, Junjiro Ohshima, Kanako C. Hatanaka, Emi Takakuwa, Hiroyuki Kobayashi, Shunsuke Terasaka, Kiyohiro Houkin
    JOURNAL OF NEUROSURGERY-PEDIATRICS, 18, 1, 41, 45, Jul. 2016, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • Clinical impact of targeted amplicon sequencing for meningioma as a practical clinical-sequencing system
    Sayaka Yuzawa, Hiroshi Nishihara, Shigeru Yamaguchi, Hiromi Mohri, Lei Wang, Taichi Kimura, Masumi Tsuda, Mishie Tanino, Hiroyuki Kobayashi, Shunsuke Terasaka, Kiyohiro Houkin, Norihiro Sato, Shinya Tanaka
    MODERN PATHOLOGY, 29, 7, 708, 716, Jul. 2016, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • [Efficiency of Embosphere in the Pre-Operative Embolization of Meningioma:Clinical Experience].
    Yusuke Shimoda, Toshiya Osanai, Syunsuke Terasaka, Hiroyuki Kobayashi, Shigeru Yamaguchi, Shogo Endo, Kanako Hatanaka, Kiyohiro Houkin
    No shinkei geka. Neurological surgery, 44, 7, 555, 60, Jul. 2016, [Peer-reviewed], [Domestic magazines]
    Japanese, Scientific journal, Embosphere® was approved in Japan for embolizing intracranial arteries for the reduction of intraoperative bleeding in January 2014. Until August 2015, we performed embolization for four meningiomas using Embosphere®. We performed an initial evaluation of all the cases, including evaluation of the clinical courses, change in the maximum tumor diameters and volumes, alteration in the appearance on magnetic resonance imaging(MRI), amount of intraoperative bleeding, complications, and histopathological findings. After embolization, the maximum tumor diameters and volumes slightly decreased on MRI, whereas the signal change on diffusion-weighted imaging(DWI)or fluid-attenuated inversion recovery(FLAIR)varied in each case. One case demonstrated a partial signal change on DWI one day after the initial procedure, and another case demonstrated a decrease in perifocal edema on FLAIR. Among our patients, least bleeding was recorded at 6 days after the embolization. Histopathological analysis revealed coagulative necrotic lesions in two cases. The von Kossa stain was used to distinguish Embosphere® from the psammoma body. One case involved a thromboembolic complication of the retinocentral artery caused by an Embosphere® of 100-300 μm. Our early-stage experience suggests that an Embosphere® of 300-500 μm should be used for safe embolization before resection to avoid thromboembolic complications because an Embosphere® of 100-300 μm can pass through the dangerous anastomosis. Our present strategy was to resect the tumor approximately seven days after the embolization using Embosphere®. However, further studies and discussion on the size of Embosphere®, and the interval between pre-operative embolization and surgical removal are needed.
  • Use of convolutional neural network as the first step of fully automated tumor detection on 11C-methionine brain PET
    Hirata Kenji, Takeuchi Wataru, Yamaguchi Shigeru, Kobayashi Hiroyuki, Terasaka Shunsuke, Toyonaga Takuya, Watanabe Shiro, Kobayashi Kentaro, Manabe Osamu, Kobashi Keiji, Shiga Tohru, Tamaki Nagara
    JOURNAL OF NUCLEAR MEDICINE, 57, 01 May 2016, [Peer-reviewed]
  • Prognostic Imaging Biomarkers in Glioblastoma: Development and Independent Validation on the Basis of Multiregion and Quantitative Analysis of MR Images
    Yi Cui, Khin Khin Tha, Shunsuke Terasaka, Shigeru Yamaguchi, Jeff Wang, Kohsuke Kudo, Lei Xing, Hiroki Shirato, Ruijiang Li
    RADIOLOGY, 278, 2, 546, 553, Feb. 2016, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • Genetic analysis of revertants isolated from the rod-fragile fliF mutant of Salmonella.
    Hitomi Komatsu, Fumio Hayashi, Masahiro Sasa, Koji Shikata, Shigeru Yamaguchi, Keiichi Namba, Kenji Oosawa
    Biophysics and physicobiology, 13, 13, 25, 2016, [Domestic magazines]
    English, Scientific journal, FliF is the protein comprising the MS-ring of the bacterial flagellar basal body, which is the base for the assembly of flagellar axial structures. From a fliF mutant that easily releases the rod-hook-filament in viscous environments, more than 400 revertants that recovered their swarming ability in viscous conditions, were isolated. The second-site mutations were determined for approximately 70% of them. There were three regions where the mutations were localized: two in Region I, 112 in Region II, and 71 in Region III including the true reversion. In Region I, second-site mutations were found in FlgC and FlgF of the proximal rod, suggesting that they affect the interaction between the MS-ring and the rod. In Region II, there were 69 and 42 mutations in MotA and MotB, respectively, suggesting that the second-site mutations in MotA and MotB may decrease the rotational speed of the flagellar motor to reduce the probability of releasing the rod under this condition. One exception is a mutation in FlhC that caused a down regulation of the flagellar proteins production but it may directly affect transcription or translation of motA and motB. In Region III, there were 44, 24, and 3 mutations in FliG, FliM, and FliF, respectively. There were no second-site mutations identified in FliN although it is involved in torque generation as a component of the C-ring. Many of the mutations were involved in the motor rotation, and it is suggested that such reduced speeds result in stabilizing the filament attachment to the motor.
  • Application of endoscopic ultrasonography to intraventricular lesions
    Hiroaki Motegi, Hiroyuki Kobayashi, Shunsuke Terasaka, Shigeru Yamaguchi, Yukitomo Ishi, Yasuhiro Ito, Kiyohiro Houkin
    ACTA NEUROCHIRURGICA, 158, 1, 87, 92, Jan. 2016, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • Endoscopic transsphenoidal surgery using pedicle vascularized nasoseptal flap for cholesterol granuloma in petrous apex: A technical note
    Yukitomo Ishi, Hiroyuki Kobayashi, Hiroaki Motegi, Shogo Endo, Shigeru Yamaguchi, Shunsuke Terasaka, Kiyohiro Houkin
    NEUROLOGIA I NEUROCHIRURGIA POLSKA, 50, 6, 504, 510, 2016, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • キャンサーボードが機能した1症例               
    遠藤 将吾, 寺坂 俊介, 小林 浩之, 山口 秀, 茂木 洋晃, 金子 貞洋, 井口 晶裕, 長 祐子, 大島 淳二郎, 寺坂 友佳代, 杉山 未奈子, 橋本 孝之, 鬼丸 力也, 清水 伸一, 有賀 正, 白戸 博樹, 寳金 清博
    日本小児血液・がん学会雑誌, 52, 3, 343, 343, (NPO)日本小児血液・がん学会, Oct. 2015
    Japanese
  • PORPHYRIN DERIVATIVES-MEDIATED SONODYNAMIC THERAPY FOR MALIGNANT GLIOMAS IN VITRO
    Shogo Endo, Nobuki Kudo, Shigeru Yamaguchi, Koki Sumiyoshi, Hiroaki Motegi, Hiroyuki Kobayashi, Shunsuke Terasaka, Kiyohiro Houkin
    ULTRASOUND IN MEDICINE AND BIOLOGY, 41, 9, 2458, 2465, Sep. 2015, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • 悪性神経膠腫におけるギリアデル留置後の有害事象とその要因の検討
    吉田 道春, 山口 秀, 伊師 雪友, 遠藤 将吾, 茂木 洋晃, 小林 浩之, 浅岡 克行, 鴨嶋 雄大, 寺坂 俊介, 寳金 清博
    Neurological Surgery, 43, 7, 603, 610, (株)医学書院, Jul. 2015
    Japanese
  • Risk factors for adverse events after implantation of BCNU wafers in high-grade gliomas
    Michiharu Yoshida, Shigeru Yamaguchi, Yukitomo Ishi, Shogo Endo, Hiroaki Motegi, Hiroyuki Kobayashi, Katsuyuki Asaoka, Yuuta Kamoshima, Shunsuke Terasaka, Kiyohiro Houkin
    Neurological Surgery, 43, 7, 603, 610, Igaku-Shoin Ltd, 01 Jul. 2015, [Peer-reviewed], [Domestic magazines]
    Japanese, Scientific journal
  • Prognostic value of volume-based measurements on (11)C-methionine PET in glioma patients.
    Kentaro Kobayashi, Kenji Hirata, Shigeru Yamaguchi, Osamu Manabe, Shunsuke Terasaka, Hiroyuki Kobayashi, Tohru Shiga, Naoya Hattori, Shinya Tanaka, Yuji Kuge, Nagara Tamaki
    European journal of nuclear medicine and molecular imaging, 42, 7, 1071, 80, Jun. 2015, [Peer-reviewed], [International Magazine]
    English, Scientific journal, PURPOSE: (11)C-methionine (MET) PET is an established diagnostic tool for glioma. Studies have suggested that MET uptake intensity in the tumor is a useful index for predicting patient outcome. Because MET uptake is known to reflect tumor expansion more accurately than MRI, we aimed to elucidate the association between volume-based tumor measurements and patient prognosis. METHODS: The study population comprised 52 patients with newly diagnosed glioma who underwent PET scanning 20 min after injection of 370 MBq MET. The tumor was contoured using a threshold of 1.3 times the activity of the contralateral normal cortex. Metabolic tumor volume (MTV) was defined as the total volume within the boundary. Total lesion methionine uptake (TLMU) was defined as MTV times the mean standardized uptake value (SUVmean) within the boundary. The tumor-to-normal ratio (TNR), calculated as the maximum standardized uptake value (SUVmax) divided by the contralateral reference value, was also recorded. All patients underwent surgery (biopsy or tumor resection) targeting the tissue with high MET uptake. The Kaplan-Meier method was used to estimate the predictive value of each measurement. RESULTS: Grade II tumor was diagnosed in 12 patients (3 diffuse astrocytoma, 2 oligodendroglioma, and 7 oligoastrocytoma), grade III in 18 patients (8 anaplastic astrocytoma, 6 anaplastic oligodendroglioma, and 4 anaplastic oligoastrocytoma), and grade IV in 22 patients (all glioblastoma). TNR, MTV and TLMU were 3.1 ± 1.2, 51.6 ± 49.9 ml and 147.7 ± 153.3 ml, respectively. None of the three measurements was able to categorize the glioma patients in terms of survival when all patients were analyzed. However, when only patients with astrocytic tumor (N = 33) were analyzed (i.e., when those with oligodendroglial components were excluded), MTV and TLMU successfully predicted patient outcome with higher values associated with a poorer prognosis (P < 0.05 and P < 0.01, respectively), while the predictive ability of TNR did not reach statistical significance (P = NS). CONCLUSION: MTV and TLMU may be useful for predicting outcome in patients with astrocytic tumor.
  • Improvement of cerebral hypometabolism after resection of radiation-induced necrotic lesion in a patient with cerebral arteriovenous malformation.
    Yae Harada, Kenji Hirata, Naoki Nakayama, Shigeru Yamaguchi, Michiharu Yoshida, Shunsuke Onodera, Osamu Manabe, Tohru Shiga, Satoshi Terae, Hiroki Shirato, Nagara Tamaki
    Acta radiologica open, 4, 6, 2058460115584112, 2058460115584112, Jun. 2015, [Peer-reviewed], [International Magazine]
    English, A 55-year-old woman underwent radiosurgery for a left cerebral hemisphere arteriovenous malformation (AVM) and developed radiation-induced necrosis causing a massive edema in the surrounding brain tissues. Despite various therapies, the edema expanded to the ipsilateral hemisphere and induced neurological symptoms. The radiation-induced necrotic lesion was surgically removed 4 years after radiosurgery. While the preoperative FDG PET revealed severe hypometabolism in the left cerebrum, the necrotomy significantly ameliorated the brain edema, glucose metabolism (postoperative FDG PET), and symptoms. This case indicates that radiation necrosis-induced neurological deficits may be associated with brain edema and hypometabolism, which could be reversed by appropriate necrotomy.
  • Oligodendroglial component complicates the prediction of tumour grading with metabolic imaging.
    Osamu Manabe, Naoya Hattori, Shigeru Yamaguchi, Kenji Hirata, Kentaro Kobayashi, Shunsuke Terasaka, Hiroyuki Kobayashi, Hiroaki Motegi, Tohru Shiga, Keiichi Magota, Noriko Oyama-Manabe, Ken-ichi Nishijima, Yuji Kuge, Nagara Tamaki
    European journal of nuclear medicine and molecular imaging, 42, 6, 896, 904, May 2015, [Peer-reviewed], [International Magazine]
    English, Scientific journal, PURPOSE: Previous radiological investigations have generally shown the superiority of metabolic imaging in distinguishing high-grade from low-grade glioma, but the presence of an oligodendroglial component may affect the diagnostic accuracy. We investigated the diagnostic accuracy of PET imaging using (11)C-methionine (MET) and (18)F-fluorodeoxyglucose (FDG) in distinguishing high-grade from low-grade glioma, in correlation with the oligodendroglial component. METHODS: The study population comprised adult patients who underwent preoperative PET imaging using both MET and FDG within 1 week and successful excision of the tumour tissue, which confirmed WHO grade II-IV glioma. We examined the tumour metabolic activity in terms of lesion-to-normal uptake ratios (L/N ratio) in both MET PET and FDG PET images. We assessed the correlation between the imaging results and the histological findings to determine the diagnostic accuracy of receiver operating characteristics (ROC) analysis in detecting high-grade tumours. RESULTS: We studied 46 patients with glioma (13 low-grade and 33 high-grade), including 26 with an oligodendroglial components. The L/N ratios of the PET images showed significantly higher metabolic activities in high-grade gliomas than in low-grade gliomas for both MET (4.29 ± 1.22 and 2.36 ± 0.72, respectively; p < 0.0001) and FDG (1.72 ± 0.91 and 0.77 ± 0.26, respectively; p = 0.0007) images, although significant overlaps in L/N ratio were observed between high-grade and low-grade gliomas. Excluding the 26 patents with an oligodendroglial component improved the separation for both MET (4.62 ± 1.14 vs. 2.16 ± 0.63; p < 0.001) and FDG (1.76 ± 0.87 vs. 0.71 ± 0.14; p < 0.05) images. The ROC analyses demonstrated the clinical utility of the metabolic radiotracers in distinguishing high-grade from low-grade gliomas, showing similar AUC values for MET (0.91) and FDG (0.92). Excluding the 26 patents with an oligodendroglial component also further improved the diagnostic accuracy for both MET (AUC 0.98), and FDG (AUC 1.00) images. The metabolic radiotracers were significantly correlated with the MIB-1 labelling index (R = 0.52, p < 0.05 for MET; R = 0.52, p < 0.05, for FDG) only in gliomas without an oligodendroglial component. CONCLUSION: For better characterization of gliomas and for risk assessment, the results of metabolic PET imaging should be revised after obtaining the pathological report, because oligodendroglial differentiation may positively influence the substrate metabolism and thus complicated the preoperative evaluation.
  • Combined use of 18 F-FDG PET and corticosteroid for diagnosis of deep-seated primary central nervous system lymphoma without histopathological confirmation
    Shigeru Yamaguchi, Kenji Hirata, Sadahiro Kaneko, Hiroyuki Kobayashi, Tohru Shiga, Kentaro Kobayashi, Rikiya Onimaru, Hiroki Shirato, Nagara Tamaki, Shunsuke Terasaka, Kiyohiro Houkin
    ACTA NEUROCHIRURGICA, 157, 2, 187, 194, Feb. 2015, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • The diagnostic role of (18)F-FDG PET for primary central nervous system lymphoma.
    Shigeru Yamaguchi, Kenji Hirata, Hiroyuki Kobayashi, Tohru Shiga, Osamu Manabe, Kentaro Kobayashi, Hiroaki Motegi, Shunsuke Terasaka, Kiyohiro Houkin
    Annals of nuclear medicine, 28, 7, 603, 9, Aug. 2014, [Peer-reviewed], [Domestic magazines]
    English, Scientific journal, OBJECTIVE: (18)F-FDG PET has become one of the most important methods for studying malignant lymphoma, but its diagnostic role for primary central nervous system lymphoma (PCNSL) has not been established. The aim of this study was to determine the appropriate cut-off values of FDG uptake and to investigate how corticosteroid administration influences PCNSL. METHODS: We retrospectively reviewed 82 patients with contrast-enhanced brain tumors who underwent an FDG PET scan at onset, including 19 PCNSLs. FDG uptake of the lesion was assessed by the maximum standardized uptake value (SUVmax) and the ratio of tumor to normal contralateral cortex activity (T/N ratio). Receiver operating characteristic (ROC) curves were generated from the SUVmax and T/N ratios. To investigate the influence of corticosteroid application before a FDG PET scan, we evaluated the association between the FDG uptake of the lesion and the cumulative dose of corticosteroid administration on 13 PCNSL patients who had received steroid treatment before an FDG PET examination. RESULTS: The mean FDG SUVmax and T/N ratio of PCNSLs were 22.6 and 2.79, respectively, and these values were significantly higher than those of the other malignant brain tumors. ROC analysis indicated that the evaluation of FDG uptake using the T/N ratio was more reliable than the SUVmax with respect to the differential diagnosis. When PCNSL patients went without steroid application before FDG PET, the accuracy of the T/N ratio with a cut-off point of 2.0 was 91.1%, the sensitivity was 94.7%, and the specificity was 87.3%. Although there are no significant differences in the FDG T/N ratio for PCNSL patients with or without steroid treatment, a negative correlation was found between the T/N ratio and cumulative dose of corticosteroid before PET study (r = -0.71, p = 0.032). CONCLUSIONS: We concluded that the T/N ratio was superior to SUVmax for FDG uptake assessment as for distinguishing PCNSLs from other malignant brain tumors; the appropriate T/N ratio cut-off point was 2.0. In addition, FDG uptake could be influenced by cumulative doses of corticosteroid before a PET scan, and thus this fact should be taken into consideration when evaluating FDG PET for PCNSL diagnosis.
  • Novel somatic and germline mutations in intracranial germ cell tumours
    Linghua Wang, Shigeru Yamaguchi, Matthew D. Burstein, Keita Terashima, Kyle Chang, Ho-Keung Ng, Hideo Nakamura, Zongxiao He, Harshavardhan Doddapaneni, Lora Lewis, Mark Wang, Tomonari Suzuki, Ryo Nishikawa, Atsushi Natsume, Shunsuke Terasaka, Robert Dauser, William Whitehead, Adesina Adekunle, Jiayi Sun, Yi Qiao, Gabor Marth, Donna M. Muzny, Richard A. Gibbs, Suzanne M. Leal, David A. Wheeler, Ching C. Lau
    NATURE, 511, 7508, 241, +, Jul. 2014, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • Immunohistochemical evaluation of O-6-methylguanine DNA methyltransferase (MGMT) expression in 117 cases of glioblastoma
    Masaya Miyazaki, Hiroshi Nishihara, Shunsuke Terasaka, Hiroyuki Kobayashi, Shigeru Yamaguchi, Tamio Ito, Yuuta Kamoshima, Shin Fujimoto, Sadao Kaneko, Masahito Katoh, Nobuaki Ishii, Hiromi Mohri, Mishie Tanino, Taichi Kimura, Shinya Tanaka
    NEUROPATHOLOGY, 34, 3, 268, 276, Jun. 2014, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • 小児脳腫瘍における急性期水頭症管理
    山口 秀, 寺坂 俊介, 小林 浩之, 茂木 洋晃, 宝金 清博
    日本小児血液・がん学会雑誌, 51, 2, 183, 184, (一社)日本小児血液・がん学会, Jun. 2014
    Japanese
  • 北海道大学病院陽子線治療センターの小児陽子線治療開始準備状況               
    橋本 孝之, 清水 伸一, 鬼丸 力也, 大島 淳二郎, 長 祐子, 井口 晶裕, 山口 秀, 小林 浩之, 寺坂 俊介, 岡田 忠雄, 本田 昌平, 武冨 紹信, 岡村 麗香, 中村 宏治, 白土 博樹
    日本小児血液・がん学会雑誌, 51, 2, 183, 183, (NPO)日本小児血液・がん学会, Jun. 2014
    Japanese
  • Prognostic Factors for Survival in Patients with High-Grade Meningioma and Recurrence-Risk Stratification for Application of Radiotherapy
    Shigeru Yamaguchi, Shunsuke Terasaka, Hiroyuki Kobayashi, Katsuyuki Asaoka, Hiroaki Motegi, Hiroshi Nishihara, Hiromi Kanno, Rikiya Onimaru, Yoichi M. Ito, Hiroki Shirato, Kiyohiro Houkin
    PLOS ONE, 9, 5, e97108, May 2014, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • Successful removal of a metastatic gastrointestinal stromal tumor in the craniovertebral junction using an occipital artery to posterior inferior cerebellar artery bypass
    Yukitomo Ishi, Naoki Nakayama, Hiroyuki Kobayashi, Shigeru Yamaguchi, Shunsuke Terasaka, Kiyohiro Houkin
    Case Reports in Neurology, 6, 2, 139, 143, S. Karger AG, 16 Apr. 2014, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • Hemorrhagic onset of hemangioblastoma located in the dorsal medulla oblongata presenting with tako-tsubo cardiomyopathy and neurogenic pulmonary edema: A case report
    Masayuki Gekka, Shigeru Yamaguchi, Ken Kazumata, Hiroyuki Kobayashi, Hiroaki Motegi, Shunsuke Terasaka, Kiyohiro Houkin
    Case Reports in Neurology, 6, 1, 68, 73, S. Karger AG, 2014, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • Usefulness of FMISO-PET for Glioma Analysis
    Hiroyuki Kobayashi, Kenji Hirata, Shigeru Yamaguchi, Shunsuke Terasaka, Tohru Shiga, Kiyohiro Houkin
    NEUROLOGIA MEDICO-CHIRURGICA, 53, 11, 773, 778, Nov. 2013, [Peer-reviewed], [Domestic magazines]
    English, Scientific journal
  • IDH1 mutation as a potential novel biomarker for distinguishing pseudoprogression from true progression in patients with glioblastoma treated with temozolomide and radiotherapy
    Hiroaki Motegi, Yuuta Kamoshima, Shunsuke Terasaka, Hiroyuki Kobayashi, Shigeru Yamaguchi, Mishie Tanino, Junichi Murata, Kiyohiro Houkin
    BRAIN TUMOR PATHOLOGY, 30, 2, 67, 72, Apr. 2013, [Peer-reviewed], [Domestic magazines]
    English, Scientific journal
  • Primary rhabdoid tumor with low grade glioma component of the central nervous system in a young adult
    Shogo Endo, Shunsuke Terasaka, Shigeru Yamaguchi, Hitoshi Ikeda, Tsutomu Kato, Hiroyuki Kobayashi, Shinya Tanaka, Kiyohiro Houkin
    NEUROPATHOLOGY, 33, 2, 185, 191, Apr. 2013, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • Prognostic Implication of Histological Oligodendroglial Tumor Component: Clinicopathological Analysis of 111 Cases of Malignant Gliomas
    Hiromi Kanno, Hiroshi Nishihara, Takuhito Narita, Shigeru Yamaguchi, Hiroyuki Kobayashi, Mishie Tanino, Taichi Kimura, Shunsuke Terasaka, Shinya Tanaka
    PLOS ONE, 7, 7, e41669, Jul. 2012, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • F-18-Fluoromisonidazole positron emission tomography may differentiate glioblastoma multiforme from less malignant gliomas
    Kenji Hirata, Shunsuke Terasaka, Tohru Shiga, Naoya Hattori, Keiichi Magota, Hiroyuki Kobayashi, Shigeru Yamaguchi, Kiyohiro Houkin, Shinya Tanaka, Yuji Kuge, Nagara Tamaki
    EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING, 39, 5, 760, 770, May 2012, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • The Impact of Extent of Resection and Histological Subtype on the Outcome of Adult Patients with High-grade Gliomas
    Shigeru Yamaguchi, Hiroyuki Kobayashi, Shunsuke Terasaka, Nobuaki Ishii, Jun Ikeda, Hiromi Kanno, Hiroshi Nishihara, Shinya Tanaka, Kiyohiro Houkin
    JAPANESE JOURNAL OF CLINICAL ONCOLOGY, 42, 4, 270, 277, Apr. 2012, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • A case of surgical treatment for giant hemangioblastoma in the dorsal medulla oblongata
    Yuuta Kamoshima, Shunsuke Terasaka, Yusuke Shimoda, Hiroyuki Kobayashi, Satoshi Kuroda, Takeshi Asano, Shigeru Yamaguchi, Junichi Murata, Kiyohiro Houkin
    Neurological Surgery, 40, 3, 229, 234, 3, 10 Mar. 2012, [Peer-reviewed], [Domestic magazines]
    Japanese, Scientific journal
  • Analyses of IDH1 mutation and MGMT promoter methylation status for 5 cases of long-term survivors with glioblastoma
    Yuuta Kamoshima, Hiroaki Motegi, Shunsuke Terasaka, Hiroyuki Kobayashi, Shigeru Yamaguchi, Junichi Murata, Shinya Tanaka, Kiyohiro Houkin
    Neurological Surgery, 40, 2, 129, 135, 2, 10 Feb. 2012, [Peer-reviewed], [Domestic magazines]
    Japanese, Scientific journal
  • Giant Skull Base Atypical Meningioma Presenting With Rapidly Progressive Impaired Consciousness Caused by Severe Venous Congestion-Case Report
    Shigeru Yamaguchi, Shunsuke Terasaka, Hiroyuki Kobayashi, Katsuyuki Asaoka, Junichi Murata, Kiyohiro Houkin
    NEUROLOGIA MEDICO-CHIRURGICA, 51, 11, 789, 792, Nov. 2011, [Peer-reviewed], [Domestic magazines]
    English, Scientific journal
  • Sonodynamic therapy using water-dispersed TiO2-polyethylene glycol compound on glioma cells: Comparison of cytotoxic mechanism with photodynamic therapy
    Shigeru Yamaguchi, Hiroyuki Kobayashi, Takuhito Narita, Koki Kanehira, Shuji Sonezaki, Nobuki Kudo, Yoshinobu Kubota, Shunsuke Terasaka, Kiyohiro Houkin
    ULTRASONICS SONOCHEMISTRY, 18, 5, 1197, 1204, Sep. 2011, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • Primary Central Nervous System Mucosa-Associated Lymphoid Tissue Lymphoma-Case Report
    Yuuta Kamoshima, Yutaka Sawamura, Taku Sugiyama, Shigeru Yamaguchi, Kiyohiro Houkin, Kanako Kubota
    NEUROLOGIA MEDICO-CHIRURGICA, 51, 7, 527, 530, Jul. 2011, [Peer-reviewed], [Domestic magazines]
    English, Scientific journal
  • High grade meningiomaの治療成績とMib-1 indexの関係の検討               
    成田 拓人, 菅野 宏美, 湯澤 明夏, 寺坂 俊介, 小林 浩之, 村田 純一, 山口 秀, 西原 広史, 宝金 清博, 田中 伸哉
    Brain Tumor Pathology, 28, Suppl., 092, 092, 日本脳腫瘍病理学会, May 2011
    Japanese
  • 画像と病理所見から多中心性神経膠腫と診断した一例               
    茂木 洋晃, 寺坂 俊介, 小林 浩之, 鴨嶋 雄大, 山口 秀, 遠藤 将吾, 宝金 清博, 高阪 真路, 田中 伸哉, 村田 純一
    Brain Tumor Pathology, 28, Suppl., 123, 123, 日本脳腫瘍病理学会, May 2011
    Japanese
  • Anterior Interhemispheric Approach for Tuberculum Sellae Meningioma
    Shunsuke Terasaka, Katsuyuki Asaoka, Hiroyuki Kobayashi, Shigeru Yamaguchi
    NEUROSURGERY, 68, 3, 84, 89, Mar. 2011, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • Dural Opening/Removal for Combined Petrosal Approach: Technical Note
    Shunsuke Terasaka, Katsuyuki Asaoka, Hiroyuki Kobayashi, Taku Sugiyama, Shigeru Yamaguchi
    SKULL BASE-AN INTERDISCIPLINARY APPROACH, 21, 2, 123, 127, Mar. 2011, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • Anterior Interhemispheric Approach for Tuberculum Sellae Meningioma
    Shunsuke Terasaka, Katsuyuki Asaoka, Hiroyuki Kobayashi, Shigeru Yamaguchi
    NEUROSURGERY, 68, Mar. 2011, [Peer-reviewed]
    English, Scientific journal
  • Detection of histological anaplasia in gliomas with oligodendroglial components using positron emission tomography with F-18-FDG and C-11-methionine: report of two cases
    Shigeru Yamaguchi, Hiroyuki Kobayashi, Kenji Hirata, Tohru Shiga, Shinya Tanaka, Junichi Murata, Shunsuke Terasaka
    JOURNAL OF NEURO-ONCOLOGY, 101, 2, 335, 341, Jan. 2011, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • Multiple infectious intracranial lesions of Mycobacterium genavense in an immunocompromised patient
    Haruto Uchino, Shunsuke Terasaka, Shigeru Yamaguchi, Hiroyuki Kobayashi, Kagari Kawai, Kanako Kubota, Shinji Ooe, Kiyohiro Houkin
    Brain and Nerve, 63, 1, 79, 83, 1, 01 Jan. 2011, [Peer-reviewed], [Domestic magazines]
    Japanese, Scientific journal
  • 原発性免疫不全症患者に合併したMycobacterium genavense感染による多発脳病変の1例
    内野 晴登, 寺坂 俊介, 山口 秀, 小林 浩之, 川合 かがり, 久保田 佳奈子, 大江 真司, 宝金 清博
    BRAIN and NERVE: 神経研究の進歩, 63, 1, 79, 83, (株)医学書院, Jan. 2011
    Japanese
  • Natural history and surgical results of petroclival meningiomas
    Shunsuke Terasaka, Katsuyuki Asaoka, Hiroyuki Kobayashi, Shigeru Yamaguchi, Yutaka Sawamura
    Neurological Surgery, 38, 9, 817, 824, 9, 10 Sep. 2010, [Peer-reviewed], [Domestic magazines]
    English, Scientific journal
  • Novel Photodynamic Therapy Using Water-dispersed TiO2-Polyethylene Glycol Compound: Evaluation of Antitumor Effect on Glioma Cells and Spheroids In Vitro
    Shigeru Yamaguchi, Hiroyuki Kobayashi, Takuhito Narita, Koki Kanehira, Shuji Sonezaki, Yoshinobu Kubota, Shunsuke Terasaka, Yoshinobu Iwasaki
    PHOTOCHEMISTRY AND PHOTOBIOLOGY, 86, 4, 964, 971, Jul. 2010, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • Combined use of positron emission tomography with 18F- fluorodeoxyglucose and 11C-methionine for preoperative evaluation of gliomas
    Shigeru Yamaguchi, Shunsuke Terasaka, Hiroyuki Kobayashi, Takuhito Narita, Kenji Hirata, Satoshi Shiga, Reiko Usui, Shinya Tanaka, Kanako Kubota, Junichi Murata, Katsuyuki Asaoka
    Neurological Surgery, 38, 7, 621, 628, 7, Jul. 2010, [Peer-reviewed], [Domestic magazines]
    Japanese, Scientific journal
  • Clinical outcomes of stereotactic brain and/or body radiotherapy for patients with oligometastatic lesions.
    Inoue T, Katoh N, Aoyama H, Onimaru R, Taguchi H, Onodera S, Yamaguchi S, Shirato H
    Jpn J Clin Oncol, 40, 8, 788, 94, 2010, [Peer-reviewed]
  • Ruptured Distal Anterior Inferior Cerebellar Artery Aneurysm Following Stereotactic Irradiation for Vestibular Schwannoma -Case Report-
    Shigeru Yamaguchi, Tsutornu Kato, Makoto Takeda, Hitoshi Ikeda, Kei Kitamura
    NEUROLOGIA MEDICO-CHIRURGICA, 49, 5, 202, 205, May 2009, [Peer-reviewed], [Domestic magazines]
    English, Scientific journal
  • Indolent dorsal midbrain tumor: new findings based on positron emission tomography
    Shigeru Yamaguchi, Shunsuke Terasaka, Hiroyuki Kobayashi, Tohru Shiga, Reiko Usui, Kenji Hirata, Kanako Kubota, Junichi Murata, Yoshinobu Iwasaki
    JOURNAL OF NEUROSURGERY-PEDIATRICS, 3, 4, 270, 275, Apr. 2009, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • Melanocytic medulloblastoma with ganglioneurocytomatous differentiation: A case report
    Kanako C. Kubota, Tomoo Itoh, Yosuke Yamada, Shigeru Yamaguchi, Yuji Ishida, Yoko Nakasu, Reiko Watanabe, Ichiro Ito, Yutaka Sawamura, Yoshihiro Matsuno, Kazuo Nagashima
    NEUROPATHOLOGY, 29, 1, 72, 77, Feb. 2009, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • The Case of a Large Intra and Extra Medullary Abscess of the Spinal Cord due to Dermal Sinus
    Kota Kurisu, Kazutoshi Hida, Shunsuke Yano, Shigeru Yamaguchi, Hiroaki Motegi, Kanako Kubota, Yoshinobu Iwasaki
    NEUROLOGICAL SURGERY, 36, 12, 1127, 1132, Dec. 2008, [Peer-reviewed], [Domestic magazines]
    Japanese, Scientific journal
  • A Case of Catecholamine-secreting Glomus Jugulare Tumor: Treatment Strategy and Perioperative Management
    Hiroaki Motegi, Shunsuke Terasaka, Shigeru Yamaguchi, Hiroyuki Kobayashi, Katsuyuki Asaoka, Yoshinobu Iwasaki
    NEUROLOGICAL SURGERY, 36, 11, 1029, 1034, Nov. 2008, [Peer-reviewed], [Domestic magazines]
    Japanese, Scientific journal
  • Neoadjuvant therapy in a patient with clival plasmacytoma associated with multiple myeloma: a case report
    Shigeru Yamaguchi, Shunsuke Terasaka, Sachiko Ando, Toshiya Shinohara, Yoshinobu Iwasaki
    SURGICAL NEUROLOGY, 70, 4, 403, 407, Oct. 2008, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • Role of surgery for optic pathway/hypothalamic astrocytomas in children
    Yutaka Sawamura, Kyousuke Kamada, Yuuta Kamoshima, Shigeru Yamaguchi, Toshihiro Tajima, Junko Tsubaki, Takamitsu Fujimaki
    NEURO-ONCOLOGY, 10, 5, 725, 733, Oct. 2008, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • シロスタゾールによる頸動脈内膜剥離術後のプラーク増大の抑制効果               
    藤本 真, 吉本 哲之, 白坂 智英, 善積 威, 山内 亨, 杉山 拓, 山口 秀, 徳田 耕一, 金子 貞男, 柏葉 武, 村木 睦子
    日本脳神経外科学会総会CD-ROM抄録集, 67回, 2J, 05, (一社)日本脳神経外科学会, Oct. 2008
    Japanese
  • Primary Ewing's sarcoma: peripheral primitive neuroectodermal tumour of the jugular foramen
    H. Kobayashi, S. Terasaka, S. Yamaguchi, K. Kubota, Y. Iwasaki
    ACTA NEUROCHIRURGICA, 150, 8, 817, 821, Aug. 2008, [Peer-reviewed]
    English, Scientific journal
  • A case of cervical paraspinal arteriovenous fistulae with a huge intracanalicular varix successfully treated with transvenous embolization
    Shigeru Yamaguchi, Kazutoshi Hida, Takeshi Asano, Shunsuke Yano, Daina Kashiwazaki, Yoshinobu Iwasaki
    NEUROLOGICAL SURGERY, 36, 6, 547, 553, Jun. 2008, [Peer-reviewed], [Domestic magazines]
    Japanese, Scientific journal
  • Langerhans cell histiocytosis of the temporal bones with infiltration of temporal muscle: A case report
    Yuuta Kamoshima, Yutaka Sawamura, Taku Sugiyama, Shigeru Yamaguchi, Yoshinobu Iwasaki, Kanako Kubota
    NEUROLOGICAL SURGERY, 36, 5, 435, 439, May 2008, [Peer-reviewed], [Domestic magazines]
    Japanese, Scientific journal
  • Intramedullary spinal cord metastasis treated with radiation therapy: Report of 3 cases
    Shogo Endo, Kazutoshi Hida, Shunsuke Yano, Masaki Ito, Shigeru Yamaguchi, Daina Kashiwazaki, Rumiko Kinoshita, Hiroki Shirato, Yoshinobu Iwasaki
    NEUROLOGICAL SURGERY, 36, 4, 345, 349, Apr. 2008, [Peer-reviewed], [Domestic magazines]
    Japanese, Scientific journal
  • CNS sarcoidosis presenting with intracerebral hemorrhage: Case report
    Shigeru Yamaguchi, Satoshi Kuroda, Hiroyuki Kobayashi, Katsuhiko Maruichi, Kanako Kubota, Tomohiro Ito, Yoshinobu Iwasaki
    NEUROLOGICAL SURGERY, 34, 8, 839, 842, Aug. 2006, [Peer-reviewed], [Domestic magazines]
    Japanese, Scientific journal
  • The effects of neuronal induction on gene expression profile in bone marrow stromal cells (BMSC) - a preliminary study using microarray analysis
    S Yamaguchi, S Kuroda, H Kobayashi, H Shichinohe, S Yano, K Hida, K Shinpo, S Kikuchi, Y Iwasaki
    BRAIN RESEARCH, 1087, 15, 27, May 2006, [Peer-reviewed]
    English, Scientific journal
  • Nonsuture dural repair using polyglycolic acid mesh and fibrin glue: Clinical application to spinal surgery
    K Hida, S Yamaguchi, T Seki, S Yano, M Akino, S Terasaka, T Uchida, Y Iwasaki
    SURGICAL NEUROLOGY, 65, 2, 136, 143, Feb. 2006, [Peer-reviewed]
    English, Scientific journal
  • A case of lymphocytic hypophysitis mimicking pituitary macroadenoma
    S Yamaguchi, T Kato, M Takeda, J Anzai, HA Ikeda
    NEUROLOGICAL SURGERY, 33, 10, 971, 977, Oct. 2005, [Peer-reviewed], [Domestic magazines]
    Japanese, Scientific journal
  • Joint therapy of a dural arteriovenous fistula in the transverse-sigmoid sinus using surgical excision and direct sinus packing: A case report
    S Yamaguchi, S Kuroda, S Ushikoshi, T Ishikawa, R Nanba, M Hokari, T Asano, Y Iwasaki
    NEUROLOGICAL SURGERY, 32, 7, 747, 751, Jul. 2004, [Peer-reviewed], [Domestic magazines]
    English, Scientific journal

Other Activities and Achievements

Affiliated academic society

  • 日本頭蓋底外科学会               
  • 日本脳腫瘍の外科学会               
  • 日本脳腫瘍学会               
  • THE JAPAN SOCIETY OF BRAIN TUMOR PATHOLOGY               
  • THE JAPANESE CONGRESS OF NEUROLOGICAL SURGEONS               
  • THE JAPAN NEUROSURGICAL SOCIETY               

Research Themes

  • 膠芽腫における低酸素内糖代謝亢進メカニズムの検証
    科学研究費助成事業
    01 Apr. 2022 - 31 Mar. 2025
    山口 秀, 平田 健司, 茂木 洋晃
    日本学術振興会, 基盤研究(C), 北海道大学, 22K09225
  • Photodynamic diagnosis for low-grade gliomas: functional analysis of porphyrin synthesis pathway
    Grants-in-Aid for Scientific Research
    01 Apr. 2019 - 31 Mar. 2022
    Yamaguchi Shigeru
    5-ALA-mediated fluorescence cannot always be detected in grade II/III gliomas. We investigated gene expression patterns in the Protoporphyrin IX (PpIX) synthesis pathway, and attempted to identify the key molecule of 5-ALA-mediated fluorescence. Using 50 surgically obtained specimens, we analyzed gene expression within the PpIX synthesis pathway to identify candidate molecules according to intraoperative 5-ALA-mediated fluorescence status. Among the genes involved in the porphyrin synthesis pathway, the mRNA expression of Peptide transporter 2(PEPT2) in fluorescence-positive gliomas was significantly higher than that in fluorescence-negative gliomas. The siRNA-mediated downregulation of the mRNA and protein expression of PEPT2 led to decreased PpIX fluorescence intensity, as confirmed by fluorescence spectrum analysis. The results suggest PEPT2 is an important candidate molecule in 5-ALA-mediated FGS in grade II/III gliomas.
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Hokkaido University, 19K09495
  • Analysis of disease mechanism and discovery of novel treatment for neurofibromatosis type 2 using patient-derived induced pluripotent stem cell
    Grants-in-Aid for Scientific Research
    01 Apr. 2019 - 31 Mar. 2022
    Shunsuke Terasaka
    We established patient-derived iPS cell using peripheral blood mononuclear cells harvested from 5 patients with neurofibromatosis type 2 (NF2). Expression of stem cell markers were observed in all of established iPSC lines. In a case with NF2 mosaicism, presence or absence of NF2 mutation differed between iPSC clones, while expression of genes in pathways associated with NF2 gene were not different between these iPSC clones, which suggested that biallelic inactivation of NF2 is necessary for tumorigenesis in NF2 patient. We tried to establish in vitro model of schwannoma by differentiation induction for shcwann cell, but it was failed to differentiate neural crest to schwann cell using iPSC derived from healthy human.
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Hokkaido University, 19K09519
  • Exploration of methionine uptake mechanism on glioma through microRNA analysis               
    科学研究費助成事業 若手B
    Apr. 2016 - Mar. 2018
    Shigeru Yamaguchi
    日本学術振興会, Principal investigator, Competitive research funding