Faculty Profiles - OOISHI Makoto

Papers - OOISHI Makoto

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【脳神経画像Critical Findings-おさえておきたい症状とCT/MRI画像所見】特徴的な画像所見を示す新しい概念の脳腫瘍異形成性小脳神経節細胞腫(レルミット・ダクロス病)

岡本浩一郎, 棗田学, 大石誠, 藤井幸彦

Neurological Surgery 49 ( 2 ) 395 - 399 2021.3

Language：Japanese Publisher：(株)医学書院

＜文献概要＞Point ・レルミット・ダクロス病は,小脳回が腫大し変形する比較的境界明瞭な小脳半球の稀な良性腫瘍,あるいは過誤腫性病変である.・虎縞様層構造(tiger-striped striation)が特徴的MRI所見で,拡散制限はない.・カウデン症候群の主要な中枢神経系の病変で,小児〜高齢者の広い年齢層で認められる.・カウデン症候群の診断がついていない場合,カウデン症候群に伴う全身の過誤腫性・腫瘍性病変の検索を行う.

Other Link： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2021&ichushi_jid=J01228&link_issn=&doc_id=20210406190026&doc_link_id=10.11477%2Fmf.1436204404&url=https%3A%2F%2Fdoi.org%2F10.11477%2Fmf.1436204404&type=%88%E3%8F%91.jp_%83I%81%5B%83%8B%83A%83N%83Z%83X&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

【脳神経画像Critical Findings-おさえておきたい症状とCT/MRI画像所見】特徴的な画像所見を示す新しい概念の脳腫瘍黒色腫(メラニン細胞)系腫瘍

岡本浩一郎, 棗田学, 大石誠, 藤井幸彦

Neurological Surgery 49 ( 2 ) 389 - 394 2021.3

Language：Japanese Publisher：(株)医学書院

＜文献概要＞Point ・単純CTで高吸収,T1WIで高信号を認める場合,出血・石灰化に加えメラニン含有性病変を考える.・頭蓋内にメラニン含有性病変を認めた場合,皮膚病変(母斑)の有無を確認する.・無症状でも大きな,あるいは多発する先天性母斑を認める場合,神経皮膚黒色症を疑う.・神経皮膚黒色症の40〜60%に悪性黒色腫が発生し,予後不良である.

Other Link： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2021&ichushi_jid=J01228&link_issn=&doc_id=20210406190025&doc_link_id=10.11477%2Fmf.1436204403&url=https%3A%2F%2Fdoi.org%2F10.11477%2Fmf.1436204403&type=%88%E3%8F%91.jp_%83I%81%5B%83%8B%83A%83N%83Z%83X&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

GLI3 Is Associated With Neuronal Differentiation in SHH-Activated and WNT-Activated Medulloblastoma. International journal

Manabu Natsumeda, Hiroaki Miyahara, Junichi Yoshimura, Satoshi Nakata, Takanori Nozawa, Junko Ito, Yu Kanemaru, Jun Watanabe, Yoshihiro Tsukamoto, Masayasu Okada, Makoto Oishi, Junko Hirato, Takafumi Wataya, Sama Ahsan, Kensuke Tateishi, Tetsuya Yamamoto, Fausto J Rodriguez, Hitoshi Takahashi, Volker Hovestadt, Mario L Suva, Michael D Taylor, Charles G Eberhart, Yukihiko Fujii, Akiyoshi Kakita

Journal of neuropathology and experimental neurology 80 ( 2 ) 129 - 136 2021.1

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

Glioma-associated oncogene homolog 3 (GLI3), whose main function is to inhibit GLI1, has been associated with neuronal differentiation in medulloblastoma. However, it is not clear what molecular subtype(s) show increased GLI3 expression. GLI3 levels were assessed by immunohistochemistry in 2 independent cohorts, including a total of 88 cases, and found to be high in both WNT- and SHH-activated medulloblastoma. Analysis of bulk mRNA expression data and single cell RNA sequencing studies confirmed that GLI1 and GLI3 are highly expressed in SHH-activated medulloblastoma, whereas GLI3 but not GLI1 is highly expressed in WNT-activated medulloblastoma. Immunohistochemical analysis has shown that GLI3 is expressed inside the neuronal differentiated nodules of SHH-activated medulloblastoma, whereas GLI1/2 are expressed in desmoplastic areas. In contrast, GLI3 is diffusely expressed in WNT-activated medulloblastoma, whereas GLI1 is suppressed. Our data suggest that GLI3 may be a master regulator of neuronal differentiation and morphology in these subgroups.

DOI： 10.1093/jnen/nlaa141

Hemodynamic features of an intracranial aneurysm rupture predicted by perianeurysmal edema: A case report. International journal

Tomoaki Suzuki, Hitoshi Hasegawa, Kazuhiro Ando, Kohei Shibuya, Haruhiko Takahashi, Shoji Saito, Jotaro On, Makoto Oishi, Yukihiko Fujii

Surgical neurology international 12 49 - 49 2021

Language：English

Background: Perianeurysmal edema (PAE) has been suggested as an indicator of potential aneurysm rupture; however, the hemodynamic features of these aneurysms are still unknown. A computational fluid dynamic (CFD) analysis was performed to evaluate the hemodynamic features of a very rare case of a ruptured middle cerebral artery (MCA) aneurysm with PAE. Case Description: A 65-year-old woman presented with disturbed consciousness. A subarachnoid hemorrhage due to an azygos anterior cerebral artery (ACA) aneurysm rupture was suspected. An unruptured MCA aneurysm with PAE was identified in the left temporal lobe. Although the ACA aneurysm was clipped to prevent re-bleeding, the MCA aneurysm subsequently ruptured 6 days later. Clipping of the MCA aneurysm was performed, and hemosiderin deposits suggestive of sentinel bleeding were found on the surface of the aneurysm dome. CFD analysis revealed unstable hemodynamic stress at the expanded bleb area after rupture, localized to the rupture site. Moreover, this analysis revealed flow impingement with pressure elevation and low wall shear stress, which indicated increased inflammation and aneurysm wall thinning that likely led to rupture. Conclusion: Hemosiderin deposits at the aneurysm wall and PAE indicates leakage from a cerebral aneurysm. Hemodynamic stress at the aneurysm may promote an inflammatory response and lead to wall weakening accompanied by PAE. Based on our findings, we recommend that surgical intervention should be considered as the first line of treatment for such aneurysms to prevent rupture.

DOI： 10.25259/SNI_780_2020

Phosphorylated T172 in GAP-43: A novel molecular marker of axonal growth and regeneration in primate neurons identifi ed by phosphoproteomics

Okada Masayasu, Kawasaki Asami, Kaneko Naoko, Natsumeda Manabu, Oishi Makoto, Fujii Yukihiko, Igarashi Michihiro

Cytometry Research 31 ( 1 ) 7 - 13 2021

Language：Japanese Publisher：Japan Cytometry Society

<p>For post-translational protein modifications such as phosphorylation, the involved residues have been recently identified by mass spectrometers. However, it is not easy to efficiently detect the therapeutic target from the vast amount of proteomic data. Neuronal growth cones are specialized, highly motile structures formed at the tip of axons, that are indispensable for synaptogenesis in the developing brain and for neuronal plasticity in the adult brain. However, there is lack of information on the molecular basis of growth cones in the mammalian brain. We performed a phosphoproteomic analysis of growth cone membrane fractions (2 mg) isolated from the rat forebrain on postnatal day 1. We chose the more abundant peptides as research-targets, based on the hypothesis that abundant phosphorylated sites are involved in important biological functions. The phosphopeptides detected with high frequency at the 1st (Serine [S] 96) and 9th (Threonine [T] 172) positions were the phosphorylation sites of neuronal growth-associated protein - 43 kDa (GAP 43). C-jun N-terminal kinase (JNK) was responsible for phosphorylation at these sites, which increased during neuronal development and axonal regeneration. T172 phosphorylation was also confi rmed in rodents and primates. This review introduces our methodology for fi nding novel phospho-proteins as therapeutic molecular targets for specifi c diseases, along with their regulatory kinases. We believe that our serial approach, as illustrated here, can be applied to various research fi elds. In future research, we propose to demonstrate that pT172 antibody can be utilized as an axonal growth and regeneration marker in humans.</p>

DOI： 10.18947/cytometryresearch.31.1_7

Pott's puffy tumour: a rare and life-threatening disease. International journal

Nahoko Ikoma, Yuta Aizawa, Takanobu Sasaki, Makoto Oishi, Naka Saito, Hiroshi Yoshida, Akihiko Saitoh

The Lancet. Infectious diseases 20 ( 12 ) 1482 - 1482 2020.12

Safety and feasibility of the distal transradial approach: A novel technique for diagnostic cerebral angiography. International journal

Shoji Saito, Hitoshi Hasegawa, Tomoyoshi Ota, Toru Takino, Yuichi Yoshida, Kazuhiro Ando, Kohei Shibuya, Haruhiko Takahashi, Tomoaki Suzuki, Makoto Oishi, Yukihiko Fujii

Interventional neuroradiology : journal of peritherapeutic neuroradiology, surgical procedures and related neurosciences 26 ( 6 ) 713 - 718 2020.12

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

PURPOSE: We aimed to evaluate the safety and feasibility of the distal transradial approach (DTRA) as a novel technique for cerebral angiography based on our institutional initial experience. METHODS: We retrospectively analyzed our institutional database of consecutive diagnostic cerebral angiographies performed with DTRA from December 2018 to August 2019. Patient demographics and clinical and procedural data were recorded. RESULTS: In total, 51 diagnostic cerebral angiographies in 51 patients (age, 15-83 years; mean age, 59.4 years, SD 13.5; 35 (69%) females) were performed or attempted with DTRA. Ultrasound evaluation showed that the mean inner distal radial artery diameter was significantly smaller than the mean inner forearm radial artery diameter (2.19 mm vs. 2.56 mm, P < 0.001). Cannulation via the distal radial artery was successful in 47 (92%) procedures. In the four procedures that failed, operators converted to the ipsilateral transradial approach without repositioning or redraping. Selective catheterization of the intended vessel was achieved in 64 (91%) of 70 vessels. In the remaining six, operators achieved the objective of the examination with angiography injecting from proximal and conversion to another approach was not required. One patient experienced temporary numbness around the puncture site after the procedure. No radial artery occlusion was identified in the patients who underwent ultrasound evaluation. CONCLUSION: Our results demonstrate that DTRA could become a standard approach for diagnostic cerebral angiography owing to the low complication rate and the high cannulation success rate.

DOI： 10.1177/1591019920925709

栄養動脈塞栓術を行い摘出したhypervascular cerebellopontine angle pilocytic astrocytomaの一例

吉村淳一, 棗田学, 長谷川仁, 大石誠, 藤井幸彦

小児の脳神経 45 ( 3 ) 256 - 256 2020.10

脳腫瘍の遺伝子診断とゲノム医療2 ゲノム医療を想定したBRAF V600E変異を有する脳腫瘍の臨床病理像

棗田学, 金丸優, 齋藤祥二, 塚本佳広, 岡田正康, 大石誠, 柿田明美, 藤井幸彦

Brain Tumor Pathology 37 ( Suppl. ) 076 - 076 2020.8

[Endovascular Revascularization for Acute Ischemic Stroke Related to Blunt Carotid Injury:A Case Report].

Shoji Saito, Hitoshi Hasegawa, Daisuke Sato, Kazuhiro Ando, Kunio Motohashi, Manabu Natsumeda, Bumpei Kikuchi, Makoto Oishi, Yukihiko Fujii

No shinkei geka. Neurological surgery 48 ( 6 ) 527 - 532 2020.6

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

Although blunt carotid artery injury is known as an important cause of ischemic stroke, the role of the endovascular treatment for acute ischemic stroke related to blunt carotid injuries remains unclear. We report the case of a patient with acute ischemic stroke secondary to blunt carotid artery injury who was treated with endovascular revascularization. A 46-year-old man suffered from sudden left-sided hemiparesis a day after a strike from a Japanese fencing staff on his right neck. 3D-CT angiography revealed tandem internal carotid artery occlusions of the cervical and C1 portions. We performed endovascular revascularization with carotid artery stenting and direct aspiration of the thrombus and achieved complete recanalization. The patient recovered almost completely. We conclude that endovascular revascularization should not be withheld from patients with acute ischemic stroke related to blunt carotid injury.

DOI： 10.11477/mf.1436204223

Vascular Hyperintensity on Fluid-Attenuated Inversion Recovery Indicates the Severity of Hypoperfusion in Acute Stroke. International journal

Toshiharu Nomura, Kouichirou Okamoto, Hironaka Igarashi, Masato Watanabe, Hitoshi Hasegawa, Makoto Oishi, Yukihiko Fujii

Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association 29 ( 2 ) 104467 - 104467 2020.2

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

BACKGROUND AND AIM: Although fluid-attenuated inversion recovery vascular hyperintensities may be frequently seen in acute large-artery ischemic stroke, reports on their prognostic utility had been conflicting due to lack of quantitative evaluation of the perfusion status based on the signal intensity. We hypothesized that greater hyperintensity represents more severe hypoperfusion. METHODS: Overall, 27 patients with acute occlusion of the proximal middle cerebral artery were divided into 2 groups, based on their signal intensity in the insular segment of middle cerebral artery on the affected side, relative to that of the insular cortex: the low signal intensity group (hypo- or isointense signals, n = 12) and the high signal intensity group (hyperintense signals, n = 15). Using dynamic susceptibility contrast magnetic resonance imaging, we assessed the time of the maximum value of the residue function and mean transit time, in the entire middle cerebral artery cortical area and diffusion-weighted imaging-Alberta Stroke Program Early Computed Tomography Score regions, including the corona radiata. RESULTS: The high signal intensity group had significantly longer time of the maximum value of the residue function in all the diffusion-weighted imaging-Alberta Stroke Program Early Computed Tomography Score regions, except the M3 and M6 regions, and significantly longer mean transit time in the M1 and M4 regions. CONCLUSIONS: Quantitative analysis of the perfusion parameters revealed more severely compromised and widely disturbed perfusion status in the high signal intensity group than in the low signal intensity group.

DOI： 10.1016/j.jstrokecerebrovasdis.2019.104467

Possibility of Worsening Flow Diversion Effect Due to Morphological Changes of a Stented Artery With Multiple Overlapping Stents for Partially Thrombosed Vertebral Artery Aneurysms. International journal

Tomoaki Suzuki, Hitoshi Hasegawa, Kazuhiro Ando, Kouhei Shibuya, Haruhiko Takahashi, Shoji Saito, Makoto Oishi, Yukihiko Fujii

Frontiers in neurology 11 611124 - 611124 2020

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

Background: Morphological changes of a stented artery can cause a flow diversion effect to reduce intra-aneurysmal flow; however, there is a potential for the negative effect of increased intra-aneurysmal flow. We present cases with multiple overlapping stents for a partially thrombosed vertebral artery aneurysm and characterize the hemodynamic properties of a recurrent case by focusing on the morphological changes of the stented artery. Methods: Between October 2017 and April 2019, four consecutive cases of symptomatic unruptured large and giant partially thrombosed vertebral artery aneurysms were treated with multiple overlapping low-profile visualized intraluminal support stents and no coils. Both angiographic and clinical outcomes were assessed. Computational fluid dynamics analysis was performed to clarify hemodynamic features. The degree of pressure elevation was calculated as the pressure difference (Pd). Wall shear stress (WSS) was also calculated. Results: In three of the four cases, successful flow reduction was achieved with no morphological change of the stented arteries. The patients' symptoms were gradually improved. The remaining case required additional stents after the initial treatment. In the recurrent case, Pd was noticeably elevated at the aneurysm neck after treatment, and WSS was generally increased in the area due to altered blood flow into the aneurysm dome caused by morphological changes of the stented artery. Conclusion: Overlapping stents can be used for the treatment of large and giant thrombosed vertebral artery aneurysms with flow diversion effect; however, morphological changes of the stented artery requires careful attention as it may lead to an increase in the intra-aneurysmal flow, causing negative outcomes.

DOI： 10.3389/fneur.2020.611124

Comparison of circulating tumor DNA between body fluids in patients with primary central nervous system lymphoma. International journal

Jun Watanabe, Manabu Natsumeda, Yu Kanemaru, Masayasu Okada, Makoto Oishi, Akiyoshi Kakita, Yukihiko Fujii

Leukemia & lymphoma 60 ( 14 ) 3587 - 3589 2019.12

High Detection Rate of MYD88 Mutations in Cerebrospinal Fluid From Patients With CNS Lymphomas. International journal

Jun Watanabe, Manabu Natsumeda, Masayasu Okada, Daiki Kobayashi, Yu Kanemaru, Yoshihiro Tsukamoto, Makoto Oishi, Akiyoshi Kakita, Yukihiko Fujii

JCO precision oncology 3 1 - 13 2019.12

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

PURPOSE: Biopsy is the gold standard for the diagnosis of primary CNS lymphoma (PCNSL). However, surgical biopsy has problems of morbidity related to hemorrhagic complications and false-negative findings, so safer and more reliable diagnostic methods are required. The aim of this study is to detect the MYD88 mutation, an important driver mutation, in the cerebrospinal fluid (CSF) of patients with CNS lymphoma. PATIENTS AND METHODS: Twenty-six patients with CNS lymphoma (20 primary CNS lymphoma and six CNS relapse from systemic lymphoma) were studied. We extracted cell-free DNA (cfDNA) from CSF by lumbar puncture. cfDNA was extracted from 1 mL of CSF, and Sanger sequencing and droplet digital polymerase chain reaction (ddPCR) were performed. Furthermore, we performed DNA sequencing of MYD88 in 21 cases with available surgically obtained formalin-fixed paraffin-embedded (FFPE) tissue and compared the results. RESULTS: The median cfDNA amount extracted from 1 mL CSF was 219 ng/mL (25th to 75th percentile, 129 to 333 ng/mL). MYD88 mutations were detected from CSF in 76.9% (20 of 26 cases), and L265P in exon 5 was the most frequent mutation in 19 out of 20 (95.0%) cases. S219C in exon 3 was detected in one case. In four patients, MYD88 mutation was confirmed by ddPCR but not by Sanger sequencing. In all 21 cases with sufficient FFPE tissue for DNA analysis, the detection of MYD88 mutation from cfDNA was consistent with those of tumor-derived DNA from FFPE tissue. CONCLUSION: This pilot study provided evidence that the somatic driver mutation MYD88 can be reliably detected by combination of Sanger sequencing and ddPCR in the cfDNA taken from 1 mL of CSF in patients with CNS lymphomas.

DOI： 10.1200/PO.18.00308

Podoplanin Expression and IDH-Wildtype Status Predict Venous Thromboembolism in Patients with High-Grade Gliomas in the Early Postoperative Period. International journal

Jun Watanabe, Manabu Natsumeda, Masayasu Okada, Yu Kanemaru, Yoshihiro Tsukamoto, Makoto Oishi, Akiyoshi Kakita, Yukihiko Fujii

World neurosurgery 128 e982-e988 2019.8

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

OBJECTIVE: Venous thromboembolism (VTE) often is encountered in patients with high-grade gliomas. The underlying mechanisms are unclear, as is the optimal prophylactic protocol. The purpose of the present study was to identify risk factors of VTE and examine the validity of early VTE detection in high-grade gliomas. METHODS: We reviewed the medical records of 165 patients with newly diagnosed high-grade glioma treated at Niigata University Hospital during the years 2009 to 2016. If the serum D-dimer levels increased to 5.0 μg/mL or more, computed tomography was performed to detect VTE. Furthermore, immunohistochemistry with antibodies against podoplanin was performed on available 101 tumor tissues. RESULTS: Of the 165 patients, 44 (26.7%) developed VTE. Of the 44 patients, 34 (79.5%) developed VTE within 7 days after surgery. No fatal VTE occurred and major complications secondary to anticoagulation occurred in only 2 (1.2%) patients. On multivariate analysis, lower Karnofsky Performance Scale status, podoplanin expression, and isocitrate dehydrogenase-wildtype status were independently associated with the risk of VTE (P < 0.05). CONCLUSIONS: We found that most VTEs occurred early in the postoperative period and commonly in patients with lower Karnofsky Performance Scale status and isocitrate dehydrogenase-wildtype gliomas, which expressed podoplanin.

DOI： 10.1016/j.wneu.2019.05.049

Dramatic response of BRAF V600E-mutant epithelioid glioblastoma to combination therapy with BRAF and MEK inhibitor: establishment and xenograft of a cell line to predict clinical efficacy. International journal

Yu Kanemaru, Manabu Natsumeda, Masayasu Okada, Rie Saito, Daiki Kobayashi, Takeyoshi Eda, Jun Watanabe, Shoji Saito, Yoshihiro Tsukamoto, Makoto Oishi, Hirotake Saito, Masayuki Nagahashi, Takahiro Sasaki, Rintaro Hashizume, Hidefumi Aoyama, Toshifumi Wakai, Akiyoshi Kakita, Yukihiko Fujii

Acta neuropathologica communications 7 ( 1 ) 119 - 119 2019.7

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

Epithelioid glioblastoma is a rare aggressive variant of glioblastoma (GBM) characterized by a dismal prognosis of about 6 months and frequent leptomeningeal dissemination. A recent study has revealed that 50% of epithelioid GBMs harbor three genetic alterations - BRAF V600E mutation, TERT promoter mutations, and homozygous deletions of CDKN2A/2B. Emerging evidence support the effectiveness of targeted therapies for brain tumors with BRAF V600E mutation. Here we describe a dramatic radiographical response to combined therapy with BRAF and MEK inhibitors in a patient with epithelioid GBM harboring BRAF V600E mutation, characterized by thick spinal dissemination. From relapsed tumor procured at autopsy, we established a cell line retaining the BRAF V600E mutation, TERT promoter mutation and CDKN2A/2B loss. Intracranial implantation of these cells into mice resulted in tumors closely resembling the original, characterized by epithelioid tumor cells and dissemination, and invasion into the perivascular spaces. We then confirmed the efficacy of treatment with BRAF and MEK inhibitor both in vitro and in vivo. Epithelioid GBM with BRAF V600E mutation can be considered a good treatment indication for precision medicine, and this patient-derived cell line should be useful for prediction of the tumor response and clarification of its biological characteristics.

DOI： 10.1186/s40478-019-0774-7

Malignant Hyperthermia and Cerebral Venous Sinus Thrombosis After Ventriculoperitoneal Shunt in Infant with Schizencephaly and COL4A1 Mutation. International journal

Jun Watanabe, Kouichirou Okamoto, Tsukasa Ohashi, Manabu Natsumeda, Hitoshi Hasegawa, Makoto Oishi, Satoko Miyatake, Naomichi Matsumoto, Yukihiko Fujii

World neurosurgery 127 446 - 450 2019.7

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

BACKGROUND: Schizencephaly is a rare congenital central nervous system malformation characterized by linear, thickened clefts of the cerebral mantle. Recently, germline mutations in collagen type IV alpha 1 (COL4A1) have been reported to be a genetic cause of schizencephaly as a result of prenatal stroke. Patients with COL4A1 mutation demonstrate a variety of disease phenotypes. However, little is known about the potential complications of patients with COL4A1 mutations before and after neurologic surgery. CASE DESCRIPTION: A 9-month-old boy with schizencephaly and a congenital cataract underwent a ventriculoperitoneal shunt for progressive hydrocephalus. Postoperatively, he developed malignant hyperthermia and cerebral venous thrombosis. Early treatment with dantrolene sodium and hydration was effective. Genetic testing revealed a germline COL4A1 mutation. CONCLUSIONS: To our knowledge, malignant hyperthermia and cerebral venous thrombosis have not been reported in the literature in patients with COL4A1 mutations after surgery. Schizencephaly arising from COL4A1 mutations might be a disease prone to these adverse effects because this mutation is known to be associated with venous tortuosity, venous vulnerability, and muscle spasms due to basement membrane protein abnormalities. We need to better understand the wide spectrum of clinical phenotypes of COL4A1 mutations and potential complications in order to better manage surgery of patients with schizencephaly.

DOI： 10.1016/j.wneu.2019.04.156

小児症例における内視鏡下経鼻経蝶形骨洞手術の解剖学的制限と安全性の検討

温城太郎, 岡田正康, 中村公彦, 米岡有一郎, 大石誠, 藤井幸彦

小児の脳神経 44 ( 2 ) 166 - 166 2019.4

EGFRvIII Is Expressed in Cellular Areas of Tumor in a Subset of Glioblastoma.

Takanori Nozawa, Masayasu Okada, Manabu Natsumeda, Takeyoshi Eda, Hideaki Abe, Yoshihiro Tsukamoto, Kouichirou Okamoto, Makoto Oishi, Hitoshi Takahashi, Yukihiko Fujii, Akiyoshi Kakita

Neurologia medico-chirurgica 59 ( 3 ) 89 - 97 2019.3

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

Epidermal growth factor receptor variant III (EGFRvIII) is a tumor-specific cell surface antigen often expressed in glioblastoma and has drawn much attention as a possible therapeutic target. We performed immunohistochemistry on histology sections of surgical specimens taken from 67 cases with glioblastoma, isocitrate dehydrogenase-wild type, and evaluated the morphological characteristics and distribution of the EGFRvIII-positive tumor cells. We then evaluated the localization of EGFRvIII-expression within the tumor and peritumoral areas. EGFRvIII immunopositivity was detected in 15 specimens taken from 13 patients, including two recurrent specimens taken from the same patient at relapse. Immunofluorescence staining demonstrated that EGFRvIII-positive cells were present in cells positive for glial fibrillary acidic protein (GFAP), and some showed astrocytic differentiation with multiple fine processes and others did not shown. The EGFRvIII-positive cells were located in cellular areas of the tumor, but not in the invading zone. In the two recurrent cases, EGFRvIII-positive cells were markedly decreased in one case and retained in the other. With regard to overall survival, univariate analysis indicated that EGFRvIII-expression in patients with glioblastoma was not significantly associated with a favorable outcome. Double-labeling immunofluorescence staining of EGFRvIII and GFAP showed that processes of large, well differentiated, GFAP-positive glia extend to and surround less differentiated, EGFRvIII-positive glial cells in cellular areas of tumor. However, in the tumor periphery, EGFRvIII-positive tumor cells were not observed. This finding suggests that EGFRvIII is involved in tumor proliferation, but that invading glioma cells lose their EGFRvIII expression.

DOI： 10.2176/nmc.oa.2018-0078

[Posterior Quadrantectomy for Infant with Refractory Epilepsy:A Case Report].

Taiki Saito, Makoto Oishi, Masafumi Fukuda, Yoshihiro Tsukamoto, Tsukasa Ohashi, Jun Watanabe, Takuma Nemoto, Tadashi Kawaguchi, Yukihiko Fujii

No shinkei geka. Neurological surgery 47 ( 3 ) 349 - 356 2019.3

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

We present the case of an 11-month-old girl with linear nevus sebaceous syndrome who underwent posterior quadrantectomy(PQ)for intractable epilepsy due to cortical dysplasia extending from the temporal, parietal, and occipital lobes in the right hemisphere. Epileptic spasms started at 4 months after birth, and the frequency of her seizures gradually increased to 10 episodes per day. Electroencephalograms in the interictal periods showed hypsarrhythmia. Magnetic resonance imaging(MRI)suggested cortical dysplasia in the right temporal, parietal, and occipital lobes. Ictal single-photon emission computed tomography revealed increased cerebral blood flow in similar areas as the cortical dysplasia suggested on MRI. Several antiepileptic drugs were administered to control the epileptic spasms, without success. In addition, her developmental delay gradually became evident. Because the epileptic foci extended into the posterior region of the right hemisphere, we did not execute a focused resection, but performed a PQ. The epileptic spasms completely disappeared after surgery and her developmental delay gradually improved. Early surgical intervention via PQ is useful in patients with drug-resistant epilepsy in whom the epileptic foci have extended into the temporal, parietal, and occipital lobes. This intervention not only controls intractable seizures but also helps to facilitate normal development.

DOI： 10.11477/mf.1436203943

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