Faculty Profiles - SAITO Ryuta

Papers - SAITO Ryuta

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Kanamori, M, Saito, R, Tominaga, T

Japanese Journal of Neurosurgery Vol. 29 ( 4 ) 2020

A multicenter randomized phase III study for newly diagnosed maximally resected glioblastoma comparing carmustine wafer implantation followed by chemoradiotherapy with temozolomide with chemoradiotherapy alone; Japan Clinical Oncology Group Study JCOG1703 (MACS study). International journal Open Access

Tomohiro Kadota, Ryuta Saito, Toshihiro Kumabe, Junki Mizusawa, Hiroshi Katayama, Minako Sumi, Hiroshi Igaki, Manabu Kinoshita, Takashi Komori, Koichi Ichimura, Yoshitaka Narita, Ryo Nishikawa

Japanese journal of clinical oncology Vol. 49 ( 12 ) page： 1172 - 1175 2019.12

Language：English Publishing type：Research paper (scientific journal) Publisher：OXFORD UNIV PRESS

A randomized phase III trial in Japan commenced in June 2019. The present standard treatment for newly diagnosed glioblastoma is maximal resection followed by chemoradiotherapy with temozolomide. The purpose of this study is to confirm the superiority of maximal resection with carmustine wafer implantation followed by chemoradiotherapy with temozolomide over the standard maximal resection followed by chemoradiotherapy with temozolomide in terms of overall survival for newly diagnosed glioblastoma. A total of 250 patients will be accrued from 35 Japanese institutions in 5.5 years. Patients with >90% surgical resection will be registered and randomly assigned to each group with 1:1 allocation. The primary endpoint is overall survival and the secondary endpoints are progression-free survival, loco-regional progression-free survival and incidence of adverse events. This trial has been registered in the Japan Registry of Clinical Trial, as jRCT1031190035 [https://jrct.niph.go.jp/en-latest-detail/jRCT1031190035].

DOI： 10.1093/jjco/hyz169

Web of Science

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Experience of Low Dose Perampanel to Add-on in Glioma Patients with Levetiracetam-uncontrollable Epilepsy. Reviewed Open Access

Chonan M, Saito R, Kanamori M, Osawa SI, Watanabe M, Suzuki H, Nakasato N, Tominaga T

Neurologia medico-chirurgica Vol. 60 ( 1 ) page： 37 - 44 2019.11

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

After introduction of levetiracetam (LEV), treatment of seizures in patients with malignant brain tumors has prominently improved. On the other hand, we still experience some cases with LEV-uncontrollable epilepsy. Perampanel (PER) is a noncompetitive a-amino-3-hydroxy-5-methyl-4-isoaxazolepropionate acid receptor antagonist that has recently been approved for treating focal epilepsy as a secondary drug of choice. Available literature reporting PER medication in patients with gliomas is still sparse. Here, we report our initial experience with glioma patients and report efficacy of adding low dose 2–4 mg PER to LEV in patients whose seizure were uncontrollable with LEV monotherapy. Clinical outcome data of 18 consecutive patients were reviewed. This included nine males and nine females aged 24–76 years (median, 48.5 years), treated for glioma between June 2009 to December 2018. We added PER to patients with LEV-uncontrollable epilepsy. Adverse effects, irritability occurred in two patients, but continuous administration was possible in all cases. Though epileptic seizures occurred in four cases receiving 2 mg PER, 17 cases achieved seizure freedom by dose increments; final dose, 2–4 mg PER added to LEV 500–3000 mg. Our study revealed anti-epileptic efficacy of low dose PER 2–4 mg as first add-on therapy to LEV in glioma patients who have failed or intolerable to LEV monotherapy. Low dose PER added on to LEV may have favorable efficacy with tolerable adverse effects in glioma patients with LEV-uncontrollable epilepsy.

DOI： 10.2176/nmc.oa.2018-0245

超選択的Wada testによる血管解剖と機能解剖のハイブリッド評価 Reviewed

大沢伸一郎, 鈴木匡子, 新妻邦泰, 浮城一司, 柿沼一雄, 上利大, 神一敬, 斎藤竜太, 金森政之, 中里信和, 冨永悌二

脳血管内治療 Vol. 4 ( Suppl. ) page： S383 - S383 2019.11

Unilateral chronic subdural hematoma due to spontaneous intracranial hypotension: a report of four cases. Reviewed International journal

Osada Y, Shibahara I, Nakagawa A, Sakata H, Niizuma K, Saito R, Kanamori M, Fujimura M, Suzuki S, Tominaga T

British journal of neurosurgery Vol. 34 ( 6 ) page： 1 - 6 2019.9

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

Background: Chronic subdural hematoma (CSDH) is a common neurosurgical disease. A subset of patients with CSDH may exhibit underlying spontaneous intracranial hypotension (SIH). Bilateral CSDH has a causal relationship with SIH, but there is no known causal relationship between unilateral CSDH and SIH.Case description: We encountered four cases of unilateral CSDH due to SIH. The patients' age ranged between 44 and 64 years; there were three males and one female. All patients presented with headache as their initial symptom, and then became comatose. Computed tomography demonstrated unilateral CSDH and transtentorial herniation in all patients. Treatments were emergency epidural blood patch (EBP) and evacuation of CSDH. The site of cerebrospinal fluid leak could not be identified in three patients; therefore, EBP was performed at upper and lower spine. All patients recovered from SIH; however, one patient experienced poor outcome due to Duret hemorrhage and ischemic complications of transtentorial herniation. Cranial asymmetry was present in all four patients, and unilateral CSDH was located on the side of the most curved cranial convexity.Conclusions: Unilateral CSDH, asymmetric cranial morphology, and transtentorial herniation in relatively young patients may indicate underlying SIH.

DOI： 10.1080/02688697.2019.1667482

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Coexistence of Intracranial Germ Cell Tumor with Growing Arteriovenous Fistula.

Ishida T, Endo H, Saito R, Kanamori M, Sato K, Matsumoto Y, Endo T, Fujimura M, Tominaga T

World neurosurgery Vol. 127 page： 126 - 130 2019.7

Phase I study of a brain penetrant mutant IDH1 inhibitor DS-1001b in patients with recurrent or progressive IDH1 mutant gliomas. Reviewed Open Access

Atsushi Natsume, Toshihiko Wakabayashi, Yasuji Miyakita, Yoshitaka Narita, Yohei Mineharu, Yoshiki Arakawa, Fumiyuki Yamasaki, Kazuhiko Sugiyama, Nobuhiro Hata, Yoshihiro Muragaki, Ryo Nishikawa, Naoki Shinojima, Toshihiro Kumabe, Ryuta Saito, Kazumi Ito, Masaya Tachibana, Yasuyuki Kakurai, Soichiro Nishijima, Hiroshi Tsubouchi

JOURNAL OF CLINICAL ONCOLOGY Vol. 37 ( 15 ) page： . 2019.5

脳幹部神経膠腫診断におけるメチオニンPET検査の有用性

齋藤竜太, 金森政之, 高浪健太郎, 園田順彦, 冨永悌二

Brain Tumor Pathology Vol. 36 ( Suppl. ) page： 090 - 090 2019.5

IDH遺伝子変異型星細胞腫の予後因子

金森政之, 渡辺みか, 斎藤竜太, 長田佳整, 柴原一陽, 園田順彦, 隈部俊宏, 冨永悌二

Brain Tumor Pathology Vol. 36 ( Suppl. ) page： 102 - 102 2019.5

Coexistence of an intracranial germ cell tumor with a growing arteriovenous fistula: a case report. Reviewed

Ishida T, Endo H, Saito R, Kanamori M, Sato K, Matsumoto Y, Endo T, Fujimura M, Tominaga T

2019.4

Incidence of initial spinal metastasis in glioblastoma patients and the importance of spinal screening using MRI. Reviewed International journal

Ichiyo Shibahara, Ryuta Saito, Yoshinari Osada, Masayuki Kanamori, Yukihiko Sonoda, Toshihiro Kumabe, Shunji Mugikura, Mika Watanabe, Teiji Tominaga

Journal of neuro-oncology Vol. 141 ( 2 ) page： 337 - 345 2019.1

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

PURPOSE: Intracranial glioblastomas with simultaneous spinal lesions prior to chemoradiation therapy or craniotomy, defined as initial spinal metastasis, are not well understood. Herein, we investigated intracranial glioblastoma and demonstrated the importance of spinal screening using gadolinium enhanced spinal magnetic resonance imaging (Gd-MRI). METHODS: Consecutive adult patients with intracranial glioblastoma were treated between 2010 and 2014 and received spinal screening using Gd-MRI. Spinal screening was performed regardless of spine-related symptoms, and patients presenting with and without initial spinal metastasis (spinal and non-spinal groups, respectively) were compared based on patient demographics, tumor characteristics, radiological and molecular features, and overall survival (OS). RESULTS: During the study period, 116 glioblastoma cases were treated and 87 of these (76%) underwent spinal screening. Among these patients, 11 (13%) were included in the spinal group, and 76 (87%) were included in the non-spinal group. All patients of the spinal group were free of symptoms related to spinal lesions. Compared with the non-spinal group, intracranial lesions of the spinal group presented higher incidences of intracranial dissemination and were located at subventricular zones (P = 0.0012 and 0.020, respectively). MIB-1 labeling index, molecular alterations such as IDH1 mutation, TERT promoter mutation, and immunoreactivity of ATRX and MGMT did not differ between two groups. OS was significantly shorter in the spinal group than in the non-spinal group (P = 0.0054). CONCLUSIONS: This study revealed a relatively high incidence of spinal metastasis. A subset of glioblastoma patients benefited from spinal screening, through which early detection of asymptomatic spinal metastasis was achieved.

DOI： 10.1007/s11060-018-03036-4

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Significance of molecular classification of ependymomas: C11orf95-RELA fusion-negative supratentorial ependymomas are a heterogeneous group of tumors. Reviewed International journal Open Access

Kohei Fukuoka, Yonehiro Kanemura, Tomoko Shofuda, Shintaro Fukushima, Satoshi Yamashita, Daichi Narushima, Mamoru Kato, Mai Honda-Kitahara, Hitoshi Ichikawa, Takashi Kohno, Atsushi Sasaki, Junko Hirato, Takanori Hirose, Takashi Komori, Kaishi Satomi, Akihiko Yoshida, Kai Yamasaki, Yoshiko Nakano, Ai Takada, Taishi Nakamura, Hirokazu Takami, Yuko Matsushita, Tomonari Suzuki, Hideo Nakamura, Keishi Makino, Yukihiko Sonoda, Ryuta Saito, Teiji Tominaga, Yasuhiro Matsusaka, Keiichi Kobayashi, Motoo Nagane, Takuya Furuta, Mitsutoshi Nakada, Yoshitaka Narita, Yuichi Hirose, Shigeo Ohba, Akira Wada, Katsuyoshi Shimizu, Kazuhiko Kurozumi, Isao Date, Junya Fukai, Yousuke Miyairi, Naoki Kagawa, Atsufumi Kawamura, Makiko Yoshida, Namiko Nishida, Takafumi Wataya, Masayoshi Yamaoka, Naohiro Tsuyuguchi, Takehiro Uda, Mayu Takahashi, Yoshiteru Nakano, Takuya Akai, Shuichi Izumoto, Masahiro Nonaka, Kazuhisa Yoshifuji, Yoshinori Kodama, Masayuki Mano, Tatsuya Ozawa, Vijay Ramaswamy, Michael D Taylor, Toshikazu Ushijima, Soichiro Shibui, Mami Yamasaki, Hajime Arai, Hiroaki Sakamoto, Ryo Nishikawa, Koichi Ichimura

Acta neuropathologica communications Vol. 6 ( 1 ) page： 134 - 134 2018.12

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

Extensive molecular analyses of ependymal tumors have revealed that supratentorial and posterior fossa ependymomas have distinct molecular profiles and are likely to be different diseases. The presence of C11orf95-RELA fusion genes in a subset of supratentorial ependymomas (ST-EPN) indicated the existence of molecular subgroups. However, the pathogenesis of RELA fusion-negative ependymomas remains elusive. To investigate the molecular pathogenesis of these tumors and validate the molecular classification of ependymal tumors, we conducted thorough molecular analyses of 113 locally diagnosed ependymal tumors from 107 patients in the Japan Pediatric Molecular Neuro-Oncology Group. All tumors were histopathologically reviewed and 12 tumors were re-classified as non-ependymomas. A combination of RT-PCR, FISH, and RNA sequencing identified RELA fusion in 19 of 29 histologically verified ST-EPN cases, whereas another case was diagnosed as ependymoma RELA fusion-positive via the methylation classifier (68.9%). Among the 9 RELA fusion-negative ST-EPN cases, either the YAP1 fusion, BCOR tandem duplication, EP300-BCORL1 fusion, or FOXO1-STK24 fusion was detected in single cases. Methylation classification did not identify a consistent molecular class within this group. Genome-wide methylation profiling successfully sub-classified posterior fossa ependymoma (PF-EPN) into PF-EPN-A (PFA) and PF-EPN-B (PFB). A multivariate analysis using Cox regression confirmed that PFA was the sole molecular marker which was independently associated with patient survival. A clinically applicable pyrosequencing assay was developed to determine the PFB subgroup with 100% specificity using the methylation status of 3 genes, CRIP1, DRD4 and LBX2. Our results emphasized the significance of molecular classification in the diagnosis of ependymomas. RELA fusion-negative ST-EPN appear to be a heterogeneous group of tumors that do not fall into any of the existing molecular subgroups and are unlikely to form a single category.

DOI： 10.1186/s40478-018-0630-1

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Development and evaluation of ultrasound-facilitated drug delivery device Reviewed

Inoue Kenji, Sato Aya, Saito Ryuta, Jia Wenting, Okuno Saori, Ohashi Yuji, Kamada Kei, Yoshikawa Akira, Tominaga Teiji

JAPANESE JOURNAL OF APPLIED PHYSICS Vol. 57 ( 11 ) 2018.11

Publishing type：Research paper (international conference proceedings)

We developed a new ultrasound-facilitated delivery (UFD) device with a drug infusion sapphire needle enabling real-time magnetic resonance imaging (MRI) observation and an ultrasound piezoelectric transducer (drive frequency: 260 kHz) with an effective structure for increasing drug diffusion. The sapphire needle (outside diameter: 0.6 mm, inside diameter: 0.3 mm, length: 150 mm) was grown by a micro-pulling-down method. The transducer is composed of two-stacked layers of lead zirconate titanate (PZT) on a brass base. The sound pressure distribution of the developed UFD device in water was measured with a miniature probe hydrophone, showing good agreement with the value simulated by the finite element method (FEM) analysis. The developed UFD device demonstrated high efficiency and reliability of drug diffusion, exhibiting an 8.5% increase in the volume of drug diffusion with 80% higher reproducibility and 66% lower driving voltage than the previous device. Consequently, the operating temperature of the new UFD device was decreased from 60 °C to room temperature.

DOI： 10.7567/JJAP.57.11UD07

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DEVELOPMENT OF ULTRASOUND-FACILITATED DRUG DELIVERY DEVICE FOR LOCAL DRUG INFUSION AGAINST BRAIN TUMORS Reviewed

Saito Ryuta, Sato Aya, Inoue Kenji, Jia Wenting, Okuno Saori, Ohashi Yuji, Kamada Kei, Yoshikawa Akira, Tominaga Teiji

NEURO-ONCOLOGY Vol. 20 page： 88 2018.11

SMART (stroke-like migraine attacks after radiation therapy) syndrome responded to steroid pulse therapy: Report of a case and review of the literature. Reviewed International journal

Wenting Jia, Ryuta Saito, Masayuki Kanamori, Naoya Iwabuchi, Masaki Iwasaki, Teiji Tominaga

eNeurologicalSci Vol. 12 page： 1 - 4 2018.9

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

This report presents a case of stroke-like migraine attacks after radiation therapy (SMART) syndrome in a 31-year-old man in whom symptoms and radiological findings resolved with steroid pulsed therapy and reviews the literatures with special emphasis on the use of steroids against SMART syndrome. The patient had a past history of left temporal anaplastic astrocytoma and was treated with surgery followed by local 72 Gy radiation therapy and chemotherapy using Nimustine Hydrochloride. Four years after the surgery, he was suffering from subacute progressing symptoms of headache, right hemianopia, right hemiparesis and aphasia from 2 to 4 days before admission to our hospital. At first he was diagnosed as symptomatic epilepsy but after extensive examination, the final diagnosis was SMART syndrome. His symptoms soon improved with steroid pulse therapy. In the literature, steroid pulse therapy is not necessarily a standard of care for SMART syndrome, but it seemed to decrease the need of biopsy. As the lesions of SMART syndrome require differential diagnosis from recurrences, biopsy was performed in some cases. However, lack of benefit and possible detriment is reported with biopsy of SMART lesions. Through this experience we suggest that steroid pulse therapy may provide speedy recovery from symptoms, and it should be considered before other invasive investigations or treatments.

DOI： 10.1016/j.ensci.2018.05.003

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Indications for salvage surgery during treatment for intracranial germ cell tumors. Reviewed International journal

Masayuki Kanamori, Toshihiro Kumabe, Mika Watanabe, Masashi Chonan, Ryuta Saito, Yoji Yamashita, Yoshikazu Ogawa, Yukihiko Sonoda, Teiji Tominaga

Journal of neuro-oncology Vol. 138 ( 3 ) page： 601 - 607 2018.7

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

This study retrospectively reviewed our single institute experience to clarify the optimal indication and timing of salvage surgery. Retrospective analysis of 159 consecutive cases with germ cell tumors identified 20 cases with salvage surgery. These cases were classified based on the radiological response to neoadjuvant treatment before salvage surgery into increase (growing group, five cases), no change (stable group, seven cases), and decrease (shrinkage group, eight cases) in tumor size. Changes in tumor markers, histological findings, and the pattern of failure after salvage surgery were reviewed. Growing teratoma syndrome (GTS) is defined as enlargement of tumor consisting of mature teratoma after chemotherapy with normalization of tumor markers. In growing group, two cases presented GTS, whereas other three cases did not fulfill the criteria for GTS. All cases in stable and shrinkage group had elevated levels of tumor markers at presentation and decreased levels after neoadjuvant treatment. Histologically, sparse components of mature teratoma with extensive fibrosis were found in cases with GTS and seven of eight cases in shrinkage group, whereas mature teratoma without fibrosis was found in six of seven cases in stable group. Six cases recurred after salvage surgery. We identified three factors as risks for recurrence after salvage surgery, as follows: (1) growing lesion which did not fulfill the criteria for GTS, (2) non-normalized level of tumor marker before salvage surgery, and (3) residual germinoma component. In conclusion, salvage surgery is recommended for patients with GTS, or with normalized tumor markers in stable or shrinkage group.

DOI： 10.1007/s11060-018-2827-3

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[A Case of Ventriculoperitoneal Shunt Dysfunction in an Adult Secondary to Constipation]. Reviewed

Nakamura L, Saito R, Kanamori M, Morita T, Tashiro R, Tominaga T

No shinkei geka. Neurological surgery Vol. 46 ( 5 ) page： 385 - 389 2018.5

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

INTRODUCTION: Ventriculoperitoneal(VP)shunts function because of the pressure differential between the intracranial space and the peritoneal cavity. Although chronic constipation is often a cause of VP shunt dysfunction in children, it is not well recognized in adults. We present a case of shunt dysfunction that not only resolved after resolution of constipation but also resulted in overdrainage. CASE REPORT: A 28-year-old woman who had a VP shunt placed 11 years prior for hydrocephalus was referred to our department because of an enlarged ventricle diagnosed with computed tomography(CT). She had a previous history of pineal germinoma and a VP shunt was placed to treat the associated hydrocephalus. At presentation, she complained of headache and somnolence. Shunt dysfunction was suspected, but no problem was detected in the shunt system, including pressure settings. As constipation was detected, we treated this condition. Soon after, her symptoms resolved and ventricle size normalized. She was discharged without any deficit, but overdrainage was detected with CT obtained 1 month later. CONCLUSION: Although constipation is not a common cause of shunt dysfunction in adult patients, it is important to consider to avoid unnecessary shunt revision. In the present case, resolution of chronic constipation resulted in resolution of shunt dysfunction. This suggests the importance of resolution of constipation in case of shunt adjustment, even in adult cases.

DOI： 10.11477/mf.1436203739

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Clinical Features of Precocious, Synchronous, and Metachronous Brain Metastases and the Role of Tumor Resection. Reviewed International journal

Ichiyo Shibahara, Masayuki Kanamori, Takashi Watanabe, Akihiro Utsunomiya, Hiroyoshi Suzuki, Ryuta Saito, Yukihiko Sonoda, Hidefumi Jokura, Hiroshi Uenohara, Teiji Tominaga

World neurosurgery Vol. 113 page： e1-e9 - e9 2018.5

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

OBJECTIVE: The purpose of this study was to clarify clinical features, outcomes, and the role of tumor resection in precocious, synchronous, and metachronous brain metastases. METHODS: Brain metastases were found before primary cancer detection in the precocious group, within 2 months after primary cancer detection in the synchronous group, and 2 months or later after primary cancer detection in the metachronous group. RESULTS: Of 471 patients with brain metastases, 93 (20%) were included in the precocious group, 76 (16%) in the synchronous group, and 302 (64%) in the metachronous group. The precocious group tended to be symptomatic, show a low Karnofsky Performance Status, and have a large single tumor, infrequent extracranial metastases, and frequent tumor resection compared with the other 2 groups. There were no differences in overall survival from the detection of brain metastases among the 3 groups in univariate and multivariate analyses. Of 471 cases, 97 (21%) underwent surgeries. Among this surgical cohort, overall survival from surgery was significantly shorter in the precocious group than in the metachronous group (P = 0.039). After adjustment for age, sex, tumor size, primary cancer, and the Graded Prognostic Assessment score, the hazard ratio for metachronous metastases was 0.52 (confidence interval, 0.29-0.95; P = 0.035). CONCLUSIONS: The timing of brain metastasis diagnosis is not a modifiable factor but affects patient demographics and treatment strategies. In particular, the precocious group is a unique subset of brain metastases that require special consideration during clinical decision making.

DOI： 10.1016/j.wneu.2017.10.145

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[Results for Treatment of Newly-Diagnosed Glioblastoma Using Carmustine Wafers(Gliadel<sup>®</sup>)]. Reviewed

Kumabe T, Shibahara I, Saito R

No shinkei geka. Neurological surgery Vol. 46 ( 5 ) page： 367 - 376 2018.5

カルムスチン脳内留置用剤(ギリアデル)による初発膠芽腫の治療成績

隈部俊宏, 柴原一陽, 齋藤竜太

Neurological Surgery Vol. 46 ( 5 ) page： 367 - 376 2018.5

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Papers - SAITO Ryuta