Papers - SAITO Ryuta

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

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

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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

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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

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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

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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

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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

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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

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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^®)]. Reviewed

Kumabe T, Shibahara I, Saito R

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

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DOI： 10.11477/mf.1436203736

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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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Language：Japanese   Publisher：(株)医学書院  

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2018&ichushi_jid=J01228&link_issn=&doc_id=20180528190004&doc_link_id=10.11477%2Fmf.1436203736&url=https%3A%2F%2Fdoi.org%2F10.11477%2Fmf.1436203736&type=%E5%8C%BB%E6%9B%B8.jp_%E3%82%AA%E3%83%BC%E3%83%AB%E3%82%A2%E3%82%AF%E3%82%BB%E3%82%B9&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

Three case reports of radiation-induced glioblastoma after complete remission of acute lymphoblastic leukemia Reviewed

Takumi Kajitani, Masayuki Kanamori, Ryuta Saito, Yuko Watanabe, Hiroyoshi Suzuki, Mika Watanabe, Shigeo Kure, Teiji Tominaga

Brain Tumor Pathology   Vol. 35 ( 2 ) page： 1 - 9   2018.4

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Springer Tokyo  

Radiation therapy is sometimes performed to control intracranial acute lymphoblastic leukemia (ALL), but may lead to radiation-induced malignant glioma. The clinical, radiological, histological, and molecular findings are described of three cases of radiation-induced glioblastoma after the treatment for ALL. They received radiation therapy at age 6–8 years. The latency from radiation therapy to the onset of radiation-induced glioblastoma was 5–10 years. Magnetic resonance imaging demonstrated diffuse lesions with multiple small enhanced lesions in all cases. Histological examination showed that the tumors consisted of mainly small round astrocytic atypical cells in one case, and astrocytic atypical cells with elongated cytoplasm and nuclear pleomorphism with small cell component in two cases. Microvascular proliferation was present in all cases. Immunohistochemical analysis for B-Raf V600E, and mutational analysis for the isocitrate dehydrogenase (IDH) 1, IDH2, and H3F3A gene revealed the wild-type alleles in all three cases. The integrated diagnoses were IDH wild-type glioblastoma, and local irradiation and concomitant temozolomide were performed. After the initial treatment, significant shrinkage of the diffuse lesion and enhanced lesion was found in all cases. Radiation-induced glioblastoma occurring after the treatment for ALL had unique clinical, radiological, histological, and molecular characteristics in our three cases.

DOI： 10.1007/s10014-018-0316-1

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Rapid detection of mutation in isocitrate dehydrogenase 1 and 2 genes using mass spectrometry. Reviewed

Masayuki Kanamori, Masamitsu Maekawa, Ichiyo Shibahara, Ryuta Saito, Masashi Chonan, Miki Shimada, Yukihiko Sonoda, Toshihiro Kumabe, Mika Watanabe, Nariyasu Mano, Teiji Tominaga

Brain tumor pathology   Vol. 35 ( 2 ) page： 90 - 96   2018.4

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The 2016 World Health Organization classification of tumors of the central nervous system was recently revised. Mutations in the isocitrate dehydrogenase 1 (IDH1) and IDH2 genes and chromosome 1p/19q codeletion are especially important for both the integrated diagnosis and the determination of surgical strategy. To establish a method for intraoperative molecular diagnosis, a simple, rapid method was developed for the measurement of 2-hydroxyglutarate (2-HG), a specific oncometabolite formed in the presence of IDH gene mutation, using liquid chromatography/electrospray ionization tandem mass spectrometry (LC/ESI-MS/MS). This method requires only 10 min to measure the level of 2-HG from tissue preparation to completion of examination. Using this method, the level of 2-HG was analyzed in 105 patients with diffuse infiltrating glioma, and showed that IDH mutated glioma had significantly higher level of 2-HG compared to IDH wild-type glioma. Receiver operating characteristic curve analysis showed the area under the curve, sensitivity, and specificity were 0.9815, 97.5, and 100%, respectively. In contrast, tumor grade and presence of chromosome 1p/19q codeletion in the IDH mutated glioma could not be predicted from the level of 2-HG. Measurement of 2-HG level using LC/ESI-MS/MS can provide rapid and accurate information of mutation status in the IDH gene.

DOI： 10.1007/s10014-018-0317-0

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Convection-enhanced delivery of sulfasalazine prolongs survival in a glioma stem cell brain tumor model. Reviewed International journal

Shinya Haryu, Ryuta Saito, Wenting Jia, Takuhiro Shoji, Yui Mano, Aya Sato, Masayuki Kanamori, Yukihiko Sonoda, Oltea Sampetrean, Hideyuki Saya, Teiji Tominaga

Journal of neuro-oncology   Vol. 136 ( 1 ) page： 23 - 31   2018.1

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Expression of CD44 in glioma cells was previously correlated with tumor grade and is considered a stem cell marker. CD44 stabilizes the cystine-glutamate transporter (xCT) and inhibits apoptosis in cancer stem cells (CSCs). Recently it was found that Sulfasalazine (SSZ), an anti-inflammatory drug, acts as an inhibitor of xCT and therefore has potential as a targeted therapy for CSCs. In this study, we tested an efficacy of SSZ against glioma stem cell model developed in rats. As poor penetration of blood-brain barrier resulted in insufficient efficacy of systemic SSZ treatment, SSZ was delivered locally with convection-enhanced delivery (CED). In vitro, expression of CD44 in glioma cells and efficacy of SSZ against glioma cells and glioma stem cells were confirmed. SSZ demonstrated anti-proliferative activity in a dose dependent manner against these cells. This activity was partially reversible with the addition of antioxidant, N-acetyl-L-cysteine, to the medium. In vivo, CED successfully delivered SSZ into the rat brain parenchyma. When delivered at 5 mM concentration, which was the highest possible concentration when SSZ was dissolved in water, CED of SSZ resulted in almost no tissue damage. Against highly malignant bRiTs-G3 brain tumor xenografted rat model; the glioma stem cell model, CED of SSZ at 5 mM concentration induced apoptosis and prolonged survival. Consequently, CED of SSZ induced glioma stem cell death without evidence of tissue damage to normal brain parenchyma. This strategy may be a promising targeted treatment against glioma stem cells.

DOI： 10.1007/s11060-017-2621-7

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Fingolimod-associated PML with mild IRIS in MS: A clinicopathologic study. Reviewed International journal

Shuhei Nishiyama, Tatsuro Misu, Yukiko Shishido-Hara, Kazuo Nakamichi, Masayuki Saijo, Yoshiki Takai, Kentarou Takei, Naoki Yamamoto, Hiroshi Kuroda, Ryuta Saito, Mika Watanabe, Teiji Tominaga, Ichiro Nakashima, Kazuo Fujihara, Masashi Aoki

Neurology(R) neuroimmunology & neuroinflammation   Vol. 5 ( 1 ) page： e415   2018.1

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Objective: To clarify the clinical, neuropathologic, and virologic characteristics of progressive multifocal leukoencephalopathy (PML) and its immune reconstitution inflammatory syndrome (IRIS) in a patient with fingolimod-treated MS. Methods: A case study. Results: A 34-year-old patient with MS using fingolimod for 4 years had a gradual progression of right hemiparesis and aphasia with a new subcortical white matter lesion in the precentral gyrus by initial MRI. Blood tests were normal, except for lymphopenia (160 cells/μL). One month after the cessation of fingolimod, brain MRI depicted a diffusely exacerbated hyperintensity on fluid-attenuated inversion recovery and diffusion-weighed imaging in the white matter with punctate gadolinium enhancement, suggesting PML-IRIS. A very low level of JC virus (JCV)-DNA (15 copies/mL) was detected in the CSF as judged by quantitative PCR. Brain tissues were biopsied from the left frontal lesion, which showed some small demyelinated foci with predominant loss of myelin-associated glycoprotein with infiltrations of lymphocytes and macrophages, but clear viral inclusion was not observed with hematoxylin-eosin staining. JCV-DNA was uniquely detectable in an active inflammatory demyelinating lesion by in situ hybridization, possibly suggesting an early phase of PML. DNA extracted from the brain sample was positive for JCV-DNA (151 copies/cell). It took 3 months to normalize the blood lymphocyte count. The patient was treated with 1 g of IV methylprednisolone for 3 days and a weekly oral dose (375 mg) of mefloquine, and her symptoms gradually improved. Conclusion: Low CSF JCV-DNA and unfound viral inclusions initially made her diagnosis difficult. The clinical course of fingolimod-associated PML may be associated with mild immune reconstitution.

DOI： 10.1212/NXI.0000000000000415

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Glioblastoma in neurofibromatosis 1 patients without IDH1, BRAF V600E, and TERT promoter mutations. Reviewed

Ichiyo Shibahara, Yukihiko Sonoda, Hiroyoshi Suzuki, Akifumi Mayama, Masayuki Kanamori, Ryuta Saito, Yasuhiro Suzuki, Shoji Mashiyama, Hiroshi Uenohara, Mika Watanabe, Toshihiro Kumabe, Teiji Tominaga

Brain tumor pathology   Vol. 35 ( 1 ) page： 10 - 18   2018.1

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Pilocytic astrocytomas and low-grade gliomas are more common compared with glioblastomas in patients with neurofibromatosis 1 (NF1). A recent genome-wide analysis has shown frequent NF1 gene alterations in the mesenchymal subtype of a glioblastoma; however, little is known about clinicopathological features of glioblastomas in NF1 patients (NF1 glioblastomas). We analyzed four NF1 glioblastomas. Radiographical and intraoperative findings showed well-circumscribed tumors from surrounding brain. Pathological analysis presented a paucity of processes with an eosinophilic cytoplasm, bizarre nuclei, xanthomatous-like appearance, multinucleated giant cells, and histiocytoid appearance. During the follow-up period, one patient died at 49 months and others remained alive for 60, 87, and 106 months; thus, patients with NF1 glioblastoma presented a relatively favorable survival. None of the NF1 glioblastomas harbored isocitrate dehydrogenase 1 (IDH1) gene mutation, v-RAF murine sarcoma viral oncogene homolog B1 (BRAF) gene mutation, and telomerase reverse transcriptase (TERT) gene promoter mutation. We identified that NF1 glioblastoma is a unique subset of glioblastoma.

DOI： 10.1007/s10014-017-0302-z

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Opening the ventricle during surgery diminishes survival among patients with newly diagnosed glioblastoma treated with carmustine wafers: a multi-center retrospective study Reviewed International journal

Yukihiko Sonoda, Ichiyo Shibahara, Ken-ichiro Matsuda, Ryuta Saito, Tomoyuki Kawataki, Masaya Oda, Yuichi Sato, Hirokazu Sadahiro, Sadahiro Nomura, Toshio Sasajima, Takaaki Beppu, Masayuki Kanamori, Kaori Sakurada, Toshihiro Kumabe, Teiji Tominaga, Hiroyuki Kinouchi, Hiroaki Shimizu, Kuniaki Ogasawara, Michiyasu Suzuki

JOURNAL OF NEURO-ONCOLOGY   Vol. 134 ( 1 ) page： 83 - 88   2017.8

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Carmustine wafers (CW) were approved in Japan for newly diagnosed and recurrent malignant gliomas during 2013. The ventricle is often opened during surgery to achieve maximum resection. While not generally recommended in such situations, CW might be safely achieved by occluding an opened ventricle using gelform or collagen sheets. However, whether CW implantation actually confers a survival benefit for patients who undergo surgery with an open ventricle to treat glioblastoma remains unclear. Clinical, imaging, and survival data were collected in this multicenter retrospective study of 122 consecutive patients with newly diagnosed glioblastoma to determine adverse events and efficacy. Overall, 54 adverse events of all grades developed in 35 (28.6%) patients, with the most common being new seizures (16%). Adverse events did not significantly differ between patients with opened and closed ventricles during surgery. The 10- and 21.7-month, median, progression-free (PFS) and overall survival (OS), respectively did not significantly differ according to resection rates. However, median PFS and OS were significantly longer among patients with closed, than open ventricles (12.8 vs. 7.4 months; p = 0.0039 and 26.9 vs. 18.6 months; p = 0.011, respectively). Implanting CW into the resection cavity during concomitant radiochemotherapy with temozolomide seems to yield better survival rates without increased adverse events. Occlusion of the ventricular opening during surgery might be safe for CW implantation, but less so for treating patients with newly diagnosed glioblastoma.

DOI： 10.1007/s11060-017-2488-7

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Distant recurrences limit the survival of patients with thalamic high-grade gliomas after successful resection Reviewed International journal

Ryuta Saito, Toshihiro Kumabe, Masayuki Kanamori, Yukihiko Sonoda, Teiji Tominaga

NEUROSURGICAL REVIEW   Vol. 40 ( 3 ) page： 469 - 477   2017.7

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The indications of surgery for thalamic high-grade gliomas are not well established. The present study investigated the outcome of 21 patients treated by surgery and reports the high incidence of distant recurrences including disseminations after successful removal. Twenty-one patients with thalamic high-grade gliomas not invading the pyramidal tract or midbrain underwent cytoreductive surgery at our institute from June 1997 to August 2015. Surgery was performed with the aid of a neuronavigation system, electrophysiological monitoring, and fluorescence navigation. Tumor histology included 12 cases of the World Health Organization grade III and nine cases of grade IV. Gross total resection was achieved in six cases, subtotal in 13, and partial in two. Motor weakness accompanied by sensory disturbance deteriorated immediately after surgery in 13 patients. However, five patients were determined to show deterioration at 2 months after surgery. Postoperative radiation and chemotherapy were given to every patient, and median progression-free survival of patients with grade III and IV tumors was 12.1 and 7.0 months, respectively. Median overall survival of patients with grade III and IV tumors was 25.6 and 12.6 months, respectively. High incidence of distant recurrences was found, with distant lesions at recurrence in 13 of 19 patients with recurrence, suggesting the life-restricting factor in these patients. Thalamic high-grade glioma without invasion into the pyramidal tract and brainstem can be considered as a candidate for surgical resection. Distant lesion limits the survival of patients after successful resection.

DOI： 10.1007/s10143-016-0804-x

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Convection-enhanced delivery of a hydrophilic nitrosourea ameliorates deficits and suppresses tumor growth in experimental spinal cord glioma models Reviewed International journal

Shogo Ogita, Toshiki Endo, Shinichiro Sugiyama, Ryuta Saito, Tomoo Inoue, Akira Sumiyoshi, Hiroi Nonaka, Ryuta Kawashima, Yukihiko Sonoda, Teiji Tominaga

ACTA NEUROCHIRURGICA   Vol. 159 ( 5 ) page： 939 - 946   2017.5

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Convection-enhanced delivery (CED) is a technique allowing local infusion of therapeutic agents into the central nervous system, circumventing the blood-brain or spinal cord barrier.
To evaluate the utility of nimustine hydrochloride (ACNU) CED in controlling tumor progression in an experimental spinal cord glioma model.
Toxicity studies were performed in 42 rats following the administration of 4 mu l of ACNU CED into the mid-thoracic spinal cord at concentrations ranging from 0.1 to 10 mg/ml. Behavioral analyses and histological evaluations were performed to assess ACNU toxicity in the spinal cord. A survival study was performed in 32 rats following the implantation of 9 L cells into the T8 spinal cord. Seven days after the implantation, rats were assigned to four groups: ACNU CED (0.25 mg/ml; n = 8); ACNU intravenous (i.v.) (0.4 mg; n = 8); saline CED (n = 8); saline i.v. (n = 8). Hind limb movements were evaluated daily in all rats for 21 days. Tumor sizes were measured histologically.
The maximum tolerated ACNU concentration was 0.25 mg/ml. Preservation of hind limb motor function and tumor growth suppression was observed in the ACNU CED (0.25 mg/ml) and ACNU i.v. groups. Antitumor effects were more prominent in the ACNU CED group especially in behavioral analyses (P < 0.05; log-rank test).
ACNU CED had efficacy in controlling tumor growth and preserving neurological function in an experimental spinal cord tumor model. ACNU CED can be a viable treatment option for spinal cord high-grade glioma.

DOI： 10.1007/s00701-017-3123-2

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Intraoperative Visualization of Subependymal Arteries at the Atrium Supplying the Descending Motor Pathway Reviewed International journal

Mitsuto Hanihara, Sumito Sato, Ichiyo Shibahara, Ryuta Saito, Masayuki Kanamori, Yukihiko Sonoda, Hiroyuki Kinouchi, Teiji Tominaga, Toshihiro Kumabe

WORLD NEUROSURGERY   Vol. 101   page： 296 - 303   2017.5

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE INC  

OBJECTIVE: We previously disclosed that damage to the subependymal arteries (SEAs) caused by coagulation of the choroid plexus at the atrium can result in infarction within the lateral posterior choroidal artery territory, followed by hemiparesis. The present study describes the intra-operative anatomical findings of the SEAs and choroid plexus at the atrium, which were verified only by a few cadaveric studies.
METHODS: Locations of the SEA and descending motor pathway were determined with the neuronavigation system and subcortical electrical stimulation in 8 cases of periatrial brain tumor. Indocyanine green videoangiography was performed to verify the blood flowin the choroid plexus and SEAs.
RESULTS: Intraoperative visualization of the SEAs was performed successfully in all patients. The neuronavigation system and subcortical electrical stimulation mapping demonstrated that these SEAs penetrated into the descending motor pathway. Indocyanine green depicted the blood flow of the SEAs entering the wall of the lateral ventricle and adjacent brain parenchyma. The blood flow directions between the SEAs and choroid plexus were not uniform, because the SEAs were filled ahead of the choroid plexus in 3 cases, whereas the choroid plexus was filled first in the other 2 cases.
CONCLUSIONS: Manipulations to the inner side of the choroid plexus at the transition from the atrium to the body of lateral ventricle can damage the SEAs. Not only coagulation of the SEAs themselves, but also coagulation of choroid plexus itself may reduce the blood flow in the SEAs, resulting in ischemic complications at descending motor pathway.

DOI： 10.1016/j.wneu.2017.02.022

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術中迅速診断へのmass spectrometryの応用

金森 政之, 前川 正充, 柴原 一陽, 斎藤 竜太, 園田 順彦, 渡辺 みか, 冨永 悌二

Brain Tumor Pathology   Vol. 34 ( Suppl. ) page： 105 - 105   2017.5

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Language：Japanese   Publisher：日本脳腫瘍病理学会  

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Convection-enhanced Delivery of Therapeutics for Malignant Gliomas Reviewed

Ryuta Saito, Teiji Tominaga

NEUROLOGIA MEDICO-CHIRURGICA   Vol. 57 ( 1 ) page： 8 - 16   2017.1

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：JAPAN NEUROSURGICAL SOC  

Convection-enhanced delivery (CED) circumvents the blood-brain barrier by delivering agents directly into the tumor and surrounding parenchyma. CED can achieve large volumes of distribution by continuous positive-pressure infusion. Although promising as an effective drug delivery method in concept, the administration of therapeutic agents via CED is not without challenges. Limitations of distribution remain a problem in large brains, such as those of humans. Accurate and consistent delivery of an agent is another challenge associated with CED. Similar to the difficulties caused by immunosuppressive environments associated with gliomas, there are several mechanisms that make effective local drug distribution difficult in malignant gliomas. In this review, methods for local drug application targeting gliomas are discussed with special emphasis on CED. Although early clinical trials have failed to demonstrate the efficacy of CED against gliomas, CED potentially can be a platform for translating the molecular understanding of glioblastomas achieved in the laboratory into effective clinical treatments. Several clinical studies using CED of chemotherapeutic agents are ongoing. Successful delivery of effective agents should prove the efficacy of CED in the near future.

DOI： 10.2176/nmc.ra.2016-0071

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