Faculty Profiles - SAITO Ryuta

Papers - SAITO Ryuta

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交流電場腫瘍療法下における悪性神経膠腫の再発様式の検討

滝戸悠平, 大岡史治, 本村和也, 芝良樹, 山口純矢, 前田紗知, 清水大輝, 野平翔太, 山本諒, 齋藤竜太

Brain Tumor Pathology Vol. 41 ( Suppl. ) page： 137 - 137 2024.5

小児脳腫瘍の分子診断の現状と展望上衣腫診断におけるH3K27me3染色所見のサロゲートマーカーとしての有用性についての検討

芝良樹, 山口純矢, 大岡史治, 本村和也, 齋藤竜太

Brain Tumor Pathology Vol. 41 ( Suppl. ) page： 107 - 107 2024.5

小児脳腫瘍の分子診断の現状と展望 Diffuse hemispheric glioma,H3 G34-mutantの白質病変および進行形式に関する考察

木部祐士, 大岡史治, ルシュン・チャリセ, 本村和也, 山口純矢, 西川知秀, 前田紗知, 清水大輝, 滝戸悠平, 齋藤竜太

Brain Tumor Pathology Vol. 41 ( Suppl. ) page： 108 - 108 2024.5

初回術後早期に再発を認めた星芽細胞腫の1例

滝戸悠平, 本村和也, 大岡史治, 平戸純子, 信澤純人, 山口純矢, 前田紗知, 木部祐士, 清水大輝, 野平翔太, 山本諒, 齋藤竜太

日本小児血液・がん学会雑誌 Vol. 61 ( 1 ) page： 100 - 100 2024.5

当院における小児脳腫瘍に対するがんパネル検査についての検討

清水大輝, 大岡史治, 本村和也, 山口純矢, 前田紗知, 木部祐士, 滝戸悠平, 齋藤竜太

日本小児血液・がん学会雑誌 Vol. 61 ( 1 ) page： 101 - 102 2024.5

脳腫瘍の分子診断と治療2 高速リアルタイムPCR装置を用いたCDKN2A homozygous deletionの術中解析

清水大輝, 大岡史治, 本村和也, 山口純矢, 芝良樹, 木部祐士, 前田紗知, 滝戸悠平, 山本諒, 齋藤竜太

Brain Tumor Pathology Vol. 41 ( Suppl. ) page： 101 - 101 2024.5

画像と病理1 メチオニンPET陰性腫瘍の病理

齋藤竜太, 本村和也, 大岡史治, 青木恒介, 出口誠一, 芝良樹, 山口純矢, 前田紗知, 木部祐士, 清水大輝

Brain Tumor Pathology Vol. 41 ( Suppl. ) page： 082 - 082 2024.5

Obstructive Hydrocephalus Due to Aggressive Posterior Fossa Tumor Exhibiting Histological Characteristics of Pilocytic Astrocytoma in Two Adult Neurofibromatosis Type 1 (NF1) Cases. Reviewed International journal Open Access

Shigeaki Nawa, Fumiharu Ohka, Kazuya Motomura, Kazuhito Takeuchi, Yuichi Nagata, Junya Yamaguchi, Ryuta Saito

Cureus Vol. 16 ( 4 ) page： e58697 2024.4

Language：English

Neurofibromatosis type 1 (NF1) is an autosomal dominant syndrome caused by germline alteration of the NF1gene. Among various NF1-related manifestations, obstructive hydrocephalus especially in adult NF1 cases is less frequently found. We report two adult NF1 cases exhibiting obstructive hydrocephalus due to an aggressive posterior fossa tumor exhibiting pathological characteristics of pilocytic astrocytoma as NF1-related manifestations. In these two cases, we performed endoscopic third ventriculostomy (ETV) and tumor biopsy as an initial treatment. The initial pathological diagnosis of the tumor is conventional pilocytic astrocytoma. After biopsy both cases revealed rapid tumor growth, therefore, we performed tumor removal, chemotherapy, and radiation therapy during an aggressive clinical course. However, both cases revealed dismal prognosis due to the progression of the tumor in spite of successful management of hydrocephalus by an initial ETV. DNA methylation analysis revealed that the tumor of one case matched high-grade astrocytoma with piloid features (HGAP). Most central nervous system tumors developed in NF1 are less aggressive such as pilocytic astrocytoma; however, recently a few studies revealed that HGAP, which has been a newly introduced malignant tumor in the World Health Organization Classification of Tumors of the Central Nervous System, 5th edition (WHO CNS 5), rarely develops in NF1 cases. These findings suggested that HGAP might be one of the important causes of obstructive hydrocephalus in adult NF1 cases.

DOI： 10.7759/cureus.58697

Pediatric-type high-grade gliomas with PDGFRA amplification in adult patients with Li-Fraumeni syndrome: clinical and molecular characterization of three cases. Reviewed International journal Open Access

Yuji Kibe, Fumiharu Ohka, Kosuke Aoki, Junya Yamaguchi, Kazuya Motomura, Eiji Ito, Kazuhito Takeuchi, Yuichi Nagata, Satoshi Ito, Nobuhiko Mizutani, Yoshiki Shiba, Sachi Maeda, Tomohide Nishikawa, Hiroki Shimizu, Ryuta Saito

Acta neuropathologica communications Vol. 12 ( 1 ) page： 57 - 57 2024.4

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

Li-Fraumeni syndrome (LFS) is an autosomal dominant tumor predisposition syndrome caused by heterozygous germline mutations or deletions in the TP53 tumor suppressor gene. Central nervous system tumors, such as choroid plexus tumors, medulloblastomas, and diffuse gliomas, are frequently found in patients with LFS. Although molecular profiles of diffuse gliomas that develop in pediatric patients with LFS have been elucidated, those in adults are limited. Recently, diffuse gliomas have been divided into pediatric- and adult-type gliomas, based on their distinct molecular profiles. In the present study, we investigated the molecular profiles of high-grade gliomas in three adults with LFS. These tumors revealed characteristic histopathological findings of high-grade glioma or glioblastoma and harbored wild-type IDH1/2 according to whole exome sequencing (WES). However, these tumors did not exhibit the key molecular alterations of glioblastoma, IDH-wildtype such as TERT promoter mutation, EGFR amplification, or chromosome 7 gain and 10 loss. Although WES revealed no other characteristic gene mutations or copy number alterations in high-grade gliomas, such as those in histone H3 genes, PDGFRA amplification was found in all three cases together with uniparental disomy of chromosome 17p, where the TP53 gene is located. DNA methylation analyses revealed that all tumors exhibited DNA methylation profiles similar to those of pediatric-type high-grade glioma H3-wildtype and IDH-wildtype (pHGG H3-/IDH-wt), RTK1 subtype. These data suggest that high-grade gliomas developed in adult patients with LFS may be involved in pHGG H3-/IDH-wt. PDGFRA and homozygous alterations in TP53 may play pivotal roles in the development of this type of glioma in adult patients with LFS.

DOI： 10.1186/s40478-024-01762-7

Development of a rapid and comprehensive genomic profiling test supporting diagnosis and research for gliomas. Reviewed

Takuma Nakashima, Ryo Yamamoto, Makoto Ohno, Hirokazu Sugino, Masamichi Takahashi, Yusuke Funakoshi, Shohei Nambu, Atsuhito Uneda, Shunsuke Yanagisawa, Takeo Uzuka, Yoshiki Arakawa, Ryosuke Hanaya, Joji Ishida, Koji Yoshimoto, Ryuta Saito, Yoshitaka Narita, Hiromichi Suzuki

Brain tumor pathology Vol. 41 ( 2 ) page： 50 - 60 2024.4

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

A prompt and reliable molecular diagnosis for brain tumors has become crucial in precision medicine. While Comprehensive Genomic Profiling (CGP) has become feasible, there remains room for enhancement in brain tumor diagnosis due to the partial lack of essential genes and limitations in broad copy number analysis. In addition, the long turnaround time of commercially available CGPs poses an additional obstacle to the timely implementation of results in clinics. To address these challenges, we developed a CGP encompassing 113 genes, genome-wide copy number changes, and MGMT promoter methylation. Our CGP incorporates not only diagnostic genes but also supplementary genes valuable for research. Our CGP enables us to simultaneous identification of mutations, gene fusions, focal and broad copy number alterations, and MGMT promoter methylation status, with results delivered within a minimum of 4 days. Validation of our CGP, through comparisons with whole-genome sequencing, RNA sequencing, and pyrosequencing, has certified its accuracy and reliability. We applied our CGP for 23 consecutive cases of intracranial mass lesions, which demonstrated its efficacy in aiding diagnosis and prognostication. Our CGP offers a comprehensive and rapid molecular profiling for gliomas, which could potentially apply to clinical practices and research primarily in the field of brain tumors.

DOI： 10.1007/s10014-023-00476-3

脳腫瘍2 小児上衣腫に対する手術摘出度と分子学的マーカーを用いた治療層別化による集学的治療の安全性と有効性を評価する第II相試験

齋藤竜太, 谷口理恵子, 前林勝也, 五味玲, 義岡孝子, 信澤純人, 市村幸一, 山崎夏維, 荒川芳輝, 隈部俊宏

小児の脳神経 Vol. 49 ( 2 ) page： 131 - 131 2024.4

Characteristics of deceased subjects transported to a postmortem imaging center due to unusual death related to epilepsy Reviewed

Ito, Y; Hata, N; Maesawa, S; Tanei, T; Ishizaki, T; Mutoh, M; Hashida, M; Kobayashi, Y; Saito, R

EPILEPSIA OPEN Vol. 9 ( 2 ) page： 592 - 601 2024.4

Authorship：Last author Language：English Publishing type：Research paper (scientific journal) Publisher：Epilepsia Open

Objective: Patients with epilepsy have high risk of experiencing uncommon causes of death. This study aimed to evaluate patients who underwent unusual deaths related to epilepsy and identify factors that may contribute to these deaths and may also include sudden unexpected death in epilepsy (SUDEP). Methods: We analyzed 5291 cases in which a postmortem imaging (PMI) study was performed using plane CT, because of an unexplained death. A rapid troponin T assay was performed using peripheral blood samples. Clinical information including the cause of death suspected by the attending physician, body position, place of death, medical history, and antiseizure medications was evaluated. Results: A total of 132 (2.6%) patients had an obvious history of epilepsy, while 5159 individuals had no history of epilepsy (97.4%). Cerebrovascular disease was the cause of death in 1.6% of patients in the group with epilepsy, and this was significantly lower than that in the non-epilepsy group. However, drowning was significantly higher (9.1% vs. 4.4%). Unspecified cause of death was significantly more frequent in the epilepsy group (78.0% vs. 57.8%). Furthermore, the proportion of patients who demonstrated elevation of troponin T levels without prior cardiac disease was significantly higher in the epilepsy group (37.9% vs. 31.1%). At discovery of death, prone position was dominant (30.3%), with deaths occurring most commonly in the bedroom (49.2%). No antiseizure medication had been prescribed in 12% of cases, while 29.5% of patients were taking multiple antiseizure medications. Significance: The prevalence of epilepsy in individuals experiencing unusual death was higher than in the general population. Despite PMI studies, no definitive cause of death was identified in a significant proportion of cases. The high troponin T levels may be explained by long intervals between death and examination or by higher incidence of myocardial damage at the time of death. Plain Language Summary: This study investigated unusual deaths in epilepsy patients, analyzing 5291 postmortem imaging cases. The results showed that 132 cases (2.6%) had a clear history of epilepsy. In these cases, only 22% cases were explained after postmortem examination, which is less than in non-epilepsy group (42.2%). Cerebrovascular disease was less common in the epilepsy group, while drowning was more common. Elevated troponin T levels, which suggest possibility of myocardial damage or long intervals between death and examination, were also more frequent in the epilepsy group compared to non-epilepsy group.

DOI： 10.1002/epi4.12891

Cerebellar and thalamic connector hubs facilitate the involvement of visual and cognitive networks in essential tremor Reviewed International coauthorship

Bagarinao, E; Maesawa, S; Kato, S; Mutoh, M; Ito, Y; Ishizaki, T; Tanei, T; Tsuboi, T; Suzuki, M; Watanabe, H; Hoshiyama, M; Isoda, H; Katsuno, M; Sobue, G; Saito, R

PARKINSONISM & RELATED DISORDERS Vol. 121 page： 106034 2024.4

Authorship：Last author Language：English Publishing type：Research paper (scientific journal) Publisher：Parkinsonism and Related Disorders

Introduction: Connector hubs are specialized brain regions that connect multiple brain networks and therefore have the potential to affect the functions of multiple systems. This study aims to examine the involvement of connector hub regions in essential tremor. Methods: We examined whole-brain functional connectivity alterations across multiple brain networks in 27 patients with essential tremor and 27 age- and sex-matched healthy controls to identify affected hub regions using a network metric called functional connectivity overlap ratio estimated from resting-state functional MRI. We also evaluated the relationships of affected hubs with cognitive and tremor scores in all patients and with motor function improvement scores in 15 patients who underwent postoperative follow-up evaluations after focused ultrasound thalamotomy. Results: We have identified affected connector hubs in the cerebellum and thalamus. Specifically, the dentate nucleus in the cerebellum and the dorsomedial thalamus exhibited more extensive connections with the sensorimotor network in patients. Moreover, the connections of the thalamic pulvinar with the visual network were also significantly widespread in the patient group. The connections of these connector hub regions with cognitive networks were negatively associated (FDR q < 0.05) with cognitive, tremor, and motor function improvement scores. Conclusion: In patients with essential tremor, connector hub regions within the cerebellum and thalamus exhibited widespread functional connections with sensorimotor and visual networks, leading to alternative pathways outside the classical tremor axis. Their connections with cognitive networks also affect patients’ cognitive function.

DOI： 10.1016/j.parkreldis.2024.106034

Outcomes and Prognostic Factors of Magnetic Resonance-guided Focused Ultrasound Thalamotomy for Essential Tremor at 2-year Follow-up Reviewed

HASHIDA Miki, MAESAWA Satoshi, KATO Sachiko, NAKATSUBO Daisuke, TSUGAWA Takahiko, TORII Jun, TANEI Takafumi, ISHIZAKI Tomotaka, MUTOH Manabu, ITO Yoshiki, TSUBOI Takashi, MIZUNO Satomi, SUZUKI Masashi, WAKABAYASHI Toshihiko, KATSUNO Masahisa, SAITO Ryuta

Neurologia medico-chirurgica Vol. 64 ( 4 ) page： 137 - 146 2024.4

Authorship：Last author Language：English Publisher：The Japan Neurosurgical Society

<p>Magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy is an effective treatment for essential tremor (ET). However, its long-term outcomes and prognostic factors remain unclear. This study aimed to retrospectively investigate 38 patients with ET who underwent MRgFUS thalamotomy and were followed up for >2 years. The improvement in tremor was evaluated using the Clinical Rating Scale for Tremor (CRST). Adverse events were documented, and correlations with factors, such as skull density ratio (SDR), maximum mean temperature (T-max), and lesion size, were examined. Furthermore, the outcomes were compared between two groups, one that met the cutoff values, which was previously reported (preoperative CRST-B ≤ 25, T-max ≥ 52.5°C, anterior-posterior size of lesion ≥ 3.9 mm, superior-inferior [SI] size of lesion > 5.5 mm), and the other that did not. The improvement rate was 59.4% on average at the 2-year follow-up. Adverse events, such as numbness (15.8%), dysarthria (10.5%), and lower extremity weakness (2.6%), were observed even after 2 years, although these were mild. The factors correlated with tremor improvement were the T-max and SI size of the lesion (p < 0.05), whereas the SDR showed no significance. Patients who met the aforementioned cutoff values demonstrated a 69.8% improvement at the 2-year follow-up, whereas others showed a 43.6% improvement (p < 0.05). In conclusion, MRgFUS is effective even after 2 years. The higher the T-max and the larger the lesion size, the better the tremor control. Previously reported cutoff values clearly predict the 2-year prognosis, indicating the usefulness of MRgFUS.</p>

DOI： 10.2176/jns-nmc.2023-0202

脳腫瘍1 高速定量PCR装置を用いた小児脳腫瘍の迅速遺伝子解析法の確立

大岡史治, 前田紗知, 清水大輝, 本村和也, 芝良樹, 山口純矢, 竹内和人, 永田雄一, 木部祐士, 滝戸悠平, 齋藤竜太

小児の脳神経 Vol. 49 ( 2 ) page： 168 - 168 2024.4

上衣腫診断におけるサロゲートマーカーの有用性

芝良樹, 山口純矢, 滝戸悠平, 清水大輝, 木部祐士, 大岡史治, 本村和也, 齋藤竜太

小児の脳神経 Vol. 49 ( 2 ) page： 210 - 210 2024.4

小児頭蓋内上衣腫に対する手術摘出の意義について

本村和也, 大岡史治, 芝良樹, 山口純矢, 西川知秀, 木部祐士, 清水大輝, 滝戸悠平, 齋藤竜太

小児の脳神経 Vol. 49 ( 2 ) page： 211 - 211 2024.4

全摘出後に放射線治療・大量化学療法を施行したEmbryonal tumour with multilayered rosettesの1例

滝戸悠平, 本村和也, 大岡史治, 津村悠介, 片岡伸介, 村松秀城, 平戸純子, 義岡孝子, 市村幸一, 芝良樹, 山口純矢, 高橋義行, 齋藤竜太

小児の脳神経 Vol. 49 ( 2 ) page： 227 - 227 2024.4

Molecular insights and the role of 18F-FDG-PET/CT in the diagnosis of spinal gliomas Reviewed

Nagashima, Y; Nishimura, Y; Eguchi, K; Yamaguchi, J; Haimoto, S; Ohka, F; Motomura, K; Abe, T; Matsuo, M; Tsukamoto, E; Hara, M; Saito, R

ACTA NEUROCHIRURGICA Vol. 166 ( 1 ) page： 154 2024.3

Authorship：Last author Language：English Publisher：Acta Neurochirurgica

Background: In recent years, molecular findings on spinal gliomas have become increasingly important. This study aimed to investigate the role of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) in the diagnosis of spinal glioma. Methods: This study included patients diagnosed with spinal cord glioma who underwent 18F-FDG-PET examination at the Department of Neurosurgery, Nagoya University Hospital between January 2016 and November 2023. The gliomas were divided into two groups, high-grade and low-grade, based on pathological and molecular studies. The maximum standardized uptake values (SUVmax) of the tumors were quantified and subsequently represented using receiver operating characteristic (ROC) curves. Results: Eighteen participants were included in this study. Of the participants, seven had high-grade glioma with an SUVmax of 6.76 ± 0.72, and eleven had low-grade glioma with an SUVmax of 4.02 ± 1.78, and a statistically significant difference between the two groups. The ROC curve delineated an SUVmax cutoff value of 5.650, with an area under the curve (AUC) of approximately 0.909. Based on the cutoff value, the results of the diagnostic performance rendered a sensitivity and negative predictive value of 1.0, whereas the specificity and positive predictive value were 0.909 and 0.875, respectively. Conclusions: The present study shows that 18F-FDG-PET exhibits a markedly sensitive and negative predictive value in the assessment of spinal gliomas. Additionally, these findings have potential implications for the qualitative assessment of spinal gliomas using 18F-FDG-PET/CT. This imaging modality may be useful for making timely treatment decisions in situations where a detailed diagnosis by molecular analysis is not possible.

DOI： 10.1007/s00701-024-06039-5

Neonatal Ventricular Reservoir Implantation for Hydrocephalus Management in Chiari III Malformations: A Case Report. Reviewed International journal Open Access

Risa Ito, Yutaro Fuse, Keishi Ito, Hisashi Hatano, Ryuta Saito

Cureus Vol. 16 ( 3 ) page： e55896 2024.3

Language：English

Chiari III malformation, a rare and severe subtype of Chiari malformations, is frequently associated with hydrocephalus. The conventional treatment approaches for hydrocephalus in Chiari III malformations have mainly focused on ventriculoperitoneal (VP) shunting, but optimal methods and timing remain uncertain. We report a case of a newborn girl with Chiari III malformation who underwent surgical closure of an occipitocervical encephalocele and ventricular reservoir implantation on her third day of life. This procedure successfully managed her hydrocephalus without significant short-term complications. Three months post-surgery, she developed secondary external hydrocephalus, which was managed through subdural-peritoneal shunting, allowing her to thrive until at least five years of age. This case demonstrates the potential of ventricular reservoir implantation in treating hydrocephalus associated with Chiari III malformation and brings to light secondary external hydrocephalus, subsequently managed by VP shunting.

DOI： 10.7759/cureus.55896

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