研究者詳細 - 齋藤　竜太

論文 - 齋藤　竜太

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Aphasic status epilepticus after glioma resection: two case reports. 国際誌

Shimoda Y, Kanamori M, Saito R, Osawa S, Mugikura S, Tominaga T

Acta neurochirurgica 163 巻 ( 11 ) 頁： 3109 - 3113 2021年11月

Techniques, Indications, and Outcomes in Magnetic Resonance-guided Focused Ultrasound Thalamotomy for Tremor Open Access

Maesawa, S; Nakatsubo, D; Tsugawa, T; Kato, S; Shibata, M; Takai, S; Torii, J; Ishizaki, T; Wakabayashi, T; Saito, R

NEUROLOGIA MEDICO-CHIRURGICA 61 巻 ( 11 ) 頁： 629 - 639 2021年11月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Neurologia Medico Chirurgica

Magnetic resonance (MR)-guided focused ultrasound surgery (MRgFUS) is the latest minimally invasive stereotactic procedure, and thalamotomy using this novel modality has demonstrated its effectiveness and safety, especially for patients with essential tremor (ET) and Parkinson’s disease (PD). In Japan, the application of MRgFUS to treat ET and PD has recently been covered by health insurance. Technically, the transducer with 1024 elements emits ultrasound beams, which are then focused on the target with a phase control, resulting in optimal ablation by thermal coagulation. The technical advantages of MRgFUS are continuous intraoperative monitoring of clinical symptoms and MR images and fine adjustment of the target by the steering function. Postoperative tremor control is compatible with other modalities, although long-term follow-up is necessary. The adverse effects are usually transient and acceptable. Prognostic factors for good tremor control include high temperature and large lesion size. A high skull density ratio is a factor to achieve high temperature and large lesioning, but it may not be necessary and sufficient for clinical outcomes. For patients with advanced symptoms such as bilateral tremor or head/neck tremor, deep brain stimulation may be recommended because of the adjustability of stimulation and the possibility of bilateral treatment. Patients have high expectations of MRgFUS because of its non-invasiveness. To perform this treatment safely and effectively, physicians need to understand the technological aspects, the physiological principles. To choose the appropriate modality, physicians also should recognize the clinical advantages and disadvantages of MRgFUS compared to other modalities.

DOI： 10.2176/nmc.ra.2021-0187

Newly established patient-derived organoid model of intracranial meningioma 国際誌 Open Access

Yamazaki, S; Ohka, F; Hirano, M; Shiraki, Y; Motomura, K; Tanahashi, K; Tsujiuchi, T; Motomura, A; Aoki, K; Shinjo, K; Murofushi, Y; Kitano, Y; Maeda, S; Kato, A; Shimizu, H; Yamaguchi, J; Adilijiang, A; Wakabayashi, T; Saito, R; Enomoto, A; Kondo, Y; Natsume, A

NEURO-ONCOLOGY 23 巻 ( 11 ) 頁： 1936 - 1948 2021年11月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Neuro Oncology

Background: Recent comprehensive studies have revealed several molecular alterations that are frequently found in meningiomas. However, effective treatment reagents targeting specific molecular alterations have not yet been identified because of the limited number of representative research models of meningiomas. Methods: We performed organoid cultures using meningioma cells and meningioma tumor tissues. Using immunohistochemistry and molecular analyses consisting of whole-exome sequencing, RNA-seq, and DNA methylation analyses, we compared the histological findings and molecular profiling of organoid models with those of parental tumors. Further, using these organoid models together with a public database of meningiomas, we explored molecular alterations, which are a potent treatment target for meningioma. Results: We established 18 organoid models comprising of two malignant meningioma cells (HKBMM and IOMM-Lee), 10 benign meningiomas, four malignant meningiomas, and two solitary fibrous tumors (SFTs). The organoids exhibited consistent histological features and molecular profiles with those of the parental tumors. Using a public database, we identified that upregulated forkhead box M1 (FOXM1) was correlated with increased tumor proliferation. Overexpression of FOXM1 in benign meningioma organoids increased organoid proliferation; depletion of FOXM1 in malignant organoids decreased proliferation. Additionally, thiostrepton, a FOXM1 inhibitor combined with radiation therapy, significantly inhibited the proliferation of malignant meningioma organoid models. Conclusions: An organoid model for meningioma enabled us to elucidate the tumor biology of meningioma along with potent treatment targets for meningioma.

DOI： 10.1093/neuonc/noab155

Effects of oxytocin on responses to nociceptive and non-nociceptive stimulation in the upper central nervous system 国際誌 Open Access

Saito, H; Hidema, S; Otsuka, A; Suzuki, J; Kumagai, M; Kanaya, A; Murakami, T; Takei, Y; Saito, K; Sugino, S; Toyama, H; Saito, R; Tominaga, T; Nishimori, K; Yamauchi, M

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 574 巻頁： 8 - 13 2021年10月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Biochemical and Biophysical Research Communications

Oxytocin is known as a social bonding hormone, but it also functions as an anxiolytic or analgesic neurotransmitter. When oxytocin regulates pain or anxiousness centrally as a neurotransmitter, it is secreted by neurons and directly projected to targeted regions. Although the function of oxytocin at the spinal level is well studied, its effects at the supraspinal level are poorly understood. We aimed to investigate the effect of oxytocin at the supraspinal level in vivo using C57BL/6J (wild-type [WT]), oxytocin-deficient (Oxt−/−), oxytocin receptor-deficient (Oxtr−/−), and oxytocin receptor-Venus (OxtrVenus/+) mice lines. Response thresholds in Oxtr−/− mice in Hargreaves and von-Frey tests were significantly lower than those in WT mice, whereas open field and light/dark tests showed no significant differences. Moreover, response thresholds in Oxt−/− mice were raised to those in WT mice after oxytocin administration. Following the Hargreaves test, we observed the co-localisation of c-fos with Venus or the oxytocin receptor in the periaqueductal gray (PAG), medial amygdala (MeA), and nucleus accumbens (NAc) regions in OxtrVenus/+ mice. Furthermore, in the PAG, MeA, and NAc regions, the co-localisation of oxytocin with c-fos and gamma-aminobutyric acid was much stronger in Oxtr−/− mice than in WT mice. However, following von-Frey test, the same findings were observed only in the MeA and NAc regions. Our results suggest that oxytocin exerts its analgesic effect on painful stimulation via the PAG region and a self-protective effect on unpleasant stimulation via the MeA and NAc regions.

DOI： 10.1016/j.bbrc.2021.08.042

Triggering of Carotid Sinus Reflex during Deployment the Flow-diverter Device Open Access

Goto, S; Izumi, T; Nishihori, M; Tsukada, T; Araki, Y; Uda, K; Yokoyama, K; Saito, R

NEUROLOGIA MEDICO-CHIRURGICA 61 巻 ( 10 ) 頁： 583 - 590 2021年10月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Neurologia Medico Chirurgica

The carotid sinus reflex (CSR) is a rare complication of the Pipeline Embolization Device (PED) deployment. No study has assessed the potential risk factors in a case series. The purpose of this study was to examine CSR triggering during PED deployment. Thirty-seven consecutive patients who underwent PED deployment were included. All procedures were performed under local anesthesia with mild sedation. We retrospectively analyzed patient characteristics, PED deployment time, and vital signs during the procedure. The vital signs included the pulse rate (PR) and systolic blood pressure (SBP) obtained at three timepoints (pre-deployment, during deployment, post-deployment). We examined the triggering of the CSR during PED deployment by comparing the vital signs at the three timepoints. Moreover, risk factors for CSR were analyzed with univar-iate analysis. The patients’ average age was 66.3 years. The average size of the aneurysm was 18.0 mm. Six patients (16.2%) showed a decline in the SBP or PR defined as CSR. One patient had a transient cardiac arrest and two had severe transient bradycardia. Deployment into the ophthalmic segment of the internal carotid artery (C2 segment) aneurysm (p = 0.022), prolonged PED deployment time more than 14.5 minutes (p = 0.005), and an acute angle of the anterior genu less than 51.5 degrees (p = 0.005) were risk factors in triggering CSR. CSR may be triggered during PED deployment under local anesthesia with mild sedation. Deployment to the C2 segment aneu-rysm, prolonged PED deployment time, and an acute angle of the anterior genu were associated with CSR triggering.

DOI： 10.2176/nmc.oa.2021-0049

Sellar arachnoid cystに対する経鼻内視鏡手術

永田雄一, 竹内和人, 山本太樹, 水野晃宏, 永谷哲也, 齋藤竜太

日本内分泌学会雑誌 97 巻 ( S.HPT ) 頁： 49 - 51 2021年9月

内視鏡下経鼻頭蓋底手術後の再建戦略

竹内和人, 永田雄一, 山本太樹, 原田英幸, 齋藤竜太

日本内分泌学会雑誌 97 巻 ( S.HPT ) 頁： 16 - 18 2021年9月

Mathematical Modeling and Mutational Analysis Reveal Optimal Therapy to Prevent Malignant Transformation in Grade II IDH-Mutant Gliomas 国際誌 Open Access

Aoki, K; Suzuki, H; Yamamoto, T; Yamamoto, KN; Maeda, S; Okuno, Y; Ranjit, M; Motomura, K; Ohka, F; Tanahashi, K; Hirano, M; Nishikawa, T; Shimizu, H; Kitano, Y; Yamaguchi, J; Yamazaki, S; Nakamura, H; Takahashi, M; Narita, Y; Nakada, M; Deguchi, S; Mizoguchi, M; Momii, Y; Muragaki, Y; Abe, T; Akimoto, J; Wakabayashi, T; Saito, R; Ogawa, S; Haeno, H; Natsume, A

CANCER RESEARCH 81 巻 ( 18 ) 頁： 4861 - 4873 2021年9月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Cancer Research

Isocitrate dehydrogenase-mutant low-grade gliomas (IDHmut- LGG) grow slowly but frequently undergo malignant transformation, which eventually leads to premature death. Chemotherapy and radiotherapy treatments prolong survival, but can also induce genetic (or epigenetic) alterations involved in transformation. Here, we developed a mathematical model of tumor progression based on serial tumor volume data and treatment history of 276 IDHmut- LGGs classified by chromosome 1p/19q codeletion (IDHmut/ 1p19qcodel and IDHmut/1p19qnoncodel) and performed genomewide mutational analyses, including targeted sequencing and longitudinal whole-exome sequencing data. These analyses showed that tumor mutational burden correlated positively with malignant transformation rate, and chemotherapy and radiotherapy significantly suppressed tumor growth but increased malignant transformation rate per cell by 1.8 to 2.8 times compared with before treatment. This model revealed that prompt adjuvant chemoradiotherapy prolonged malignant transformation-free survival in small IDHmut-LGGs (≤ 50 cm3). Furthermore, optimal treatment differed according to genetic alterations for large IDHmut-LGGs (> 50 cm3); adjuvant therapies delayed malignant transformation in IDHmut/1p19qnoncodel but often accelerated it in IDHmut/1p19qcodel. Notably, PI3K mutation was not associated with malignant transformation but increased net postoperative proliferation rate and decreased malignant transformation-free survival, prompting the need for adjuvant therapy in IDHmut/1p19qcodel. Overall, this model uncovered therapeutic strategies that could prevent malignant transformation and, consequently, improve overall survival in patients with IDHmut-LGGs.

DOI： 10.1158/0008-5472.CAN-21-0985

A Super-selective Wada Test Successfully Detected an Artery That Supplied Broca's Area in a Case of Left Frontal Lobe Glioblastoma: Technical Case Report. Open Access

Yamashita S, Saito R, Osawa SI, Niizuma K, Ukishiro K, Kanamori M, Kakinuma K, Suzuki K, Tominaga T

Neurologia medico-chirurgica 61 巻 ( 11 ) 頁： 661 - 666 2021年8月

[Magnetic Resonance-guided Focused Ultrasound Ablation:Techniques and Neurological Applications].

Maesawa S, Nakatsubo D, Tsugawa T, Kato S, Shibata M, Takai S, Torii J, Wakabayashi T, Saito R

No shinkei geka. Neurological surgery 49 巻 ( 4 ) 頁： 847 - 856 2021年7月

記述言語：日本語掲載種別：研究論文（学術雑誌）出版者・発行元：株式会社医学書院

Magnetic resonance(MR)-guided focused ultrasound ablation(FUS)is a minimally invasive technique for targeted tissue thermo-ablation and is promising for neuromodulation in various neurological disorders. The effectiveness and safety of this technique have been recognized worldwide. In Japan, the applications of FUS for the treatment of essential tremors and Parkinson's disease have recently been covered under health insurance. The FUS system is composed of a phased-array transducer with 1024 elements, with a beam of ultrasound emerging from each element. The phase and amplitude of the beam are computed and controlled to focus on the target with the calculation of computed tomography(CT)profiles, resulting in optimal thermo-ablation. To utilize FUS safely and effectively, a deep understanding of the physics of this technology is necessary. Furthermore, the technique should be compared with other options including deep brain stimulation(DBS)and radiofrequency thermo-ablation. Although FUS has received attention because of minimally invasive characteristics and a possibility of procedural target refinement, DBS has some advantages on bilateral implantation, a potential of postoperative adjustment, and control of head/leg tremors. In this article, we first reviewed the physics of FUS and demonstrated the typical treatment protocols. Second, we reviewed the outcomes from the existing literature, and revealed the advantages and disadvantages of this procedure, with the evaluation of the optimal condition for FUS.

DOI： 10.11477/mf.1436204463

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Association between IDH mutational status and tumor-associated epilepsy or venous thromboembolism in patients with grade II and III astrocytoma.

Osada Y, Saito R, Miyata S, Shoji T, Shibahara I, Kanamori M, Sonoda Y, Kumabe T, Watanabe M, Tominaga T

Brain tumor pathology 38 巻 ( 3 ) 頁： 218 - 227 2021年7月

頭蓋内胚腫治療後にてんかんを発症した症例群の検討

下田由輝, 金森政之, 大沢伸一郎, 齋藤竜太, 園田順彦, 隈部俊宏, 中里信和, 冨永悌二

てんかん研究 39 巻 ( 2 ) 頁： 305 - 305 2021年7月

Impact of the extent of resection on the survival of patients with grade II and III gliomas using awake brain mapping 国際誌 Open Access

Motomura, K; Chalise, L; Ohka, F; Aoki, K; Tanahashi, K; Hirano, M; Nishikawa, T; Yamaguchi, J; Shimizu, H; Wakabayashi, T; Saito, R

JOURNAL OF NEURO-ONCOLOGY 153 巻 ( 2 ) 頁： 361 - 372 2021年6月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Journal of Neuro Oncology

Purpose: The aim of this study was to assess the effect of the extent of resection (EOR) of tumors on survival in a series of patients with grade II and III gliomas (GII/III-gliomas) who underwent awake brain mapping. Methods: We retrospectively analyzed 126 patients with GII/III-gliomas in the dominant and non-dominant hemisphere who underwent awake brain surgery at the same institution between December 2012 and May 2020. Results: EOR cut-off values for improved progression-free survival (PFS) were determined by a receiver operator characteristic (ROC) analysis of 5-year PFS. The ROC for EOR showed a cut-off value of ≥ 85.3%. The median PFS rate of patients with GII/III-gliomas in the group with an EOR ≥ 100%, including supratotal resection (n = 47; median survival [MS], not reached), was significantly higher than that in the group with an EOR < 90% (n = 52; MS, 43.1 months; 95% CI 37.7–48.5 months; p = 0.03). In patients with diffuse astrocytomas and anaplastic astrocytomas, the group with EOR ≥ 100%, including supratotal resection (n = 25; MS, not reached), demonstrated a significantly better PFS rate than did the group with an EOR < 100% (n = 45; MS, 35.8 months; 95% CI 19.9–51.6 months; p = 0.03). Supratotal or gross total resection was correlated with better PFS in IDH-mutant type of diffuse astrocytomas and anaplastic astrocytomas (n = 19; MS, not reached vs. n = 35; MS, 40.6 months; 95% CI 22.3–59.0 months; p = 0.02). By contrast, supratotal or gross total resection was not associated with longer PFS rates in patients with IDH-wild type of diffuse astrocytomas and anaplastic astrocytomas. Conclusions: The present study demonstrates a significant association between tumor EOR and survival in patients with GII/III gliomas. The EOR cut-off value for 5-year PFS was ≥ 85.3%. It is noteworthy that supratotal or gross total resection significantly correlated with better PFS in IDH-mutant type of WHO grade II and III astrocytic tumors. In light of our finding that EOR did not correlate with PFS in patients with aggressive IDH-wild type of diffuse astrocytomas and anaplastic astrocytomas, we suggest treatments that are more intensive will be needed for the control of these tumors.

DOI： 10.1007/s11060-021-03776-w

Postcentral gyrus resection of opercular gliomas is a risk factor for motor deficits caused by damaging the radiologically invisible arteries supplying the descending motor pathway. 国際誌

Shibahara I, Sato S, Hide T, Saito R, Kanamori M, Sonoda Y, Tominaga T, Kumabe T

Acta neurochirurgica 163 巻 ( 5 ) 頁： 1269 - 1278 2021年5月

[Chemotherapy for Glioma].

Saito R

No shinkei geka. Neurological surgery 49 巻 ( 3 ) 頁： 588 - 596 2021年5月

記述言語：日本語掲載種別：研究論文（学術雑誌）出版者・発行元：株式会社医学書院

Chemotherapeutic treatment of malignant gliomas is extremely challenging. Tumor accumulation of systemically-administrated chemotherapy is always hindered by the blood-brain barrier(BBB). Although temozolomide administered orally or intravenously represents the standard of care for malignant gliomas, its efficacy is unsatisfactory. Local chemotherapy bypasses the BBB and, therefore, achieves a high drug concentration at the site the drug is administered. Carmustine wafers are clinically available local chemotherapeutic agents. However, their efficacy is limited because of limited drug penetration into the tumor. Combined with the highly chemoresistant features of glioma itself, ongoing chemotherapy is far from satisfactory in terms of efficacy. This review covers several important issues regarding temozolomide chemotherapy, including the reactivation of hepatitis B virus, assessment of

DOI： 10.11477/mf.1436204432

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高速リアルタイムPCR法を用いた迅速IDH1、H3F3A、BRAF遺伝子変異解析

大岡史治, 北野詳太郎, 本村和也, 清水浩之, 棚橋邦明, 青木恒介, 平野雅規, 山口純矢, 夏目敦至, 齋藤竜太

Brain Tumor Pathology 38 巻 ( Suppl. ) 頁： 075 - 075 2021年5月

中枢神経系原発悪性リンパ腫におけるMYD88/CD79b変異の臨床的意義と迅速変異検出システムの開発

山口純矢, 大岡史治, 清水浩之, 平野雅規, 青木恒介, 棚橋邦明, 本村和也, 夏目敦至, 齋藤竜太

Brain Tumor Pathology 38 巻 ( Suppl. ) 頁： 072 - 072 2021年5月

側脳室下角に存在する脈絡叢腫瘍に対する島下境界溝を介した摘出術

柴原一陽, 百武佑理, 豊田茉梨子, 半田肇, 猿田和貴子, 犬飼円, 佐藤澄人, 秀拓一郎, 齋藤竜太, 金森政之, 園田順彦, 冨永悌二, 隈部俊宏

小児の脳神経 46 巻 ( 2 ) 頁： 179 - 179 2021年4月

Effect of endoscope flexibility on tissue dissection profile assessed with pulsed water jet device: ensuring safety, efficacy, and handling of thin devices for neuroendoscopic surgery. 国際誌 Open Access

Kusunoki T, Kawaguchi T, Nakagawa A, Noguchi Y, Osawa SI, Endo H, Endo T, Saito R, Kanamori M, Niizuma K, Tominaga T

BMC research notes 14 巻 ( 1 ) 頁： 64 - 64 2021年2月

Hepatitis B virus reactivation during temozolomide administration for malignant glioma.

Shoji T, Kanamori M, Inoue J, Saito R, Osada Y, Shimoda Y, Chonan M, Uenohara H, Masamune A, Tominaga T

International journal of clinical oncology 26 巻 ( 2 ) 頁： 305 - 315 2021年2月

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