Faculty Profiles - SAITO Ryuta

Papers - SAITO Ryuta

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Radiographic Prediction of the Occipito-C2 Angle Variation with Changes in Distance between the Mandible and Cervical Vertebrae: A Preliminary Study. Open Access

Yoshitaka Nagashima, Yusuke Nishimura, Takayuki Awaya, Nobuhiro Hata, Takafumi Tanei, Motonori Ishii, Takahiro Oyama, Tomoya Nishii, Nobuhisa Fukaya, Takashi Abe, Hiroyuki Kato, Ryuta Saito

Neurologia medico-chirurgica Vol. 63 ( 5 ) page： 200 - 205 2023.5

Language：English Publishing type：Research paper (scientific journal) Publisher：The Japan Neurosurgical Society

The Occipito (O) -C2 angle reflects the correct craniocervical spine alignment; however, the poor image quality of standard intraoperative fluoroscopy at times lead to inaccurate measurements. Herein, we preliminarily investigated the relationship between the O-C2 angle and the Gonion-C2 distance, which is based on the positioning of the mandible and the cervical spine. We enrolled patients who underwent cervical spine radiography in neutral, flexion, and extension positions from January 2020 to October 2020. The difference by posture changes for each parameter was defined as the Δ value, and the Spearman's rank correlation coefficient was determined. Furthermore, we determined the cutoff value of the ΔGonion-C2 distance to predict a decrease of > 10° in the ΔO-C2 angle, which is reported to be related to dysphagia and dyspnea. Seventy-four patients were included. Spearman's rank correlations for the neutral, flexion, and extension positions were 0.630 (P < 0.001), 0.471 (P < 0.001), and 0.625 (P < 0.001), respectively, while the cutoff values of the ΔGonion-C2 distance for predicting > 10° in the ΔO-C2 angle were 9.3 mm for the neutral flexion change (sensitivity: 0.435, specificity: 0.882) and 8.3 mm for the extension-neutral change (sensitivity: 0.712, specificity: 0.909). The O-C2 angle and Gonion-C2 distances correlated; however, this correlation was weaker in the flexed position. Nevertheless, the ΔGonion-C2 distance can be used as a warning sign for postoperative complications after posterior occipital bone fusion surgery, because a decrease of > 10° in the ΔO-C2 angle can be predicted with high specificity.

DOI： 10.2176/jns-nmc.2022-0251

Clinical Impacts of Stereotactic Electroencephalography on Epilepsy Surgery and Associated Issues in the Current Situation in Japan. Open Access

Satoshi Maesawa, Tomotaka Ishizaki, Manabu Mutoh, Yoshiki Ito, Jun Torii, Takafumi Tanei, Daisuke Nakatsubo, Ryuta Saito

Neurologia medico-chirurgica Vol. 63 ( 5 ) page： 179 - 190 2023.5

Language：English Publishing type：Research paper (scientific journal) Publisher：The Japan Neurosurgical Society

Stereotactic electroencephalography (SEEG) is receiving increasing attention as a safe and effective technique in the invasive evaluation for epileptogenic zone (EZ) detection. The main clinical question is whether the use of SEEG truly improves outcomes. Herein, we compared outcomes in our patients after three types of intracranial EEG (iEEG): SEEG, the subdural electrode (SDE), and a combined method using depth and strip electrodes. We present here our preliminary results from two demonstrative cases. Several international reports from large epilepsy centers found the following clinical advantages of SEEG: 1) three-dimensional analysis of structures, including bilateral and multilobar structures; 2) low rate of complications; 3) less pneumoencephalopathy and less patient burden during postoperative course, which allows the initiation of video-EEG monitoring immediately after implantation and does not require resection to be performed in the same hospitalization; and 4) a higher rate of good seizure control after resection. In other words, SEEG more accurately identified the EZ than the SDE method. We obtained similar results in our preliminary experiences under limited conditions. In Japan, as of August 2022, dedicated electrodes and SEEG accessories have not been approved and the use of the robot arm is not widespread. The Japanese medical community is hopeful that these issues will soon be resolved and that the experience with SEEG in Japan will align with that of large epilepsy centers internationally.

DOI： 10.2176/jns-nmc.2022-0271

Erratum to: Evaluation of Posterior Ligamentous Complex Injury in Thoracolumbar Burst Fractures: Correlation Analysis of CT and MRI Findings (Neurol Med Chir (Tokyo) 63, 158-164, 2023) Open Access

Yoshikawa, S, Nishimura, Y, Nagashima, Y, Ito, H, Oyama, T, Nishii, T, Gonda, T.M, Ryu, H, Nomura, K, Hara, M, Takayasu, M, Ginsberg, H.J, Kanemura, T, Saito, R

Neurologia Medico-Chirurgica Vol. 63 ( 5 ) page： 220 - 220 2023.5

[Intraoperative Functional Monitoring in Brain Tumor Surgery]. Invited Reviewed

Kazuya Motomura, Ryuta Saito

No shinkei geka. Neurological surgery Vol. 51 ( 3 ) page： 481 - 489 2023.5

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

Invasive brain tumors, especially gliomas, often arise in the eloquent areas of the brain that are involved in language and motor function. The most important goal of brain tumor removal is to safely remove the maximum amount of tumor while preserving neurological function. Maximizing the amount of removed tumor is thought to improve prognosis by prolonging both the progression-free and overall survival periods of patients. In the present study, we review the intraoperative monitoring techniques for motor function-sparing surgery for gliomas arising near the eloquent areas of the brain and electrophysiological monitoring techniques for motor function-sparing surgery for brain tumors arising deep within the brain. In brain tumor surgery, monitoring of direct cortical motor evoked potentials(MEPs), transcranial MEPs, and subcortical MEPs is integral for preserving motor function.

DOI： 10.11477/mf.1436204772

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Secondary aneurysmal bone cyst of the frontal bone with fibrous dysplasia showing rapid expansion: a case report. Reviewed Open Access

Yuta Koketsu, Takafumi Tanei, Kyoko Kuwabara, Toshinori Hasegawa, Takenori Kato, Satoshi Maesawa, Yusuke Nishimura, Yoshio Araki, Ryuta Saito

Nagoya journal of medical science Vol. 85 ( 2 ) page： 395 - 401 2023.5

Language：English

A 19-year-old woman presented with swelling of the left forehead without pain. She did not have any relevant past or family history. Computed tomography showed destruction of the outer cortex of the frontal bone. A solitary mass lesion with a fluid collection was detected with magnetic resonance imaging. Because the swelling of the left forehead had enlarged rapidly with osteolytic changes, surgical removal of the lesion was performed. The lesion appeared to be enveloped in a fibrous capsule. The soft lesion was removed from the frontal bone. The outer frontal bone was absent, although the inner frontal bone was preserved. Then, the frontal bone was resected with margins from the edge of the erosion. The dura mater under the lesion was intact. A cranioplasty was performed using titanium mesh. On histological examination, the trabecular bones revealed irregular shapes and arrangements, indicating fibrous dysplasia. There was a continuous high-cell-concentration pathological lesion outside the fibrous dysplasia. There were numerous cells, such as mononuclear cells, osteoclast-like multinucleated giant cells, foam cells, and red blood cells. The osteoclast-like multinucleated giant cells and other cells did not show significant nuclear atypia. Immunostaining with H3.3G34W was negative, and the ubiquitin-specific peptidase 6/Tre-2 gene showed no rearrangements. The histopathological diagnosis was secondary aneurysmal bone cyst with fibrous dysplasia. Additional postsurgical therapy was not performed. There has been no evidence of recurrence of the lesion for two years.

DOI： 10.18999/nagjms.85.2.395

IDH変異型と野生型の2相性の病理所見を呈したastrocytoma,IDH-mutantの1例

山口純矢, 大岡史治, 本村和也, 奥村優香, 清水大輝, 木部祐士, 加留部謙之輔, 齋藤竜太

Brain Tumor Pathology Vol. 40 ( Suppl. ) page： 115 - 115 2023.5

小児脳腫瘍におけるRNAカスタムパネルを用いたNTRK,ROS1,ALK遺伝子融合異常の解析

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

Brain Tumor Pathology Vol. 40 ( Suppl. ) page： 092 - 092 2023.5

がんゲノム診断とバイオインフォマティクス大規模全ゲノムおよびトランスクリプトーム解析によるGlioblastoma,IDH-wild typeの多様性の解明

中島拓真, 舟越勇介, 畝田篤仁, 田中將太, 石田穣治, 齋藤竜太, 花谷亮典, 吉本幸司, 成田善孝, 鈴木啓道

Brain Tumor Pathology Vol. 40 ( Suppl. ) page： 066 - 066 2023.5

WHO2021脳腫瘍分類に基づいた島回グリオーマの治療成績と予後因子について

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

Brain Tumor Pathology Vol. 40 ( Suppl. ) page： 097 - 097 2023.5

成人Li Fraumeni症候群症例に生じたPDGFRA増幅陽性IDH野生型悪性神経膠腫3例の報告

木部祐士, 大岡史治, 青木恒介, 本村和也, 山口純矢, 前田紗知, 西川知秀, 清水大輝, 齋藤竜太

Brain Tumor Pathology Vol. 40 ( Suppl. ) page： 096 - 096 2023.5

Effects of superficial temporal artery to middle cerebral artery bypass on postoperative infarction rates among young children (≤ 5 years old) with moyamoya disease. Reviewed International journal

Syuntaro Takasu, Fumiaki Kanamori, Norikazu Hatano, Yukio Seki, Ryuta Saito

Neurosurgical review Vol. 46 ( 1 ) page： 87 - 87 2023.4

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

Revascularization surgery for young children with moyamoya disease (MMD) is challenging. Although indirect revascularization is preferred because of the technical difficulty in direct anastomosis, higher risks of postoperative infarction remain a problem. We aimed to investigate the effect of superficial temporal artery to middle cerebral artery (STA-MCA) bypass on postoperative outcomes during the acute postoperative period in young children ≤ 5 years old with MMD. This retrospective study included consecutive young children with MMD who underwent surgical revascularization of the anterior cerebral circulation. Groups were determined according to the procedures performed, namely, the combined (STA-MCA bypass with indirect revascularization) and the indirect revascularization groups. The incidences of radiological or symptomatic infarction, transient neurological events, and new neurological deficits that remained at discharge were compared between groups. Of 38 surgical procedures, there were 23 combined and 15 indirect revascularizations. The median age of the patients was 3.0 years, which was significantly different between groups (P < .01). When comparing the postoperative outcomes between groups, the incidences of radiological and symptomatic infarction and new neurological deficits that remained at discharge were significantly lower in the combined revascularization group (P < .05). Logistic regression analysis adjusted for potential confounders found that surgical modality was a statistically significant independent risk factor associated with radiological and symptomatic infarctions (indirect/combined, odds ratio: 10.2; 95% confidence interval: 1.30-79.7; P < .05). STA-MCA bypass combined with indirect revascularization can reduce the incidence of postoperative infarction in young children with MMD and might lead to better neurological outcomes.

DOI： 10.1007/s10143-023-01999-1

Machine learning models predict delayed hyponatremia post-transsphenoidal surgery using clinically available features. Reviewed International journal

Yutaro Fuse, Kazuhito Takeuchi, Hiroshi Nishiwaki, Takahiro Imaizumi, Yuichi Nagata, Kinji Ohno, Ryuta Saito

Pituitary Vol. 26 ( 2 ) page： 237 - 249 2023.4

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

PURPOSE: Delayed hyponatremia (DHN), a unique complication, is the leading cause of unexpected readmission after pituitary surgery. Therefore, this study aimed to develop tools for predicting postoperative DHN in patients undergoing endoscopic transsphenoidal surgery (eTSS) for pituitary neuroendocrine tumors (PitNETs). METHODS: This was a single-center, retrospective study involving 193 patients with PitNETs who underwent eTSS. The objective variable was DHN, defined as serum sodium levels < 135 mmol/L at ≥ 1 time between post operative days 3 and 9. We trained four machine learning models to predict this objective variable using the clinical variables available preoperatively and on the first postoperative day. The clinical variables included patient characteristics, pituitary-related hormone levels, blood test results, radiological findings, and postoperative complications. RESULTS: The random forest (RF) model demonstrated the highest (0.759 ± 0.039) area under the curve of the receiver operating characteristic curve (ROC-AUC), followed by the support vector machine (0.747 ± 0.034), the light gradient boosting machine (LGBM: 0.738 ± 0.026), and the logistic regression (0.710 ± 0.028). The highest accuracy (0.746 ± 0.029) was observed in the LGBM model. The best-performing RF model was based on 24 features, nine of which were clinically available preoperatively. CONCLUSIONS: The proposed machine learning models with pre- and post-resection features predicted DHN after the resection of PitNETs.

DOI： 10.1007/s11102-023-01311-w

Increased cerebrospinal fluid S100B protein levels in patients with trigeminal neuralgia and hemifacial spasm. Reviewed International journal

Eiji Ito, Yukio Seki, Kiyoshi Saito, Ryuta Saito

Acta neurochirurgica Vol. 165 ( 4 ) page： 959 - 965 2023.4

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

BACKGROUND: The pathophysiology of neurovascular compression syndrome has not been fully elucidated, and cerebrospinal fluid levels of nerve tissue-related markers involved in this disorder have not yet been reported. METHODS: We measured cerebrospinal fluid levels of S100B protein, neuron-specific enolase, and myelin basic protein in 21 patients with trigeminal neuralgia, 9 patients with hemifacial spasms, and 10 patients with non-ruptured intracranial aneurysms (control). Cerebrospinal fluid levels of these markers were determined using commercially available assay kits. RESULTS: Both trigeminal neuralgia and hemifacial spasm groups showed significantly increased cerebrospinal fluid levels of S100B compared with the control group (1120 [IQR 391-1420], 766 [IQR 583-1500], and 255 [IQR 190-285] pg/mL, respectively; p = 0.001). There were no statistically significant differences in cerebrospinal fluid levels of neuron-specific enolase or myelin basic protein among the groups. CONCLUSION: Cerebrospinal fluid S100B levels were significantly higher in patients with trigeminal neuralgia and hemifacial spasm than in controls, which suggests the involvement of S100B in the underlying pathophysiology of neurovascular compression syndrome.

DOI： 10.1007/s00701-022-05434-0

Butterfly needle tap and suction (BTS) technique: a treatment for recurrent chronic subdural hematoma after burr hole craniostomy. Reviewed International journal Open Access

Shun Yamamoto, Yoshitaka Nagashima, Hideki Maki, Yusuke Nishimura, Yoshio Araki, Masahiro Nishihori, Tomoyuki Noda, Tasuku Imai, Teppei Kawabata, Masahiro Ueno, Yasumasa Nishida, Ryuta Saito

Acta neurochirurgica Vol. 165 ( 4 ) page： 841 - 848 2023.4

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

BACKGROUND: In this study, we propose a butterfly needle tap and suction (BTS) technique for recurrent chronic subdural hematoma (CSDH) as an alternative to reoperation with burr hole craniostomy (BHC) and investigate its efficacy and safety. The procedure involves percutaneous puncture through the burr hole created during the previous surgery and subsequent hematoma evacuation using a butterfly needle. METHODS: This retrospective study included patients who underwent BTS for CSDH at Ogaki Municipal Hospital between January 2017 and December 2020. The follow-up CT scans were reviewed after several weeks. We evaluated the number of percutaneous punctures required to resolve CSDH during the BTS technique, the volume of the evacuated hematoma, and procedure-related complications. RESULTS: Twenty-six patients were enrolled in the study, 21 of whom achieved resolution of the hematoma using punctures with the BTS technique alone (mean, 2.2 ± 1.5). Five patients had a recurrence of hematoma after one or more punctures during the BTS technique, and they underwent reoperation with BHC according to the surgeon's decision or patient requests. Among the 55 punctures, 43.0 ± 16.0 ml of hematoma was evacuated per puncture. The evacuated hematoma volume was 41.9 ± 16.4 ml in the BTS-alone group and 49.4 ± 12.9 ml in the reoperation group, with no significant difference (p = 0.25). Three patients complained of a headache during the puncture procedure, and no other complications, including intracranial hemorrhage or infection, were reported therein. CONCLUSIONS: The BTS technique is an effective alternative to reoperation with BHC.

DOI： 10.1007/s00701-023-05543-4

Clinical characteristics and radiological features of glioblastoma, IDH-wildtype, grade 4 with histologically lower-grade gliomas. Reviewed Open Access

Kazuya Motomura, Yuji Kibe, Fumiharu Ohka, Kosuke Aoki, Junya Yamaguchi, Ryuta Saito

Brain tumor pathology Vol. 40 ( 2 ) page： 48 - 55 2023.4

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

The 2021 World Health Organization (WHO) classification of central nervous system tumors applied molecular criteria and further integrated histological and molecular diagnosis of gliomas. This classification allows for the diagnosis of isocitrate dehydrogenase wild-type (IDHwt) glioblastoma (GBM), and WHO grade 4 with histologically lower-grade gliomas (LrGGs), even in the absence of high-grade histopathologic features, such as necrosis and/or microvascular proliferation. They contain at least one of the following molecular features: epidermal growth factor receptor amplification, chromosome 7 gain/10 loss, or telomerase reverse transcriptase promoter mutation. In the imaging features at the time of histological diagnosis, a gliomatosis cerebri growth pattern was frequently observed in these tumors. Furthermore, this growth pattern was significantly higher in IDHwt GBM, WHO grade 4, with histological grade II gliomas. Although the exact prognosis of IDHwt GBM, WHO grade 4, with histologically LGGs remains unknown, its OS was approximately 1-2 years similar to that of histologically IDHwt GBM, WHO grade 4, despite histopathological features similar to IDHmut LrGGs. These findings reinforce the need for the analysis of molecular features, regardless of presenting similar clinical characteristics and imaging features to IDHmut LrGGs.

DOI： 10.1007/s10014-023-00458-5

Easy-to-use machine learning system for the prediction of IDH mutation and 1p/19q codeletion using MRI images of adult-type diffuse gliomas. Reviewed

Tomohide Nishikawa, Fumiharu Ohka, Kosuke Aoki, Hiromichi Suzuki, Kazuya Motomura, Junya Yamaguchi, Sachi Maeda, Yuji Kibe, Hiroki Shimizu, Atsushi Natsume, Hideki Innan, Ryuta Saito

Brain tumor pathology Vol. 40 ( 2 ) page： 85 - 92 2023.4

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

Adult-type diffuse gliomas are divided into Astrocytoma, IDH-mutant, Oligodendroglioma, IDH-mutant and 1p/19q-codeleted and Glioblastoma, IDH-wildtype based on the IDH mutation, and 1p/19q codeletion status. To determine the treatment strategy for these tumors, pre-operative prediction of IDH mutation and 1p/19q codeletion status might be effective. Computer-aided diagnosis (CADx) systems using machine learning have been noted as innovative diagnostic methods. However, it is difficult to promote the clinical application of machine learning systems at each institute because the support of various specialists is essential. In this study, we established an easy-to-use computer-aided diagnosis system using Microsoft Azure Machine Learning Studio (MAMLS) to predict these statuses. We constructed an analysis model using 258 adult-type diffuse glioma cases from The Cancer Genome Atlas (TCGA) cohort. Using MRI T2-weighted images, the overall accuracy, sensitivity, and specificity for the prediction of IDH mutation and 1p/19q codeletion were 86.9%, 80.9%, and 92.0%, and 94.7%, 94.1%, and 95.1%, respectively. We also constructed an reliable analysis model for the prediction of IDH mutation and 1p/19q codeletion using an independent Nagoya cohort including 202 cases. These analysis models were established within 30 min. This easy-to-use CADx system might be useful for the clinical application of CADx in various institutes.

DOI： 10.1007/s10014-023-00459-4

Evaluation of Posterior Ligamentous Complex Injury in Thoracolumbar Burst Fractures: Correlation Analysis of CT and MRI Findings. Open Access

Satoshi Yoshikawa, Yusuke Nishimura, Yoshitaka Nagashima, Hiroshi Ito, Takahiro Oyama, Tomoya Nishii, Tomomi Gonda, Hiroshi Ryu, Kei Nomura, Masahito Hara, Masakazu Takayasu, Howard J Ginsberg, Tokumi Kanemura, Ryuta Saito

Neurologia medico-chirurgica Vol. 63 ( 4 ) page： 158 - 164 2023.4

Language：English Publishing type：Research paper (scientific journal) Publisher：The Japan Neurosurgical Society

The goal of this study is to perform correlation analysis of Computed tomography (CT) and magnetic resonance imaging (MRI) results in posterior ligament complex (PLC) injury and define the morphological traits of thoracolumbar (TL) burst fractures connected to PLC injury. Forty patients with surgically repaired TL burst fractures between January 2013 and December 2020 were retrospectively analyzed. The patients were split into two groups for comparison based on MRI (Group P: patients with a confirmed or suspected PLC injury; Group N: patients with PLC injury denied). The radiographic morphological examination based on CT scans and clinical evaluation was performed and compared between two groups. The thoracolumbar injury classification and severity score (TLICS), the load sharing classification (LSC) scores, and the number of patients with neurological impairments were considerably greater in Group P. Loss of height of the fracture (loss height), local kyphosis of the fracture (local kyphosis), and supraspinous distance were significantly higher in Group P and significantly associated with PLC injuries indicating severe vertebral body destruction and traumatic kyphosis in multivariate logistic analysis [odds ratio: 1.90, 1.06, and 1.13, respectively]. Cutoff value for local kyphosis obtained from the receiver operating characteristic curve was 18.8. If local kyphosis is greater than 18.8 degrees on CT scans, we should take into account the probability of the highly damaged burst fracture associated with PLC injury. In this situation, we should carefully assess MRI to identify the spinal cord injury or spinal cord compression in addition to PLC injury because these instances likely present with neurological abnormalities.

DOI： 10.2176/jns-nmc.2021-0390

Salvage craniospinal irradiation for recurrent intracranial germinoma: a single institution analysis Reviewed International journal Open Access

Masayuki Kanamori, Yoshiteru Shimoda, Rei Umezawa, Osamu Iizuka, Shunji Mugikura, Kyoko Suzuki, Hisanori Ariga, Keiichi Jingu, Ryuta Saito, Yukihiko Sonoda, Toshihiro Kumabe, Teiji Tominaga

Journal of Radiation Research Vol. 64 ( 2 ) page： 428 - 437 2023.3

Language：English Publishing type：Research paper (scientific journal) Publisher：Oxford University Press (OUP)

Abstract

This study investigated the effectiveness and safety of low-dose salvage craniospinal irradiation (CSI) for recurrent germinoma. We retrospectively reviewed long-term tumor control and late adverse effects in 15 recurrent germinoma patients treated at our hospital between 1983 and 2019. Following the first recurrence of germinoma, seven were treated with 24–30 Gy of salvage CSI, three underwent non-CSI, and five were treated with only chemotherapy. CSI achieved a significantly better recurrence-free survival rate after the first recurrence compared to other strategies (100% vs 33%, p &lt; 0.001: log-rank test). To evaluate the safety of salvage CSI, we assessed the outcomes at the final follow-up of seven patients who received salvage CSI at first recurrence and three patients who received salvage CSI at second recurrence. The median follow-up period was 220 months after initial treatment. Five patients who received 40–50 Gy of radiation therapy or underwent multiple radiation therapy before salvage CSI were classified into Group A, whereas five patients treated with platinum-based chemotherapy and 24–32 Gy of radiation therapy to the primary site, whole ventricle, or whole brain were classified into Group B. In Group A, one had endocrine dysfunction and the other had visual dysfunction. None were socially independent. Meanwhile, in Group B, no endocrine or visual dysfunction was found, and three patients were socially independent. Salvage CSI achieved excellent tumor control in recurrent germinoma and was safe in patients initially treated with low-dose radiation therapy and chemotherapy.

DOI： 10.1093/jrr/rrac095

Subcutaneous transplantation of human embryonic stem cells-derived pituitary organoids. Reviewed International journal Open Access

Hiroo Sasaki, Hidetaka Suga, Kazuhito Takeuchi, Yuichi Nagata, Hideyuki Harada, Tatsuma Kondo, Eiji Ito, Sachi Maeda, Mayu Sakakibara, Mika Soen, Tsutomu Miwata, Tomoyoshi Asano, Hajime Ozaki, Shiori Taga, Atsushi Kuwahara, Tokushige Nakano, Hiroshi Arima, Ryuta Saito

Frontiers in endocrinology Vol. 14 page： 1130465 - 1130465 2023.3

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

INTRODUCTION: The pituitary gland, regulating various hormones, is central in the endocrine system. As spontaneous recovery from hypopituitarism is rare, and exogenous-hormone substitution is clumsy, pituitary replacement via regenerative medicine, using pluripotent stem cells, is desirable. We have developed a differentiation method that in mice yields pituitary organoids (POs) derived from human embryonic stem cells (hESC). Efficacy of these POs, transplanted subcutaneously into hypopituitary mice, in reversing hypopituitarism was studied. METHODS: hESC-derived POs were transplanted into inguinal subcutaneous white adipose tissue (ISWAT) and beneath dorsal skin, a relatively avascular region (AR), of hypophysectomized severe combined immunodeficient (SCID) mice. Pituitary function was evaluated thereafter for ¾ 6mo, assaying basal plasma ACTH and ACTH response to corticotropin-releasing hormone (CRH) stimulation. Histopathologic examination of organoids 150d after transplantation assessed engraftment. Some mice received an inhibitor of vascular endothelial growth factor (VEGF) to permit assessment of how angiogenesis contributed to subcutaneous engraftment. RESULTS: During follow-up, both basal and CRH-stimulated plasma ACTH levels were significantly higher in the ISWAT group (p < 0.001 - 0.05 and 0.001 - 0.005, respectively) than in a sham-operated group. ACTH secretion also was higher in the ISWAT group than in the AR group. Histopathologic study found ACTH-producing human pituitary-cell clusters in both groups of allografts, which had acquired a microvasculature. POs qPCR showed expression of angiogenetic factors. Plasma ACTH levels decreased with VEGF-inhibitor administration. CONCLUSIONS: Subcutaneous transplantation of hESC-derived POs into hypopituitary SCID mice efficaciously renders recipients ACTH-sufficient.

DOI： 10.3389/fendo.2023.1130465

Long noncoding RNA profile of the intracranial artery in patients with moyamoya disease. Reviewed International journal

Takashi Mamiya, Fumiaki Kanamori, Kinya Yokoyama, Akinobu Ota, Sivasundaram Karnan, Kenji Uda, Yoshio Araki, Satoshi Maesawa, Kazuhiro Yoshikawa, Ryuta Saito

Journal of neurosurgery Vol. 138 ( 3 ) page： 709 - 716 2023.3

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

OBJECTIVE: Moyamoya disease (MMD) is a rare cerebrovascular disease characterized by progressive stenosis of the internal carotid artery (ICA) and secondary formation of collateral vessels. Revascularization surgery is performed in patients with MMD to prevent stroke; however, the pathogenesis of MMD remains unknown. Recently, long noncoding RNAs (lncRNAs) have been found to play a key role in gene regulation and are implicated in various vascular diseases. However, the lncRNA expression profile in MMD lesions has not been investigated. In this study the authors aimed to determine the characteristics of lncRNA expression in MMD lesions. METHODS: The authors collected microsamples of the middle cerebral artery (MCA) from patients with MMD (n = 21) and patients with control conditions (n = 11) who underwent neurosurgical treatment. Using microarray experiments, the authors compared the profiles of lncRNA expression in the MCAs of the MMD and control patient groups and identified differentially expressed lncRNAs (fold change > 2, q < 0.05). In addition, the neighboring coding genes, whose transcription can be regulated in cis by the identified differentially expressed lncRNAs, were investigated and Gene Ontology (GO) analysis was applied to predict associated biological functions. RESULTS: The authors detected 308 differentially expressed lncRNAs (fold change > 2, q < 0.05), including 306 upregulated and 2 downregulated lncRNAs in the MCA from patients with MMD. Regarding the prediction of biological function, GO analyses with possible coding genes whose transcription was regulated in cis by the identified differentially expressed lncRNAs suggested involvement in the antibacterial humoral response, T-cell receptor signaling pathway, positive regulation of cytokine production, and branching involved in blood vessel morphogenesis. CONCLUSIONS: The profile of lncRNA expression in MMD lesions was different from that in the normal cerebral artery, and differentially expressed lncRNAs were identified. This study provides new insights into the pathophysiology of MMD.

DOI： 10.3171/2022.5.JNS22579

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Papers - SAITO Ryuta