Education 【 display / non-display 】

Education 【 display / non-display 】

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  1995

  Sapporo Medical University  

Degree 【 display / non-display 】

Degree 【 display / non-display 】

• M.D., Ph.D.

Professional Memberships 【 display / non-display 】

Professional Memberships 【 display / non-display 】

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  日本脳神経外科学会

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  The Japan Stroke Society

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  Japan Neurosurgical Society

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  Japanese Association for Acute Medicine

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  日本脊髄外科学会

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Research Areas 【 display / non-display 】

Research Areas 【 display / non-display 】

• Life sciences   Neurosurgery  

Affiliation 【 display / non-display 】

Affiliation 【 display / non-display 】

• Sapporo Medical University   附属病院 脳神経外科学講座   講師  

Research Interests 【 display / non-display 】

Research Interests 【 display / non-display 】

• 脳神経外科学

• 脳卒中

• 外傷

• 脊髄外科

• Neuroscience

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Papers 【 display / non-display 】

Papers 【 display / non-display 】

• Machine learning-based analyses of contributing factors for the development of hypertension: a comparative study.

  Marenao Tanaka, Yukinori Akiyama, Kazuma Mori, Itaru Hosaka, Keisuke Endo, Toshifumi Ogawa, Tatsuya Sato, Toru Suzuki, Toshiyuki Yano, Hirofumi Ohnishi, Nagisa Hanawa, Masato Furuhashi

  Clinical and experimental hypertension (New York, N.Y. : 1993)   47 ( 1 ) 2449613 - 2449613  2025.12  [International journal]

  　View Summary

  OBJECTIVES: Sufficient attention has not been given to machine learning (ML) models using longitudinal data for investigating important predictors of new onset of hypertension. We investigated the predictive ability of several ML models for the development of hypertension. METHODS: A total of 15 965 Japanese participants (men/women: 9,466/6,499, mean age: 45 years) who received annual health examinations were randomly divided into a training group (70%, n = 11,175) and a test group (30%, n = 4,790). The predictive abilities of 58 candidates including fatty liver index (FLI), which is calculated by using body mass index, waist circumference and levels of γ-glutamyl transferase and triglycerides, were investigated by statistics analogous to the area under the curve (AUC) in receiver operating characteristic curve analyses using ML models including logistic regression, random forest, naïve Bayes, extreme gradient boosting and artificial neural network. RESULTS: During a 10-year period (mean period: 6.1 years), 2,132 subjects (19.1%) in the training group and 917 subjects (19.1%) in the test group had new onset of hypertension. Among the 58 parameters, systolic blood pressure, age and FLI were identified as important candidates by random forest feature selection with 10-fold cross-validation. The AUCs of ML models were 0.765-0.825, and discriminatory capacity was significantly improved in the artificial neural network model compared to that in the logistic regression model. CONCLUSIONS: The development of hypertension can be simply and accurately predicted by each ML model using systolic blood pressure, age and FLI as selected features. By building multiple ML models, more practical prediction might be possible.

  DOI PubMed

• Clinical significance of intraoperative bidirectional corticocortical evoked potential monitoring to evaluate language function.

  Chie Kamada, Yusuke Kimura, Shoto Yamada, Ryohei Saito, Katsuya Komatsu, Rei Enatsu, Yukinori Akiyama, Nobuhiro Mikuni

  Journal of neurosurgery     1 - 9  2025.01  [International journal]

  　View Summary

  OBJECTIVE: Awake craniotomy is commonly used to resect lesions located near the language area during brain surgery. However, it is often difficult to perform language tasks due to several limitations such as difficulty in awakening during surgery and intraoperative seizures. This study investigated the clinical significance of bidirectional corticocortical evoked potential (CCEP) monitoring as a new approach to evaluate intraoperative language function. METHODS: This study enrolled 12 patients who underwent awake brain tumor resection with intraoperative CCEP monitoring to assess language function. Electrodes were placed on the frontal and temporoparietal lobes based on the location of the arcuate fasciculus identified with preoperative diffusion tensor imaging to measure CCEPs intraoperatively in two directions: from the frontal lobe to the temporoparietal lobe of the language-dominant side, and vice versa. Correlations between CCEP amplitudes or latencies before and after tumor removal in each direction and postoperative language function assessed with the Western Aphasia Battery were analyzed. RESULTS: Nine of the 12 patients showed language-related CCEP responses in both directions before, during, and after tumor removal. One patient who showed decreased CCEP amplitudes in both directions after tumor removal exhibited aphasia for as long as 1 month postoperatively. In contrast, of the 6 patients whose CCEP amplitude in only a single direction was reduced or disappeared, 4 had no deterioration of language function and the other 2 had temporary deterioration of language function during the 1st postoperative week, which improved by 1 month postoperatively. CONCLUSIONS: This study indicated that bidirectional CCEP measurement may increase the precision of intraoperative language function monitoring.

  DOI PubMed

• Efficacy and safety of carmustine wafers, followed by radiation, temozolomide, and bevacizumab therapy, for newly diagnosed glioblastoma with maximal resection.

  Masayuki Kanamori, Ichiyo Shibahara, Yoshiteru Shimoda, Yukinori Akiyama, Takaaki Beppu, Shigeo Ohba, Toshiyuki Enomoto, Takahiro Ono, Yuta Mitobe, Mitsuto Hanihara, Yohei Mineharu, Joji Ishida, Kenichiro Asano, Yasuyuki Yoshida, Manabu Natsumeda, Sadahiro Nomura, Tatsuya Abe, Hajime Yonezawa, Ryuichi Katakura, Soichiro Shibui, Toshihiko Kuroiwa, Hiroyoshi Suzuki, Hidehiro Takei, Haruo Matsushita, Ryuta Saito, Yoshiki Arakawa, Yukihiko Sonoda, Yuichi Hirose, Toshihiro Kumabe, Takuhiro Yamaguchi, Hidenori Endo, Teiji Tominaga

  International journal of clinical oncology   30 ( 1 ) 51 - 61  2025.01  [Domestic journal]

  　View Summary

  BACKGROUND: To improve the outcome in newly diagnosed glioblastoma patients with maximal resection, we aimed to evaluate the efficacy and safety of implantation of carmustine wafers (CWs), radiation concomitant with temozolomide and bevacizumab, and maintenance chemotherapy with six cycles of temozolomide and bevacizumab. METHOD: This prospective phase II study enrolled glioblastoma patients considered candidates for complete resection (> 90%) of a contrast-enhanced lesion. The CWs were intraoperatively implanted into the resection cavity after achieving maximal resection. Patients without a measurable contrast-enhanced lesion on magnetic resonance imaging within 48 h after resection received concomitant radiotherapy and chemotherapy with temozolomide and bevacizumab, followed by maintenance treatment with up to six cycles of temozolomide and bevacizumab. The primary endpoint was the 2-year overall survival rate in glioblastoma patients with protocol treatment. RESULTS: From October 2015 to April 2018, we obtained consent for the first registration from 70 patients across 17 institutions in Japan, and 49 patients were treated according to the protocol. We evaluated the safety in 49 patients who were part of the second registration and the efficacy in 45 glioblastoma patients treated according to the protocol. The profile of hematological and most of the non-hematological adverse effects was similar to that in previous studies, but stroke occurred in 12% of cases (6/49 patients). The estimated 2-year overall survival rate was 51.3%. CONCLUSION: Implantation of CWs, followed by concomitant radiation, temozolomide, and bevacizumab, and six cycles of temozolomide and bevacizumab may offer some benefit to survival in Japanese glioblastoma patients with maximal resection. TRIAL ID: jRCTs021180007.

  DOI PubMed

• Urinary fatty acid-binding protein 4 is a promising biomarker for glomerular damage in patients with diabetes mellitus.

  Marenao Tanaka, Tatsuya Sato, Tomohito Gohda, Nozomu Kamei, Maki Murakoshi, Erika Ishiwata, Keisuke Endo, Wataru Kawaharata, Hiroki Aida, Kei Nakata, Yukinori Akiyama, Mitsunobu Kubota, Michiyoshi Sanuki, Toru Suzuki, Yusuke Suzuki, Masato Furuhashi

  Journal of diabetes investigation    2024.12  [Domestic journal]

  　View Summary

  AIMS/INTRODUCTION: Fatty acid-binding protein (FABP) 4, which acts as an adipokine secreted by adipocytes, macrophages, and capillary endothelial cells, is expressed in injured glomerular cells. It has been reported that urinary (U-) FABP4 is associated with renal dysfunction and proteinuria in several glomerular kidney diseases. However, the clinical significance of U-FABP4 in diabetic kidney disease (DKD) remains undetermined. MATERIALS AND METHODS: Immunohistological analyses of FABP4 and FABP1 (liver-type FABP), an established biomarker for impaired proximal tubules, were performed in the kidneys of patients with DKD and nonobese diabetic mice (KK-Ta/Akita mice). The associations between U-FABP4 and U-FABP1 with kidney function and metabolic indices were also investigated in patients with type 1 diabetes (n = 57, mean age: 61 years) and patients with type 2 diabetes (n = 608, mean age: 65 years). RESULTS: In both patients with diabetes and diabetic mice, FABP4 was expressed in injured glomeruli with increased markers of endoplasmic reticulum stress in addition to peritubular capillaries, whereas FABP1 was mainly expressed in proximal tubules. Levels of U-FABP4 and U-FABP1 were independently associated with each other, and both levels were independently associated with estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratio (UACR) after adjustment of age, sex, type of diabetes, duration of diabetes, and systolic blood pressure in patients with diabetes. CONCLUSIONS: Urinary level of FABP4 derived from injured glomeruli with increased endoplasmic reticulum stress is independently associated with eGFR and UACR, suggesting a promising biomarker for glomerular damage in patients with diabetes.

  DOI PubMed

• Congenital extraventricular neurocytoma with atypical features in a 3-day-old neonate.

  Sho Matsunaga, Yusuke Kimura, Yukinori Akiyama, Masaki Yamamoto, Nobuhiro Mikuni

  Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery   41 ( 1 ) 64 - 64  2024.12  [International journal]

  　View Summary

  Extraventricular neurocytoma (EVN) is a rare neuronal tumor with a marked tendency towards ganglionic or glial differentiation. Although EVN commonly occurs in young adults, congenital cases are extremely rare, and standardized therapeutic strategies remain undetermined. The presence of atypical features such as increased mitotic activity on histological analysis is correlated with a higher rate of recurrence and poor prognosis. A 3-d-old infant with no abnormalities at birth presented with recurrent apnea and paroxysmal eye deviation on the upper right side. Magnetic resonance imaging revealed a large intracranial tumor located anterior to the brainstem. The patient underwent biopsy via craniotomy, leading to a histological diagnosis of EVN with atypical features. Despite the absence of adjuvant radiation therapy or chemotherapy, the lesion remained stable over 18 months, and the patient's growth was within normal limits. EVN is an important differential diagnosis of congenital brain tumors. Therapeutic strategies for congenital cases should be distinguished from those used for older children, and treatment decisions should be based on individual patient risks.

  DOI PubMed

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Misc 【 display / non-display 】

Misc 【 display / non-display 】

• Trastuzumab Based Chemotherapy in Two Patients with HER2-Positive Metastatic Carcinoma ex Pleomorphic Adenoma

  Yohei Arihara, Kazuyuki Murase, Kohichi Takada, Naotaka Hayasaka, Shogo Miura, Koji Miyanishi, Masayoshi Kobune, Makoto Kurose, Yukinori Akiyama, Junji Kato

  ANNALS OF ONCOLOGY ( OXFORD UNIV PRESS )  27  2016.07

  Research paper, summary (international conference)  

• arterial spin labeling法による髄膜腫内血流の評価

  鰐渕 昌彦, 小松 克也, 秋山 幸功, 長濱 宏史, 三國 信啓

  脳循環代謝 ( 日本脳循環代謝学会 )  27 ( 1 ) 183 - 183  2015.10

• arterial spin labeling法による腫瘍内血流評価

  鰐渕 昌彦, 秋山 幸功, 長濱 宏史, 三國 信啓

  脳循環代謝 ( 日本脳循環代謝学会 )  25 ( 1 ) 141 - 141  2013.11

• Multimodality Fusion Imaging for the Evaluation of Cerebral Aneurysms Around the Optic Nerve

  MIKAMI Takeshi, OHTAKI Syunya, HIRANO Tohru, AKIYAMA Yukinori, WANIBUCHI Masahiko, HOUKIN Kiyohiro, MIKUNI Nobuhiro

  Surgery for Cerebral Stroke ( The Japanese Society on Surgery for Cerebral Stroke )  41 ( 4 ) 264 - 268  2013.07

  　View Summary

  In patients with cerebral aneurysms around the optic nerve, preoperative recognition of the interaction between the optic nerve and the aneurysms will contribute to visual preservation following surgery. The aim of this study was to introduce the value of multimodality fusion imaging in order to visualize the relationship between the aneurysm and the optic nerve.
  Three patients with cerebral aneurysm around the optic nerve underwent computed tomography angiography (CTA) and cycled Fast Imaging Employing Steady-state Acquisition (FIESTA-c) sequence. Fusion imaging of both was created using a workstation (Ziostation; Ziosoft Inc., Tokyo, Japan). We evaluated the preoperative deformation of the optic nerve compressed by the aneurysms using the fusion imaging. All magnetic resonance imaging examinations were performed using a 3.0T Signa HDx scanner (GE Medical Systems Milwaukee, WI, USA) with an 8-channel head coil. A CT examination was performed using a multidetector row CT scanner (GE Light Speed VCT; GE Healthcare, Milwaukee, WI, USA). The optic nerves were distinguished from aneurysms using fusion imaging, and this technique allowed visualization of optic nerve deformation induced by the aneurysm.
  Fusion imaging was useful for demonstrating the optic nerve status when surrounded by aneurysms. It was also useful in establishing a surgical strategy, enhancing intra-operative spatial orientation and increasing surgeon's confidence.
  

  DOI CiNii J-GLOBAL

• Primary clear cell carcinoma of the skull base and paranasal cavity: A case report

  Kengo Suzuki, Masahiko Wanibuchi, Yukinori Akiyama, Jun Ikeda, Yoshihiro Minamida, Tadashi Hasegawa, Kiyohiro Houkin, Nobuhiro Mikuni

  Neurological Surgery   40 ( 7 ) 617 - 621  2012.07

  　View Summary

  We described a case of primary clear cell carcinoma (CCC) of the paranasal cavity and skull base. A 59-year-old female experienced chronic nasal obstruction and double vision. Computed tomography (CT) scan revealed a mass lesion of the paranasal cavity, reaching the skull base and intracranial zone. We performed a biopsy by endonasal endoscopic surgery and pathological examinations revealed the tumor was a clear cell carcinoma. No primary tumor was identified on evaluation of the whole body by CT scan and FDG-PET ( 18fluorodeoxy glucose positron emission tomography) scan, so we diagnosed a primary CCC of the paranasal cavity. We decided to use stereotactic radiation therapy. Neurologically, her diplopia was improved. The patient is well at 2 years of follow-up with no evidence of local enlargement. There are some reports about the metastatic sinonasal CCC, but there are few reports about primary nasal and sinonasal CCC. This is the fourth case report of primary nasal and sinonasal CCC.

  PubMed J-GLOBAL

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Research Projects 【 display / non-display 】

Research Projects 【 display / non-display 】

• 革新的なAIによる脳腫瘍のMRI画像検出ソフトウェアの開発

  基盤研究(C)

  Project Year :

  2024.04

  -

  2027.03

   

  秋山 幸功, 三國 信啓

• 深層学習による吻合技術評価システムの開発とニューロフィードバックの検討

  基盤研究(C)

  Project Year :

  2023.04

  -

  2026.03

   

  三上 毅, 秋山 幸功, 三國 信啓, 小松 克也

  　View Summary

  顕微鏡の使用機器はzeissNC4を用い、人工血管による端側吻合を手技の課題として、これまで様々な経験年数の15人の人工血管吻合手技を同一機器、同一録画方式で保存し、それらの動画情報や術者情報を収集した。深層学習を行うためには、データ数を増やすことが最も適していると考えており、脳卒中の外科指導医であるエキスパートによる評価情報も収集し、技術評価できるような深層学習を実施するため、手技評価情報や術者情報との関連付けを行った。手技評価項目は、①ズーム、フォーカス、センタリングの適正②吻合操作の適切なセットアップ③無理のない操作④ドナーの準備⑤レシピエントの準備⑥吻合操作が愛護的に行われているか⑥吻合操作において、カウンターフォースが適切に行われているか⑦吻合血管への針刺しの角度や位置⑧糸結びが円滑に行われているか⑨血管の引きつれや吻合間隔のバランス⑩操作時間 同時に、日本光電社の脳波測定システムを用い、手技中の脳波を持続的に測定した。使用するシステムは、低周波帯域のみならず、高次脳機能を反映するβ波やγ波などの高周波帯域のパワースペクトラム解析を行った。電極の留置は、キャップ型の脳波電極を使用した。解析は、MATLAB (Mathworks, Natick, Massachusetts, USA) と日本光電社製のオンコンソールのソフトを用いた。解析方法は、これまでにわれわれが当施設でこれまで行ってきた研究と同様の手法であり、行ってきた吻合手技評価ツールで得られた評価において、高評価群と低評価群の脳波パワースペクトラムの特徴を比較し、比較検討した。また、当直や疲労などの心因性のマイナス要因を減らすことにより、脳波の変化や評価上昇が得られるかを検討した。現状では、経験値が低いほどβ波を中心とした帯域のスペクトラムパワー値が低く、集中ができていない傾向がみられた。

• Functional Connectivity解析による脳記憶機能地図の解明

  基盤研究(C)

  Project Year :

  2022.04

  -

  2025.03

   

  千葉 遼平, 秋山 幸功, 三國 信啓

• 中枢神経Glymphatic systemの機能解明と新たな認知症治療薬の開発

  基盤研究(C)

  Project Year :

  2021.04

  -

  2024.03

   

  秋山 幸功, 三上 毅, 三國 信啓, 石合 純夫

  　View Summary

  Glymphatic systemの機能障害は様々な脳疾患を引き起こすと考えられている。とくに認知機能には大きな影響を与えると考えられており、その治療法の開発を行う。 方法：マウスを用いてGlymphatic systemのdrainage部分である静脈の閉塞モデルの作成を行い、その認知機能障害の進行、程度を評価する。静脈は側副血行路が発達していることが多いため、両側内・外頚静脈閉塞モデルを作成する予定である。 モデル作成後動物用7.0 Tesla-MRIを用いて静脈のうっ滞、MR spectroscopyにて脳実質内代謝産物の定量を行う。 結果：静脈結紮モデルを安定して作成することに成功した。静脈非閉塞のコントロールモデルと比較して、頭蓋内静脈の拡大を認め、眼球の突出などが認められたモデルも存在し、頭蓋内圧亢進状態が得られた。 考察：両側内・外頚静脈閉塞モデルは頭蓋内圧亢進モデルとして確立できるものと考えられ、今後頭蓋内圧亢進状態が高次機能へどのように影響を与えるか、また、髄液ドレナージなどによる頭蓋内圧降下療法がその高次機能障害を抑制できるか評価したいと考えている。

• 線維芽細胞に着目したくも膜炎症の分子機構の解明と新たな脳保護薬の開発

  基盤研究(C)

  Project Year :

  2020.04

  -

  2023.03

   

  三上 毅, 鈴木 比女, 秋山 幸功, 三國 信啓, 小松 克也, 平野 司

  　View Summary

  臨床データから得られた知見として、慢性脳虚血性疾患に対する開頭血行再建術で得られたくも膜と脳脊髄液を使用した。対象群として開頭による非虚血性疾患で得られた前頭葉皮質血管(M4)直上のくも膜を使用した。これまでの研究成果としては、くも膜の厚さは年齢や疾患が影響しており、厚いくも膜では内層に線維芽細胞やマクロファージが増勢し、VEGFαやTGFβなどの炎症マーカーが増加していた。また、くも膜内の線維化や慢性炎症が確認されていることを基に、免疫組織学的に線維化に関わる炎症マーカーや間葉系幹細胞の存在、血管新生の有無を確認した。虚血性疾患において、強い炎症反応が認められており、疾患による影響もみられることがわかった。 また、実験動物として両側総頸動脈閉塞による認知症モデルによる評価を行った。8週のWister kyotoラットにおいて、両側総頚動脈閉塞モデルを作成し、頚動脈閉塞後4週間目に実験用7.0TMRIで脳小血管病性変化を計測した。また、電気生理学的な影響を測定するため、Pinnacle Technology社の大脳皮質脳波測定システムで、てんかん波や高次脳機能を反映するβ波やγ波などの高周波帯域のパワースペクトラム解析を行った。虚血によるてんかん原生が非常に強く影響を及ぼしていることを見出すとともに、MRI及び電気生理学的な虚血の影響を推し量れるシステムを確立した。また、両側頚動脈閉塞と再灌流の電気生理学的変化や組織変化、MRI画像変化の違いを検討し、組織学的変化が及ぼす電気生理学的異常について検討中である。

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