研究者詳細 - 竹内　和人

論文 - 竹内　和人

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Pediatric-type high-grade gliomas with PDGFRA amplification in adult patients with Li-Fraumeni syndrome: clinical and molecular characterization of three cases 査読有り国際誌 Open Access

Kibe, Y; Ohka, F; Aoki, K; Yamaguchi, J; Motomura, K; Ito, E; Takeuchi, K; Nagata, Y; Ito, S; Mizutani, N; Shiba, Y; Maeda, S; Nishikawa, T; Shimizu, H; Saito, R

ACTA NEUROPATHOLOGICA COMMUNICATIONS 12 巻 ( 1 ) 頁： 57 - 57 2024年4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：Acta Neuropathologica Communications

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

Safety and efficacy of the endoscopic transsphenoidal transclival approach performed using direct cortical stimulation for pontine cavernous malformations 査読有り国際誌

Takeuchi, K; Nagata, Y; Sasagawa, Y; Ito, E; Yamamoto, T; Mizuno, A; Sasaki, H; Kondo, T; Araki, Y; Nakada, M; Saito, R

JOURNAL OF NEUROSURGERY 140 巻 ( 2 ) 頁： 469 - 477 2024年2月

担当区分：筆頭著者,　責任著者記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Journal of Neurosurgery

OBJECTIVE Surgical treatment of brainstem cavernous malformations (CMs) is challenging. Surgery using the endoscopic transsphenoidal transclival approach (eTSTCA) is reported as a useful alternative for ventral brainstem CMs. However, CMs located in the ventral midline of the brainstem are rare, and only a small number of case reports on these CMs treated with the eTSTCA exist. The efficacy and safety of the eTSTCA have not yet been fully examined. METHODS A retrospective analysis was performed for 5 consecutive patients who underwent surgery via the eTSTCA for treating ventral pontine CMs. RESULTS The average maximum CM diameter was 26.0 mm (18–38 mm). All patients underwent MR–diffusion tensor imaging, which confirmed that the corticospinal tract (CST) deviated posteriorly or laterally to the CM. Direct brainstem cortical stimulation was performed to localize the CST before making the cortical incision. After the excision of the CM, the cavity was filled with artificial CSF to make an aqueous surgical field (wet-field technique) for observing the tumor cavity and confirming complete hemostasis and resection. Total removal was achieved in all patients. The preoperative modified Rankin Scale score was 3 in 3 patients and 4 in 2 patients, whereas it was 1 in 2 patients and 0 in 3 patients 3 months after surgery. Postoperative CSF leakage was observed in 1 patient, and transient abducens nerve palsy was observed in 1 patient. No other intra- or postoperative complications were observed. CONCLUSIONS MR–diffusion tensor imaging and direct brainstem cortical stimulation were useful to ascertain the proximity of the CST to the CM. The endoscope provides a clear view even underwater, and it was safe and effective to observe the entire CM cavity and confirm complete hemostasis without additional retraction of the brainstem parenchyma, including the CST. The eTSTCA provides a direct access point to the lesion and may be a safer alternative treatment for patients whose CST deviates laterally or posteriorly to the CM.

DOI： 10.3171/2023.6.JNS23324

Extended Endoscopic Endonasal Transplanum and Transdorsum Sellar Approach for the Resection of Retroinfundibular Craniopharyngioma With Two-Piece Dural Opening: A Technical Case Report 査読有り国際誌 Open Access

Matmusayev, M; Kariev, GM; Asadullaev, U; Takeuchi, K; Nagata, Y; Harada, H; Saito, R

CUREUS JOURNAL OF MEDICAL SCIENCE 16 巻 ( 1 ) 頁： e51850 2024年1月

A Case of Papillary Craniopharyngioma Mimicking Rathke's Cleft Cyst. 査読有り Open Access

Harada H, Takeuchi K, Nagata Y, Inoshita N, Ito E, Okumura E, Kondo T, Sato Y, Saito R

NMC case report journal 11 巻 ( 0 ) 頁： 191 - 194 2024年

Endoscopic Cylinder Surgery for Ventricular Lesions.

Takeuchi K

Advances and technical standards in neurosurgery 52 巻頁： 91 - 104 2024年

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Advances and Technical Standards in Neurosurgery

Cylinder retractors have been developed to reduce the risk of brain retraction injury during surgery by dispersing retraction pressure on the brain. In recent years, various types of cylinder retractors have been developed and widely used in neurosurgery. The ventricles, being deep structures within the brain, present an effective area for cylinder retractor utilization. Endoscopy provides a bright, wide field of view in the deep surgical field, even through narrow corridors.This chapter introduces surgical techniques using an endoscope through a cylinder. Given the deep and complex shapes of the ventricles, preoperative planning is paramount. Two main surgical techniques are employed in endoscopic cylinder surgery. The wet-field technique involves the continuous irrigation of artificial cerebrospinal fluid (CSF) during the procedure, maintaining ventricle shape with natural water pressure, facilitating tumor border identification, and achieving spontaneous hemostasis. Conversely, the dry-field technique involves CSF drainage, providing a clear visual field even during hemorrhage encounters. In intraventricular surgery, both techniques are used and switched as needed.Specific approaches for lateral, third, and fourth ventricular tumors are discussed, considering their locations and surrounding anatomical structures. Detailed intraoperative findings and strategies for tumor removal and hemostasis are presented.Endoscopic cylinder surgery offers a versatile and minimally invasive option for intraventricular tumors, leading to improved surgical outcomes. Overall, this technique enhances surgical precision and patient outcomes in intraventricular tumor cases.

DOI： 10.1007/978-3-031-61925-0_7

Scopus

PubMed

Endoscopic debulking canalization for optic pathway glioma with obstructive hydrocephalus 招待有り査読有り国際誌

Takeuchi, K; Ohka, F; Nagata, Y; Ito, E; Harada, H; Saito, R

CHILDS NERVOUS SYSTEM 39 巻 ( 12 ) 頁： 3421 - 3425 2023年12月

担当区分：筆頭著者,　責任著者記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Child S Nervous System

Optic pathway gliomas (OPGs) are benign tumors that can stop growing or even shrink. In recent years, surgical resection has not been considered the first-line treatment because of its high risk of complications. Chemotherapy is the mainstay of treatment for growing OPGs. Surgical treatment for OPGs with obstructive hydrocephalus is required. Ventriculoperitoneal shunting is effective for all types of hydrocephalus. However, long-term management is required, especially in pediatric cases, and there is a risk of shunt-related complications over a long lifespan. Debulking surgery for OPGs allows us to avoid shunt placement by creating a waterway and releasing the hydrocephalus. To reduce the surgical risk and invasiveness, we used an endoscopic canalization technique with a small-diameter cylinder. In this article, we present a case of endoscopic canalization of an obstructive hydrocephalus caused by OPGs in a 14-year-old female to illustrate our surgical technique. (Trial registration Registry name and number: Efficacy and safety of the neuro-endoscopic treatment for brain tumors (2019–0254)).

DOI： 10.1007/s00381-023-06053-5

Deep learning based identification of pituitary adenoma on surgical endoscopic images: a pilot study 査読有り

Fuse, Y; Takeuchi, K; Hashimoto, N; Nagata, Y; Takagi, Y; Nagatani, T; Takeuchi, I; Saito, R

NEUROSURGICAL REVIEW 46 巻 ( 1 ) 頁： 291 2023年11月

担当区分：責任著者記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Neurosurgical Review

Accurate tumor identification during surgical excision is necessary for neurosurgeons to determine the extent of resection without damaging the surrounding tissues. No conventional technologies have achieved reliable performance for pituitary adenomas. This study proposes a deep learning approach using intraoperative endoscopic images to discriminate pituitary adenomas from non-tumorous tissue inside the sella turcica. Static images were extracted from 50 intraoperative videos of patients with pituitary adenomas. All patients underwent endoscopic transsphenoidal surgery with a 4 K ultrahigh-definition endoscope. The tumor and non-tumorous tissue within the sella turcica were delineated on static images. Using intraoperative images, we developed and validated deep learning models to identify tumorous tissue. Model performance was evaluated using a fivefold per-patient methodology. As a proof-of-concept, the model’s predictions were pathologically cross-referenced with a medical professional’s diagnosis using the intraoperative images of a prospectively enrolled patient. In total, 605 static images were obtained. Among the cropped 117,223 patches, 58,088 were labeled as tumors, while the remaining 59,135 were labeled as non-tumorous tissues. The evaluation of the image dataset revealed that the wide-ResNet model had the highest accuracy of 0.768, with an F1 score of 0.766. A preliminary evaluation on one patient indicated alignment between the ground truth set by neurosurgeons, the model’s predictions, and histopathological findings. Our deep learning algorithm has a positive tumor discrimination performance in intraoperative 4-K endoscopic images in patients with pituitary adenomas.

DOI： 10.1007/s10143-023-02196-w

その他リンク： https://link.springer.com/article/10.1007/s10143-023-02196-w/fulltext.html

ESTABLISHMENT OF ORGANOID MODELS OF PATIENT-DERIVED GH-PRODUCING PITUITARY ADENOMA

Maeda, S; Ohka, F; Kanamori, F; Okumura, Y; Takeuchi, K; Nagata, Y; Motomura, K; Yamaguchi, J; Kibe, Y; Harada, H; Shimizu, H; Takido, Y; Saito, R

NEURO-ONCOLOGY 25 巻 2023年11月

INTRA-OPERATIVE ANALYSES OF GENETIC ALTERATIONS IN THE CENTRAL NERVOUS SYSTEM TUMORS USING RAPID QUANTITATIVE PCR DEVICE

Ohka, F; Maeda, S; Yamaguchi, J; Shimizu, H; Motomura, K; Takeuchi, K; Nagata, Y; Nishikawa, T; Kibe, Y; Takido, Y; Saito, R

NEURO-ONCOLOGY 25 巻 2023年11月

Glossopharyngeal neurinoma of incidental finding in a 65-year-old female patient: case report 査読有り Open Access

Kabulo, KDM; Takeuchi, K; Yamada, Y; Sharafundeen, A; Kalangu, KKN; Kato, Y

EGYPTIAN JOURNAL OF NEUROSURGERY 38 巻 ( 1 ) 2023年9月

再生医療実現に向けたヒト多能性幹細胞由来下垂体細胞の皮下移植

佐々木博勇, 須賀英隆, 竹内和人, 永田雄一, 原田英幸, 近藤辰磨, 伊藤英治, 有馬寛, 齋藤竜太

日本内分泌学会雑誌 99 巻 ( S.HPT ) 頁： 4 - 6 2023年8月

[Prevention of Cerebrospinal Fluid Leakage and Endocrinological Management after Transsphenoidal Surgery].

Takeuchi K

No shinkei geka. Neurological surgery 51 巻 ( 4 ) 頁： 697 - 705 2023年7月

Rapid detection of the MYD88 L265P mutation for pre- and intra-operative diagnosis of primary central nervous system lymphoma 国際誌 Open Access

Yamaguchi, J; Ohka, F; Kitano, Y; Maeda, S; Motomura, K; Aoki, K; Takeuchi, K; Nagata, Y; Hattori, H; Tsujiuchi, T; Motomura, A; Nishikawa, T; Kibe, Y; Shinjo, K; Kondo, Y; Saito, R

CANCER SCIENCE 114 巻 ( 6 ) 頁： 2544 - 2551 2023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：Cancer Science

The myeloid differentiation primary response gene 88 (MYD88) L265P mutation is a disease-specific mutation of primary central nervous system lymphoma (PCNSL) among the central nervous system tumors. Accordingly, this mutation is considered a reliable diagnostic molecular marker of PCNSL. As the intra-operative diagnosis of PCNSL is sometimes difficult to achieve using histological examinations alone, intra-operative detection of the MYD88 L265P mutation could be effective for the accurate diagnosis of PCNSL. Herein, we aimed to develop a novel rapid genotyping system (GeneSoC) using real-time polymerase chain reaction (PCR) based on microfluidic thermal cycling technology. This real-time PCR system shortened the analysis time, which enabled the detection of the MYD88 L265P mutation within 15 min. Rapid detection of the MYD88 L265P mutation was performed intra-operatively using GeneSoC in 24 consecutive cases with suspected malignant brain tumors, including 10 cases with suspected PCNSL before surgery. The MYD88 L265P mutation was detected in eight cases in which tumors were pathologically diagnosed as PCNSL after the operation, while wild-type MYD88 was detected in 16 cases. Although two of the 16 cases with wild-type MYD88 were pathologically diagnosed as PCNSL after the operation, MYD88 L265P could be detected in all eight PCNSL cases harboring MYD88 L265P. The MYD88 L265P mutation could also be detected using cell-free DNA derived from the cerebrospinal fluid of two PCNSL cases. Detection of the MYD88 L265P mutation using GeneSoC might not only improve the accuracy of intra-operative diagnosis of PCNSL but also help the future pre-operative diagnosis through liquid biopsy of cerebrospinal fluid.

DOI： 10.1111/cas.15762

Machine learning models predict delayed hyponatremia post-transsphenoidal surgery using clinically available features 査読有り国際誌

Fuse, Y; Takeuchi, K; Nishiwaki, H; Imaizumi, T; Nagata, Y; Ohno, K; Saito, R

PITUITARY 26 巻 ( 2 ) 頁： 237 - 249 2023年4月

担当区分：責任著者記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Pituitary

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

Subcutaneous transplantation of human embryonic stem cells-derived pituitary organoids 査読有り Open Access

Sasaki, H; Suga, H; Takeuchi, K; Nagata, Y; Harada, H; Kondo, T; Ito, E; Maeda, S; Sakakibara, M; Soen, M; Miwata, T; Asano, T; Ozaki, H; Taga, S; Kuwahara, A; Nakano, T; Arima, H; Saito, R

FRONTIERS IN ENDOCRINOLOGY 14 巻頁： 1130465 2023年3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：Frontiers in Endocrinology

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

The importance of preserving the superior hypophyseal artery infundibular branch in craniopharyngioma surgery 国際誌

Sasaki, H; Takeuchi, K; Nagata, Y; Tanahashi, K; Mizuno, A; Harada, H; Kishida, Y; Watanabe, T; Nagatani, T; Saito, R

ACTA NEUROCHIRURGICA 165 巻 ( 3 ) 頁： 667 - 675 2023年3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：Acta Neurochirurgica

Purpose: Postoperative pituitary dysfunction, a critical problem in the treatment of craniopharyngiomas, can occur even when the pituitary stalk is preserved. We hypothesized that compromise of the primary superior hypophyseal artery (pSHA) might be related to this occurrence. Methods: We performed a retrospective review of 131 patients with craniopharyngioma who underwent surgery from April 2009 to September 2021. The inclusion criteria were initial surgery, endoscopic transsphenoidal surgery, preoperative normal pituitary function or pituitary dysfunction in one axis, and morphological preservation of the pituitary stalk. The branches of the pSHA consist mainly of the chiasmatic branches (Cb), infundibular branches (Ib), and descending branches (Db). We analyzed the association between postoperative pituitary function and preservation of these branches. Results: Twenty patients met the criteria. Preoperative anterior pituitary function was normal in 18 patients, and there was isolated growth hormone deficiency in two patients. No patient had preoperative diabetes insipidus (DI). Anterior pituitary function was unchanged postoperatively in eight patients. Of these eight patients, bilateral preservation of pSHA Ib was confirmed in seven patients. Bilateral preservation of pSHA Ib was the only factor associated with preserved anterior pituitary function (p < 0.01). Fifteen patients were free of permanent DI, and the preservation of any given pSHA branch produced no significant difference in the postoperative occurrence of permanent DI. Conclusions: Our study shows that bilateral preservation of pSHA Ib provides favorable postoperative anterior pituitary function in craniopharyngioma surgery; however, such preservation may have little effect on the postoperative occurrence of DI.

DOI： 10.1007/s00701-022-05415-3

CD79B Y196 mutation is a potent predictive marker for favorable response to R-MPV in primary central nervous system lymphoma 国際誌 Open Access

Yamaguchi, J; Ohka, F; Lushun, C; Motomura, K; Aoki, K; Takeuchi, K; Nagata, Y; Ito, S; Mizutani, N; Ohno, M; Suzaki, N; Takasu, S; Seki, Y; Kano, T; Wakabayashi, K; Oyama, H; Kurahashi, S; Tanahashi, K; Hirano, M; Shimizu, H; Kitano, Y; Maeda, S; Yamazaki, S; Wakabayashi, T; Kondo, Y; Natsume, A; Saito, R

CANCER MEDICINE 12 巻 ( 6 ) 頁： 7116 - 7126 2023年3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 Medicine

Background: Rituximab, high-dose methotrexate (HD-MTX), procarbazine and vincristine (R-MPV), has significantly prolonged the survival of patients with primary central nervous system lymphoma (PCNSL), but predictive factors for response to R-MPV have not yet been investigated. Herein, we investigated the correlation of MYD88 L265P and CD79B Y196 mutations, which are the most frequently found molecular alterations in PCNSL, with prognosis of patients with PCNSL treated with R-MPV. Methods: We investigated the long-term clinical course and status of MYD88 and CD79B genes in 85 patients with PCNSL treated with R-MPV or HD-MTX treatment, and the correlation of these genetic mutations with prognosis. Results: R-MPV achieved an excellent tumor control rate (61.6% and 69.9% of 5-year progression-free and overall survival rates, respectively). While MYD88 L265P mutation had no significant effect on survival, patients with CD79B Y196 mutations exhibited prolonged survival (p < 0.05). However, the association of CD79B Y196 mutation with a better prognosis was not observed in the HD-MTX cohort, which indicated that CD79B Y196 mutation was a predictive marker for a favorable response to R-MPV. Furthermore, we established an all-in-one rapid genotyping system for these genetic mutations. Conclusions: In conclusion, CD79B Y196 mutation is a potent predictive marker for favorable response to R-MPV in PCNSL. The rapid identification of MYD88 L265P and CD79B Y196 mutations can be helpful not only for the accurate molecular diagnosis of PCNSL but also for the prediction of response to R-MPV.

DOI： 10.1002/cam4.5512

放射線治療とパシレオチドの併用が奏功したクッシング病の1例

村瀬萌絵, 安田康紀, 杉山摩利子, 永田雄一, 竹内和人, 井下尚子, 有馬寛

日本内分泌学会雑誌 98 巻 ( 5 ) 頁： 1401 - 1401 2023年3月