Faculty Profiles - Tanaka Shota

Papers - Tanaka Shota

Division display 61 - 80 of about 213 ／ All the affair displays >>

Accurate Preoperative Identification of Motor Speech Area as Termination of Arcuate Fasciculus Depicted by Q-Ball Imaging Tractography. International journal

Tsukasa Koike, Shota Tanaka, Taichi Kin, Yuichi Suzuki, Shunsaku Takayanagi, Hirokazu Takami, Kazuha Kugasawa, Shohei Nambu, Takaki Omura, Erika Yamazawa, Yoshihiro Kushihara, Yasuyuki Furuta, Ryoko Niwa, Katsuya Sato, Tatsuya Uchida, Yasuhiro Takeda, Satoshi Kiyofuji, Toki Saito, Hiroshi Oyama, Nobuhito Saito

World neurosurgery 164 e764-e771 2022.8

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

BACKGROUND: Tractography is one way to predict the distribution of cortical functional domains preoperatively. Diffusion tensor tractography (DTT) is commonly used in clinical practice, but is known to have limitations in delineating crossed fibers, which can be overcome by Q-ball imaging tractography (QBT). We aimed to compare the reliability of these 2 methods based on the spatial correlation between the arcuate fasciculus depicted by tractography and direct cortical stimulation during awake surgery. METHODS: In this study, 15 patients with glioma underwent awake surgery with direct cortical stimulation. Tractography was depicted in a three-dimensional computer graphic model preoperatively, which was integrated with a photograph of the actual brain cortex using our novel mixed-reality technology. The termination of the arcuate fasciculus depicted by either DTT or QBT and the results of direct cortical stimulation were compared, and sensitivity and specificity were calculated in speech-associated brain gyri: pars triangularis, pars opercularis, ventral precentral gyrus, and middle frontal gyrus. RESULTS: QBT had significantly better sensitivity and lower false-positive rate than DTT in the pars opercularis. The same trend was noted for the other gyri. CONCLUSIONS: QBT is more reliable than DTT in identification of the motor speech area and may be clinically useful in brain tumor surgery.

DOI： 10.1016/j.wneu.2022.05.041

Prognostic Factors and Histopathological Features of Pediatric Intracranial Ependymomas: Nationwide Brain Tumor Registry-based Study of Japan.

Takahiro Sasaki, Yuji Uematsu, Junya Fukai, Shota Tanaka, Akitake Mukasa, Nobuhito Saito, Yoshitaka Narita, Naoyuki Nakao

Neurologia medico-chirurgica 62 ( 7 ) 322 - 327 2022.7

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

To assess the clinicopathological features and prognostic factors of pediatric intracranial ependymomas and to explore the current diagnostic practice, we analyzed clinical data from the Brain Tumor Registry of Japan (BTRJ). Data of fifty children under 18 years of age diagnosed with intracranial ependymoma were extracted from the BTRJ database. Cases were reviewed for overall survival (OS) and progression-free survival (PFS), with attention to gender, preoperative Karnofsky performance status score, location of the tumor, the extent of resection, World Health Organization (WHO) histopathological grading, and adjuvant therapy. The median age at diagnosis was 6.1 years, ranging from 7 months to 17.6 years. Based on the WHO histopathological grading, 27 patients were classified under grade 2 (54%) and 23 patients were classified under grade 3 (46%). Gross total resection (GTR) was achieved in 30 patients (60%). The median follow-up time was 65 months. Five-year PFS and OS were 47.2 ± 7.3% and 73.3 ± 6.7%, respectively. GTR was associated with longer OS (P = 0.02). The histopathological grading was not an independent prognostic factor for the OS. Mitosis and microvascular proliferation were higher among patients with grade 3 than in those with grade 2, which aided in deciding the WHO grade. This nationwide study revealed the characteristics and outcomes of patients with childhood ependymomas. GTR was the factor most consistently associated with improved survival. In contrast, the histopathological grading in this cohort was not a significant prognostic factor. More reproducible and practical criteria for the diagnosis of intracranial ependymomas should be further pursued in future studies.

DOI： 10.2176/jns-nmc.2022-0027

MRI-Based Radiomics Differentiates Skull Base Chordoma and Chondrosarcoma: A Preliminary Study

Erika Yamazawa, Satoshi Takahashi, Masahiro Shin, Shota Tanaka, Wataru Takahashi, Takahiro Nakamoto, Yuichi Suzuki, Hirokazu Takami, Nobuhito Saito

Cancers 14 ( 13 ) 3264 - 3264 2022.7

Publishing type：Research paper (scientific journal) Publisher：MDPI AG

Chordoma and chondrosarcoma share common radiographic characteristics yet are distinct clinically. A radiomic machine learning model differentiating these tumors preoperatively would help plan surgery. MR images were acquired from 57 consecutive patients with chordoma (N = 32) or chondrosarcoma (N = 25) treated at the University of Tokyo Hospital between September 2012 and February 2020. Preoperative T1-weighted images with gadolinium enhancement (GdT1) and T2-weighted images were analyzed. Datasets from the first 47 cases were used for model creation, and those from the subsequent 10 cases were used for validation. Feature extraction was performed semi-automatically, and 2438 features were obtained per image sequence. Machine learning models with logistic regression and a support vector machine were created. The model with the highest accuracy incorporated seven features extracted from GdT1 in the logistic regression. The average area under the curve was 0.93 ± 0.06, and accuracy was 0.90 (9/10) in the validation dataset. The same validation dataset was assessed by 20 board-certified neurosurgeons. Diagnostic accuracy ranged from 0.50 to 0.80 (median 0.60, 95% confidence interval 0.60 ± 0.06%), which was inferior to that of the machine learning model (p = 0.03), although there are some limitations, such as the risk of overfitting and the lack of an extramural cohort for truly independent final validation. In summary, we created a novel MRI-based machine learning model to differentiate skull base chordoma and chondrosarcoma from multiparametric signatures.

DOI： 10.3390/cancers14133264

The Role of Stereotactic Frame-Based Biopsy for Brainstem Tumors in the Era of Molecular-Based Diagnosis and Treatment Decisions. International journal

Yudai Hirano, Yuki Shinya, Toshiya Aono, Hirotaka Hasegawa, Mariko Kawashima, Masahiro Shin, Hirokazu Takami, Shunsaku Takayanagi, Motoyuki Umekawa, Masako Ikemura, Tetsuo Ushiku, Kazuki Taoka, Shota Tanaka, Nobuhito Saito

Current oncology (Toronto, Ont.) 29 ( 7 ) 4558 - 4565 2022.6

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

Stereotactic frame-based brain tumor biopsy (SFB) is a potent diagnostic tool considering its minimal invasiveness, though its diagnostic power and safety for brainstem lesions remain to be discussed. Here, we aimed to examine the usefulness of SFB for brainstem tumors. Twenty-two patients with brainstem tumors underwent 23 SFBs at our institution during 2002-2021. We retrospectively analyzed patient characteristics, tumor pathology, surgical procedures, and outcomes, including surgery-related complications and the diagnostic value. Seven (32%) tumors were located from the midbrain to the pons, eleven (50%) in the pons only, and four (18%) from the pons to the medulla oblongata. The target lesions were in the middle cerebellar peduncles in sixteen procedures (70%), the cerebellum in four (17%), the inferior cerebellar peduncles in two (9%), and the superior cerebellar peduncles in one (4%). A definitive diagnosis was made in 21 patients (95%) at the first SFB. The diagnoses were glioma in seventeen (77%) cases, primary central nervous system lymphoma in four (18%), and a metastatic brain tumor in one (5%). The postoperative complications (cranial nerve palsy in three [13%] cases, ataxia in one [4%]) were all transient. SFB for brainstem tumors yields a high diagnostic rate with a low risk of morbidity.

DOI： 10.3390/curroncol29070360

A phase II, multicenter, single-arm trial of eribulin in patients with bevacizumab-resistant recurrent glioblastoma.

Masamichi Takahashi, Satoshi Kawashima, Yohei Otake, Natsuko Satomi-Tsushita, Aya Kuchiba, Ryo Sadachi, Keiko Ohata, Hitoshi Ozawa, Kan Yonemori, Motoo Nagane, Yoshiki Arakawa, Akitake Mukasa, Shota Tanaka, Ryo Nishikawa, Yoshihiro Muragaki, Kenkichi Masutomi, Koichi Ichimura, Kenichi Nakamura, Yoshitaka Narita

Journal of Clinical Oncology 40 ( 16_suppl ) 2036 - 2036 2022.6

Publishing type：Research paper (scientific journal) Publisher：American Society of Clinical Oncology (ASCO)

2036

Background: Glioblastoma (GBM) is one of the worst prognostic cancers and there is no effective treatment after failure of bevacizumab. Eribulin is a microtubule inhibitor used for the treatment of patients with metastatic breast cancer and liposarcoma. We previously reported that eribulin strongly inhibits the RNA-dependent RNA polymerase (RdRP) activity of TERT protein in cancer cells, and has a strong anti-tumor effect against GBM cells with TERT promoter mutation. In this study we aim to investigate the efficacy and safety of eribulin in patients with bevacizumab-resistant recurrent GBM. Methods: This is an open-label, multicenter, single-arm phase II trial. Eligible patients aged 20-75 years with bevacizumab-resistant recurrent GBM were enrolled from 2018-2020. Patients received eribulin 1.4 mg/m² on days 1 and 8 of 21-day cycle until disease progression or intolerable toxicity was observed. The primary endpoint was one-year overall survival rate (1yOS%). The 35 patients are needed to achieve an 80% power at a one-sided alpha of 10%, under threshold 1yOS% of 10% and expected 1yOS% of 25%. Results: Thirty-seven patients aged 26-73 (median: 54) years were treated. Twenty-six of 37 (70.3%) patients were diagnosed as IDH-wildtype GBM, 4 (10.8%) were with IDH-mutant GBM and 7 (18.9%) were GBM, NOS. Thirty-four (91.9%) patients had a Karnofsky performance status of 70 or 80 at the registration. Thirty-one (83.8%) patients received additional treatments, including 28 (75.7%) bevacizumab, 11 (29.7%) re-irradiation and 3 (8.1%) resection after failure of eribulin. Among 37 subjects, 32 surgical specimens were analyzed for TERT promoter mutation and 15 for RdRP activity. 1yOS% was 29.7% [80% CI: 20.5 to 39.5 (p < 0.0001), 95% CI: 16.1 to 44.6]. Median OS was 9.0 months [95% CI: 6.2 to 11.0] and median progression-free survival was 1.5 months [95% CI: 1.4 to 1.7]. Neither TERT nor RdRP statuses was associated with prolonged OS. Among all the target lesions evaluated, two lesions decreased more than 50% in size and the patients survived more than one year, however no obvious PR was confirmed at the final evaluation. The disease control rate was 25.7% [95% CI: 12.5 to 43.3]. Common ≥ grade 2 AEs were neutropenia (70.3%), leukopenia (56.8%), lymphopenia (27.0%), elevation of γ-GTP (13.5%), elevation of ALT (10.8%), elevation of AST (8.1%), alopecia (8.1%). Treatment-related grade 3 or 4 AEs occurred in 59.5% of subjects. There were no AEs leading to death. Conclusions: Eribulin was safely applied for the patients with recurrent GBM. This phase II study met its primary endpoint of 1yOS%, although no obvious response was observed. Further investigation to reveal the biomarkers related to longer survival is underway. Clinical trial information: UMIN000030359.

DOI： 10.1200/jco.2022.40.16_suppl.2036

Performance of an artificial intelligence-based annotation algorithm for reporting cancer genomic profiling tests.

Hidenori Kage, Takashi Aoki, Aya Shinozaki-Ushiku, Kousuke Watanabe, Nana Akiyama, Hideaki Isago, Kazunaga Ishigaki, Nariaki Odawara, Yusuke Sato, Kazuhito Sasaki, Shota Tanaka, Michihiro Tanikawa, Motohiro Kato, Masahiko Tanabe, Kenji Tatsuno, Tetsuo Ushiku, Kiyoshi Miyagawa, Kunihiro Nishimura, Hiroyuki Aburatani, Katsutoshi Oda

Journal of Clinical Oncology 40 ( 16_suppl ) 1551 - 1551 2022.6

Publishing type：Research paper (scientific journal) Publisher：American Society of Clinical Oncology (ASCO)

1551

Background: Cancer genomic profiling (CGP) tests have been approved in Japan since June 2019, with the requisite that all test results be discussed by molecular tumor boards (MTBs). More than 20,000 patients in over 200 designated hospitals have taken CGP tests by December 2021. As CGP tests have entered clinical practice, streamlining decision making by MTBs and standardizing interpretation of test results and treatment recommendations have become urgent issues. Here, we evaluated the utility of Chrovis, an annotation algorithm for reporting CGP tests to support MTBs make their recommendations. Methods: We retrospectively reviewed the reporting process of all approved CGP tests done at The University of Tokyo Hospital between December 2019 and November 2021. Chrovis provided annotation for each genetic variant by incorporating biologic, clinical, and therapeutic information by referencing several public knowledge databases and using natural language processing, and generated reports using the automated program. The MTB reviewed and made any necessary changes before finalizing the report. Changes in disclosure of germline findings were made according to the recommendations of a national guideline with consideration of past and family history. Results: Of the 243 tests, 91 changes in 81 Chrovis reports (33% of all reports) were made by the MTB. The most common type of change was germline disclosure with 26 changes (29%), followed by clinical trial information in Japan (18 changes, 20%) and recommendation of the patient-proposed national basket trial with multiple targeted agents (17 changes, 19%). Changes in germline disclosure increased from June 2021, when an update to a national guideline was released, while the proportion of changes in the latter two types remained unchanged. Gene alterations that led to the highest number of changes was TP53, with 13 changes. Changes in therapeutic recommendations were frequently observed in the RAS/MAPK pathway ( BRAF, KRAS, NF1, NRAS) with 12 changes. More changes were required with a tumor-only tissue CGP panel (57 of 149) compared with a matched tumor/normal tissue CGP panel (24 of 94, p = 0.04), mostly due to germline disclosure (24 vs. 2 changes). Conclusions: We observed that automated algorithm-based reporting was sufficient in 67% of reports. Recommendation for germline disclosure still requires manual supervision, particularly with tumor-only tissue CGP panels if algorithms do not incorporate medical history. The process of recommending clinical trials needs improvement, e.g., standardizing database formats for inclusion and exclusion criteria.

DOI： 10.1200/jco.2022.40.16_suppl.1551

12p gain is predominantly observed in non-germinomatous germ cell tumors and identifies an unfavorable subgroup of central nervous system germ cell tumors

Kaishi Satomi, Hirokazu Takami, Shintaro Fukushima, Satoshi Yamashita, Yuko Matsushita, Yoichi Nakazato, Tomonari Suzuki, Shota Tanaka, Akitake Mukasa, Nobuhito Saito, Masayuki Kanamori, Toshihiro Kumabe, Teiji Tominaga, Keiichi Kobayashi, Motoo Nagane, Toshihiko Iuchi, Koji Yoshimoto, Kaoru Tamura, Taketoshi Maehara, Keiichi Sakai, Kazuhiko Sugiyama, Kiyotaka Yokogami, Hideo Takeshima, Masahiro Nonaka, Akio Asai, Toshikazu Ushijima, Masao Matsutani, Ryo Nishikawa, Koichi Ichimura

Neuro-Oncology 24 ( 5 ) 834 - 846 2022.5

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

Abstract

Background

Central nervous system (CNS) germ cell tumors (GCTs) are neoplasms predominantly arising in pediatric and young adult populations. While germinomas generally respond to chemotherapy and radiation, non-germinomatous GCTs (NGGCTs) require more intensive treatment. This study aimed to determine whether 12p gain could predict the prognosis of CNS GCTs.

Methods

Eighty-two CNS GCTs were included in this study. The 12p gain was defined by an additional 12p in the background of potential polyploidy or polysomy. Cases were analyzed using an Illumina methylation 450K array for copy number investigations and validated by fluorescence in situ hybridization (FISH).

Results

A 12p gain was found in 25-out-of-82 cases (30%) and was more frequent in NGGCTs (12% of germinoma cases and 50% of NGGCT cases), particularly in cases with malignant components, such as immature teratoma, yolk sac tumor, choriocarcinoma, and embryonal carcinoma. 12p gain and KIT mutation were mutually exclusive events. The presence of 12p gain correlated with shorter progression-free (PFS) and overall survival (OS) (10-year OS: 59% vs. 94%, with and without 12p gain, respectively, P = 0.0002), even with histology and tumor markers incorporated in the multivariate analysis. Among NGGCTs, 12p gain still had prognostic significance for PFS and OS (10-year OS: 47% vs. 90%, respectively, P = 0.02). The 12p copy number status was shared among histological components in mixed GCTs.

Conclusions

12p gain may predict the presence of malignant components of NGGCTs, and poor prognosis of the patients. It may be associated with early tumorigenesis of CNS GCT.

DOI： 10.1093/neuonc/noab246

Other Link： https://academic.oup.com/neuro-oncology/article-pdf/24/5/834/43548783/noab246.pdf

網羅的メチル化解析を施行した成人脳室内pilocytic astrocytomaの一例

高柳俊作, 矢島寛久, 高見浩数, 田中將太, 池村雅子, 齊藤延人

Brain Tumor Pathology 39 ( Suppl. ) 081 - 081 2022.5

脳腫瘍研究のcutting edge-先端画像、実験/分子病理、デジタル病理- 脳腫瘍分子診断時代における網羅的メチル化解析の有用性と課題

矢島寛久, 田中將太, 高見浩数, 高柳俊作, 池村雅子, 齊藤延人

Brain Tumor Pathology 39 ( Suppl. ) 072 - 072 2022.5

脳神経外科学がん遺伝子パネル検査による脳腫瘍治療

高柳俊作, 田中將太, 齊藤延人

医学のあゆみ 281 ( 2 ) 193 - 195 2022.4

12p gainは中枢神経系胚細胞腫瘍の予後不良群を同定する

里見介史, 高見浩数, 福島慎太郎, 山下聡, 松下裕子, 中里洋一, 鈴木智成, 田中將太, 武笠晃丈, 齊藤延人, 金森政之, 隈部俊宏, 冨永悌二, 小林啓一, 永根基雄, 井内俊彦, 吉本幸司, 田村郁, 前原健寿, 酒井圭一, 杉山一彦, 横上聖貴, 竹島秀雄, 埜中正博, 淺井昭雄, 牛島俊和, 松谷雅生, 西川亮, 市村幸一, 頭蓋内胚細胞腫コンソーシアム

日本病理学会会誌 111 ( 1 ) 220 - 220 2022.3

Transcriptome and Methylome Analysis of CNS Germ Cell Tumor Finds its Cell-of-Origin in Embryogenesis and Reveals Shared Similarities with Testicular Counterparts. International journal

Hirokazu Takami, Asmaa Elzawahry, Yasin Mamatjan, Shintaro Fukushima, Kohei Fukuoka, Tomonari Suzuki, Takaaki Yanagisawa, Yuko Matsushita, Taishi Nakamura, Kaishi Satomi, Shota Tanaka, Akitake Mukasa, Nobuhito Saito, Masayuki Kanamori, Toshihiro Kumabe, Teiji Tominaga, Keiichi Kobayashi, Motoo Nagane, Toshihiko Iuchi, Kaoru Tamura, Taketoshi Maehara, Kazuhiko Sugiyama, Koji Yoshimoto, Keiichi Sakai, Masahiro Nonaka, Akio Asai, Kiyotaka Yokogami, Hideo Takeshima, Yoshitaka Narita, Soichiro Shibui, Yoichi Nakazato, Natsuko Hama, Yasushi Totoki, Mamoru Kato, Tatsuhiro Shibata, Ryo Nishikawa, Masao Matsutani, Koichi Ichimura

Neuro-oncology 24 ( 8 ) 1246 - 1258 2022.2

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

BACKGROUND: CNS germ cell tumors (GCTs) predominantly develop in pediatric and young adult patients with variable responses to surgery, radiation, and chemotherapy. This study aimed to examine the complex and largely unknown pathogenesis of CNS GCTs. METHODS: We used a combined transcriptomic and methylomic approach in 84 cases and conducted an integrative analysis of the normal cells undergoing embryogenesis and testicular GCTs. RESULTS: Genome-wide transcriptome analysis in CNS GCTs indicated that germinoma had a transcriptomic profile representative of primitive cells during early embryogenesis with high meiosis/mitosis potentials, while non-germinomatous GCTs (NGGCTs) had differentiated phenotypes oriented toward tissue formation and organogenesis. Co-analysis with the transcriptome of human embryonic cells revealed that germinomas had expression profiles similar to those of primordial germ cells, while the expression profiles of NGGCTs were similar to those of embryonic stem cells. Some germinoma cases were characterized by extensive immune-cell infiltration and high expression of cancer-testis antigens. NGGCTs had significantly higher immune-cell infiltration, characterized by immune-suppression phenotype. CNS and testicular GCTs (TGCTs) had similar mutational profiles; TGCTs showed enhanced copy number alterations. Methylation analysis clustered germinoma/seminoma and non-germinoma/non-seminoma separately. Germinoma and seminoma were co-categorized based on the degree of the tumor microenvironment balance. CONCLUSIONS: These results suggested that the pathophysiology of GCTs was less dependent on their site of origin and more dependent on the state of differentiation as well as on the tumor microenvironment balance. This study revealed distinct biological properties of GCTs, which will hopefully lead to future treatment development.

DOI： 10.1093/neuonc/noac021

[Molecularly Targeted Therapy for Craniopharyngioma].

Shota Tanaka, Shunsaku Takayanagi, Hirokazu Takami, Nobuhito Saito

No shinkei geka. Neurological surgery 50 ( 1 ) 171 - 178 2022.1

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

Craniopharyngioma is a pathologically benign but clinically malignant brain tumor typically located in the parasellar region. It is treated by surgical resection, but in most cases, total removal is not amenable due to its adhesion to the adjacent vital structures, such as the optic nerve, hypothalamus, and pituitary stalk. Often, tumor regrowth or recurrence occursand it is usually treated with either re-resection or radiotherapy, including stereotactic radiosurgery. Either treatment carries some important risks, including blindness, hypopituitarism, and cognitive impairment. A recent comprehensive genomic analysis revealed that the majority of papillary craniopharyngioma cases harbor a hotspot BRAF-V600E mutation. Several case reports have illustrated dramatic response of the residual or recurrent papillary craniopharyngioma to molecularly targeted therapy with a BRAF inhibitor(vemurafenib or dabrafenib)and a MEK inhibitor(trametinib), which are currently approved for melanoma and non-small cell lung carcinoma. This medical treatment can potentially be a wonderful treatment option for papillary craniopharyngioma, given its freedom from the aforementioned serious risks associated with surgery and radiotherapy.

DOI： 10.11477/mf.1436204542

[Evolving Exploration of the Pathogenesis of CNS Germ Cell Tumors with Regard to Precision Medicine].

Hirokazu Takami, Shunsaku Takayanagi, Shota Tanaka, Nobuhito Saito

No shinkei geka. Neurological surgery 50 ( 1 ) 39 - 50 2022.1

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

Genomic and epigenomic analyses have progressed the exploration of the pathogenesis of CNS germ cell tumors(GCTs)in the past decade. GCTs are characterized by mutations in MAPK or PI3K pathways(55%)and unstable chromosomes, especially 12p gain(45%), as well as global hypomethylation in germinoma. Highly specific microRNA, miR-371a-3p, can be a diagnostic marker in serum and cerebrospinal fluid. Tumor cell content examined in H-E specimens has a prognostic value in germinoma: cases with higher tumor cell content show a worse prognosis. 12p gain in non-germinomatous GCTs(NGGCTs)has an unfavorable prognostic significance. PD-L1 and PD-1 are highly expressed in germinomas and the tumor cell microenvironment, respectively, highlighting the potential effectiveness of immune checkpoint inhibitors. Clinical trials from the Children's Oncology Group(COG)in the US and the Society for Paediatric Oncology(SIOP)in Europe and Japan have shown that whole ventricular irradiation is the most appropriate for germinomas, and that radiation fields can be reduced to the whole ventricle or a local area for localized NGGCTs. Toward personalized medicine, investigations into the structural abnormalities and variants in non-coding regions are needed to develop targeted therapy. A stratified treatment regimen is expected by incorporating newly-found biomarkers to reduce the treatment burden for generally young patients and circumvent late toxicity and sequelae. Establishing effective treatments is crucial for relapsed GCT that has a dismal prognosis.

DOI： 10.11477/mf.1436204530

[Hemangioblastoma and von Hippel-Lindau Disease].

Shunsaku Takayanagi, Hirokazu Takami, Shota Tanaka, Nobuhito Saito

No shinkei geka. Neurological surgery 50 ( 1 ) 101 - 110 2022.1

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

Hemangioblastoma(HB)is a tumor that frequently occurs in von Hippel-Lindau(VHL)disease, a hereditary tumor disease. It is a benign tumor and excision is the first choice of treatment, but in VHL disease, where HB occurs frequently, the emergence of more promising molecularly-targeted therapeutic agents has been desired. In this paper, we first explain HB and VHL disease and then outline the function of the VHL gene and the mechanism of onset of VHL disease. After that, we explain the analysis technology and frequency of VHL gene abnormalities and finally describe HIF2α inhibitors, which are promising as molecularly-targeted therapeutic agents for VHL disease. As the medical system for personalized medicine/precision medicine is being developed in Japan, it is expected that HB and VHL diseases will attract attention as target diseases in the future.

DOI： 10.11477/mf.1436204535

Primary Intracranial Spindle Cell Sarcoma, DICER1-Mutant, with MDM2 Amplification Diagnosed on the Basis of Extensive Molecular Profiling. International journal

Takahide Nejo, Shunsaku Takayanagi, Shota Tanaka, Aya Shinozaki-Ushiku, Shinji Kohsaka, Keisuke Nagata, Munehiro Yokoyama, Shigeo Sora, Tetsuo Ushiku, Akitake Mukasa, Hiroyuki Aburatani, Hiroyuki Mano, Nobuhito Saito

Clinical medicine insights. Case reports 15 11795476221131189 - 11795476221131189 2022

Language：English

Primary intracranial spindle cell sarcoma is an extremely rare mesenchymal tumor, the molecular pathogenesis of which is poorly understood. Because of the lack of specific markers, diagnosis sometimes relies on ruling out all possible differential diagnoses, often making it difficult to reach a definitive diagnosis. In this case study, we report a 69 year-old female patient for whom the integration of multi-layered molecular analyses contributed to making the diagnosis. The disease exhibited aggressive clinical behavior, requiring two sequential surgeries because of rapid regrowth within a short period. Primary and recurrent tumors exhibited similar histological features, in which spindle-shaped cells arranged in interlacing fascicles without any specific architectures, implicating sarcomatous tumors. In immunohistochemistry testing, tumor cells were immunopositive for vimentin but lacked any specific findings that contribute to narrowing down the differential diagnoses. Seeking further diagnostic clues, we performed DNA methylation-based analysis. The copy number analysis revealed MDM2 gene amplification and loss of heterozygosity of 22q. Moreover, dimension reduction clustering analysis implicated a methylation pattern comparable to aggressive types of sarcomas. In addition, an in-house next-generation sequencing panel ("Todai-OncoPanel") analysis identified somatic mutations in DICER1, NF2, and ATRX genes. Taken all together, we finally made the diagnosis of primary intracranial spindle cell sarcoma, DICER1-mutant, with MDM2 gene amplification. This case report suggests that even for the tumors with insufficient morphological and immuno-histological diagnostic clues, integration of multi-layered molecular analyses can contribute to making the diagnoses as well as to understanding the rare tumors by elucidating unexpected genetic and epigenetic features.

DOI： 10.1177/11795476221131189

Novel case of primary intracranial solitary plasmacytoma presenting with significant intratumoral hemorrhage. International journal

Daisuke Sato, Shunsaku Takayanagi, Hirokazu Takami, Tetsuaki Iwamoto, Masashi Nomura, Shohei Nambu, Masako Ikemura, Shota Tanaka, Nobuhito Saito

Surgical neurology international 13 157 - 157 2022

Language：English

Background: Solitary plasmacytoma is a localized lesion comprising monoclonal neoplastic proliferation of plasma cells. This disease is rarely encountered and few reports have described primary intracranial solitary plasmacytoma (PISP). Case Description: We report a case of PISP that presented initially as status epilepticus and exhibited massive intratumoral hemorrhage at the subcortical area. To the best of our knowledge, this is the first recorded presentation of this pathology in this manner. Following evacuation of the hematoma and decompressive craniectomy, the patient underwent radiation therapy and showed no sign of tumor recurrence at 3 years after diagnosis. Conclusion: This case reveals that PISP can present as subcortical intraparenchymal hemorrhage. It should be emphasized that the precise diagnosis of this disease is of utmost importance, because solitary plasmacytoma without a background of multiple myeloma responds well to radiation therapy.

DOI： 10.25259/SNI_66_2022

Development of a New Image-Guided Neuronavigation System: Mixed-Reality Projection Mapping Is Accurate and Feasible

Tsukasa Koike, Taichi Kin, Shota Tanaka, Katsuya Sato, Tatsuya Uchida, Yasuhiro Takeda, Hiroki Uchikawa, Satoshi Kiyofuji, Toki Saito, Hirokazu Takami, Shunsaku Takayanagi, Akitake Mukasa, Hiroshi Oyama, Nobuhito Saito

Operative Neurosurgery 21 ( 6 ) 549 - 557 2021.12

Publishing type：Research paper (scientific journal)

BACKGROUND: Image-guided systems improve the safety, functional outcome, and overall survival of neurosurgery but require extensive equipment. OBJECTIVE: To develop an image-guided surgery system that combines the brain surface photographic texture (BSP-T) captured during surgery with 3-dimensional computer graphics (3DCG) using projection mapping. METHODS: Patients who underwent initial surgery with brain tumors were prospectively enrolled. The texture of the 3DCG (3DCG-T) was obtained from 3DCG under similar conditions as those when capturing the brain surface photographs. The position and orientation at the time of 3DCG-T acquisition were used as the reference. The correct position and orientation of the BSP-T were obtained by aligning the BSP-T with the 3DCG-T using normalized mutual information. The BSP-T was combined with and displayed on the 3DCG using projection mapping. This mixed-reality projection mapping (MRPM) was used prospectively in 15 patients (mean age 46.6 yr, 6 males). The difference between the centerlines of surface blood vessels on the BSP-T and 3DCG constituted the target registration error (TRE) and was measured in 16 fields of the craniotomy area. We also measured the time required for image processing. RESULTS: The TRE was measured at 158 locations in the 15 patients, with an average of 1.19 ± 0.14 mm (mean ± standard error). The average image processing time was 16.58 min. CONCLUSION: Our MRPM method does not require extensive equipment while presenting information of patients' anatomy together with medical images in the same coordinate system. It has the potential to improve patient safety.

DOI： 10.1093/ons/opab353

透明中隔に生じたmyxoid glioneuronal tumor、PDGFRA p.K385-mutantの1例

藤井源太, 田中將太, 辛正廣, 菊池美佑, 高見浩数, 高柳俊作, 齊藤延人

脳神経外科ジャーナル 30 ( 12 ) 871 - 875 2021.12

Language：Japanese Publisher：(一社)日本脳神経外科コングレス

Myxoid glioneuronal tumor、PDGFRA p.K385-mutantは近年新たに提唱された中枢神経系腫瘍の概念である。その発生母地としては透明中隔や側脳室が考えられている。提唱後間もないため症例報告は少なく、その治療法や予後については一定の見解が得られていない。今回われわれは、透明中隔に生じたmyxoid glioneuronal tumor、PDGFRA p.K385-mutantに対し全摘出を行い、その後再発なく良好な経過を辿った1例を経験したので報告する。(著者抄録)

Other Link： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2021&ichushi_jid=J02632&link_issn=&doc_id=20211202230007&doc_link_id=1390572012410134912&url=https%3A%2F%2Fcir.nii.ac.jp%2Fcrid%2F1390572012410134912&type=CiNii&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00003_3.gif

Efficacy and safety of nivolumab in Japanese patients with first recurrence of glioblastoma: an open-label, non-comparative study.

Tomokazu Aoki, Naoki Kagawa, Kazuhiko Sugiyama, Toshihiko Wakabayashi, Yoshiki Arakawa, Shigeru Yamaguchi, Shota Tanaka, Eiichi Ishikawa, Yoshihiro Muragaki, Motoo Nagane, Mitsutoshi Nakada, Satoshi Suehiro, Nobuhiro Hata, Junichiro Kuroda, Yoshitaka Narita, Yukihiko Sonoda, Yasuo Iwadate, Manabu Natsumeda, Yoichi Nakazato, Hironobu Minami, Yuki Hirata, Shunsuke Hagihara, Ryo Nishikawa

International journal of clinical oncology 26 ( 12 ) 2205 - 2215 2021.12

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

BACKGROUND: An open-label, non-comparative study assessed the efficacy and safety of nivolumab in Japanese patients with first recurrence glioblastoma. METHODS: Patients with first recurrence of histologically confirmed World Health Organization Grade IV glioma, after treatment with temozolomide and radiotherapy, received nivolumab 3 mg/kg every 2 weeks until confirmed disease progression (Response Assessment in Neuro-Oncology criteria) or toxicity. Primary endpoint was 1-year overall survival rate assessed by Bayesian approach. The prespecified efficacy criterion was that the Bayesian posterior probability threshold for exceeding the 1-year overall survival of bevacizumab (34.5%) from the Japanese phase 2 study (JO22506) would be 93%. RESULTS: Of the 50 enrolled patients, 44 (88.0%) had recurrent malignant glioma (glioblastoma, gliosarcoma), and of these, 26 (59.1%) had at least one measurable lesion at baseline. The Bayesian posterior mean 1-year overall survival (90% Bayesian credible intervals) with nivolumab was 54.4% (42.27-66.21), and the Bayesian posterior probability of exceeding the threshold of the 1-year overall survival rate of bevacizumab (34.5%) was 99.7%. Median (90% confidence interval) overall and progression-free survival was 13.1 (10.4-17.7) and 1.5 (1.4-1.5) months, respectively. One partial response was observed (objective response rate 1/26 evaluable patients [3.8%]). Treatment-related adverse event rates were 14.0% for Grade 3-4 and 2.0% for Grade 5; most adverse events resolved and were manageable. CONCLUSIONS: The 1-year overall survival with nivolumab monotherapy in Japanese patients with glioblastoma met the prespecified efficacy criterion. The safety profile of nivolumab was consistent with that observed in other tumor types. CLINICAL TRIAL REGISTRATION: JapicCTI-152967.

DOI： 10.1007/s10147-021-02028-1

　 PREV - NEXT 　

1
2
3
4
5
6
7
8
9
10
11