Faculty Profiles - Tanaka Shota

Loss of H3K27 trimethylation in a distinct group of de-differentiated chordoma of the skull base

Naohiro Makise, Tatsunori Shimoi, Kuniko Sunami, Yasuko Aoyagi, Hiroshi Kobayashi, Shota Tanaka, Akira Kawai, Kan Yonemori, Tetsuo Ushiku, Akihiko Yoshida

Histopathology 82 ( 3 ) 420 - 430 2023.2

Publishing type：Research paper (scientific journal)

De-differentiated chordoma is defined as a high-grade sarcoma lacking notochordal differentiation, which arises in association with conventional chordoma. The mechanism underlying de-differentiation remains unclear. We immunohistochemically investigated trimethylation at lysine 27 of histone 3 (H3K27me3) in nine de-differentiated chordomas. The tumours occurred at the skull base (n = 5) or the sacrum (n = 4) in four men and five women with a median age of 50 years. De-differentiation occurred de novo in four cases and at recurrence/metastasis in five cases. Five tumours retained H3K27me3, whereas four showed complete loss of H3K27me3 only in the de-differentiated component, while the conventional chordoma component retained H3K27me3. All the H3K27me3-negative tumours showed co-loss of dimethylation at H3K27 (H3K27me2), consistent with inactivation of polycomb repressive complex 2. Two genetically analysed H3K27me3-negative tumours harboured EED homozygous deletions. All four H3K27me3-negative de-differentiated chordomas affected the skull base of young or middle-aged women. Unlike dense proliferation of highly pleomorphic spindle or epithelioid cells in the H3K27me3-positive de-differentiated chordomas, all H3K27me3-negative tumours displayed swirling fascicles of relatively uniform spindle cells with alternating cellularity and perivascular accentuation, resembling malignant peripheral nerve sheath tumour (MPNST). Rhabdomyoblastic differentiation was present in one H3K27me3-negative tumour. We identified a novel group of de-differentiated chordomas in the skull base that lost H3K27me3/me2 only in the de-differentiated component, which was associated with EED homozygous deletion and MPNST-like histology. Our data suggest a distinct ‘polycomb-type’ de-differentiation pathway in chordoma, similar to a recently described de-differentiated chondrosarcoma with H3K27me3 loss.

DOI： 10.1111/his.14823

Safety and efficacy of tumour-treating fields (TTFields) therapy for newly diagnosed glioblastoma in Japanese patients using the Novo-TTF System: a prospective post-approval study. International journal

Ryo Nishikawa, Fumiyuki Yamasaki, Yoshiki Arakawa, Yoshihiro Muragaki, Yoshitaka Narita, Shota Tanaka, Shigeru Yamaguchi, Akitake Mukasa, Masayuki Kanamori

Japanese journal of clinical oncology 53 ( 5 ) 371 - 377 2023.1

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

BACKGROUND: Tumour-treating fields therapy is a locoregional, anti-cancer treatment. Efficacy and safety of tumour-treating fields therapy in adults with newly diagnosed glioblastoma were demonstrated in the pivotal phase 3 EF-14 study (NCT00916409). Here, we report post-approval data of tumour-treating fields therapy in Japanese patients with newly diagnosed glioblastoma. METHODS: Unsolicited post-marketing surveillance data from Japanese patients with newly diagnosed glioblastoma treated with tumour-treating fields therapy (December 2016-June 2020) were retrospectively analysed. The primary endpoints were skin, neurological and psychiatric adverse events. The secondary endpoints were 1- and 2-year overall survival rates, and the 6-month progression-free survival. adverse events were analysed using MedDRA v24.0. The overall survival and progression-free survival were assessed using the Kaplan-Meier survival analysis (log-rank testing). The Cox proportional hazard regression analyses were also performed. RESULTS: Forty patients with newly diagnosed glioblastoma were enrolled (62.5% male; median age 59 years; median baseline Karnofsky Performance Scale score 90). The most common tumour-treating-fields-therapy-related adverse event was beneath-array local skin reaction (60% of patients). The adverse events were mostly mild to moderate in severity. Neurological disorders were observed in 2.5% patients (one patient reported dysesthesia). No psychiatric disorders were reported. The 1- and 2-year overall survival rates were 77.9% (95% CI 60.6-88.3) and 53.6% (35.5-68.7%), respectively. The 6-month progression-free survival was 77.5% (61.2-87.6%). These survival rates compare favourably with those in the EF-14 trial (1- and 2-year overall survival rates: 73% [69-77%] and 43% [39-48%], respectively; 6-month progression-free survival rate: 56% (51-61%). CONCLUSION: This post-approval, real-world evidence study revealed no new safety signals and suggests the safety and efficacy of tumour-treating fields therapy in Japanese patients with newly diagnosed glioblastoma.

DOI： 10.1093/jjco/hyad001

Clinical utility of Todai OncoPanel in the setting of approved comprehensive cancer genomic profiling tests in Japan. International journal

Hidenori Kage, Aya Shinozaki-Ushiku, Kazunaga Ishigaki, Yusuke Sato, Masahiko Tanabe, Shota Tanaka, Michihiro Tanikawa, Kousuke Watanabe, Shingo Kato, Kiwamu Akagi, Keita Uchino, Kinuko Mitani, Shunji Takahashi, Yuji Miura, Sadakatsu Ikeda, Yasushi Kojima, Kiyotaka Watanabe, Hitoshi Mochizuki, Hironori Yamaguchi, Yoshimasa Kawazoe, Kosuke Kashiwabara, Shinji Kohsaka, Kenji Tatsuno, Tetsuo Ushiku, Kazuhiko Ohe, Yutaka Yatomi, Yasuyuki Seto, Hiroyuki Aburatani, Hiroyuki Mano, Kiyoshi Miyagawa, Katsutoshi Oda

Cancer science 114 ( 4 ) 1710 - 1717 2023.1

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

Comprehensive cancer genome profiling (CGP) has been nationally reimbursed in Japan since June 2019. Less than 10% of the patients have been reported to undergo recommended treatment. Todai OncoPanel (TOP) is a dual DNA-RNA panel as well as a paired tumor-normal matched test. Two hundred patients underwent Todai OncoPanel as part of Advanced Medical Care B with approval by the Ministry of Health, Labour and Welfare between September 2018 and December 2019. Tests were performed in patients with cancers without standard treatment or when patients had already undergone standard treatment. Data from DNA and RNA panels were analyzed in 198 and 191 patients, respectively. The percentage of patients who were given therapeutic or diagnostic recommendations was 61% (120/198). One hundred and four samples (53%) harbored gene alterations that were detected with the DNA panel and had potential treatment implications, and 14 samples (7%) had a high tumor mutational burden. Twenty-two samples (11.1%) harbored 30 fusion transcripts or MET exon 14 skipping that were detected by the RNA panel. Of those thirty transcripts, six had treatment implications and four had diagnostic implications. Thirteen patients (7%) were found to have pathogenic or likely pathogenic germline variants and genetic counseling was recommended. Overall, 12 patients (6%) received recommended treatment. In summary, patients benefited from both TOP DNA and RNA panels while following the same indication as the approved CGP tests. (UMIN000033647).

DOI： 10.1111/cas.15717

Morphologically, genetically and spatially mixed astrocytoma and oligodendroglioma; chronological acquisition of 1p/19q codeletion and CDKN2A deletion: a case report

Hirokazu Takami, Akitake Mukasa, Shunsaku Takayanagi, Tsukasa Koike, Reiko Matsuura, Masako Ikemura, Tetsuo Ushiku, Gakushi Yoshikawa, Junji Shibahara, Shota Tanaka, Nobuhito Saito

Brain Tumor Pathology 40 ( 1 ) 26 - 34 2023.1

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

"Oligoastrocytoma" disappeared as of the revised fourth edition of the World Health Organization Classification of Tumours of the Central Nervous System, except where appended with "not otherwise specified (NOS)". However, histopathological and genetic backgrounds of cases with dual features of astrocytoma/oligodendroglioma have been sparsely reported. We encountered a 54-year-old man with right frontal glioma comprising two distinct parts on imaging and histopathological examination: grade 4 astrocytoma with IDH1-R132H, ATRX loss, p53-positivity and intact 1p/19q; and oligodendroglioma with IDH1-R132H, intact ATRX, p53-negativity and partially deleted 1p/19q. At recurrence, histopathology showed low-grade mixed astrocytic and oligodendroglial features: the former with IDH1-R132H, ATRX loss, p53-positivity and intact 1p/19q and the latter showing IDH1-R132H, intact ATRX, p53-negativity and 1p/19q codeletion. At second recurrence, histopathology was astrocytoma grade 4 with IDH1-R132H, ATRX loss, p53-positivity and intact 1p/19q. Notably, 1p/19q codeletion was acquired at recurrence and CDKN2A was deleted at second recurrence. These findings suggest insights into tumorigenesis: (1) gliomas with two distinct lineages might mix to produce "oligoastrocytoma"; and (2) 1p/19q codeletion and CDKN2A deletion might be acquired during chemo-radiotherapy. Ultimately, astrocytic and oligodendroglial clones might co-exist developmentally or these two lineages might share a common cell-of-origin, with IDH1-R132H as the shared molecular feature.

DOI： 10.1007/s10014-022-00448-z

Indocyanine green illuminates the way to cut the tentorium in occipital transtentorial approach: technical note International journal

Hirokazu Takami, Shota Tanaka, Shunsaku Takayanagi, Hirofumi Nakatomi, Nobuhito Saito

British Journal of Neurosurgery 37 ( 6 ) 1925 - 1927 2023

Language：English

BACKGROUND AND IMPORTANCE: The occipital transtentorial approach is used to address lesions at the posterior incisural space or upper cerebellum. This approach is rarely used, making standardization of the surgical procedure challenging. Here we describe the effectiveness of indocyanine green (ICG) and dye markings before tentorial incision in charting a safe and bloodless surgical trajectory for improved manoeuvrability. CLINICAL PRESENTATION: The first case was a 40-year-old man with a residual pineal mass after chemoradiation therapy for pathologically-proven germinoma. Surgical resection was performed via left occipital craniotomy. Incision of the left cerebellar tentorium by a radiofrequency knife was preceded by visualization of the straight sinus and venous lake, which were marked with dye, enabling safe entry into the quadrigeminal cistern. Finally, total-resection of the mature teratoma was achieved. The second case was a 50-year-old man with an enhancing mass at the cerebellar vermis and left hemisphere. Left occipital craniotomy was followed by ICG administration, illuminating the straight sinus and a complex structure of dural venous channels, which were marked with dye. This visualization maximized the tentorial incision by carefully avoiding venous structures and widely exposed the upper cerebellum. Subtotal-resection of the tumor was achieved, with a diagnosis of glioblastoma. CONCLUSION: ICG administration and dye marking are feasible and useful methods for precise identification/visualization of venous structures. They enable maximization as well as safe and appropriate tentorial incision to provide a sufficient surgical corridor for the occipital transtentorial approach.

DOI： 10.1080/02688697.2021.1927982

Recurrent glioblastoma metastatic to the lumbar vertebra: A case report and literature review: Surgical oncology. International journal

Ako Matsuhashi, Shota Tanaka, Hirokazu Takami, Masashi Nomura, Masako Ikemura, Yoshitaka Matsubayashi, Yusuke Shinoda, Keisuke Yamada, Yu Sakai, Yasuaki Karasawa, Shunsaku Takayanagi, Nobuhito Saito

Frontiers in oncology 13 1101552 - 1101552 2023

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

BACKGROUND: Glioblastoma is a malignant tumor, and its prognosis is as poor as 1.5 to 2 years. Most cases recur within one year even under the standard treatment. The majority of recurrences are local, and in rare cases, metastasize mostly within the centra nervous system. Extradural metastasis of glioma is exceedingly rare. Here, we present a case of vertebral metastasis of glioblastoma. CASE PRESENTATION: We present a 21-year-old man post total resection of the right parietal glioblastoma, diagnosed with lumbar metastasis. He originally presented with impaired consciousness and left hemiplegia and underwent gross total resection of the tumor. Given the diagnosis of glioblastoma, he was treated with radiotherapy combined with concurrent and adjuvant temozolomide. Six months after tumor resection, the patient presented with severe back pain, and was diagnosed as metastatic glioblastoma on the first lumbar vertebrae. Posterior decompression with fixation and postoperative radiotherapy were conducted. He went on to receive temozolomide and bevacizumab. However, at 3 months after the diagnosis of lumbar metastasis, further disease progression was noted, and his care was transitioned to best supportive care. Comparison on copy number status between primary and metastatic lesions on methylation array analysis revealed more enhanced chromosomal instability including 7p loss, 7q gain and 8 gain in the metastatic lesion. CONCLUSION: Based upon the literature review and our case, younger age of initial presentation, multiple surgical interventions, and long overall survival seem to be the risk factors of vertebral metastasis. As the prognosis of glioblastoma improves over time, its vertebral metastasis is seemingly more common. Therefore, extradural metastasis should be kept in mind in the treatment of glioblastoma. Further, detailed genomic analysis on multiple paired specimens is mandated to elucidate the molecular mechanisms of vertebral metastasis.

DOI： 10.3389/fonc.2023.1101552

Case report and literature review: exploration of molecular therapeutic targets in recurrent malignant meningioma through comprehensive genetic analysis with Todai OncoPanel. International journal

Kenta Ohara, Satoru Miyawaki, Hirofumi Nakatomi, Atsushi Okano, Yu Teranishi, Yuki Shinya, Daiichiro Ishigami, Hiroki Hongo, Shunsaku Takayanagi, Shota Tanaka, Aya Shinozaki-Ushiku, Shinji Kohsaka, Hidenori Kage, Katsutoshi Oda, Kiyoshi Miyagawa, Hiroyuki Aburatani, Hiroyuki Mano, Kenji Tatsuno, Nobuhito Saito

Frontiers in neurology 14 1270046 - 1270046 2023

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

BACKGROUND: Despite accumulating research on the molecular characteristics of meningiomas, no definitive molecularly targeted therapy for these tumors has been established to date. Molecular mechanisms underlying meningioma progression also remain unclear. Comprehensive genetic testing approaches can reveal actionable gene aberrations in meningiomas. However, there is still limited information on whether profiling the molecular status of subsequent recurrent meningiomas could influence the choice of molecular-targeted therapies. CASE PRESENTATION: We report a case of meningioma with malignant progression and multiple recurrences. We performed matched tumor pair analysis using the Todai OncoPanel to investigate the possibility of additional standard treatments. The loss of several chromosomal regions, including NF2 and CDKN2A, which is associated with aggressive meningiomas, was considered a significant driver event for malignant progression. Using additional matched tumor pair analysis, mutations in TRAF7, ARID1A, and ERBB3 were identified as subclonal driver events at the time of recurrence. No genetic aberrations were found for which evidence-based targeted therapy was applicable. We also reviewed previous reports of molecular therapies in meningioma to discuss issues with the current molecular testing approach. CONCLUSION: Gene panel testing platforms such as the Todai OncoPanel represent a powerful approach to elucidate actionable genetic alterations in various types of tumors, although their use is still limited to the diagnosis and prediction of prognosis in meningiomas. To enable targeted molecular therapy informed by gene-panel testing, further studies including matched tumor pair analyses are required to understand the molecular characteristics of meningiomas and develop treatments based on genetic abnormalities.

DOI： 10.3389/fneur.2023.1270046

Bevacizumab beyond Progression for Newly Diagnosed Glioblastoma (BIOMARK): Phase II Safety, Efficacy and Biomarker Study. International journal

Motoo Nagane, Koichi Ichimura, Ritsuko Onuki, Daichi Narushima, Mai Honda-Kitahara, Kaishi Satomi, Arata Tomiyama, Yasuhito Arai, Tatsuhiro Shibata, Yoshitaka Narita, Takeo Uzuka, Hideo Nakamura, Mitsutoshi Nakada, Yoshiki Arakawa, Takanori Ohnishi, Akitake Mukasa, Shota Tanaka, Toshihiko Wakabayashi, Tomokazu Aoki, Shigeki Aoki, Soichiro Shibui, Masao Matsutani, Keisuke Ishizawa, Hideaki Yokoo, Hiroyoshi Suzuki, Satoshi Morita, Mamoru Kato, Ryo Nishikawa

Cancers 14 ( 22 ) 2022.11

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

We evaluated the efficacy and safety of bevacizumab beyond progression (BBP) in Japanese patients with newly diagnosed glioblastoma and explored predictors of response to bevacizumab. This phase II study evaluated a protocol-defined primary therapy by radiotherapy with concurrent and adjuvant temozolomide plus bevacizumab, followed by bevacizumab monotherapy, and secondary therapy (BBP: bevacizumab upon progression). Ninety patients received the protocol-defined primary therapy (BBP group, n = 25). Median overall survival (mOS) and median progression-free survival (mPFS) were 25.0 and 14.9 months, respectively. In the BBP group, in which O6-methylguanine-DNA methyltransferase (MGMT)-unmethylated tumors predominated, mOS and mPFS were 5.8 and 1.9 months from BBP initiation and 16.8 and 11.4 months from the initial diagnosis, respectively. The primary endpoint, the 2-year survival rate of the BBP group, was 27.0% and was unmet. No unexpected adverse events occurred. Expression profiling using RNA sequencing identified that Cluster 2, which was enriched with the genes involved in macrophage or microglia activation, was associated with longer OS and PFS independent of the MGMT methylation status. Cluster 2 was identified as a significantly favorable independent predictor for PFS, along with younger age and methylated MGMT. The novel expression classifier may predict the prognosis of glioblastoma patients treated with bevacizumab.

DOI： 10.3390/cancers14225522

再発膠芽腫に対するエリブリンの第2相多施設単群医師主導治験

高橋雅道, 川嶋聡, 口羽文, 佐立崚, 米盛勧, 永根基雄, 荒川芳輝, 武笠晃丈, 田中將太, 西川亮, 村垣善浩, 増富健吉, 市村幸一, 中村健一, 成田善孝

日本癌治療学会学術集会抄録集 60回 EN6 - 3 2022.10

Oligodendroglioma,IDH-mutant and 1p/19q-codeletedのマルチオミクス解析による全ゲノム解析の全貌(Whole genome multi-omics landscape of Oligodenderoglioma, IDH-mutant and 1p/19q-codeleted)

舟越勇介, 南部翔平, 中島拓真, 畝田篤仁, 片山琴絵, 井元清哉, 花谷亮典, 田中將太, 齋藤竜太, 吉本幸司, 成田善孝, 鈴木啓道

日本癌学会総会記事 81回 E - 1041 2022.9

【神経疾患とゲノム医療】個別病態・疾患のゲノム医療脳腫瘍

高柳俊作, 田中將太, 齊藤延人

Clinical Neuroscience 40 ( 9 ) 1100 - 1103 2022.9

Revisitation of imaging features of skull base chondrosarcoma in comparison to chordoma. International journal

Hirotaka Hasegawa, Masahiro Shin, Ryoko Niwa, Satoshi Koizumi, Shoko Yoshimoto, Naoyuki Shono, Yuki Shinya, Hirokazu Takami, Shota Tanaka, Motoyuki Umekawa, Shiori Amemiya, Taichi Kin, Nobuhito Saito

Journal of neuro-oncology 159 ( 3 ) 581 - 590 2022.9

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

PURPOSE: Pre-surgical diagnosis of skull base chondrosarcoma (SBC) is often challenging due to the resemblance to chordoma. The goal of this study was to develop an optimal method for predicting SBC diagnosis. METHODS: This retrospective study included patients with histologically diagnosed SBC and skull base chordoma. Their clinical and radiologic features were compared, and the predictive factors of SBC were examined. RESULTS: Forty-one patients with SBC and 41 with chordoma were included. Most SBCs exhibited hypointensity (25, 64.1%) or isointensity (12, 30.8%) on T1-weighted images, and hyperintensity (34, 87.1%) or mixed intensity (5, 12.8%) on T2-weighted images. MRI contrast enhancement was usually avid or fair (89.7%) with "arabesque"-like pattern (41.0%). The lateral/paramidline location was more common in SBC than in chordoma (85.4% vs. 9.8%; P < 0.01), while midline SBCs (14.6%) were also possible. Multivariate analysis demonstrated that higher apparent diffusion coefficient (ADC) value (unit odds ratio 1.01; 95% confidence interval 1.00-1.02; P < 0.01) was associated with an SBC diagnosis. An ADC value of ≥ 1750 × 10-6 mm2/s demonstrated a strong association with an SBC diagnosis (odds ratio 5.89 × 102; 95% confidence interval 51.0-6.80 × 103; P < 0.01) and yielded a sensitivity of 93.9%, specificity of 97.4%, positive predictive value of 96.9%, and negative predictive value of 95.0%. CONCLUSION: The ADC-based method is helpful in distinguishing SBC from chordoma and readily applicable in clinical practice. The prediction accuracy increases when other characteristics of SBC, such as non-midline location and arabesque-like enhancement, are considered together.

DOI： 10.1007/s11060-022-04097-2

東大オンコパネル(TOP)を用いたプレシジョンメディシン(先進医療B)(Precision Medicine with Todai OncoPanel(TOP) in Advanced Medicine Care B)

鹿毛秀宣, 牛久綾, 石垣和祥, 佐藤悠佑, 田辺真彦, 田中將太, 谷川道洋, 渡邊広祐, 高阪真路, 辰野健二, 牛久哲男, 油谷浩幸, 間野博行, 宮川清, 織田克利

日本癌学会総会記事 81回 P - 1070 2022.9

ゲノムおよびトランスクリプトーム解析による膠芽腫の分子的多様性の解明(Dissecting the molecular complexity underlying glioblastoma by genomic and transcriptome profiling)

中島拓真, 舟越勇介, 南部翔平, 畝田篤仁, 片山琴絵, 花谷亮典, 井元清哉, 田中將太, 齋藤竜太, 吉本幸司, 成田善孝, 鈴木啓道

日本癌学会総会記事 81回 E - 1040 2022.9

星細胞腫IDH変異型の全ゲノムシークエンスと包括的な分子学的解析(Whole-genome sequencing and comprehensive molecular profiling of Astrocytoma, IDH-mutant)

舟越勇介, 中島拓真, 南部翔平, 畝田篤仁, 片山琴絵, 井元清哉, 花谷亮典, 田中將太, 齋藤竜太, 吉本幸司, 成田善孝, 鈴木啓道

日本癌学会総会記事 81回 E - 1038 2022.9

中島拓真, 舟越勇介, 南部翔平, 畝田篤仁, 片山琴絵, 花谷亮典, 井元清哉, 田中將太, 齋藤竜太, 吉本幸司, 成田善孝, 鈴木啓道

日本癌学会総会記事 81回 E - 1040 2022.9

Metformin with Temozolomide for Newly Diagnosed Glioblastoma: Results of Phase I Study and a Brief Review of Relevant Studies. International journal

Makoto Ohno, Chifumi Kitanaka, Yasuji Miyakita, Shota Tanaka, Yukihiko Sonoda, Kazuhiko Mishima, Eiichi Ishikawa, Masamichi Takahashi, Shunsuke Yanagisawa, Ken Ohashi, Motoo Nagane, Yoshitaka Narita

Cancers 14 ( 17 ) 2022.8

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

Glioblastoma (GBM) inevitably recurs due to a resistance to current standard therapy. We showed that the antidiabetic drug metformin (MF) can induce the differentiation of stem-like glioma-initiating cells and suppress tumor formation through AMPK-FOXO3 activation. In this study, we design a phase I/II study to examine the clinical effect of MF. We aim to determine a recommended phase II MF dose with maintenance temozolomide (TMZ) in patients with newly diagnosed GBM who completed standard concomitant radiotherapy and TMZ. MF dose-escalation was planned using a 3 + 3 design. Dose-limiting toxicities (DLTs) were assessed during the first six weeks after MF initiation. Three patients were treated with 1500 mg/day MF and four patients were treated with 2250 mg/day MF between February 2021 and January 2022. No DLTs were observed. The most common adverse effects were appetite loss, nausea, and diarrhea, all of which were manageable. Two patients experienced tumor progression at 6.0 and 6.1 months, and one died 12.2 months after initial surgery. The other five patients remained stable at the last follow-up session. The MF dose of up to 2250 mg/day combined with maintenance TMZ appeared to be well tolerated, and we proceeded to a phase II study with 2250 mg/day MF.

DOI： 10.3390/cancers14174222

Chronological Progression and Management of Syringobulbia Caused by Spinal Hemangioblastoma: A Case Series and Review of the Literature. International journal

Takahiro Tsuchiya, Hirokazu Takami, Shoko Yoshimoto, Shohei Nambu, Shunsaku Takayanagi, Shota Tanaka, Nobuhito Saito

World neurosurgery 167 e127-e136 2022.8

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

BACKGROUND: Syringomyelia often accompanies spinal hemangioblastoma (SHB). It often shows progression to the medulla oblongata, dubbed as "syringobulbia", which presents critical symptoms such as dysphagia and respiratory compromise. Appropriate management of chronological syringomyelia progression toward syringobulbia is not set in stone. This study aims to unravel the clinical and chronological behavior of syringobulbia and its management. METHODS: A single-institution case series study of 5 patients operated for SHB with syringobulbia was conducted. Serial preoperative magnetic resonance imaging scans were analyzed in further details, especially focusing on the chronological progression of syringomyelia. A literature review was performed to describe clinical/imaging characteristics. RESULTS: Chronological imaging analyses revealed that despite the relatively steady progression of syringomyelia over years, it accelerated when developing syringobulbia. Intramedullary signal change ("presyringomyelia") was observed in the area where syringomyelia subsequently occurred. Literature review yielded another 15 cases of SHB with syringobulbia, totaling 20 cases. Bulbar dysfunction was seen in 4 cases (20%). Gross total resection was performed in all cases except 1, which underwent just syringotomy. Rapid postoperative symptom improvement was observed in all cases, as well as immediate imaging resolution of syringomyelia. CONCLUSIONS: The symptoms associated with syringobulbia often become life-threatening. Notably, its resolution may be near-synchronous to surgical resection of the spinal lesion. The speed of progression of syringomyelia is usually steady, but it may accelerate when extending to syringobulbia. Regular imaging follow-up is thus highly recommended to determine the best timing of intervention when presyringomyelia and syringomyelia are ascending toward the medulla oblongata.

DOI： 10.1016/j.wneu.2022.07.118