Faculty Profiles - OZAKI Toshifumi

Papers - OZAKI Toshifumi

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がん遺伝子パネルによるfusion gene同定の診断的意義

中田英二, 國定俊之, 板野拓人, 片山晴喜, 安藤輝彦, 藤原智洋, 尾崎敏文

中国・四国整形外科学会雑誌 36 ( 3 ) 361 - 361 2024.10

脛骨高原骨折の治療戦略脛骨近位端骨折に対するプレート固定単顆骨折および両顆骨折に対する使用の基本と応用

依光正則, 望月雄介, 長谷川翼, 奥田龍一郎, 安藤輝彦, 尾崎敏文

中部日本整形外科災害外科学会雑誌 68 ( 秋季学会 ) 59 - 59 2024.10

AIとメタバースを用いた骨軟部腫瘍診療革命早期診断から患者支援まで

長谷井嬢, 藤原智洋, 中田英二, 国定俊之, 尾崎敏文

日本癌治療学会学術集会抄録集 62回 PSP14 - 4 2024.10

Factors Affecting Dynamic Postural Control Ability in Adolescent Idiopathic Scoliosis.

Ryoko Yamawaki, Yoshiaki Oda, Shuhei Yamane, Koji Uotani, Haruo Misawa, Yoshimi Katayama, Masanori Hamada, Toshifumi Ozaki

Acta medica Okayama 78 ( 5 ) 357 - 362 2024.10

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

Research on postural control in patients with adolescent idiopathic scoliosis (AIS) has focused on static postural control, with few studies assessing dynamic postural control. We aimed to identify factors affecting index of postural stability (IPS), a dynamic postural control parameter, in patients with AIS. The participants comprised 50 female patients with AIS. We measured the IPS using stabilometry to evaluate dynamic postural control ability. We investigated age of the participants, major curve position (thoracic or thoracolumbar/lumbar), Cobb angle, and coronal balance. We then assessed the relationships between stabilometry parameters and other variables. IPS was analyzed with a linear regression model. Coronal balance, major curve position, and age each correlated with dynamic postural control ability. The Cobb angle showed no correlation with any of the parameters. Our results offer new insights into the assessment of postural control in patients with AIS.

DOI： 10.18926/AMO/67655

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小児・AYA世代がんのゲノム医療小児・AYA世代の肉腫におけるゲノム医療の意義

中田英二, 遠西大輔, 二宮貴一朗, 冨田秀太, 山本英喜, 岡崎哲也, 平沢晃, 豊岡伸一, 尾崎敏文

日本癌治療学会学術集会抄録集 62回 OSY16 - 2 2024.10

The use of biologic disease-modifying antirheumatic drugs does not increase surgical site infection or delayed wound healing after orthopaedic surgeries for rheumatoid arthritis International journal

Yohei Kiso, Keiichiro Nishida, Ryozo Harada, Yoshihisa Nasu, Ryuichi Nakahara, Yoshifumi Hotta, Shuichi Naniwa, Toshifumi Ozaki

Modern Rheumatology 2024.9

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

ABSTRACT

Objective

To investigate the effect of the use of biologic disease-modifying antirheumatic drugs (bDMARDs) on surgical site infection (SSI) and delayed wound healing (DWH) in rheumatoid arthritis (RA) patients undergoing orthopaedic surgery.

Methods

We retrospectively reviewed the records of 965 elective orthopaedic procedures undertaken in RA patients. The incidences of SSI and DWH were compared between the bDMARDs user and nonuser groups. Subsequently, univariate and multivariate logistic regression analyses were performed to evaluate risk factors for SSI and DWH after propensity score matching. The incidence of postoperative flare-up was also examined.

Results

In 965 procedures, SSI and DWH were identified in 12 and 28 cases, respectively. SSI and DWH were identified in 3 and 17 of 414 procedures treated with bDMARDs, respectively. Flare-up occurred in 21 cases. Propensity score matching identified 315 cases in both groups, with no significant difference in incidence between the two groups. No risk factors for SSI were identified, whereas age, diabetes mellitus, foot and ankle surgery, and a history of musculoskeletal-related infection were identified as risk factors for DWH.

Conclusion

The use of bDMARDs was not associated with an increased incidence of SSI or DWH, with the incidence of flare-up being relatively low.

DOI： 10.1093/mr/roae089

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Identification of ENO-1 positive extracellular vesicles as a circulating biomarker for monitoring of Ewing sarcoma. International journal

Koji Uotani, Tomohiro Fujiwara, Koji Ueda, Aki Yoshida, Shintaro Iwata, Takuya Morita, Masahiro Kiyono, Toshiyuki Kunisada, Ken Takeda, Joe Hasei, Yusuke Yoshioka, Takahiro Ochiya, Toshifumi Ozaki

Cancer science 2024.9

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

The lack of circulating biomarkers for tumor monitoring is a major problem in Ewing sarcoma management. The development of methods for accurate tumor monitoring is required, considering the high recurrence rate of drug-resistant Ewing sarcoma. Here, we describe a sensitive analytical technique for tumor monitoring of Ewing sarcoma by detecting circulating extracellular vesicles secreted from Ewing sarcoma cells. Proteomic analysis of Ewing sarcoma cell-derived extracellular vesicles identified 564 proteins prominently observed in extracellular vesicles from three Ewing sarcoma cell lines. Among these, CD99, SLC1A5, and ENO-1 were identified on extracellular vesicles purified from sera of patients with Ewing sarcoma before treatment but not on extracellular vesicles from those after treatment and healthy individuals. Notably, not only Ewing sarcoma-derived extracellular vesicles but also Ewing sarcoma cells demonstrated proteomic expression of CD99 and ENO-1 on their surface membranes. ENO-1+CD63+ extracellular vesicle detection was reduced after tumor resection while both CD99+CD63+ and ENO-1+CD63+ extracellular vesicles were detected in serum from Ewing sarcoma-bearing mice. Finally, the accuracy of liquid biopsy targeting these candidates was assessed using extracellular vesicles from the sera of patients with Ewing sarcoma. Elevated ENO-1+CD81+ extracellular vesicles in the serum of patients before treatments distinguished patients with Ewing sarcoma from healthy individuals with an area under the curve value of 0.92 (P < 0.001) and reflected the tumor burden in patients with Ewing sarcoma during multidisciplinary treatments. Collectively, circulating ENO-1+CD81+ extracellular vesicle detection could represent a novel tool for tumor monitoring of Ewing sarcoma.

DOI： 10.1111/cas.16343

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p53-armed oncolytic virotherapy induces abscopal effect in osteosarcoma by promoting immunogenic cell death. International journal

Koji Demiya, Hiroshi Tazawa, Hiroya Kondo, Miho Kure, Yusuke Mochizuki, Tadashi Komatsubara, Aki Yoshida, Koji Uotani, Joe Hasei, Tomohiro Fujiwara, Toshiyuki Kunisada, Yasuo Urata, Shunsuke Kagawa, Toshifumi Ozaki, Toshiyoshi Fujiwara

Molecular therapy. Oncology 32 ( 3 ) 200845 - 200845 2024.9

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

Osteosarcoma (OS), the most frequent primary malignant tumor of bone in children and adolescents, is refractory to immune checkpoint inhibitors due to its poor antitumor immune response. Chemotherapy and virotherapy induce immunogenic cell death (ICD) and antitumor immune responses, leading to the abscopal effect in untreated tumors. We previously demonstrated the antitumor activity of the telomerase-specific replication-competent oncolytic adenoviruses OBP-301 and p53-armed OBP-702 in human OS cells. Here, we show the therapeutic potential of chemotherapeutic drugs (doxorubicin, cisplatin) and telomerase-specific oncolytic adenoviruses (OBP-301, p53-armed OBP-702) to induce ICD in human OS cells (U2OS, MNNG/HOS, SaOS-2) and murine OS cells (NHOS). OBP-702 induced more profound ICD via the secretion of adenosine triphosphate (ATP) and high-mobility group box protein B1 (HMGB1) compared with chemotherapy and OBP-301 in human OS cells. Murine NHOS cells were also more sensitive to OBP-702 than OBP-301. Subcutaneous NHOS tumor models demonstrated that intratumoral injection of OBP-702 significantly increased the tumor infiltration of cytotoxic CD8+ T cells and induced the abscopal effect against non-treated tumors compared with OBP-301. Our results suggest that OBP-702 is a promising antitumor reagent to induce ICD with secretion of ATP and HMGB1 and the abscopal effect against OS.

DOI： 10.1016/j.omton.2024.200845

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High-quality expert annotations enhance artificial intelligence model accuracy for osteosarcoma X-ray diagnosis. International journal

Joe Hasei, Ryuichi Nakahara, Yujiro Otsuka, Yusuke Nakamura, Tamiya Hironari, Naoaki Kahara, Shinji Miwa, Shusa Ohshika, Shunji Nishimura, Kunihiro Ikuta, Shuhei Osaki, Aki Yoshida, Tomohiro Fujiwara, Eiji Nakata, Toshiyuki Kunisada, Toshifumi Ozaki

Cancer science 2024.9

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

Primary malignant bone tumors, such as osteosarcoma, significantly affect the pediatric and young adult populations, necessitating early diagnosis for effective treatment. This study developed a high-performance artificial intelligence (AI) model to detect osteosarcoma from X-ray images using highly accurate annotated data to improve diagnostic accuracy at initial consultations. Traditional models trained on unannotated data have shown limited success, with sensitivities of approximately 60%-70%. In contrast, our model used a data-centric approach with annotations from an experienced oncologist, achieving a sensitivity of 95.52%, specificity of 96.21%, and an area under the curve of 0.989. The model was trained using 468 X-ray images from 31 osteosarcoma cases and 378 normal knee images with a strategy to maximize diversity in the training and validation sets. It was evaluated using an independent dataset of 268 osteosarcoma and 554 normal knee images to ensure generalizability. By applying the U-net architecture and advanced image processing techniques such as renormalization and affine transformations, our AI model outperforms existing models, reducing missed diagnoses and enhancing patient outcomes by facilitating earlier treatment. This study highlights the importance of high-quality training data and advocates a shift towards data-centric AI development in medical imaging. These insights can be extended to other rare cancers and diseases, underscoring the potential of AI in transforming diagnostic processes in oncology. The integration of this AI model into clinical workflows could support physicians in early osteosarcoma detection, thereby improving diagnostic accuracy and patient care.

DOI： 10.1111/cas.16330

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p53-armed oncolytic virotherapy induces abscopal effect in osteosarcoma by promoting immunogenic cell death

Molecular Therapy: Oncology 32 ( 3 ) 200845 - 200845 2024.9

悪性末梢神経鞘腫瘍における悪性化を促進する新規メカニズム転写因子PRRX1とTOP2Aのタンパク質間相互作用の発見

たき平将太, 山田大祐, 大曽根達則, 高尾知佳, 板野拓人, 藤原智洋, 中田英二, 国定俊之, 尾崎敏文, 宝田剛志

日本整形外科学会雑誌 98 ( 8 ) S1957 - S1957 2024.9

大腿骨変形癒合に対して一期的矯正骨切り術(三次元骨切り術)を行った1例

奥田龍一郎, 山田和希, 鉄永智紀, 小浦卓, 井上智博, 尾崎敏文

整形・災害外科 67 ( 10 ) 1291 - 1295 2024.9

Language：Japanese Publisher：金原出版(株)

＜文献概要＞右片側肥大症の男子で,6cmの脚長差に対して10歳時に左大腿骨延長術を施行し,7cm延長した。10ヵ月で抜釘したが骨延長部が骨折した。保存療法にて骨癒合を得たが,内反屈曲変形が残存したため,14歳時に一期的矯正骨切り術(三次元骨切り術)を施行した。3Dプリンターにより分割造形した骨モデルを用いて術前計画し,正確な手術が可能であった。術後9ヵ月で骨癒合を認め,スポーツ活動も可能となった。

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関節軟骨におけるLRP4とAGRINの発現調節因子とβ-catenin signalへの影響

浪花崇一, 市川千夏, 林徳てい, 志水紀之, 中原龍一, 那須義久, 尾崎敏文, 西田圭一郎

日本整形外科学会雑誌 98 ( 8 ) S1934 - S1934 2024.9

肉腫におけるゲノム医療の進歩 C-CATデータを用いた肉腫のゲノム解析

中田英二, 遠西大輔, 二宮貴一朗, 山本英喜, 冨田秀太, 国定俊之, 藤原智洋, 二川摩周, 平沢晃, 豊岡伸一, 尾崎敏文

日本整形外科学会雑誌 98 ( 8 ) S1727 - S1727 2024.9

Insomnia among patients with chronic pain: A retrospective study

Masataka Ueda, Tomoko Tetsunaga, Tomonori Tetsunaga, Keiichiro Nishida, Ryo Takatori, Hisakazu Shitozawa, Koji Uotani, Kennsuke Shinohara, Yoshiaki Oda, Toshifumi Ozaki

Medicine 103 ( 32 ) e39113 - e39113 2024.8

Publishing type：Research paper (scientific journal) Publisher：Ovid Technologies (Wolters Kluwer Health)

Insomnia can coexist with chronic pain and is a major cause of rapidly increasing medical expenses. However, insomnia has not been fully evaluated in patients with chronic pain. This retrospective study aimed to identify the risk factors for insomnia in patients with chronic non-cancer pain. A total of 301 patients with chronic non-cancer pain were enrolled. Patients with the Athens insomnia scale scores ≥ 6 and < 6 were classified into insomnia (+) and insomnia (−) groups, respectively. All patients completed self-report questionnaires as part of their chronic pain treatment approach. Univariate and multivariate analyses were performed to predict insomnia. We found that 219 of 301 (72.8%) patients met the AIS criteria for insomnia. Significant differences were depicted between patients with and without insomnia in terms of body mass index, numeric rating scale, pain catastrophizing scale, hospital anxiety, and depression scale (HADS), pain disability assessment scale, EuroQol 5 dimension (EQ5D), and pain self-efficacy questionnaire. Multiple regression analysis identified the numeric rating scale, HADS, and EQ5D scores as factors related to insomnia in patients with chronic non-cancer pain. Anxiety, depression, and disability were associated with a greater tendency toward insomnia. HADS and EQ5D scores are useful screening tools for preventing insomnia in patients with chronic non-cancer pain.

DOI： 10.1097/md.0000000000039113

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Navigation-Guided C-arm-Free Minimally Invasive Transforaminal Lumbar Interbody Fusion: A Comparative Study of Cage Orientation and Screw Insertion Accuracy Against the Conventional C-arm-Assisted Technique. International journal

Koji Uotani, Masato Tanaka, Chetan Kumawat, Sharvari Gunjotikar, Yoshiaki Oda, Kensuke Shinohara, Tadashi Komatsubara, Shinya Arataki, Toshifumi Ozaki

Cureus 16 ( 8 ) e66070 2024.8

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

BACKGROUND: Minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) is a widely utilized technique in spine surgery. This study compares the efficacy and safety of MIS-TLIF performed with traditional C-arm fluoroscopy and C-arm-free O-arm navigation. To the best of our knowledge, our study is the first to compare cage positioning between C-arm-free and C-arm techniques for MIS- TLIF. METHODS: A retrospective, comparative analysis was conducted on 43 patients undergoing MIS-TLIF. The group was divided based on the utilization of C-arm fluoroscopy or C-arm-free O-arm navigation. Key parameters analyzed included cage orientation, screw insertion accuracy, operative efficiency, and postoperative recovery. Radiographic measurements were used to assess surgical precision and perioperative complications were documented. RESULTS: The study encompassed 43 patients, with no significant differences in demographic characteristics between the two groups. Surgical time and blood loss were comparable between C-arm-free and C-arm groups. O-arm navigation significantly reduced pedicle screw misplacement (p=0.024). Cage positioning differed between groups (p=0.0063): O-arm cages were mostly mid-center, while C-arm cages were more anterior-center. Such differences in the cage location did not cause any impact on clinical outcome. No significant differences were observed in postoperative complications (screw loosenings, dural tears, surgical site infections) between groups. The Oswestry Disability Index scores at the final follow-up showed no significant difference between the O-arm and C-arm groups, indicating similar levels of postoperative disability. CONCLUSION: Despite the clinically insignificant difference in cage placement between C-arm-free and C-arm dependent, C-arm-free MIS-TLIF significantly improves screw placement accuracy and reduces radiation exposure to operating stuff. This suggests its potential as a valuable tool for safer and more precise spinal fusion surgery.

DOI： 10.7759/cureus.66070

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Efficacy and safety of denosumab de‑escalation in giant cell tumor of bone. International journal

Eiji Nakata, Toshiyuki Kunisada, Tomohiro Fujiwara, Haruyoshi Katayama, Takuto Itano, Toshifumi Ozaki

Oncology letters 28 ( 2 ) 387 - 387 2024.8

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

Giant cell tumor of bone (GCTB) is a locally aggressive intermediate bone tumor. Denosumab has shown effectiveness in GCTB treatment; however, the benefits of denosumab de-escalation for unresectable GCTB have not been well discussed. The present study investigated the efficacy and safety of denosumab de-escalation for GCTB. The medical records of 9 patients with unresectable GCTB or resectable GCTB not eligible for resection, who received de-escalated denosumab treatment at Okayama University Hospital (Okayama, Japan) between April 2014 and December 2021, were retrospectively reviewed. The denosumab treatment interval was gradually extended to every 8, 12 and 24 weeks. The radiographic changes and clinical symptoms during standard and de-escalated denosumab therapy were assessed. The denosumab interval was de-escalated after a median of 12 months of a standard 4-weekly treatment. Imaging showed that the re-ossification of osteolytic lesions obtained with the 4-weekly treatment were sustained with 8- and 12-weekly treatments. The extraskeletal masses reduced significantly with standard treatment, while tumor reduction was sustained during de-escalated treatment. During the 24-weekly treatment, 2 patients remained stable, while 2 patients developed local recurrence. The clinical symptoms improved significantly with standard treatment and remained improved during de-escalated treatment. There were severe adverse events including osteonecrosis of the jaw (2 patients), atypical femoral fracture (1 patient) and malignant transformation of GCTB (1 patient). In conclusion, 12-weekly de-escalated denosumab treatment showed clinical benefits as a maintenance treatment in patients with unresectable GCTB, in addition to sustained stable tumor control and improved clinical symptoms with standard treatment. A 24-weekly treatment can also be administered, with careful attention paid to detecting local recurrence.

DOI： 10.3892/ol.2024.14520

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どうする?関節包切開股関節鏡手術における関節包切開

山田和希, 鉄永智紀, 小浦卓, 井上智博, 奥田龍一郎, 尾崎敏文

Hip Joint 50 ( 2 ) 7 - 7 2024.8

寛骨臼骨折術後障害に対するTHAの治療成績

奥田龍一郎, 鉄永智紀, 山田和希, 小浦卓, 井上智博, 尾崎敏文

Hip Joint 50 ( 1 ) 542 - 545 2024.8

Efficacy and safety of nivolumab monotherapy in patients with unresectable clear cell sarcoma and alveolar soft part sarcoma (OSCAR Trial/NCCH1510). International journal

Tadaaki Nishikawa, Shigeki Kakunaga, Kenji Tamura, Masashi Ando, Toshifumi Ozaki, Akira Kawai, Takafumi Ueda, Mamiko Kawasaki, Sawako Tomatsuri, Nobuko Okamura, Masahisa Kamikura, Akinobu Hamada, Akihiko Yoshida, Akihiro Hirakawa, Taro Shibata, Kenichi Nakamura, Kan Yonemori

Cancer 2024.7

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

BACKGROUND: Clear cell sarcoma (CCS) and alveolar soft part sarcoma (ASPS) are rare, and standard systemic therapy is not established except for sunitinib in ASPS. It is known that CCS and ASPS have a common biological feature of melanoma and Xp11.2/TFE3 translocation renal cell carcinoma, and immune-checkpoint inhibitors (ICIs) are effective in these tumors. The authors conducted a phase 2 trial to evaluate the efficacy and safety of nivolumab for CCS and ASPS. METHODS: The number of patients expected to be enrolled was 15-25 and was determined based on the Bayesian design. The primary end point was the confirmed objective response rate (ORR) according to the central review and the secondary end points included ORR, progression-free survival (PFS), overall survival (OS), and safety. RESULTS: A total of 26 patients (CCS, 12; ASPS, 14) were enrolled. Efficacy and safety were analyzed on 25 and 26 patients, respectively. The minimum number of responses required for a positive conclusion regarding the efficacy was four. However, only one patient (4.0%) with ASPS had a partial response. Complete response, stable disease, progression disease, and not evaluable were 0%, 60%, 32%, and 4.0%, respectively. Adverse events of grade 3 or 4 occurred in 57.7% (15 of 26). The median PFS was 4.9 months (95% confidence interval [CI], 3.7-8.6 months) and the median OS was 15.8 months (95% CI, 8.2-not reached). CONCLUSIONS: The primary end point of the ORR was not met for CCS and ASPS on the central review. Further studies are needed to evaluate ICIs in patients with ASPS.

DOI： 10.1002/cncr.35483

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Papers - OZAKI Toshifumi