Faculty Profiles - OZAKI Toshifumi

Papers - OZAKI Toshifumi

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A newly-developed guide can create tibial tunnel at an optimal position during medial meniscus posterior root repairs.

Takaaki Hiranaka, Takayuki Furumatsu, Yuki Okazaki, Keisuke Kintaka, Tadashi Yamawaki, Toshifumi Ozaki

Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association 2021.5

Authorship：Last author Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: During transtibial pullout repair of medial meniscus (MM) posterior root tears (MMPRTs), accurate tibial tunnel creation within the anatomic MM posterior root attachment seems critical. This study aimed to evaluate the tibial tunnel position created by a newly-developed Precision guide during pullout repair of MMPRTs. METHODS: In 40 patients who underwent transtibial pullout repairs, the tibial tunnel was created using the Unicorn Meniscal Root (UMR) (n = 20) or Precision guide (n = 20). Three-dimensional computed tomography images of the tibial surface were evaluated postoperatively, using Tsukada's measurement method. The expected anatomic center of the MM posterior root attachment was defined as the center of three tangential lines corresponding to anatomic bony landmarks. The expected anatomic center (AC) and the tibial tunnel center (TC) were evaluated using the percentage-based posterolateral location on the tibial surface. The difference in the mediolateral and anteroposterior percentage distance between the AC and TC was calculated, as was the absolute distance between the AC and TC. RESULTS: The mean AC was located 77.4% posterior and 40.1% lateral. The mean TC was similar in the UMR and Precision guide groups. There was no significant difference in the mediolateral percentage distance (UMR 3.9% vs. Precision 3.6%, p = 0.405), but a significant difference was observed in the anteroposterior percentage distance (UMR 3.5% vs. Precision 2.6%, p = 0.031). The mean absolute distance between the AC and TC was 3.9 mm and 3.5 mm (UMR and Precision guide groups, respectively) (p = 0.364). CONCLUSIONS: The new Precision guide can create tibial tunnel in an optimal and stable position during pullout repair of MMPRTs.

DOI： 10.1016/j.jos.2021.04.002

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A randomized phase II trial of second-line treatment for advanced soft tissue sarcoma comparing trabectedin, eribulin and pazopanib (2ND-STEP, JCOG1802).

Makoto Endo, Kazuhiro Tanaka, Yoshihiro Matsumoto, Hiroaki Hiraga, Shintaro Iwata, Satoshi Tsukushi, Munenori Watanuki, Toru Akiyama, Tsukasa Yonemoto, Robert Nakayama, Keisuke Ae, Hiroyuki Kawashima, Hiroyuki Tsuchiya, Hirohisa Katagiri, Akihito Nagano, Satoshi Takenaka, Tomoko Kataoka, Ryunosuke Machida, Haruhiko Fukuda, Toshifumi Ozaki

Journal of Clinical Oncology 39 ( 15_suppl ) TPS11580 - TPS11580 2021.5

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

TPS11580

Background: Soft tissue sarcomas (STS) are a rare type of malignancy, which comprises of a variety of histologies. Chemotherapy is the standard treatment for patients with advanced STS. Doxorubicin alone or in combination with ifosfamide is widely accepted as the first-line chemotherapy for advanced STS. While a combination with gemcitabine and docetaxel is regarded as a standard regimen of the second-line chemotherapy after failure of doxorubicin-based first-line regimen, the efficacy is not sufficient. Trabectedin, eribulin, and pazopanib are the candidates of the second-line chemotherapy for advanced STS, although there is no clear evidence showing which is better among those agents. The purpose of this clinical trial conducted by Bone and Soft Tissue Tumor Study Group of Japan Clinical Oncology Group (JCOG) is to determine the most promising regimen among trabectedin, eribulin and pazopanib as the test arm regimen in the future phase III trial of the second-line treatment for patients with advanced STS. Methods: The study, JCOG1802, is a multicenter, selection design, randomized phase II trial comparing trabectedin (1.2 mg/m² IV, every 3 weeks), eribulin (1.4 mg/m² IV, days 1 and 8, every 3 weeks) and pazopanib (800 mg PO, everyday) for patients with unresectable or metastatic STS refractory to doxorubicin-based first-line chemotherapy. Eligibility criteria include 16 year-old or older, unresectable and/or metastatic STS, an exacerbation within 6 months prior to registration, histological diagnosis of STS other than Ewing sarcoma, well-differentiated liposarcoma and myxoid liposarcoma, a history of chemotherapy for STS other than doxorubicin-based regimen, ECOG (Eastern Cooperative Oncology Group) performance status 0 to 2, and sufficient organ function. Primary endpoint is progression-free survival (PFS), and secondary endpoints include overall survival, disease-control rate, response rate, and adverse events. To select the most promising regimen in median PFS (3 months in the worst regimen and 4 months in the best regimen) with a probability of at least 80%, a total of 120 patients will be enrolled from 37 institutions in Japan. After JCOG1802, a subsequent phase III trial comparing the winner of this study and a combination of gemcitabine and docetaxel will be planned. The study was activated at December 5, 2019 and 22 of planned 120 patients have been enrolled as of February 15, 2021. Clinical trial information: jRCTs031190152.

DOI： 10.1200/jco.2021.39.15_suppl.tps11580

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Prevalence of Psychological Distress and Its Risk Factors in Patients with Primary Bone and Soft Tissue Tumors. International journal

Masato Ise, Eiji Nakata, Yoshimi Katayama, Masanori Hamada, Toshiyuki Kunisada, Tomohiro Fujiwara, Ryuichi Nakahara, Shouta Takihira, Kohei Sato, Yoshiteru Akezaki, Masuo Senda, Toshifumi Ozaki

Healthcare (Basel, Switzerland) 9 ( 5 ) 2021.5

Authorship：Last author Language：English Publishing type：Research paper (scientific journal)

Psychological distress is common in patients with soft tissue and bone tumors. We first investigated its frequency and the associated risk factors in patients with pre-operative bone and soft tissue tumors. Participants included 298 patients with bone and soft tissue tumors who underwent surgery in our institution between 2015 and 2020. Psychological distress was evaluated by the Distress and Impact Thermometer (DIT) that consists of two types of questions (questions about the severity of the patient's distress (DIT-D) and its impact (DIT-I)). We used a cut-off point of 4 on the DIT-D and 3 on the DIT-I for screening patients with psychological distress. We therefore investigated: (1) the prevalence of psychological distress as assessed with DIT or distress thermometer (DT), which can be decided by DIT-D ≥ 4, (2) what are the risk factors for the prevalence of psychological distress, and (3) what is the number of patients who consulted a psychiatrist for psychological distress in patients with pre-operative bone and soft tissue tumors. With DIT and DT, we identified 64 patients (21%) and 95 patients (32%), respectively, with psychological distress. Multivariate logistic regression revealed that older age, sex (female), malignancy (malignant or intermediate tumor), a lower Barthel Index, and higher numeric rating scale were risk factors for psychological distress. Two patients (3%) consulted a psychiatrist after surgery. In conclusion, careful attention to psychological distress is needed, especially for female patients, older patients, and those with malignant soft or bone tissue tumors who have more than moderate pain.

DOI： 10.3390/healthcare9050566

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Comparison of posterior root remnant cells and horn cells of the medial meniscus. International journal

Ximing Zhang, Takayuki Furumatsu, Yuki Okazaki, Takaaki Hiranaka, Haowei Xue, Keisuke Kintaka, Shinichi Miyazawa, Toshifumi Ozaki

Connective tissue research 1 - 10 2021.5

Authorship：Last author Language：English Publishing type：Research paper (scientific journal)

Purpose/Aim of the study: Previous studies have noted distinctions between medial meniscus posterior root and horn cells. However, the characteristics of root remnant cells have not been explored in detail. The purpose of this study was to evaluate the gene expression levels, proliferation, and resistance to mechanical stress of remnant and horn cells.Materials and Methods: Medial meniscus tissue samples were obtained from patients who underwent total or uni-compartmental knee arthroplasty. Cellular morphology, sry-type HMG box 9, type II collagen, and chondromodulin-I gene expression levels were analyzed. Collagen synthesis was assessed by immunofluorescence staining. Proliferation analysis after 4 h-cyclic tensile strain was performed.Results: Horn cells displayed triangular morphology, whereas root remnant cells appeared fibroblast-like. sry-type HMG box 9 mRNA expression levels were similar in both cells, but type II collagen and chondromodulin-I mRNA expressions were observed only in horn cells. The ratio of type II collagen-positive cells in horn cells was about 10-fold higher than that in root remnant cells, whereas the ratio of sry-type HMG box 9-positive cells was similar. A significant increase in proliferation was observed in root remnant cells compared to that in horn cells. Further, under cyclic tensile strain, the survival rate was higher in root remnant cells than in horn cells.Conclusions: Medial meniscus root remnant cells showed higher proliferation and resistant properties to cyclic tensile strain than horn cells and showed no chondromodulin-I expression. Preserving the medial meniscus posterior root remnant during pullout repair surgery might maintain mechanical stress-resistant tissue and support healing.

DOI： 10.1080/03008207.2021.1920935

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A retro-odontoid pseudotumor treated with fixation and tumor resection by the lateral approach: illustrative case. International journal

Yoshiaki Oda, Takamitsu Tokioka, Toshifumi Ozaki

Journal of neurosurgery. Case lessons 1 ( 19 ) CASE20160 2021.5

Language：English

BACKGROUND: A retro-odontoid pseudotumor is not a condition that requires resection. However, pathological diagnosis is required when a tumor such as a meningeal tumor or chordoma is suspected. The authors report a case of a large lesion treated with posterior fixation and tumor resection using a lateral approach. OBSERVATIONS: A 77-year-old man visited the authors' department complaining of neck pain and decreased dexterity of the upper extremities. Magnetic resonance imaging showed a large, beak-shaped lesion behind the dens and severe compression of the spinal cord. Surgery consisted of occipitocervical-C2 fixation, followed by tumor resection with a left lateral approach. The pathological diagnosis was consistent with a retro-odontoid pseudotumor. The tumor was resected to a relatively large extent and shrank over time, leading to complete disappearance. LESSONS: Pathological examination is also possible with a posterior approach if the tumor can be reached through the lateral edge of the dura. In that situation, the amount of resection is limited, and there is a risk of spinal cord compression. Intradural dissemination of tumors is a concern with the transdural approach. If tumor resection by the posterior approach is difficult, the lateral approach can facilitate tumor resection.

DOI： 10.3171/CASE20160

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Risk factors of postoperative delayed wound healing in patients with rheumatoid arthritis treated with a biological agent. International journal

Shunji Okita, Hajime Ishikawa, Asami Abe, Satoshi Ito, Kiyoshi Nakazono, Akira Murasawa, Keiichiro Nishida, Toshifumi Ozaki

Modern rheumatology 31 ( 3 ) 587 - 592 2021.5

Authorship：Last author Language：English Publishing type：Research paper (scientific journal)

OBJECTIVES: This retrospective study aimed to investigate the risk factors associated with delayed wound healing (DWH) after orthopedic surgery in rheumatoid arthritis (RA) patients treated with biological disease-modifying antirheumatic drugs (bDMARDs). METHODS: We reviewed medical records of 276 orthopedic procedures for 187 RA patients treated with bDMARDs. As a preoperative nutritional status assessment, we evaluated body mass index, prognostic nutritional index (PNI), and controlling nutritional status (CONUT). We evaluated DAS28-CRP, DAS28-ESR, face scale, global health, and HAQ-DI to assess the disease activity. Univariate and multivariate logistic regression analyses were performed to evaluate the risk factors for DWH. RESULTS: In 276 procedures, DWH was identified in 24 patients (8.7%). Disease duration, foot and ankle surgery, and preoperative use of tocilizumab were significant in the univariate analyses. These variables were entered into a multivariate model, and it was revealed that preoperative use of tocilizumab and procedures in the foot and ankle were associated with an increased risk of DWH. CONCLUSION: The current retrospective study suggested that preoperative use of tocilizumab and procedures in the foot and ankle were risk factors for DWH.

DOI： 10.1080/14397595.2020.1790138

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Telomerase-specific oncolytic immunotherapy for promoting efficacy of PD-1 blockade in osteosarcoma. International journal

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

Cancer immunology, immunotherapy : CII 70 ( 5 ) 1405 - 1417 2021.5

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

Immune checkpoint inhibitors including anti-programmed cell death 1 (PD-1) antibody have recently improved clinical outcome in certain cancer patients; however, osteosarcoma (OS) patients are refractory to PD-1 blockade. Oncolytic virotherapy has emerged as novel immunogenic therapy to augment antitumor immune response. We developed a telomerase-specific replication-competent oncolytic adenovirus OBP-502 that induces lytic cell death via binding to integrins. In this study, we assessed the combined effect of PD-1 blockade and OBP-502 in OS cells. The expression of coxsackie and adenovirus receptor (CAR), integrins αvβ3 and αvβ5, and programmed cell death ligand 1 (PD-L1) was analyzed in two murine OS cells (K7M2, NHOS). The cytopathic activity of OBP-502 in both cells was analyzed using the XTT assay. OBP-502-induced immunogenic cell death was assessed by analyzing the level of extracellular ATP and high-mobility group box protein B1 (HMGB1). Subcutaneous tumor models for K7M2 and NHOS cells were used to evaluate the antitumor effect and number of tumor-infiltrating CD8+ cells in combination therapy. K7M2 and NHOS cells showed high expression of integrins αvβ3 and αvβ5, but not CAR. OBP-502 significantly suppressed the viability of both cells, in which PD-L1 expression and the release of ATP and HMGB1 were significantly increased. Intratumoral injection of OBP-502 significantly augmented the efficacy of PD-1 blockade on subcutaneous K2M2 and NHOS tumor models via enhancement of tumor-infiltrating CD8+ T cells. Our results suggest that telomerase-specific oncolytic virotherapy is a promising antitumor strategy to promote the efficacy of PD-1 blockade in OS.

DOI： 10.1007/s00262-020-02774-7

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High body mass index is a risk factor for unfavorable clinical outcomes after medial meniscus posterior root repair in well-aligned knees.

Ximing Zhang, Takayuki Furumatsu, Yuki Okazaki, Takaaki Hiranaka, Yuya Kodama, Haowei Xue, Yoshiki Okazaki, Toshifumi Ozaki

Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association 26 ( 3 ) 430 - 434 2021.5

Authorship：Last author Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Severe chondral lesions and varus knee alignment are associated with poor outcomes following transtibial pullout repair for medial meniscus posterior root tears and meniscus tear is strongly associated with body mass index. The prognostic factors in well-aligned knees (femorotibial angle < 180°) with mild chondral lesions are unknown. Therefore, we investigated the prognostic factors in these patients. We hypothesized that high body mass index would lead to poor clinical outcomes following pullout repair of medial meniscus posterior root tears. METHODS: We retrospectively reviewed the files of 28 patients who had undergone pullout repair of medial meniscus posterior root tears between October 2016 and December 2017. We recorded the baseline characteristics (age, gender, height, weight, and body mass index) and the time between injury and surgery. We recorded the International Knee Documentation Committee scores, Knee injury and Osteoarthritis Outcome Scores, and pain visual analog scale scores. Using magnetic resonance imaging preoperatively and 1 year after surgery, we measured the medial meniscus body width and absolute and relative medial meniscus extrusion. Pearson correlation and multivariate linear regression analyses were used to assess potential associations between these factors and clinical outcomes. RESULTS: Age positively correlated (coefficient = 0.49, P < 0.01) and body mass index negatively correlated with the postoperative International Knee Documentation Committee score (coefficient = -0.64, P < 0.01). In multivariate linear regression analysis, body mass index was a significant factor leading to poor postoperative International Knee Documentation Committee score (R2 = 0.29, P < 0.05). CONCLUSIONS: Body mass index > 30 kg/m2 is a risk factor for unfavorable clinical outcomes following pullout repair of medial meniscus posterior root tears in well-aligned knees. LEVEL OF EVIDENCE: III, Comparative retrospective study.

DOI： 10.1016/j.jos.2020.04.018

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周術期のリハビリテーション医療

千田益生, 濱田全紀, 堅山佳美, 伊勢真人, 本郷匡一, 尾崎敏文

The Japanese Journal of Rehabilitation Medicine 58 ( 特別号 ) SL41 - SL41 2021.5

脊椎転移に対する集学的治療麻痺を認めない脊椎SREに対する保存的治療の成績

中田英二, 国定俊之, 藤原智洋, 尾崎敏文

The Japanese Journal of Rehabilitation Medicine 58 ( 特別号 ) JSY39 - 1 2021.5

中等度特発性手根管症候群患者に対する、電気生理学的検査による機能的予後予測の検討

伊勢真人, 本郷匡一, 堅山佳美, 濱田全紀, 千田益生, 尾崎敏文

The Japanese Journal of Rehabilitation Medicine 58 ( 特別号 ) 3 - 2 2021.5

肺癌・食道癌患者の術前におけるがんロコモ・サルコペニアの発生頻度

堅山佳美, 千田益生, 濱田全紀, 中田英二, 伊勢真人, 本郷匡一, 尾崎敏文

The Japanese Journal of Rehabilitation Medicine 58 ( 特別号 ) 2 - 9 2021.5

65歳以下の慢性疼痛患者におけるロコモティブシンドロームと体組成及び運動機能評価

辻寛謙, 三澤治夫, 千田益生, 西田圭一郎, 濱田全紀, 堅山佳美, 鉄永智紀, 小田孔明, 伊勢真人, 梶木裕矢, 尾崎敏文

The Japanese Journal of Rehabilitation Medicine 58 ( 特別号 ) 2 - 7 2021.5

慢性疼痛患者に対するロコモティブシンドローム診断における診断時の特徴及び注意点

辻寛謙, 三澤治夫, 千田益生, 西田圭一郎, 濱田全紀, 堅山佳美, 鉄永智紀, 小田孔明, 伊勢真人, 梶木裕矢, 尾崎敏文

The Japanese Journal of Rehabilitation Medicine 58 ( 特別号 ) 2 - 6 2021.5

周術期のリハビリテーション医療

千田益生, 濱田全紀, 堅山佳美, 伊勢真人, 本郷匡一, 尾崎敏文

The Japanese Journal of Rehabilitation Medicine 58 ( 特別号 ) SL41 - SL41 2021.5

中等度特発性手根管症候群患者に対する、電気生理学的検査による機能的予後予測の検討

伊勢真人, 本郷匡一, 堅山佳美, 濱田全紀, 千田益生, 尾崎敏文

The Japanese Journal of Rehabilitation Medicine 58 ( 特別号 ) 3 - 2 2021.5

肺癌・食道癌患者の術前におけるがんロコモ・サルコペニアの発生頻度

堅山佳美, 千田益生, 濱田全紀, 中田英二, 伊勢真人, 本郷匡一, 尾崎敏文

The Japanese Journal of Rehabilitation Medicine 58 ( 特別号 ) 2 - 9 2021.5

65歳以下の慢性疼痛患者におけるロコモティブシンドロームと体組成及び運動機能評価

辻寛謙, 三澤治夫, 千田益生, 西田圭一郎, 濱田全紀, 堅山佳美, 鉄永智紀, 小田孔明, 伊勢真人, 梶木裕矢, 尾崎敏文

The Japanese Journal of Rehabilitation Medicine 58 ( 特別号 ) 2 - 7 2021.5

慢性疼痛患者に対するロコモティブシンドローム診断における診断時の特徴及び注意点

辻寛謙, 三澤治夫, 千田益生, 西田圭一郎, 濱田全紀, 堅山佳美, 鉄永智紀, 小田孔明, 伊勢真人, 梶木裕矢, 尾崎敏文

The Japanese Journal of Rehabilitation Medicine 58 ( 特別号 ) 2 - 6 2021.5

脊椎転移に対する集学的治療麻痺を認めない脊椎SREに対する保存的治療の成績

中田英二, 国定俊之, 藤原智洋, 尾崎敏文

The Japanese Journal of Rehabilitation Medicine 58 ( 特別号 ) JSY39 - 1 2021.5

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Papers - OZAKI Toshifumi