Faculty Profiles - OZAKI Toshifumi

Papers - OZAKI Toshifumi

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Alveolar soft part sarcoma: progress toward improvement in survival? A population-based study. International journal

Tomohiro Fujiwara, Eiji Nakata, Toshiyuki Kunisada, Toshifumi Ozaki, Akira Kawai

BMC cancer 22 ( 1 ) 891 - 891 2022.8

Language：English Publishing type：Research paper (scientific journal) Publisher：Springer Science and Business Media LLC

BACKGROUND: Alveolar soft part sarcoma (ASPS) is a rare histological subtype of soft-tissue sarcoma, which remains refractory to conventional cytotoxic chemotherapy. We aimed to characterize ASPS and investigate whether the oncological outcome has improved over the past decade. METHODS: One hundred and twenty patients with newly diagnosed ASPS from 2006 to 2017, identified from the Bone and Soft-Tissue Tumor Registry in Japan, were analyzed retrospectively. RESULTS: The study cohort comprised 34 (28%) patients with localized ASPS and 86 (72%) with metastatic disease at presentation. The 5-year disease-specific survival (DSS) was 68% for all patients and 86% and 62% for localized and metastatic disease, respectively (p = 0.019). Metastasis at presentation was the only adverse prognostic factor for DSS (hazard ratio [HR]: 7.65; p = 0.048). Patients who were > 25 years (80%; p = 0.023), had deep-seated tumors (75%; p = 0.002), and tumors > 5 cm (5-10 cm, 81%; > 10 cm, 81%; p < 0.001) were more likely to have metastases at presentation. In patients with localized ASPS, adjuvant chemotherapy or radiotherapy did not affect survival, and 13 patients (45%) developed distant metastases in the lung (n = 12, 92%) and brain (n = 2, 15%). In patients with metastatic ASPS (lung, n = 85 [99%]; bone, n = 12 [14%]; and brain n = 9 [11%]), surgery for the primary or metastatic site did not affect survival. Prolonged survival was seen in patients who received pazopanib treatment (p = 0.045), but not in those who received doxorubicin-based cytotoxic chemotherapy. Overall, improved DSS for metastatic ASPS has been observed since 2012 (5-year DSS, from 58 to 65%) when pazopanib was approved for advanced diseases, although without a statistically significant difference (p = 0.117). CONCLUSION: The national study confirmed a unique feature of ASPS with frequent metastasis to the lung and brain but an indolent clinical course. An overall trend toward prolonged survival after the introduction of targeted therapy encourages continuous efforts to develop novel therapeutic options for this therapeutically resistant soft-tissue sarcoma.

DOI： 10.1186/s12885-022-09968-5

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Other Link： https://link.springer.com/article/10.1186/s12885-022-09968-5/fulltext.html

Risk Factors for Infection Following Operative Treatment of Traumatic Upper Extremity Amputation Injury. International journal

Taichi Saito, Takenori Uehara, Ryuichi Nakahara, Yasunori Shimamura, Atsunori Nakao, Toshifumi Ozaki

The journal of hand surgery Asian-Pacific volume 27 ( 4 ) 691 - 697 2022.8

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

Background: Identification of the risk factors for surgical site infection (SSI) can be a straightforward and cost-effective measure to reduce or prevent the occurrence of SSI. However, there are no studies that revealed risk factors for SSI for traumatic upper extremity amputation. The aim of this study is to investigate the risk factors that promote SSI after surgery for traumatic upper extremity amputation using a large nationwide database. Methods: We used data from the Japan Trauma Data Bank. Diagnoses were defined using the Abbreviated Injury Scale code. We applied multivariate logistic regression to evaluate the infection risk factor. We chose age, sex, vital signs, cause and type of trauma, concomitant injury, diabetes, amputation level, Glasgow coma scale, Injury Severity Score (ISS) and blood transfusion within 24 hours following hospital arrival as confounders. Receiver operating characteristic (ROC) curve analysis was adopted to identify thresholds for change in infection risk. We also applied propensity score (PS) matching to adjust for confounding factors that may affect the outcome. Results: A total of 1,150 patients (967 males, 183 females) had traumatic upper extremity amputation. The mean patient age was 46.5 years. A total of 21 patients (1.8%) suffered from SSI. ISS, blood transfusion, systolic blood pressure (BP) and the upper extremity amputation except for finger were identified as the independent significant risk factors for SSI occurrence by the multivariate analysis (p < 0.05, p < 0.005, p < 0.05 and p < 0.005, respectively). ROC modelling revealed that patients with ISS of over 9 or systolic BP of over 160 had a risk for SSI. After PS matching, the patients with blood transfusion or systolic BP of over 160 had a significantly higher risk of infection (OR 9.0; p = 0.01 and OR 7.0; p = 0.03, respectively). Conclusions: In treating patients with these risk factors, we must be especially careful in performing thorough debridement and wound care. Level of Evidence: Level II (Therapeutic).

DOI： 10.1142/S2424835522500709

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Late-onset implant-related neuropathy: Three years after proximal humeral fracture. International journal

Yasuaki Yamakawa, Yusuke Kamatsuki, Toshiyuki Matsumoto, Tomoyuki Noda, Toshifumi Ozaki

Trauma case reports 40 100670 - 100670 2022.8

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

There are currently no reports of implant-related neuropathy associated with humeral proximal fracture surgery. Herein, we report a case of implant-related late-onset neuropathy that developed 3 years after proximal humeral fracture surgery. A 51-year-old man underwent minimally invasive plate osteosynthesis for a left proximal humeral fracture 3 years prior. Left upper limb pain and reduced angle of elevation of the shoulder were recognized 1 month before the outpatient consultation. Numbness was noted on the ulnar side of the hand, and radiating pain to the ulnar nerve region was noted during shoulder abduction and compression of the medial side of the upper arm. Computed tomography revealed close proximity of the neurovascular bundle to the locking screw along with muscle atrophy around the shoulder. Hence, the patient was diagnosed with neuropathy. After implant removal, the pain in the ulnar nerve region improved, and the upper arm could be elevated. In our case, the cause of muscle atrophy was axillary nerve manipulation and cervical myelopathy caused by the operation. When late-onset neuropathy occurs, implant-related neuropathy with muscle atrophy should be considered.

DOI： 10.1016/j.tcr.2022.100670

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Perioperative Adriamycin plus ifosfamide vs. gemcitabine plus docetaxel for high-risk soft tissue sarcomas: randomised, phase II/III study JCOG1306. International journal

Kazuhiro Tanaka, Ryunosuke Machida, Akira Kawai, Robert Nakayama, Satoshi Tsukushi, Kunihiro Asanuma, Yoshihiro Matsumoto, Hiroaki Hiraga, Koji Hiraoka, Munenori Watanuki, Tsukasa Yonemoto, Satoshi Abe, Hirohisa Katagiri, Yoshihiro Nishida, Akihito Nagano, Yoshiyuki Suehara, Hiroyuki Kawashima, Masanori Kawano, Takeshi Morii, Hiroshi Hatano, Junya Toguchida, Tomotake Okuma, Masanobu Takeyama, Satoshi Takenaka, Toshihiro Akisue, Taisuke Furuta, Makoto Emori, Toru Hiruma, Hidetatsu Outani, Tetsuji Yamamoto, Tomoko Kataoka, Haruhiko Fukuda, Toshifumi Ozaki, Yukihide Iwamoto

British journal of cancer 127 ( 8 ) 1487 - 1496 2022.7

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

BACKGROUND: This randomised phase II/III trial aimed to determine whether perioperative chemotherapy with gemcitabine plus docetaxel (GD) is non-inferior to the standard Adriamycin plus ifosfamide (AI) in terms of overall survival (OS) in patients with soft tissue sarcoma (STS). METHODS: Patients with localised high-risk STS in the extremities or trunk were randomised to receive AI or GD. The treatments were repeated for three preoperative and two postoperative courses. The primary endpoint was OS. RESULTS: Among 143 enrolled patients who received AI (70 patients) compared to GD (73 patients), the estimated 3-year OS was 91.4% for AI and 79.2% for GD (hazard ratio 2.55, 95% confidence interval: 0.80-8.14, P = 0.78), exceeding the prespecified non-inferiority margin in the second interim analysis. The estimated 3-year progression-free survival was 79.1% for AI and 59.1% for GD. The most common Grade 3-4 adverse events in the preoperative period were neutropenia (88.4%), anaemia (49.3%), and febrile neutropenia (36.2%) for AI and neutropenia (79.5%) and febrile neutropenia (17.8%) for GD. CONCLUSIONS: Although GD had relatively mild toxicity, the regimen-as administered in this study-should not be considered a standard treatment of perioperative chemotherapy for high-risk STS in the extremities and trunk. CLINICAL TRIAL REGISTRATION: jRCTs031180003.

DOI： 10.1038/s41416-022-01912-5

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Evaluation of SARC-F and SARC-CalF for sarcopenia screening in patients with chronic musculoskeletal pain: A prospective cross-sectional study. International journal

Hironori Tsuji, Tomoko Tetsunaga, Tomonori Tetsunaga, Haruo Misawa, Yoshiaki Oda, Shinichiro Takao, Keiichiro Nishida, Toshifumi Ozaki

Medicine 101 ( 29 ) e29568 2022.7

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

OBJECTIVES: Early sarcopenia detection using screening tools, such as SARC-F and SARC-CalF, has been proven reliable. However, the relationship between chronic musculoskeletal pain with sarcopenia is unknown. This study assessed sarcopenia morbidity as well as the reliability of sarcopenia screening with SARC-F and SARC-CalF in patients with chronic musculoskeletal pain. METHODS: Overall, 172 patients with chronic musculoskeletal pain were included in this cross-sectional study. All participants completed the SARC-F, SARC-CalF, numeric rating scale (NRS), and pain disability assessment scale (PDAS) assessments. Sarcopenia was diagnosed using the Asian Working Group for Sarcopenia criteria 2019. Correlations between SARC-F and SARC-CalF scores and each measured variable were evaluated using univariate and multiple linear regression analyses. A receiver operating characteristic curve analysis was conducted, and reliabilities of SARC-F and SARC-CalF scores for diagnosing sarcopenia were compared. RESULTS: Thirty-nine patients were diagnosed with sarcopenia. Among these, 10 patients were <65 years old, and 29 were >65 years old. Both SARC-F and SARC-CalF scores significantly correlated with grip power, gait speed, skeletal mass index, numeric rating scale score, and PDAS score. In multiple linear regression analysis, SALC-F and SALC-CalF scores significantly correlated with PDAS score, skeletal mass index, and gait speed. The area under the curve were 0.70 for SARC-F and 0.88 for SARC-CalF; SARC-CalF had a significantly higher area under the curve than SARC-F. DISCUSSION: Sarcopenia was diagnosed in patients aged <65 years with chronic musculoskeletal pain. SALC-F and SARC-CalF scores showed a significant correlation with disability due to pain and were reliable sarcopenia screening tools for chronic musculoskeletal pain. SARC-CalF was more reliable than SARC-F.

DOI： 10.1097/MD.0000000000029568

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Arthroscopic Meniscal Healing following Medial Meniscus Posterior Root Repair: A Comparison between Two Suture Materials. International journal

Yuki Okazaki, Takayuki Furumatsu, Takaaki Hiranaka, Ximing Zhang, Keisuke Kintaka, Naohiro Higashihara, Masanori Tamura, Yuya Kodama, Yusuke Kamatsuki, Toshifumi Ozaki

The journal of knee surgery 2022.7

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

Recently, transtibial pullout repair of the medial meniscus (MM) posterior root tear (PRT) has become widely accepted and provides satisfactory clinical outcomes. Widening after cyclic loading or ultimate failure load using different suture materials and configurations has been studied. However, no study has compared the clinical outcomes using different suture materials. This study aimed to evaluate the clinical outcomes after performing MMPRT pullout repair using different suture materials. We hypothesized that better clinical outcomes would be achieved using ultra-high molecular weight polyethylene (UHMWPE) tape compared with a normal polyester suture. Thirty-seven patients who underwent MM posterior root repair between November 2019 and May 2020 were retrospectively investigated. Pullout repair was performed using a hollow no. 0 polyester suture (n = 14) and UHMWPE tape (n = 23). Clinical outcomes were assessed preoperatively and at 1 year postoperatively, using the Lysholm knee score, Knee Injury and Osteoarthritis Outcome Score, and visual analogue scale (VAS) pain score. The meniscal healing status was assessed using an arthroscopic scoring system (range: 0-10). All clinical scores were improved significantly in both groups. However, significantly higher meniscal healing scores and decreased VAS pain scores were observed in the UHMWPE group (7.3 ± 0.9 and 7.7 ± 11.3, respectively) than in the polyester group (5.6 ± 2.1 and 18.4 ± 18.6, respectively; p < 0.01). Suture cut-out and loss of the root continuity were observed in some cases (three cases [21.4%] in the polyester suture group and one case [4.3%] in the UHMWPE tape group). Both suture materials led to satisfactory clinical outcomes at 1 year postoperatively, whereas the UHMWPE tape was useful for obtaining good meniscal healing and decreasing the VAS pain score.

DOI： 10.1055/s-0042-1750047

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モジュラー型人工関節・骨軟部腫瘍領域感染腫瘍用人工関節の術後感染

中田英二, 藤原智洋, 国定俊之, 尾崎敏文

日本骨・関節感染症学会プログラム・抄録集 45回 108 - 108 2022.7

小児化膿性股関節炎に対するα-ディフェンシン検出キットの使用経験

小浦卓, 鉄永智紀, 山田和希, 佐藤嘉洋, 廣瀬一樹, 尾崎敏文

日本骨・関節感染症学会プログラム・抄録集 45回 224 - 224 2022.7

Larger sagittal inter-screw distance/tibial width ratio reduces delayed union or non-union after arthroscopic ankle arthrodesis. International journal

Suguru Yokoo, Kenta Saiga, Koji Demiya, Hideki Ohashi, Masahiro Horita, Toshifumi Ozaki

European journal of orthopaedic surgery & traumatology : orthopedie traumatologie 2022.6

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

BACKGROUND: Arthroscopic ankle arthrodesis (AAA) has risks of complications, such as delayed union and non-union. The number and direction of the inserted screws have been reported as important factors affecting the time to union of AAA. However, the ratio of inter-screw distance (ISD) to tibial width (TW) in different planes has not been investigated. Therefore, we aimed to explore the effect of this ratio on bone union following AAA. METHODS: We retrospectively enrolled 63 patients (64 ankles) undergoing AAA from 2013 to 2019. Then, their age, body mass index (BMI), sex, diabetes mellitus (DM) status, Takakura-Tanaka classification, number of screws and radiographic parameters were analysed. RESULTS: The patients had a mean age of 70.3 (range, 45-91) years. Bone fusion was achieved in 57 ankles (89%) in a mean period of 3.3 (range, 2-6) postoperative months. There were four cases of delayed union and three of non-union. No significant differences in age, BMI, sex, DM, Takakura-Tanaka classification, and number of screws could be detected between the groups. However, the sagittal ISD/TW ratio was significantly larger in the union group than in the delayed/non-union group with a cut-off value of 57.0%. CONCLUSION: Larger sagittal ISD/TW ratios result in reduced post-AAA delayed union or non-union. The surgeon should be aware that the anterior and posterior screw widths should be approximately 60% or more of the anteroposterior width of the tibia.

DOI： 10.1007/s00590-022-03307-x

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脛骨プラトー・骨幹部合併骨折の治療経験

福岡史朗, 依光正則, 佐藤浩平, 畑利彰, 上原健敬, 尾崎敏文

骨折 44 ( Suppl. ) S285 - S285 2022.6

The mechanosensitive ion channel PIEZO1 is expressed in tendons and regulates physical performance

Ryo Nakamichi, Shang Ma, Takayuki Nonoyama, Tomoki Chiba, Ryota Kurimoto, Hiroki Ohzono, Merissa Olmer, Chisa Shukunami, Noriyuki Fuku, Guan Wang, Errol Morrison, Yannis P. Pitsiladis, Toshifumi Ozaki, Darryl D’Lima, Martin Lotz, Ardem Patapoutian, Hiroshi Asahara

Science Translational Medicine 14 ( 647 ) 2022.6

Publishing type：Research paper (scientific journal) Publisher：American Association for the Advancement of Science (AAAS)

How mechanical stress affects physical performance via tendons is not fully understood. Piezo1 is a mechanosensitive ion channel, and E756del PIEZO1 was recently found as a gain-of-function variant that is common in individuals of African descent. We generated tendon-specific knock-in mice using R2482H Piezo1 , a mouse gain-of-function variant, and found that they had higher jumping abilities and faster running speeds than wild-type or muscle-specific knock-in mice. These phenotypes were associated with enhanced tendon anabolism via an increase in tendon-specific transcription factors, Mohawk and Scleraxis, but there was no evidence of changes in muscle. Biomechanical analysis showed that the tendons of R2482H Piezo1 mice were more compliant and stored more elastic energy, consistent with the enhancement of jumping ability. These phenotypes were replicated in mice with tendon-specific R2482H Piezo1 replacement after tendon maturation, indicating that PIEZO1 could be a target for promoting physical performance by enhancing function in mature tendon. The frequency of E756del PIEZO1 was higher in sprinters than in population-matched nonathletic controls in a small Jamaican cohort, suggesting a similar function in humans. Together, this human and mouse genetic and physiological evidence revealed a critical function of tendons in physical performance, which is tightly and robustly regulated by PIEZO1 in tenocytes.

DOI： 10.1126/scitranslmed.abj5557

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人工知能による骨肉腫X線読影システムの開発と骨端線認識への挑戦

長谷井嬢, 中原龍一, 国定俊之, 中澤慎二, 韓昌煕, 藏品豊, 木浪陽, 藤原一夫, 臼井正明, 尾崎敏文

日本整形外科学会雑誌 96 ( 6 ) S1333 - S1333 2022.6

Hip Fractures after Intramedullary Nailing Fixation for Atypical Femoral Fractures: Three Cases.

Norio Yamamoto, Tomoo Inoue, Yusuke Mochizuki, Tomoyuki Noda, Keisuke Kawasaki, Toshifumi Ozaki

Acta medica Okayama 76 ( 3 ) 317 - 321 2022.6

Authorship：Last author Language：English Publishing type：Research paper (bulletin of university, research institution)

Secondary hip fractures (SHFs) rarely occur after intramedullary nailing (IMN) fixation without femoral neck fixation for atypical femoral fractures (AFFs). We report three cases of older Japanese women who sustained SHFs presumably caused by osteoporosis and peri-implant stress concentration around the femoral neck after undergoing IMN without femoral neck fixation for AFF. All cases were fixed with malalignment. In AFF patients, postoperative changes due to postoperative femoral bone malalignment may affect the peri-implant mechanical environment around the femoral neck, which can result in insufficiency fractures. At the first AFF surgery, we recommend femoral neck fixation after adequate reduction is achieved.

DOI： 10.18926/AMO/63741

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遺伝性骨・軟部腫瘍外来の取り組み

中田英二, 藤原智洋, 国定俊之, 二川摩周, 平沢晃, 尾崎敏文

日本整形外科学会雑誌 96 ( 6 ) S1315 - S1315 2022.6