Faculty Profiles - OZAKI Toshifumi

Papers - OZAKI Toshifumi

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Transtibial pullout repair techniques using two simple stitches for medial meniscus posterior root tear can prevent the progression of medial meniscus extrusion and obtain successful outcomes. International journal

Takaaki Hiranaka, Takayuki Furumatsu, Shinichi Miyazawa, Yuki Okazaki, Keisuke Kintaka, Yuya Kodama, Yusuke Kamatsuki, Toshifumi Ozaki

European journal of orthopaedic surgery & traumatology : orthopedie traumatologie 2021.6

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

PURPOSE: Transtibial pullout repairs using two simple stitches (TSS) and a combination of TSS with posteromedial pullout repair (TSS + PMP) using an all-inside meniscal repair device have been reported previously for the treatment of medial meniscus (MM) posterior root tears. This study aimed to investigate the postoperative clinical outcomes of these techniques including MM extrusion (MME). METHODS: Fifty-two patients who underwent transtibial pullout repair were investigated and divided into TSS (n = 27) and TSS + PMP (n = 25) groups. The clinical outcomes were assessed using the Lysholm knee score and Knee Injury and Osteoarthritis Outcome Score 1 year postoperatively and compared between two groups. MME was measured using magnetic resonance imaging at 1 year postoperatively and compared between two groups. RESULTS: A significant improvement in each clinical score was observed in both groups, and no significant difference was seen in clinical outcomes. Moreover, no significant difference in postoperative MME was observed in both groups (TSS and TSS + PMP: 3.5 mm and 3.8 mm, respectively). Though no significant progression of MME was observed in TSS group, a significant progression of it was observed in TSS + PMP group postoperatively. CONCLUSIONS: This study demonstrated that both techniques improved clinical outcomes in the short-term postoperative period. However, MME was progressed significantly in TSS + PMP group 1 year postoperatively, which indicated that PMP might not be a useful additional procedure for reducing the postoperative MME.

DOI： 10.1007/s00590-021-03035-8

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Adrenergic signaling promotes the expansion of cancer stem-like cells of malignant peripheral nerve sheath tumors. International journal

Rongsheng Huang, Atsushi Fujimura, Eiji Nakata, Shota Takihira, Hirofumi Inoue, Soichiro Yoshikawa, Takeshi Hiyama, Toshifumi Ozaki, Atsunori Kamiya

Biochemical and biophysical research communications 557 199 - 205 2021.6

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

Malignant peripheral nerve sheath tumor (MPNST), a highly malignant tumor that arises in peripheral nerve tissues, is known to be highly resistant to radiation and chemotherapy. Although there are several reports on genetic mutations and epigenetic changes that define the pathogenesis of MPNST, there is insufficient information regarding the microenvironment that contributes to the malignancy of MPNST. In the present study, we demonstrate that adrenaline increases the cancer stem cell population in MPNST. This effect is mediated by adrenaline stimulation of beta-2 adrenergic receptor (ADRB2), which activates the Hippo transducer, YAP/TAZ. Inhibition and RNAi experiments revealed that inhibition of ADRB2 attenuated the adrenaline-triggered activity of YAP/TAZ and subsequently attenuated MPNST cells stemness. Furthermore, ADRB2-YAP/TAZ axis was confirmed in the MPNST patients' specimens. The prognosis of patients with high levels of ADRB2 was found to be significantly worse. These data show that adrenaline exacerbates MPNST prognosis and may aid the development of new treatment strategies for MPNST.

DOI： 10.1016/j.bbrc.2021.03.172

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Clinical outcome of patients with recurrent or refractory localized Ewing's sarcoma family of tumors: A retrospective report from the Japan Ewing Sarcoma Study Group. International journal

Katsutsugu Umeda, Takako Miyamura, Kenji Yamada, Hideki Sano, Ako Hosono, Minako Sumi, Hajime Okita, Tadashi Kumamoto, Akira Kawai, Junya Hirayama, Ryoji Jyoko, Akihisa Sawada, Hideki Nakayama, Yosuke Hosoya, Naoko Maeda, Nobuyuki Yamamoto, Chihaya Imai, Daiichiro Hasegawa, Motoaki Chin, Toshifumi Ozaki

Cancer reports (Hoboken, N.J.) 4 ( 3 ) e1329 2021.6

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

BACKGROUND: Patients with Ewing's sarcoma family of tumors (ESFT) who experience relapse or progression have a poor prognosis. AIM: This study aimed to identify the prognostic and therapeutic factors affecting overall survival (OS) of patients with recurrent or refractory localized ESFT. METHODS AND RESULTS: Thirty-eight patients with localized ESFT who experienced first relapse or progression between 2000 and 2018 were retrospectively reviewed. The 5-year OS rate of the entire cohort was 48.3% (95% confidence interval, 29.9%-64.5%). Multivariate analysis of OS identified time to relapse or progression, but not stem cell transplantation (SCT), as the sole independent risk factor (hazard ratio, 35.8; P = .002). Among 31 patients who received salvage chemotherapy before local treatment, 21 received chemotherapy regimens that are not conventionally used for newly diagnosed ESFT. The objective response rate to first-line salvage chemotherapy was 55.2% in the 29 evaluable patients. Time to relapse or progression was significantly associated with response to first-line salvage chemotherapy (P = .006). CONCLUSIONS: The present study fails to demonstrate significant clinical benefit of SCT for recurrent or refractory localized ESFT. Recently established chemotherapy regimens may increase the survival rate of patients with recurrent or refractory localized ESFT while attenuating the beneficial effect of SCT.

DOI： 10.1002/cnr2.1329

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骨・軟部腫瘍のgermline findingsに対する遺伝子医療部門の取り組み

二川摩周, 中田英二, 十川麗美, 加藤芙美乃, 浦川優作, 河内麻里子, 山本英喜, 国定俊之, 平沢晃, 尾崎敏文

日本整形外科学会雑誌 95 ( 6 ) S1251 - S1251 2021.6

がんロコモの現状と課題遠隔転移のないがん患者における周術期のがんロコモの発生率とそのリスクファクター

堅山佳美, 中田英二, 明崎禎輝, 千田益生, 国定俊之, 濱田全紀, 尾崎敏文

日本整形外科学会雑誌 95 ( 6 ) S1298 - S1298 2021.6

がんロコモの現状と課題がんロコモ発生予防のための院内システムの構築

中田英二, 堅山佳美, 明崎禎輝, 濱田全紀, 国定俊之, 藤原智洋, 千田益生, 尾崎敏文

日本整形外科学会雑誌 95 ( 6 ) S1241 - S1241 2021.6

DDH治療後の腸腰筋断面積の検討

佐藤嘉洋, 鉄永智紀, 山田和希, 廣瀬一樹, 尾崎敏文

日本小児整形外科学会雑誌 30 ( 1 ) 44 - 46 2021.6

Authorship：Last author Language：Japanese Publishing type：Research paper (scientific journal) Publisher：(一社)日本小児整形外科学会

発育性股関節形成不全(以下、DDH)に対して、当院では観血的整復術(広範囲展開法:田邊法、以下、OR)の適応を保存的整復不成功例や歩行開始後の診断遅延例とし、ORで腸腰筋前方移行を行っている。本研究の目的は、腸腰筋の断面積をOR群とRiemenbuegel装具による保存的整復(以下、CR)群で比較し、ORにおける腸腰筋前方移行の影響を明らかにすることである。対象はDDH症例26例26股(女:男23:3)。OR群13例、CR群13例、CT axial viewで、S2椎間孔、臼蓋上縁、恥骨結合の各高位で腸腰筋断面積の健側に対する患側の割合(以下、%Area)を求め、OR群とCR群で比較した。結果、各高位の%Area(%)はOR群で有意に小さく、腸腰筋前方移行により長期的には腸腰筋のボリュームが低下していた。腸腰筋の機能として股関節屈曲、腰椎屈曲、側屈に加え姿勢制御がある。最終観察時に症状はなかったが、長期的には腰痛等生じる可能性はあり、注意深い経過観察が必要である。(著者抄録)

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人工知能による骨肉腫X線像読影システム

長谷井嬢, 中原龍一, 板野拓人, 沖田駿治, 三宅孝昌, 杉本佳久, 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 95 ( 6 ) S1250 - S1250 2021.6

前腕に発生した肉腫の治療成績

畑利彰, 佐藤浩平, 近藤宏也, たき平将太, 藤原智洋, 中田英二, 国定俊之, 尾崎敏文

日本整形外科学会雑誌 95 ( 6 ) S1354 - S1354 2021.6

肉腫の心臓転移

板野拓人, 中田英二, 国定俊之, 藤原智洋, 尾崎敏文

日本整形外科学会雑誌 95 ( 6 ) S1389 - S1389 2021.6

がん遺伝子パネルによる肉腫における融合遺伝子の検出

佐藤浩平, 中田英二, 近藤宏也, 畑利彰, たき平将太, 藤原智洋, 国定俊之, 尾崎敏文

日本整形外科学会雑誌 95 ( 6 ) S1269 - S1269 2021.6

がんゲノム中核拠点病院における肉腫のがんゲノム医療

中田英二, 国定俊之, 藤原智洋, 尾崎敏文

日本整形外科学会雑誌 95 ( 6 ) S1252 - S1252 2021.6

肉腫における免疫療法

たき平将太, 佐藤浩平, 畑利彰, 近藤宏也, 中田英二, 藤原智洋, 国定俊之, 尾崎敏文

日本整形外科学会雑誌 95 ( 6 ) S1338 - S1338 2021.6

寛骨臼を含む骨盤発生Ewing肉腫に対する英国集約化施設における治療変遷とその成績

藤原智洋, Stevenson Jonathan, Parry Michael, 津田祐輔, 中田英二, 国定俊之, 尾崎敏文, Grimer Robert, Jeys Lee

日本整形外科学会雑誌 95 ( 6 ) S1272 - S1272 2021.6

NICE軟部肉腫ガイドラインは英国における軟部肉腫患者の診療体制や生存予後にどのような影響を与えたか

藤原智洋, Grimer Robert, Evans Scott, 津田祐輔, 中田英二, 国定俊之, 尾崎敏文, Abudu Adesegun

日本整形外科学会雑誌 95 ( 6 ) S1371 - S1371 2021.6

骨肉腫における腫瘍関連マクロファージの臨床病理学的意義

近藤宏也, 藤原智洋, 吉田晶, 佐藤浩平, 畑利彰, たき平将太, 中田英二, 国定俊之, 尾崎敏文

日本整形外科学会雑誌 95 ( 6 ) S1410 - S1410 2021.6

Postoperative computed tomography assessment of anteromedial cortex reduction is a predictor for reoperation after intramedullary nail fixation for pertrochanteric fractures. International journal

Norio Yamamoto, Takahiro Imaizumi, Tomoyuki Noda, Tomoo Inoue, Keisuke Kawasaki, Toshifumi Ozaki

European journal of trauma and emergency surgery : official publication of the European Trauma Society 2021.5

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

PURPOSE: Postoperative radiographs are routinely used to assess fracture reduction following intramedullary nail fixation for pertrochanteric fractures, even though computed tomography (CT) is a superior modality. We aimed to determine the association between reduction quality assessed by CT and rates of reoperation and to evaluate the association of reoperation and reduction quality according to the assessment modality (plain radiographs vs. CT). METHODS: A retrospective analysis of 299 consecutive patients treated with intramedullary nail fixation for pertrochanteric fractures was conducted. Fracture reduction measured by postoperative radiographs and CT was categorized as anatomical type, extramedullary type, or intramedullary type. Postoperative data for analysis included reduction status, tip-apex distance (TAD), screw position in the femoral head, sliding distance, and conditions associated with reoperation. RESULTS: Of the 299 patients included with a mean age of 83.1 ± 8.2 years, there were six patients who required reoperation (2.0%). According to the CT assessments, there were 42 intramedullary reductions (14.0%). Patients with a non-intramedullary reduction based on postoperative CT images were significantly more likely to have proper placement of the screw, a reduced TAD, a reduced sliding distance, and a lower reoperation rate than those with an intramedullary reduction (P < 0.05). The reduction quality assessed by postoperative CT was significantly associated with reoperation (95% CI, 1.45-29.31). CONCLUSIONS: Intramedullary reduction assessed by CT was associated with reoperation. The reduction quality based on CT findings was more predictive for reoperation than that from plain radiographs.

DOI： 10.1007/s00068-021-01718-9

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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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Papers - OZAKI Toshifumi