Faculty Profiles - OZAKI Toshifumi

Medial meniscus posterior root tear induces pathological posterior extrusion of the meniscus in the knee-flexed position: An open magnetic resonance imaging analysis Reviewed

S. Masuda, T. Furumatsu, Y. Okazaki, Y. Kodama, T. Hino, Y. Kamatsuki, S. Miyazawa, T. Ozaki

Revue de Chirurgie Orthopedique et Traumatologique 104 ( 4 ) 339 2018.6

Language：English Publishing type：Research paper (scientific journal) Publisher：Elsevier Masson SAS

DOI： 10.1016/j.rcot.2018.04.006

中高齢者原発性悪性骨腫瘍に対する補助化学療法の検討 JCOG骨軟部腫瘍グループアンケート結果より

Les l?sions de la racine post?rieure du m?nisque m?dial induisent une extrusion m?niscale post?rieure anormale en semi-flexion Reviewed International journal

Masuda S, Furumatsu T, Okazaki Y, Kodama Y, Hino T, Kamatsuki Y, Miyazawa S, Ozaki T

Revue de Chirurgie Orthopedique et Traumatologique, Revue de Chirurgie Orthopedique et Reparatrice de l'Appareil Moteur, Revue d'orthope?die et de chirurgie de l'appareil moteur 104 ( 4 ) 2018.6

永野昭仁, 松本誠一, 川井章, 大隈知威, 平賀博明, 松本嘉寛, 西田佳弘, 米本司, 保坂正美, 高橋満, 吉川秀樹, 尾崎敏文, 淺沼邦洋, 中紀文, 江森誠人, 久保忠彦, 川島寛之, 河本旭哉, 横山良平, 筑紫聡

日本整形外科学会雑誌 92 ( 6 ) S1408 - S1408 2018.6

骨肉腫の細胞内外microRNA-25-3p発現異常の腫瘍学的意義

吉田晶, 藤原智洋, 魚谷弘二, 森田卓也, 清野正普, 横尾賢, 長谷井嬢, 中田英二, 国定俊之, 尾崎敏文

日本整形外科学会雑誌 92 ( 6 ) S1460 - S1460 2018.6

骨転移治療に対する院内コンセンサス形成整形外科としての骨転移への関わりがん専門病院の立場から

杉原進介, 魚谷弘二, 中田英二, 尾崎敏文

日本整形外科学会雑誌 92 ( 6 ) S1509 - S1509 2018.6

Utility of Bayesian Single-Arm Design in New Drug Application for Rare Cancers in Japan: A Case Study of Phase 2 Trial for Sarcoma Reviewed

Akihiro Hirakawa, Tadaaki Nishikawa, Kan Yonemori, Taro Shibata, Kenichi Nakamura, Masashi Ando, Takafumi Ueda, Toshifumi Ozaki, Kenji Tamura, Akira Kawai, Yasuhiro Fujiwara

Therapeutic Innovation and Regulatory Science 52 ( 3 ) 334 - 338 2018.5

Language：English Publishing type：Research paper (scientific journal) Publisher：SAGE Publications Inc.

Investigational drugs for rare cancers are often approved based solely on a single-arm phase II trial that primarily evaluates response rate in Japan. Such trials typically use a fixed sample size determined on the basis of the frequentist manner. However, since predicting the speed of patient enrollment is challenging because of the disease rarity, the time needed to complete the enrollment of the fixed number of patients is prolonged in some cases. A Bayesian design without fixing the sample size is useful for single-arm phase II trials of rare cancers. However, the arbitrariness of prior distribution specifications and the frequentist operating characteristics are regulatory issues. We recently started a Bayesian single-arm phase II trial of nivolumab in patients with sarcoma for new drug application in Japan and examined the statistical rationale and design consideration. In the Bayesian design, we specify the minimum and maximum numbers of enrolled patients during the enrollment period and the prior distributions of response rates. Considering these parameters, we obtain the minimum number of responders needed for the positive conclusion of the efficacy of nivolumab for each sample size. Simulation studies demonstrated that the operating characteristics of this design would be acceptable from the frequentist view. The Bayesian design provided an adaptive decision rule for efficacy conclusion for the drug without fixing the sample size. We hope our trial’s success will provide a new drug development option for rare cancers in Japan.

DOI： 10.1177/2168479017728989

骨粗鬆性骨折患者における骨粗鬆治療薬の骨折予防効果システマティックレビュー

斎藤太一, 島村安則, 千田益生, 尾崎敏文

運動器リハビリテーション 29 ( 2 ) 249 - 249 2018.5

Relationship between displacement of the psoas major muscle and spinal alignment in patients with adult spinal deformity Reviewed

Yoshiaki Oda, Tomoyuki Takigawa, Ryo Ugawa, Yasuyuki Shiozaki, Haruo Misawa, Yoshihisa Sugimoto, Masato Tanaka, Toshifumi Ozaki

Asian Spine Journal 12 ( 2 ) 335 - 342 2018.4

Language：English Publishing type：Research paper (scientific journal) Publisher：Korean Society of Spine Surgery

Study Design: Cross sectional study. Purpose: To clarify the difference in position of the psoas muscle between adult spinal deformity (ASD) and lumbar spinal stenosis (LSS). Overview of Literature: Although it is known that the psoas major muscle deviates in ASD patients, no report is available regarding the difference in comparison with LSS patients. Methods: This study investigates 39 patients. For evaluating spinal alignment, pelvic tilt (PT), pelvic incidence (PI), sacral slope, lumbar lordosis (LL), PI-LL, Cobb angle, and the convex side, the lumbar curves were measured. For measuring the position of the psoas major at the L4/5 disk level, magnetic resonance imaging was used. The displacements of psoas major muscle were measured separately in the anterior-posterior and lateral directions. We examined the relationship between the radiographic parameters and anterior displacement (AD) and lateral displacement (LD) of the psoas major muscle. Results: AD was demonstrated in 15 cases with ASD and nine cases with LSS (p &gt
0.05). LD was observed in 13 cases with ASD and no cases with LSS (p &lt
0.01). The Cobb angle was significantly greater in cases with AD than in those without AD (p =0.04). PT, LL, PI- LL, and Cobb angle were significantly greater in cases with LD (p &lt
0.05). All cases with LD had AD, but no case without AD had LD (p &lt
0.001). The side of greater displacement at L4/5 and the convex side of the lumbar curve were consistent in all cases. Conclusions: Despite AD being observed in LSS as well, LD was observed only in the ASD group. Radiographic parameters were worse when LD was seen, rather than AD.

DOI： 10.4184/asj.2018.12.2.335

Clinical and Functional Significance of Intracellular and Extracellular microRNA-25-3p in Osteosarcoma. Reviewed

Yoshida A, Fujiwara T, Uotani K, Morita T, Kiyono M, Yokoo S, Hasei J, Nakata E, Kunisada T, Ozaki T

Acta medica Okayama 72 ( 2 ) 165 - 174 2018.4

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

Although there is considerable evidence indicating that the dysregulation of microRNAs (miRNAs) in malignant tumors plays a role in tumor development, the overall function of miRNAs and their clinicopathological significance are not well understood. In this retrospective analysis of 45 biopsy specimens from osteosarcoma (OS) patients, we investigated the functional and clinical significance of miR-25-3p in OS, which we previously identified as a highly expressed miRNA in OS patients' serum. We observed that miR-25-3p dysregulation in human OS tissues was negatively correlated with the clinical prognosis, whereas the expression level of its target gene, Dickkopf WNT Signaling Pathway Inhibitor 3 (DKK3), was positively correlated with the clinical prognosis. Endogenous miR-25-3p upregulation promoted tumor growth, invasion, and drug resistance, which was consistent with DKK3 silencing in OS cells. In addition, secretory miR-25-3p was embedded in tumor-derived exosomes, where it promoted capillary formation and the invasion of vascular endothelial cells. Overall, our results show that miR-25-3p has intracellular and extracellular oncogenic functions as well as clinicopathological relevance in OS, indicating its potential as a novel diagnostic and therapeutic tool for the clinical management of this disease.

DOI： 10.18926/AMO/55857

足関節脱臼骨折後遺残変形に対し腓骨延長を行った2例

雑賀建多, 大橋秀基, 堀田昌宏, 出宮光二, 横尾賢, 内野崇彦, 清野正普, 望月雄介, 小松原将, 吉村将秀, 中道亮, 山川泰明, 齋藤太一, 野田知之, 尾崎敏文

中国・四国整形外科学会雑誌 30 ( 1 ) 163 - 163 2018.4

脊椎に原発した骨肉腫の5例

塩崎泰之, 瀧川朋亨, 三澤治夫, 尾崎敏文, 中田英二, 国定俊之

中国・四国整形外科学会雑誌 30 ( 1 ) 79 - 82 2018.4

Language：Japanese Publisher：中国・四国整形外科学会

当院で経験した脊椎原発の骨肉腫5例(男性2例、女性3例、診断時平均年齢52歳)について検討した。発生高位はT1が1例、L2が1例、L3が1例、L5が2例であった。初診時の症状は腰椎発生の3例では全例に腰痛が認められ、2例に下肢不全麻痺が合併していた。胸椎発生の2例では、それぞれ背部痛と上肢痛を認められた。治療は全摘出術を2例、重粒子線治療を3例に行った。また、化学療法は4例に行った。予後は、治療中の2例を除き、3例は診断後平均66ヵ月で死亡していた。

Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2018&ichushi_jid=J02438&link_issn=&doc_id=20180621090018&doc_link_id=%2Fcm4ortho%2F2018%2F003001%2F018%2F0079-0082%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fcm4ortho%2F2018%2F003001%2F018%2F0079-0082%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

【運動器画像診療の最前線】部位別・疾患別画像診療の最前線骨腫瘍の画像診療

中田英二, 国定俊之, 長谷井嬢, 藤原智洋, 尾崎敏文

関節外科 37 ( 4月増刊 ) 130 - 143 2018.4

Language：Japanese Publisher：(株)メジカルビュー社

＜画像診療のポイント＞●骨腫瘍の診療において、画像検査は鑑別診断や治療効果判定だけではなく、手術にも有用である。●鑑別診断について、初診医は一般整形外科医であることが多く、悪性を疑う所見を見逃さないことが重要である。●骨腫瘍にはそれぞれ特徴的な年齢分布や好発部位があり、年齢や既往歴などの臨床情報も踏まえ、複数の画像検査の情報を組み合わせて診断を行う。●単純X線像の読影では、腫瘍の局在と性状に注目する。●CTは、単純X線検査では評価が困難な部位の診断、微細な石灰化や骨化の有無の検出などを調べるのに適している。また、三次元的に骨病変を評価することができ、術前計画にも有用である。さらに、近年はコンピュータ支援手術により術中に短時間で高画質の2D・3D画像が取得でき、画像データをナビゲーションシステムに送信することで、より低侵襲かつ安全で確実な手術が可能となっている。●MRIは優れたコントラスト分解能をもち、腫瘍の進展や質的診断、治療効果判定などに有用である。●PET/CTは、良悪性の鑑別診断、病期診断、治療効果判定に有用である。●各画像検査には長所と短所があるため、その特徴を理解しておくことが重要である。(著者抄録)

Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2018&ichushi_jid=J00282&link_issn=&doc_id=20180406150013&doc_link_id=10.18885%2FJ00282.2018192551&url=https%3A%2F%2Fdoi.org%2F10.18885%2FJ00282.2018192551&type=%88%E3%8F%91.jp_%83I%81%5B%83%8B%83A%83N%83Z%83X&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

MiRNA-133a-5p inhibits the expression of osteoblast differentiation-associated markers by targeting the 3′ UTR of RUNX2 Reviewed

Wei Zhang, Yonggang Wu, Yasuyuki Shiozaki, Yoshihisa Sugimoto, Tomoyuki Takigawa, Masato Tanaka, Akihiro Matsukawa, Toshifumi Ozaki

DNA and Cell Biology 37 ( 3 ) 199 - 209 2018.3

Language：English Publishing type：Research paper (scientific journal) Publisher：Mary Ann Liebert Inc.

Recent studies have recognized the involvement of microRNAs (miRNAs) in the development of osteoporosis, which regulate the balance between osteogenesis and osteoclasis. In this study, we investigated the regulation by miRNA-133a-5p on the osteoblast differentiation-associated markers in the mouse osteoblast-like MC3T3-E1 cells by RUNX2. First, we manipulated the miRNA-133a level in the MC3T3-E1 cells with 20 or 40 nM miR-133a-5p mimics, miR-133a-5p inhibitor, or scramble miRNA. Then, we quantified with real-time polymerase chain reaction (qRT-PCR) the expression of Collagen I, osteocalcin (OCN), and osteopontin (OPN) in the miR-133a-5p-manipulated MC3T3-E1 cells. And the confocal microscopy was also utilized to confirm the regulation by miR-133a-5p on the expression of the three molecules. We also investigated the extracellular matrix (ECM) mineralization and the alkaline phosphatase (ALP) activity in the miR-133a-5p-manipulated MC3T3-E1 cells. In addition, we explored the possible targeting by miR-133a-5p on RUNX2, which was a well-recognized promoter to osteoblast differentiation, with luciferase reporter, qRT-PCR, and Western blotting assay. Results demonstrated that the miRNA-133a-5p mimics markedly reduced, whereas the miRNA-133a-5p inhibitor significantly promoted the expression of Collagen I, OCN, and OPN, the ECM mineralization, and the ALP activity in MC3T3-E1 cells. The alignment analysis demonstrated a high homology between miRNA-133a-5p and the 3′ UTR of RUNX2. Moreover, the luciferase reporter assay demonstrated that miRNA-133a-5p targeted the 3′ UTR of RUNX2, and inhibited the expression of RUNX2 in both mRNA and protein levels. In conclusion, we identified the inhibition by miRNA-133a-5p to the expression of osteoblast differentiation markers, to the ECM mineralization, and to the ALP activity in MC3T3-E1 cells, by targeting the 3′ UTR of RUNX2. Our study suggests that miRNA-133a-5p might be an important target to inhibit osteoblast differentiation in osteoporosis.

DOI： 10.1089/dna.2017.3936

Outcomes of Resection and Joint-Preserving Arthroplasty for Forefoot Deformities for Rheumatoid Arthritis Reviewed

Masahiro Horita, Keiichiro Nishida, Kenzo Hashizume, Yoshihisa Nasu, Kenta Saiga, Ryuichi Nakahara, Takahiro Machida, Hideki Ohashi, Toshifumi Ozaki

Foot and Ankle International 39 ( 3 ) 292 - 299 2018.3

Language：English Publishing type：Research paper (scientific journal) Publisher：SAGE Publications Inc.

Background: We investigated the clinical outcomes of resection and joint-preserving arthroplasty for forefoot deformities in patients with rheumatoid arthritis. Methods: Sixteen feet of 14 women (average age, 67.1 years
range, 53-82) underwent resection arthroplasty of the metatarsal head (resection group), and 18 feet of 15 women (average age, 61.3 years
range, 40-73) underwent a metatarsophalangeal joint-preserving procedure with shortening oblique metatarsal osteotomies of the lesser toes (joint preservation group). The mean disease duration in the resection and joint preservation groups was 23.6 and 19.1 years, and the average follow-up period was 37.3 and 33.5 months, respectively. The classification of Larsen was used to assess the severity of destruction of the metatarsophalangeal (MTP) joint. Preoperative and postoperative clinical evaluation included Japanese Society for Surgery of the Foot (JSSF) score and postoperative complications. Results: The number of preoperative radiographic destruction of the MTP joints (Larsen grade II, III, IV, and V) was 0, 29, 39, and 12 joints in the resection group and 13, 67, 9, and 1 joints in the joint preservation group. The mean JSSF score improved significantly from 61.3 to 83.9 points in the resection group (P &lt
.001) and from 62.2 to 90.8 points in the joint preservation group (P &lt
.001). In the resection group, recurrence of callosities and claw toe deformity was observed in 6 and 3 feet, respectively. In the joint-preserving group, recurrence of callosities and hammer toe deformity was observed in 1 foot each. Conclusion: The resection arthroplasty and joint-preserving procedure showed satisfactory clinical outcomes. However, whether both procedures can maintain the good clinical results without the recurrence of forefoot deformity will require longer follow-up. Level of Evidence: Level III, retrospective comparative series.

DOI： 10.1177/1071100717743996