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Improvement in the medial meniscus posterior shift following anterior cruciate ligament reconstruction 査読

Hiroto Inoue, Takayuki Furumatsu, Shinichi Miyazawa, Masataka Fujii, Yuya Kodama, Toshifumi Ozaki

Knee Surgery, Sports Traumatology, Arthroscopy 26 ( 2 ) 434 - 441 2018年2月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Springer Verlag

Purpose: Anterior cruciate ligament (ACL) reconstruction can reduce the risk of developing osteoarthritic knees. The goals of ACL reconstruction are to restore knee stability and reduce post-traumatic meniscal tears and cartilage degradation. A chronic ACL insufficiency frequently results in medial meniscus (MM) injury at the posterior segment. How ACL reconstruction can reduce the deformation of the MM posterior segment remains unclear. In this study, we evaluated the form of the MM posterior segment and anterior tibial translation before and after ACL reconstruction using open magnetic resonance imaging (MRI). Methods: Seventeen patients who underwent ACL reconstructions without MM injuries were included in this study. MM deformation was evaluated using open MRI before surgery and 3 months after surgery. We measured medial meniscal length (MML), medial meniscal height (MMH), medial meniscal posterior body width (MPBW), MM–femoral condyle contact width (M-FCW) and posterior tibiofemoral distance (PTFD) at knee flexion angles of 10° and 90°. Results: There were no significant pre- and postoperative differences during a flexion angle of 10°. At a flexion angle of 90°, MML decreased from 43.7 ± 4.5 to 41.4 ± 4.5 mm (P &lt
0.001), MMH from 7.5 ± 1.4 to 6.9 ± 1.4 mm (P = 0.006), MPBW from 13.1 ± 2.0 to 12.2 ± 1.9 mm (P &lt
0.001) and M-FCW from 10.0 ± 1.5 to 8.5 ± 1.5 mm (P &lt
0.001) after ACL reconstruction. The PTFD increased from 2.1 ± 2.8 to 2.7 ± 2.4 mm after ACL reconstruction (P = 0.015). Conclusions: ACL reconstruction affects the contact pattern between the MM posterior segment and medial femoral condyle and can reduce the deformation of the MM posterior segment in the knee-flexed position by reducing abnormal anterior tibial translation. It possibly prevents secondary injury to the MM posterior segment and cartilage that progresses to knee osteoarthritis. Level of evidence: IV.

DOI： 10.1007/s00167-017-4729-x

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Extensive Bilateral Patellar Tendon Ossification in a Spinal Cord Injury Patient.

Norio Yamamoto, Takaaki Miki, Akihiro Nishiyama, Tomoyuki Dan'ura, Yuzuru Matsui, Toshifumi Ozaki

Acta medica Okayama 72 ( 1 ) 89 - 93 2018年2月

記述言語：英語掲載種別：研究論文（学術雑誌）

This is the first report of extensive bilateral patellar tendon ossification occurring over a prolonged time after a unilateral knee injury. An 84-year-old Japanese man with a spinal cord injury caused by a burst fracture of the T12 vertebra presented with a bony hard prominence on the left knee, which was injured in a traffic accident when he was 77 years old. Radiography revealed extensive ossification of the bilateral patellar tendons. We review the English literature with a focus on the localization of bilateral heterotopic ossification of the knee in patients who had a central nervous system injury.

DOI： 10.18926/AMO/55670

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骨折治療の最前線多発骨折・多発外傷における近年の治療戦略と変化リハビリテーション治療と関連して

山川泰明, 野田知之, 大塚貴久, 堅山佳美, 尾崎敏文, 千田益生

Journal of Clinical Rehabilitation 27 ( 2 ) 162 - 167 2018年2月

Collagen-Binding Hepatocyte Growth Factor (HGF) alone or with a Gelatin- furfurylamine Hydrogel Enhances Functional Recovery in Mice after Spinal Cord Injury. 査読国際誌

Kentaro Yamane, Tetsuro Mazaki, Yasuyuki Shiozaki, Aki Yoshida, Kensuke Shinohara, Mariko Nakamura, Yasuhiro Yoshida, Di Zhou, Takashi Kitajima, Masato Tanaka, Yoshihiro Ito, Toshifumi Ozaki, Akihiro Matsukawa

Scientific reports 8 ( 1 ) 917 - 917 2018年1月

記述言語：英語掲載種別：研究論文（学術雑誌）

The treatment of spinal cord injury (SCI) is currently a significant challenge. Hepatocyte growth factor (HGF) is a multipotent neurotrophic and neuroregenerative factor that can be beneficial for the treatment of SCI. However, immobilized HGF targeted to extracellular matrix may be more effective than diffusible, unmodified HGF. In this study, we evaluated the neurorestorative effects of an engineered HGF with a collagen biding domain (CBD-HGF). CBD-HGF remained in the spinal cord for 7 days after a single administration, while unmodified HGF was barely seen at 1 day. When a gelatin-furfurylamine (FA) hydrogel was applied on damaged spinal cord as a scaffold, CBD-HGF was retained in gelatin-FA hydrogel for 7 days, whereas HGF had faded by 1 day. A single administration of CBD-HGF enhanced recovery from spinal cord compression injury compared with HGF, as determined by motor recovery, and electrophysiological and immunohistochemical analyses. CBD-HGF alone failed to improve recovery from a complete transection injury, however CBD-HGF combined with gelatin-FA hydrogel promoted endogenous repair and recovery more effectively than HGF with hydrogel. These results suggest that engineered CBD-HGF has superior therapeutic effects than naïve HGF. CBD-HGF combined with hydrogel scaffold may be promising for the treatment of serious SCI.

DOI： 10.1038/s41598-018-19316-y

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Accuracy of Cup Positioning With the Computed Tomography-Based Two-dimensional to Three-Dimensional Matched Navigation System: A Prospective, Randomized Controlled Study 査読

Kazuki Yamada, Hirosuke Endo, Tomonori Tetsunaga, Takamasa Miyake, Tomoaki Sanki, Toshifumi Ozaki

Journal of Arthroplasty 33 ( 1 ) 136 - 143 2018年1月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Churchill Livingstone Inc.

Background The accuracy of various navigation systems used for total hip arthroplasty has been described, but no publications reported the accuracy of cup orientation in computed tomography (CT)-based 2D-3D (two-dimensional to three-dimensional) matched navigation. Methods In a prospective, randomized controlled study, 80 hips including 44 with developmental dysplasia of the hips were divided into a CT-based 2D-3D matched navigation group (2D-3D group) and a paired-point matched navigation group (PPM group). The accuracy of cup orientation (absolute difference between the intraoperative record and the postoperative measurement) was compared between groups. Additionally, multiple logistic regression analysis was performed to evaluate patient factors affecting the accuracy of cup orientation in each navigation. Results The accuracy of cup inclination was 2.5° ± 2.2° in the 2D-3D group and 4.6° ± 3.3° in the PPM group (P =.0016). The accuracy of cup anteversion was 2.3° ± 1.7° in the 2D-3D group and 4.4° ± 3.3° in the PPM group (P =.0009). In the PPM group, the presence of roof osteophytes decreased the accuracy of cup inclination (odds ratio 8.27, P =.0140) and the absolute value of pelvic tilt had a negative influence on the accuracy of cup anteversion (odds ratio 1.27, P =.0222). In the 2D-3D group, patient factors had no effect on the accuracy of cup orientation. Conclusion The accuracy of cup positioning in CT-based 2D-3D matched navigation was better than in paired-point matched navigation, and was not affected by patient factors. It is a useful system for even severely deformed pelvises such as developmental dysplasia of the hips.

DOI： 10.1016/j.arth.2017.08.001

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Iatrogenic injury of the lateral meniscus anterior insertion following anterior cruciate ligament reconstruction: A case report 査読

Takayuki Furumatsu, Toshifumi Ozaki

Journal of Orthopaedic Science 23 ( 1 ) 197 - 201 2018年1月

La R?paration en ?pull out? transtibial des l?sions de la racine post?rieure du m?nisque m?dial restaure la rotation physiologique du m?nisque m?dial sur un genou fl?chi 査読国際誌

Okazaki Y, Furumatsu T, Kodama Y, Hino T, Kamatsuki Y, Masuda S, Miyazawa S, Endo H, Tetsunaga Tomonori, Yamada K, 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 2018年1月

The clinical course of patients with rheumatoid arthritis who underwent orthopaedic surgeries under disease control by tofacitinib. 査読国際誌

Nishida K, Harada R, Nasu Y, Takeshita A, Nakahara R, Matsumeda M, Ozaki T

Modern rheumatology 28 ( 6 ) 1 - 8 2018年1月

Molecular radiosensitization of p53-armed telomerase-dependent oncolytic adenovirus against human soft-tissue sarcoma

Tadashi Komatsubara, Hiroshi Tazawa, Yusuke Mochizuki, Kazuhisa Sugiu, Toshinori Omori, Yasuaki Yamakawa, Syuhei Osaki, Joe Hasei, Tomohiro Fujiwara, Toshiyuki Kunisada, Yasuo Urata, Toshifumi Ozaki, Toshiyoshi Fujiwara

CANCER SCIENCE 109 454 - 454 2018年1月

Liquid biopsy using tumor-derived exosomes for Ewing sarcoma patients

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

CANCER SCIENCE 109 312 - 312 2018年1月

肺がん骨転移に対するニボルマブの治療効果

中田英二, 杉原進介, 上月稔幸, 原田大二郎, 武智宣佳, 尾崎敏文

中部日本整形外科災害外科学会雑誌 61 ( 1 ) 39 - 40 2018年1月

記述言語：日本語出版者・発行元：(一社)中部日本整形外科災害外科学会

抗PD-1抗体であるニボルマブの肺がん転移に対する治療効果について検討した。平成28年1月〜平成29年3月に当院でニボルマブの治療を行った非小細胞肺がん骨転移16例(男性11例、女性5例、平均年齢65歳)を対象とした。治療効果はPR 3例、SD 3例、PD 10例で、奏効率19%、病勢コントロール率38%であった。PRの全例、SDの1例で骨転移巣の骨形成や骨外腫瘤の縮小を認めたが、他の症例では不変あるいは骨破壊の進行を認めた。4例で骨転移巣に骨形成を認め、骨転移に対する治療効果はCR1例、PR3例、SD10例、PD2例であった。Second lineとしてニボルマブ投与が行われた5例の治療効果はPR2例、SD2例、PD1例で、骨転移に対する治療効果はCR1例、PR2例、SD2例であった。CRの1例は有害事象により投与開始後2ヵ月でニボルマブの投与を休止し、その後抗がん剤投与を行わなかったが、経時的に原発巣と肺転移巣の縮小と骨転移巣の骨形成を認め、最終観察時(投与中止後6ヵ月)には再増大を認めなかった。

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肘関節尺側側副靱帯損傷の不安定性の評価関節造影ストレス撮影とMRI画像所見との関連性

内野崇彦, 島村安則, 島村好信, 名越充, 井上博登, 山脇正, 中道亮, 齋藤太一, 野田知之, 尾崎敏文

日本肘関節学会雑誌 25 ( 1 ) S59 - S59 2018年1月

Intercondylar and central regions of complete discoid lateral meniscus have different cell and matrix organizations 査読

Takayuki Furumatsu, Ami Maehara, Yuki Okazaki, Toshifumi Ozaki

Journal of Orthopaedic Science 23 ( 5 ) 811 - 818 2018年

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Elsevier

Background: A complete discoid lateral meniscus (DLM) has a high risk of horizontal tear. However, cellular phenotypes and extracellular matrix organizations in complete DLMs are still unclear. The aim of this study was to investigate histological and cellular biological characteristics in both the intercondylar and central regions of complete DLM. Materials and methods: Meniscal samples were obtained from the intercondylar and central regions of complete DLM (n = 6). Blood vessels and aggregated cell ratio were measured in each region. Depositions of type I/II collagens and safranin O-stained proteoglycans in the extracellular matrix were assessed. Experiments in gene expression, morphology, proliferation, and effect of mechanical stretch were performed using cultured cells derived from each region. Results: Blood vessel counts were significantly higher in the intercondylar region than in the central region. The ratio of aggregated cells was lower in the intercondylar region than in the central region. Deposition of type I collagen was comparable for both regions. The central region contained a larger quantity of type II collagen and safranin O staining density compared with the intercondylar region. Proliferation of the fibroblastic intercondylar cells was not affected by 5%-stretching. However, stretching treatments decreased relative proliferation of the chondrocytic central cells. Conclusions: This study demonstrated that the central region of complete DLM had different cellular properties and collagen components compared with the intercondylar region. Our results suggest that the central region of complete DLM may have a low healing potential like the inner avascular region of the meniscus.

DOI： 10.1016/j.jos.2018.05.006

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A rare manifestation of extraskeletal myxoid chondrosarcoma with a huge expanding hematoma 査読

Toshinori Omori, Tomohiro Fujiwara, Toshiyuki Kunisada, Ken Takeda, Joe Hasei, Aki Yoshida, Hiroyuki Yanai, Toshifumi Ozaki

Journal of Orthopaedic Science 24 ( 2 ) 377 - 381 2018年

Meniscal Extrusion Progresses Shortly after the Medial Meniscus Posterior Root Tear. 査読国際誌

Furumatsu T, Kodama Y, Kamatsuki Y, Hino T, Okazaki Y, Ozaki T

Knee surgery & related research 29 ( 4 ) 295 - 301 2017年12月

Autonomous feedback loop of RUNX1-p53-CBFB in acute myeloid leukemia cells 査読

Ken Morita, Mina Noura, Chieko Tokushige, Shintaro Maeda, Hiroki Kiyose, Gengo Kashiwazaki, Junichi Taniguchi, Toshikazu Bando, Kenichi Yoshida, Toshifumi Ozaki, Hidemasa Matsuo, Seishi Ogawa, Pu Paul Liu, Tatsutoshi Nakahata, Hiroshi Sugiyama, Souichi Adachi, Yasuhiko Kamikubo

SCIENTIFIC REPORTS 7 ( 1 ) 16604 2017年11月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：NATURE PUBLISHING GROUP

Although runt-related transcription factor 1 (RUNX1) and its associating core binding factor-beta (CBFB) play pivotal roles in leukemogenesis, and inhibition of RUNX1 has now been widely recognized as a novel strategy for anti-leukemic therapies, it has been elusive how leukemic cells could acquire the serious resistance against RUNX1-inhibition therapies and also whether CBFB could participate in this process. Here, we show evidence that p53 (TP53) and CBFB are sequentially up-regulated in response to RUNX1 depletion, and their mutual interaction causes the physiological resistance against chemotherapy for acute myeloid leukemia (AML) cells. Mechanistically, p53 induced by RUNX1 gene silencing directly binds to CBFB promoter and stimulates its transcription as well as its translation, which in turn acts as a platform for the stabilization of RUNX1, thereby creating a compensative RUNX1-p53-CBFB feedback loop. Indeed, AML cells derived from relapsed cases exhibited higher CBFB expression levels compared to those from primary AML cells at diagnosis, and these CBFB expressions were positively correlated to those of p53. Our present results underscore the importance of RUNX1-p53-CBFB regulatory loop in the development and/or maintenance of AML cells, which could be targeted at any sides of this triangle in strategizing anti-leukemia therapies.

DOI： 10.1038/s41598-017-16799-z

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Circulating MicroRNA-92b-3p as a Novel Biomarker for Monitoring of Synovial Sarcoma 査読

Koji Uotani, Tomohiro Fujiwara, Aki Yoshida, Shintaro Iwata, Takuya Morita, Masahiro Kiyono, Suguru Yokoo, Toshiyuki Kunisada, Ken Takeda, Joe Hasei, Kunihiko Numoto, Yutaka Nezu, Tsukasa Yonemoto, Takeshi Ishii, Akira Kawai, Takahiro Ochiya, Toshifumi Ozaki

SCIENTIFIC REPORTS 7 ( 1 ) 14634 2017年11月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：NATURE PUBLISHING GROUP

The lack of useful biomarkers is a crucial problem for patients with soft tissue sarcomas (STSs). Emerging evidence has suggested that circulating microRNAs (miRNAs) in body fluids have novel impact as biomarkers for patients with malignant diseases, but their significance in synovial sarcoma (SS) patients remains unknown. Initial global miRNA screening using SS patient serum and SS cell culture media identified a signature of four upregulated miRNAs. Among these candidates, miR-92b-3p secretion from SS cells was confirmed, which was embedded within tumour-derived exosomes rather than argonaute-2. Animal experiments revealed a close correlation between serum miR-92b-3p levels and tumour dynamics. Clinical relevance was validated in two independent clinical cohorts, and we subsequently identified that serum miR-92b-3p levels were significantly higher in SS patients in comparison to that in healthy individuals. Moreover, serum miR-92b-3p was robust in discriminating patients with SS from the other STS patients and reflected tumour burden in SS patients. Overall, liquid biopsy using serum miR-92b-3p expression levels may represent a novel approach for monitoring tumour dynamics of SS.

DOI： 10.1038/s41598-017-12660-5

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Inhibitory effect of JAK inhibitor on mechanical stress-induced protease expression by human articular chondrocytes. 国際誌

Takahiro Machida, Keiichiro Nishida, Yoshihisa Nasu, Ryuichi Nakahara, Masatsugu Ozawa, Ryozo Harada, Masahiro Horita, Ayumu Takeshita, Daisuke Kaneda, Aki Yoshida, Toshifumi Ozaki

Inflammation research : official journal of the European Histamine Research Society ... [et al.] 66 ( 11 ) 999 - 1009 2017年11月

記述言語：英語掲載種別：研究論文（学術雑誌）

OBJECTIVE: To investigate whether janus kinase (JAK) inhibitor exhibits a chondro-protective effect against mechanical stress-induced expression of a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) and matrix metalloproteinase (MMPs) in human chondrocytes. MATERIALS AND METHODS: Normal human articular chondrocytes were seeded onto stretch chambers and incubated with or without tofacitinib (1000 nM) for 12 h before mechanical stimulation or cytokine stimulation. Uni-axial cyclic tensile strain (CTS) (0.5 Hz, 10% elongation, 30 min) was applied and the gene expression levels of type II collagen α1 chain (COL2A1), aggrecan (ACAN), ADAMTS4, ADAMTS5, MMP13, and runt-related transcription factor 2 (RUNX-2) were examined by real-time polymerase chain reaction. Nuclear translocation of RUNX-2 and nuclear factor-κB (NF-κB) was examined by immunocytochemistry, and phosphorylation of mitogen-activated protein kinase (MAPK) and signaling transducer and activator of transcription (STAT) 3 was examined by western blotting. The concentration of interleukin (IL)-1β, IL-6, and tumor necrosis factor-α in the supernatant was examined by enzyme-linked immunosorbent assay. RESULTS: COL2A1 and ACAN gene expression levels were decreased by CTS, but these catabolic effects were canceled by tofacitinib. Tofacitinib significantly down-regulated CTS-induced expression of ADAMTS4, ADAMTS5, MMP13, and RUNX2, and the release of IL-6 in supernatant by chondrocytes. Tofacitinib also reduced CTS-induced nuclear translocation of RUNX-2 and NF-κB, and phosphorylation of MAPK and STAT3. CONCLUSION: Tofacitinib suppressed mechanical stress-induced expression of ADAMTS4, ADAMTS5, and MMP13 by human chondrocytes through inhibition of the JAK/STAT and MAPK cascades.

DOI： 10.1007/s00011-017-1083-x

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Tibial eminence width can predict the presence of complete discoid lateral meniscus: A preliminary study.

Tomohito Hino, Takayuki Furumatsu, Masataka Fujii, Yuya Kodama, Shinichi Miyazawa, Yusuke Kamatsuki, Kazuki Yamada, Toshifumi Ozaki

Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association 22 ( 6 ) 1084 - 1088 2017年11月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: To compare the plain knee radiograph finding of tibial eminence width between knees with complete discoid lateral meniscus, incomplete discoid lateral meniscus, and normal lateral meniscus. MATERIALS AND METHODS: The study included 27 knees with discoid lateral meniscus, including 13 knees with complete discoid lateral meniscus and 14 knees with incomplete discoid lateral meniscus. A control group of 14 knees with normal lateral meniscus was also included. Tibial eminence width and the lateral slope angle of the medial tibial eminence were assessed using plain frontal knee radiographs. Individual differences in knee size were corrected by dividing tibial eminence width by tibial width to obtain the tibial eminence width percentage. RESULTS: Mean tibial eminence width and tibial eminence width percentage in the complete discoid lateral meniscus group was significant larger than other groups. Mean lateral slope angle in the complete discoid lateral meniscus group was significantly smaller than other groups. A tibial eminence width cut-off of 13.9 mm showed a sensitivity and specificity of 100% and 83%, respectively. A tibial eminence width percentage cut-off of 18.8% showed a sensitivity and specificity of 100% and 90%, respectively. A lateral slope angle cut-off of 27.1° showed a sensitivity and specificity of 71% and 83%, respectively. CONCLUSION: There were clear differences in tibial eminence width, tibial eminence width percentage, and lateral slope angle between the complete discoid lateral meniscus group and the other groups. The plain radiographic parameters identified by this study could be useful for complete discoid lateral meniscus screening. STUDY DESIGN: Clinical.

DOI： 10.1016/j.jos.2017.07.011

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側彎症手術を行った重症脳性麻痺患者における健康関連QOL調査の試み

小田孔明, 瀧川朋亨, 杉本佳久, 田中雅人, 尾崎敏文

中部日本整形外科災害外科学会雑誌 60 ( 6 ) 1049 - 1050 2017年11月

記述言語：日本語出版者・発行元：(一社)中部日本整形外科災害外科学会

肢体不自由児施設入所中の脳性麻痺(CP)患者79名(平均年齢13.3歳)を対象に、日本語に翻訳したCaregiver Priorities and Child Health Index of Life with Disabilities(CPCHILD)がQOL調査に使用可能であるか検討した。アンケート結果の内的整合性を検討し、更に、2週間の間隔を開け2回調査して再現性も検討した。また、当大学病院で側彎症手術を受けたGMFCS IVまたはVの重症CP患者6名(平均年齢13.3歳)に対してもアンケートを用いてQOL調査を行った。内的整合性をみたCronbachのα係数および再現性の結果は、いずれも0.6を上回っていた。CPCHILDのスコアをGMFCS level別に比較したところ、section 1～3とtotal scoreでGMFCSの重症度とCPCHILDスコアは相関していた。術前CPCHILDスコアはsection 1～6で19.7、19.1、76.8、91.9、72.2、56.7、術後のスコアは20.7、14.7、75.2、93.4、75.0、60.0であり、統計学的有意差は認めなかった。以上、日本語翻訳したCPCHILDは内的妥当性と再現性は良好であり、脳性麻痺の重症度もスコアに反映していたが、術後QOLの改善は認めなかった。

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