Language：Japanese   Publisher：(公社)日本整形外科学会  

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Giant cell tumor of bone (GCTB) is a locally aggressive intermediate bone tumor. Denosumab has shown effectiveness in GCTB treatment; however, the benefits of denosumab de-escalation for unresectable GCTB have not been well discussed. The present study investigated the efficacy and safety of denosumab de-escalation for GCTB. The medical records of 9 patients with unresectable GCTB or resectable GCTB not eligible for resection, who received de-escalated denosumab treatment at Okayama University Hospital (Okayama, Japan) between April 2014 and December 2021, were retrospectively reviewed. The denosumab treatment interval was gradually extended to every 8, 12 and 24 weeks. The radiographic changes and clinical symptoms during standard and de-escalated denosumab therapy were assessed. The denosumab interval was de-escalated after a median of 12 months of a standard 4-weekly treatment. Imaging showed that the re-ossification of osteolytic lesions obtained with the 4-weekly treatment were sustained with 8- and 12-weekly treatments. The extraskeletal masses reduced significantly with standard treatment, while tumor reduction was sustained during de-escalated treatment. During the 24-weekly treatment, 2 patients remained stable, while 2 patients developed local recurrence. The clinical symptoms improved significantly with standard treatment and remained improved during de-escalated treatment. There were severe adverse events including osteonecrosis of the jaw (2 patients), atypical femoral fracture (1 patient) and malignant transformation of GCTB (1 patient). In conclusion, 12-weekly de-escalated denosumab treatment showed clinical benefits as a maintenance treatment in patients with unresectable GCTB, in addition to sustained stable tumor control and improved clinical symptoms with standard treatment. A 24-weekly treatment can also be administered, with careful attention paid to detecting local recurrence.

DOI： 10.3892/ol.2024.14520

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Unidirectional porous hydroxyapatite (UDPHAp) was developed as a remarkable scaffold characterized by a distinct structure with unidirectional pores oriented in the horizontal direction and connected through interposes. We evaluated the radiographic changes, clinical outcomes, and complications following UDPHAp implantation for the treatment of bone tumors. Excellent bone formation within and around the implant was observed in all patients treated with intralesional resection and UDPHAp implantation for benign bone tumors. The absorption of UDPHAp and remodeling of the bone marrow space was observed in 45% of the patients at a mean of 17 months postoperatively and was significantly more common in younger patients. Preoperative cortical thinning was completely regenerated in 84% of patients at a mean of 10 months postoperatively. No complications related to the implanted UDPHAp were observed. In a pediatric patient with bone sarcoma, when the defect after fibular resection was filled with UDPHAp implants, radiography showed complete resorption of the implant and clear formation of cortex and marrow in the resected part of the fibula. The patient could walk well without crutches and participate in sports activities. UDPHAp is a useful bone graft substitute for the treatment of benign bone tumors, and the use of this material has a low complication rate. We also review and discuss the potential of UDPHAp as a bone graft substitute in the clinical setting of orthopedic surgery.

DOI： 10.3390/biomimetics9050294

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

BACKGROUND: Paired related-homeobox 1 (PRRX1) is a transcription factor in the regulation of developmental morphogenetic processes. There is growing evidence that PRRX1 is highly expressed in certain cancers and is critically involved in human survival prognosis. However, the molecular mechanism of PRRX1 in cancer malignancy remains to be elucidated. METHODS: PRRX1 expression in human Malignant peripheral nerve sheath tumours (MPNSTs) samples was detected immunohistochemically to evaluate survival prognosis. MPNST models with PRRX1 gene knockdown or overexpression were constructed in vitro and the phenotype of MPNST cells was evaluated. Bioinformatics analysis combined with co-immunoprecipitation, mass spectrometry, RNA-seq and structural prediction were used to identify proteins interacting with PRRX1. RESULTS: High expression of PRRX1 was associated with a poor prognosis for MPNST. PRRX1 knockdown suppressed the tumorigenic potential. PRRX1 overexpressed in MPNSTs directly interacts with topoisomerase 2 A (TOP2A) to cooperatively promote epithelial-mesenchymal transition and increase expression of tumour malignancy-related gene sets including mTORC1, KRAS and SRC signalling pathways. Etoposide, a TOP2A inhibitor used in the treatment of MPNST, may exhibit one of its anticancer effects by inhibiting the PRRX1-TOP2A interaction. CONCLUSION: Targeting the PRRX1-TOP2A interaction in malignant tumours with high PRRX1 expression might provide a novel tumour-selective therapeutic strategy.

DOI： 10.1038/s41416-024-02632-8

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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

Malignant peripheral nerve sheath tumors (MPNSTs) are malignant tumors that are derived from Schwann cell lineage around peripheral nerves. As in many other cancer types, cancer stem cells (CSCs) have been identified in MPNSTs, and they are considered the cause of treatment resistance, recurrence, and metastasis. As an element defining the cancer stemness of MPNSTs, we previously reported a molecular mechanism by which exogenous adrenaline activates a core cancer stemness factor, YAP/TAZ, through β2 adrenoceptor (ADRB2). In this study, we found that MPNST cells express catecholamine synthases and that these enzymes are essential for maintaining cancer stemness, such as the ability to self-renew and maintain an undifferentiated state. Through gene knockdown and inhibition of these enzymes, we confirmed that catecholamines are indeed synthesized in MPNST cells. The results confirmed that catecholamine synthase knockdown in MPNST cells reduces the activity of YAP/TAZ. These data suggest that a mechanism of YAP/TAZ activation by de novo synthesized adrenaline, as well as exogenous adrenaline, may exist in the maintenance of cancer stemness of MPNST cells. This mechanism not only helps to understand the pathology of MPNST, but could also contribute to the development of therapeutic strategies for MPNST.

DOI： 10.1111/cas.16077

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：日本レックリングハウゼン病学会  

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Language：Japanese   Publisher：日本レックリングハウゼン病学会  

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Language：Japanese   Publisher：日本レックリングハウゼン病学会  

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Publishing type：Research paper (scientific journal)   Publisher：SAGE Publications  

Objective: Precise assessment of spinal instability is critical before and after radiotherapy (RT) for evaluating the effectiveness of RT. Therefore, we retrospectively evaluated the efficacy of RT in spinal instability over a period of 6 months after RT, utilizing the spinal instability neoplastic score (SINS) in patients with painful spinal metastasis. We retrospectively evaluated 108 patients who received RT for painful vertebral metastasis in our institution. Mechanical pain at metastatic vertebrae, radiological responses of irradiated vertebrae, and spinal instability were assessed. Follow-up assessments were done at the start of and at intervals of 1, 2, 3, 4, and 6 months after RT, with the pain disappearing in 67%, 85%, 93%, 97%, and 100% of the patients, respectively. The median SINS were 8, 6, 6, 5, 5, and 4 at the beginning and after 1, 2, 3, 4, and 6 months of RT, respectively. Multivariate analysis revealed that posterolateral involvement of spinal elements (PLISE) was the only risk factor for continuous potentially unstable/unstable spine at 1 month. In conclusion, there was improvement of pain, and recalcification results in regaining spinal stability over time after RT although vertebral body collapse and malalignment occur in some irradiated vertebrae. Clinicians should pay attention to PLISE in predicting continuous potentially unstable/unstable spine.

DOI： 10.1177/10732748241250219

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Other Link： https://journals.sagepub.com/doi/full-xml/10.1177/10732748241250219

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Most patients with developmental dysplasia of the hip (DDH) now receive closed-reduction treatment within 6 months after birth. The long-term outcomes of patients with late-detection DDH have remained unclear. We reviewed the clinical records of 18 patients who underwent Colonna capsular arthroplasty (n=8) or closed reduction (n=10) for developmental dysplasia of the hip as infants or young children and underwent total hip arthroplasty approximately in midlife. Both the Colonna capsular arthroplasty and closed reduction groups achieved good clinical results after total hip arthroplasty. However, the operating time was longer and the improvements of hip range of motion and clinical score were significantly worse in the Colonna capsular arthroplasty group than in the closed reduction group.

DOI： 10.18926/AMO/66159

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Language：Japanese   Publisher：(株)医学書院  

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2023&ichushi_jid=J01554&link_issn=&doc_id=20231129020009&doc_link_id=10.11477%2Fmf.1408202843&url=https%3A%2F%2Fdoi.org%2F10.11477%2Fmf.1408202843&type=%E5%8C%BB%E6%9B%B8.jp_%E3%82%AA%E3%83%BC%E3%83%AB%E3%82%A2%E3%82%AF%E3%82%BB%E3%82%B9&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

Language：Japanese   Publisher：(一社)日本移植学会  

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

AIMS: Clear cell sarcoma (CCS) of soft-tissue is a rare melanocytic subtype of mesenchymal malignancy. The aim of this study was to investigate the clinical and therapeutic factors associated with increased survival, stratified by clinical stage, in order to determine the optimal treatment. METHODS: The study was a retrospective analysis involving 117 patients with histologically confirmed CCS, between July 2016 and November 2017, who were enrolled in the Bone and Soft Tissue Tumour Registry in Japan. RESULTS: The five- and ten-year survival rates were 41% (95% confidence interval (CI) 29 to 52) and 37% (95% CI 25 to 49), respectively. On multivariable analysis, the size of the tumour of > 10 cm (p = 0.006), lymph node metastasis at the time of diagnosis (p < 0.001), distant metastases at the time of diagnosis (p < 0.001), and no surgery for the primary tumour (p = 0.019) were independently associated with a poor survival. For N0M0 CCS (n = 68), the development of distant metastases was an independent prognostic factor for survival (early (< 12 months), hazard ratio (HR) 116.78 (95% CI 11.69 to 1,166.50); p < 0.001; late (> 12 months), HR 14.79 (95% CI 1.66 to 131.63); p = 0.016); neoadjuvant/adjuvant chemotherapy (p = 0.895) and/or radiotherapy (p = 0.216) were not significantly associated with survival. The five-year cumulative incidence of local recurrence was 19% (95% CI 8 to 35) and the size of the tumour was significantly associated with an increased rate of local recurrence (p = 0.012). For N1M0 CCS (n = 18), the risk of mortality was significantly lower in patients who underwent surgery for both the primary tumour and lymph node metastases (HR 0.03 (95% CI 0.00 to 0.56); p = 0.020). For M1 CCS (n = 31), excision of the primary tumour was independently associated with better survival (HR 0.26 (95% CI 0.09 to 0.76); p = 0.013). There was no significant difference in survival between the different types of systemic treatment (p = 0.523). CONCLUSION: Complete excision of the primary tumour and lymph nodes is associated with a better survival in patients with CCS. Systemic treatment appears to provide limited benefits, demonstrating a pressing need for novel systemic agents.

DOI： 10.1302/0301-620X.105B11.BJJ-2022-0743.R3

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

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

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Language：Japanese   Publisher：(株)全日本病院出版会  

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

Alveolar soft part sarcoma is a rare neoplasm of uncertain histogenesis that belongs to a newly defined category of ultra-rare sarcomas. The neoplasm is characterized by a specific chromosomal translocation, der (17) t(X; 17)(p11.2;q25), that results in ASPSCR1-TFE3 gene fusion. The natural history of alveolar soft part sarcoma describes indolent behaviour with slow progression in deep soft tissues of the extremities, trunk and head/neck in adolescents and young adults. A high rate of detection of distant metastasis at presentation has been reported, and the most common metastatic sites in decreasing order of frequency are the lung, bone and brain. Complete surgical resection remains the standard treatment strategy, whereas radiotherapy is indicated for patients with inadequate surgical margins or unresectable tumours. Although alveolar soft part sarcoma is refractory to conventional doxorubicin-based chemotherapy, monotherapy or combination therapy using tyrosine kinase inhibitors and immune checkpoint inhibitors have provided antitumor activity and emerged as new treatment strategies. This article provides an overview of the current understanding of this ultra-rare sarcoma and recent advancements in treatments according to the clinical stage of alveolar soft part sarcoma.

DOI： 10.1093/jjco/hyad102

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：医歯薬出版(株)  

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2023&ichushi_jid=J02606&link_issn=&doc_id=20230802090003&doc_link_id=%2Faa7clrie%2F2023%2F003209%2F004%2F0841-0847%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Faa7clrie%2F2023%2F003209%2F004%2F0841-0847%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：日本結合組織学会  

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Language：Japanese   Publisher：日本結合組織学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：日本運動器科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本リハビリテーション医学会  

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Language：Japanese   Publisher：(公社)日本リハビリテーション医学会  

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

BACKGROUND/OBJECTIVE: Accurate tibial tunnel creation is crucial for successful transtibial pullout repair of medial meniscus (MM) posterior root tears (MMPRTs). This study aimed to evaluate the accuracy of the newly developed Zimmer Biomet Root Aiming (ZeBRA) guide for transtibial pullout repair of MMPRTs. METHODS: This study included 50 patients who underwent transtibial pullout repair using the Unicorn Meniscal Root (UMR) (n = 25) and ZeBRA (n = 25) guides. The expected anatomic centre (AC) and tibial tunnel centre (TC) were assessed using three-dimensional postoperative computed tomography (CT) images. The expected AC was defined as the centre of the circle tangent to the triangular footprint of the MM posterior root. The expected AC and TC on the tibial surface were assessed using the percentage-based posterolateral location on the tibial surface. The absolute distance between the AC and TC (mm) was evaluated. RESULTS: The mean AC location was 76.1% ± 3.1% posterior and 40.8% ± 2.1% lateral, whereas the mean TC location was 76.7% ± 5.3% posterior and 37.2% ± 3.6% lateral using the UMR guide and 75.8% ± 3.1% posterior and 36.5% ± 2.4% lateral using the ZeBRA guide. No significant difference was observed in the absolute distance between the UMR and ZeBRA guides (3.9 ± 1.4 and 3.8 ± 1.3 mm, respectively; p = 0.617). CONCLUSIONS: The newly developed ZeBRA guide allows accurate tibial tunnel creation, and its accuracy is comparable to that of the conventional UMR guide. Tibial tunnels were created at optimal positions using both guides, and the choice of the guide would depend on the surgeon's preference.

DOI： 10.1016/j.asmart.2023.03.001

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Language：Japanese   Publisher：(一社)日本移植学会  

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Language：Japanese   Publisher：(一社)日本移植学会  

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

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(株)癌と化学療法社  

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2023&ichushi_jid=J00296&link_issn=&doc_id=20230324430008&doc_link_id=%2Fab8gtkrc%2F2023%2F005003%2F009%2F0314-0320%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fab8gtkrc%2F2023%2F005003%2F009%2F0314-0320%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

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

Spinal metastases are common in patients with advanced stages of cancer and frequently cause vertebral body collapse (VBC). Although conventional radiotherapy (RT) is used for spinal metastases, the rates of occurrence of new VBC and progression of VBC at RT initiation have not been fully investigated. The present retrospective study assessed VBC and its associated risk factors after RT over time and evaluated new VBC and progression of VBC in patients who presented with VBC at RT initiation. The study evaluated 177 patients who received RT for vertebral metastases without paralysis between July 2012 and November 2016. Radiological responses of the irradiated vertebrae were assessed using computed tomography. Follow-up assessments were performed at RT initiation and 1, 2, 3, 4 and 6 months after RT. New VBC occurred in 12% of patients with no prior VBC within 1 month of RT. Multivariate analysis revealed that numeric rating scale (NRS) score (≥4) [relative risk (RR), 27.1; 95% confidence interval (CI), 1.86 to 394.9; P=0.016] was associated with the occurrence of new VBC at the 1 month follow-up time point. VBC progression occurred in 51% of the patients with collapse at RT initiation. Multivariate analysis revealed that bone quality (lytic metastases) (RR, 3.1; 95% CI, 1.28 to 7.70; P=0.013), NRS score (≥4) (RR, 3.0; 95% CI, 1.18 to 7.45; P=0.021) and tumor involvement of posterolateral elements of the spine (RR, 2.7; 95% CI, 1.03 to 7.29; P=0.04) were associated with the progression of VBC at the 1 month follow-up time point. The current study findings suggested that clinicians should pay attention to the factors that predict the occurrence of new VBC and VBC progression to ensure proper evaluation of conservative treatment effectiveness and facilitate the determination of patients who need close monitoring.

DOI： 10.3892/ol.2023.13695

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(一社)中部日本整形外科災害外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(一社)中部日本整形外科災害外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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

BACKGROUND: Cell sheet fabrication for articular cartilage regenerative medicine necessitates a large number of chondrocytes of consistent quality as a cell source. Previously, we have developed human-induced pluripotent stem cell (iPSC)-derived expandable PRRX1+ limb-bud mesenchymal cells (ExpLBM) with stable expansion and high chondrogenic capacity, while in this study; our ExpLBM technology was combined with cell sheet engineering to assess its potential as a stable cell source for articular cartilage regeneration. METHODS: ExpLBM cells derived from human-induced pluripotent stem cells (hiPSCs), including 414C2 and Ff-KVs09 (HLA homozygous), were seeded onto a culture plate and two-dimensional chondrogenic induction (2-DCI) was initiated. After 2-DCI, ExpLBM-derived chondrocytes were stripped and transferred to temperature-responsive culture inserts and the chondrocyte sheets were histologically examined or transplanted into osteochondral knee defects of immunodeficient rats. RESULTS: Immunohistochemistry revealed that ExpLBM-derived cell sheets were positive for Safranin O, COL2, and ACAN but that they were negative for COL1 and RUNX2. Furthermore, the engrafted tissues in osteochondral knee defects in immunodeficient rats were stained with SafO, human VIMENTIN, ACAN, and COL2. CONCLUSIONS: The present study is the first to report the chondrocyte sheet fabrication with hiPSC-derived cell source. hiPSC-derived ExpLBM would be a promising cell source for cell sheet technology in articular cartilage regenerative medicine.

DOI： 10.1186/s13287-023-03252-4

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

Cancer stem-like cells (CSCs) have a unique translation mode, but little is understood about the process of elongation, especially the contribution of tRNA modifications to the maintenance of CSCs properties. Here, it is reported that, contrary to the initial aim, a tRNA-modifying methylthiotransferase CDKAL1 promotes CSC-factor SALL2 synthesis by assembling the eIF4F translation initiation complex. CDKAL1 expression is upregulated in patients with worse prognoses and is essential for maintaining CSCs in rhabdomyosarcoma (RMS) and common cancers. Translatome analysis reveals that a group of mRNAs whose translation is CDKAL1-dependent contains cytosine-rich sequences in the 5' untranslated region (5'UTR). Mechanistically, CDKAL1 promotes the translation of such mRNAs by organizing the eIF4F translation initiation complex. This complex formation does not require the enzyme activity of CDKAL1 but requires only the NH2 -terminus domain of CDKAL1. Furthermore, sites in CDKAL1 essential for forming the eIF4F complex are identified and discovered candidate inhibitors of CDKAL1-dependent translation.

DOI： 10.1002/advs.202206542

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Language：Japanese   Publisher：日本レックリングハウゼン病学会  

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Language：Japanese   Publisher：日本レックリングハウゼン病学会  

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Language：Japanese   Publisher：日本レックリングハウゼン病学会  

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

Osteoarthritis (OA) occurs not only in the knee but also in peripheral joints throughout the whole body. Previously, we have shown that the expression of cellular communication network factor 3 (CCN3), a matricellular protein, increases with age in knee articular cartilage, and the misexpression of CCN3 in cartilage induces senescence-associated secretory phenotype (SASP) factors, indicating that CCN3 promotes cartilage senescence. Here, we investigated the correlation between CCN3 expression and OA degenerative changes, principally in human femoral head cartilage. Human femoral heads obtained from patients who received total hip arthroplasty were categorized into OA and femoral neck fracture (normal) groups without significant age differences. Gene expression analysis of RNA obtained from femoral head cartilage revealed that CCN3 and MMP-13 expression in the non-weight-bearing part was significantly higher in the OA group than in the normal group, whereas the weight-bearing OA parts and normal cartilage showed no significant differences in the expression of these genes. The expression of COL10A1, however, was significantly higher in weight-bearing OA parts compared with normal weight-bearing parts, and was also higher in weight-bearing parts compared with non-weight-bearing parts in the OA group. In contrast, OA primary chondrocytes from weight-bearing parts showed higher expression of CCN3, p16, ADAMTS4, and IL-1β than chondrocytes from the corresponding normal group, and higher ADAMTS4 and IL-1β in the non-weight-bearing part compared with the corresponding normal group. Acan expression was significantly lower in the non-weight-bearing group in OA primary chondrocytes than in the corresponding normal chondrocytes. The expression level of CCN3 did not show significant differences between the weight-bearing part and non-weight-bearing part in both OA and normal primary chondrocytes. Immunohistochemical analysis showed accumulated CCN3 and aggrecan neoepitope staining in both the weight-bearing part and non-weight-bearing part in the OA group compared with the normal group. The CCN3 expression level in cartilage had a positive correlation with the Mankin score. X-ray analysis of cartilage-specific CCN3 overexpression mice (Tg) revealed deformation of the femoral and humeral head in the early stage, and immunohistochemical analysis showed accumulated aggrecan neoepitope staining as well as CCN3 staining and the roughening of the joint surface in Tg femoral and humeral heads. Primary chondrocytes from the Tg femoral head showed enhanced expression of Ccn3, Adamts5, p16, Il-6, and Tnfα, and decreased expression of Col2a1 and -an. These findings indicate a correlation between OA degenerative changes and the expression of CCN3, irrespective of age and mechanical loading. Furthermore, the Mankin score indicates that the expression level of Ccn3 correlates with the progression of OA.

DOI： 10.3390/ijms232315311

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Language：Japanese   Publisher：(公社)日本生化学会  

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Language：Japanese   Publisher：(一社)中部日本整形外科災害外科学会  

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Language：English   Publisher：(一社)日本癌治療学会  

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Language：English   Publisher：(一社)日本癌治療学会  

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Language：Japanese   Publisher：(公社)日本リハビリテーション医学会  

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Language：Japanese   Publisher：(公社)日本リハビリテーション医学会  

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Language：Japanese   Publisher：(公社)日本リハビリテーション医学会  

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Language：Japanese   Publisher：(一社)日本小児血液・がん学会  

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Language：Japanese   Publisher：(公社)日本リハビリテーション医学会  

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

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Language：Japanese   Publisher：(公社)日本リハビリテーション医学会  

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

Giant cell tumor of bone (GCTB) is an intermediate bone tumor that rarely undergoes malignant transformation. Secondary malignant GCTB (SMGCTB) is defined as a lesion in which high-grade sarcoma occurs at the site of previously treated GCTB. The present study retrospectively reviewed the medical records of patients with GCTB treated at Okayama University Hospital between April 1986 and April 2020. The clinicopathological and histological features of patients with SMGCTB without prior radiotherapy were investigated. A total of three patients (4%) with SMGCTB were detected, and the tumor sites were the distal ulna, distal femur and sacrum. Two of the patients had been treated with curettage and bone graft, and one had been treated with denosumab. In all cases, the lesions were made up of two components, the conventional GCTB component and the malignant component. The Ki67 labeling index was higher in the malignant components of SMGCTB and metastatic lesions compared with that in primary and recurrent conventional GCTB, or the conventional GCTB component of SMGCTB. Moreover, p53 expression was higher in these same components in patients who underwent curettage and bone grafting; however, there was no difference in the patient that received denosumab treatment. In this patient, clinical cancer genomic profiling revealed loss of CDKN2A, CDKN2B and MTAP expression. All three patients developed distant metastasis. The patients with SMGCTB in the ulna and femur died 13 and 54 months after detection of malignant transformation, respectively. The patient with SMGCTB in the sacrum received carbon-ion radiotherapy to the sacrum and pazopanib; the treatment was effective and the patient was alive at the last follow-up 3 years later. In conclusion, p53 may be associated with malignant transformation in GCTB. Future studies should investigate the association of between denosumab treatment and malignant transformation, as well as molecular targeted therapy to improve the clinical outcomes of SMGCTB.

DOI： 10.3892/ol.2022.13439

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：English   Publisher：(一社)日本癌学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：English   Publisher：(一社)日本癌学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：English   Publisher：(一社)日本癌学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：English   Publisher：(一社)日本癌学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Publishing type：Research paper (scientific journal)   Publisher：Hindawi Limited  

Lateral meniscus (LM) posterior root tear (LMPRT) is mainly caused by trauma, especially trauma associated with anterior cruciate ligament (ACL) injuries. Although a transtibial pullout repair or a side-to-side repair is commonly performed for LMPRT, to the best of our knowledge, there is no clinical report of LMPRT with tissue loss using the pullout technique. Thus, the purpose of this report was to describe a clinical, radiographic, and arthroscopic outcome after pullout repair for a case of LMPRT with a large defect with a chronic ACL tear and complex medial meniscus (MM) tears. A 31-year-old man complained of knee pain and restricted range of motion after twisting his knee when he stepped on an iron pipe. The patient had a football-related injury to his right knee 14 years before presentation, and since then, the patient’s knee has given out more than 10 times but was left unassessed. Magnetic resonance imaging showed LMPRT with tissue loss, ACL tears, and complex MM tears. Transtibial pullout repair of the LMPRT with ACL reconstruction and MM repairs were performed. Following the pullout repair of the LMPRT, an approximately 6 mm gap remained between the LM posterior root and root insertion. However, magnetic resonance imaging and second-look arthroscopy at 1 year postoperatively revealed meniscal healing, gap filling with some regeneration tissue, of the LM posterior root. Furthermore, the lateral meniscus extrusion in the coronal plane improved from 3.1 mm (preoperative) to 1.6 mm (1 year postoperatively). Transtibial pullout repair with the remaining gap could be a viable treatment option for LMPRT with tissue loss, combined with ACL reconstruction.

DOI： 10.1155/2022/9776388

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Other Link： http://downloads.hindawi.com/journals/crior/2022/9776388.xml

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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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Language：Japanese   Publisher：(一社)日本骨・関節感染症学会  

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Language：Japanese   Publisher：大道学館出版部  

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Language：Japanese   Publisher：(一社)日本遺伝カウンセリング学会  

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Language：Japanese   Publisher：日本運動器科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：日本運動器科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本リハビリテーション医学会  

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Language：Japanese   Publisher：(公社)日本リハビリテーション医学会  

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Language：Japanese   Publisher：(公社)日本リハビリテーション医学会  

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Language：Japanese   Publisher：(公社)日本リハビリテーション医学会  

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

Bone marrow edema (BME) after meniscus injury and risk factors for subchondral insufficiency fracture of the knee (SIFK) have been reported. However, their association with medial meniscus posterior root tear (MMPRT) remains unknown. We investigated the association of BME volume (BME-V), posterior shinycorner lesion (PSCL), and SIFK with MMPRT to examine the correlations between BME-V and medial meniscus extrusion (MME), PSCL and duration from injury to the time of magnetic resonance imaging (duration), and SIFK and duration. Twenty-nine patients who underwent surgery for MMPRT were included (mean age, 59.2; range, 39-84). The presence of PSCL, femoral BME-V (cm3), and SIFK grade (1-4) were evaluated. Preoperative factors, such as MME (mm) and duration (weeks), were investigated using multivariate linear/ logistic regression analyses. Multivariate linear regression analysis revealed duration as a significant factor for high-grade SIFK (p<0.01). Multivariate logistic regression analysis revealed duration as a significant factor for the presence of PSCL (odds ratio=0.94, p<0.05). A long duration of MMPRT leads to severe MME and highgrade SIFK (3 and 4), often resulting in knee arthroplasty. Early diagnosis of MMPRT and pullout repair can prevent severe MME and high-grade SIFK.

DOI： 10.18926/AMO/63405

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Language：Japanese   Publisher：(一社)中部日本整形外科災害外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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

Stem cell-based therapies and experimental methods rely on efficient induction of human pluripotent stem cells (hPSCs). During limb development, the lateral plate mesoderm (LPM) produces limb-bud mesenchymal (LBM) cells that differentiate into osteochondroprogenitor cells and form cartilage tissues in the appendicular skeleton. Previously, we generated PRRX1-tdTomato reporter hPSCs to establish the protocol for inducing the hPSC-derived PRRX1+ LBM-like cells. However, surface antigens that assess the induction efficiency of hPSC-derived PRRX1+ LBM-like cells from LPM have not been identified. Here, we used PRRX1-tdTomato reporter hPSCs and found that high pluripotent cell density suppressed the expression of PRRX1 mRNA and tdTomato after LBM-like induction. RNA sequencing and flow cytometry suggested that PRRX1-tdTomato+ LBM-like cells are defined as CD44high CD140Bhigh CD49f-. Importantly, other hPSC lines, including four human induced pluripotent stem cell lines (414C2, 1383D2, HPS1042, HPS1043) and two human embryonic stem cell lines (SEES4, SEES7), showed the same results. Thus, an appropriate cell density of hPSCs before differentiation is a prerequisite for inducing the CD44high CD140Bhigh CD49f- PRRX1+ LBM-like cells.

DOI： 10.3390/ijms23052661

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

Objective: This study aimed to investigate the association between overall survival (OS) and activities of daily living (ADL) in patients with skeletal-related events. In this study, 265 patients whose clinical parameters were available before radiotherapy were investigated. Methods: Age, sex, ADL, pain, the primary site, spinal level of bone metastases, spinal instability, treatment strategy, including chemotherapy or palliative treatment, and OS were investigated. ADL patients with a Barthel index of ≥90 were classified as the high ADL group, while those with a score < 90 were classified as the low ADL group. For OS, patients surviving ≥160 days were classified as the non-poor prognosis group, and those who survived <160 days were classified as the poor prognosis group. Results: Age, sex, ADL, pain, the primary site, and treatment strategy for OS were different between the two groups (p < 0.1). Logistic regression analysis revealed that ADL, the primary site, and treatment strategy were significant predictors of OS (p < 0.05). High ADL, breast cancer, and chemotherapy had a positive effect on OS. Conclusions: It is suggested that improvements may be obtained by performing rehabilitation interventions to maintain and improve ADL, by constructing a system for monitoring spinal bone metastases with images before ADL decreases, and by performing interventions such as changes in treatment methods such as RT or surgery at appropriate times.

DOI： 10.3390/healthcare10020350

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Language：Japanese   Publisher：(一社)日本移植学会  

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

DOI： 10.1007/s10147-022-02119-7

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Other Link： https://link.springer.com/article/10.1007/s10147-022-02119-7/fulltext.html

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This study examined changes in the quality of life (QOL), as well as the factors affecting QOL, among patients with painful spinal bone metastases without paralysis for 1 month after radiotherapy. METHODS: This study included 79 participants (40 male and 39 female; median age, 65 (42-88) years) who had undergone radiotherapy for painful spinal bone metastases without paralysis. Patients' age, sex, activities of daily living (Barthel index), pain, spinal instability (spinal instability neoplastic score [SINS]), and QOL (EORTC QLQ-C30) were investigated. RESULTS: Having an unstable SINS score was a positive factor for global health status (p < 0.05). The improvement in activities of daily living and response to pain were positive factors for physical function (p < 0.05). A positive effect on emotional function was confirmed among female patients (p < 0.05). CONCLUSION: Engaging in rehabilitation along with radiotherapy leads to improvements in QOL for patients with spinal bone metastases.

DOI： 10.3390/healthcare9111499

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

Early prediction of future acetabular development is important to determine an additional surgery for developmental dysplasia of the hip (DDH). The purpose of this study was to investigate the predictive factors of acetabular development using MRI. We retrospectively investigated dislocated 40 hips and 34 normal hips in 37 pediatric patients (9 males and 28 females) with DDH who underwent open reduction after walking age. We evaluated the cartilaginous acetabulum and labrum of the patients using coronal MRI T2*-weighted images at 5 years of age. The mean age at the time of surgery was 22 months, and the mean age at the final survey was 19 years. We divided patients into two groups in accordance with the Severin classification at the final follow-up. Groups with good outcomes (affected 26 hips and unaffected 27 hips) and poor outcomes (14 hips and 7 hips) were compared using the MRI parameters on each side. Predictive factors of acetabular development were identified using univariate and multiple logistic regression analyses. Using multiple logistic regression analysis, labral acetabular roof depth and labral hip center distance at 5 years of age represented predictors after open reduction (odds ratio 0.27, P = 0.035; odds ratio 3.4, P = 0.028, respectively) on the affected side, and bony hip center distance represented a predictor on the unaffected side (odds ratio 2.6, P = 0.049). Acetabular development in the unaffected side could be predicted by bony assessment, while acetabular development in the affected side had to be assessed by labrum using MRI.

DOI： 10.1097/BPB.0000000000000799

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Publisher：Research Square Platform LLC  

Abstract

Only few reports have assessed the characteristics and oncological and functional outcomes of forearm soft tissue sarcomas (STS). Then, we aimed to investigate the clinical features and survival-related factors for forearm STS who underwent surgical excision at our institution. There were 38 patients. Fourteen patients (41%) were referred to our institution after an unplanned excision and tumor size and grade were significantly associated with the receipt of it. The postoperative median Musculoskeletal Tumor Society rating scale (MSTS) score was 28. Bone resection or major nerve palsy was the only factor influencing the postoperative MSTS score (P &lt; 0.001). There was no significant difference in MSTS scores according to the reconstruction procedures (the use of flap or tendon reconstruction). The 5-year local recurrence-free survival (LRFS) rate was 86%. Univariate analysis revealed that the histological diagnosis of myxofibrosarcoma was the only factor that influenced LRFS (P = 0.047). The 5-year metastasis-free survival rate was 77%. The 5-year overall survival (OS) rate was 94%. Age was the only factor that influenced OS (P = 0.01). In conclusion, reconstruction of the skin and tendon can compensate for function. Careful follow-up is important, especially in patients with myxofibrosarcoma, due to its likelihood of local recurrence.

DOI： 10.21203/rs.3.rs-1028963/v1

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Other Link： https://www.researchsquare.com/article/rs-1028963/v1.html

Language：English  

DOI： 10.1016/j.jos.2018.12.030

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Language：Japanese   Publisher：(一社)日本小児整形外科学会  

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Language：Japanese   Publisher：(株)医学書院  

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Language：Japanese   Publisher：(株)医学書院  

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

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Language：Japanese   Publisher：(一社)中部日本整形外科災害外科学会  

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Language：Japanese   Publisher：(一社)中部日本整形外科災害外科学会  

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

BACKGROUND: The purpose of this study was to investigate the factors related to patient's participation in leisure activity in breast cancer patients with axillary lymph node dissection at 3 months after surgery. METHODS: In total, 160 women who were employed before their surgery were evaluated. Age, body mass index (BMI), employment, level of lymph node dissection, marital status, children, coresident household members, preoperative chemotherapy, postoperative chemotherapy, postoperative hormonal therapy, postoperative radiotherapy, shoulder range of motion test, upper limb function, quality of life, and patient's participation in leisure activity were evaluated. RESULTS: Patients who undertook leisure activities constituted the leisure activity group, and patients who did not constituted the non-leisure activity group. Global health status, emotional function, social function, and dyspnea were significantly different between the leisure activity group and the non-leisure activity group at 3 months after surgery (p < 0.05). Regarding factors that affected participation in leisure activities, logistic regression analysis showed that only participation in leisure activities before surgery was significantly associated with participation in leisure activities at 3 months after surgery (p < 0.05). CONCLUSION: Patients who did not participate in leisure activities prior to surgery were unlikely to participate 3 months after surgery and thus require intervention to encourage their involvement.

DOI： 10.3390/healthcare9081078

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

Current protocols for the differentiation of human pluripotent stem cells (hPSCs) into chondrocytes do not allow for the expansion of intermediate progenitors so as to prospectively assess their chondrogenic potential. Here we report a protocol that leverages PRRX1-tdTomato reporter hPSCs for the selective induction of expandable and ontogenetically defined PRRX1+ limb-bud-like mesenchymal cells under defined xeno-free conditions, and the prospective assessment of the cells' chondrogenic potential via the cell-surface markers CD90, CD140B and CD82. The cells, which proliferated stably and exhibited the potential to undergo chondrogenic differentiation, formed hyaline cartilaginous-like tissue commensurate to their PRRX1-expression levels. Moreover, we show that limb-bud-like mesenchymal cells derived from patient-derived induced hPSCs can be used to identify therapeutic candidates for type II collagenopathy and we developed a method to generate uniformly sized hyaline cartilaginous-like particles by plating the cells on culture dishes coated with spots of a zwitterionic polymer. PRRX1+ limb-bud-like mesenchymal cells could facilitate the mass production of chondrocytes and cartilaginous tissues for applications in drug screening and tissue engineering.

DOI： 10.1038/s41551-021-00778-x

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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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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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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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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Language：Japanese   Publisher：(公社)日本リハビリテーション医学会  

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Language：Japanese   Publisher：(公社)日本リハビリテーション医学会  

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Language：Japanese   Publisher：(公社)日本リハビリテーション医学会  

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Language：Japanese   Publisher：(公社)日本リハビリテーション医学会  

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Language：Japanese   Publisher：(公社)日本リハビリテーション医学会  

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

The lack of noninvasive biomarkers that can be used for tumor monitoring is a major problem for soft-tissue sarcomas. Here we describe a sensitive analytical technique for tumor monitoring by detecting circulating extracellular vesicles (EVs) of patients with synovial sarcoma (SS). The proteomic analysis of purified EVs from SYO-1, HS-SY-II, and YaFuSS identified 199 common proteins. DAVID GO analysis identified monocarboxylate transporter 1 (MCT1) as a surface marker of SS-derived EVs, which was also highly expressed in SS patient-derived EVs compared with healthy individuals. MCT1+CD9+ EVs were also detected from SS-bearing mice and their expression levels were significantly correlated with tumor volume (p = 0.003). Furthermore, serum levels of MCT1+CD9+ EVs reflected tumor burden in SS patients. Immunohistochemistry revealed that MCT1 was positive in 96.7% of SS specimens and its expression on the cytoplasm/plasma membrane was significantly associated with worse overall survival (p = 0.002). Silencing of MCT1 reduced the cellular viability, and migration and invasion capability of SS cells. This work describes a new liquid biopsy technique to sensitively monitor SS using circulating MCT1+CD9+ EVs and indicates the therapeutic potential of MCT1 in SS.

DOI： 10.3390/cancers13081823

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Sarcomas are a heterogeneous group of malignancies of mesenchymal origin; their molecular and genomic mechanisms differ with regard to histology. These characteristics lead to the presentation of varied immunological profiles based on the tumor microenvironment. Various immunotherapies are considered for the treatment of sarcoma. These treatments are performed either in isolation or in combination with other methods such as cytotoxic chemotherapy or the use of molecular target agents. Among these, two recently emerging immunotherapies include T-cell receptor gene therapy and immune checkpoint inhibitor therapy, which are expected to be effective for many types of sarcoma. A sarcoma with a disease-specific translocation and a limited number of mutations, such as synovial sarcoma, expresses high levels of self-antigens, like the New York esophageal squamous cell carcinoma 1, which has been targeted in T-cell receptor gene therapy. On the other hand, sarcomas with a greater number of mutations, such as undifferentiated pleomorphic sarcomas, myxofibrosarcoma and dedifferentiated liposarcomas, can be good candidates for immune checkpoint inhibitors. Among immune checkpoint inhibitor therapies, programmed cell death-1 blockade (nivolumab and pembrolizumab) and cytotoxic T-lymphocyte-associated antigen 4 blockade (ipilimumab) have been investigated most often in sarcoma. Although the sole use of immune checkpoint inhibitors provides limited efficacy, combined immunotherapy with immune checkpoint inhibitors or molecular target agents, especially antiangiogenic agents, has shown moderate results against some types of sarcoma, such as the alveolar soft part sarcoma. Several clinical trials utilizing immunotherapy, including T-cell receptor gene therapy and immune checkpoint inhibitors, in sarcomas are under progress. By clarifying the tumor microenvironment and biomarker-predictive capacity of immunotherapy in sarcomas, better clinical trials can be designed; this could lead to improved outcomes for immunotherapy in sarcoma.

DOI： 10.1093/jjco/hyab005

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Language：Japanese   Publisher：(株)南江堂  

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Language：Japanese   Publisher：保健医療学学会  

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Language：Japanese   Publisher：(株)南江堂  

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Language：Japanese   Publisher：(株)南江堂  

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Language：Japanese   Publisher：(株)南江堂  

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Sarcomas are complex tissues in which sarcoma cells maintain intricate interactions with their tumor microenvironment. Tumor-associated macrophages (TAMs) are a major component of tumor-infiltrating immune cells in the tumor microenvironment and have a dominant role as orchestrators of tumor-related inflammation. TAMs promote tumor growth and metastasis, stimulate angiogenesis, mediate immune suppression, and limit the antitumor activity of conventional chemotherapy and radiotherapy. Evidence suggests that the increased infiltration of TAMs and elevated expression of macrophage-related genes are associated with poor prognoses in most solid tumors, whereas evidence of this in sarcomas is limited. Based on these findings, TAM-targeted therapeutic strategies, such as inhibition of CSF-1/CSF-1R, CCL2/CCR2, and CD47/SIRPα, have been developed and are currently being evaluated in clinical trials. While most of the therapeutic challenges that target sarcoma cells have been unsuccessful and the prognosis of sarcomas has plateaued since the 1990s, several clinical trials of these strategies have yielded promising results and warrant further investigation to determine their translational benefit in sarcoma patients. This review summarizes the roles of TAMs in sarcomas and provides a rationale and update of TAM-targeted therapy as a novel treatment approach for sarcomas.

DOI： 10.3390/cancers13051086

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Language：Japanese   Publisher：(株)日本臨床社  

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Language：Japanese   Publisher：(株)総合医学社  

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Language：Japanese   Publisher：(一社)中部日本整形外科災害外科学会  

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OBJECTIVE: The purpose of this study was to investigate factors related to early quality of life (QOL) three months after surgery in breast cancer patients with axillary lymph node dissection. METHODS: The subjects of this study were 195 consecutive patients who underwent axillary lymph node dissection for breast cancer. Age, body mass index, level of lymph node dissection, marriage, children, co-resident household members, neoadjuvant chemotherapy, postoperative chemotherapy, postoperative hormonal therapy, postoperative radiotherapy, upper limb function (disabilities of the arm, shoulder, and hand (DASH)), and QOL (European Organization for the Treatment and Research of Cancer Quality of Life Questionnaire (EORTC QLQ-C30)) were evaluated. For each item of the EORTC QLQ-C30, compared with preoperative status and three months after surgery, those who improved or remained unchanged in the three months after surgery were classified as the maintenance and improved groups, and those with worsening status were classified as the worsened group. RESULTS: Age, level of lymph node dissection, DASH, neoadjuvant chemotherapy, postoperative chemotherapy, and postoperative radiotherapy were significantly associated with QOL (p < 0.05). CONCLUSIONS: The early QOL of postoperative patients with breast cancer is affected by multiple factors, such as upper limb function and postoperative chemotherapy, and thus comprehensive intervention is required.

DOI： 10.3390/healthcare9020213

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Background: Video-assisted thoracoscopic surgery (VATS) has been increasingly used as an approach for lung lobectomy. However, the recovery of respiratory and physical function may be insufficient at discharge because the average length of hospital stay is decreasing after surgery. In this study, we investigated the changes in physical function, lung function, and quality of life (QOL) of lung cancer patients after VATS, and factors for QOL were also evaluated. METHODS: The subjects of this study were 41 consecutive patients who underwent video-assisted lung lobectomy for lung cancer. Rehabilitation was performed both before and after surgery. Lung function testing, physical function testing (timed up and go test (TUG) and the 30-s chair-stand test (CS-30)), and QOL (EORTC QLQ-C30) were measured before and 1 week after surgery. RESULTS: Postoperative VC recovered to 76.3% ± 15.6% 1 week after surgery. TUG, CS-30, and QOL were significantly worse after surgery (p < 0.05). Lung function and physical function were found to affect QOL. Postoperative complications included pneumonia in 1 patient. There were no patients who discontinued rehabilitation. CONCLUSION: Our rehabilitation program was safe and useful for patients after VATS.

DOI： 10.3390/healthcare9020136

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In this study, we examined whether axillary web syndrome (AWS) in patients with breast cancer following axil-lary lymph node dissection affects range of motion (ROM), upper extremity function, and quality of life (QOL). The risk factors for AWS were also evaluated in a total of 238 consecutive breast cancer patients follow-ing axillary lymph node dissection. At 1, 2, and 3 months after surgery, there were no significant differences between the AWS group and the non-AWS group in upper-limb function or QOL. At 2 months after surgery, shoulder flexion and abduction ROM were significantly higher in the AWS group than in the non-AWS group (p < 0.05). Self-training time at home was not significantly different between the groups at 1, 2, or 3 months. Only age was a significant predictor of AWS at 1 month after surgery (p < 0.05). The AWS group in the present study did not have worse results for shoulder joint ROM, upper-limb function, and QOL than the non-AWS group. Younger age should be useful for predicting the development of AWS in the early postoperative period.

DOI： 10.18926/AMO/61432

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Language：Japanese   Publisher：西日本泌尿器科学会  

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Other Link： https://search.jamas.or.jp/link/ui/2021210988

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Paired related homeobox 1 (PRRX1) is a marker of limb bud mesenchymal cells, and deficiency of p53 or Rb in Prrx1-positive cells induces osteosarcoma in several mouse models. However, the regulatory roles of PRRX1 in human osteosarcoma have not been defined. In this study, we performed PRRX1 immunostaining on 35 human osteosarcoma specimens to assess the correlation between PRRX1 level and overall survival. In patients with osteosarcoma, the expression level of PRRX1 positively correlated with poor prognosis or the ratio of lung metastasis. Additionally, we found PRRX1 expression on in 143B cells, a human osteosarcoma line with a high metastatic capacity. Downregulation of PRRX1 not only suppressed proliferation and invasion but also increased the sensitivity to cisplatin and doxorubicin. When 143B cells were subcutaneously transplanted into nude mice, PRRX1 knockdown decreased tumor sizes and rates of lung metastasis. Interestingly, forskolin, a chemical compound identified by Connectivity Map analysis using RNA expression signatures during PRRX1 knockdown, decreased tumor proliferation and cell migration to the same degree as PRRX1 knockdown. These results demonstrate that PRRX1 promotes tumor malignancy in human osteosarcoma.

DOI： 10.1016/j.tranon.2020.100960

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BACKGROUND: The identification of factors that are related to return to work after surgery for breast cancer could help healthcare professionals accurately identify patients at risk of return to work-related difficulties in order to provide them with appropriate support during breast cancer management. OBJECTIVE: The aim of this study was to identify factors related to return to work in breast cancer patients three months after axillary lymph node dissection. METHODS: Seventy-three women who were working before the surgery were evaluated. Age, body mass index, level of lymph node dissection, marital status, children, co-resident household members, preoperative chemotherapy, postoperative chemotherapy, postoperative hormonal therapy, postoperative radiotherapy, shoulder range of motion, upper limb function (Disabilities of the Arm, Shoulder and Hand; DASH), and work were evaluated. Patients who had returned to work constituted the return to work group, and those who had not returned to work constituted the no return to work group. RESULTS: Of the patients, 36 returned to work at three months. Logistic regression analysis including the five variables showed that shoulder flexion range of motion and DASH were significantly associated with return to work (p < 0.05). CONCLUSIONS: The observation that the symptoms and limitations of upper limb function and shoulder flexion range of motion affect return to work may indicate the importance of postoperative rehabilitation in breast cancer patients following axillary lymph node dissection.

DOI： 10.3233/WOR-213571

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Unidirectional porous hydroxyapatite (UDPHAp) was developed as an excellent scaffold with unidirectional pores oriented in the horizontal direction with interpore connections. The purpose of this study was to assess radiographic changes and clinical outcomes and complications following UDPHAp implantation to treat benign bone tumors. We retrospectively analyzed 44 patients treated with intralesional resection and UDPHAp implantation for benign bone tumors between 2010 and 2015. Clinical and radiographic findings were evaluated postoperatively at regular follow-up visits. The mean follow-up was 49 months. Radiographic changes were classified into five stages based on bone formation in the implanted UDPHAp according to Tamai's classification. All patients showed excellent bone formation inside and around implanted UDPHAp. Absorption of UDPHAp and bone marrow cavity remodeling was identified in 20 patients at a mean of 17 months postoperatively, and was significantly more common in young patients. Preoperative cortical thinning was completely regenerated in 26 of 31 patients on average 10 months after surgery. There were no cases of delayed wound healing, postoperative infection, or allergic reaction related to implanted UDPHAp. UDPHAp is a useful bone-filling substitute for treating benign bone tumor, and the use of this material has a low complication rate.

DOI： 10.1038/s41598-020-78409-9

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Language：Japanese   Publisher：(株)医学書院  

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BACKGROUND: Dedifferentiated liposarcoma (DDLPS) is a rare malignancy that transitions from an atypical lipomatous tumor to a sarcoma with a variable morphologic appearance. The behavior of this tumor in the retroperitoneum is aggressive, but the behavior of DDLPS in the extremities is less well-defined because it is rare. Few reports have assessed the imaging features and clinical outcomes of primary DDLPS in the extremities. QUESTIONS/PURPOSES: In patients with primary DDLPS of the extremity, we asked the following questions: (1) How frequently do additional primary malignancies occur in patients with DDLPS? (2) What is the rate of overall survival, metastases, and local recurrence in DDLPS? (3) What factors are associated with metastasis-free survival and local recurrence in DDLPS? METHODS: We defined DDLPS as a biphasic neoplasm that transitions from an atypical lipomatous tumor (ALT) to a sarcoma of variable morphologic appearance and histologic grades. We retrospectively evaluated the medical records of patients with DDLPS of the extremities who underwent surgery in our institution between 2003 and 2017. During that time, 16 patients were treated for this diagnosis; one was excluded from this study because the patient did not have an MRI, leaving 15 patients (nine men, six women; their median [range] age was 67 years [42 to 87]) for evaluation. All had a minimum of 2 years follow-up (median [range] 54 months [25 to 136]); 14 of 15 have been seen in the last 5 years (one patient, who was doing well at the time, was lost after 9 years of follow-up). In 11 patients, MRI demonstrated two components: an ALT component with high intensity on both T1-weighed and T2-weighted sequences and a dedifferentiated component low-to-intermediate intensity on T1-weighed and heterogeneous hyperintensity on T2-weighted sequence. Nine patients were evaluated using 2-deoxy-2-18F-fluoro-D-glucose positron emission tomography (FDG-PET) combined with CT (PET/CT). PET/CT showed a biphasic pattern with a close relationship to MRI findings. The dedifferentiated component presented with high FDG uptake (median [range] maximum standardized uptake value 5.1 [1.9 to 22.6]), while the atypical lipomatous tumor component showed almost no FDG uptake. In all patients, immunohistochemical studies of p16 and cyclin-dependent kinase-4 (CDK4) were investigated. Positive staining for both p16 and CDK4 were seen in 13 of 15 patients.We retrospectively evaluated the electronic medical records of all patients in our institution for the presence of additional primary malignancies, local recurrence-free survival, metastasis-free survival, and overall survival. The survival rate was estimated using the Kaplan-Meier method. The Wilcoxon exact test was used to determine the prognostic importance of the following survival variables: age, sex, maximum tumor size, radiotherapy, and surgical margin. RESULTS: Seven additional primary malignancies developed in five of 15 patients (two lung cancers, two sarcomas, one renal cell cancer, one uterine cancer, and one non-Hodgkin lymphoma). The 3- and 5-year metastasis-free survival rates were 86% (95% CI 0.67 to 1.00) and 75% (95% CI 0.49 to 1.00), respectively. With the numbers available, we found no factors associated with metastasis-free survival. The 3- and 5-year overall survival rates were 100% (95% CI 1.00 to 1.00) and 88% (95% CI 0.65 to 1.00), respectively. Three of 15 patients had local recurrence. The 3- and 5-year local recurrence-free survival rates were 86% (95% CI 0.67 to 1.00) and 75% (95% CI 0.49 to 1.00), respectively. Large (> 15 cm) tumors were more likely to have a local recurrence (p = 0.04). CONCLUSIONS: In this small series, we found that the extremities are a favorable site for DDLPS compared with the retroperitoneum, although we did not directly compare the two sites. This rare tumor has a relatively high likelihood of being associated with other malignancies. We believe patients should be assessed and monitored carefully for this possibility. In the future, larger studies are needed to better define predictors of local recurrence, although the tumor's size may be associated with a greater propensity for local recurrence. LEVEL OF EVIDENCE: Level II, prognostic study.

DOI： 10.1097/CORR.0000000000001338

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Aging is a major risk factor of osteoarthritis, which is characterized by the degeneration of articular cartilage. CCN3, a member of the CCN family, is expressed in cartilage and has various physiological functions during chondrocyte development, differentiation, and regeneration. Here, we examine the role of CCN3 in cartilage maintenance. During aging, the expression of Ccn3 mRNA in mouse primary chondrocytes from knee cartilage increased and showed a positive correlation with p21 and p53 mRNA. Increased accumulation of CCN3 protein was confirmed. To analyze the effects of CCN3 in vitro, either primary cultured human articular chondrocytes or rat chondrosarcoma cell line (RCS) were used. Artificial senescence induced by H2O2 caused a dose-dependent increase in Ccn3 gene and CCN3 protein expression, along with enhanced expression of p21 and p53 mRNA and proteins, as well as SA-β gal activity. Overexpression of CCN3 also enhanced p21 promoter activity via p53. Accordingly, the addition of recombinant CCN3 protein to the culture increased the expression of p21 and p53 mRNAs. We have produced cartilage-specific CCN3-overexpressing transgenic mice, and found degradative changes in knee joints within two months. Inflammatory gene expression was found even in the rib chondrocytes of three-month-old transgenic mice. Similar results were observed in human knee articular chondrocytes from patients at both mRNA and protein levels. These results indicate that CCN3 is a new senescence marker of chondrocytes, and the overexpression of CCN3 in cartilage may in part promote chondrocyte senescence, leading to the degeneration of articular cartilage through the induction of p53 and p21.

DOI： 10.3390/ijms21207556

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Language：Japanese   Publisher：(株)日本臨床社  

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The effect of nivolumab and the relation between bone response and tumor control in patients with non-small-cell lung cancer (NSCLC) with bone metastases are not clear. The outcome of nivolumab monotherapy was investigated, and whether the response of bone metastases is useful as an early predictor of tumor control in patients with NSCLC with bone metastases was examined. The participants included 15 patients who received nivolumab monotherapy for NSCLC with bone metastases in our institution between 2015 and 2017. Tumor control was defined using Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST1.1). Response of bone metastases was assessed by the MD Anderson response criteria (MDA criteria). Responses according to RECIST1.1 and the MDA criteria were classified as responder (complete response or partial response) and non-responder [progressive disease (PD) or stable disease]. Progression-free survival (PFS) was investigated using the Kaplan-Meier method. With RECIST1.1, the overall response rate was 20%. Multivariate analysis showed that the MDA criteria were the only risk factor for patients with PD (RECIST1.1). Median PFS was 1.9 months, with PFS of 20% at 6 months. Univariate analysis showed that being a non-responder according to the MDA criteria was the only risk factor for PFS. In patients who were responders (MDA criteria) within 3 months, PFS was 83 and 50% at 3 and 6 months, respectively, though all non-responder (MDA criteria) patients converted to PD (RECIST1.1) within 3 months. Response according to RECIST1.1 was significantly correlated with response according to the MDA criteria (P<0.05). In patients who were both responders according to RECIST1.1 and the MDA criteria, time to response with the MDA criteria (1.4-2.0 months) was earlier than with RECIST1.1 (2.8-3.0 months) in all patients. In conclusion, application of the MDA criteria within 2 months of nivolumab monotherapy is useful for early prediction of response and prognosis in patients with NSCLC with bone metastases.

DOI： 10.3892/ol.2020.11856

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Language：Japanese   Publisher：医歯薬出版(株)  

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Language：Japanese   Publisher：(株)アークメディア  

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Language：Japanese   Publisher：(株)南江堂  

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Language：Japanese   Publisher：(株)南江堂  

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Language：Japanese   Publisher：(株)三輪書店  

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Malignant spinal cord compression (MSCC) is a serious complication of cancers. The present study aimed to establish a multidisciplinary treatment system for urgent magnetic resonance imaging (MRI) and referral to orthopedists in order to prevent neurological deficits caused by MSCC. In the present study, the extent to which this system achieved early diagnosis and treatment and prevented MSCC-caused neurological deficits was examined. The records from patients with neurological deficits caused by MSCC before (between April 2007 and March 2012; group A) and after (between April 2012 and March 2017; group B) the establishment of the multidisciplinary system at the Shikoku Cancer Center (Ehime, Japan) were retrospectively evaluated. The numbers of patients with neurological deficits were 38 and 7 in groups A and B, respectively. All patients received radiotherapy. The incidence of neurological deficits was 13.2 and 3.4% in groups A and B, respectively (P<0.001). The proportion of patients with improvement in the severity of neurological deficits was 5.3 and 28.6% in groups A and B, respectively (P<0.001). The interval between physicians' recognition of a neurological deficit and MRI and the start of treatment, the number of cases, and the severity of neurological deficits were evaluated in groups A and B. The median interval between recognition of a neurological deficit by physicians and MRI was 3 and 0 days in groups A and B, respectively (P<0.001). The median interval between physicians' recognition of a neurological deficit and the start of treatment was 3 and 0 days in groups A and B, respectively (P<0.001). By using a multidisciplinary treatment system, the incidence and severity of neurological deficits following treatment were significantly improved. Therefore, the multidisciplinary treatment system used in the present study may be useful for early diagnosis, treatment and prevention of MSCC in patients with bone metastases.

DOI： 10.3892/ol.2020.11415

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Language：Japanese   Publisher：保健医療学学会  

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BACKGROUND: The purpose of this study was to investigate the factors related to early postoperative psychological conditions in breast cancer patients with axillary lymph node dissection 3 months after the surgery. METHODS: The subjects of this study were 200 consecutive patients who underwent axillary lymph node dissection for breast cancer at our hospital. Age, body mass index, surgical side, work, marriage, presence of children, presence of co-resident household members, resection of the pectoralis minor muscle, preoperative chemotherapy, postoperative chemotherapy, postoperative hormonal therapy, postoperative radiotherapy, shoulder range of motion, upper limb function (Disabilities of the Arm, Shoulder and Hand; DASH), and psychological conditions were evaluated. In this study, a Distress and Impact Thermometer was used to classify patients with adjustment disorders, depression, or major depression and suicidal ideation into a group with psychological problems and the remaining patients into a group with no psychological problems. RESULTS: Logistic regression analysis showed that only DASH was statistically significantly associated with psychological conditions (p < 0.05). Using receiver operating characteristic curve analysis, a DASH score of 18 or greater was found to be very specific for predicting psychological conditions. CONCLUSIONS: The observation that somatic symptoms and disability of upper limb function are related to psychological conditions may indicate the importance of postoperative rehabilitation in breast cancer patients with axillary lymph node dissection.

DOI： 10.1007/s12282-019-01020-y

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Language：Japanese   Publisher：日本CAOS研究会・日本最小侵襲整形外科学会  

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OBJECTIVE: To investigate the factors affecting the discharge destination of patients with spinal bone metastases. METHODS: We reviewed the medical records of patients admitted to our institute with a diagnosis of skeletalrelated events secondary to malignant disease. Exclusion criteria comprised decreased cognitive function and hypercalcemia, brain metastasis, peritoneal dissemination, and pleural dissemination. The factors examined included the discharge destination, age, sex, the Barthel Index (BI) at admission and discharge, pain at admission and discharge, number of co-resident household members, length of hospital stay, treatment strategy, spinal instability neoplastic score, vertebral body collapse, spinal level of bone metastases, and motor paralysis. For the discharge destination, patients at discharge were grouped into two categories. The home group included patients discharged to their own homes, and the non-home group included patients discharged to other hospitals. RESULTS: Of 140 patients, the home group comprised 120 patients and the non-home group comprised 20 patients. Activities of daily living (ADL) and pain at rest and during motion improved significantly in the home group, whereas only pain at rest and during motion improved significantly in the non-home group. The results indicated that discharge BI and motor paralysis were the best predictors of the discharge destination; a BI cut-off value of 72.5 predicted discharge to home. CONCLUSION: This study showed that the ADL level on discharge and motor paralysis affected the discharge destination of patients with spinal bone metastases. These results are likely to be helpful in predicting the discharge destination of patients with spinal bone metastases.

DOI： 10.5535/arm.2020.44.1.69

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Medial meniscus posterior root tear causes rapid knee cartilage degradation by inducing posteromedial displacement of the medial meniscus. We evaluated medial meniscus posterior extrusion before and after pullout repair for medial meniscus posterior root tear using magnetic resonance images. Twenty-eight patients with symptomatic medial meniscus posterior root tear were included. The inclusion criteria were: acute (< 3 months) or chronic (≥3 months) medial meniscus posterior root tear after painful popping events. The exclusion criteria were: other meniscus and anterior cruciate ligament injuries. We measured medial meniscus posterior extrusion and medial meniscus anteroposterior interval at knee flexion angles of 10° and 90° preoperatively and at 3 months postoperatively. The posterior extrusion at 90° knee flexion decreased from 4.42±1.38 mm preoperatively to 3.09±1.06 mm (p<0.001) postoperatively, while at 10° knee flexion it was -4.17±1.63 mm preoperatively and -3.77±1.72mm postoperatively, showing no significant change. The anteroposterior interval at 10° knee flexion increased from 19.74±4.27 mm preoperatively to 22.15±5.10 mm postoperatively (p<0.001); at 90° knee flexion, it increased from 16.81±4.51 mm preoperatively to 19.20±4.30 mm postoperatively (p<0.001). Medial meniscus posterior extrusion and movement decreased after pullout repair. Pullout repair for medial meniscus posterior root tear improves medial meniscus posterior extrusion, especially at 90° knee flexion.

DOI： 10.18926/AMO/57713

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The case of an individual with a bilateral anterior cruciate ligament (ACL) tear combined with a medial meniscus (MM) posterior root tear is described. A 34-year-old Japanese man with bilateral ACL rupture that occurred > 10 years earlier was diagnosed with bilateral ACL tear combined with MM posterior root tear (MMPRT). We performed a transtibial pullout repair of the MMPRT with ACL reconstruction. The tibial tunnels for the MM posterior root repair and ACL reconstruction were created separately. Postoperatively, a good clinical outcome and meniscal healing were obtained. Our surgical technique may thus contribute to anatomical MM posterior root repair and ACL reconstruction.

DOI： 10.18926/AMO/57717

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

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BACKGROUND: Several studies have demonstrated that posttraumatic knee osteoarthritis progresses even after anterior cruciate ligament reconstruction. Few reports described zone-specific cartilaginous damages after anterior cruciate ligament reconstruction. This study aimed to compare the status of articular cartilage at anterior cruciate ligament reconstruction with that at second-look arthroscopy. METHODS: This study included 20 patients (20 knees, 10 males and 10 females, mean age 22.4 years, Body mass index 24.4 kg/m2) that underwent arthroscopic anatomic double-bundle anterior cruciate ligament reconstruction and second-look arthroscopy. Mean periods from injury to reconstruction and from reconstruction to second-look arthroscopy were 3.4 and 15.3 months, respectively. Cartilage lesions were evaluated arthroscopically in the 6 articular surfaces and 40 articular subcompartments independently, and these features were graded with the International Cartilage Repair Society articular cartilage injury classification; comparisons were made between the grades at reconstruction and at second-look arthroscopy. Furthermore, clinical outcomes were assessed at reconstruction and at second-look arthroscopy, using the Lysholm knee score, Tegner activity scale, International Knee Documentation Committee score, Knee injury and Osteoarthritis Outcome Score, side-to-side difference of the KT-2000 arthrometer, and pivot shift test. RESULTS: Each compartment showed a deteriorated condition at second-look arthroscopy compared with the pre-reconstruction period. A significant worsening of the articular cartilage was noted in all compartments except the lateral tibial plateau and was also observed in the central region of the medial femoral condyle and trochlea after reconstruction. However, each clinical outcome was significantly improved postoperatively. CONCLUSIONS: Good cartilage conditions were restored in most subcompartments at second-look arthroscopy. Furthermore, posttraumatic osteoarthritic changes in the patellofemoral and medial compartments progressed even in the early postoperative period, although good knee stability and clinical outcomes were obtained. Care is necessary regarding the progression of osteoarthritis and the appearance of knee symptoms in patients undergoing anterior cruciate ligament reconstruction.

DOI： 10.1016/j.jos.2019.08.001

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Language：Japanese   Publisher：(株)医学書院  

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BACKGROUND: The choice of reconstructive procedure to restore limb function is challenging after internal hemipelvectomy. Hip transposition arthroplasty, also known as resection arthroplasty, removes a malignant or aggressive tumor of the pelvis and acetabulum after which the remaining femoral head is moved proximally to the lateral surface side of the sacrum or the underside of the resected ilium after internal hemipelvectomy. It may provide reasonable functional results and have some advantages such as lowering the risk of an infected implant compared with other reconstructions because no foreign implants are used. Hip transposition is generally managed with prolonged bed rest or immobilization postoperatively to stabilize the soft tissue surrounding the remaining femur. Because enabling patients to be mobile while the soft tissues heal might be advantageous, we reviewed our experience with an external fixation for this procedure. QUESTIONS/PURPOSES: (1) Does temporary external fixation facilitate postoperative physiotherapy in patients who undergo hip transposition arthroplasty? (2) What functional Musculoskeletal Tumor Society (MSTS) scores were achieved at short term in a small series of patients treated with hip transposition and temporary external fixation? (3) What were the complications of using external fixation in a small series of patients who received it for malignant tumors? METHODS: Between 2008 and 2012, we treated seven patients (three men and four women; median age, 37 years; age range, 18-53 years) with acetabular resection for malignant bone tumors; all were managed with a hip transposition, initially stabilized using external fixation. No other types of procedures were used for this indication in this period. Minimum followup in this retrospective study was 45 months, except for one patient who died at 18 months (range of followup duration, 18-90 months; median followup, 57 months), and no patients were lost to followup. The pins for external fixation were inserted into the affected side of the femur and the healthy contralateral ilium. External fixation was removed 6 weeks postoperatively and weightbearing was started at that time. Preoperative chemotherapy was administrated in four patients, but postoperative chemotherapy was delayed since it was given after external fixation removal in three patients. The postoperative rehabilitation course and functional results were assessed by chart review, functional results were determined using MSTS scores, tallied by physiotherapists who were not part of the surgical team, and complications were ascertained through chart review. Major complications were defined as complications that were treated with additional operations, such as deep infection, or ones that could cause severe postoperative dysfunction, such as nerve injury. RESULTS: With temporary external fixation, standing next to a bed was achieved in median 7 days (range, 6-9 days) postoperatively, transferring to a wheel chair in median 8 days (range, 6-28 days), and gait training using parallel bars in median 15 days (range, 7-48 days). At most recent followup, three patients could walk without a crutch or cane, three could walk with a cane, and one could walk with a crutch. The median MSTS score at most recent followup (median, 57 months) was 63%. Two patients had complications that resulted in reoperations; one had a wound dehiscence, and one had an abdominal herniation that gradually developed, and which was reconstructed using polypropylene mesh 2 years after pelvic resection. Two patients had nerve palsies that recovered by the end of the first year. All patients had pin tract infections that resolved with nonsurgical approaches. CONCLUSIONS: Hip transposition with temporary external fixation can stabilize the bone soft tissue after pelvic resection. Although we did not have a comparison group of patients, we believe that external fixation facilitates early postoperative physiotherapy and rehabilitation and provides good functional results without major surgical complications. Because it delays the resumption of chemotherapy, more patients with longer followup are needed to determine whether this will be associated with poorer oncologic results. LEVEL OF EVIDENCE: Level IV, therapeutic study.

DOI： 10.1097/CORR.0000000000000764

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Language：Japanese   Publisher：保健医療学学会  

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BACKGROUND: Acetabular dysplasia of the hip following open reduction can complicate the treatment of developmental dysplasia of the hip (DDH). The purposes of this retrospective study were to investigate the long-term results of open reduction performed via an extensive anterolateral approach for DDH after walking age and to predict acetabular development using postoperative radiographs and arthrograms. METHODS: From 1973 to 2001, we performed open reduction for 131 hips in 119 pediatric patients with DDH after failed closed reduction. Of these, 85 hips of 73 patients who underwent arthrography at 5 years old were followed-up radiologically until skeletal maturity. Mean age at the time of surgery was 17 ± 4.6 months (range, 10-33 months), and mean age at final survey was 19 ± 5.7 years (range, 14-33 years). Mean follow-up time was 17.7 ± 5.8 years (range, 13-32 years). Groups with satisfactory outcomes (66 hips) and unsatisfactory outcomes (19 hips) according to the Severin classification were compared. Factors predicting acetabular development were identified using univariate and multiple logistic analyses. RESULTS: Univariate analysis showed a significant between-group difference in acetabular index (AI) at 2 months postoperatively, and in center-edge (CE) angle, cartilaginous AI (CAI), and cartilaginous CE angle at 5 years old (p < 0.05 each). In multiple logistic regression analysis, CAI at 5 years old represented a predictor of acetabular development after open reduction for DDH (odds ratio, 1.81; 95% confidence interval (CI), 1.04-3.13; p < 0.05). Area under the receiver operating characteristic curve for CAI at 5 years old was 0.93 (95%CI, 0.85-1.0), and the optimal cut-off was 10° (81.8% sensitivity, 92% specificity). CONCLUSIONS: A CAI ≥10° on hip arthrograms at 5 years old may offer a useful indicator of the need for corrective surgery following open reduction after walking age.

DOI： 10.1016/j.jos.2018.09.015

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BACKGROUND: Although osteoid osteomas have traditionally been treated by surgical excision, radiofrequency ablation (RFA) has gained favor as a less invasive procedure. However, RFA is contraindicated for osteoid osteomas close to the skin or crucial neurovascular structures, and is not covered by national health insurance in Japan. The aim of the present study was to evaluate the efficacy of surgical excision of osteoid osteomas using intraoperative navigation. METHODS: We performed a retrospective review of five patients with osteoid osteoma who underwent a mini-open excision using O-arm/Stealth navigation at our institution. The osteoid osteomas were excised using a cannulated cutter or curetted out with the assistance of navigation. RESULTS: Complete excision was achieved in all patients, which was confirmed by pathological examination. The mean skin incision was 2.1 cm (range, 1.5 to 3.0 cm) and the mean duration required for setup three-dimensional image was 15 min (range, 12 to 20 min). Although the mean visual analog scale score was 7 (range, 4 to 8) before surgery, all patients experienced relief from their characteristic pain immediately after surgery, with the mean scores of 2.2 (range, 1 to 3) and 0 at 2 days and 4 weeks after surgery, respectively. There was no intra-operative complication related to the navigation and no recurrence was observed during the mean follow-up period of 25 months (range, 13 to 33 months). CONCLUSIONS: Mini-open excision using intraoperative O-arm/Stealth navigation is a safe and accurate procedure for patients with osteoid osteoma, which could cover the limitation of RFA.

DOI： 10.1016/j.jos.2018.09.017

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BACKGROUND: To evaluate the therapeutic outcomes in patients with bone metastases receiving radiotherapy (RT), it is important to use objective radiological response criteria. The aim of this study was to investigate the changes in pain and re-ossification after RT for painful vertebral bone metastases without paralysis by malignant spinal cord compression. METHODS: The participants included 55 patients who received RT for painful vertebral bone metastases without paralysis in our institution between 2012 and 2016. Bone modifying agents (BMAs) were administered in all patients. Follow-up assessments were done just before the start of RT and at 1, 2, 3, 4, and 6 months after RT. Radiological responses of irradiated vertebrae by RT were assessed by computed tomography (CT) using MD Anderson response classification criteria (MDA criteria) and the pain response was assessed by Numeric Rating Scale (NRS). Response was classified as complete response (CR), partial response (PR), progressive disease (PD), and stable disease (SD). RESULTS: The rates of CR were 2%, 7%, 20%, 30%, and 56% at 1, 2, 3, 4, and 6 months, respectively. The rates of CR or PR were 15%, 49%, 77%, 91%, and 91% at 1, 2, 3, 4, and 6 months, respectively. The rates of CR or PR were significantly higher in patients with breast cancer than in patients with lung cancer (p = 0.043). At one month, there was an association between the NRS and radiological response assessed by MDA criteria. There was a significant trend that, with a better response, there were more patients without pain (p = 0.021). CONCLUSIONS: Under BMAs administration, successful RT for vertebral bone metastases decreased pain and caused re-ossification. The MD Anderson criteria could be useful for assessment of radiological responses of irradiated vertebrae.

DOI： 10.1016/j.jos.2018.08.018

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INTRODUCTION: Medial meniscus posterior root tear (MMPRT) can occur in middle-aged patients who have a posteromedial painful popping during light activities. MMPRTs are more common in patients with increased age, female gender, sedentary lifestyle, obesity, and varus knee alignment. However, injury mechanisms of minor traumatic MMPRTs are still unclear. We hypothesized that high flexion activities are the major cause of MMPRTs. The aim of this study was to clarify injury patterns of MMPRTs. MATERIALS AND METHODS: One hundred patients were diagnosed having MMPRTs after posteromedial painful popping episodes. Details of posteromedial painful popping episode, situation of injury, and position of injured leg were obtained from the patients by careful interviews. Injury patterns were divided into 8 groups: descending knee motion, walking, squatting, standing up action, falling down, twisting, light exercise, and minor automobile accident. RESULTS: A descending knee motion was the most common cause of MMPRTs (38%) followed by a walking injury pattern (18%) and a squatting action related to high flexion activities of the knee (13%). The other injury patterns were less than 10%. DISCUSSION: Descending knee motions associated with descending stairs, step, and downhill slope are the most common injury pattern of MMPRTs. High flexion activities of the knee are not the greatest cause of MMPRTs. Our results suggest that the descending action with a low knee flexion angle may trigger minor traumatic MMPRTs. LEVEL OF EVIDENCE: IV, retrospective cohort study.

DOI： 10.1016/j.otsr.2018.10.001

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A fibula graft is one of the most common orthopedic procedures for reconstruction of a bone defect, and some complications related to persistent defects of the fibula have been reported previously. We believe that regeneration of the fibula may be critical for postoperative function and prevention of complications. This report describes a 9-year-old female with Ewing sarcoma of the pelvis who was treated with the double-barrel fibula grafts for pelvic bone defect following tumor resection. The defect after fibular resection was filled with unidirectional porous hydroxyapatite (UDPHAp) implants. A plain radiograph revealed new bone formation and a callus-like structure at one month after surgery and bony union between each UDPHAp implant 5 months after surgery. Resorption of implanted UDPHAp was identified, and partial remodeling of the bone marrow cavity could be seen 1 year 2 months after surgery. A radiograph at final follow-up (5 years 10 months after surgery) demonstrated almost complete absorption of the implanted UDPHAp and clear formation of the cortex and bone marrow in the resected part of the fibula. The patient is able to walk well without any walking supports and to take part in sports activities.

DOI： 10.1155/2019/9024643

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BACKGROUND: Radiation therapy (RT) is the common treatment for painful vertebral bone metastases without paralysis by malignant spinal cord compression. However, no studies have focused on the time course of pain after RT. Then, we investigated the change of pain after RT for painful vertebral bone metastases without paralysis. METHODS: Participants included 101 patients who received RT for painful vertebral bone metastases without paralysis in our institution between 2012 and 2016. All patients received RT and pain response was evaluated by Numeric Rating Scale (NRS). Follow-up assessments were performed just before the start of RT and every month for six months after RT. Pain response was classified as complete response (CR), partial response (PR), pain progression (PP), and indeterminate response (IR) based on the response criteria of International Bone Metastases Consensus Working Party. Responders were classified as either CR or PR, and non-responders as either PP or IR. RESULTS: Median NRS scores for pain were 5 before RT, decreasing to 0 by one month after RT and remaining zero until last follow-up, representing a significant decrease over time (P < 0.001). The rate of responders at each month from one to six months was 93, 96, 95, 100, 98, and 96%, respectively. Multivariate analysis revealed that Spinal Instability Neoplastic Score (SINS) was the only risk factor for response to RT at one month. At one month pain disappeared in 88% of the patients with spinal stability (SINS < 7), although pain disappeared 58% of the patients with spinal instability (SINS ≥ 7), which was significant (P = 0.002). CONCLUSIONS: Pain decreased significantly over time and 93% of patients were classified as responders as early as one month after RT in patients with painful vertebral bone metastases without paralysis. Pretreatment SINS could be a predictor of pain response to RT.

DOI： 10.1016/j.jos.2018.07.007

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BACKGROUND: Although emerging evidence has suggested that computer-assisted navigation allows surgeons to plan the optimal level of resection without compromising the surgical margins, the precise accuracy of the procedures has been unclear. The aim of this study was to investigate the accuracy and safety of the musculoskeletal tumor resection using O-arm/Stealth intraoperative navigation assistance. METHODS: A retrospective study of six patients with bone and soft tissue tumors who underwent surgical resection using O-arm/Stealth navigation system was performed. The histological diagnosis was osteosarcoma, metastatic bone tumor, leiomyosarcoma, undifferentiated sarcoma, and synovial sarcoma, respectively. Tumor resection was performed according to planned osteotomy planes determined on O-arm/Stealth three-dimensional intraoperative images. The resection accuracy, length of time for the procedures, surgical margins, and perioperative complications were evaluated. RESULTS: The distances between the entry and exit points for the planned and actual cuts were 1.5 ± 0.3 mm and 2.3 ± 0.3 mm, respectively, and the mean discrepancy of the osteotomy angle was 2.8 ± 1.2°. The mean length of time required for navigation was 14 min. A histological examination revealed clear margins in all patients. There were no complications related to navigation, and no patients developed local recurrence during a mean follow-up of 30.6 months. CONCLUSIONS: The O-arm/Stealth intraoperative CT navigation system provides safe and accurate osteotomy in musculoskeletal tumor resections. However, surgeons should keep in mind and be careful of minimal errors during osteotomy, which are around 2 mm from the planned line.

DOI： 10.1016/j.jos.2018.06.012

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Language：Japanese   Publisher：(一社)日本関節病学会  

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Language：Japanese   Publisher：(一社)中部日本整形外科災害外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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

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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

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

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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

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Language：Japanese   Publisher：保健医療学学会  

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Language：Japanese   Publishing type：Research paper (international conference proceedings)   Publisher：Japanese Society of National Medical Services  

Scopus

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Language：Japanese   Publisher：(一社)中部日本整形外科災害外科学会  

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Language：Japanese   Publisher：(一社)日本脊椎脊髄病学会  

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Language：Japanese   Publisher：(公社)愛媛県理学療法士会  

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Language：Japanese   Publisher：(一社)中部日本整形外科災害外科学会  

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2018&ichushi_jid=J00831&link_issn=&doc_id=20180409210014&doc_link_id=10.11359%2Fchubu.2018.39&url=https%3A%2F%2Fdoi.org%2F10.11359%2Fchubu.2018.39&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_2.gif

Language：Japanese   Publisher：(一社)中部日本整形外科災害外科学会  

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2017&ichushi_jid=J00831&link_issn=&doc_id=20180117120020&doc_link_id=10.11359%2Fchubu.2017.1033&url=https%3A%2F%2Fdoi.org%2F10.11359%2Fchubu.2017.1033&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_2.gif

Language：Japanese   Publisher：日本臨床外科学会  

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

BACKGROUND: Atypical femoral fractures (AFFs) have been reported to occur in patients with bone metastases who received long-term bisphosphonate treatment. However, the incidence of AFFs in breast cancer patients with bone metastases who received intravenous bisphosphonate is unclear. The purpose of this study is to examine the incidence of AFFs in breast cancer patients with bone metastases who received intravenous bisphosphonate. In addition, we estimated the number of dose and duration of intravenous bisphosphonate at the time of occurrence of AFFs. METHODS: We identified 356 female breast cancer patients with bone metastases who received intravenous bisphosphonate between November 2004 and October 2013 in our institution. The median number of doses of intravenous bisphosphonate was 18 (range, 1-103). The median duration of intravenous bisphosphonate treatment was 16 months (range, 1-102 months). We estimated the incidence of AFFs in patients who received intravenous bisphosphonate and used Poisson regression model to obtain the incidence rates of AFFs. RESULTS: Three AFFs in two patients were identified and the estimated incidence of AFFs was 2.99 per 1000 person-years. At the time of occurrence of AFFs, the patients had received 41 and 83 doses of intravenous bisphosphonate, for 37 and 79 months, respectively. The patients underwent open reduction and internal fixation with intramedullary nail. The frequency and incidence of AFFs in patients who received intravenous bisphosphonate for at least 41 or 83 doses or for more than 37 or 79 months were 2/60 (3.3%), 1/7 (14.3%), 2/70 (2.9%), and 1/9 (11.1%), respectively. CONCLUSIONS: The incidence of AFFs is low in breast cancer patients with bone metastases who received intravenous bisphosphonate. Careful observation is warranted and radiography should be performed to investigate AFFs when clinical signs such as thigh pain appear. STUDY DESIGN: Clinical study.

DOI： 10.1016/j.jos.2017.04.011

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Language：Japanese   Publisher：西日本整形・災害外科学会  

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

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Language：Japanese   Publisher：(公社)日本リハビリテーション医学会  

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

BACKGROUND: Symptomatic skeletal events (SSEs) affect many patients with bone metastases from breast cancer. However, predictive models of SSEs in patients with bone metastases from breast cancer have not been established for clinical use. The purpose of this study is to examine risk factors for SSEs in those patients and by combining these risk factors patients are classified into several groups. With this risk-stratification model, we can identify patients at higher risk of SSEs and require close follow-up to maintain ADL. METHODS: Participants included 189 female patients with bone metastases from breast cancer and treated in our institute between 2009 and 2012. To assess risk factors for the first SSEs, clinical data at the time of registration were assessed. To estimate the effects of covariates, we used cause-specific hazard modeling. RESULTS: Multivariate analysis revealed that a high number of metastasized vertebral bodies (≥20) (p < 0.001) and elevated carcinoembryonic antigen (CEA) level (>5 ng/mL) (p = 0.003) were risk factors for SSEs. Patients were classified into four subgroups according to the combination of the number of vertebral metastases and CEA level: patients with CEA level > 5 ng/mL and ≥20 vertebral metastases; patients with CEA level ≤ 5 ng/mL and ≥20 vertebral metastases; patients with CEA level > 5 ng/mL and <20 vertebral metastases; and patients with CEA level ≤ 5 ng/mL and <20 vertebral metastases. Cumulative incidences of SSEs in these four subgroups at 6 months were 35.6%, 15.6%, 9.3%, and 3.7%, respectively. CONCLUSIONS: Patients with elevated CEA level (>5 ng/mL) and extensive vertebral metastases (≥20) should be closely monitored in routine clinical care, to allow prevention of pathological fracture or paraplegia with the intervention of orthopedists or radiologists.

DOI： 10.1016/j.jos.2017.03.014

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

J-GLOBAL

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

J-GLOBAL

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

J-GLOBAL

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

J-GLOBAL

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

J-GLOBAL

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Language：Japanese   Publisher：中部日本整形外科災害外科学会  

CiNii Article

J-GLOBAL

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

The aim of this study was to assess the ability of a new magnetic resonance (MR) angiography technique that does not use contrast enhancement medium to depict the vascularity of musculoskeletal neoplasms, and evaluate its clinical utility. We performed 3D fresh blood imaging (FBI) MR angiography in 57 patients with bone or soft tissue tumors, and the detection of vessels in and around the tumor was evaluated. Moreover, differences in vascularity between benign and malignant tumors were analyzed. In the lower leg, large arteries such as femoral or popliteal arteries were visible. In the trunk or arm, large vessels such as subclavian or iliac arteries were visible. Discrimination between benign and malignant tumors was impossible in bone tumors; however, the mean value of vascularity differed between benign and malignant tumors in the soft tissue tumors. This is the first trial of the FBI method for bone and soft tissue tumors. The still developing method of MRA without contrast materials could clearly depict major arteries in the trunk and the extremities, this method may replace conventional MRA of bone and soft tissue tumors because it produces vivid images while being non-invasive.

PubMed

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

To investigate the localization and expression of connective tissue growth factor/hypertrophic chondrocyte-specific gene product 24/CCN family member 2 (CTGF/Hcs24/CCN2) during distraction osteogenesis in the rat femur, we studied a total of 54 male rats (11 weeks old). We performed osteotomy in the midshaft of the right femur. After 7 days (lag phase), distraction was started, at the rate of 0.25 mm/12 h for 21 days (distraction phase) by using a small external fixator, and this was followed by a 7-day consolidation phase. Localization and expression of CTGF/Hcs24 during distraction osteogenesis in the femur were examined by immunostaining, in situ hybridization, and reverse transcriptase polymerase chain reaction (RT-PCR). Immunostaining showed the localization of CTGF/Hcs24 in various cells located in the bone-forming area around the osteotomy site. During the distraction phase, in situ hybridization showed that CTGF/Hcs24 mRNA was expressed not only in hypertrophic chondrocytes and osteoblasts but also in fibroblast-like cells and mesenchymal cells at sites of end-ochondral ossification, and not only in osteoblasts but also in pre-osteoblasts and fibroblast-like cells at sites of intramembranous ossification. RT-PCR showed higher level expression of CTGF/Hcs24 mRNA in the distracted group than in the nondistracted group. These results revealed an elevated pattern of CTGF/Hcs24 mRNA expression during distraction osteogenesis, and suggest that CTGF/Hcs24 may play some roles in the endochondral and intramembranous ossification processes that occur during distraction osteogenesis.

PubMed

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Language：Japanese   Publisher：(一社)日本骨代謝学会  

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J-GLOBAL

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J-GLOBAL

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J-GLOBAL

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Language：Japanese   Publisher：(一社)日本遺伝カウンセリング学会  

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J-GLOBAL

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J-GLOBAL

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J-GLOBAL

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J-GLOBAL

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J-GLOBAL

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J-GLOBAL

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：日本運動器科学会  

J-GLOBAL

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Language：Japanese   Publisher：(公社)日本整形外科学会  

J-GLOBAL

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Language：Japanese   Publisher：(一社)日本移植学会  

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Language：Japanese   Publisher：(一社)中部日本整形外科災害外科学会  

J-GLOBAL

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Language：Japanese   Publisher：(NPO)日本肺癌学会  

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Language：English   Publisher：(一社)日本癌治療学会  

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

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Language：Japanese   Publisher：(一社)中部日本整形外科災害外科学会  

J-GLOBAL

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Language：Japanese   Publishing type：Research paper, summary (national, other academic conference)   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

J-GLOBAL

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Language：English   Publisher：(公社)日本生化学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本リハビリテーション医学会  

J-GLOBAL

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Language：Japanese   Publisher：(公社)日本整形外科学会  

J-GLOBAL

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(一社)中部日本整形外科災害外科学会  

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Language：Japanese   Publisher：(一社)中部日本整形外科災害外科学会  

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Language：Japanese   Publisher：(一社)中部日本整形外科災害外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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

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

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

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Language：English   Publisher：(一社)日本癌治療学会  

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Language：English   Publisher：(一社)日本癌治療学会  

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

J-GLOBAL

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

J-GLOBAL

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

researchmap

Language：Japanese   Publisher：(一社)中部日本整形外科災害外科学会  

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Language：Japanese   Publisher：(一社)中部日本整形外科災害外科学会  

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Language：Japanese   Publisher：(一社)中部日本整形外科災害外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：日本運動器科学会  

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Language：Japanese   Publisher：日本運動器科学会  

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Language：Japanese   Publisher：日本運動器科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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