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：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：(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

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

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  

＜文献概要＞がんは高齢者に多いため,ロコモティブシンドロームが発生しやすい.がんの切除を行う患者の約9割は,ロコモを合併している.したがって,がん患者では,適切ながんロコモのスクリーニングが重要である.また,最近,がん治療は外来に移行しつつあり,がん患者が日常生活動作を維持することが求められ,がんロコモ予防に対する社会のニーズが増えている.したがって,各施設において,診療科横断的にがんロコモ予防に取り組む体制を構築することが重要である.

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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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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  

椎体転移では腫瘍が増大すると腫瘍が直接神経を圧迫したり,椎体圧潰により脊髄が圧迫され,知覚障害や運動麻痺が生じることがある.ほとんどの骨転移患者は,麻痺が発生する前に脊椎転移部に痛みを自覚している.したがって,痛みは麻痺の危険信号であり,脊椎転移部に痛みが出現した場合,早急に治療を開始することが重要である.麻痺を予防するために,最も基本的で重要な対処法は,脊椎転移部に痛みが出現した場合,脊椎SREsの発生も考え,早急に画像検査を行い,痛みの原因と考えられる著しい椎体破壊や脊髄圧迫を認めた場合,早急に治療(RTなど)を行うことである(Red Flag).なお,早急に画像検査が行えない場合,直近のCT等を見直し,椎体破壊の有無を確認すべきである.Red Flagに対して早急に対処し,麻痺が出現する前に治療が開始できれば,麻痺発生数を減らすことができる.(著者抄録)

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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：(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：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：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：中国・四国整形外科学会  

症例は21歳男性で、左下腿脛骨外側部のグロムス腫瘍切除術後2ヵ月経過した時点で左下腿の疼痛が再燃した。MRIでは左脛骨前面、脛骨後面、脛腓間、腓骨周囲に多発性の腫瘤を認め、これら全病変を辺縁切除した。病理検査では全てグロムス腫瘍と診断され、術後1年の時点で疼痛の再燃や腫瘍の再発は認めず、趣味のダンスも再開している。

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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：Japanese   Publisher：(公社)日本整形外科学会  

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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：(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

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

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

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

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  

＜文献概要＞脊椎転移による痛みに対しては,麻痺がない場合は放射線治療(RT)単独で早期に除痛が得られ,経時的に骨形成を認める場合が多い.標準的なRTは前後対向2門照射を用いた通常照射(分割照射:30Gy/10回)であるが,予後不良(3〜6ヵ月以内)であれば8Gy単回照射で十分である.麻痺を認める場合は除圧術とRTの併用を検討すべきである.最近,体幹部定位放射線治療の有用性が報告されているが,治療計画に時間を要するなどの欠点がある.なお,脊椎転移を有する患者に背部痛が出現した場合,脊椎転移による麻痺リスクを考慮し,早急に画像検査を行うべきである(red flag).

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Language：Japanese   Publisher：(株)医学書院  

＜文献概要＞脊椎転移による痛みに対しては,麻痺がない場合は放射線治療(RT)単独で早期に除痛が得られ,経時的に骨形成を認める場合が多い.標準的なRTは前後対向2門照射を用いた通常照射(分割照射:30Gy/10回)であるが,予後不良(3〜6ヵ月以内)であれば8Gy単回照射で十分である.麻痺を認める場合は除圧術とRTの併用を検討すべきである.最近,体幹部定位放射線治療の有用性が報告されているが,治療計画に時間を要するなどの欠点がある.なお,脊椎転移を有する患者に背部痛が出現した場合,脊椎転移による麻痺リスクを考慮し,早急に画像検査を行うべきである(red flag).

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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

PubMed

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

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  

＜文献概要＞はじめに-リキッドバイオプシーとは リキッドバイオプシーとは,血液,尿,唾液などの体液中に含まれる細胞,核酸,蛋白質,代謝物などの生体分子の解析から病態の把握をめざす病態診断技術の総称である.この用語は,2010年代に血液中に存在する循環腫瘍細胞(circulating tumor cells:CTC)の検出による診断法に与えられたものであり,その後,核酸,蛋白質,代謝物などのさまざまな生体分子を対象とした解析法に対しても用いられるようになっている.現在では,循環腫瘍DNA(circulating tumor DNA:ctDNA),疾患特異的なマイクロRNA(microRNA:miRNA)などの核酸分子や,癌細胞由来のエクソソームの検出による疾患診断法の開発が精力的にすすめられている(図1).リキッドバイオプシーは非侵襲的かつ簡便に施行することができ,同一症例に対して繰り返し施行することが可能であるため,診断だけでなく治療効果や予後の予測に有用であり,次世代の診断技術の基盤として期待が集まっている.骨・軟部腫瘍には,消化器癌,前立腺癌,婦人科癌などの存在診断,治療効果予測,再発リスクの予測,術後再発のモニタリングなどに用いられる血液腫瘍マーカーがきわめて少ない.2012年の『軟部腫瘍診療ガイドライン』では,「臨床検査値で異常を示す腫瘍は?」というクリニカルクエスチョンに対して「軟部腫瘍で特異的な腫瘍マーカーは一般的にはない」と記載されている.癌腫と同様に乳酸脱水素酵素(LDH)の上昇を認めることがあるが,一般的には腫瘍サイズの大きな高悪性度軟部肉腫,あるいは多発性に転移して進行した軟部肉腫に限られる.このような背景から,肉腫細胞由来の生体分子を用いたリキッドバイオプシーの開発は,骨・軟部腫瘍の診療における新しいブレイクスルーとなる可能性があり,研究開発が精力的に行われている.本稿では,リキッドバイオプシーの骨・軟部腫瘍における研究開発の動向を生体分子別に述べ,本法の将来展望について論じる.

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Language：Japanese   Publisher：保健医療学学会  

【目的】本研究では、肺葉切除術を施行された患者を対象として、入院中におけるリハビリテーション実施後の身体機能の推移を検討した。また術前慢性閉塞性肺疾患(Chronic Obstructive Pulmonary Disease:COPD)合併の有無による違いも分析した。【方法】肺葉切除術を施行しリハビリテーションを実施した35例(開胸8例/Video assisted thoracoscopic surgery 27例、平均年齢69.5歳)を対象とし、術前、術後7日目の骨格筋量、握力、6分間歩行距離の推移とCOPD合併有無による差異を検討した。【結果】術後の骨格筋量に関して四肢骨格筋指数の有意な低下(p=0.108)は認めなかったが、部位別に検討すると下肢筋指数は有意に低下(p=0.003)していた。また握力(p=0.012)、6分間歩行距離(p<0.0001)もそれぞれ有意な低下を認めた。COPD合併有無による各項目の差異は認めなかった。【結論】肺葉切除患者において、運動耐容能に加えて上肢筋指数、下肢筋指数の評価の重要性が明らかになった。また軽症、中等症COPD合併患者では、骨格筋指数や運動耐容能にはCOPD合併の有無の影響が少ないことが示された。(著者抄録)

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Language：Japanese   Publisher：(株)南江堂  

＜文献概要＞はじめに 肉腫における免疫療法の歴史は古く,1891年,William Coley博士は切除不能で転移性の肉腫の患者において免疫療法の効果を最初に示した.その後,免疫調節薬,ワクチンなどさまざまな免疫療法が開発され,最近は免疫チェックポイント阻害薬(immune-check point inhibitor:ICI)や活性化自己リンパ球輸注療法などの有望な治療法が登場している(表1).本稿では肉腫の免疫療法についてレビューを行う.

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2021&ichushi_jid=J04037&link_issn=&doc_id=20210514600029&doc_link_id=10.15106%2Fj_besei79_149&url=https%3A%2F%2Fdoi.org%2F10.15106%2Fj_besei79_149&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：(株)南江堂  

＜文献概要＞はじめに わが国では歴史的に整形外科が中心となって肉腫(サルコーマ)の治療方針を決め,主に手術と化学療法を担当してきた.一方,欧米では腫瘍内科が肉腫の化学療法を担当することが一般的であり,わが国の治療状況とは大きく異なる.肉腫治療例の増加とともに進行例が増加し,新規治療薬も開発され,整形外科医のみで治療していくことがむずかしくなってきた.また,化学療法以外にも,肉腫の診断,手術には多くの診療科の協力が必要で,多職種による集学的医療チームによる治療が重要である.当院では肉腫患者によりよい治療を提供する目的で,2014年4月に大学病院の診療部門としては日本ではじめてサルコーマセンターを設立した.本稿では,当院サルコーマセンターの活動を紹介する.

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Language：Japanese   Publisher：(株)南江堂  

＜文献概要＞はじめに がんにはさまざまな遺伝子異常を認め,同一のがん種でも発現する遺伝子が異なることが少なくない.最近,次世代シークエンサー(next generation sequencer:NGS)を用いて遺伝子異常を同時多重性(マルチプレックス)に検出するがん遺伝子パネルが登場した.がんゲノム医療では,がん遺伝子パネルで同定した遺伝子変異に基づいて薬剤を選択する,精密医療(precision medicine)が行われる.本稿では,肉腫におけるゲノム医療の意義について述べる.

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

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

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

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

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  

症例は30代,女性。過去に左腋窩皮膚生検で神経線維腫と診断され,特徴的な皮膚所見や家族歴などから神経線維腫症1型(NF-1;von Recklinghausen病)を疑われていたが放置していた。20XX年2月に右大腿部痛,背部痛を主訴に近医を受診しMRI,造影CTで約13cm大の後腹膜腫瘤を指摘され,L2神経根からの発生と脊柱管内の浸潤も疑われ,神経線維腫の疑いとして手術目的に当科紹介された。合同での手術が必要と考えられたため,整形外科に紹介しMRIガイド下生検で悪性末梢神経鞘腫瘍の可能性を示唆された。同年6月に腫瘍の動脈塞栓術施行後に右後腹膜腫瘍摘出術を施行し,病理結果から悪性末梢神経鞘腫瘍と診断された。術後10ヵ月現在再発認めず,外来通院中である。後腹膜原発腫瘍において悪性末梢神経鞘腫瘍は極めて稀な症例であり,有効な治療法は確立されていない。今回,後腹膜原発の悪性末梢神経鞘腫瘍の1例を経験したので,若干の文献的考察を加えて報告する。(著者抄録)

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

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

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  

＜文献概要＞はじめに 現在,がん罹患者は増加しているものの,化学療法など治療の進歩で生存率が向上している.がんのリハビリテーションは,手術前後の介入だけでなく,化学療法・放射線治療による体力の低下・維持に対する介入も求められる.終末期の患者では,ADL向上によって満足度が高まる.また,「がんロコモ」も注目され,リハビリテーションの必要性が広がっている.本稿では,進行がん患者を対象に,高額な機器を用いず実施可能なフィジカルアセスメントを述べる.

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

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  

＜文献概要＞はじめに 国民の健康を増進・維持するためには,疾病に対する有効な診断法,治療法,予防法のシーズ探索から臨床開発に向けた臨床研究がきわめて重要である.医療分野の研究開発には多額の費用が必要であり,研究資金の獲得が欠かせない.臨床研究は公的資金だけでなく,企業の寄附金や助成金を使用して行われているものも多い.本稿では,これらの臨床研究の資金の提供を行っている組織の事業について紹介する.

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Language：Japanese   Publisher：(株)三輪書店  

＜文献概要＞はじめに Weinstein-Boriani-Biagini分類(WBB分類)は,原発性脊椎腫瘍を腫瘍学的に取り扱うために考案された分類である.四肢の骨軟部腫瘍に対してはAJCC(the American Joint Committee on Cancer)のTNM分類やEnneking分類が使用されることが多く,病期や術式の選択,実際の切除縁など決定して治療成績が報告されてきた.脊椎腫瘍に対する根治的切除としての椎体切除は1971年にStenerらが報告している.当時,腫瘍学的な原則に基づいた治療方法の選択のために統一された基準はなく,切除という言葉は論文ごとに別の意味で使用されていた.この問題点に対しEnneking分類を巨細胞腫などの原発性脊椎腫瘍に適応させようという試みが行われ,1997年にWBB分類が提唱された.腫瘍学的に不十分あるいは不適切な切除により局所再発が増加し,生存期間が短くなるというエビデンスがあり,脊椎腫瘍においても腫瘍学的な選択を十分考慮すべきである.本稿ではWBB分類について述べる.

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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  

本研究では,乳がん術後患者を対象に入院中のリハビリテーション介入および退院後の自宅での運動療法指導の実施による肩関節可動域,体組成,Quality of lifeの推移について1症例を対象に検討した.症例は40代の女性で乳がん診断後,当院にてリンパ節郭清を伴う乳房切除術を施行した.肩関節屈曲,外転の関節可動域は,術後1週,1ヵ月で低下を認めたが,術後2ヵ月で改善を示した.体脂肪量,体脂肪率は,退院後2ヵ月まで増加傾向であった.術側上肢筋量は,術後1週と比較して術後1ヵ月では低下を示し,術後2ヵ月では改善傾向を示したが,術後1週よりも低値であった.Quality of lifeは症状尺度の全ての項目が,術後2ヵ月経過後も改善を認めなかった.これらのことから,乳がん術後患者のリハビリテーションでは,上肢機能に加えて体組成,Quality of lifeについて評価し適切に介入する必要性が示唆された.(著者抄録)

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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  

スポーツを活発に行う年齢層が骨・軟部腫瘍の好発年齢と一致しているため,スポーツ外傷や障害と骨・軟部腫瘍との鑑別診断は重要である。それらの病変のなかには,(1)偶然発見されたX線像に写った無症候性の病変,(2)疼痛などの症状を伴い骨腫瘍疑いと紹介されてきたが骨腫瘍ではなかった病変,そして(3)骨腫瘍疑いで紹介されてきて真の治療を要する骨腫瘍であった症例などがある。スポーツ外傷・障害を診断するうえで骨腫瘍の知識は重要であるが,それに加えて,外傷,骨折,炎症性疾患など整形外科疾患全般の基本知識も重要である。(著者抄録)

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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  

＜文献概要＞骨軟部腫瘍専門医ががんロコモ予防のため取り組むべき課題として,骨転移の取り組み,がんのリハビリテーションなどがあげられる.筆者らは,骨転移に対する体系的な診療システムを構築し,麻痺の予防に取り組んだ.麻痺予防のために最も重要な対処法は,脊椎転移部に痛みが出現した場合,早急に画像検査を行い,痛みの原因と考えられる椎体破壊や脊髄圧迫を認めた場合,早急に治療(放射線治療など)を行うことである(Red flag).また,多職種連携チーム医療が重要であり,カンファレンスで情報を共有し,医療従事者の早期介入によりADLを向上させることが重要である.

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

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  

本研究では、リンパ節郭清を伴う乳房切除術を施行した乳がん患者144例を対象に術後上肢機能の短期間で変化を検討した。リハビリテーションは手術前後に実施した。調査項目は、Disabilities of the Arm, Shoulder and Hand(DASH)について検討した。測定は、手術前、術後3ヵ月で実施した。その結果、術後3ヵ月では、術前と比較して23項目(障害)のうち18項目に困難感の回答が多く、7項目(症状)のうち5項目で症状ありの回答が多く認められた(p<0.05)。したがって、乳がん術後患者は、退院後にも定期的な上肢機能評価やリハビリテーションが必要であることが明らかとなった。(著者抄録)

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

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

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

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

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

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  

当院では、重篤なskeletal related event(SRE)の発生を防ぐ目的で、2009年9月に骨転移登録システムを確立し稼働している。同システムでは骨転移が確認された時点で登録され、リスクに応じて画像フォローや診察を行い、metastatic spinal cord compression(MSCC)を認めた症例において、麻痺発生リスクが高いと判断された場合には放射線照射を積極的に施行している。システム稼働後、骨折や麻痺などの重篤なSRE発生は減少しているものの、麻痺を生じて当科紹介となる症例が依然散見されている。今回、麻痺を発症し最終的に歩行不能となった最近の4症例を振り返り、問題点について検討した。4例中2例は麻痺出現前から画像上MSCCが確認可能であったが、他の2例は確認困難であった。

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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  

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

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

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

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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  

今回、乳がん多発骨転移でskeletal related events発生リスクの高い患者に対し、当院で実施しているリハビリテーション中の病的骨折リスクマネージメントの効果を検討した。対象は、63歳の乳がん骨転移患者である、リハビリテーション開始前には、医師が画像と診察で病的骨折などのリスク評価を行った。また多職種カンファレンスなどで情報共有を行った。その結果、入院中に骨転移部の2ヶ所で新たに疼痛などのskeletal related eventsの発生を認めたが、円滑な情報伝達により重篤なskeletal related eventsを発症することなくリハビリテーションを継続することが可能であった。またActivities of daily livingは改善した。これらのことから、当院のシステムは、病的骨折リスクの高い骨転移患者にリハビリテーションを行う場合のマネージメントに有用であると考えられた。(著者抄録)

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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  

2015年8月〜2016年10月の下肢リンパ浮腫患者13例(男2例、女11例、平均年齢72歳)19肢を対象に、リンパ浮腫チームによる複合的治療を2週間毎日実施し、成績を報告した。リンパ浮腫チームは形成外科医師・乳腺外科医師・理学療法士・病棟看護師で構成し、複合的治療はスキンケア・用手的リンパドレナージ・バンテージによる圧迫療法・圧迫下での運動療法・日常生活指導にて構成した。患肢周径は全ての部位で経時的に改善し、入院後1、2週目における平均下肢周径は入院時と比べ有意に改善した。入院時と入院後1・2週目、入院後1週目と2週目の平均体重および平均細胞内水分量に有意な減少を認めた。体水分量は入院時と入院後1・2週目に有意な減少を認めた。細胞外水分比は全身・体幹・患肢でそれぞれ、入院後1・2週目の値が入院時と比べ有意に減少した。

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

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

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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  

大腿骨近位部病的骨折にて手術を行った24例24肢(男性6例、女性18例、平均年齢63歳)の治療成績を検討した。原発巣は乳癌12例、肺癌6例、その他6例、部位は頸部14例、転子部5例、転子下5例であった。頸部骨折に対しては人工骨頭置換術14例、転子部骨折に対しては髄内釘3例、腫瘍用人工骨頭置換術2例、転子下骨折に対しては髄内釘1例、プレート1例、DHS 1例、腫瘍用人工骨頭置換術2例が施行された。術後PSは術前PSと比較し22例(83%)で改善を認めた。術後合併症は1例に認め、深部感染1例(腫瘍用人工骨頭置換術例)であった。人工骨頭群と髄内釘・プレート群の1年累積生存率は各々58%、17%で有意差を認めた。

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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

PubMed

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

【目的】当院では、脊椎SREに保存的治療を行う場合、アルゴリズムを作成して安静度を決定し、廃用症候群予防のため早期離床させる取り組みを行っている。今回、麻痺の無い脊椎SREに対するRTの治療成績について報告する。【対象と方法】H24年7月よりH27年12月迄に当院で治療を行った麻痺を認めない脊椎SRE 201例を対象とした。全例保存的治療(RT 188例)が行われた。このうち、再発を除く175例の脊椎不安定性(SINS)、脊椎SRE部の体動時の疼痛(Numerical Rating Scale(NRS))、ADL(Barthel Index(BI))、QOL(EORTC-QLQ C30のglobal health status)の治療開始時と開始後1、2、3、4、6ヵ月の比較をWilcoxonの符号付順位和検定を用いて検討した。【結果】経時的にSINS、NRS、BI、C30の改善が認められた。再発例を除く症例では、経過中に固定術を要する不安定性や疼痛の増悪は認めなかった。【考察】麻痺を認めない症例は保存的治療で良好な成績が得られた。したがって、根治的治療(TES)の適応がない場合、不安定性が著明でなければ、保存的治療が第一選択と考えられた。(著者抄録)

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2017&ichushi_jid=J00766&link_issn=&doc_id=20171110150062&doc_link_id=%2Fdl8ortra%2F2017%2F006604%2F062%2F0921-0925%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fdl8ortra%2F2017%2F006604%2F062%2F0921-0925%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

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

PubMed

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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)  

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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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：(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：(一社)日本移植学会  

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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  

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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   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  

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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  

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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：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  

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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  

J-GLOBAL

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

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