Language：Japanese   Publisher：Japanese Society for Surgery of the Hand  

<p>肘部管症候群と頚椎疾患は⼿指のしびれ，疼痛，筋⼒低下などの類似する臨床症状を呈し，鑑別が必要となることがあるが，脊髄圧迫病変との関連については報告が少ない．今回，肘部管症候群術後の予後評価と脊髄圧迫病変の関連について調査した．対象は2012 年1 ⽉～2023 年2 ⽉に尺⾻神経皮下前⽅移所術を⾏った27 例28 肘とした．脊髄圧迫病変の評価はMRI のT2 強調像⽮状断で圧迫なし群，圧迫あり群の2 群に分けて行った．脊髄圧迫病変の有無は圧迫なし12 例（44.4％），圧迫あり15 例（55.6％）であった．平均年齢は圧迫なし群58.1 歳，圧迫あり群68.9 歳（p＝0.024）と圧迫あり群が有意に高かった．術後評価は赤堀の予後評価基準で優，良，可が，圧迫なし群はそれぞれ5，5，3，圧迫あり群はそれぞれ5，7，3（p＝0.71）であった．術前頸椎MRI で53.6％の症例に脊髄圧迫病変を認めたが，圧迫病変の有無は術後成績に影響を与えなかった．</p>

DOI： 10.60304/jjssh.41.4_429

CiNii Research

Language：English   Publisher：In Vivo  

Background/Aim: Despite the well-publicized clinical outcomes after unplanned excision (UE) and re-excision (re-excision) in patients with soft-tissue sarcoma (STS), there is little information about the real-life referral patterns for UE, such as patient profile, details of procedures, and subsequent management after UE. We aimed to investigate the characteristics of patients with UE who were referred to sarcoma-specific centers. Patients and Methods: Between May 2022 and June 2023, we registered 97 patients who underwent UE and were referred to sarcoma-specific centers in Japan. We excluded those with well-differentiated liposarcomas and dermatofibrosarcoma protuberances. We investigated the details of UE and additional treatment after UE. Results: There were 49 men and 48 women, with a mean age of 62 years. A broad range of surgeons performed UE; 36 plastic surgeons, 22 orthopedic surgeons, 17 general surgeons, 17 dermatologists, and 5 others. The mean tumor size was 4.1 cm. Local anesthesia was administered to 58 patients. Forty-five patients underwent UE without prior magnetic resonance imaging. Inappropriate transverse skin incisions were performed in 42 patients. Of the 97 patients, 82 underwent re-excision after UE. The mean time between UE and date of initial presentation at the referral hospital was 46 days. The mean interval between UE and re-excision was 96 days. Of the 82 patients, 59 underwent soft-tissue reconstruction after re-excision. Conclusion: A broad range of surgeons performed UE. Continuous education about STS should be considered for all surgeons. UE should be avoided because residual tumors are common, and reconstructive surgery may be necessary.

DOI： 10.21873/invivo.13749

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Language：English   Publisher：Oxford University Press  

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

Background: Limited epidemiological research has focused on translocations in soft tissue sarcomas, with no studies on bone sarcomas. This study aimed to clarify the epidemiology, prognosis, and genetic information of translocation-related sarcoma (TRS) and non-TRS patients. Materials and methods: This retrospective cohort study used data from the Bone and Soft Tissue Tumor Registry in Japan (BSTTRJ) (2001-2019), the Kyushu University Hospital (KUH) repository (2001-2021), and a publicly available online dataset (MSK). The patients were categorized into TRS and non-TRS groups, and epidemiological, prognostic, and mutational diversity were compared. Results: This study included 25 383 participants, of whom 4864 (19.2%) were TRS and 20 519 (80.8%) were non-TRS patients. TRS patients had significantly younger onset ages (median: 43 years, interquartile range: 29-59 years) than non-TRS patients (median: 63 years, interquartile range: 46-73 years). In the MSK cohort, microsatellite instability and tumor mutation burden scores in non-TRS were higher than in TRS, although they were rather low compared with the pan-cancer analysis. In the BSTTRJ cohort, survival analyses with the propensity score matching revealed that patients with TRS had better overall [hazard ratio (HR): 0.71, 95% confidence interval (CI) 0.63-0.81], metastasis-free (HR: 0.75, 95% CI 0.67-0.84), and recurrence-free (HR: 0.47, 95% CI 0.39-0.57) survival. Conclusions: This study highlights differences in the epidemiology and genetic rearrangements of sarcoma.

DOI： 10.1016/j.esmoop.2024.103726

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Language：Japanese   Publisher：West-Japanese Society of Orthopedics & Traumatology  

<p>【目的】鏡視下腱板修復術後における腱板MRI信号強度の経時的変化について検討した．【対象と方法】当院で2013年から2021年に行った鏡視下腱板修復術のうち術前にStump分類を行い，2年以上経過観察を行なった41症例（男：女＝18：23，平均年齢67歳，Type1：10肩，Type2：16肩，Type3：15肩）である．術後3か月，6か月，1年，2年時点でMRI検査を行い，Type毎の経時的変化や各期間におけるType間差を検討した．評価にはStump分類で用いる腱板断端（C）/三角筋（D）の平均信号強度を使用した．【結果】全Typeにおいて術後6か月までC/D比が上昇し，術後2年で術前と同等の信号強度となった．全期間を通してType間のC/D比に差はなかった．【考察】ARCR後の腱板は術後6か月まで手術侵襲の影響が残存し，Typeに関わらず修復過程は同様の経過をたどることが推察された．</p>

DOI： 10.5035/nishiseisai.73.638

CiNii Research

Language：Japanese   Publisher：West-Japanese Society of Orthopedics & Traumatology  

<p>【背景】一般的に悪性腫瘍手術の術後創部感染は術後化学療法の実施を困難にし，生命予後を悪化させる因子の1つとされる．一方で骨肉腫では，基礎実験等で免疫の活性化による骨肉腫の進行抑制が報告されるなど，感染による免疫の活性化が生命予後を改善させる可能性が示唆されている．【対象と方法】2006年から2021年に当科で診療を行った78例のうち，手術を実施し，データ入手可能であった66例を対象とし，後方視的に臨床情報を収集した．【結果】対象群の診断時年齢中央値は17歳，部位は大腿骨が最多で29例，続いて脛骨が17例であった．66例中，11例（16.7％）に創部感染を発症した．5年及び10年生存率は，感染例100％/88.9％，非感染例78.6％/66.2％であった（p＝0.1342）．【結語】骨肉腫患者では術後創部感染は予後を悪化させず，むしろ感染例で予後良好である傾向を示した．しかし，最終的な結論を得るにはより多数例での解析が必要である．</p>

DOI： 10.5035/nishiseisai.73.847

CiNii Research

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Scientific Reports  

The coronavirus disease (COVID-19) pandemic negatively affected the diagnosis and treatment of several cancer types. However, this pandemic's exact impact and extent on bone and soft tissue sarcomas need to be clarified. We aimed to investigate the effect of the COVID-19 pandemic and emergency declaration by the local government on consultation behavior and clinical stage at diagnosis of bone and soft tissue sarcoma. A total of 403 patients diagnosed with bone and soft tissue sarcoma who initially visited three sarcoma treatment hospitals between January 2018 and December 2021 were included. The monthly number of newly diagnosed soft tissue sarcoma patients was reduced by 25%, and the proportion of soft tissue patients with stage IV disease at diagnosis significantly increased by 9% during the COVID-19 pandemic compared to before the COVID-19 pandemic. Furthermore, the monthly number of new primary bone and soft tissue sarcoma patients significantly decreased by 43% during the state of emergency declaration. The COVID-19 pandemic had a negative impact on soft tissue sarcoma patients' consultation behavior and increased the proportion of advanced-stage patients at initial diagnosis. An emergency declaration by the local government also negatively affected primary bone and soft tissue sarcoma patients' consultation behavior.

DOI： 10.1038/s41598-024-71830-4

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

【目的】鏡視下腱板修復術後における腱板MRI信号強度の経時的変化について検討した.【対象と方法】当院で2013年から2021年に行った鏡視下腱板修復術のうち術前にStump分類を行い,2年以上経過観察を行なった41症例(男:女=18:23,平均年齢67歳,Type1:10肩,Type2:16肩,Type3:15肩)である.術後3ヵ月,6ヵ月,1年,2年時点でMRI検査を行い,Type毎の経時的変化や各期間におけるType間差を検討した.評価にはStump分類で用いる腱板断端(C)/三角筋(D)の平均信号強度を使用した.【結果】全Typeにおいて術後6ヵ月までC/D比が上昇し,術後2年で術前と同等の信号強度となった.全期間を通してType間のC/D比に差はなかった.【考察】ARCR後の腱板は術後6ヵ月まで手術侵襲の影響が残存し,Typeに関わらず修復過程は同様の経過をたどることが推察された.(著者抄録)

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

【背景】一般的に悪性腫瘍手術の術後創部感染は術後化学療法の実施を困難にし,生命予後を悪化させる因子の1つとされる.一方で骨肉腫では,基礎実験等で免疫の活性化による骨肉腫の進行抑制が報告されるなど,感染による免疫の活性化が生命予後を改善させる可能性が示唆されている.【対象と方法】2006年から2021年に当科で診療を行った78例のうち,手術を実施し,データ入手可能であった66例を対象とし,後方視的に臨床情報を収集した.【結果】対象群の診断時年齢中央値は17歳,部位は大腿骨が最多で29例,続いて脛骨が17例であった.66例中,11例(16.7%)に創部感染を発症した.5年及び10年生存率は,感染例100%/88.9%,非感染例78.6%/66.2%であった(p=0.1342).【結語】骨肉腫患者では術後創部感染は予後を悪化させず,むしろ感染例で予後良好である傾向を示した.しかし,最終的な結論を得るにはより多数例での解析が必要である.(著者抄録)

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Japanese Journal of Clinical Oncology  

BACKGROUND AND OBJECTIVE: Surgical site infection (SSI) is common in surgery for malignant musculoskeletal tumours, specifically those arising from the trunk. In this study, we investigated the risk factors for SSI after resection of musculoskeletal tumours of the trunk. METHODS: This retrospective observational study included 125 patients (72 males, 53 females) with musculoskeletal tumours of the trunk in our hospital from 1 April 2008 to 31 August 2023. The incidence of SSI and its risk factors were investigated. RESULTS: SSI was observed in 26% (32/125), and the median time to SSI was 22 days. On multivariate analysis, the following were identified as risk factors for SSI: tumours arising caudal to Jacoby's line (hazard ratio [HR] 4.04; P = .0107), soft tissue reconstruction (HR 3.43; P = .0131), and low Geriatric Nutritional Risk Index (GNRI) (HR 0.96; P = .0304). Patients were classified into two risk categories based on GNRI scores: the risk group (GNRI ≤98) and no risk group (>98). The risk group showed a significantly lower overall noninfection survival rate (P = .023). CONCLUSION: Tumours arising caudal to Jacoby line, soft tissue reconstruction, and lower GNRI were risk factors for SSI. Preoperative and postoperative nutritional interventions should be considered to improve GNRI.

DOI： 10.1093/jjco/hyae095

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Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/j.joscr.2024.01.001

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

74歳男性。神経線維腫症1型の既往歴があった。数年前より左大腿に腫瘍を自覚しており、2013年に当院を受診した。初診時、体幹に多発するカフェオレ斑と神経線維腫、および左大腿後面に径14cm大の軟部腫瘤を認めた。画像評価より、左大腿の腫瘤は筋膜まで達し、肺に多発結節が生じていた。大腿の原発巣と肺腫瘍の双方に対し針生検を施行した結果、悪性グロームス腫瘍と診断した。ドキソルビシン投与および大腿腫瘍への放射線照射を行ったが、原発巣、転移巣ともに拡大した。そこで初診から4ヵ月後に、経口パゾパニブへ切り替えた。投与初期には高血圧が出現したが、カルシウム拮抗薬により良好なコントロールを得た。肺腫瘍の拡大は止まり、治療効果は安定と判定した。しかし、パゾパニブ開始2ヵ月後には新たな肺結節が数個出現し、既存の結節も拡大し、開始5ヵ月後に腫瘍死した。

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：西日本脊椎研究会  

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Language：Japanese   Publisher：West-Japanese Society of Orthopedics & Traumatology  

<p>手根管症候群患者に対して術前に頸椎MRIを施行し，頸髄圧迫病変と手根管開放術後の症状改善の有無について調査した．対象は2011年8月から2021年9月に手根管開放術を行った50例65手で頸髄圧迫病変の有無とその男女比，年齢での比較，術後6ヵ月での症状改善の有無，手根管開放術後の頚椎手術歴について評価した．手根管開放術を行った50例中26例で頸髄圧迫病変を認めたがほぼ全例で症状改善を認めた．手術適応のある手根管症候群患者では頸髄圧迫病変が多い傾向があった．また，年齢での比較においては，65歳以上が65歳未満より頚髄圧迫病変の割合が有意に多かった．診断の際には神経症状や電気生理学的検査，必要であれば頚椎MRI検査を行い総合的に判断することが重要と考える．</p>

DOI： 10.5035/nishiseisai.73.307

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Skeletal Radiology  

Low-grade central osteosarcoma (LGCOS), which arises from the intramedullary cavity of the metaphysis of long bones, occasionally exhibits extraosseous spread. Approximately 10-30% of patients with LGCOS exhibit dedifferentiation, but it is rare to experience a primary tumor with a dedifferentiated component. A 38-year-old female patient presented with right knee pain for two months. Imaging studies revealed a bone mass with extraosseous involvement. Wide resection was performed, and pathologic examination led to the diagnosis of LGCOS with a dedifferentiated extraosseous lesion. A single defect in the bone cortex constituted the boundary between the low- and high-grade components. The extraosseous high-grade component included more tumor cells with p53 overexpression and more murine double minute 2 (MDM2) copies compared with the low-grade component. These genetic mutations and copy number alterations can be associated with malignant transformation of LGCOS.

DOI： 10.1007/s00256-024-04647-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：西日本整形・災害外科学会  

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2024&ichushi_jid=J00766&link_issn=&doc_id=20240515240032&doc_link_id=%2Fdl8ortra%2F2024%2F007302%2F032%2F0307-0308%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fdl8ortra%2F2024%2F007302%2F032%2F0307-0308%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

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

手根管症候群患者に対して術前に頸椎MRIを施行し,頸髄圧迫病変と手根管開放術後の症状改善の有無について調査した.対象は2011年8月から2021年9月に手根管開放術を行った50例65手で頸髄圧迫病変の有無とその男女比,年齢での比較,術後6ヵ月での症状改善の有無,手根管開放術後の頸椎手術歴について評価した.手根管開放術を行った50例中26例で頸髄圧迫病変を認めたがほぼ全例で症状改善を認めた.手術適応のある手根管症候群患者では頸髄圧迫病変が多い傾向があった.また,年齢での比較においては,65歳以上が65歳未満より頸髄圧迫病変の割合が有意に多かった.診断の際には神経症状や電気生理学的検査,必要であれば頸椎MRI検査を行い総合的に判断することが重要と考える.(著者抄録)

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

DOI： 10.1007/s42399-024-01648-8

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Other Link： https://link.springer.com/article/10.1007/s42399-024-01648-8/fulltext.html

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Npj Precision Oncology  

Prognosis after neoadjuvant chemotherapy (NAC) for osteosarcoma is generally predicted using manual necrosis-rate assessments; however, necrosis rates obtained in these assessments are not reproducible and do not adequately reflect individual cell responses. We aimed to investigate whether viable tumor cell density assessed using a deep-learning model (DLM) reflects the prognosis of osteosarcoma. Seventy-one patients were included in this study. Initially, the DLM was trained to detect viable tumor cells, following which it calculated their density. Patients were stratified into high and low-viable tumor cell density groups based on DLM measurements, and survival analysis was performed to evaluate disease-specific survival and metastasis-free survival (DSS and MFS). The high viable tumor cell density group exhibited worse DSS (p = 0.023) and MFS (p = 0.033). DLM-evaluated viable density showed correct stratification of prognosis groups. Therefore, this evaluation method may enable precise stratification of the prognosis in osteosarcoma patients treated with NAC.

DOI： 10.1038/s41698-024-00515-y

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：British Journal of Cancer  

BACKGROUND: Leiomyosarcomas are among the most common histological types of soft tissue sarcoma (STS), with no effective treatment available for advanced patients. Lung metastasis, the most common site of distant metastasis, is the primary prognostic factor. We analysed the immune environment targeting lung metastasis of STS to explore new targets for immunotherapy. METHODS: We analysed the immune environment of primary and lung metastases in 38 patients with STS using immunohistochemistry. Next, we performed gene expression analyses on primary and lung metastatic tissues from six patients with leiomyosarcoma. Using human leiomyosarcoma cell lines, the effects of the identified genes on immune cells were assessed in vitro. RESULTS: Immunohistochemistry showed a significant decrease in CD8+ cells in the lung metastases of leiomyosarcoma. Among the genes upregulated in lung metastases, epithelial cellular adhesion molecule (EPCAM) showed the strongest negative correlation with the number of CD8+ cells. Transwell assay results showed that the migration of CD8+ T cells was significantly increased in the conditioned media obtained after inhibition or knock down of EPCAM. CONCLUSIONS: EPCAM was upregulated in lung metastases of leiomyosarcoma, suggesting inhibition of CD8+ T cell migration. Our findings suggest that EPCAM could serve as a potential novel therapeutic target for leiomyosarcoma.

DOI： 10.1038/s41416-024-02576-z

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Journal of Orthopaedic Surgery and Research  

BACKGROUND: Impingement is a common complication of reverse shoulder arthroplasty. Placement of the baseplate with a wide impingement-free angle is ideal; however, there are few studies on Asian populations, which have smaller height and physique, and there is a lack of guidance on achieving optimal outcomes. The purpose of the present study was to explore the impingement-free range of motion reverse shoulder arthroplasty and analyze the suitable baseplate position or tilt for the Asian population using simulation software. METHODS: We uploaded computed tomography scan data from 20 Asian patients to three-dimensional (3D) simulation software. The implantation of the reverse shoulder arthroplasty component was performed on the 3D humerus and scapula using software, and range of motion was assessed until impingement occurred. RESULTS: The range of motion in flexion significantly improved when the baseplate was lowered up to 3 mm inferiorly. Range of motion in abduction and internal and external rotation significantly improved as the baseplate was lowered up to 4 mm. There was no significant difference in range of motion in any motion after changing the inferior tilt, except in internal and external rotation. CONCLUSIONS: The range of motion in abduction, flexion, and internal and external rotations significantly improved with increased inferior offset. These results may prove valuable in determining the optimal baseplate position for RSA, particularly in Asian populations.

DOI： 10.1186/s13018-023-04506-w

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Bone and Joint Open  

AIMS: To evaluate mid-to long-term patient-reported outcome measures (PROMs) of endoprosthetic reconstruction after resection of malignant tumours arising around the knee, and to investigate the risk factors for unfavourable PROMs. METHODS: The medical records of 75 patients who underwent surgery between 2000 and 2020 were retrospectively reviewed, and 44 patients who were alive and available for follow-up (at a mean of 9.7 years postoperatively) were included in the study. Leg length discrepancy was measured on whole-leg radiographs, and functional assessment was performed with PROMs (Toronto Extremity Salvage Score (TESS) and Comprehensive Outcome Measure for Musculoskeletal Oncology Lower Extremity (COMMON-LE)) with two different aspects. The thresholds for unfavourable PROMs were determined using anchor questions regarding satisfaction, and the risk factors for unfavourable PROMs were investigated. RESULTS: The thresholds for favourable TESS and COMMON were 64.8 and 70.4 points, respectively. Multivariate analysis showed that age at surgery (p = 0.004) and postoperative leg length discrepancy (p = 0.043) were significant risk factors for unfavourable TESS results, while age at surgery (p < 0.001) was a significant risk factor for unfavourable COMMON-LE results. Following receiver operating characteristic analysis, the threshold for both TESS and COMMON-LE was 29 years of age at surgery. Additionally, a leg length discrepancy of 8.2 mm was the threshold for unfavourable TESS. CONCLUSION: Patients aged > 29 years at the time of surgery require appropriate preoperative counselling and adequate postoperative physical and socioemotional support. Reconstruction equivalent to the length of the resected bone can reduce the risk of functional disabilities in daily living.

DOI： 10.1302/2633-1462.412.BJO-2023-0125.R1

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Kurume University School of Medicine  

<p><b>Summary:</b> <i><b>Background</b></i><b>:</b> Small-sized tumors tend to be resected without thorough assessment and are often managed in a sarcoma center after a malignancy is diagnosed. The lack of knowledge about the features of smallsized sarcomas may lead to unplanned resection. The features of small-sized soft tissue sarcomas were investigated by comparing them with those of small benign soft tissue tumors. </p><p><i><b>Methods</b></i><b>:</b> We included 17 soft tissue sarcoma cases (7 on the hands and feet and 10 on the limbs and trunk) with a diameter of under 2 cm. The features of small-sized sarcomas were compared to those of 39 benign soft tissue tumors with a diameter of under 2 cm and non-specific imaging findings (30 on the hands and feet and 9 on the limbs and trunk). The investigated features were age, sex, presence of pain, subjective increasing tumor size, and duration of observation. </p><p><i><b>Results</b></i><b>:</b> When we compared the tumors in the hands and feet, those <40 years of age (5/7 [71%] vs. 8/30 [27%], p=0.03) experiencing pain (7/7 [100%] vs. 13/30 [43%], p=0.007) were more common in patients with sarcomas than in patients with benign tumors. When we compared the tumors in the limbs and trunk, there was no significant difference in all investigated features. </p><p><i><b>Conclusion</b></i><b>:</b> Although clinical features were ineffective in distinguishing malignancy in most small-sized soft tissue tumors, we should pay attention to painful tumors of the hands and feet in younger patients.</p>

DOI： 10.2739/kurumemedj.MS69120015

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

腱板断裂患者における神経因性疼痛の有病率とその関連因子について検討した。腱板断裂患者391例を対象に疼痛DETECT質問票日本語版(PDQ-J)スコアを用いて神経因性疼痛の有病率を調査した。PDQ-Jスコア19点以上の神経因性疼痛(NeP)群が28例(男性19例、女性9例、平均66.4±11.6)歳、スコア13～18点のニューロパチー疑い群が97例(男性48例、女性49例、平均68.4±11.2歳)、スコア12点以下の侵害受容性疼痛群が266例(男性138例、女性128例、平均67.7±10.4歳)であった。単変量解析では、NePとUCLA肩関節スコア、初診時の疼痛、直近4週以内の重度疼痛、直近4週以内の平均疼痛、自動前屈、外転、初期回旋、Neer/Hawkinsインピンジメントテスト陽性、棘上筋テスト陽性、棘下筋テスト陽性との間に有意な関連が認められ、多重ロジスティック回帰分析では疼痛VASスコアとUCLA肩関節スコアがNeP発症と有意に関連していた。腱板断裂患者における神経因性疼痛の有病率は7.2%であり、アウトカムに悪影響を及ぼすことから、有痛性腱板断裂の治療に際してその有無を評価することが重要であると考えられた。

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

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

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

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

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Language：Japanese   Publisher：West-Japanese Society of Orthopedics & Traumatology  

<p>【目的】Stump分類Type 3の腱板断裂に対し鏡視下腱板修復術（以下ARCR）後における腱板のMRI信号強度の推移を検討した．【対象と方法】2013～2019年にARCRを行った126例中，術前Stump分類がType 3かつ術後2年以上フォローしえた15肩（Cofield分類：小断裂3肩，中断裂5肩，大断裂3肩，広範囲断裂4肩）を対象とし術前，術後3ヶ月，6ヶ月，1年，2年時のMRIでの腱板と三角筋の平均信号強度の比（以下C/D）および断裂サイズ別のC/Dの推移を検討した．C/DはIshitaniらの報告^4）に準じて計測した．【結果】C/Dは術後1年時と術前で有意差は認めなかったが，術後2年時は術前，術後3ヶ月，6ヶ月と比較し有意に減少していた．断裂サイズ別のC/Dの改善度に有意差は認めなかった．【考察】ARCR後のStump分類Type 3の腱板は術後1年から2年の間に修復が進むことが推察された．</p>

DOI： 10.5035/nishiseisai.72.821

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Language：Japanese   Publisher：(一社)日本肩関節学会  

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Language：Japanese   Publisher：(一社)日本肩関節学会  

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

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2023&ichushi_jid=J00766&link_issn=&doc_id=20231208120058&doc_link_id=10.5035%2Fnishiseisai.72.821&url=https%3A%2F%2Fdoi.org%2F10.5035%2Fnishiseisai.72.821&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

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

【目的】Stump分類Type 3の腱板断裂に対し鏡視下腱板修復術(以下ARCR)後における腱板のMRI信号強度の推移を検討した.【対象と方法】2013～2019年にARCRを行った126例中,術前Stump分類がType 3かつ術後2年以上フォローしえた15肩(Cofield分類:小断裂3肩,中断裂5肩,大断裂3肩,広範囲断裂4肩)を対象とし術前,術後3ヵ月,6ヵ月,1年,2年時のMRIでの腱板と三角筋の平均信号強度の比(以下C/D)および断裂サイズ別のC/Dの推移を検討した.C/DはIshitaniらの報告4)に準じて計測した.【結果】C/Dは術後1年時と術前で有意差は認めなかったが,術後2年時は術前,術後3ヵ月,6ヵ月と比較し有意に減少していた.断裂サイズ別のC/Dの改善度に有意差は認めなかった.【考察】ARCR後のStump分類Type 3の腱板は術後1年から2年の間に修復が進むことが推察された.(著者抄録)

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

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

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

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

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

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

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

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

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

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

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Language：Japanese   Publisher：(一社)日本ペインリハビリテーション学会  

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

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Language：Japanese   Publisher：西日本整形・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：The Japanese Society for Spine Surgery and Related Research  

<p><b>Introduction: </b>The spinal instability neoplastic score (SINS) is a classification system used to diagnose neoplastic spinal instability. Several reports have also described its use as a screening tool to identify patients at risk of skeletal-related events. We investigated the efficacy of SINS to detect the risk of neurological deficit in patients with spinal metastases by assessing spinal metastatic instability before the onset of myelopathy.</p><p><b>Methods: </b>We performed surgery on 81 patients with cervical or thoracic lesions classified as metastatic spine disease between 2004 and 2019. In this cohort, spinal instability was assessed in 29/81 patients before the occurrence of myelopathy. Spinal instability was evaluated by SINS with computed tomography (CT) performed within 6 months of the neurological deficit. We defined patients with a score of 7 or higher as at-risk patients.</p><p><b>Results: </b>CT was performed at an average of 72 days before the onset of neurological deficits. The SINS were 2 no-metastases cases, 4 of less than 7 (stability), 15 of 7-12 (indeterminate instability), and 8 of 13-18 (instability). We were unable to detect 21% (6/29) patients at risk of SINS.</p><p><b>Conclusions: </b>We may not be able to detect approximately 20% at-risk patients with neurological deficits by SINS before myelopathy presents.</p>

DOI： 10.34371/jspineres.2022-0021

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Language：Japanese  

はじめに:Spinal Instability Neoplastic Score(SINS)は転移性脊椎腫瘍の不安定性評価法であるが,骨有害事象リスク患者を検出する際のスクリーニング手段としても使用が報告されている.転移性脊椎腫瘍による脊髄症状発症例から,脊髄症状発症前のSINSを測定することにより,SINSによるリスク患者検出の有効性について検証した.対象と方法:2004年から2019年,頸胸椎部の転移性脊椎腫瘍に対する手術例81例から,脊髄症状発症前の画像評価が可能であった29例について調査した.脊髄症状発症半年以内に撮影されたCTからSINSを測定し,SINS7以上をリスク患者とした.結果:CT撮影時期は脊髄症状発症の平均72日前であった.SINSは転移なし2例,7未満(stability)4例,7以上～13未満(indeterminate instability)15例,13以上(instability)8例であり,21%(6/29)はリスク患者とならなかった.結語:脊髄症状発症前のSINSによる評価では約20%で脊髄症状発症の危険性を検出できない可能性が示唆された.(著者抄録)

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

はじめに:Spinal Instability Neoplastic Score(SINS)は転移性脊椎腫瘍の不安定性評価法であるが,骨有害事象リスク患者を検出する際のスクリーニング手段としても使用が報告されている.転移性脊椎腫瘍による脊髄症状発症例から,脊髄症状発症前のSINSを測定することにより,SINSによるリスク患者検出の有効性について検証した.対象と方法:2004年から2019年,頸胸椎部の転移性脊椎腫瘍に対する手術例81例から,脊髄症状発症前の画像評価が可能であった29例について調査した.脊髄症状発症半年以内に撮影されたCTからSINSを測定し,SINS7以上をリスク患者とした.結果:CT撮影時期は脊髄症状発症の平均72日前であった.SINSは転移なし2例,7未満(stability)4例,7以上～13未満(indeterminate instability)15例,13以上(instability)8例であり,21%(6/29)はリスク患者とならなかった.結語:脊髄症状発症前のSINSによる評価では約20%で脊髄症状発症の危険性を検出できない可能性が示唆された.(著者抄録)

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Journal of Orthopaedic Science  

BACKGROUND: The management of pain in patients with rotator cuff tears can be challenging. Neuropathic pain is reportedly associated with pain occurrence in musculoskeletal diseases. However, to date, few studies have reported on the prevalence of neuropathic pain in patients with rotator cuff tears or identified the factors associated with neuropathic pain in a multicenter study. METHODS: A total of 391 patients (205 males and 186 females; median age, 67.7 years; range, 27-92 years) with rotator cuff tears were included in this study. The prevalence of neuropathic pain in rotator cuff tears was investigated using the Japanese version of the painDETECT questionnaire for all patients. In addition, factors significantly associated with the occurrence of neuropathic pain were examined using multivariate logistic regression analysis. RESULTS: Twenty-eight patients (7.2%) were classified into the neuropathic pain group (score ≥19), 97 (24.8%) into the uncertainty regarding neuropathy group (score 13-18), and 266 (68.0%) into the nociceptive pain group (score ≤12). According to the multivariate logistic regression analysis, the independent predictors of neuropathic pain were the VAS score (most severe pain during the past 4 weeks; odds ratio, 1.55; 95% confidence interval [CI], 1.23-2.09) and UCLA shoulder score (odds ratio, 0.81; 95% CI, 0.65-0.97). CONCLUSIONS: Based on the study findings, the prevalence of neuropathic pain in patients with rotator cuff tear was 7.2%. It is important to investigate the presence or absence of neuropathic pain when treating patients with painful rotator cuff tears, because neuropathy associated with rotator cuff tears may adversely affect patient outcomes.

DOI： 10.1016/j.jos.2022.10.015

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Language：English   Publisher：Oxford University Press  

症例は20歳男性で、重度の右肩関節痛と可動域(ROM)制限を訴えた。1年前に皮膚筋炎と診断されてステロイドパルス療法を開始されたが、その後、両側肩関節痛、股関節痛、軽度膝関節痛をきたした。両側上腕骨頭、大腿骨頭、大腿顆に生じた骨壊死と診断され、肩関節のUCLAスコアは17点、JOAスコアは48点を示し、肩関節前後方向X線検査では上腕骨頭にcrescent sign、CTにて軟骨下骨挫滅を認め、右上腕骨頭のステロイド誘発性骨壊死と診断した。本例は若年で忍容性が高いと判断し、人工関節置換術ではなく自家骨を用いた骨軟骨カラム移植を行う方針とした。術中所見では長軸に沿って22mm、短軸に沿って20mmの範囲で軟骨下骨の挫滅が認められ、内側滑車と外側滑車の非荷重領域より計三つの自家骨を採取し、骨壊死部に埋入した。術後、右上肢に三角巾をかけて固定し、2週後に振り子運動、3週後にROM運動を許可した。1年後のCTでは自家骨の完全癒合がみられ、1年半後、無痛状態を維持しておりROM改善が得られていた。

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

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Language：Japanese   Publisher：West-Japanese Society of Orthopedics & Traumatology  

<p>【目的】リバース型人工肩関節置換術におけるbaseplate pegの下方傾斜とpegの逸脱との関連を検討すること．【対象と方法】43例を対象とした．Equinoxe baseplateを使用し，専用のsoftwareを用いて解析を行った．CT dataを基に肩甲骨の3D画像を作成した．pegの位置を関節窩中心（C群），前方1mm，（A1群）前方2mm（A2群）の3群に分け，下方傾斜を0°，5°，10°の3パターンでpegの非逸脱率を評価した．また上記検討をstandardとsmallの2sizeで施行し，baseplate sizeによる非逸脱率の評価も行った．【結果】pegの非逸脱率の割合は，双方のsizeで下方傾斜0°が5°，10°に比べて高かったが有意差は認めなかった．また関節窩中心より前方にpegを配置すると非逸脱率が高い傾向にあった．【考察】baseplate pegを肩甲骨長軸より前方2mmでかつ下方傾斜を0°に刺入すると骨外への逸脱を最も軽減できることが示唆された．</p>

DOI： 10.5035/nishiseisai.71.402

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

【目的】リバース型人工肩関節置換術におけるbaseplate pegの下方傾斜とpegの逸脱との関連を検討すること.【対象と方法】43例を対象とした.Equinoxe baseplateを使用し,専用のsoftwareを用いて解析を行った.CT dataを基に肩甲骨の3D画像を作成した.pegの位置を関節窩中心(C群),前方1mm,(A1群)前方2mm(A2群)の3群に分け,下方傾斜を0°,5°,10°の3パターンでpegの非逸脱率を評価した.また上記検討をstandardとsmallの2sizeで施行し,baseplate sizeによる非逸脱率の評価も行った.【結果】pegの非逸脱率の割合は,双方のsizeで下方傾斜0°が5°,10°に比べて高かったが有意差は認めなかった.また関節窩中心より前方にpegを配置すると非逸脱率が高い傾向にあった.【考察】baseplate pegを肩甲骨長軸より前方2mmでかつ下方傾斜を0°に刺入すると骨外への逸脱を最も軽減できることが示唆された.(著者抄録)

Language：English   Publisher：Oxford University Press  

骨軟部腫瘍の手術を受ける患者を対象に、止血作用や抗炎症作用などを有するトラネキサム酸(TXA)投与の有効性と安全性を検討するため、後方視的な傾向スコアマッチング解析を行った。2017年1月から2018年12月までに切開生検、辺縁切除、掻爬、広範切除を受けた骨軟部腫瘍の患者連続454例を対象とした。TXA投与の有無によってTXA投与群211例(平均47.6±20.7歳)とTXA非投与群243例(平均45.1±22.1歳)に分けた。患者454例のうち、切開生検は102例、辺縁切除は175例、掻爬は54例、広範切除は123例で行われた。術中出血量は、辺縁切除、広範切除ともにTXA投与群がTXA非投与群に比べて有意に少なかった(辺縁切除:17.3g vs.70.3g、P=0.045;広範切除:128.8g vs.273.1g、P=0.023)。周術期出血量および推定出血量も、広範切除ではTXA投与群でTXA非投与群に比べて有意に少なかった(周術期出血量:341.5g vs.686.5g、P=0.0039;推定出血量:320.7mL vs.550.6mL、P=0.030)。静脈血栓塞栓症は両群とも発生しなかった。以上より、TXA投与は、有害事象の発生率を上昇させずに、特に広範な切除術において安全かつ効果的に出血量を減少させることが示唆された。

Language：English   Publisher：久留米大学医学部  

小型軟部肉腫の臨床的特徴を小型良性軟部腫瘍と比較する後ろ向き研究を行った。2006～2019年に当院で手術が施行された直径2cm以下の軟部肉腫患者17例と、直径2cm以下で非特異的な画像所見を示す良性軟部組織腫瘍患者39例を対象とした。病変部位が手足の患者は軟部肉腫群7例(40歳未満71%、男性43%)、良性軟部組織腫瘍群30例(同27%、27%)、病変部位が四肢・体幹の患者はそれぞれ10例(同30%、30%)と9例(同44%、33%)であった。手足の腫瘍を比較した結果、40歳未満の患者と疼痛を経験した患者は軟部肉腫群が良性軟部組織腫瘍群よりも有意に多かった。四肢・体幹の腫瘍を比較した結果、調査したすべての特徴に有意差はみられなかった。以上から、大半の小型軟部腫瘍において臨床的特徴は悪性の鑑別に有効ではなかったが、若年患者における手足の有痛性腫瘍には注意を払う必要があることが示唆された。

Language：English   Publishing type：Research paper (scientific journal)   Publisher：International Orthopaedics  

PURPOSE: Baseplate positioning may affect clinical outcome after reverse total shoulder arthroplasty (RTSA). The aim of this study was to evaluate the risk of penetration of the baseplate peg in RTSA. METHODS: Forty-four patients with rotator cuff arthropathy or massive rotator cuff tears were included. Using their computed tomography data, ten insertion patterns of the baseplate pegs were simulated. First, in the axial plane, the baseplate was placed perpendicular to the Friedman axis (Friedman placement) and parallel to the glenoid surface (glenoid placement). Second, each of these placements were classified into the following groups: The baseplate peg was placed 2 mm anterior to the long axis of the glenoid (group A2), 1 mm anterior (group A1), on the long axis (group C0), 1 mm posterior (group P1), and 2 mm posterior (group P2). Cases in which the baseplate peg was within the scapular neck were defined as non-penetration, and the non-penetration rates among each group were evaluated and compared between sexes, and their relationship with patient height was evaluated. RESULTS: In both the Friedman and glenoid placements, the non-penetration rate was significantly higher in groups A2 (68.2% and 70.5%) and A1 (65.9% and 65.9%) compared with groups P1 (18.2% and 29.5%) and P2 (9.1% and 13.6%; p < 0.001) and in males than in females (p < 0.05). Furthermore, the non-penetration rate tended to be higher as the patient's height increased. CONCLUSIONS: It is recommended that the baseplate peg be placed anterior to the long axis of the glenoid.

DOI： 10.1007/s00264-022-05328-x

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：British Journal of Cancer  

BACKGROUND: Dedifferentiated chondrosarcoma (DDCS) is an aggressive bone tumour with a poor prognosis and no effective treatment. Because changes in DNA methylation play critical roles in DDCS, we explored the roles that DNA methylation plays in oncogenesis to potentially identify an effective epigenetic treatment. METHODS: We identified genes downregulated in DDCS vs. conventional chondrosarcoma (CCS) due to DNA methylation using in silico analysis. The results were validated in DDCS clinical samples, and the molecular functions of the genes of interest were investigated in multiple chondrosarcoma cell lines (NDCS-1, SW1353, and OUMS-27). The therapeutic effect of decitabine, a DNA methyltransferase inhibitor, was evaluated in vitro and in vivo. RESULTS: PRKCZ was specifically downregulated by DNA methylation in DDCS. Overexpression of PRKCZ decreased the proliferation of NDCS-1 and SW1353 cells. PRKCZ directly bound to and activated ATM, which was followed by phosphorylation of CHK2 and subsequent apoptosis. Decitabine increased PRKCZ expression through de-methylating the promoter region of PRKCZ, which activated the ATM/CHK2 pathway and inhibited cell proliferation by inducing apoptosis. CONCLUSIONS: Increased DNA methylation and reduced expression of PRKCZ prevents apoptosis via inactivation of the ATM/CHK2 pathway in DDCS. Decitabine-induced expression of PRKCZ represents a promising therapy for DDCS.

DOI： 10.1038/s41416-021-01695-1

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Japanese Journal of Clinical Oncology  

OBJECTIVE: The aim of this study was to investigate the efficacy and safety of tranexamic acid in patients undergoing surgery for bone and soft tissue tumors. METHODS: Data were retrospectively collected from 454 consecutive patients with bone and soft tissue tumors who underwent open biopsy, marginal resection, curettage or wide resection between January 2017 and December 2018. We performed propensity score matching of patients who received tranexamic acid with those who did not. The primary outcome variables were intra-operative, peri-operative and estimated blood loss (IBL, PBL and EBL, respectively). RESULTS: Tranexamic acid (+) and tranexamic acid (-) groups were defined according to whether patients received tranexamic acid or not. Among the 454 patients, open biopsy was performed in 102, marginal resection in 175, curettage in 54 and wide resection in 123. Intra-operative blood loss was significantly lower in the tranexamic acid (+) group than in the tranexamic acid (-) group for both marginal and wide resection (marginal resection: 17.3 vs. 70.3 g, respectively, P = 0.045; wide resection: 128.8 vs. 273.1 g, respectively, P = 0.023). Peri-operative blood loss and estimated blood loss were also significantly lower in the tranexamic acid (+) group for wide resection (peri-operative blood loss: 341.5 vs. 686.5 g, respectively, P = 0.0039; estimated blood loss: 320.7 vs. 550.6 ml, respectively, P = 0.030). No venous thromboembolism occurred in either group. CONCLUSION: This study suggests that TXA administration safely and effectively reduces blood loss, in particular for wide resection, with no increase in the rate of adverse events.

DOI： 10.1093/jjco/hyac078

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Modern Rheumatology Case Reports  

To our knowledge, only one previous report described the treatment of osteochondral autograft for steroid-induced osteonecrosis of the humeral head (ONHH) in a middle-aged patient. The present report describes a 20-year-old man who was found to have avascular osteonecrosis of the right humeral head after corticosteroid pulse treatment, followed by oral corticosteroid therapy. The patient complained of serious right shoulder pain and limited range of motion (ROM). Anteroposterior (AP) radiographs of the right shoulder revealed a crescent sign at the humeral head, indicating subchondral bone collapse with a linear sclerotic change and normal articular surface of the glenoid. The case was categorized as stage 3 according to the Cruess classification. In general, Cruess classification stage 3 is treated with humeral head replacement and shoulder arthroplasty. The patient underwent surgical treatment involving osteochondral autograft transplantation. Autografts were harvested from the right knee. At the 1.5-year follow up, the patient was pain-free and showed an improved active ROM. Furthermore, AP radiographs demonstrated that the glenohumeral joint space was maintained, and no progression of humeral head collapse was observed. This case may be helpful in decision making if young patients with ONHH require surgical treatment. Further, osteochondral autograft transplantation may be an effective treatment for ONHH.

DOI： 10.1093/mrcr/rxac037

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Journal of Clinical Medicine  

Periosteal chondrosarcoma is an extremely rare malignant cartilage-forming tumour that originates from the periosteum and occurs on the surface of bone. Often, it is difficult to distinguish periosteal chondrosarcoma from other tumours, and reports in the literature are scarce. This study aims to investigate the characteristics of periosteal chondrosarcoma, focusing particularly on medullary invasion. Among 33 periosteal cartilaginous tumours, seven patients with pathologically proven periosteal chondrosarcoma were identified retrospectively. The average tumour size was 5.4 cm in the long axis; two tumours were smaller than 3.0 cm. Six tumours were resected with a wide margin, and the remaining tumour had a marginal margin. Histology revealed that six tumours (85.7%) had invaded the medullary cavity; three of these did not show invasion into the medullary cavity on MRI evaluation. Neither local recurrence nor metastasis was observed among these patients. The frequency of invasion of the medullary cavity was higher than that reported previously. The recommended treatment for periosteal chondrosarcoma is resection with an adequate margin. Therefore, surgeons should consider the possibility of medullary invasion when attempting to achieve a histologically negative margin, even if the tumour does not show invasion into the medullary cavity on MRI.

DOI： 10.3390/jcm11072062

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Language：Japanese   Publisher：(一社)日本手外科学会  

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Language：Japanese   Publisher：(一社)日本手外科学会  

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Publisher：Gan to Kagaku Ryoho Cancer Chemotherapy  

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Language：Japanese   Publisher：金原出版  

DOI： 10.18888/se.0000002057

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

Language：Japanese  

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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)  

Pazopanib, trabectedin, and eribulin are administered for the treatment of soft tissue sarcomas (STSs); however, there is little consensus on which agent should be preferentially used in a clinical setting. This study assessed whether peripheral immune-related markers served as a useful reference when selecting pazopanib, trabectedin, or eribulin. This study included 63 patients who were administered pazopanib, trabectedin, or eribulin for advanced STSs between March 2015 and December 2020. Patients were divided into three groups based on the first drug administered among these three drugs. Differences in overall survival (OS) or progression-free survival (PFS) among the three groups were analyzed. OS showed no significant differences among the drugs administered first. For patients with low neutrophil-to-lymphocyte ratio (NLR), the OS of patients administered pazopanib as the first choice was shorter than the others (hazard ratio [HR] = 9.53, 95&#37; confidence interval [CI] = 1.94-18.13, p = 0.0018). In the low platelet-to-lymphocyte ratio (PLR) subgroup, the OS of the patients administered eribulin for the first choice was longer than that of the others (HR = 0.32, 95&#37;CI = 0.10-0.98, p = 0.046). Therefore, NLR and PLR might be used as prognostic indicators to dictate whether STS patients receive pazopanib, trabectedin, or eribulin.

DOI： 10.3390/jcm10214972

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

BACKGROUND Giant cell tumor of bone (GCTB) is a locally aggressive, intermediate tumor that rarely metastasizes. GCTB typically affects the ends of long bones and rarely involves the ribs. Curettage is typically the treatment of choice for GCTB in long bones. However, the optimal treatment of GCTB in ribs remains unclear. We report the case of a patient with asymptomatic GCTB of the first rib that was successfully treated with combined preoperative denosumab therapy and surgery via a transmanubrial approach without resection of the clavicle. CASE REPORT A healthy 27-year-old woman presented with a bone tumor involving the left first rib that was incidentally discovered on routine chest X-ray. Histological examination of core-needle biopsy specimens of the lesion led to a pathological diagnosis of GCTB. After preoperative denosumab treatment for 6 months, en bloc resection via a transmanubrial approach was performed. There were no serious postoperative complications. The patient remained free of symptoms and had no recurrence 4.5 years after surgery. CONCLUSIONS Compared with other ribs, masses located in the first rib can be challenging to treat surgically because of the clavicle and neighboring neurovascular structures. This report is the first to describe GCTB located on the anterior aspect of the first rib that was successfully treated with combined preoperative denosumab therapy and surgery via a transmanubrial approach, with no recurrence or functional impairment of the shoulder girdle.

DOI： 10.12659/AJCR.931796

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

BACKGROUND CIC-rearranged sarcoma (CRS) is a recently described subset of undifferentiated small-round-cell sarcomas of bone and soft tissue. DUX4 is the most common gene involved in CRS. CRS usually presents in the soft tissue of the trunk and extremities, and is recognized as being clinically aggressive, with poor prognosis. Our case highlights an unusual presentation of CRS with cardiac tamponade. CASE REPORT A 48-year-old man presented with hypotension caused by hemorrhagic cardiac tamponade. ¹⁸F-fluorodeoxyglucose-positron emission tomography showed increased uptake in multiple lesions, including lesions in the left proximal humerus and several lymph nodes. Biopsy specimens of the humerus revealed proliferation of round-shaped cells. In addition, CIC-DUX4 gene rearrangement was detected by polymerase chain reaction and direct sequencing, leading to a diagnosis of cardiac tamponade caused by CRS. Although the patient received systemic chemotherapy as well as radiotherapy to the mediastinal lesion and left humerus, he died of progressive disease 12 months after diagnosis. CONCLUSIONS Because CRS is a recently proposed entity that is distinct from Ewing sarcoma, the clinical presentation and outcome of CRS has not been well documented in the literature. This is the first case report of CRS presenting as cardiac tamponade. Although cardiac tamponade due to metastatic sarcoma is extremely rare, CRS can be included in the differential diagnosis.

DOI： 10.12659/AJCR.929349

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

Periprosthetic osteolysis remains as a major complication of total joint replacement surgery. Modulation of macrophage polarization with interleukin-4 (IL-4) has emerged as an effective means to limit wear particle-induced osteolysis. The aim of this study was to evaluate the efficacy of local IL-4 delivery in treating preexisting particle-induced osteolysis. To this end, recently established 8 week modification of murine continuous femoral intramedullary particle infusion model was utilized. Subcutaneous infusion pumps were used to deliver polyethylene (PE) particles into mouse distal femur for 4 weeks to induce osteolysis. IL-4 was then added to the particle infusion for another 4 weeks. This delayed IL-4 treatment (IL-4 Del) was compared to IL-4 delivered continuously (IL-4 Cont) with PE particles from the beginning and to the infusion of particles alone for 8 weeks. Both IL-4 treatments were highly effective in preventing and repairing preexisting particle-induced bone loss as assessed by μCT. Immunofluorescence indicated a significant reduction in the number of F4/80 + iNOS + M1 macrophages and increase in the number of F4/80 + CD206 + M2 macrophages with both IL-4 treatments. Reduction in the number of tartrate resistant acid phosphatase + osteoclasts and increase in the amount of alkaline phosphatase (ALP) + osteoblasts was also observed with both IL-4 treatments likely explaining the regeneration of bone in these samples. Interesting, slightly more bone formation and ALP + osteoblasts were seen in the IL-4 Del group than in the IL-4 Cont group although these differences were not statistically significant. The study is a proof of principle that osteolytic lesions can be repaired via modulation of macrophage polarization.

DOI： 10.1002/jbm.a.37142

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

"Senile osteoporosis" is defined as significant aging-associated bone loss, and is accompanied by increased fat in the bone marrow. The proportion of adipocytes in bone marrow is inversely correlated with bone formation, and is associated with increased risk of fracture. NF-κB is a transcription factor that functions as a master regulator of inflammation and bone remodeling. NF-κB activity increases during aging; furthermore, constitutive activation of NF-κB significantly impairs skeletal development in neonatal mice. However, the effects of NF-κB activation using a skeletally mature animal model have not been examined. In the current study, an osteoprogenitor (OP)-specific, doxycycline-regulated NF-κB activated transgenic mouse model (iNF-κB/OP) was generated to investigate the role of NF-κB in bone remodeling in skeletally mature mice. Reduced osteogenesis in the OP-lineage cells isolated from iNF-κB/OP mice was only observed in the absence of doxycycline in vitro. Bone mineral density in the metaphyseal regions of femurs and tibias was reduced in iNF-κB/OP mice. No significant differences in bone volume fraction and cortical bone thickness were observed. Osmium-stained bone marrow fat was increased in epiphyseal and metaphyseal areas in the tibias of iNF-κB/OP mice. These findings suggest that targeting NF-κB activity as a therapeutic strategy may improve bone healing and prevent aging-associated bone loss in aged patients.

DOI： 10.1007/s40883-019-00112-7

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

Macrophage-mediated inflammatory reaction to implant wear particles drives bone loss around total joint replacements (TJR). Although most TJR recipients are elderly, studies linking wear particle-activated macrophages and peri-implant osteolysis have not taken into account the multiple effects that aging has on the innate immune system and, in particular, on macrophages. To address this, we compared the wear particle responses of bone marrow macrophages obtained from young (2-month) and aged (18-month) mice. Macrophages were polarized to M0, M1, or M2 phenotypes in vitro, challenged with titanium particles, and their inflammatory response was characterized at multiple time points by quantitative reverse-transcription polymerase chain reaction and enzyme-linked immunosorbent assay. In addition, age-dependent changes in activation of transcription factor nuclear factor-κB were analyzed by a lentiviral vector-based luciferase reporter system. The particle stimulation experiment was further repeated using human primary macrophages isolated from blood donors of different ages. We found that the pro-inflammatory responses were generally higher in macrophages obtained from young mice, but differences between the age groups remained small and of uncertain biological significance. Noteworthily, M2 polarization effectively suppressed the particle-induced inflammation in both young and aged macrophages. These results suggest that aging of the innate immune system per se plays no significant role in the response of macrophages to titanium particles, whereas induction of M2 polarization appears a promising strategy to limit macrophage-mediated inflammation regardless of age. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:405-416, 2020.

DOI： 10.1002/jor.24461

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

Osteonecrosis of the femoral head (ONFH) is a debilitating disease that may progress to femoral head collapse and subsequently, degenerative arthritis. Although injection of bone marrow-derived mononuclear cells (BMMCs) is often performed with core decompression (CD) in the early stage of ONFH, these treatments are not always effective in prevention of disease progression and femoral head collapse. We previously described a novel 3D printed, customized functionally-graded scaffold (FGS) that improved bone growth in the femoral head after CD in a normal healthy rabbit, by providing structural and mechanical guidance. The present study demonstrates similar results of the FGS in a rabbit steroid-induced osteonecrosis model. Furthermore, the injection of BMMCs into the CD decreased the osteonecrotic area in the femoral head. Thus, the combination of FGS and BMMC provides a new therapy modality that may improve the outcome of CD for early stage of ONFH by providing both enhanced biological and biomechanical cues to promote bone regeneration in the osteonecrotic area.

DOI： 10.1016/j.biomaterials.2018.09.030

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

BACKGROUND: Mesenchymal stem cells (MSCs) are capable of immunomodulation and tissue regeneration, highlighting their potential translational application for treating inflammatory bone disorders. MSC-mediated immunomodulation is regulated by proinflammatory cytokines and pathogen-associated molecular patterns such as lipopolysaccharide (LPS). Previous studies showed that MSCs exposed to interferon gamma (IFN-γ) and the proinflammatory cytokine tumor necrosis factor alpha (TNF-α) synergistically suppressed T-cell activation. METHODS: In the current study, we developed a novel preconditioning strategy for MSCs using LPS plus TNF-α to optimize the immunomodulating ability of MSCs on macrophage polarization. RESULTS: Preconditioned MSCs enhanced anti-inflammatory M2 macrophage marker expression (Arginase 1 and CD206) and decreased inflammatory M1 macrophage marker (TNF-α/IL-1Ra) expression using an in-vitro coculture model. Immunomodulation of MSCs on macrophages was significantly increased compared to the combination of IFN-γ plus TNF-α or single treatment controls. Increased osteogenic differentiation including alkaline phosphate activity and matrix mineralization was only observed in the LPS plus TNF-α preconditioned MSCs. Mechanistic studies showed that increased prostaglandin E2 (PGE2) production was associated with enhanced Arginase 1 expression. Selective cyclooxygenase-2 inhibition by Celecoxib decreased PGE2 production and Arginase 1 expression in cocultured macrophages. CONCLUSIONS: The novel preconditioned MSCs have increased immunomodulation and bone regeneration potential and could be applied to the treatment of inflammatory bone disorders including periprosthetic osteolysis, fracture healing/nonunions, and osteonecrosis.

DOI： 10.1186/s13287-017-0730-z

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

Periprosthetic osteolysis and subsequent aseptic loosening of total joint replacements are driven by byproducts of wear released from the implant. Wear particles cause macrophage-mediated inflammation that culminates with periprosthetic bone loss. Most current animal models of particle-induced osteolysis are based on the acute inflammatory reaction induced by wear debris, which is distinct from the slowly progressive clinical scenario. To address this limitation, we previously developed a murine model of periprosthetic osteolysis that is based on slow continuous delivery of wear particles into the murine distal femur over a period of 4 weeks. The particle delivery was accomplished by using subcutaneously implanted osmotic pumps and tubing, and a hollow titanium rod press-fit into the distal femur. In this study, we report a modification of our prior model in which particle delivery is extended to 8 weeks to better mimic the progressive development of periprosthetic osteolysis and allow the assessment of interventions in a setting where the chronic particle-induced osteolysis is already present at the initiation of the treatment. Compared to 4-week samples, extending the particle delivery to 8 weeks significantly exacerbated the local bone loss observed with μCT and the amount of both peri-implant F4/80+ macrophages and tartrate-resistant acid phosphatase-positive osteoclasts detected with immunohistochemical and histochemical staining. Furthermore, systemic recruitment of reporter macrophages to peri-implant tissues observed with bioluminescence imaging continued even at the later stages of particle-induced inflammation. This modified model system could provide new insights into the mechanisms of chronic inflammatory bone loss and be particularly useful in assessing the efficacy of treatments in a setting that resembles the clinical scenario of developing periprosthetic osteolysis more closely than currently existing model systems.

DOI： 10.1089/ten.TEC.2017.0166

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

The modulation of macrophage phenotype from pro-inflammatory (M1) to tissue healing (M2) via exogenous addition of interleukin-4 (IL-4) facilitates osteogenesis; however, the molecular mediators underlying this phenomenon remain unknown. This study characterizes the IL-4-dependent paracrine crosstalk between macrophages and osteoprogenitors and its effect on osteogenesis in vitro. Primary murine M1 were co-cultured with MC3T3 cells (M1-MC3T3) in both transwell plates and direct co-cultures. To modulate M1 to M2, M1-MC3T3 were treated with IL-4 (20 ng/mL) at day 3 after seeding (M1 + IL-4-MC3T3). Selected molecular targets were assessed at days 3 and 6 after seeding at protein and mRNA levels. Mineralization was assessed at day 21. Transwell M1 + IL-4-MC3T3 significantly enhanced the secretion of CCL2/MCP-1, IGF-1 and to a lesser degree, CCL5/RANTES at day 6. At day 3, alkaline phosphatase (Alpl) was upregulated in direct M1-MC3T3. At day 6, Smurf2 and Insulin growth factor-1 (IGF-1) were downregulated and upregulated, respectively, in direct M1 + IL-4-MC3T3. Finally, M1 + IL-4-MC3T3 increased bone matrix mineralization compared with MC3T3 cells in transwell, but this was significantly less than M1-MC3T3. Taken together, macrophage subtypes enhanced the osteogenesis in transwell setting and the transition from M1 to M2 was associated with an increase in bone anabolic factors CCL2/MCP-1, CCL5/RANTES and IGF-1 in vitro. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 3069-3076, 2017.

DOI： 10.1002/jbm.a.36166

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

Bone fractures are among the most common orthopaedic problems that affect individuals of all ages. Immediately after injury, activated macrophages dynamically contribute to and regulate an acute inflammatory response that involves other cells at the injury site, including mesenchymal stem cells (MSCs). These macrophages and MSCs work in concert to modulate bone healing. In this study, we co-cultured undifferentiated M0, pro-inflammatory M1, and anti-inflammatory M2 macrophages with primary murine MSCs in vitro to determine the cross-talk between polarized macrophages and MSCs and their effects on osteogenesis. After 4 weeks of co-culture, MSCs grown with macrophages, especially M1 macrophages, had enhanced bone mineralization compared to MSCs grown alone. The level of bone formation after 4 weeks of culture was closely associated with prostaglandin E2 (PGE2) secretion early in osteogenesis. Treatment with celecoxib, a cyclooxygenase-2 (COX-2) selective inhibitor, significantly reduced bone mineralization in all co-cultures but most dramatically in the M1-MSC co-culture. We also found that the presence of macrophages reduced the secretion of osteoprotegerin (OPG), the decoy RANKL receptor, suggesting that macrophages may indirectly modulate osteoclast activity in addition to enhancing bone formation. Taken together, these findings suggest that an initial pro-inflammatory phase modulated by M1 macrophages promotes osteogenesis in MSCs via the COX-2-PGE2 pathway. Understanding the complex interactions between macrophages and MSCs provide opportunities to optimize bone healing and other regenerative processes via modulation of the inflammatory response. This study provides one possible biological mechanism for the adverse effects of non-steroidal anti-inflammatory drugs on fracture healing and bone regeneration. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2378-2385, 2017.

DOI： 10.1002/jor.23553

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

Excessive production of wear particles from total joint replacements induces chronic inflammation, macrophage infiltration, and consequent bone loss (periprosthetic osteolysis). This inflammation and bone remodeling are critically regulated by the transcription factor NF-κB. We previously demonstrated that inhibition of NF-κB signaling by using the decoy oligodeoxynucleotide (ODN) mitigates polyethylene wear particle-induced bone loss using in vitro and in vivo models. However, the mechanisms of NF-κB decoy ODN action, and in particular its impact on systemic macrophage recruitment, remain unknown. In the current study, this systemic macrophage infiltration was examined in our established murine femoral continuous particle infusion model. RAW264.7 murine macrophages expressing a luciferase reporter gene were injected into the systemic circulation. Quantification of bioluminescence showed that NF-κB decoy ODN reduced the homing of these reporter macrophages into the distal femurs exposed to continuous particle delivery. Particle-induced reduction in bone mineral density at the distal diaphysis of the femur was also mitigated by infusion of decoy ODN. Histological staining showed that the decoy ODN infusion decreased osteoclast and macrophage numbers, but had no significant effects on osteoblasts. Local infusion of NF-κB decoy ODN reduced systemic macrophage infiltration and mitigated particle-induced bone loss, thus providing a potential strategy to treat periprosthetic osteolysis. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 3169-3175, 2017.

DOI： 10.1002/jbm.a.36169

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

Joint replacement is a commonly performed, highly successful orthopaedic procedure, for which surgeons have a large choice of different materials and implant designs. The materials used for joint replacement must be both biologically acceptable to minimize adverse local tissue reactions, and robust enough to support weight bearing during common activities of daily living. Modern joint replacements are made from metals and their alloys, polymers, ceramics, and composites. This review focuses on the biological response to the different biomaterials used for joint replacement. In general, modern materials for joint replacement are well tolerated by the body as long as they are in bulk (rather than in particulate or ionic) form, are mechanically stable and noninfected. If the latter conditions are not met, the prosthesis will be associated with an acute/chronic inflammatory reaction, peri-prosthetic osteolysis, loosening and failure. This article (Part 1 of 2) is dedicated to the use of metallic devices in orthopaedic surgery including the associated biological response to metallic byproducts is a review of the basic science literature regarding this topic. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 2162-2173, 2017.

DOI： 10.1002/jbm.b.33734

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

Chronic inflammation is associated with up-regulation of the transcription factor nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and excessive inflammatory cytokine secretion by M1 macrophages. The anti-inflammatory cytokine interleukin (IL)-4 converts pro-inflammatory M1 macrophages into an anti-inflammatory and tissue-regenerative M2 phenotype, thus reducing inflammation and enhancing tissue regeneration. We have generated NF-κB responsive, or constitutively active IL-4 expression lentiviral vectors transduced into murine bone marrow-derived mesenchymal stromal cells (MSCs). MSCs with a constitutively active IL-4 expression vector produced large quantities of IL-4 continuously, whereas IL-4 secretion was significantly induced by lipopolysaccharide (LPS) in the NF-κB sensing MSCs. In contrast, LPS had no effect on MSCs with IL-4 secretion driven by a constitutively active promoter. We also found that intermittent and continuous LPS treatment displayed distinct NF-κB activation profiles, and this regulation was independent of IL-4 signaling. The supernatant containing IL-4 from the LPS-treated MSCs suppressed M1 marker (inducible nitric oxide synthase [iNOS] and tumor necrosis factor alpha [TNFα]) expression and enhanced M2 marker (Arginase 1, CD206 and IL1 receptor antagonist [IL1Ra]) expression in primary murine macrophages. The IL-4 secretion at the basal, non-LPS induced level was sufficient to suppress TNFα and enhance Arginase 1 at a lower level, but had no significant effects on iNOS, CD206 and IL1Ra expression. Finally, IL-4 secretion at basal or LPS-induced levels significantly suppressed osteogenic differentiation of MSCs. Our findings suggest that the IL-4 secreting MSCs driven by NF-κB sensing or constitutive active promoter have great potential for mitigating the effects of chronic inflammation and promoting earlier tissue regeneration.

DOI： 10.1016/j.jcyt.2017.06.008

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

Peri-prosthetic osteolysis remains as the main long-term complication of total joint replacement surgery. Research over four decades has established implant wear as the main culprit for chronic inflammation in the peri-implant tissues and macrophages as the key cells mediating the host reaction to implant-derived wear particles. Wear debris activated macrophages secrete inflammatory mediators that stimulate bone resorbing osteoclasts; thus bone loss in the peri-implant tissues is increased. However, the balance of bone turnover is not only dictated by osteoclast-mediated bone resorption but also by the formation of new bone by osteoblasts; under physiological conditions these two processes are tightly coupled. Increasing interest has been placed on the effects of wear debris on the cells of the bone-forming lineage. These cells are derived primarily from multipotent mesenchymal stem cells (MSCs) residing in bone marrow and the walls of the microvasculature. Accumulating evidence indicates that wear debris significantly impairs MSC-to-osteoblast differentiation and subsequent bone formation. In this review, we summarize the current understanding of the effects of biomaterial implant wear debris on MSCs. Emerging treatment options to improve initial implant integration and treat developing osteolytic lesions by utilizing or targeting MSCs are also discussed. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1195-1207, 2017.

DOI： 10.1002/jbm.a.35978

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

Synovial sarcoma (SS) is a rare high-grade malignant mesenchymal tumour with a relatively poor prognosis despite intensive multimodal therapy. Although pazopanib, a multi-kinase inhibitor, is often used for advanced SS, most cases eventually become resistant to pazopanib. In the present study, we investigated the mechanisms of acquired pazopanib resistance in SS. To examine acquired pazopanib resistance, two SS cell lines, SYO-1 and HS-SY-II, were isolated after multiple selection steps with increasing concentrations of pazopanib. SYO-1 was also used in vivo. Then, pazopanib-resistant clones were investigated to assess potential mechanisms of acquired pazopanib resistance. Stable pazopanib-resistant clones were established and exhibited enhanced cell cycle progression, cell growth with increased ERK1/2 phosphorylation, and higher sensitivity than parental cells to a MEK-inhibitor, trametinib, both in vitro and in vivo. Furthermore, addition of low-dose trametinib partially reversed the pazopanib resistance. In the pazopanib-resistant clones, dual specificity phosphatase 6 (DUSP6) was downregulated. Inhibition of DUSP6 expression in parental HS-SY-II cells partially recapitulated acquired pazopanib resistance. Acquired pazopanib resistance in SS was associated with activation of ERK1/2 through downregulation of DUSP6 expression. Simultaneous treatment with pazopanib and a MEK inhibitor could be a promising strategy to overcome pazopanib resistance in SS.

DOI： 10.1038/srep45332

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

Aging is associated with significant bone loss and delayed fracture healing. NF-κB activation is highly correlated with inflammatory-associated bone diseases including infection, wear particle exposure, and chronic inflammation during natural aging processes. The critical roles of NF-κB in both the pro-inflammatory response and osteoclast-mediated bone resorption have been well defined. However, the biological effects of NF-κB activation in mesenchymal stem cell (MSC)-mediated bone formation remain largely unknown. In the current study, bone marrow-MSCs were isolated from young (8 weeks old) and aged (72 weeks old) mice. NF-κB activity in MSCs at basal levels and under different biological conditions were determined by our recently established lentiviral vector-based luciferase reporter assay. We found that NF-κB activity was increased in aged MSCs at basal levels or when exposed to low dose (10 or 100 ng/ml) lipopolysaccharide (LPS); this effect was not seen when the cells were exposed to higher dose (1 μg/ml) LPS. During osteogenesis, NF-κB activity was increased in aged MSCs at weeks 1 and 2, but showed no significant difference at week 3. Both Smurf2 and TAZ, the NF-κB target genes that regulate osteogenic differentiation, were increased in aged MSCs. In addition, the expression of RANKL was dramatically increased, and OPG was decreased in aged MSCs. Our findings suggest that targeting NF-κB activity in MSCs has the potential to modulate aging-associated bone loss, or enhance bone-healing in aged patients. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:281-288, 2017.

DOI： 10.1002/jor.23270

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

Wear particle-induced osteolysis limits the long-term survivorship of total joint replacement (TJR). Monocyte/macrophages are the key cells of this adverse reaction. Monocyte Chemoattractant Protein-1 (MCP-1/CCL2) is the most important chemokine regulating trafficking of monocyte/macrophages in particle-induced inflammation. 7ND recombinant protein is a mutant of CCL2 that inhibits CCL2 signaling. We have recently developed a layer-by-layer (LBL) coating platform on implant surfaces that can release biologically active 7ND. In this study, we investigated the effect of 7ND on wear particle-induced bone loss using the murine continuous polyethylene (PE) particle infusion model with 7ND coating of a titanium rod as a local drug delivery device. PE particles were infused into hollow titanium rods with or without 7ND coating implanted in the distal femur for 4 weeks. Specific groups were also injected with RAW 264.7 as the reporter macrophages. Wear particle-induced bone loss and the effects of 7ND were evaluated by microCT, immunohistochemical staining, and bioluminescence imaging. Local delivery of 7ND using the LBL coating decreased systemic macrophage recruitment, the number of osteoclasts and wear particle-induced bone loss. The development of a novel orthopaedic implant coating with anti-CCL2 protein may be a promising strategy to mitigate peri-prosthetic osteolysis.

DOI： 10.1016/j.biomaterials.2016.11.039

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

UNLABELLED: Total joint replacement is a cost-effective surgical procedure for patients with end-stage arthritis. Wear particle-induced chronic inflammation is associated with the development of periprosthetic osteolysis. Modulation of NF-κB signaling in macrophages, osteoclasts, and mesenchymal stem cells could potentially mitigate this disease. In the current study, we examined the effects of local delivery of decoy NF-κB oligo-deoxynucleotide (ODN) on wear particle-induced bone loss in a murine continuous femoral particle infusion model. Ultra-high molecular weight polyethylene particles (UHMWPE) with or without lipopolysaccharide (LPS) were infused via osmotic pumps into hollow titanium rods placed in the distal femur of mice for 4weeks. Particle-induced bone loss was evaluated by μCT, and immunohistochemical analysis of sections from the femur. Particle infusion alone resulted in reduced bone mineral density and trabecular bone volume fraction in the distal femur. The decoy ODN reversed the particle-associated bone volume fraction loss around the implant, irrespective of the presence of LPS. Particle-infusion with LPS increased bone mineral density in the distal femur compared with particle-infusion alone. NF-κB decoy ODN reversed or further increased the bone mineral density in the femur (3-6mm from the distal end) exposed to particles alone or particles plus LPS. NF-κB decoy ODN also inhibited macrophage infiltration and osteoclast number, but had no significant effects on osteoblast numbers in femurs exposed to wear particles and LPS. Our study suggests that targeting NF-κB activity via local delivery of decoy ODN has great potential to mitigate wear particle-induced osteolysis. STATEMENT OF SIGNIFICANCE: Total joint replacement is a cost-effective surgical procedure for patients with end-stage arthritis. Chronic inflammation is crucial for the development of wear particle-associated bone loss. Modulation of NF-κB signaling in macrophages (pro-inflammatory cells), osteoclasts (bone-resorbing cells), and osteoblasts (bone-forming cells) could potentially mitigate this disease. Here we demonstrated that local delivery of decoy NF-κB oligo-deoxynucleotide (ODN) mitigated ultra-high molecular weight polyethylene (UHMWPE) wear particle induced bone loss in a clinically relevant murine model. The protective effects of decoy ODN was associated with reduced macrophage infiltration and osteoclast activation, but had no significant effects on osteoblast numbers. Our study suggests that targeting NF-κB activity via local delivery of decoy ODN has great potential to mitigate wear particle-induced bone loss.

DOI： 10.1016/j.actbio.2016.05.038

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

Ewing sarcoma (ES) is a small round-cell tumor of the bones and soft tissues. ES frequently causes distant metastases, particularly in the lung and bone, which worsens patient prognosis. Cadherin-11 (Cad-11) is an adhesion molecule that is highly expressed in osteoblasts. Its expression is associated with bone metastases in prostate and breast cancer patients, and is known to occur in ES. Here we investigated the effects of Cad-11 on bone metastases of ES. Human ES cell lines RD-ES, SK-ES-1, SK-N-MC, and TC-71 cells were transduced with lentivirus containing Cad-11 shRNA or control shRNA (ES/Cad-11 and ES/Ctr). RD-ES and TC-71 were infected with a lentivirus luciferase vector. Adhesion assays were performed using these cells and recombinant Cad-11-Fc chimera or mouse osteoblast cell line MC3T3-E1. Cell motility was investigated via wound-healing assay. Intracardiac injection of RD-ES/Cad-11 and RD-ES/Ctr was used to create a mouse model of experimental bone metastasis. The association between Cad-11 expression and bone metastases and clinical prognosis in ES patients was analyzed by immunohistochemistry. We found knockdown of Cad-11 in ES cells resulted in reduced attachment ability and cell motility. In a mouse model of metastasis, RD-ES/Cad-11 cells caused fewer metastases than RD-ES/Ctr cells. The expression of Cad-11 in ES patients was significantly related to bone metastases (P < 0.05, logistic regression) and poorer overall survival (P < 0.05, log-rank test). These findings may explain that Cad-11 in ES cells may be essential for cell adhesion and motility, and is a promising molecular target for patients with ES.

DOI： 10.1007/s10585-015-9729-y

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

BACKGROUND: Myxoid liposarcoma (MLS) is the second most common subtype of liposarcoma, and metastasis occurs in up to one-third of cases. However, the mechanisms of invasion and metastasis remain unclear. Tumour-associated macrophages (TAMs) have important roles in tumour invasion, metastasis, and/or poor prognosis. The aim of this study was to investigate the relationship between TAMs and MLS. METHODS: Using 78 primary MLS samples, the association between clinical prognosis and macrophage infiltration was evaluated by immunochemistry. The effects of macrophages on cell growth, cell motility, and invasion of MLS cell lines were investigated in vitro. In addition, clinicopathological factors were analysed to assess their prognostic implications in MLS. RESULTS: Higher levels of CD68-positive macrophages were associated with poorer overall survival in MLS samples. Macrophage-conditioned medium enhanced MLS cell motility and invasion by activating epidermal growth factor receptor (EGFR), with the key ligand suggested to be heparin-binding EGF-like growth factor (HB-EGF). The phosphoinositide 3-kinase/Akt pathway was mostly involved in HB-EGF-induced cell motility and invasion of MLS. The expression of phosphorylated EGFR in MLS clinical samples was associated with macrophage infiltration. In addition, more significant macrophage infiltration was associated with poor prognosis even in multivariate analysis. CONCLUSIONS: Macrophage infiltration in MLS predicts poor prognosis, and the relationship between TAMs and MLS may be a new candidate for therapeutic targets of MLS.

DOI： 10.1038/bjc.2014.637

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

BACKGROUND: Diverse functions of microRNAs (miRNAs), including effects on tumorigenesis, proliferation, and differentiation, have been reported, and several miRNAs have also been demonstrated to play an important role in apoptosis. In this study, we investigated the possible role that miRNAs may play in the development of chemoresistance in Ewing sarcoma/primitive neuroectodermal tumor (EWS). METHODS: We screened doxorubicin (Dox)-resistant EWS cells to identify any distinct miRNA sequences that may regulate the chemoresistance of EWS cells. The effects of miRNAs were evaluated using a chemosensitivity assay. The possible target genes of the miRNAs were predicted using a web-based prediction program. RESULTS: We found miR-125b to be upregulated in two different Dox-resistant EWS cell lines. The upregulation of miR-125b was also confirmed in the EWS tumors having survived chemotherapy regimen which includes doxorubicin. When miR-125b was knocked down in EWS cells, both the Dox-resistant and parental cells showed an enhanced sensitivity to doxorubicin, which was associated with the upregulation of the pro-apoptotic molecules, p53 and Bak. Inversely, the overexpression of miR-125b in parental EWS cells resulted in enhanced drug resistance, not only to doxorubicin, but also to etoposide and vincristine. CONCLUSIONS: Our findings suggest that miR-125b may play a role in the development of chemoresistance in EWS by suppressing the expression of the apoptotic mediators, such as p53 and Bak.

DOI： 10.1186/1475-2867-13-21

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

BACKGROUND: Prognosis of osteosarcoma (OS) with distant metastasis and local recurrence is still poor. Y-box binding protein-1 (YB-1) is a multifunctional protein that can act as a regulator of transcription and translation and its high expression of YB-1 protein was observed in OS, however, the role of YB-1 in OS remains unclear. METHODS: Y-box binding protein-1 expression in OS cells was inhibited by specific small interfering RNAs to YB-1 (si-YB-1). The effects of si-YB-1 in cell proliferation and cell cycle transition in OS cells were analysed in vitro and in vivo. The association of nuclear expression of YB-1 and clinical prognosis was also investigated by immunohistochemistry. RESULTS: Proliferation of OS cell was suppressed by si-YB-1 in vivo and in vitro. The expression of cyclin D1 and cyclin A were also decreased by si-YB-1. In addition, si-YB-1 induced G1/S arrest with decreased cyclin D1 and cyclin A in OS cell lines. Direct binding of YB-1 in OS cell lines was also observed. Finally, the nuclear expression of YB-1 was significantly related to the poorer overall survival in OS patients. CONCLUSION: Y-box binding protein-1 would regulate cell cycle progression at G1/S and tumour growth in human OS cells in vitro and in vivo. Nuclear expression of YB-1 was closely associated with the prognosis of OS, thus, YB-1 simultaneously could be a potent molecular target and prognostic biomarker for OS.

DOI： 10.1038/bjc.2012.579

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はじめに:Spinal Instability Neoplastic Score(SINS)は転移性脊椎腫瘍の不安定性評価法であるが,骨有害事象リスク患者を検出する際のスクリーニング手段としても使用が報告されている.転移性脊椎腫瘍による脊髄症状発症例から,脊髄症状発症前のSINSを測定することにより,SINSによるリスク患者検出の有効性について検証した.対象と方法:2004年から2019年,頸胸椎部の転移性脊椎腫瘍に対する手術例81例から,脊髄症状発症前の画像評価が可能であった29例について調査した.脊髄症状発症半年以内に撮影されたCTからSINSを測定し,SINS7以上をリスク患者とした.結果:CT撮影時期は脊髄症状発症の平均72日前であった.SINSは転移なし2例,7未満(stability)4例,7以上～13未満(indeterminate instability)15例,13以上(instability)8例であり,21%(6/29)はリスク患者とならなかった.結語:脊髄症状発症前のSINSによる評価では約20%で脊髄症状発症の危険性を検出できない可能性が示唆された.(著者抄録)

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Clinical Outcome of Extensor Tendon Ruptures in Rheumatoid Hands

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Language：Japanese   Publisher：(一社)日本ペインリハビリテーション学会  

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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)日本肩関節学会  

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CiNii Research

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悪性軟部腫瘍に対する薬物療法は,周術期化学療法として行う場合と,切除不能・進行病変に対して行う場合に大別される.非円形細胞肉腫では,AI(adriamycin,ifosfamide)療法が周術期化学療法の標準治療であり,高悪性度腫瘍に対して実施が検討される.軟部肉腫に対する周術期化学療法は,メタ解析により,生存期間の有意な延長が示されている.わが国ではJCOG0304試験にて,良好な治療成績が示されており,これが事実上の標準治療となっている.進行例に対する一次治療の第1選択はアドリアマイシンを含むレジメンであり,ガイドライン等で推奨されている.二次治療では,トラベクテジン,エリブリン,パゾパニブや,GD(gemcitabine,docetaxel)療法が治療選択肢となるが,各国のガイドラインを参照しても,どの薬物を優先して用いるべきか明確にされていない.現在,進行軟部肉腫を対象として,JCOG1802試験が行われており,進行軟部肉腫に対する二次治療について,3剤の使い分けに関する貴重なデータが得られることが期待される.(著者抄録)

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J-GLOBAL

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J-GLOBAL

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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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J-GLOBAL

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Language：Japanese   Publisher：(一社)日本手外科学会  

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Language：Japanese   Publisher：(一社)日本手外科学会  

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

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

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Language：Japanese   Publisher：金原出版(株)  

＜文献概要＞進行軟部肉腫に対する化学療法の一次治療で頻用されるドキソルビシン(アドリアマイシン)には不可逆的累積毒性である心毒性があり,総投与量が上限に近づいた場合や,抵抗性を示す症例ではセカンドライン化学療法が必要となる。トラベクテジン,エリブリン,パゾパニブは2010年代に悪性軟部腫瘍を適応症として薬事承認された比較的新しい薬剤であり,それらに加え,GD療法(ゲムシタビン+ドセタキセル併用療法,悪性軟部腫瘍については薬事未承認)がセカンドライン化学療法の治療選択肢となる。実臨床におけるそれぞれの薬剤の治療成績や副作用について徐々に明らかになってきたとはいえ,それらを直接比較したランダム化比較試験(RCT)は存在せず,どの薬剤を選択すべきかに関する明確なエビデンスは乏しい状況である。現在行われているJCOG1802試験により,薬剤選択において参考となる比較データが得られることが期待されている。

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

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