Language：Japanese  

【はじめに】狭心症様の左前胸部痛が初発症状であった胸椎転移の1例を経験したので報告する.【症例】患者は76歳男性で去勢抵抗性前立腺癌加療中による右大腿骨近位部骨転移の病的骨折に対して,右大腿骨近位部置換術を施行した.術後8日目の夜間及び朝方に15分程度の前胸部痛を生じた.心電図・心エコーでは明らかな器質的疾患を認めなかったが,その後も頻回に症状があり,冠攣縮性狭心症の診断で内服薬治療を開始した.しかし改善がなく胸椎転移の可能性を念頭に診察を行うと背部に叩打痛があった.MRIにてTh5の棘突起の転移があり脊髄圧迫を伴っていた.第5胸椎に対して放射線治療を行ったところ,胸痛症状は改善した.【考察】狭心症様の前胸部痛を呈する患者では虚血性心疾患以外にも胸椎疾患の可能性に留意することが望まれる.(著者抄録)

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

BACKGROUND: Vertebroplasty with posterior spinal fusion (VP + PSF) is one of the most widely accepted surgical techniques for treating osteoporotic vertebral collapse (OVC). Nevertheless, the effect of the extent of fusion on surgical outcomes remains to be established. This study aimed to evaluate the surgical outcomes of short- versus long-segment VP + PSF for OVC with neurological impairment in thoracolumbar spine. METHODS: We retrospectively collected data from 133 patients (median age, 77 years; 42 men and 91 women) from 27 university hospitals and their affiliated hospitals. We divided patients into two groups: a short-segment fusion group (S group) with 2- or 3-segment fusion (87 patients) and a long-segment fusion group (L group) with 4- through 6-segment fusion (46 patients). Surgical invasion, clinical outcomes, local kyphosis angle (LKA), and complications were evaluated. RESULTS: No significant differences between the two groups were observed in terms of neurological recovery, pain scale scores, and complications. Surgical time was shorter and blood loss was less in the S group, whereas LKA at the final follow-up and correction loss were superior in the L group. CONCLUSION: Although less invasiveness and validity of pain and neurological relief are secured by short-segment VP + PSF, surgeons should be cautious regarding correction loss.

DOI： 10.1186/s12891-020-03539-0

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

BACKGROUND: The optimal treatment of osteoporosis after reconstruction surgery for osteoporotic vertebral fractures (OVF) remains unclear. In this multicentre retrospective study, we investigated the effects of typically used agents for osteoporosis, namely, bisphosphonates (BP) and teriparatide (TP), on surgical results in patients with osteoporotic vertebral fractures. METHODS: Retrospectively registered data were collected from 27 universities and affiliated hospitals in Japan. We compared the effects of BP vs TP on postoperative mechanical complication rates, implant-related reoperation rates, and clinical outcomes in patients who underwent posterior instrumented fusion for OVF. Data were analysed according to whether the osteoporosis was primary or glucocorticoid-induced. RESULTS: A total of 159 patients who underwent posterior instrumented fusion for OVF were included. The overall mechanical complication rate was significantly lower in the TP group than in the BP group (BP vs TP: 73.1% vs 58.2%, p = 0.045). The screw backout rate was significantly lower and the rates of new vertebral fractures and pseudoarthrosis tended to be lower in the TP group than in the BP group. However, there were no significant differences in lumbar functional scores and visual analogue scale pain scores or in implant-related reoperation rates between the two groups. The incidence of pseudoarthrosis was significantly higher in patients with glucocorticoid-induced osteoporosis (GIOP) than in those with primary osteoporosis; however, the pseudoarthrosis rate was reduced by using TP. The use of TP also tended to reduce the overall mechanical complication rate in both primary osteoporosis and GIOP. CONCLUSIONS: The overall mechanical complication rate was lower in patients who received TP than in those who received a BP postoperatively, regardless of type of osteoporosis. The incidence of pseudoarthrosis was significantly higher in patients with GIOP, but the use of TP reduced the rate of pseudoarthrosis in GIOP patients. The use of TP was effective to reduce postoperative complications for OVF patients treated with posterior fusion.

DOI： 10.1186/s12891-020-03452-6

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

BACKGROUND: There have been few reports on the incidence and risk factors of the complications after spinal fixation surgery for osteoporotic vertebral collapse (OVC) with neurological deficits. This study aimed to identify the incidence and risk factors of the complications after OVC surgery. METHODS: In this retrospective multicenter study, a total of 403 patients (314 women and 89 men; mean age 73.8 years) who underwent spinal fixation surgery for OVC with neurological deficits between 2005 and 2014 were enrolled. Data on patient demographics were collected, including age, sex, body mass index, smoking, steroid use, medical comorbidities, and surgical procedures. All postoperative complications that occurred within 6 weeks were recorded. Patients were classified into two groups, namely, complication group and no complication group, and risk factors for postoperative complications were investigated by univariate and multivariate analyses. RESULTS: Postoperative complications occurred in 57 patients (14.1&#37;), and the most common complication was delirium (5.7&#37;). In the univariate analysis, the complication group was found to be older (p = 0.039) and predominantly male (p = 0.049), with higher occurrence rate of liver disease (p = 0.001) and Parkinson's disease (p = 0.039) compared with the no-complication group. In the multivariate analysis, the significant independent risk factors were age (p = 0.021; odds ratio [OR] 1.051, 95&#37; confidence interval [CI] 1.007-1.097), liver disease (p < 0.001; OR 8.993, 95&#37; CI 2.882-28.065), and Parkinson's disease (p = 0.009; OR 3.636, 95&#37; CI 1.378-9.599). CONCLUSIONS: Complications after spinal fixation surgery for OVC with neurological deficits occurred in 14.1&#37;. Age, liver disease, and Parkinson's disease were demonstrated to be independent risk factors for postoperative complications.

DOI： 10.1016/j.jos.2019.08.015

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

BACKGROUND: A consensus on the optimal surgical procedure for thoracolumbar OVF has yet to be reached due to the previous relatively small number of case series. The study was conducted to investigate surgical outcomes for osteoporotic vertebral fracture (OVF) in the thoracolumbar spine. METHODS: In total, 315 OVF patients (mean age, 74 years; 68 men and 247 women) with neurological symptoms who underwent spinal fusion with a minimum 2-year follow-up were included. The patients were divided into 5 groups by procedure: anterior spinal fusion alone (ASF group, n = 19), anterior/posterior combined fusion (APSF group, n = 27), posterior spinal fusion alone (PSF group, n = 40), PSF with 3-column osteotomy (3CO group, n = 92), and PSF with vertebroplasty (VP + PSF group, n = 137). RESULTS: Mean operation time was longer in the APSF group (p < 0.05), and intraoperative blood loss was lower in the VP + PSF group (p < 0.05). The amount of local kyphosis correction was greater in the APSF and 3CO groups (p < 0.05). Clinical outcomes were approximately equivalent among all groups. CONCLUSION: All 5 procedures resulted in acceptable neurological outcomes and functional improvement in walking ability. Moreover, they were similar with regard to complication rates, prevalence of mechanical failure related to the instrumentation, and subsequent vertebral fracture. Individual surgical techniques can be adapted to suit patient condition or severity of OVF.

DOI： 10.1016/j.jos.2019.07.018

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

Chondrosarcoma is the second most common malignant bone tumor. It is characterized by low vascularity and an abundant extracellular matrix, which confer these tumors resistance to chemotherapy and radiotherapy. There are currently no effective treatment options for relapsed or dedifferentiated chondrosarcoma, and new targeted therapies need to be identified. Isocitrate dehydrogenase (IDH) mutations, which are detected in ~50&#37; of chondrosarcoma patients, contribute to malignant transformation by catalyzing the production of 2-hydroxyglutarate (2-HG), a competitive inhibitor of α-ketoglutarate-dependent dioxygenases. Mutant IDH inhibitors are therefore potential novel anticancer drugs in IDH mutant tumors. Here, we examined the efficacy of the inhibition of mutant IDH1 as an antitumor approach in chondrosarcoma cells in vitro and in vivo, and investigated the association between the IDH mutation and chondrosarcoma cells. DS-1001b, a novel, orally bioavailable, selective mutant IDH1 inhibitor, impaired the proliferation of chondrosarcoma cells with IDH1 mutations in vitro and in vivo, and decreased 2-HG levels. RNA-seq analysis showed that inhibition of mutant IDH1 promoted chondrocyte differentiation in the conventional chondrosarcoma L835 cell line and caused cell cycle arrest in the dedifferentiated JJ012 cell line. Mutant IDH1-mediated modulation of SOX9 and CDKN1C expression regulated chondrosarcoma tumor progression, and DS-1001b upregulated the expression of these genes via a common mechanism involving the demethylation of H3K9me3. DS-1001b treatment reversed the epigenetic changes caused by aberrant histone modifications. The present data strongly suggest that inhibition of mutant IDH1 is a promising therapeutic approach in chondrosarcoma, particularly for the treatment of relapsed or dedifferentiated chondrosarcoma.

DOI： 10.1038/s41388-019-0929-9

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

INTRODUCTION: Approximately 3&#37; of osteoporotic vertebral fractures develop osteoporotic vertebral collapse (OVC) with neurological deficits, and such patients are recommended to be treated surgically. However, a proximal junctional fracture (PJFr) following surgery for OVC can be a serious concern. Therefore, the aim of this study is to identify the incidence and risk factors of PJFr following fusion surgery for OVC. METHODS: This study retrospectively analyzed registry data collected from facilities belonging to the Japan Association of Spine Surgeons with Ambition (JASA) in 2016. We retrospectively analyzed 403 patients who suffered neurological deficits due to OVC below T10 and underwent corrective surgery; only those followed up for ≥2 years were included. Potential risk factors related to the PJFr and their cut-off values were calculated using multivariate logistic regression analysis and receiver operating characteristic (ROC) analysis. RESULTS: Sixty-three patients (15.6&#37;) suffered PJFr during the follow-up (mean 45.7 months). In multivariate analysis, the grade of osteoporosis (grade 2, 3: adjusted odds ratio (aOR) 2.92; p=0.001) and lower instrumented vertebra (LIV) level (sacrum: aOR 6.75; p=0.003) were independent factors. ROC analysis demonstrated that lumbar bone mineral density (BMD) was a predictive factor (area under curve: 0.72, p=0.035) with optimal cut-off value of 0.61 g/cm2 (sensitivity, 76.5&#37;; specificity, 58.3&#37;), but that of the hip was not (p=0.228). CONCLUSIONS: PJFr was found in 16&#37; cases within 4 years after surgery; independent risk factors were severe osteoporosis and extended fusion to the sacrum. The lumbar BMD with cut-off value 0.61 g/cm2 may potentially predict PJFr. Our findings can help surgeons select perioperative adjuvant therapy, as well as a surgical strategy to prevent PJFr following surgery.

DOI： 10.22603/ssrr.2018-0068

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

BACKGROUND: To date, there have been little published data on surgical outcomes for patients with PD with thoracolumbar OVF. We conducted a retrospective multicenter study of registry data to investigate the outcomes of fusion surgery for patients with Parkinson's disease (PD) with osteoporotic vertebral fracture (OVF) in the thoracolumbar junction. METHODS: Retrospectively registered data were collected from 27 universities and their affiliated hospitals in Japan. In total, 26 patients with PD (mean age, 76 years; 3 men and 23 women) with thoracolumbar OVF who underwent spinal fusion with a minimum of 2 years of follow-up were included (PD group). Surgical invasion, perioperative complications, radiographic sagittal alignment, mechanical failure (MF) related to instrumentation, and clinical outcomes were evaluated. A control group of 296 non-PD patients (non-PD group) matched for age, sex, distribution of surgical procedures, number of fused segments, and follow-up period were used for comparison. RESULTS: The PD group showed higher rates of perioperative complications (p < 0.01) and frequency of delirium than the non-PD group (p < 0.01). There were no significant differences in the degree of kyphosis correction, frequency of MF, visual analog scale of the symptoms, and improvement according to the Japanese Orthopaedic Association scoring system between the two groups. However, the PD group showed a higher proportion of non-ambulators and dependent ambulators with walkers at the final follow-up (p < 0.01). CONCLUSIONS: A similar surgical strategy can be applicable to patients with PD with OVF in the thoracolumbar junction. However, physicians should pay extra attention to intensive perioperative care to prevent various adverse events and implement a rehabilitation regimen to regain walking ability.

DOI： 10.1186/s12891-019-2473-8

Language：Japanese  

【はじめに】一次修復不能な広範囲腱板断裂で偽性麻痺肩に対する鏡視下上方関節包再建術(以下ASCR)を行ったので、その治療成績を報告する。【対象と方法】2015年2月から2016年5月までにASCRを行った12肩(男性7肩、女性5肩)平均年齢72.5歳(67～80歳)を対象とした。術後平均観察期間は18.2ヵ月(13～28ヵ月)であった。可動域、MRI所見、JOAスコアを術前後で比較検討した。【結果】屈曲は術前平均52.5度が術後平均120.0度に、外転は術前平均51.2度が術後平均119.1度に改善した(p<0.05)。外旋は術前平均27.5度が術後平均30.0度と有意な改善は得られなかった。JOAスコアは術前47.5点から術後70.7点と有意に改善した(p<0.05)。術後屈曲90度以上の改善が得られなかったのは2例であり、いずれも立位での浜田分類グレード3であった。【結論】ASCRは良好な機能回復を認め、患者の満足度も高かった。良好な術後成績獲得のため適応を慎重に検討する必要があると思われた。(著者抄録)

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)  

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：Japanese  

骨粗鬆症の罹患患者数は2011年現在で1280万人と言われており,大腿骨頸部骨折・椎体骨折の発生リスクを抑えるため,内服・注射などによる治療を行うことが推奨されている.それに伴い,ビスフォスフォネート製剤(以下,BP製剤)を長期にわたって用いる症例が増えてきている.近年BP製剤の長期内服患者において,非外傷性あるいは低エネルギー外傷性の大腿骨転子下骨折や大腿骨骨幹部骨折などのいわゆる非定型骨折を生じるという報告が散見される.今回,ステロイド長期内服による骨粗鬆症に対してBP製剤内服を開始し,内服開始から5年目および8年目に両側大腿骨非定型骨折と思われる大腿骨転子下骨折を受傷した症例を経験したため報告する.(著者抄録)

Language：Japanese  

目的:腰椎椎間板ヘルニア(以下LDH)及び腰部脊柱管狭窄症(以下LCS)による腰部神経根症に対する選択的神経根ブロック(以下SNRB)の有効性を調査した.対象:2008年4月～2009年11月にSNRBを施行した78例(LDH49例・LCS29例)を対象とした.方法:SNRBは手術適応のある患者に原則1回行い,外来にて透視下に施行した.臨床成績は最終観察時にMacnabの判定基準にて評価した.各項目(年齢・罹病期間・各時期のVAS score・効果持続時間)と臨床成績との相関関係を評価した.結果:有効率はLDH47&#37;,LCS24&#37;とLDHが有意に高かった.手術移行率はLDH 39&#37;,LCS 59&#37;であった.有効群では24時間以上効果が持続する症例が有意に多かった.結語:神経根症を有するLDH及びLCSに対し,SNRBは手術療法前に一度は試みてもよい保存療法であると考えられた.(著者抄録)