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

The activation and proliferation of microglia is characteristic of the early stages of brain pathologies. In this study, we aimed to identify a factor that promotes microglial activation and proliferation and examined the in vitro effects on these processes. We cultured microglial cell lines, EOC 2 and SIM-A9, with various growth factors and evaluated cell proliferation, death, and viability. The results showed that only transforming growth factor beta (TGF-β) caused an increase in the in vitro proliferation of both microglial cell lines. It has been reported that colony-stimulating factor 1 promotes the proliferation of microglia, while TGF-β promotes both proliferation and inhibition of cell death of microglia. However, upon comparing the most effective doses of both (assessed from the proliferation assay), we identified no statistically significant difference between the two factors in terms of cell death; thus, both have a proliferative effect on microglial cells. In addition, a TGF-β receptor 1 inhibitor, galunisertib, caused marked inhibition of proliferation in a dose-dependent manner, indicating that inhibition of TGF-β signalling reduces the proliferation of microglia. Therefore, galunisertib may represent a promising therapeutic agent for the treatment of neurodegenerative diseases via inhibition of nerve injury-induced microglial proliferation, which may result in reduced inflammatory and neuropathic and cancer pain.

DOI： 10.3390/brainsci10010020

PubMed

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

Undifferentiated pleomorphic sarcoma (UPS) is the second most common soft tissue sarcoma. For patients with unresectable or metastatic disease, chemotherapies are considered, but in many cases they are not curative. There is a need to identify specific molecular dysregulations that can be therapeutic targets. We focused on neurotensin receptor 1 (NTSR1), which belongs to the G-protein-coupled receptor. NTSR1 expression was upregulated in specimens from patients with UPS. Real-time polymerase chain reaction showed that expression of NTSR1 messenger RNA was 5- to 7-fold increased in UPS cells compared with myoblasts. Western blot showed a high expression of NTSR1 protein in UPS cell lines. Knockdown of NTSR1 prevented UPS cell proliferation and invasion. We confirmed that SR48692, an inhibitor of NTSR1, exhibited antitumor activities in UPS cells. The combination index showed that SR48692 and standard chemotherapeutic drugs prevented UPS cell proliferation synergistically. Mouse xenograft models showed that SR48692 inhibited extracellular signal-regulated kinase phosphorylation and enhanced the response to standard chemotherapeutic drugs. Inhibition of NTSR1 improved the effect of standard chemotherapeutic drugs for UPS. SR48692 may be a new drug for targeted UPS therapy.

DOI： 10.1002/mc.23111

PubMed

DOI： 10.1016/j.jos.2018.10.027

PubMed

Publisher：西日本整形・災害外科学会  

【はじめに】褐色脂肪腫は褐色脂肪組織に由来するまれな軟部腫瘍であり,悪性軟部腫瘍,とくに脂肪肉腫との鑑別が問題となる.褐色脂肪腫はFDG-PETで高度集積を来すことが報告されており,脂肪肉腫との鑑別としてFDG-PETが有用であるとされる.【症例】40歳女性,4ヵ月前より背部の腫瘤を自覚.MRI上,僧帽筋下に脂肪成分を含み造影効果を有する80mm大の腫瘤を認めた.FDG-PETにてSUV59.5→70.5と非常に強いFDGの集積を認めたため開放生検を施行し,褐色細胞腫と診断されたため辺縁切除術を施行した.術後2年の現在,再発もなく術後経過良好である.【考察】褐色脂肪腫は一般的にFDGの高度集積を来すことが報告されているが,なかにはFDGの集積が低い症例も報告されている.褐色脂肪に対するFDGの集積は外気温や薬剤による影響を受けやすく,注意が必要と考えられた.(著者抄録)

Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

Tranilast [N‑(3',4'‑dimethoxycinnamoyl)‑anthranilic acid], initially developed as an antiallergic drug, also exhibits a growth inhibitory effect on various types of cancer. Osteosarcoma is treated mainly with high‑dose methotrexate, doxorubicin, cisplatin and ifosfamide; however, 20‑30% of patients cannot be cured of metastatic disease. We investigated whether tranilast enhances the anticancer effects of chemotherapeutic drugs and analyzed its mechanism of action in osteosarcomas. Tranilast inhibited proliferation of HOS, 143B, U2OS and MG‑63 osteosarcoma cells in a dose‑dependent manner, as well as enhancing the effects of cisplatin and doxorubicin. The average combination index at effect levels for tranilast in combination with cisplatin was 0.57 in HOS, 0.4 in 143B, 0.39 in U2OS and 0.51 in MG‑63 cells. Tranilast and cisplatin synergistically inhibited the viability of osteosarcoma cells. In flow cytometric analysis, although tranilast alone did not induce significant apoptosis, the combination of tranilast and cisplatin induced early and late apoptotic cell death. Expression of cleaved caspase‑3, cleaved poly(ADP‑ribose) polymerase and p‑H2AX was enhanced by tranilast in combination with cisplatin. Tranilast alone increased expression of p21 and Bim protein in a dose‑dependent manner. Cell cycle analysis using flow cytometry demonstrated that the combination of tranilast and cisplatin increased the number of cells in the G2/M phase. Compared with cisplatin alone, the combination increased levels of phospho‑cyclin‑dependent kinase 1 (Y15). In the 143B xenograft model, tumor growth was significantly inhibited by combined tranilast and cisplatin compared with the controls, whereas cisplatin alone did not significantly inhibit tumor growth. In conclusion, tranilast has a cytostatic effect on osteosarcoma cells and enhances the effect of anticancer drugs, especially cisplatin. Enhanced sensitivity to cisplatin was mediated by increased apoptosis through G2/M arrest. Since tranilast has been clinically approved and has few adverse effects, clinical trials of osteosarcoma chemotherapy in combination with tranilast are expected.

DOI： 10.3892/or.2019.7150

PubMed

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

The treatment of glioblastoma is a critical health issue, owing to its resistance to chemotherapy. The current standard of treatment is surgical resection, followed by adjuvant radiotherapy and temozolomide treatment. Long‑term local treatment of glioblastoma is rarely achieved and the majority of the patients undergo relapse. Resistance to temozolomide emerges from numerous signalling pathways that are altered in glioblastoma, including the Hedgehog signalling pathway. Hence, further research is required to identify effective treatment modalities. We investigated the effect of vismodegib, arsenic trioxide and temozolomide on glioblastoma in vitro and in vivo to apply our findings to the clinical setting. WST‑1 assay revealed that glioblastoma proliferation was inhibited following treatment with these drugs either in single or in combination; this synergistic effect was confirmed by CalcuSyn software. Western blot analysis revealed an increase in the expression of cleaved caspase‑3 and γH2AX. Furthermore, there was marked inhibition and decreased tumour growth in mice that received combination therapy, unlike those that received single agent or vehicle treatment. Our results revealed that the combination of arsenic trioxide/vismodegib and temozolomide may be an attractive therapeutic method for the treatment of glioblastoma.

DOI： 10.3892/or.2019.7100

PubMed

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

Recently, we reported highly active transforming growth factor (TGF)-β and bone morphogenetic protein (BMP) signaling in human chondrosarcoma samples and concurrent downregulation of paternally expressed gene 10 (PEG10). PEG10 expression was suppressed by TGF-β signaling, and PEG10 interfered with the TGF-β and BMP-SMAD pathways in chondrosarcoma cells. However, the roles of PEG10 in bone tumors, including chondrosarcoma, remain unknown. Here, we report that PEG10 promotes SW1353 chondrosarcoma cell growth by preventing TGF-β1-mediated suppression. In contrast, PEG10 knockdown augments the TGF-β1-induced motility of SW1353 cells. Individually, TGF-β1 and PEG10 siRNA increase AKT phosphorylation, whereas an AKT inhibitor, MK2206, mitigates the effect of PEG10 silencing on cell migration. SW1353 cell invasion was enhanced by BMP-6, which was further increased by PEG10 silencing. The effect of siPEG10 was suppressed by inhibitors of matrix metalloproteinase (MMP). BMP-6 induced expression of MMP-1, -3, and -13, and PEG10 lentivirus or PEG10 siRNA downregulated or further upregulated these MMPs, respectively. PEG10 siRNA increased BMP-6-induced phosphorylation of p38 MAPK and AKT, whereas the p38 inhibitor SB203580 and MK2206 diminished SW1353 cell invasion by PEG10 siRNA. SB203580 and MK2206 impeded the enhancing effect of PEG10 siRNA on the BMP-6-induced expression of MMP-1, -3, and -13. Our findings suggest dual functions for PEG10: accelerating cell growth by suppressing TGF-β signaling and inhibiting cell motility and invasion by interfering with TGF-β and BMP signaling via the AKT and p38 pathways, respectively. Thus, PEG10 might be a molecular target for suppressing the aggressive phenotypes of chondrosarcoma cells.

DOI： 10.1007/s00774-018-0946-8

PubMed

Publisher：(株)南江堂  

66歳女。上背部腫瘤を主訴とした。腫瘤は4cm大の弾性硬・無痛性で、MRIでは左頸板状筋、最長筋内に42×33×41mm大、T2強調像で筋組織よりもやや高輝度、辺縁不明瞭な軟部腫瘍を認めた。針生検で悪性所見は認めず経過観察としたが、6ヵ月後のCTで腫瘍径が50×45×110mmへ増大を認めたため切開生検を行った。病理所見よりデスモイド型線維腫の診断を得て、トラニラストとセレコキシブ内服を開始した。投与開始1年で腫瘍の縮小傾向を認め、3年経過時に縮小率71%で部分寛解にいたった。投与開始から3年4ヵ月でも腫瘍の再発・増大は認めていない。

Publisher：西日本整形・災害外科学会  

【はじめに】アダマンチノーマは良く知られた悪性骨腫瘍であるが、発生は非常に稀であり診断の遅れが報告されている。【症例】43歳男性、建築業。4年前から右下腿を数回打撲、3年前に近医を受診し右脛骨前面骨皮質の不整と硬化像を指摘されたが経過観察となる。1ヵ月前に再度打撲、前医を受診。MRIにて右脛骨近位部に腫瘍像を指摘され当科紹介受診された。単純X線にて脛骨近位骨幹部前面骨皮質に透亮像、その遠位と近位に骨硬化像を認めた。MRIにて骨透亮像部に骨外に進展する腫瘍を認め、生検にてアダマンチノーマの診断を得た。遠隔転移は認めず、腫瘍広範切除術を施行した。腫瘍辺縁から1cmマージンで切除後、同側腓骨を有茎血管柄付き移植し再建した。術後8ヵ月、骨癒合を認める一方再発転位は認められず、職場復帰している。【考察】職業柄、繰り返す打撲を契機に受診していたことも診断の遅れにつながった症例と考えられた。広範切除後の再建方法として有茎血管柄付き腓骨移植は簡便で有用な方法であることが示された。(著者抄録)

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

Undifferentiated pleomorphic sarcoma (UPS) is the second most frequent soft tissue sarcoma. Because of its resistance to chemotherapy, UPS patients are treated with surgical resection and complementary radiotherapy. However, since standard chemotherapy has not been established, unresectable or metastatic cases result in a poor prognosis. Therefore, the identification of a more effective therapy for UPS patients is needed. The development and progression of malignant tumors involve epigenetic alterations, and histone deacetylases (HDAC) have become a promising chemotherapeutic target. In this study, we investigated the potential effects and mechanisms of an HDAC inhibitor, LBH589, in UPS cells. We confirmed that LBH589 exhibits potent antitumor activities in four human UPS cell lines (GBS-1, TNMY-1, Nara-F, and Nara-H) and IC(50) values ranged from 7 to 13 nM. A mouse xenograft model showed that LBH589 treatment effectively suppressed tumor growth. FACS analysis showed that LBH589 induced apoptosis and G2/M cell cycle arrest. Among apoptosis-related proteins, the expressions of Bcl-2 and Bcl-xL were decreased and the expression of Bak and Bim increased. Among cell cycle-related proteins, reductions of CDK1, p-CDK1, cyclin B1, Aurora A, and Aurora B were observed after LBH589 treatment. RNA microarray identified the FOS-like antigen 1 (FOSL1) gene as a downregulated gene in response to LBH589 in UPS cells. While knockdown of FOSL1 decreased UPS cell proliferation, overexpression induced cell proliferation. Our results show that LBH589 could be a promising chemotherapeutic agent in the treatment of UPS and downregulation of the FOSL1 gene could be the new molecular target of UPS treatment.

DOI： 10.1002/mc.22922

PubMed

Publisher：西日本整形・災害外科学会  

<p>【はじめに】褐色脂肪腫は褐色脂肪組織に由来するまれな軟部腫瘍であり，悪性軟部腫瘍，とくに脂肪肉腫との鑑別が問題となる．褐色脂肪腫はFDG-PETで高度集積を来すことが報告されており，脂肪肉腫との鑑別としてFDG-PETが有用であるとされる．【症例】40歳女性，4か月前より背部の腫瘤を自覚．MRI上，僧帽筋下に脂肪成分を含み造影効果を有する80mm大の腫瘤を認めた．FDG-PETにてSUV59.5→70.5と非常に強いFDGの集積を認めたため開放生検を施行し，褐色細胞腫と診断されたため辺縁切除術を施行した．術後2年の現在，再発もなく術後経過良好である．【考察】褐色脂肪腫は一般的にFDGの高度集積を来すことが報告されているが，なかにはFDGの集積が低い症例も報告されている．褐色脂肪に対するFDGの集積は外気温や薬剤による影響を受けやすく，注意が必要と考えられた．</p>

DOI： 10.5035/nishiseisai.68.462

Publisher：西日本整形・災害外科学会  

<p>【はじめに】アダマンチノーマは良く知られた悪性骨腫瘍であるが，発生は非常に稀であり診断の遅れが報告されている．【症例】43歳男性，建築業．4年前から右下腿を数回打撲，3年前に近医を受診し右脛骨前面骨皮質の不整と硬化像を指摘されたが経過観察となる．1か月前に再度打撲，前医を受診．MRIにて右脛骨近位部に腫瘍像を指摘され当科紹介受診された．単純X線にて脛骨近位骨幹部前面骨皮質に透亮像，その遠位と近位に骨硬化像を認めた．MRIにて骨透亮像部に骨外に進展する腫瘍を認め，生検にてアダマンチノーマの診断を得た．遠隔転移は認めず，腫瘍広範切除術を施行した．腫瘍辺縁から1cmマージンで切除後，同側腓骨を有茎血管柄付き移植し再建した．術後8か月，骨癒合を認める一方再発転位は認められず，職場復帰している．【考察】職業柄，繰り返す打撲を契機に受診していたことも診断の遅れにつながった症例と考えられた．広範切除後の再建方法として有茎血管柄付き腓骨移植は簡便で有用な方法であることが示された．</p>

DOI： 10.5035/nishiseisai.68.173

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

Malignant soft-tissue sarcoma resection is associated with a relatively high incidence of surgical site infection (SSI). The known risk factors for SSI following soft-tissue sarcoma resection include tumor size and location, prolonged surgery, and massive blood loss. The geriatric nutritional risk index (GNRI) was used as a tool to help predict the occurrence of SSI after major surgery. We investigated the utility of the GNRI as a predictor of SSI following soft-tissue sarcoma resection. We retrospectively reviewed 152 patients who underwent surgical resection of soft-tissue sarcoma in our institute, and found that the incidence of SSI was 18.4% (28/152). The SSI and non-SSI groups significantly differed regarding surgical time, diameter of the skin incision, maximum tumor diameter, instrumentation, presence of an open wound, preoperative chemotherapy, preoperative C-reactive protein concentration, and GNRI. Binomial logistic regression analysis showed that the risk factors for SSI following soft-tissue sarcoma surgery were male sex, larger skin incision diameter, larger maximum tumor diameter, presence of an open wound, and lower GNRI. Our findings indicate that malnutrition is a risk factor for SSI after soft-tissue sarcoma resection, and suggest that appropriate assessment and intervention for malnutrition may reduce the incidence of SSI.

DOI： 10.3390/nu10121900

PubMed

Publisher：(一社)日本関節病学会  

本邦で生物学的製剤の使用が承認された2003年以降の関節リウマチ患者を、生物学的製剤で治療された91名(生物群)と抗リウマチ製剤のみを投与された61名(従来群)に分け、それぞれ腰椎と大腿骨での骨密度低下量、骨密度低下に関連する因子を比較調査した。従来群と生物群で平均DAS28-CRP値は2.3と2.5であったが、12ヵ月間でそれぞれ40.9%、38.5%の患者に1.9%以上の大腿骨頸部骨密度低下を認め、疾患の活動性が低くコントロールされていても骨密度の低下を抑制することはできなかった。多変量解析として有意低下以上の骨密度低下の有無で二項ロジスティック回帰分析を行うと、生物群では骨粗鬆症治療薬なしが有意な腰椎骨密度低下のリスク因子に、骨粗鬆症治療薬なしと低いBMIが有意な大腿骨頸部骨密度低下のリスク因子となっていた。

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

BACKGROUND: The suture-bridge (SB) method has recently become the mainstream means of repairing full-thickness rotator cuff tears. However, in some patients the deep and superficial layers have moved in different directions because of delamination of their rotator cuffs. In such cases, a simple suture (double-layer, double-row [DD] method) is used to repair the superficial and deep layers separately. The purpose of this study was to analyze the clinical outcomes and re-tear rates of the DD and SB methods, with patients selected according to the condition of their torn cuffs. METHODS: We retrospectively registered 74 patients with full-thickness rotator cuff tears that had been repaired arthroscopically, 35 shoulders by the DD and 39 by the SB method. Mean ages were 66.1 years in the DD and 62.9 years in the SB group. We evaluated clinical status before and after surgery (Japanese Orthopedic Association [JOA] scores) and re-tear rate. The Wilcoxon signed-ranks test was used to compare JOA scores and active ROM between before and after surgery in each group. Mann-Whitney's U test was used for comparing JOA scores, active ROM, re-tear rates, size of tear, duration of follow-up, sex, and presence of subscapular muscle repair between the DD and SB groups. A hazard ratio of less than 5% was considered to denote significance. RESULTS: JOA scores improved significantly in the DD and SB groups from preoperative means of 63.4 and 63.3 points, respectively, to postoperative means of 91.8 and 92.1 points, respectively. The active flexural ROM improved significantly from means of 110.1° and 100.0°, respectively, to postoperative means of 142.3° and 142.7°, respectively; the differences between groups were not significant. Re-tear occurred in 5.9% of the DD (two of 34 shoulders) and 7.9% of the SB group (three of 38 shoulders); its incidence did not differ significantly between the two groups. CONCLUSIONS: Both the DD and SB methods achieve satisfactory clinical outcomes that do not differ significantly. Our results suggest that careful selection of operative method on the basis of the delamination pattern in patients undergoing RCT may reduce the re-tear rate after utilizing the SB method.

DOI： 10.1186/s12891-018-2244-y

PubMed

Publisher：西日本整形・災害外科学会  

【はじめに】紡錘形細胞脂肪腫spindle cell lipomaは脂肪腫の特殊型で、中年男性の後頸部、肩、背部に好発する稀な腫瘍である。【症例】70歳男性、背部皮下に弾性軟、約8cm大の腫瘤を認めた。MRI上T2強調画像にて著明な高信号を主体とし、漸増性の増強効果を呈し内部に微小な脂肪成分を認め、分葉状の形態を呈していた。粘液型脂肪肉腫との鑑別が必要と考え、生検術を施行。肉眼的に粘液性の成分と一部線維性の組織を採取した。病理所見では粘液腫様の間質内に存在する短紡錘形の腫瘍細胞はCD34陽性、ロープ状膠原線維の存在やMDM2陰性から紡錘形細胞脂肪腫と診断し、辺縁切除術を施行した。【まとめ】紡錘形細胞脂肪腫は術前診断が難しく、他の脂肪系腫瘍である粘液型脂肪肉腫や異型脂肪腫様腫瘍との鑑別が重要である。画像所見や病理所見、臨床所見について文献的考察を加え報告する。(著者抄録)

Publisher：西日本整形・災害外科学会  

今回我々はスポーツに起因する女児に発生した骨盤疲労骨折の1例を経験したので文献的考察を踏まえて報告する。症例は10歳女児。バレーボールを始め約1ヵ月でランニング時左股関節痛が出現。近医受診するも異常なく、その後跛行出現し症状軽快しないため当院受診となった。X線、CT、MRI等の検査から、骨端症、骨髄炎、骨腫瘍の鑑別を行い、骨盤疲労骨折と診断し、スポーツ活動の禁止と安静ののち7週で疼痛改善した。(著者抄録)

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

Predicting outcomes in patients with soft tissue sarcoma (STS) is challenging. To improve these predictions, we retrospectively analyzed common nutritional assessment systems, including Glasgow prognostic score (GPS), Geriatric Nutritional Risk Index (GNRI), neutrophil⁻lymphocyte ratio (NLR), platelet⁻lymphocyte ratio (PLR), and controlling nutritional (CONUT) score against outcomes in 103 patients with STS, of whom 15 (14.6%) died within 1 year of diagnosis. GPS, GNRI, NLR, PLR, and CONUT scores significantly differed between patients who died within one year and patients who lived longer. Binomial logistic regression analysis showed that male sex, older age at diagnosis, higher GPS, higher stage, and unresectable STS were risk factors for death within a year of diagnosis. Overall survival was evaluated by Cox proportional hazards models, which correlated higher NLR, higher PLR, larger maximum diameter of tumor, higher stage, and unresectable STS with poor prognosis. We next examined prognostic factors in the 93 patients with resectable STS, and found male sex, higher GPS, and higher stage were correlated with poor prognosis in these patients. Our findings suggest that GPS, NLR, and PLR are simple predictors of outcome in patients with STS. Nutritional therapies might improve their GPS and prognosis.

DOI： 10.3390/nu10060765

PubMed

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

Although it is thought that the surgical enucleation of schwannomas can be easily performed, certain patients present with postoperative neurological symptoms. The present study examined the utility of intraoperative motor-evoked potential (MEP) in predicting neurological deficits following the surgical enucleation of peripheral nerve schwannoma. The current study included 23 patients and MEP was performed using transcranial electrical stimulation. In three cases, the MEP decreased to <50% of the preoperative value; however, in two cases that involved the peroneal nerve and tibial nerve, results appeared to be false positives induced by a tourniquet during surgery. In another case, the MEP was completely lost following enucleation of the tumor from the sciatic nerve, which recovered to 61% of the original MEP within 10 min. This patient presented with common peroneal palsy postoperatively. By contrast, another case involving the lumbar nerve root and in which there was reversible postoperative motor loss, the MEP did not change intraoperatively. Postoperative neurological deficit occurred in 22% of patients in the present study, which is similar to that of previous reports. The present study also demonstrated that even if a nerve is not transected or injured, traction or compression of a peripheral nerve may induce ischemia, which can be monitored using MEP. Although MEP alone was not able to predict postoperative transient sensory or motor deficits, the combination of MEP with other methods of neurological monitoring may improve accuracy and should be investigated in future studies.

DOI： 10.3892/ol.2018.8456

PubMed

DOI： 10.1186/s12893-018-0350-2

PubMed

Publisher：西日本整形・災害外科学会  

【背景】デノスマブは2014年に骨巨細胞腫に対する効能が承認され、切除不能な仙骨、脊椎例などで良好な成績が報告されている。一方、投与期間や手術時期など治療プロトコールは未確定である。【症例】66歳女性、S1〜4左側の骨腫瘍で生検にて骨巨細胞腫の診断にてデノスマブ投与を開始した。骨吸収マーカーであるTRACP-5bは投与1週後から正常化した。MRIではサイズの変化は認めずSDを維持し、12回投与(10ヵ月)後、治療効果判定と正常骨の評価目的で生検術を施行した。病理学的には多核巨細胞腫はほぼ消失し、紡錘形細胞の増殖能も著明に低下していた。腸骨の骨形態計測では骨吸収、骨形成とも低下が見られた。【考察】骨巨細胞腫に対するデノスマブ治療では画像上縮小が得られなくても病理学的には治療効果が明らかであった。一方正常骨代謝への影響も見られ、継続期間についての検討が必要であると思われた。(著者抄録)

DOI： 10.1002/jmri.25987

PubMed

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

Treatment of rheumatoid arthritis (RA) with biological disease-modifying anti-rheumatic drugs (bDMARDs) induces rapid remission. However, osteoporosis and its management remains a problem. The Geriatric Nutritional Risk Index (GNRI) evaluates the risk of malnutrition-related complications in elderly patients and has been shown to be a significant predictor of many diseases. We evaluated the correlation between GNRI and RA activity. In addition, risk factors for femoral neck bone loss were evaluated in RA patients treated with bDMARDs. We retrospectively examined the medical records of 146 patients with RA, collecting and recording the patients' demographic and clinical characteristics. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry. Inverse correlations were observed between GNRI and disease duration, disease activity score-28 joint count serum C-reactive protein (CRP), simple disease activity index, modified health assessment questionnaire score and CRP. GNRI showed correlation with femoral neck BMD and femoral neck BMD ≤ 70% of young adult men (YAM). Multiple regression analysis showed that female sex, increased age and lower GNRI were risk factors for lower BMD of the femoral neck. Multivariate binomial logistic regression analysis showed that female sex (odd ratio: 3.67) and lower GNRI (odd ratio: 0.87) were risk factors for BMD ≤ 70% of YAM. Because the GNRI is a simple method, it might be a simple predictor for RA activity and BMD status in RA patients. Complementary nutritional therapies might improve RA activity and osteoporosis in RA patients who have undergone treatment with bDMARDs.

DOI： 10.3390/nu10020234

PubMed

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

BACKGROUND: Langerhans cell histiocytosis (LCH) is categorized into three types, which include single-system single-site (SS-s), single-system multiple-site (SS-m) and multisystem (MS). The most commonly affected site in LCH is bone, and the bony lesion of SS-s LCH has a good prognosis. The bony lesion of SS-s LCH has been thought to regress spontaneously. Although treatments such as curettage, direct injection of corticosteroids, and chemotherapy have been performed, regular follow-up is the first line of treatment for the bony lesion of SS-s LCH. For preventing orthopedic sequelae, strict and appropriate follow-up should be performed, but the appropriate period and method of follow-up has not yet been established. METHODS: In the present study, we retrospectively analyzed a series of 7 cases of patients with SS-s LCH with a bony lesion treated in the Department of Orthopedic Surgery at Kagoshima University Hospital (Kagoshima, Japan) from 2006 to 2015. RESULTS: The bony lesion regressed spontaneously in all patients. Factors such as location, size, preoperative C-reactive protein (CRP) value, standardized uptake (SUV) value of positron emission tomography (PET), age, sex and direct steroid injection were not related to the clinical course. Temporary expansion of the lesion occurred in 3 patients and a temporary worsening of pain occurred in 1 patient during the follow-up period. These events occurred within 6 weeks after biopsy. CONCLUSION: Careful follow-up and the use of an appropriate orthosis can lead to a good clinical course for the bony lesion of SS-s LCH. Future research should seek to determine the appropriate follow-up period.

DOI： 10.1016/j.jos.2017.08.018

PubMed

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

BACKGROUND AND OBJECTIVES: Hemodialysis patients are at risk for bone loss and sarcopenia, characterized by reduced muscle mass and limited mobility/function. Osteoporosis and sarcopenia both increase the risk of hospitalization and death in affected individuals. Malnutrition also occurs as a complication of hemodialysis and has been identified as a risk factor for osteoporosis and sarcopenia. In this study, we examined the relationship between osteoporosis, muscle volume, walking ability, and malnutrition in hemodialysis patients. METHODS AND STUDY DESIGN: Forty-five hemodialysis patients were evaluated. Bone mineral density (BMD) and muscle volume were measured by dual-energy X-ray absorptiometry. Muscle volume and strength were evaluated using lean mass index (LMI), handgrip strength, and walking ability. The time required for a patient to walk 10 meters was measured to evaluate walking ability. The geriatric nutritional risk index (GNRI) was used to assess malnutrition. RESULTS: Multiple linear regression analysis showed that older age, female sex, lower LMI, and higher total type I procollagen N-terminal propeptide were correlated with lower BMD of lumbar spine. Higher age and lower LMI were correlated with lower BMD of the femoral neck. Female sex and lower GNRI were correlated with lower LMI. Longer duration of hemodialysis was correlated with lower walking ability. CONCLUSIONS: Our findings suggest that muscle preservation is required to maintain both lumbar spine and femoral neck BMD. Similarly, nutritional management is necessary to maintain BMD via preservation of muscle volume. Complementary nutritional therapies are needed to improve osteoporosis and sarcopenia in high-risk hemodialysis patients.

DOI： 10.6133/apjcn.052018.03

PubMed

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

INTRODUCTION: Reports of hypertrophic spinal pachymeningitis associated with human T-cell lymphotrophic virus-1 (HTLV-1) infection and Sjogren's syndrome in the English literature are still very rare. PRESENTATION OF CASE: We hereby present a case of a 78-year-old female with a history of lower extremity weakness after a fall, which fully resolved after conservative treatment. However, the symptoms recurred 4 years later, and the patient became unable to walk. The patient had no superficial or deep sensation below the level of T9, and she also had urinary retention. Magnetic resonance imaging showed that hypertrophic dura mater was compressing the spinal cord from T2 to T10. Blood testing revealed increased anti-HTLV-1 antibody, rheumatoid factor, elevation of anti-SS-A antibody and antinuclear antibody. The cerebrospinal fluid contained markedly elevated levels of total protein and cell numbers. Biopsy of the labial gland of the lip revealed chronic sialadenitis. DISCUSSION: In collaboration with a neurologist, we diagnosed this patient with hypertrophic spinal pachymeningitis associated with HTLV-1 infection and Sjogren's syndrome. We performed laminectomy at the affected spinal levels, resected the thickened dura, and maintained the patient on steroid therapy. The patient attained a marked recovery; she could walk with a cane and her urinary retention was improved. CONCLUSION: For the management of HSP associated with HTLV-1 and SS, we recommend surgical decompression with subsequent prolonged steroid therapy and prolonged close monitoring to achieve a good long-term outcome.

DOI： 10.1016/j.ijscr.2018.03.010

PubMed

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

OBJECTIVE: Osteoporosis is a complication of rheumatoid arthritis. We examined the risk factors for bone loss in rheumatoid arthritis patients receiving biological disease-modifying anti-rheumatic drugs. Lumbar spine and femoral neck bone mineral density was measured at two time points in 153 patients with rheumatoid arthritis managed with biological disease-modifying anti-rheumatic drugs. We examined patients' variables to identify risk factors for least significant reduction of bone mineral density. RESULTS: Least significant reduction of lumbar spine bone mineral density (≤ - 2.4%) was seen in 13.1% of patients. Least significant reduction of femoral neck bone mineral density (≤ - 1.9%) was seen in 34.0% of patients. Multiple logistic regression analysis showed that a risk factor for least significant reduction of the lumbar spine was high-dose methylprednisolone use. Multiple regression analysis showed that a risk factor for least significant reduction of the femoral neck was short disease duration. Our findings showed that a risk factor for femoral neck bone mineral density reduction was a short disease duration. These findings suggest that rheumatoid arthritis patients receiving treatment with biological disease-modifying anti-rheumatic drugs may benefit from earlier osteoporosis treatments to prevent femoral neck bone loss.

DOI： 10.1186/s13104-017-3086-7

PubMed

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

As elderly patients with hip osteoarthritis aged, acetabular dysplasia parameters decreased (Sharp's angle, acetabular roof obliquity angle, and acetabular head index) and the incidence of the atrophic type increased. Vertebral body fracture was more frequent in the atrophic type, suggesting the involvement of osteoporosis at the onset of hip osteoarthritis. INTRODUCTION: Osteoarthritis (OA) is associated with increased bone formation at a local site. However, excessive bone resorption has also been found to occur in the early stages of OA. Osteoporosis may be involved in the onset of OA in elderly patients. We conducted a cross-sectional radiographic study of patients with hip OA and examined the association between age and factors of acetabular dysplasia (Sharp's angle, acetabular roof obliquity angle, and acetabular head index) as well as the osteoblastic response to determine the potential involvement of osteoporosis. METHODS: This study included 366 patients (58 men, 308 women) who had undergone total hip arthroplasty for the diagnosis of hip OA. We measured the parameters of acetabular dysplasia using preoperative frontal X-ray images and evaluated each patient according to Bombelli classification of OA (hypertrophic, normotrophic, or atrophic type). RESULTS: As the patients aged, the parameters of acetabular dysplasia decreased. The incidence of the atrophic type of OA was significantly higher in older patients. Vertebral body fractures were more frequent in the atrophic type than in the other types. Additionally, the index of acetabular dysplasia was lower in the atrophic type. By contrast, the hypertrophic type was present in relatively younger patients and was associated with an increased index of acetabular dysplasia. CONCLUSION: In elderly patients with hip OA, the parameters of acetabular dysplasia decreased and the incidence of the atrophic type increased as the patients aged. The frequency of vertebral body fracture was high in patients with the atrophic type, suggesting the involvement of osteoporosis in the onset of hip OA.

DOI： 10.1007/s11657-017-0325-4

PubMed

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

The aim of the present study was to detect prognostic factors in patients with skeletal-related events (SREs) and bone metastasis at the time of non-small-cell lung cancer (NSCLC) diagnosis. A total of 85 NSCLC patients were retrospectively enrolled, 47 (55.2%) of whom presented with SREs at the time of NSCLC diagnosis. Multivariate logistic regression analysis identified squamous cell carcinoma as a risk factor for SRE. Kaplan-Meier analysis demonstrated that there was no difference in the overall survival between the SRE and no SRE groups. Cox hazard model revealed that a higher Eastern Cooperative Oncology Group (ECOG) performance status (PS) score was a risk factor for poor prognosis, while surgery for bone metastasis and molecular-targeted therapy were factors for better prognosis in patients with SREs at the time of NSCLC diagnosis. Multivariate analysis revealed that a higher ECOG PS score and metastasis to the adrenal gland were risk factors for poor prognosis, while surgery for bone metastasis and molecular-targeted therapy were factors for better prognosis. Thus, while surgical treatment and molecular-targeted therapy appear to improve the prognosis of patients with bone metastasis at the time of NSCLC diagnosis, those with a higher ECOG PS score and adrenal metastasis may benefit more from radiotherapy or supportive care.

DOI： 10.3892/mco.2017.1394

PubMed

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

Histological distinction between enchondroma and chondrosarcoma is difficult because of a lack of definitive biomarkers. Here, we found highly active transforming growth factor-β (TGF-β) and bone morphogenetic protein (BMP) signalling in human chondrosarcomas compared with enchondromas by immunohistochemistry of phosphorylated SMAD3 and SMAD1/5. In contrast, the chondrogenic master regulator SOX9 was dramatically down-regulated in grade 1 chondrosarcoma. Paternally expressed gene 10 (PEG10) was identified by microarray analysis as a gene overexpressed in chondrosarcoma SW1353 and Hs 819.T cells compared with C28/I2 normal chondrocytes, while TGF-β1 treatment, mimicking higher grade tumour conditions, suppressed PEG10 expression. Enchondroma samples exhibited stronger expression of PEG10 compared with chondrosarcomas, suggesting a negative association of PEG10 with malignant cartilage tumours. In chondrosarcoma cell lines, application of the TGF-β signalling inhibitor, SB431542, increased the protein level of PEG10. Reporter assays revealed that PEG10 repressed TGF-β and BMP signalling, which are both SMAD pathways, whereas PEG10 knockdown increased the level of phosphorylated SMAD3 and SMAD1/5/9. Our results indicate that mutually exclusive expression of PEG10 and phosphorylated SMADs in combination with differentially expressed SOX9 is an index to distinguish between enchondroma and chondrosarcoma, while PEG10 and TGF-β signalling are mutually inhibitory in chondrosarcoma cells.

DOI： 10.1038/s41598-017-13994-w

PubMed

Publisher：西日本整形・災害外科学会  

今回我々は,巨大な痛風結節を生じ,手術加療を要した症例を経験したので報告する.症例は37歳男性.20歳の時に痛風と診断された.度々痛風発作があったが放置.今回全身の関節に腫脹疼痛があり,手指の把握困難,起立歩行困難のため入院となった.四肢関節,特に両肘,両膝,左母趾には巨大な皮下腫瘤を認めた.両膝の関節液より尿酸Na結晶が検出され痛風関節炎と診断した.約2週間保存的に加療し全身痛は改善したが,左肘・手指・膝・母趾の疼痛が持続するため,痛風結節の掻爬術を行った.術後症状の改善がみられた.痛風の治療は,薬物療法が確立されており,痛風結節を生じる症例は稀である.痛風結節に対しては薬物療法が基本であるが,抵抗性の場合は手術が必要となる.本症例は,薬物療法に抵抗し,疼痛・機能障害が改善しないため手術を行った.尿酸値は徐々に改善しており,手術が尿酸代謝の改善に好影響を与えたものと考える.(著者抄録)

Publisher：西日本整形・災害外科学会  

デスモイド型線維腫は,軟部腫瘍のうち約3%を占める比較的まれな軟部腫瘍である.病理学的には線維芽細胞の増殖を特徴とし,遠隔転移はきたさないものの局所浸潤性に発育するのが特徴である.デスモイド型線維腫の発症誘因として外傷や先行する手術が挙げられ,また女性ホルモンとの関与も示唆されている.またその治療法も経過観察から薬物療法,手術療法,放射線治療と様々なものが報告されているが,いまだ確立していないのが現状である.今回我々は乳がん術後にデスモイド型線維腫をきたした2例を経験した.2例とも,まずは薬物療法による保存療法を行い,1例は薬物療法のみで腫瘍の縮小傾向を認めたが,2例目は薬物療法の効果乏しく腫瘍の増大傾向を認め,広範腫瘍切除術を施行した.乳がんとデスモイド型線維腫との関連について,またデスモイド型線維腫に対する治療戦略について考察したので報告する.(著者抄録)

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

Aneurysmal bone cysts (ABCs) are benign bony lesions frequently accompanied by multiple cystic lesions and aggressive bone destruction. They are relatively rare lesions, representing only 1% of bone tumors. The pathogenesis of ABCs has yet to be elucidated. In the present study, a series of 22 cases of primary and secondary ABC from patients treated in Department of Orthopedic Surgery, Kagoshima University Hospital (Kagoshima, Japan) from 2001-2015 were retrospectively analyzed. The average age at the time of diagnosis of primary ABC was 17.9 years. Intralesional curettage and artificial bone grafting were performed in the majority of the patients with primary ABC. The local recurrence rate following curettage for primary ABC was 18%, and the cause of local recurrence was considered to be insufficient curettage. Although no adjuvant therapy was administered during the surgeries, it may assist the prevention of local recurrence in certain cases. The cases of secondary ABC were preceded by benign bone tumors, including fibrous dysplasia, giant cell tumors, chondroblastoma and non-ossifying fibroma. The features of the secondary ABC typically reflected those of the preceding bone tumor. In the majority of cases, distinguishing the primary ABC from the secondary ABC was possible based on characteristic features, including age of the patient at diagnosis and the tumor location. In cases that exhibit ambiguous features, including a soft tissue mass or a thick septal enhancement on the preoperative magnetic resonance images, a biopsy must be obtained in order to exclude other types of aggressive bone tumors, including giant cell tumor, osteosarcoma and telangiectatic osteosarcoma.

DOI： 10.3892/ol.2017.5682

PubMed

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

AIM: Given that different hospitals achieve different outcomes, optimal evaluation of treatment outcomes in the local community requires evaluation of many institutions in that area. We carried out a prospective multicenter cohort study in Kagoshima Prefecture to identify factors that contribute to deterioration in activities of daily living performance and patient mortality 1 year after surgical treatment of hip fractures. METHODS: We prospectively enrolled 387 patients who underwent surgery for hip fractures in 33 registered facilities within a 6-month period from February to July 2007. Logistic regression analysis was carried out to identify factors that contribute to deterioration in activities of daily living performance and death within 1 year after surgery. RESULTS: An increased risk of Barthel Index (BI) deterioration was associated with increased age (P for trend = 0.003), worse pre-injury BI (P for trend = 0.021), trochanteric fractures (OR 2.07, 95% CI 1.31-3.27), worse BI at discharge (P for trend < 0.001) and postoperatively developed cognitive impairment (OR 6.34, 95% CI 2.15-18.7). The OR for BI deterioration in patients with newly-diagnosed disease after discharge was approximately 9.16 (95% CI 4.03-20.8). No factors except age and sex were statistically significant as the preoperative indicators of mortality risk. Only BI at discharge was a significant determinant of mortality risk (P for trend = 0.013) after adjusting for the effects of age and sex. CONCLUSIONS: Patients with poor activities of daily living performance at the time of hospital discharge were likely to show poor functional recovery and a high 1-year postoperative mortality. Geriatr Gerontol Int 2017; 17: 391-401.

DOI： 10.1111/ggi.12718

PubMed

Publisher：西日本整形・災害外科学会  

人工股関節手術における術後疼痛に関与する因子を検討した.当院で施行した人工股関節手術73股を対象とし,疼痛はVisual Analog Scale(以下VAS)で評価した.術後7日目安静時VASを目的変数とし,術前日本整形外科学会股関節機能基準JOAスコア(以下JOAスコア),麻酔法,手術内容,手術時間,出血量,術後1日目Hb,術後7日目Hb,術後7日目CRP,術後内服鎮痛剤,車椅子移乗開始日,術前安静時VAS,術後3日目安静時VASを因子として単変量解析を行ったところ,麻酔法,術前安静時VASが有意な因子であった.術後7日目安静時VASを目的変数とし,手術内容,手術時間,出血量,麻酔法,術後内服鎮痛剤,術前安静時VAS,術後3日目安静時VASを因子として重回帰分析を行ったところ,術前の安静時VAS,麻酔法が術後7日目の疼痛に有意に関与していた.術前の疼痛対策およびブロック併用による麻酔が術後7日目の疼痛管理において有効であると考えられる.(著者抄録)

Publisher：西日本整形・災害外科学会  

今回,我々は比較的稀な大腿骨頸部疲労骨折の3例を経験したので報告する.症例は全て男性で,発症時年齢は16歳から26歳.持続する股関節痛を主訴に近医を受診,3例中2例は単純X線像で明らかな異常を認めなかった.いずれの症例も基礎疾患のない少年期から青年期の男性で,転倒などの明らかな外傷機転を認めなかったが,2名は陸上部の長距離ランナー,1例は警察官で高い活動性を示していた.CT,MRI,骨シンチグラフィーにて診断を得た.全ての症例において患肢免荷による保存療法にて加療した.荷重開始許可の判断や骨癒合の判定は,単純X線像により行った.スポーツ競技もしくは労務復帰までの期間は2〜3ヵ月であった.股関節痛を認める症例に対して大腿骨頸部の疲労骨折は稀であるが,鑑別診断として考慮に入れるべき疾患である.単純X線像で異常を認めない場合でも,アスリート選手等本疾患を疑う際には,MRIが非常に有用である.(著者抄録)

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

High-dose chemotherapy and surgical treatment have improved the prognosis of osteosarcoma. However, more than 20% of patients with osteosarcoma still have a poor prognosis. We investigated the expression and function of casein kinase 2 (CK2) in osteosarcoma growth. We then examined the effects of CX-4945, a CK2 inhibitor, on osteosarcoma growth in vitro and in vivo to apply our findings to the clinical setting. We examined the expression of CK2α and CK2β by western blot analysis, and performed WST-1 assays using CK2α and CK2β siRNA or CX-4945. Flow cytometry and western blot analyses were performed to evaluate apoptotic cell death. Xenograft models were used to examine the effect of CX-4945 in vivo. Western blot analysis revealed upregulation of CK2α and CK2β in human osteosarcoma cell lines compared with human osteoblast cells or mesenchymal stem cells. WST assay showed that knockdown of CK2α or CK2β by siRNA inhibited the proliferation of human osteosarcoma cells. Treatment with 3 µM of CX-4945 inhibited osteosarcoma cell proliferation; however, the same concentration of CX-4945 did not affect the proliferation of human mesenchymal stem cells. Additionally, treatment with CX-4945 inhibited the proliferation of human osteosarcoma cells in a dose-dependent manner. Western blot and flow cytometry analyses showed that treatment with CX-4945 promoted apoptotic death of osteosarcoma cells. The xenograft model showed that treatment with CX-4945 significantly prevented osteosarcoma growth in vivo compared with control vehicle treatment. Our findings indicate that CK2 may be an attractive therapeutic target for treating osteosarcoma.

DOI： 10.3892/or.2016.5310

PubMed

Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

Intraosseous epidermoid cysts are exceedingly rare. Known as pseudotumors, not true neoplasms, intraosseous epidermoid cysts usually involve the phalanges, the skull, and the toes. Intraosseous epidermoid cysts typically present as destructive osteolytic lesions on X-ray, mimicking malignant bone tumors. Here, we present two cases of an intraosseous epidermoid cyst in the distal phalanx treated with curettage and synthetic bone graft, followed by a review of the relevant literature. In both cases, the patient presented with a painful enlargement of the fingertip following a minor trauma. Magnetic resonance imaging demonstrated lesions involving the distal phalanx that had a low signal on T1-weighted imaging (WI) and a high intensity on T2-WI. In both cases, the lesions were not enhanced by gadolinium. Good remodeling and functional recoveries were obtained. For physically active patients with substantial bone defects, synthetic bone graft may be recommended.

DOI： 10.1177/2309499016684096

PubMed

Publisher：西日本整形・災害外科学会  

今回，我々は比較的稀な大腿骨頚部疲労骨折の3例を経験したので報告する．症例は全て男性で，発症時年齢は16歳から26歳．持続する股関節痛を主訴に近医を受診，3例中2例は単純X線像で明らかな異常を認めなかった．いずれの症例も基礎疾患のない少年期から青年期の男性で，転倒などの明らかな外傷機転を認めなかったが，2名は陸上部の長距離ランナー，1例は警察官で高い活動性を示していた．CT，MRI，骨シンチグラフィーにて診断を得た．全ての症例において患肢免荷による保存療法にて加療した．荷重開始許可の判断や骨癒合の判定は，単純X線像により行った．スポーツ競技もしくは労務復帰までの期間は2～3か月であった．股関節痛を認める症例に対して大腿骨頚部の疲労骨折は稀であるが，鑑別診断として考慮に入れるべき疾患である．単純X線像で異常を認めない場合でも，アスリート選手等本疾患を疑う際には，MRIが非常に有用である．

DOI： 10.5035/nishiseisai.66.144

Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

The purpose of the present study was to analyze the effect of treatment of Paget's disease of bone (PDB) with bone scintigraphy using a computer-assisted diagnosis system (BONENAVI) that quantitatively evaluates bone metabolism. Seven patients with PDB (three male, four female; average age, 60 years; age range, 33-80 years) underwent bone scintigraphy and measurement of serum alkaline phosphatase (ALP), bone-specific ALP (BAP), serum cross-linked N-telopeptide (NTx) of type I collagen, urinary NTx, and deoxypyridinoline (DPD) before and after bisphosphonate treatment. Bone scan index (BSI), artificial neural network (ANN) value, and hotspot number (HSn) were calculated using BONENAVI software. Mean follow-up period was 22 months (range, 11-35 months). Among three BONENAVI parameters (ANN, BSI, and HSn), only BSI was significantly lower after bisphosphonate treatment as compared with before. All bone metabolic markers excluding DPD were significantly lower following bisphosphonate treatment than before. Bone formation markers (ALP and BAP) were significantly lower than bone resorption markers (U-NTx and S-NTx). The correlation of BONENAVI parameters with four bone metabolic markers was analyzed before and after bisphosphonate treatment. Before treatment, the majority of the four markers did not correlate with the BONENAVI parameters. In contrast, post-treatment ALP, BAP, and U-NTx were significantly correlated with BSI and HSn. To the best of our knowledge, this is the first study to evaluate the treatment of PDB by bone scintigraphy using a computer-assisted diagnosis system that quantitatively evaluates bone metabolism. The findings demonstrated that, using BONENAVI software, bone scintigraphy is able to quantitatively and spatially evaluate the bisphosphonate treatment effect, particularly in patients with polyostotic PDB.

DOI： 10.3892/etm.2016.3899

PubMed

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

PURPOSE: This study aimed to identify and compare risk factors for surgical site infection (SSI) and non-surgical site infections (non-SSIs), particularly urinary tract infection (UTI), after spine surgery. METHODS: We retrospectively reviewed 825 patients (median age 59.0 years (range 33-70 years); 442 males) who underwent spine surgery at Kagoshima University Hospital from January 2009 to December 2014. Patient parameters were compared using the Mann-Whitney U and Fisher's exact tests. Risk factors associated with SSI and UTI were analyzed via the multiple logistic regression analysis. P < 0.05 was considered statistically significant. RESULTS: SSI occurred in 14 of 825 cases (1.7 %), and non-SSI occurred in 23 of 825 cases (2.8 %). Most non-SSIs were UTIs (20 of 23 cases, 87.0 %). In the 14 patients with SSI, UTI occurred before SSI onset in one patient, and after SSI onset in two patients. UTI onset before SSI was not a risk factor for SSI. Multiple logistic regression analysis indicated that common risk factors for SSI and UTI were operation time (P = 0.0019 and 0.0162, respectively) and ASA classification 3 (P = 0.0132 and 0.0356, respectively). The 1 week post-operative C-reactive protein (CRP) level was a risk factor for UTI (P = 0.0299), but not for SSI (P = 0.4996). CONCLUSIONS: There was no relationship between SSI and symptomatic UTI after spine surgery. Risk factors for post-operative SSI and UTI were operative time and ASA classification 3; 1 week post-operative CRP was a risk factor for UTI only.

DOI： 10.1007/s00586-016-4674-2

PubMed

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

Allograft bone is a widely used as a convenient tool for reconstructing massive bone defects in orthopedic surgery. However, allografts are associated with the risk of viral disease transmission. One of the viruses transmitted in this manner is human T-lymphotropic virus type 1 (HTLV-1), which is found worldwide but is unevenly distributed. The southwestern parts of Japan are a highly endemic for HTLV-1. We investigated the HTLV-1 seroprevalence in candidate allograft donors at the regional bone bank in Kagoshima, Japan during its first 5 years of service. Between 2008 and 2012, we collected 282 femoral heads at the Kagoshima regional bone bank from living donors with osteoarthritis of the hip joint. Among the 282 candidate donors, 32 donors (11.3 %) were seropositive for anti-HTLV-1 antibody; notably, this prevalence is higher than that reported for blood donors in this area. Additionally, to determine if HTLV-1 genes are detectable after processing, we examined the bone marrow of the femoral heads from seropositive donors by conducting PCR assays. Our results confirm the existence of viral genes following the heat treatment processing of the femoral heads. Therefore, it is important to inactivate a virus completely by heat-treatment. Together, our findings highlight the importance of HTLV-1 screening at bone banks, particularly in HTLV-1-endemic areas such as southwest Japan.

DOI： 10.1007/s10561-016-9586-1

PubMed

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BACKGROUND: Femoral bone remodeling in response to stress shielding induces periprosthetic bone loss. Computerized finite element analysis (FEA) is employed to demonstrate differences in initial stress distribution. However, FEA is often performed without considering the precise sites at which the stem was fixed. We determined whether FEA reflects mid-term radiological examination exactly as predicted following long-term stress shielding. METHODS: Femur-stem fixation sites were evaluated radiologically according to the location of spot welds in two anatomical cementless stem designs. Based on mid-term radiological results, four femur-stem bonding site conditions were defined as: (Condition A) no bonding; (Condition B) bonding within the 10 mm area proximal to the distal border of the porous area; (Condition C) bonding of the entire porous area; and (Condition D) bonding of the entire femoral stem, prior to conducting FEA analysis. Furthermore, we radiographically evaluated mid- and long-term stress shielding, and measured bone mineral density of the femur 10 years after total hip arthroplasty. RESULTS: Spot welds appeared frequently around the border between the porous and smooth areas. FEA showed that, based on mid-term radiological evaluation, von Mises stress was reduced in condition B in the area proximal to the femur-stem bonding sites for both stem designs compared with condition A (no bonding). Conversely, von Mises stress at all areas of the femur-stem bonding sites in conditions C and D was higher than that in condition A. With respect to stress shielding progression, there was no significant difference between the two types of stem designs. However, stress shielding progressed and was significantly higher in the presence of spot welds (p = 0.001). In both stem designs, bone mineral density in zone VII was significantly lower than that in the contralateral hips. CONCLUSIONS: These results indicate that FEA based on mid-term radiological evaluation may be helpful to predict the influence of long-term stress shielding more precisely.

DOI： 10.1186/s12891-016-1260-z

PubMed

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BACKGROUND: Although most patients achieve favorable results following bipolar hip hemiarthroplasty (BHA), some experience rapid migration of the prosthesis. We retrospectively reviewed 18 patients with BHA that necessitated revision. METHODS: We examined soft tissues obtained from periprosthetic lesions. In total, 18 patients with pain and acetabular migration of the BHA prosthesis were included. The patients were divided into a polymorphonuclear leukocyte (PMN)-positive (≥5 PMNs per high-power field [HPF]) and PMN-negative (<5 PMNs/HPF) group. RESULTS: Pathological findings showed that 11 patients were PMN-positive, which was indicative of infection. All patients in the PMN-positive group showed no polyethylene particles or foreign body giant cells, while all patients in the PMN-negative group showed polyethylene debris or foreign body giant cells (p < 0.001). BHA survival, C-reactive protein (CRP) levels, and the Japanese Orthopaedic Association (JOA) hip score were significantly different between the PMN-positive and PMN-negative group (p < 0.01). A BHA survival cut-off value of 3270 days was diagnostic for PMN positivity (sensitivity: 100%; specificity: 100%). The cut-off values for CRP and the JOA hip score were 0.43 mg/dl and 56 points, respectively. Four of 11 PMN-positive patients showed no clinical symptoms of infection (asymptomatic PMN-positive group). BHA survival, CRP levels, and JOA hip scores were significantly different between the asymptomatic PMN-positive and PMN-negative group (p < 0.05). A BHA survival cut-off of 3270 days was diagnostic for asymptomatic PMN positivity (sensitivity: 100%; specificity: 100%). The cut-off values for CRP and the JOA hip score were 0.43 mg/dl and 57 points, respectively. CONCLUSION: Our findings suggest that some portion of rapid BHA prosthesis migration is caused by mild infection. Careful pathological examination should be performed to identify infection before removal of the BHA prosthesis in patients who develop migration within 9 years.

DOI： 10.1186/s12891-016-0876-3

PubMed

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High-dose chemotherapy and surgical intervention have improved long-term prognosis for non-metastatic osteosarcoma to 50-80%. However, metastatic osteosarcoma exhibits resistance to standard chemotherapy. We and others have investigated the function of Hedgehog pathway in osteosarcoma. To apply our previous findings in clinical settings, we examined the effects of Hedgehog inhibitors including arsenic trioxide (ATO) and vismodegib combined with standard anticancer agents. We performed WST-1 assays using ATO, cisplatin (CDDP), ifosfamide (IFO), doxorubicin (DOX), and vismodegib. Combination-index (CI) was used to examine synergism using CalcuSyn software. Xenograft models were used to examine the synergism in vivo. WST-1 assays showed that 143B and Saos2 cell proliferation was inhibited by ATO combined with CDDP, IFO, DOX, and vismodegib. Combination of ATO and CDDP, IFO, DOX or vismodegib was synergistic when the two compounds were used on proliferating 143B and Saos2 human osteosarcoma cells. An osteosarcoma xenograft model showed that treatment with ATO and CDDP, IFO, or vismodegib significantly prevented osteosarcoma growth in vivo compared with vehicle treatment. Our findings indicate that combination of Hedgehog pathway inhibitors and standard FDA-approved anticancer agents with established safety for human use may be an attractive therapeutic method for treating osteosarcoma.

DOI： 10.3892/ijo.2015.3236

PubMed

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Recent progress in cancer treatment has improved patient survival, but has increased the number of patients with metastatic bone tumors. Data were collected from all bone metastasis patients at Kagoshima University, where almost all patients with metastatic bone tumors who reside in Kagoshima province are treated surgically. The scoring systems used in bone metastasis patients were then evaluated to identify those most suitable for our patients. Clinical data were collected from 145 patients with bone metastases. The patients were assigned prognostic scores based on four scoring systems, namely those described by the Ratasvuori, Mizumoto, Tokuhashi and Katagiri groups. Statistical examinations were performed to assess patient distribution regarding prognostic factors and the four data sets reported in the literature. The patient distributions for all prognostic factors were significantly different between the Scandinavian Sarcoma Group (SSG) and Kagoshima data. The distributions of patients for 3 of 5 and for 5 of 7 prognostic factors were statistically different between the Kagoshima data and the Katagiri and Tokuhashi data, respectively. Additionally, the distribution of patients in each scoring group was statistically different between the Kagoshima data and the Katagiri, Tokuhashi and Mizumoto data. The predictions of prognosis were significantly different between the results of each group and ours. The Tokuhashi scoring system detected the highest survival at 6 months (88.8%) in the Kagoshima data. Patients with a life expectancy of >6 months benefited from tumor excision and reconstruction. These findings suggest that the Tokuhashi scoring system is the most suitable for identifying patients who should be assessed for curative surgical intervention. SSG scoring, however, was suitable for identifying patients expected to survive for <6 months (91.3%). Prior to selecting a scoring system to predict prognosis, it is important to determine which scoring system is the most appropriate, based on each hospital's particular characteristics.

DOI： 10.3892/mco.2015.637

PubMed

Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Most bone tumors that occur in the clavicle are malignant. A few giant cell tumors (GCTs) of the clavicle have been reported; however, the most appropriate operative method for this tumor has never been discussed. CASE PRESENTATION: A 54-year-old man noticed enlargement of the proximal aspect of the right clavicle. A plain X-ray revealed lytic change and ballooning of the proximal end of the right clavicle. The tumor was isointense on T1-weighted magnetic resonance images and showed a mixture of low- and high-intensity areas on T2-weighted images without extension to the surrounding soft tissues. Bone scintigraphy showed strong accumulation (normal/tumor ratio, 2.31), and positron emission tomography revealed strong uptake of fluorine-18-2-fluoro-2-deoxy-d-glucose (SUVmax, 6.0) in the proximal part of the right clavicle. Because we could not completely exclude malignancy, an open biopsy was performed. Pathologically, the tumor comprised mononuclear stromal cells and multinuclear giant cells, resulting in a diagnosis of a GCT of the bone. Although curettage may be considered for such lesions (Campanacci grade II), we chose resection to minimize the chance of recurrence. The tumor was resected en-bloc with the proximal half of the clavicle. No postoperative shoulder disproportion was observed, and full range of motion of the right shoulder was maintained. The patient was satisfied with the surgical outcome (Musculoskeletal Tumor Society score of 96 %). He returned to his original job as a land and house investigator without any signs of recurrence for 1 year after surgery. CONCLUSIONS: Although GCT of the bone rarely occurs in the clavicle, the typical X-ray findings demonstrated in the present case are helpful for a correct diagnosis. Although en-bloc resection without reconstruction is appropriate for GCTs in expendable bones, there has been much discussion about shoulder function after total claviculectomy. Considering the importance of the function of the clavicle, which is to support the scapula through the acromioclavicular joint, we preserved the muscle attachments of the deltoid, trapezius, and pectoralis major. Because both the oncological and functional outcomes were satisfactory, we recommend preservation of as much of the clavicle as possible in patients with clavicular bone tumors.

DOI： 10.1186/s12891-015-0604-4

PubMed

Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: The utility of ultrasound imaging in the screening of soft-part tumours (SPTs) has been reported. We classified SPTs according to their blood flow pattern on Doppler ultrasound and re-evaluated the efficacy of this imaging modality as a screening method. Additionally, we combined Doppler ultrasound with several values to improve the diagnostic efficacy and to establish a new diagnostic tool. PATIENTS AND METHODS: This study included 189 cases of pathologically confirmed SPTs (122 cases of benign disease including SPTs and tumour-like lesions and 67 cases of malignant SPTs). Ultrasound imaging included evaluation of vascularity by colour Doppler. We established a scoring system to more effectively differentiate malignant from benign SPTs (ultrasound-based sarcoma screening [USS] score). RESULTS: The mean scores in the benign and malignant groups were 1.47 ± 0.93 and 3.42 ± 1.30, respectively. Patients with malignant masses showed significantly higher USS scores than did those with benign masses (p < 1 × 10(-10)). The area under the curve was 0.88 by receiver operating characteristic (ROC) analysis. Based on the cut-off value (3 points) calculated by ROC curve analysis, the sensitivity and specificity for a diagnosis of malignant SPT was 85.1% and 86.9%, respectively. CONCLUSIONS: Assessment of vascularity by Doppler ultrasound alone is insufficient for differentiation between benign and malignant SPTs. Preoperative diagnosis of most SPTs is possible by combining our USS score with characteristic clinical and magnetic resonance imaging findings.

DOI： 10.1515/raon-2015-0011

PubMed

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BACKGROUND: Activation of the Notch pathway has been reported in various types of cancers. However, the role of the hairy/enhancer-of-split related with YRPW motif protein 1 (HEY1) in osteosarcoma is unknown. We examined the function of HEY1 in osteosarcoma. METHODS: Expression of HEY1 was studied in human osteosarcoma. The effects of HEY1 in osteosarcoma were evaluated in vitro and in a xenograft model. Moreover, we examined the function of matrix metallopeptidase 9 (MMP9) as a downstream effector of HEY1. RESULTS: HEY1 was upregulated in human osteosarcoma. Knockdown of HEY1 inhibited the invasion of osteosarcoma cell lines. In contrast, the forced expression of HEY1 increased the invasion of mesenchymal stem cell. In addition, lung metastases were significantly inhibited by the knockdown of HEY1. We found that MMP9 was a downstream effector of HEY1 that promotes the invasion of osteosarcoma cells. Knockdown of HEY1 decreased the expression of MMP9. Addition of MMP9 rescued the invasion of osteosarcoma cells that had been rendered less invasive by knockdown of HEY1 expression. CONCLUSIONS: Our findings suggested that HEY1 augmented the metastasis of osteosarcoma via upregulation of MMP9 expression. Therefore, inhibition of HEY1 may be a novel therapeutic strategy for preventing osteosarcoma metastasis.

DOI： 10.1038/bjc.2015.84

PubMed

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

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

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