Search

Background: Clear cell sarcoma (CCS) is a therapeutically unresolved, aggressive, soft tissue sarcoma (STS) that predominantly affects young adults. This sarcoma is defined by t(12;22)(q13;q12) translocation, which leads to the fusion of Ewing sarcoma gene (EWS) to activating transcription factor 1 (ATF1) gene, producing a chimeric EWS-ATF1 fusion gene. We established a novel CCS cell line called Hewga-CCS and developed an orthotopic tumor xenograft model to enable comprehensive bench-side investigation for intensive basic and preclinical research in CCS with a paucity of experimental cell lines.Methods: Hewga-CCS was derived from skin metastatic lesions of a CCS developed in a 34-year-old female. The karyotype and chimeric transcript were analyzed. Xenografts were established and characterized by morphology and immunohistochemical reactivity. Subsequently, the antitumor effects of pazopanib, a recently approved, novel, multitargeted, tyrosine kinase inhibitor (TKI) used for the treatment of advanced soft tissue sarcoma, on Hewga-CCS were assessed in vitro and in vivo.Results: Hewga-CCS harbored the type 2 EWS-ATF1 transcript. Xenografts morphologically mimicked the primary tumor and expressed S-100 protein and antigens associated with melanin synthesis (Melan-A, HMB45). Pazopanib suppressed the growth of Hewga-CCS both in vivo and in vitro. A phospho-receptor tyrosine kinase array revealed phosphorylation of c-MET, but not of VEGFR, in Hewga-CCS. Subsequent experiments showed that pazopanib exerted antitumor effects through the inhibition of HGF/c-MET signaling.Conclusions: CCS is a rare, devastating disease, and our established CCS cell line and xenograft model may be a useful tool for further in-depth investigation and understanding of the drug-sensitivity mechanism. [ABSTRACT FROM AUTHOR]

Background: Surgical treatment options of femoral metastases include intramedullary nailing (IMN) and endoprosthetic reconstruction (EPR). Previous studies have demonstrated functional and oncological advantages of EPR over IMN. The purpose of this study was to (1) report the durability of IMN and (2) establish the indication of IMN for femoral metastases., Methods: In 2003-2013, among 186 surgically treated femoral metastasis cases, we retrospectively reviewed 80 consecutive IMN cases in 75 patients, including 14 pathological and 66 impending fractures. For the decision of surgical procedure (IMN, EPR, or plating), the following factors are considered: (1) fracture pattern (impending or pathological fracture), (2) Mirels' score (≥8 or <8), (3) fracture site (femoral head, neck, intertrochanter, subtrochanter, diaphysis, or distal), (4) number of metastases (solitary or multiple), and (5) patient's estimated prognosis. Patient demographics, postoperative survival, implant survival, and early postoperative mortality were reviewed., Results: The patients were 37 males and 38 females, with a mean age of 60.1 (20-84) years. Average follow-up period was 11.4 (1-77) months. The most common fracture site was the subtrochanter (46/80), followed by the diaphysis (26/80) and the intertrochanter (8/80). The most common primary tumor was lung cancer (24/80, 32%), followed by breast cancer (24%) and melanoma (15%). With the exception of six cases, all patients underwent postoperative radiotherapy to the affected whole femur. The postoperative patient survival was 14.2 and 8.4% at 2 and 3 years from surgery, respectively, while the implant survival rate remained 94.0% at both 2 and 3 years. Three out of 46 subtrochanteric cases required revision surgeries because of proximal breakage of implant 4-50 months after initial surgery for femoral metastases, but all were replaced by mega-prosthesis and did not need further operation until their death. Early postoperative fatal complications were observed in three patients, all of which were pulmonary dysfunction., Conclusions: The performance of IMN in this study was satisfactory although a large portion of sub- and intertrochanter metastases were included. Broader indication including these parts should be considered, for IMN has advantages such as lower cost and less invasiveness and even an implant failure can be revised by mega-prosthetic reconstruction.

Background: Much attention has been paid to peak height velocity (PHV) as a possible predictor of curve progression in patients with idiopathic scoliosis (IS). The aim of this study was to analyze the relationship between the magnitude of the Cobb angle at PHV and scoliosis progression, defined as having surgery prior to skeletal maturity in female patients with IS., Methods: A retrospective review identified 56 skeletally immature female IS patients who were followed until maturity. The mean age and the mean pubertal status at the initial visit were 10 years and 24 months before menarche respectively, with a follow-up period of 5 years. They were divided into two groups: non-surgery group (NS) and surgery group (S), depending on their treatment method in use at the final follow-up visit. Surgery group was defined as an ultimately having surgery due to Cobb angle greater than 45 degrees prior to skeletal maturity regardless of conservative management. Height measurements were recorded at each visit; height velocity was calculated as the height change, in cm, divided by the time interval, in years. The PHV, chronological age at PHV (APHV), height at PHV (HPHV), and final height (FH) were determined for each group. In patients with Cobb angle greater than 30 degrees, the corrected height was calculated by Kono formula and corrected height velocity values were provided. The sensitivity, specificity, and area under the curve (AUC) of the receiver-operating -characteristic (ROC) analysis were calculated to predict spinal curve progression for various Cobb-angle cutoff values at PHV., Results: The corrected PHV had a mean value of 8.5 and 8.9 cm/year in the NS-group and S-group, respectively. The APHV was 11.9 and 11 years, the corrected HPHV was 152.9, and 149.3 cm, and the corrected FH was 159.9 and 159.3 cm, respectively. When a Cobb angle of 31.5 degrees was at PHV, ROC analysis revealed 78% sensitivity, 82% specificity, and an AUC of 0.93, acceptable values for curve progression in patients with IS., Conclusions: These findings indicate that 31.5 degrees of spinal curvature when patients are at PHV is a significant predictive indicator for progression of the curve to a magnitude requiring surgery. We suggest that the curve-progression risk assessment in patients with IS should include PHV, along with measures of skeletal and non-skeletal maturities.

Introduction: Real-world evidence of the effectiveness of pharmacological thromboprophylaxis for venous thromboembolism (VTE) is limited. Our objective was to assess the effectiveness and safety of thromboprophylactic regimens in Japanese patients undergoing joint replacement in a real-world setting., Method: Overall, 1,294 patients (1,073 females and 221 males) who underwent total knee arthroplasty (TKA) and 868 patients (740 females and 128 males) who underwent total hip arthroplasty (THA) in 34 Japanese national hospital organization (NHO) hospitals were enrolled. The primary efficacy outcome was the incidence of deep vein thrombosis (DVT) detected by mandatory bilateral ultrasonography up to post-operative day (POD) 10 and pulmonary embolism (PE) up to POD28. The main safety outcomes were bleeding (major or minor) and death from any cause up to POD28., Results: Patients undergoing TKA (n = 1,294) received fondaparinux (n = 360), enoxaparin (n = 223), unfractionated heparin (n = 72), anti-platelet agents (n = 45), or no medication (n = 594). Patients undergoing THA (n = 868) received fondaparinux (n = 261), enoxaparin (n = 148), unfractionated heparin (n = 32), anti-platelet agents (n = 44), or no medication (n = 383). The incidence rates of sonographically diagnosed DVTs up to POD10 were 24.3% in patients undergoing TKA and 12.6% in patients undergoing THA, and the incidence rates of major bleeding up to POD28 were 1.2% and 2.3%, respectively. Neither fatal bleeding nor fatal pulmonary embolism occurred. Significant risk factors for postoperative VTE identified by multivariate analysis included gender (female) in both TKA and THA groups and use of a foot pump in the TKA group. Only prophylaxis with fondaparinux reduced the occurrence of VTE significantly in both groups. Propensity score matching analysis (fondaparinux versus enoxaparin) showed that the incidence of DVT was lower (relative risk 0.70, 95% confidence interval (CI) 0.58 to 0.85, P = 0.002 in TKA and relative risk 0.73, 95% CI 0.53 to 0.99, P = 0.134 in THA) but that the incidence of major bleeding was higher in the fondaparinux than in the enoxaparin group (3.4% versus 0.5%, P = 0.062 in TKA and 4.9% versus 0%, P = 0.022 in THA)., Conclusions: These findings indicate that prophylaxis with fondaparinux, not enoxaparin, reduces the risk of DVT but increases bleeding tendency in patients undergoing TKA and THA., Trial Registration: University Hospital Medical Information Network Clinical Trials Registry: UMIN000001366. Registered 11 September 2008.