Gait analysis of a patient after femoral nerve and malignant soft tissue tumor resections: a case report.

BACKGROUND: Malignant femoral soft tissue tumors are occasionally resected together with the femoral nerves, but this can cause loss of knee extensor muscle activity. To the best of our knowledge, no previous reports have detailed the gait analysis of such cases in combination with electromyography. Herein, we report the gait analysis of a patient who underwent left groin synovial sarcoma and left femoral nerve resection 12 years ago. CASE PRESENTATION: We analyzed the gait of a 38-year-old man who was able to walk unaided after the resection of a synovial sarcoma in the left groin together with the ipsilateral femoral nerve. The muscle activities of the affected medial (MH) and lateral hamstrings (LH), and lateral heads of the gastrocnemius (GL) were increased during 50-75% of the stance phase. The hip flexion angle of the affected limb was smaller, and the ankle plantar flexion angle of the affected limb was larger than that of the non-affected limb. This means that in the affected limb, the hip and ankle angles were adjusted to prevent knee collapse, and the MH, LH, and GL muscles contributed in the mid- and late-stance phases. Moreover, we found that the hamstring and gastrocnemius of the affected limb worked together to keep the ipsilateral knee extended in the mid-stance phase and slightly flexed in the late-stance phase. CONCLUSIONS: Patients capable of walking after femoral nerve resection may control their hamstrings and gastrocnemius muscles collaboratively to prevent ipsilateral knee collapse in the mid- and late-stance phases.

Effectiveness of gelatin matrix with human thrombin for reducing blood loss in palliative decompressive surgery with posterior spinal fusion for metastatic spinal tumors.

BACKGROUND: This study aimed to investigate the effect of gelatin matrix with human thrombin (GMHT) on blood loss and survival time in patients with metastatic spinal tumors treated with palliative decompression surgery with posterior spinal fusion. METHODS: We retrospectively reviewed 67 consecutive patients with metastatic spinal tumors who underwent palliative decompression surgery with posterior spinal fusion. We compared patients in whom GMHT was not used during surgery with those in whom GMHT was used. The following baseline characteristics were evaluated: age, height, weight, sex, metastatic tumor diagnosis, medical history, use of antiplatelet drug, use of anticoagulant drug, use of NSAIDs, smoking, preoperative PLT value, preoperative APTT, preoperative PT-INR, Karnofsky Performance Status score, Charlson comorbidities index score, the percentage of patients who received perioperative chemotherapy, main tumor level, Frankel category, revised Tokuhashi score, spinal instability neoplastic score (SINS), number of fusion segments, operation time, intraoperative blood loss, drainage blood loss, red blood cell transfusion, hemoglobin level, total protein (TP), albumin values, total blood loss (TBL), hidden blood loss, postoperative bed rest and postoperative survival time. Perioperative complications were assessed. RESULTS: Age, height, weight, sex, metastatic tumor diagnosis, medical history, use of antiplatelet drug, use of anticoagulant drug, use of NSAIDs, smoking, preoperative PLT value, preoperative APTT, preoperative PT-INR, CCI score, main level of tumors, SINS score, preoperative Tokuhashi score and number of fusion segments did not differ significantly between the two groups. Operation time, intraoperative blood loss, postoperative drainage blood loss, and TBL were significantly decreased in the group with GMHT than in the group without GMHT. The total number of perioperative complications was significantly lesser in the group with GMHT than in the group without GMHT. The median postoperative survival time was significantly longer in the GMHT group than in the group without GMHT. CONCLUSION: GMHT should be considered a valid option for the treatment of patients with metastatic spinal tumors with a short life expectancy.

Analysis of accuracy of pedicle screw placement in dysplastic pedicles in adolescent idiopathic scoliosis using the pedicle expansion technique with CT-based navigation.

BACKGROUND: This study aimed to study the accuracy of pedicle screw (PS) insertion into dysplastic pedicles in adolescent idiopathic scoliosis (AIS) comparing cannulated screw using the pedicle expansion technique (PET) versus conventional technique. METHODS: Forty-two AIS patients with 766 PSs were evaluated. In total, 236 screws were inserted into dysplastic pedicles: 138 and 98 screws were inserted using the PET (PET group) and standard technique (conventional group), respectively. Both methods used CT-based navigation to determine the insertion point. In the PET, a rigid ball tip feeler was tapped with a mallet to create an insertion route, a guide wire was passed through the tap, the pedicle was enlarged, and then a cannulated PS with a diameter of 4.35 mm was inserted. Postoperative CT was used to compare the accuracy of PS insertion. RESULTS: In total, 23/236 (9.7%) perforations occurred. Regarding overall perforation, there were six (4.3%) and 17 (17.3%) cases in the PET and conventional group, respectively (P = 0.008). In terms of medial perforation, the PET group (n = 2, 1.4%) was significantly better than the conventional group (n = 7, 7.1%) (P = 0.021). In terms of lateral perforation, the PET group (n = 4, 2.9%) was significantly better than conventional group (n = 10, 10.2%) (P = 0.030). Only grade 1 perforation had occurred in the PET group, whereas grades 2 and 3 perforation occurred in the conventional group. CONCLUSION: Use of the PET with CT-based navigation significantly increased the accuracy and safety of PS insertion in dysplastic pedicles in AIS.

Survival rates of different bearing surfaces with the same model of stem in total hip arthroplasty: predictive factors for revision surgery.

INTRODUCTION: Few studies have examined the survival rates of total hip arthroplasty (THA) with the same femoral stem, and the predictive factors leading to the revision of stemmed metal-on-metal (MoM) THA remain unknown. We determined the long-term survival rate of stemmed MoM THA compared with that of metal-on-polyethylene (MoP) bearing THA, the effect of head size and cup placement angle on revision rate, and predictors of revision. MATERIALS AND METHODS: A total of 130 hips in 110 patients who underwent primary THA by the same surgeon were included. M2a-RingLoc with a metal-on-polyethylene bearing (group P, 53 hips), M2a-Taper with MoM bearing (group T, 44 hips), and M2a-Magnum with MoM bearing (group M, 33 hips) were used. The mean age at surgery was 63.1 ± 9.5 years, and the mean postoperative follow-up duration was 133.7 ± 39.1 months. Whole blood metal ion concentrations were measured preoperatively and postoperatively, and magnetic resonance imaging was performed to identify aseptic local tissue reactions (ALTRs). Kaplan-Meier survivorship analysis and multiple logistic regression analysis were performed. RESULTS: The THA survival rate up to the maximum postoperative follow-up period was 96.2% at 173 months, 46.6% at 179 months, and 47.8% at 145 months in groups P, T, and M, respectively, with revision as the endpoint. The stemmed MoM THA recorded a very low survival rate (p < 0.001). The ALTR rates were 70.5% and 63.6% in groups T and M, respectively. The risk factor for revision was the use of MoM bearing, and there was no difference in the results based on the head size in group M. Cobalt levels continued to increase postoperatively, although they were not accurate predictors of revision. CONCLUSIONS: Stemmed MoM THA has a very low survival rate and should be used with caution. It is important to monitor the patient's symptoms and perform appropriate imaging to ensure timely revision.

Analysis of the risk factors for increasing cervical sagittal vertical axis after cervical laminoplasty for cervical spondylotic myelopathy.

INTRODUCTION: The cervical sagittal vertical axis (cSVA) as another aspect of cervical alignment been recognized as one of the important factors affecting the pain and disability outcomes of cervical spine surgery. The purpose of the present study was to analyze the risk factors for increasing cSVA after cervical laminoplasty for cervical spondylotic myelopathy (CSM). MATERIALS AND METHODS: This retrospective study included 110 consecutive patients (68 males and 42 females, average age 72.6 years) who underwent laminoplasty for CSM between January 2007 and June 2018. We recorded the operative time, blood loss, Japanese Orthopaedic Association (JOA) score and the recovery rate. Radiological measurements were performed to analyze the following parameters: pre- and 1-year postoperative McGregor's slope (McGS), occiput to C2 Cobb angle (O-C2 angle), C2-C7 Cobb angle (C2-7 angle), T1-slope (T1S), C2-7 SVA (cSVA) and calculated the change (Δ). Patients were divided into two groups according to whether ΔcSVA was positive or negative. We also used Spearman's correlation coefficient and multiple regression analysis. RESULTS: ΔC2-7 angle, ΔT1S-preoperative C2-7 angle, ΔO-C2 angle were different between the two groups significantly. Correlation analysis between the ΔcSVA and the various sagittal parameters showed some independent explanatory factors including the ΔC2-7 angle (r = - 0.25, p = 0.010), T1S-preoperative C2-7 angle (r = - 0.28, p = 0.004), postoperative O-C2 angle (r = 0.26, p = 0.007), ΔO-C2 angle (r = 0.37, p = 0.001). Multiple regression analysis revealed that ΔcSVA was associated with the T1S-preoperative C2-7 angle (ß = - 0.25, p = 0.034) and ΔO-C2 angle (ß = 0.32, p = 0.001). CONCLUSIONS: The imbalance between T1S and preoperative C2-7 angle influences the change of cSVA after cervical laminoplasty. If cSVA increases postoperatively, the O-C2 angle increases to compensate and maintain the horizontal gaze.

Microvascular system of hip joint constituents with special reference to ultrastructural findings and early arteriosclerosis.

This study aimed to examine the ultrastructure of the arteries of the synovium, acetabular labrum, and ligamentum teres of the hip joint using light, scanning electron, and transmission electron microscopes to identify features of early arteriosclerosis. Tissues collected from three patients (under 40 years of age) with osteonecrosis of the femoral head were immersed in 8 N HCl at 60 °C for 20 min to digest collagen fibers for scanning electron microscopy. Tortuous arterioles and arteries were noted in the joint components, including the synovium, acetabular labrum, and ligamentum teres. The ultrastructure of the arterioles appeared normal; however, intimal thickening was found in most arteries. The thickened intima had abundant elastic fibers and many smooth muscle cells (which were of a synthetic phenotype because they had a few actin filaments and well-developed rough endoplasmic reticulum). This study illustrates that arteriosclerotic changes are present in tortuous arteries in the synovium, acetabular labrum, and ligamentum teres of the hip joint even from a relatively young age and suggests that meandering blood vessels may be the preferred foci of arteriosclerosis.

Development of a High-Throughput Quantification Method for Pazopanib Using Ultra-Performance Liquid Chromatography-Tandem Mass Spectrometry and Its Clinical Application in Patients With Soft Tissue Tumors.

BACKGROUND: Pazopanib is widely used to treat renal cell carcinomas and soft tissue tumors in Japan. Pazopanib has significant therapeutic efficacy but it is associated with frequent severe adverse effects. Therapeutic drug monitoring (TDM) may help to prevent adverse effects. A more convenient and rapid pazopanib assay is desirable for the application of TDM in clinical settings. In this study, the authors developed a high-throughput method for quantifying pazopanib in human plasma using ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). METHODS: After a simple solid-phase extraction step using a 96-well plate, pazopanib was analyzed by UHPLC-MS/MS in the positive electrospray ionization mode. RESULTS: The novel method fulfilled the requirements of the US Food and Drug Administration and the European Medicines Agency guidelines for assay validation, and the lower limit of quantification was 0.5 mcg/mL. The calibration curves were linear over the concentration range of 0.5-100 mcg/mL. The average recovery rate was 102.0% ± 3.9% (mean ± SD). The precision was below 5.0%, and the accuracy was within 12.0% for all quality control levels. Matrix effect varied between 90.9% and 97.1%. This assay was successfully applied to TDM of pazopanib trough concentrations in 3 patients treated with the drug for soft tissue tumors. CONCLUSIONS: The authors succeeded in developing a novel high-throughput UHPLC-MS/MS method for quantifying pazopanib in human plasma. This method can be applied to TDM of patients receiving pazopanib in clinical settings.

Primary clear cell sarcoma of the femur: a unique case with RT-PCR and direct sequencing confirmation of EWSR1/ATF1 fusion gene.

BACKGROUND: It is very rare for clear cell sarcomas (CCS) to arise in the bone. During diagnosis, it is important to distinguish primary CCS of bone from bone metastasis of melanoma because this difference fundamentally changes the therapeutic options. Recently, characteristic fusion genes of CCS have been detected using reverse transcription polymerase chain reaction (RT-PCR) or direct sequencing which allowed to distinguish CCS from melanoma. However, there was no study applying these analyses with positive results. In this case, we describe the use of fusion gene analysis to diagnose a primary CCS of the bone. CASE PRESENTATION: A 36-year-old male presented with a four-months history of left knee pain. Magnetic resonance imaging showed a lesion in the left femoral medial epicondyle. Histological examination of the biopsy specimen revealed proliferating oval or rounded cells. These cells had clear cytoplasm arranged in fascicles or compact nests with frequent deposits of brown pigment. Furthermore, immunohistochemistry analysis revealed that tumor cells were positive for S-100 protein, HMB-45, Melan-A, and SOX10. It stained negative for CD34 and BRAF v600e. Conclusively, detection of the EWSR1/ATF1 fusion gene using RT-PCR and direct sequencing confirmed that the lesion was a primary CCS of the bone. Wide-margin resection and reconstruction with a tumor endoprosthesis were performed. CONCLUSIONS: Herein, we diagnosed a rare case of primary CCS of the bone by detecting EWSR1/ATF1 fusion gene using RT-PCR and direct sequencing. Since fluorescence-in situ hybridization (FISH) and RT-PCR could show false positive by mainly due to technical problems, it is better to perform direct sequencing to confidently diagnose the tumor as a primary CCS especially at very rare site such as bone.

A meta-analytic evaluation of the correlation between event-free survival and overall survival in randomized controlled trials of newly diagnosed Ewing sarcoma.

BACKGROUND: In randomized controlled trials (RCTs) of adjuvant treatment for malignant tumors, event-free survival (EFS) is considered the most acceptable surrogate for overall survival (OS). However, even though EFS has repeatedly been selected as a primary endpoint in RCTs of Ewing sarcoma (ES), the surrogacy of EFS for OS has not been investigated. This study aimed to evaluate the correlation between EFS and OS in RCTs of chemotherapy for newly diagnosed ES using a meta-analytic approach. METHODS: We identified seven RCTs of newly diagnosed ES through a systematic review, and a meta-analysis was performed to evaluate the efficacy and adverse events associated with chemotherapy for previously untreated ES. The correlation between EFS and OS was investigated using weighted linear regression analysis and Spearman rank correlation coefficients (ρ). The strength of the correlation was evaluated using the coefficient of determination (R2). RESULTS: A total of 3612 patients were randomly assigned to 17 treatment arms in the eligible RCTs. The meta-analysis revealed that the hazard ratios for OS and EFS showed significantly better results in the experimental treatment groups with increasing toxicities. The correlation between the hazard ratios for EFS and OS was good (R2 = 0.747, ρ = 0.683), and the correlation tended to be more favorable in cases of localized ES (R2 = 0.818, ρ = 0.929). CONCLUSIONS: Overall, the trial-level correlation between EFS and OS was good for newly diagnosed ES and was very good in cases of localized disease. EFS may be a useful endpoint in RCTs of ES chemotherapy, and it is worth verifying using individual patient data.

Fibrinogen level on admission is a predictive marker of the need for massive blood transfusion after pelvic fracture.

OBJECTIVE: This study aimed to evaluate the usefulness of coagulation biomarkers as predictors of the need for massive transfusion (MT) in patients with pelvic fractures. METHODS: Patients who were treated for pelvic fractures in our hospital were divided into 2 groups: MT and non-MT. MT was defined as the transfusion of packed red blood cells (PRBCs) ≧10 units caused by bleeding within 24 h after admission. We compared variables between two groups, including vital signs, the scoring system and blood sample test. Additionally, we performed a multiple logistic regression analysis and a receiver operating characteristic curve analysis to reveal which value was the most useful predictive marker for MT in patients with pelvic fracture. RESULTS: There were 22 patients in the MT group and 78 patients in the non-MT group. Patients in the MT group had significantly higher ISS than did those in the non-MT group. In contrast, the patients in the MT group had significantly lower RTS, TRISS Ps, sBP, Hb, lactate, BE, and Fbg levels. Lower sBP and Fbg levels were independent predictors for MT. The optimal cut-off values for sBP and Fbg levels were ≦109 mmHg and 193.0 mg/dL, respectively. CONCLUSIONS: The results of the study indicated that Fbg levels on admission can be an independent predictor of MT in patients with pelvic fractures. The optimal cut-off value of Fbg for MT prediction in this study was 193.0 mg/dL.

Reference values for the locomotive syndrome risk test quantifying mobility of 8681 adults aged 20-89 years: A cross-sectional nationwide study in Japan.

BACKGROUND: The locomotive syndrome risk test was developed to quantify the decrease in mobility among adults, which could eventually lead to disability. The purpose of this study was to establish reference values for the locomotive syndrome risk test for adults and investigate the influence of age and sex. METHODS: We analyzed 8681 independent community dwellers (3607 men, 5074 women). Data pertaining to locomotive syndrome risk test (the two-step test, the stand-up test, and the 25-question geriatric locomotive function scale [GLFS-25]) scores were collected from seven administrative areas of Japan. RESULTS: The reference values of the three test scores were generated and all three test scores gradually decreased among young-to-middle-aged individuals and rapidly decreased in individuals aged over 60 years. The stand-up test score began decreasing significantly from the age of 30 years. The trajectories of decrease in the two-step test score with age was slightly different between men and women especially among the middle-aged individuals. The two physical test scores were more sensitive to aging than the self-reported test score. CONCLUSION: The reference values generated in this study could be employed to determine whether an individual has mobility comparable to independent community dwellers of the same age and sex.

Analysis of computed tomography-based infra-acetabular morphometry to assess the feasibility of infra-acetabular screws.

INTRODUCTION: The number of pelvic fractures based on osteoporosis has been increasing. The infra-acetabular screw (IAS), which connected both osseous columns, is a safe method of screw placement going through the infra-acetabular corridor (IAC). However, the specifics of the anatomy of IAC have been far from completely understood, especially in the Asian population. The purpose of our study was to reveal the details of the IAC using computed tomography (CT) data. MATERIALS AND METHODS: Traumatized in-patients having pelvic CT scans from 2014 to 2016 were enrolled. Pediatric and adult patients with pelvic fractures and hip prostheses were excluded. The male/female ratio and distribution of patients' age were equalized manually; 40 male and 40 female patients were included. The IAC was measured on the plane of the inlet view (25° caudal) in multi-planar reconstructed CT images. MEASUREMENTS: infra-acetabular diameter (IAD), anterior-posterior length of the IAC (APL), length from the starting point of the IAC to the medial edge of the pelvis (LME), length from the starting point of the IAC to the top of the pubic symphysis (LPS), and tilting on inlet plate (TIP). RESULTS: Age was 59 ± 22 (mean ± SD). Height was 159 ± 11 cm, and body mass index (BMI) was 22.9 ± 4.1. IAD, APL, LME, LPS, and TIP was 4.0 ± 1.3 mm, 89.5 ± 7.1 mm, 8.7 ± 3.6 mm, 57.8 ± 4.8 mm, and 4.7 ± 5.2°, respectively. Over 20% of corridors (35 of 160) were not feasible for IAS placement, because of inadequate width (less than 3.0 mm). Nine corridors (5.6%) had curvature in IAC, which meant technically demanding to insert IAS. There was no difference in IAD between male and female patients, while APL, LME, LPS, and TIP had sex-related differences. CONCLUSIONS: Surgeons should pay attention to the fact that over 20% of IACs are not feasible for infra-acetabular screw placement even with the perfect reduction of fragments when treating acetabular fractures.

Histological evaluation of the acetabular labrum after bipolar hip hemiarthroplasty: a case report.

We report herein the microstructure of the acetabular labrum obtained from a patient with stem loosening but without bipolar cup migration who had undergone hemiarthroplasty for femoral neck fracture 18 years ago. We used light and scanning electron microscopy to investigate the influence of bipolar cup on acetabular labrum in vivo. Deparaffinized blocks were treated with 2 N NaOH to digest the cell matrix, allowing the collagen fibers, constituting the acetabular labrum, to be observed under scanning electron microscopy. Although chondrocyte atrophy was seen, the basic structure was not different from the normal tissue images of the elderly. However, in the deep part of the acetabular labrum, there was an area that was not stained with Alcian blue observed with light microscopy, and there was an amorphous tissue without type II collagen fibrils observed with scanning electron microscopy. These findings proved that the acetabular labrum has partially degenerated over the long term after bipolar hemiarthroplasty, and that the acetabular labrum can survive in vivo in such a condition. Given that hemiarthroplasty has a possibility to preserve the face-to-face tissue in the long term in vivo, it may be one of the valuable options for modern or future joint reconstruction surgery.

Three-dimensional architecture of the acetabular labrum in the human hip joint.

The acetabular labrum is frequently damaged with advancing age. As collagen fibers are the main sources of strength, knowledge of their ultrastructure is important to determine the cause of age-induced changes. We aimed to investigate the ultrastructure of collagen fibers constituting the acetabular labrum using scanning electron microscopy (SEM). Acetabular labrum samples obtained during total hip arthroplasty were studied. The samples were specially prepared to observe the steric construction of collagen fibrils constituting the acetabular labrum under light microscopy followed by SEM. The acetabular labrum was mostly composed of cartilage tissue, consisting of chondrocytes and collagen type II, with a layer of collagen type I. In adults, chondrocytes with a rich cytoplasm were surrounded by a dense network of fine type II collagen fibrils, and small bundles of type I collagen fibrils were interposed in the cartilage layer. In elderly individuals, the chondrocytes atrophied and both type I and II collagen fibrils were sparse. We suggest that cartilage has three to five layers, consisting of type I and type II collagen fibrils with a solid cartilage substrate. In elderly individuals, the density of chondrocytes decreases and the cellular shape and architecture of collagen fibrils also changes.

Ultrastructure and three-dimensional architecture of the anterior cruciate ligament in the knee joints of young and old monkeys.

We examined the ultrastructure of the anterior cruciate ligament and assessed age-related changes by comparing the ligaments of young and old monkeys. Ultrathin sections of the anterior cruciate ligament were observed by transmission electron microscopy. The three-dimensional architecture of collagen fibers in the ligament was examined by scanning electron microscopy after tissue specimens were treated with 2 N NaOH to digest the extracellular matrix. At the surface layer of the cruciate ligament in young monkeys, fusiform-shaped fibroblasts actively produced collagen fibrils. The ligament consisted of parallel bundles of dense collagen fibrils of approximately 200 nm in diameter. Collagen fibrils appeared to run linearly. Ligament fibrocytes in the deep layer had a stellate form. Ligament fibrocytes decreased in number and showed marked atrophy in old age. Collagen fibrils had a looser configuration in older monkeys. Despite atrophy of fibroblasts in the deep layer of the anterior cruciate ligament, the area with atrophic fibroblasts in the ligament expands with age, which can likely cause deterioration of and a reduction in collagen fibers. This information can be applied in studies on the cause of the low repair ability of and aging-related changes in the anterior cruciate ligament in humans.

Cervical alignment after single-level anterior cervical corpectomy and fusion using autologous bone graft without spinal instrumentation for cervical pyogenic spondylitis.

BACKGROUND: Subsidence in anterior cervical corpectomy and fusion (ACCF) for cervical degenerative disease (CDD) are constantly observed during the postoperative course. Although kyphotic change of cervical alignment occurred frequently in cervical pyogenic spondylitis (CPS) postoperatively, studies on the postoperative change in segmental angle for CPS are limited. This study aimed to analyze cervical alignment after single-level ACCF using autologous bone graft without spinal instrumentation for CPS compared with that for CDD. METHODS: Six patients underwent single-level ACCF using autologous bone graft without spinal instrumentation for CPS. The control group included 18 age-matched patients who underwent single-level ACCF using autologous bone graft for CDD without spinal instrumentation for the same duration. Cervical and lateral plain radiographs and computed tomography scans were taken. The Frankel classification was used to assess the neurological status preoperatively, postoperatively, and at 2-year follow-up for CPS. RESULTS: At 2-year follow-up, the average segmental angle at the fusion level was - 12.2° ± 6.9° for CPS and - 5.2° ± 7.6° for CDD (p = 0.04). Changes in segmental angle at the fusion level were - 7.2 ± 9.0° for CPS and - 1.1° ± 7.1° for CDD (p = 0.02). At 2-year follow-up, the average anterior segmental fusion height was 23.4 ± 1.7 mm for CPS and 29.1 ± 5.1 mm for CDD (p < 0.001). At 2-year follow-up, bone fusion in the CPS group was classified as grade 5 (complete fusion) in 4 patients (66.7%) and grade 4 (probable fusion) in 2 (33.3%). In the CDD group, it was grade 5 in 13 patients (72.2%) and grade 4 in 5 patients (27.8%). Overall, both groups achieved 100% bone fusion rate. The Frankel classification in all CPS cases improved or leveled off. CONCLUSION: Progression of segmental kyphosis angle and subsidence of graft bone were observed postoperatively on all CPS cases. However, the neurological recovery and bone union were satisfactory.

Surrogacy of intermediate endpoints for overall survival in randomized controlled trials of first-line treatment for advanced soft tissue sarcoma in the pre- and post-pazopanib era: a meta-analytic evaluation.

BACKGROUND: Overall survival is the true endpoint for most randomized controlled trials (RCTs) of malignant tumors, whereas progression-free survival (PFS) is considered the most reliable surrogate endpoint for overall survival (OS). The present study aimed to evaluate the correlation between surrogate endpoints and OS in randomized trials of first-line chemotherapy with doxorubicin (DOX), the standard treatment for advanced and metastatic soft tissue sarcomas (ASTS), using a meta-analytic approach. METHODS: In a systematic review, we identified RCTs of first-line chemotherapy for ASTS that compared single-agent doxorubicin (DOX) with other chemotherapy regimens, and were published in English during January 1974-December 2017. A meta-analysis was performed to evaluate the efficacy of first-line treatments for ASTS. Surrogacy of the intermediate endpoints for OS was investigated using weighted linear regression analysis. Correlation strength was examined using the coefficient of determination (R2). RESULTS: Twenty-seven randomized trials, comprising 6156 patients (3371 patients in the experimental arm and 2785 patients in the DOX arm) were identified. The hazard ratios for OS and PFS showed that the efficacy of treatment for ASTS was not significantly different between standard DOX and experimental treatments. The median OS was significantly prolonged in RCTs published after 2012 when pazopanib was approved for treating ASTS. The median PFS, however, did not differ significantly. The correlation between PFS and OS was moderate (R2 = 0.557), but better than that between OS and 3-month PFS, 6-month PFS, and response rate (R2 = 0.200, 0.073, and 0.278, respectively). The correlation between PFS and OS tended to be more favorable in RCTs published after 2012 (R2 = 0.586 and 0.459, respectively). CONCLUSIONS: The trial-level correlation between PFS and OS was only modest; it tended to be better in RCTs published after 2012. While the effective lines of chemotherapy and the introduction of new drugs prolonged OS but not PFS, PFS is a better surrogate than other intermediate endpoints in the first-line ASTS trials even in the post-pazopanib era. Although this does not negate the need for more reliable surrogate endpoints for OS.

MicroRNA-181c prevents apoptosis by targeting of FAS receptor in Ewing's sarcoma cells.

BACKGROUND: MicroRNAs (miRNAs) are endogenous, small non-coding RNAs that play important roles in multiple biological processes. Here, we show that miRNAs play an important function in the down-regulation of FAS expression in Ewing's sarcoma (ES) cells. METHODS: To identify and characterize possible oncogenic factors in ES, we employed a microarray-based approach to profile the changes in the expression of miRNAs and their target mRNAs in five ES cell lines and human mesenchymal stem cells (hMSCs). RESULTS: MiRNA, miR-181c, was significantly up-regulated, whereas FAS receptor expression was significantly down-regulated in all tested ES cells compared with hMSCs. Introducing anti-miR-181c into ES cell lines resulted in an increased expression of FAS2. Additionally, anti-miR-181c prohibited cell growth and cell cycle progression in ES cells. Anti-miR-181c also promoted apoptosis in ES cells. Furthermore, the down-regulation of miR-181c in ES cells significantly suppressed tumor growth in vivo. CONCLUSIONS: These results suggest that unregulated expression of miR-181c could contribute to ES by targeting FAS. Reduction of miR181c increased expression of FAS. This proves that retardation of cell cycle progression removes apoptosis resistance, thereby repressing the growth of Ewing sarcoma. Since FAS signaling is involved in regulation of apoptosis and tumor proliferation, our findings might contribute to new therapeutic targets for ES.

Interaction between human osteosarcoma and mesenchymal stem cells via an interleukin-8 signaling loop in the tumor microenvironment.

BACKGROUND: Osteosarcoma (OS) is the representative primary malignant bone tumor with the highest incidence. It is known that malignant phenotypes of OS, such as proliferation, invasion, and metastasis, are significantly influenced not only by characteristics of the tumor itself, but also by the surrounding microenvironment. In other words, OS is considered to utilize cells in the vicinity of the tumor by changing the characteristics of these cells. Direct intercellular contact is believed to be important for this phenomenon. In the present study, we hypothesized that an interaction mediated by a humoral factor, requiring no cellular contact, might play a significant role in the progression of OS. METHODS: We developed a new co-culture model, using OS cells and mesenchymal stem cells (MSCs) without cellular contact, and found that both cell types expressed IL-8 at a high level, and FAK in OS cells was phosphorylated leading to an increase in the metastatic potential of the tumor in the co-culture condition. RESULTS: It was revealed that OS cells formed a loop of signal cross-talk in which they released IL-8 as a paracrine factor, stimulating MSCs to express IL-8, and received IL-8 released by MSCs to accelerate IL-8 expression in OS cells. Administration of anti-IL-8 antibody resulted in the inhibition of FAK expression, its downstream signaling, and the invasive potential of the OS cells, resulting in decrease in metastatic lesions. CONCLUSION: The present study might lead not only to the clarification of a new molecular mechanism of invasion and metastasis of OS, but also to the development of a new therapeutic strategy of blocking IL-8 in OS.

The mechanical effects of cup inclination and anteversion angle on the bearing surface.

BACKGROUND: Regarding the cup setting in total hip arthroplasty, range of motion and prevention of dislocation are important. From past reports, the wear of the bearing surface may affect long-term results. This study evaluated the stress applied to the bearing surface by the combined use of the three-dimensional rigid spring model and the finite-element analysis. METHODS: For contact pressure distribution of the bearing surface, interference analysis was performed using a three-dimensional rigid body spring model. Furthermore, stress was applied to the inner surface of the cup installed in the bone so that the same stress distribution obtained from the interference analysis was achieved. The finite-element analysis was then performed at each condition, which changed the inclination and anteversion angles of the cup to examine the relationship of maximum equivalent stress. RESULTS AND DISCUSSION: The maximum equivalent stresses on the bearing surface under the condition with fixation of an anteversion angle of 0° were 0.78, 0.85, and 1.15 MPa at inclination angles of 25°, 40°, and 55°, respectively. The stress value at 55° was approximately 1.5 times greater than that at 25°. The maximum equivalent stresses on the bearing surface under the condition with fixation of an inclination angle of 40° were 0.85, 0.9, and 1.02 MPa at anteversion angles of 0°, 15°, and 30°, respectively. The stress value at 30° was approximately 1.2 times greater than that at 0°. This study suggests that large inclination and anteversion angles may enhance the stress on the bearing surface and affect long-term results.