Targeting the chromatin structural changes of antitumor immunity.

Epigenomic imbalance drives abnormal transcriptional processes, promoting the onset and progression of cancer. Although defective gene regulation generally affects carcinogenesis and tumor suppression networks, tumor immunogenicity and immune cells involved in antitumor responses may also be affected by epigenomic changes, which may have significant implications for the development and application of epigenetic therapy, cancer immunotherapy, and their combinations. Herein, we focus on the impact of epigenetic regulation on tumor immune cell function and the role of key abnormal epigenetic processes, DNA methylation, histone post-translational modification, and chromatin structure in tumor immunogenicity, and introduce these epigenetic research methods. We emphasize the value of small-molecule inhibitors of epigenetic modulators in enhancing antitumor immune responses and discuss the challenges of developing treatment plans that combine epigenetic therapy and immunotherapy through the complex interaction between cancer epigenetics and cancer immunology.

Limitations and modifications in the clinical application of calcium sulfate.

Calcium sulfate and calcium sulfate-based biomaterials have been widely used in non-load-bearing bone defects for hundreds of years due to their superior biocompatibility, biodegradability, and non-toxicity. However, lower compressive strength and rapid degradation rate are the main limitations in clinical applications. Excessive absorption causes a sharp increase in sulfate ion and calcium ion concentrations around the bone defect site, resulting in delayed wound healing and hypercalcemia. In addition, the space between calcium sulfate and the host bone, resulting from excessively rapid absorption, has adverse effects on bone healing or fusion techniques. This issue has been recognized and addressed. The lack of sufficient mechanical strength makes it challenging to use calcium sulfate and calcium sulfate-based biomaterials in load-bearing areas. To overcome these defects, the introduction of various inorganic additives, such as calcium carbonate, calcium phosphate, and calcium silicate, into calcium sulfate is an effective measure. Inorganic materials with different physical and chemical properties can greatly improve the properties of calcium sulfate composites. For example, the hydrolysis products of calcium carbonate are alkaline substances that can buffer the acidic environment caused by the degradation of calcium sulfate; calcium phosphate has poor degradation, which can effectively avoid the excessive absorption of calcium sulfate; and calcium silicate can promote the compressive strength and stimulate new bone formation. The purpose of this review is to review the poor properties of calcium sulfate and its complications in clinical application and to explore the effect of various inorganic additives on the physicochemical properties and biological properties of calcium sulfate.

Comparison of intraoperative blood loss and perioperative complications between preoperative embolization and nonembolization combined with spinal tumor surgeries: a systematic review and meta-analysis.

PURPOSE: The present study aimed to comparatively evaluate intraoperative blood loss (IBL) and perioperative complications between preoperative embolization (PE) and nonembolization (NE) combined with spinal tumor surgeries as well as to determine the subgroup of spinal tumor surgeries suitable for PE. METHODS: A systematic search in PubMed and EMBASE and an additional search by reference lists of the retrieved studies were undertaken by two reviewers. The mean IBL and perioperative complication rate were employed as the effect size in the general quantitative synthesis through direct calculation. Meta-analysis was performed using standardized mean difference (SMD) and weighted mean difference (WMD) of IBL and the odds ratio (OR) of complications. Heterogeneity was assessed using the I2 statistic. RESULTS: The reviewers selected 17 published studies for the general quantitative synthesis and meta-analyses. The mean IBL of spinal tumor surgeries was 1786.3 mL in the NE group and 1716.4 mL in the PE group. The mean IBL between the two groups was similar. The pooled WMD and SMD of IBL in spinal tumor surgeries was 324.15 mL (95% CI 89.50-1640.9, p = 0.007) and 0.398 (95% CI 0.114-0.682, p = 0.006), respectively. The reduction of the PE group compared with the NE group for the rates of major complications and major hemorrhagic complications were 7.80% and 5.71%, respectively. The risk of PE-related complications in the PE group was only 1.53% more than in the PE group. The pooled OR of major complications in spinal tumor surgeries was 1.426 (95% CI 0.760-2.674; p = 0.269). CONCLUSIONS: PE may be suitable for spinal tumor surgeries and some subgroups. From the perspective of complications, PE may also be a feasible option for spinal tumor surgeries.

Quantile regression-based prediction of intraoperative blood loss in patients with spinal metastases: model development and validation.

PURPOSE: To develop and evaluate a quantile regression-based blood loss prediction model for open surgery of spinal metastases. METHODS: This was a multicenter retrospective cohort study. Over a 11-year period, patients underwent open surgery for spinal metastases at 6 different institutions were reviewed. The outcome measure is intraoperative blood loss (in mL). The effects of baseline, histology of primary tumor and surgical procedure on blood loss were evaluated by univariate and multivariate analysis to determine the predictors. Multivariate ordinary least squares (OLS) regression and 0.75 quantile regression were used to establish two prediction models. The performance of the two models was evaluated in the training set and the test set, respectively. RESULTS: 528 patients were included in this study. Mean age was 57.6 ± 11.2 years, with a range of 20-86 years. Mean blood loss was 1280.1 ± 1181.6 mL, with a range of 10 ~ 10,000 mL. Body mass index (BMI), tumor vascularization, surgical site, surgical extent, total en bloc spondylectomy and microwave ablation use were significant predictors of intraoperative blood loss. Hypervascular tumor, higher BMI, and broader surgical extent were related with massive blood loss. Microwave ablation is more beneficial in surgery with substantial blood loss. Compared to the OLS regression model, the 0.75 quantile regression model may decrease blood loss underestimate. CONCLUSION: In this study, we developed and evaluated a prediction model for blood loss in open surgery for spinal metastases based on 0.75 quantile regression, which may minimize blood loss underestimate.

Melatonin activates mitochondrial unfolded protein response to preserve osteogenic potential of senescent BMSCs via upregulating PDI-6.

Bone marrow stromal cells (BMSCs) possess the capability to differentiate into osteogenic or adipogenic lineages. With aging, BMSCs suffer from mitochondrial dysfunction and undergo senescence, favoring adipogenesis at the expense of osteoblastogenesis. It leads to decreased bone formation and contributes to senile osteoporosis (SOP). In the current study, RNA-seq analysis unveiled that senescent BMSCs from mice exhibited a significant suppression in the expression of the protein disulfide isomerase PDI-6, an important regulator of mitochondrial unfolded protein response (UPRmt) as well as maintenance of mitochondrial homeostasis. Overexpression of PDI-6 in senescent BMSCs partially rescued mitochondrial function and enhanced osteogenic differentiation. In contrast, osteoblastogenesis of BMSCs remarkably deteriorated under the condition of PDI-6 silencing. Furthermore, melatonin, an endocrine hormone, effectively enhanced PDI-6 expression and repaired injured mitochondria, and the effect of melatonin on PDI-6 expression was melatonin receptor dependent. We further identified that PDI-6 was a downstream effector of Wnt/ß-catenin pathway, as the inhibitor of Wnt3A/TCF signaling, Wnt-C59, inhibited PDI-6 expression. Potential ß-catenin-TCF/LEF binding sites on the promoter of PDI-6 gene were also validated by chromatin immunoprecipitation (ChIP) assay. Thus, our study suggests that PDI-6 is a pharmacological target of melatonin for the intervention of age-related osteoporosis via mitigating mitochondrial dysfunction in senescent BMSCs.

Picrosirius-Polarization Method for Collagen Fiber Detection in Tendons: A Mini-Review.

Although the structure and composition of collagen have been studied by polarized light microscopy since the early 19th century, many studies and reviews have paid little or no attention to the morphological problems of histopathological diagnosis. The morphology of collagen fibers is critical in guiding mechanical and biological properties in both normal and pathological tendons. Highlighting the organization and spatial distribution of tendon-containing collagen fibers can be very useful for visualizing a tendon's ultrastructure, biochemical and indirect mechanical properties, which benefits other researchers and clinicians. Picrosirius red (PSR) staining, relying on the birefringence of collagen fibers, is one of the best understood histochemical methods that can highly and specifically underline fibers better than other common staining techniques when combined with polarized light microscopy (PLM). Polarized light microscopy provides complementary information about collagen fibers, such as orientation, type and spatial distribution, which is important for a comprehensive assessment of collagen alteration in a tendon. Here, this brief review serves as a simplistic and important primer to research developments in which differential staining of collagen types by the Picrosirius-polarization method is increasing in diverse studies of the medical field, mainly in the assessment of the morphology, spatial distribution, and content of collagen in tendons.

A novel alginate localization molding technique for cross-sectional area measurement of human tendon to access biomechanical properties.

Accurate determination of the biomedical properties of connective tissue such as tendons and ligaments is dependent on the accurate measurement of their cross-sectional area (CSA). To date, techniques for determining cross-sectional areas of ligaments and tendons have been less than ideal due to their complex geometries and their deformations under external load. A novel non-destructive technique has been developed for determining the cross-sectional area of tendon by locating the tendon rupture, in which aqueous rapid curing alginate dental molding materials, digital photography and computerized image analysis are utilized. This technique marks tendons and alginate molds at 1 cm interval and then tendons are taken out for tensile test. Real-time video is recorded to locate the position of tendon rupture. The corresponding alginate slice is found and then analysis through computer image processing software to obtain a more accurate CSA at tendon rupture, which can be used to calculate the stress and young's modulus of tendon. The accuracy of this technique has been investigated and comparisons have been made with the alginate un-localization molding technique and ellipse estimation technique. Results show this technique can provide accurate CSA values (within 2%) and great reproducibility (coefficient of variation = 0.8%). The technique is non-destructive, can obtain morphological information of soft tissue and can detect cavities.

Cross-Sectional Area Measurement Techniques of Soft Tissue: A Literature Review.

Evaluation of the biomechanical properties of soft tissues by measuring the stress-strain relationships has been the focus of numerous investigations. The accuracy of stress depends, in part, upon the determination of the cross-sectional area (CSA). However, the complex geometry and pliability of soft tissues, especially ligaments and tendons, make it difficult to obtain accurate CSA, and the development of CSA measurement methods of soft tissues continues. Early attempts to determine the CSA of soft tissues include gravimetric method, geometric approximation technique, area micrometer method, and microtomy technique. Since 1990, a series of new methods have emerged, including medical imaging techniques (e.g. magnetic resonance imaging (MRI), computed tomography (CT), and ultrasound imaging (USI)), laser techniques (e.g. the laser micrometer method, the linear laser scanner (LLS) technique, and the laser reflection system (LRS) method), molding techniques, and three-dimensional (3D) scanning techniques.

Visceral Metastasis: A Prognostic Factor of Survival in Patients with Spinal Metastases.

OBJECTIVE: To characterize the visceral metastasis as a predictive tool for the survival of patients with spinal metastases through an exploratory meta-analysis. METHODS: Two investigators independently searched PubMed and Embase databases for eligible studies from 2000-2016. The effect estimates for the hazard ratio (HR) or risk ratio (RR) and 95% confidence interval (CI) were collected and pooled with a random- or fixed-effect model. RESULTS: In total, 18 eligible studies were retrieved with 5468 participants from nine countries. The overall pooled effect size for HR and RR was 1.50 and 3.79, respectively, which was proved to be statistically significant. In the subgroup of prostate cancer (PCa) and non-small cell lung cancer (NSCLC), statistical significance and marginal statistical significance was presented for the pooled HR (HR = 1.76, 95% CI 1.35-2.29) and (RR = 1.56, 95% CI 0.99-2.48), respectively. However, in the subgroup of thyroid cancer, breast cancer, and renal cancer, statistical significance was not achieved (HR = 1.17, 95% CI 0.75-1.83, Z = 0.70, P = 0.486). The results did not show any evidence of publication bias. CONCLUSIONS: This study demonstrated that visceral metastasis was a significant prognostic factor in patients with spinal metastases as a whole. Interestingly, the onset of visceral metastases differentially impacted the survival in different primary tumors. Therefore, the prognostic value of visceral metastasis might be related to the type of primary tumor.

Assessment of the Defatting Efficacy of Mechanical and Chemical Treatment for Allograft Cancellous Bone and Its Effects on Biomechanics Properties of Bone.

OBJECTIVE: To assess the defatting efficacy of high pressure washing and gradient alcohol and biomechanical properties of defatted bone. METHODS: Fresh cancellous bone was obtained from the femoral condyle and divided into six groups according to different defatting treatments, which were: high pressure washing for 10 s (10S group), 20 s (20S group), and 30 s (30S group), gradient alcohol immersion (Alcohol group), acetone immersion (Acetone group), and non-defatted (Fresh group). The appearance of six groups was observed, and the appearance of defatted bone and fresh bone was compared. The residual lipid content and infrared spectrum were used to compare the efficacy of defatting, the DNA content was used to compare the cell content after defatting, and the maximum stress and elastic modulus were used to compare the effects of defatting treatment on biomechanical properties. RESULTS: The fresh bone was yellow and the pores contained a lot of fat. The defatted bone was white and the porous network was clear. There was no difference in residual lipid content among the three groups with high pressure washing (1.45% ± 0.16%, 1.40% ± 0.13%, and 1.46% ± 0.11%, respectively) (P = 0.828). There was no difference in residual lipid content among the 10S, alcohol, and acetone groups (1.45% ± 0.16%, 1.28% ± 0.07%, and 1.13% ± 0.22%, respectively) (P = 0.125). Infrared spectra showed that the fat content of the five defatting groups was significantly lower than that of the fresh group. There was no difference in residual lipid content among the three groups with high pressure washing (4.53 ± 0.23 ug/mL, 4.61 ± 0.18 ug/mL, and 4.66 ± 0.25 ug/mL, respectively) (P = 0.645). There was no difference in residual lipid content among the 10S, alcohol, and acetone groups (4.53 ± 0.23 ug/mL, 4.29 ± 0.24 ug/mL, and 4.27 ± 0.29 ug/mL, respectively) (P = 0.247). The maximum stress of the bone decreased significantly with the increase of the washing time (9.95 ± 0.31 Mpa, 9.07 ± 0.45 Mpa, and 8.17 ± 0.35 Mpa, respectively) (P = 0.003). The elastic modulus of the bone decreased significantly with the increase of the washing time (116.40 ± 3.54 Mpa, 106.10 ± 5.29 Mpa, and 95.63 ± 4.08 Mpa, respectively) (P = 0.003). There was no statistical difference in the maximum stress between the fresh group, the 10S group, the alcohol group, and the acetone group (10.09 ± 0.67 Mpa, 9.95 ± 0.31 Mpa, 10.11 ± 0.07 Mpa, and 10.09 ± 0.39 Mpa, respectively) (P = 0.963). There was no statistical difference in the maximum stress between the fresh group, the 10S group, the alcohol group and the acetone group (119.93 ± 4.94 Mpa, 116.40 ± 3.54 Mpa, 118.27 ± 0.85 Mpa, 118.10 ± 4.52 Mpa, respectively) (P = 0.737). CONCLUSION: The defatting efficiency was satisfactory at a time of 10 s under high pressure washing. In terms of defatting efficiency and its effect on biomechanical properties of bone, high pressure washing and gradient alcohol were similar to conventional acetone solvent extraction defatting.

Effect of Particle Size Ratios on the Physical and Chemical Properties of Surgical-Grade Calcium Sulfate Hemihydrate.

OBJECTIVES: To analyze the optimum particle size or formula ratio of surgical-grade calcium sulfate (CS) for appropriate compressive strength, setting time, and vitro degradation rate. METHODS: Three types of calcium sulfate hemihydrate (CSH) particles with diameters of 0-37.5 µm, 37.5-75 µm, and >75 µm were screened. Based on formulation ratio of different particles, this topic is divided into 10 groups by the unconstrained third-order simplex lattice mixing design scheme in formula design experiment. The optimum formulation ratio of particle diameter for compressive strength, solidification time, and degradation rate in vitro was analyzed. RESULTS: When the percentage of the particle diameter of CS with 0-37.5 µm, 37.5-75 µm and >75 µm are 55.0%, 17.4%, and 27.6% respectively, the compressive strength of the test sample is the highest, which is 14.16 MPa. When the percentage of the particle diameter of CS with 0-37.5 µm, 37.5-75 µm, and >75 µm are 0.00%, 0.00%, and 100.00% respectively, the initial setting time of the sample is the longest, which is 410.0 s. When the percentage of the particle diameter of CS with 0-37.5 µm, 37.5-75 µm, and >75 µm are 0.00%, 0.00%, and 100.00% respectively, the final setting time of the sample is the largest, and the final setting time of the sample is 460.00 s. When the percentage of the particle diameter of CS with 0-37.5 µm, 37.5-75 µm, and >75 µm are 0.00%, 0.00%, and 100.00% respectively, the degradation rate of the sample in vitro is the slowest, which is 18.8%. CONCLUSION: The morphological structure of surgical-grade CS can affect compressive strength, setting time, and in vitro degradation rate. Surgical CS should be prepared based on different uses.

Prognostic Differences in Patients with Solitary and Multiple Spinal Metastases.

OBJECTIVES: To investigate the association between the number of metastases to the spine and survival in patients with metastatic spinal cord compression (MSCC), as well as the prognosis difference between patients with solitary spinal metastasis (SSM) and multiple spinal metastases (MSM). METHODS: Three institutional databases were searched to identify all patients who had undergone spinal surgery for metastatic spinal tumors between March 2002 and June 2010. As well as age and gender, preoperative medical conditions were collected from medical records, including primary tumor, preoperative Frankel score, other bone metastases, preoperative Karnofsky performance status (KPS), number of involved vertebrae, pathological fracture metastasis site, serum albumin, sphincter dysfunction and the time of developing motor deficits before surgery. Survival data were obtained from medical records or via telephone follow-ups. Univariate and multivariate predictors of overall survival for each group were assessed using the Cox proportional hazards model. RESULTS: The median postoperative survival time was 6.0 ± 0.6 months (95% confidence interval [CI] 4.8-7.2) in patients with SSM and 7.0 ± 1.0 months (95% CI 5.1-8.9) in patients with MSM (P = 0.238). The difference in survival was not significant between groups. Furthermore, univariate analysis showed that the number of spinal metastases had no significant association with survival (P = 0.075). Primary tumor (P = 0.004) and preoperative KPS (P < 0.001) were independent prognostic factors in the whole cohort; primary tumor (P = 0.020), time of developing motor deficit (P = 0.041) and preoperative KPS (P = 0.038) were independent prognostic factors in patients with SSM; while preoperative KPS (P = 0.001) and serum album level (P < 0.001) were independent prognostic factors in patients with MSM. CONCLUSION: The number of spinal metastases has not proven to be useful in predicting the prognosis for patients with MSCC. Consequently, more aggressive operations should be considered for patients with multiple spinal metastases.

Relationship Between Visceral Metastases and Survival in Patients with Metastasis-related Spinal Cord Compression.

OBJECTIVE: To investigate whether visceral metastases have a significant impact on survival in patients with metastasis-related spinal cord compression (MSCC), and to determine the difference in prognosis between patients with and without visceral metastases. METHODS: Three institutional databases were searched to identify all patients who had undergone spinal surgery for spinal metastases between March 2002 and June 2010. Data on patient characteristics including pre- and post-operative medical conditions, were collected from medical records or by telephone follow-up. Survival data were obtained either from medical records or by searching a governmental cancer registry. RESULTS: The mean age of study patients was 59.6 ± 10.5 years (range, 18-84 years), of whom 102 were male and 67 female. The median and mean postoperative survival times were 7.0 ± 0.5 (95% CI 6.0-8.0) months and 12.6 ± 1.2 (95% CI 10.1-15.0) months, respectively, in all patients, being 5.0 ± 0.5 (95% CI 4.0-6.0) months and 10.8 ± 2.4 (95% CI 6.1-15.5) months, respectively, for patients with visceral metastases and 7.0 ± 0.8 (95% CI 5.4-8.6) months and 13.0 ± 1.4 (95%CI 10.3-15.6) months, respectively, for patients without visceral metastases (P = 0.87). These survival times did not differ significantly between groups. Multivariate Cox proportional hazard regressions showed that visceral metastases had no statistically significant association with survival (P = 0.277), whereas rate of growth of primary tumor (P = 0.003), preoperative Karnofsky performance status (KPS) (P < 0.001), change in KPS (P < 0.001), and Frankel grade (P = 0.091) were independent prognostic factors in the whole cohort (P = 0.005). Changes in KPS (P = 0.001) and major complications (P = 0.003) were significantly associated with survival in patients with visceral metastases, whereas rate of growth of primary tumor (P = 0.016), change in KPS (P = 0.001), and preoperative KPS (P < 0.001) were significantly associated with survival in patients without visceral metastases. CONCLUSIONS: Visceral metastases do not appear to predict the prognosis of patients with MSCC; thus, more aggressive surgery should be considered in patients with MSCC who have visceral metastases. Additionally, prognostic factors differ according to visceral metastases status in these patients.

Recursive Partitioning Analysis (RPA) of Prognostic Factors for Overall Survival in Patients with Spinal Metastasis: A New System for Stratified Treatment.

BACKGROUND: Accurate survival estimate is necessary when determining the most appropriate treatment modality for metastatic spinal tumor. The main purpose of this study was to identify the prognostic factors of spinal metastasis and establish a decision tree model. METHODS: A consecutive cohort of 507 patients from 3 institutional clinical centers who were treated for metastatic spinal tumor between 2005 and 2015 were retrospectively reviewed. In total, 70% of the participants were randomly selected as a "training sample." The prognostic effect of preoperative factors was evaluated using the "training sample," and a decision tree model was established. Then, the accuracy of the new model, as well as the Tokuhashi and Tomita score, was tested by the "test sample," which consisted of the remaining 30% of participants. RESULTS: A decision tree model was generated based on the significant factors with an order of descending importance on predicting the prognosis. According to the new model, patients were classified into 3 groups, mean survival times of less than 6 months, 6-12 months, and more than 12 months, who were indicated for conservative therapy/palliative operation, palliative operation, and invasive excision, respectively. The newly established model was confirmed to be of high accuracy in predicting overall survival, whereas the Tokuhashi and Tomita scores were of modest accuracy and consistency. CONCLUSIONS: A new decision tree model for prognosis prediction in spinal metastasis was established with a satisfactory accuracy and consistency. However, the Tokuhashi and Tomita systems were presented to be less correlated between the scores and actual survival.

Prognostic effect of factors involved in revised Tokuhashi score system for patients with spinal metastases: a systematic review and Meta-analysis.

BACKGROUND: Cancer patients' survival time has obviously improved, with the development of systemic treatment techniques. However, the probability of metastases to the vertebrae has also been increased which makes some adverse effects on patients' quality of life. The prediction of survival plays a key role in choosing therapeutic modality, and Tokuhashi Score was established as one of the most commonly used predictive systems for spinal metastases. Thus, this study was conducted to identify the prognostic effect of factors involved in revised Tokuhashi Score (RTS). METHODS: Two investigators independently retrieved relevant literature on platforms of PubMed, Embase and Cochrane Library. We identified eligible studies through title/abstract and full-text perusing. Data was extracted including general information of studies, participants' characteristics, therapeutic modality, overall survival and prognostic effect of factors. Hazard ratio (HR) for each factor was synthesized if available through fixed- or random-effect models as appropriate. RESULTS: A total of 63 eligible studies with 10,411 participants were identified. Overall, cases with thyroid cancer had the highest survival rate, while the ones with non-small cell lung cancer and hepatocellular carcinoma lived for the shorted survival time. Performance status, bone metastasis, number of involved vertebrae, visceral metastasis, primary tumor and neurological status were regarded as significant predictors in 71.4, 40.0, 18.2, 63.4, 73.1 and 44.7% of the involved studies respectively. Thirty-eight articles were included in meta-analysis, and prognostic effects of five factors (apart from primary tumor) were analyzed. Factors were all proved to be significant except comparisons between KPS (Karnofsky Performance Status) 10-40 VS. 50-70 and single VS. multiple spinal metastases. CONCLUSION: All factors of RTS were significant on prognosis predicting and should be considered when choosing therapeutic modality for spinal metastases. What's more, we believe that more accurate prognosis may be obtained after removal of the cut-offs for KPS 10-40 VS. 50-70 and single VS. multiple involved vertebrae.

Is Ambulatory Status a Prognostic Factor of Survival in Patients with Spinal Metastases? An Exploratory Meta-analysis.

This study was conducted to identify the influence of ambulatory status prior to treatment on survival of patients with spinal metastases. Two investigators independently retrieved relevant electronic literature in PubMed, Embase, and Cochrane Library databases, to identify eligible studies. Effect estimates for hazard risk (HR) were extracted and synthesized through fixed-effects or random-effects models as appropriate. A total of 17 eligible studies were identified, with an accumulated number of 3962 participants. HR from 14 studies regarding comparison between ambulatory versus non-ambulatory groups were pooled using a random-effects model, and statistical significance was presented for the pooled HR (HR = 1.96; 95% confidence interval [CI], 1.65-2.34). In subgroups of mixed primary tumor and lung cancer, ambulatory status was considered to be a significant prognostic factor (P < 0.05), while in the subgroup of prostate cancer it was not (HR = 1.72; 95% CI, 0.79-3.74). HR from 4 studies related to comparison between Frankel E versus Frankel C-D were pooled using a fixed-effects model, which revealed statistical significance (HR = 1.73; 95% CI, 1.27-2.36). Ambulatory status is a significant prognostic factor in patients with spinal metastases. However, in patients with primary prostate cancer, the prognostic effect of ambulatory status has not yet been confirmed to be significant.

Intercalary prosthetic reconstruction for pathologic diaphyseal humeral fractures due to metastatic tumors: outcomes and improvements.

BACKGROUND: There is a high aseptic loosening rate for intercalary prosthetic reconstruction for malignant tumors. We evaluated outcomes and complications of intercalary prosthetic reconstruction for pathologic diaphyseal humeral fractures and report the application of an extracortical plate that can prevent early loosening. METHODS: We retrospectively analyzed 9 patients who underwent intercalary prosthetic reconstruction for pathologic diaphyseal humeral fractures secondary to metastatic diseases between March 2011 and September 2017. Procedures were intercalary prosthetic reconstruction in 4 patients (group A) and an implanted intercalary prosthesis with a plate in 5 patients (group B). Operative time, blood loss, complications, and functional score were noted. RESULTS: Mean operative time for group A and B was 80 ± 14 and 94 ± 5 minutes, respectively; blood loss was 115 ± 26 and 120 ± 31 mL respectively; and follow-up was 11.5 ± 10.1 and 6.2 ± 4.4 months, respectively. At final follow-up, all patients in group A had died, and 3 patients in group B had died; mean survival was 11.5 ± 10.1 and 9.3 ± 1.2 months, respectively. The mean postoperative Musculoskeletal Tumor Society score was 24.5 ± 2.4 and 26.2 ± 0.8, respectively. The mean postoperative American Shoulder and Elbow Surgeons score was 85.5 ± 4.20 and 87 ± 2.6, respectively. There were no significant differences between the 2 groups (P > .05). There was 1 aseptic loosening and 1 radial nerve injury in group A; there were no complications in group B. CONCLUSIONS: The intercalary prosthesis yielded satisfactory outcomes in patients with pathologic diaphyseal humeral fractures, and an extracortical plate can prevent early aseptic loosening.

Prognostic Factors of Ambulatory Status for Patients with Metastatic Spinal Cord Compression: A Systematic Review and Meta-Analysis.

BACKGROUND: This study aimed to identify prognostic factors for functional outcome of metastatic spinal cord compression (MSCC). METHODS: All full texts in English regarding the prognostic factors for functional outcome of MSCC, published between January 2007 and October 2017, were identified using the electronic databases PubMed, Embase, and the Cochrane Library. An exploratory meta-analysis was also conducted when appropriate data were available. RESULTS: A total of 25 studies, involving 4897 patients, met the inclusion criteria. Overall, 69.7% of patients across all studies were able to walk postoperatively compared with 49.0% preoperatively. Moreover, 84.7% of the patients maintained ambulation after treatment. Motor function was significantly associated with ambulatory status before treatment, time of developing motor deficits, interval from symptom to surgery, and preoperative performance status. CONCLUSIONS: Ambulatory status before treatment, interval from symptom to treatment, and time of developing motor deficits can be considered as the most significant prognostic factors for posttreatment ambulatory status. Spinal metastasis should have a higher priority, and immediate intervention should be started before the development of irreversible neurologic deficits. Moreover, short-course radiotherapy might be a good option for patients with a limited life span. Consequently, the identified prognostic factors can be regarded as a preoperative assessment tool to predict neurologic outcome and guide clinical treatment for individual patients with MSCC. However, the retrospective nature of this study with low-quality evidence must be taken into account when interpreting these results, and further research is needed to identify prognostic factors.

Short-term outcomes of reconstruction subsequent to intercalary resection of femoral diaphyseal metastatic tumor with pathological fracture: Comparison between segmental allograft and intercalary prosthesis.

Reconstruction of bone defects following femoral diaphyseal tumor resection is challenging. Segmental allograft (SA) and intercalary prosthesis (IP) are the most common reconstruction methods for femoral diaphyseal metastatic tumors with pathological fracture. However, whether the complications and functional outcomes differ between SA and IP remains unclear. To compare the clinical outcomes and complications for patients treated with SA reconstruction or IP replacement for femoral shaft tumors, 34 patients who had undergone intercalary resection for metastatic tumor with pathological fracture in the femoral diaphysis were evaluated. Of these, 18 had received SA and 16 IP. There were 11 males, and 24 females, with a mean age of 64.5±11.3 years. The most common sites of primary metastases were lung (26.5%), breast (17.6%) and liver (14.7%). The visual analog scale (VAS), implant-related complications and the Musculoskeletal Tumor Society (MSTS) scores for each patient were collected. The follow-up period for patients ranged from 2 to 27 months. At the most recent follow-up, 28 patients had succumbed to mortality, with a mean survival time of 6.9±3.7 months for the IP group and 7.4±3.0 months for the SA group. Patients with IP had a significantly shorter time to full weight bearing and hospitalization time than those who received SA (P=0.003 and P=0.002, respectively). The rates of overall complications and implant-related complications were significantly lower for IP as compared with SA (18.8 vs. 66.7%, P=0.007; 12.5 vs. 55.6%, P=0.013). The reoperation rate of the SA group was higher than that of the IP group (38.9 vs. 12.5%), however the difference between the two groups was statistically insignificant (P=0.125). MSTS scores were significantly higher for the IP group as compared with the SA group at one month after surgery (IP, 26.7±1.6 vs. SA, 20.3±1.5; P<0.05), without a significant difference at the final follow-up. There were no statistically significant differences in age, sex, length of resection, follow-up time, operative time or blood loss between the two groups. In summary, IP reconstruction may provide improved early functional outcomes and fewer early complications, particularly for patients with a shorter life expectancy due to femoral metastatic tumors with pathological fracture.

Development and proposal of a scoring system for giant cell tumour of the bone around the knee.

PURPOSE: The purpose of this study was to provide the surgeons with effective and reliable guidelines for surgical decision-making by establishing a scoring system for giant cell tumour (GCTSS) based on evidence and expert opinion. METHODS: The modified Delphi technique and analytic hierarchy process were used to establish the GCTSS. The GCTSS was defined and classified based on different surgical methods using data from 207 patients collected retrospectively between October 2003 and December 2014. Finally, prospective data of 40 patients between December 2014 and October 2015 were used to analyze concordance between score categorization and experts' consensus on surgical procedure. RESULTS: A novel GCTSS included pathological fracture, cortical bone destruction, tumour size, and articular surface involved. The total scores ranged from 1 to 12 points. The strategy for each patient was decided: a total score of 1-4 suggested intralesional curettage alone for excellent post-operative function; 5-9 points indicated intralesional curettage with internal fixation for less surgery-related complications; and 10-12 points indicated prosthesis replacement for long-term local control. The κ-statistic for the predictive validity of total score was 0.611. The κ coefficient of each group represented moderate or substantial agreement, which was acceptable. The intraclass correlation coefficient for inter- and intra-observer reliability of total score was 0.831 and 0.740, respectively. CONCLUSIONS: The novel GCTSS is a comprehensive scoring system with content validity that can aid surgeons in assessing the aggressiveness or severity of giant cell tumour and might become a prognostic tool for surgical decision-making.