ZIF-8-Encapsulated Pexidartinib Delivery via Targeted Peptide-Modified M1 Macrophages Attenuates MDSC-Mediated Immunosuppression in Osteosarcoma.

Adoptive cellular therapy is a promising strategy for cancer treatment. However, the effectiveness of this therapy is limited by its intricate and immunosuppressive tumor microenvironment. In this study, a targeted therapeutic strategy for macrophage loading of drugs is presented to enhance anti-tumor efficacy of macrophages. K7M2-target peptide (KTP) is used to modify macrophages to enhance their affinity for tumors. Pexidartinib-loaded ZIF-8 nanoparticles (P@ZIF-8) are loaded into macrophages to synergistically alleviate the immunosuppressive tumor microenvironment synergistically. Thus, the M1 macrophages decorated with KTP carried P@ZIF-8 and are named P@ZIF/M1-KTP. The tumor volumes in the P@ZIF/M1-KTP group are significantly smaller than those in the other groups, indicating that P@ZIF/M1-KTP exhibited enhanced anti-tumor efficacy. Mechanistically, an increased ratio of CD4+ T cells and a decreased ratio of MDSCs in the tumor tissues after treatment with P@ZIF/M1-KTP indicated that it can alleviate the immunosuppressive tumor microenvironment. RNA-seq further confirms the enhanced immune cell function. Consequently, P@ZIF/M1-KTP has great potential as a novel adoptive cellular therapeutic strategy for tumors.

Novel positioning guiders accurately assist in situ acetabular reconstruction for patients undergoing pelvic bone tumor resection.

PURPOSE: Acetabular reconstruction in situ after extensive pelvic resection is technically challenging. The aim of this study was to investigate the feasibility of positioning guiders for acetabular reconstruction following pelvic tumor resection and the clinical benefit brought by the approach. METHODS: The study included patients who underwent acetabular reconstruction following periacetabular tumor resection using a modular hemipelvic prosthesis. In the guider-assisted group (n = 14), guiders were designed and applied to assist acetabular reconstruction. In the traditional operation group (n = 18), the patients underwent the same surgery but without the guiders. The displacement of the hip rotation center before and after surgery was calculated. The complications and the Musculoskeletal Tumor Society-93 scores were documented. RESULTS: The overall displacement of the hip rotation center was significantly reduced in the guider-assisted group compared with the traditional operation group (13.83 ± 4.06 vs. 22.95 ± 9.18 mm in P = 0.000, 95%CI 3.90-12.96), especially in the anteroposterior axis (3.77 ± 3.03 versus 13.51 ± 9.43 mm in P = 0.000, 95%CI 3.45-13.09). Guider-assisted acetabular reconstruction reduced the risk of prosthesis dislocation compared with the traditional operation (dislocation risks: 1/14, 7.1% vs. 4/18, 22.2%). CONCLUSION: Positioning guiders can effectively and conveniently help place the modular hemipelvic prosthesis at the native position, which might potentially reduce the risk of prosthesis dislocation. LEVEL OF EVIDENCE: Therapeutic level III.

Human γδ T cells induce CD8+ T cell antitumor responses via antigen-presenting effect through HSP90-MyD88-mediated activation of JNK.

Human Vγ9Vδ2 T cells have attracted considerable attention as novel alternative antigen-presenting cells (APCs) with the potential to replace dendritic cells in antitumor immunotherapy owing to their high proliferative capacity and low cost. However, the utility of γδ T cells as APCs to induce CD8+ T cell-mediated antitumor immune response, as well as the mechanism by which they perform APC functions, remains unexplored. In this study, we found that activated Vγ9Vδ2 T cells were capable of inducing robust CD8+ T cell responses in osteosarcoma cells. Activated γδ T cells also effectively suppressed osteosarcoma growth by priming CD8+ T cells in xenograft animal models. Mechanistically, we further revealed that activated γδ T cells exhibited increased HSP90 production, which fed back to upregulate MyD88, followed by JNK activation and a subsequent improvement in CCL5 secretion, leading to enhanced CD8+ T cell cross-priming. Thus, our study suggests that Vγ9Vδ2 T cells represent a promising alternative APC for the development of γδ T cell-based tumor immunotherapy.

Vascular Derived ECM Improves Therapeutic Index of BMP-2 and Drives Vascularized Bone Regeneration.

Vascularized osteogenesis is essential for successful bone regeneration, yet its realization during large size bone defect healing remains challenging due to the difficulty to couple multiple biological processes. Herein, harnessing the intrinsic angiogenic potential of vascular derived extracellular matrix (vECM) and its specific affinity to growth factors, a vECM/GelMA based hybrid hydrogel delivery system is constructed to achieve optimized bone morphogenetic protein-2 (BMP-2) therapeutic index and provide intrinsic angiogenic induction during bone healing. The incorporation of vECM not only effectively regulates BMP-2 kinetics to match the bone healing timeframe, but also promotes angiogenesis both in vitro and in vivo. In vivo results also show that vECM-mediated BMP-2 release remarkably enhances vascularized bone formation for critical size bone defects. In particular, blood vessel ingrowth stained with CD31 marker in the defect area is substantially encouraged over the course of healing, suggesting incorporation of vECM served roles in both angiogenesis and osteogenesis. Thus, the authors' study exemplifies that affinity of growth factor towards ECM may be a promising strategy to be leveraged to develop sophisticated delivery systems endowed with desirable properties for regenerative medicine applications.

Remotely Temporal Scheduled Macrophage Phenotypic Transition Enables Optimized Immunomodulatory Bone Regeneration.

Precise timing of macrophage polarization plays a pivotal role in immunomodulation of tissue regeneration, yet most studies mainly focus on M2 macrophages for their anti-inflammatory and regenerative effects while the essential proinflammatory role of the M1 phenotype on the early inflammation stage is largely underestimated. Herein, a superparamagnetic hydrogel capable of timely controlling macrophage polarization is constructed by grafting superparamagnetic nanoparticles on collagen nanofibers. The magnetic responsive hydrogel network enables efficient polarization of encapsulated macrophage to the M2 phenotype through the podosome/Rho/ROCK mechanical pathway in response to static magnetic field (MF) as needed. Taking advantage of remote accessibility of magnetic field together with the superparamagnetic hydrogels, a temporal engineered M1 to M2 transition course preserving the essential role of M1 at the early stage of tissue healing, as well as enhancing the prohealing effect of M2 at the middle/late stages is established via delayed MF switch. Such precise timing of macrophage polarization matching the regenerative process of injured tissue eventually leads to optimized immunomodulatory bone healing in vivo. Overall, this study offers a remotely time-scheduled approach for macrophage polarization, which enables precise manipulation of inflammation progression during tissue healing.

Tumor Customized 2D Supramolecular Nanodiscs for Ultralong Tumor Retention and Precise Photothermal Therapy of Highly Heterogeneous Cancers.

Target therapy for highly heterogeneous cancers represents a major clinical challenge due to the lack of recurrent therapeutic targets identified in these tumors. Herein, the authors report a tumor-customized targeting photothermal therapy (PTT) strategy for highly heterogeneous cancers, by which 2D supramolecular self-assembled nanodiscs are modified with tumor-specific binding peptides identified by phage display techniques. Taking osteosarcoma (OS) as a model heterogeneous cancer, an OS targeting peptide (OTP) is first selected after biopanning and is demonstrated to successfully bind to this heterogeneous cancer cells/tissues. Successful conjugation of OTP to heptamethine cyanine (Cy7)-based 2D nanodiscs Cy7-TCF (2-dicyanomethylene-3-cyano-4,5,5-trimethyl-2,5-dihydrofuran,TCF) enables the 2D nanodiscs to specifically target the heterogeneous tumor. Notably, a single dose injection of this targeted nanodisc (T-ND) not only effectively induces enhanced photothermal tumor ablation under near-infrared light, but also exhibits sevenfold increase of tumor retention time (more than 24 days) compared to generic nanomedicine. Thus, the authors' findings suggest that the combination of phage display-based affinity peptides selection and 2D supramolecular nanodiscs leads to the development of a platform technology for highly heterogeneous cancers precise therapy, offering specific tumor targeting, ultralong tumor retention, and precise PTT.

Circular RNA circPDSS1 promotes osteosarcoma progression by sponging miR-502-3p and miR-4436a.

Osteosarcoma (OS) is a highly aggressive bone cancer. Patients with OS frequently develop drug resistance in clinical treatment, and the prognosis has not been improved significantly. There is an urgent need to identify novel markers and therapeutic targets. In this study, we focused on the highly expressed noncoding circular RNA circPDSS1 in OS, and studied its functional roles and downstream targets in OS cells by CCK-8, clone formation assay, transwell assays. Additionally, we performed luciferase reporter assay, RNA pull-down experiment and qRT-PCR to validate the micoRNA targets of circPDSS1. The involvement of circPDSS1 in tumorigenesis was also investigated in mouse xenografts model. The expression of circPDSS1 was significantly upregulated in OS tissues and cell lines. Patients with high circPDSS1 expression were associated with poorer progression-free survival (PFS) and overall survival (OS) as compared to those with low circPDSS1 expression. CircPDSS1 knockdown significantly inhibited the viability, clone formation ability and invasion ability of OS cells, and induced cell apoptosis, which were associated with the upregulation of proapoptotic proteins and the impairment of prosurvival signaling. Molecular mechanism study further demonstrated that circPDSS1 modulates OS cell functions by regulating the expression of miR-502-3p and miR-4436a. Our data suggest that circPDSS1 acts as a molecular sponge of miR-502-3p and miR-4436a regulates the proliferation and invasion of OS cells and promote the malignant progression of OS.

Mid-term results of giant cell tumours with pathologic fractures around the knee: a multicentre retrospective study.

OBJECTIVE: The aims of this work are to present a classification of "complex fracture" and "simple fracture", to compare their features, treatments and prognosis in patients with giant cell tumour with pathologic fractures around the knee, and to determine the best surgical method for patients who have giant cell tumour around the knee with different degrees of fracture. METHODS: Data from 130 patients with pathologic fractures from giant cell tumour around the knee who underwent surgical treatment from March 2000 to November 2015 at 6 institutes around China were collected and analysed. A multicentric study design was used to explore the epidemiological features and to compare differences in the surgical procedures and prognosis of the two fracture groups. The mean age at diagnosis was 37.1 years old (range, 13-77 years). The median follow-up was 126.5 months, ranging from 68 to 370 months. RESULTS: The general clinical and imaging features of the groups of patients with simple and complex fractures, namely, sex, age, the lesion site, living or working environment, eccentric growth patterns, Campanacci grading system, and duration of symptoms before treatment, showed varying degrees of differences, but with no statistical significance (p > 0.05). The incidence rate of surrounding soft tissue mass was 35.2% (32/91) in the group with simple fractures, whereas it was 87.2% (34/39) in the group with complex fractures, which showed a significant difference (p < 0.05). Wide resection and reconstruction with joint replacement were performed more often in patients with complex fractures (61.5%, 24/39). Intralesional procedures were performed more often in patients with simple fractures (56.0%, 51/91). The difference showed significant differences (p < 0.05). The local recurrence rate was 17.6% (16/91) in the group with simple fractures, whereas it was 10.3% (4/39) in the complex fracture group, showing a significant difference (p < 0.05). A total of 2.3% of patients (n = 3,3/130) developed a skip lesion. The complication rates were 4.6% (4/87) and 14.7% (5/34), respectively, in the two groups with simple or complex fractures, showing a significant difference (p < 0.05). The mean MSTS and TESS scores with simple fractures were 26.6 (range, 13-30) and 84.1 (range, 29-100), respectively, whereas the mean scores in the group with complex fractures were 25.5 (range, 18-30) and 78.3 (range, 30-100), respectively, also showing a significant difference (p < 0.05). CONCLUSION: Our classification of "simple fracture" and "complex fracture" could guide decisions regarding the best surgical method for lesions in patients who have giant cell tumour around the knee with different degrees of fracture.

Computational Optimization of Spectral Library Size Improves DIA-MS Proteome Coverage and Applications to 15 Tumors.

Efficient peptide and protein identifications from data-independent acquisition mass spectrometric (DIA-MS) data typically rely on a project-specific spectral library with a suitable size. Here, we describe subLib, a computational strategy for optimizing the spectral library for a specific DIA data set based on a comprehensive spectral library, requiring the preliminary analysis of the DIA data set. Compared with the pan-human library strategy, subLib achieved a 41.2% increase in peptide precursor identifications and a 35.6% increase in protein group identifications in a test data set of six colorectal tumor samples. We also applied this strategy to 389 carcinoma samples from 15 tumor data sets: up to a 39.2% increase in peptide precursor identifications and a 19.0% increase in protein group identifications were observed. Our strategy for spectral library size optimization thus successfully proved to deepen the proteome coverages of DIA-MS data.

Iodine Immobilized Metal-Organic Framework for NIR-Triggered Antibacterial Therapy on Orthopedic Implants.

Iodine has been known as an effective disinfectant with broad-spectrum antimicrobial potency yet without drug resistance risk when used in clinic. However, the exploration of iodine for antibacterial therapy in orthopedics remains sparse due to its volatile nature and poor solubility. Herein, leveraging the superior absorption capability of metal-organic frameworks (MOFs) and their inherent photocatalytic properties, iodine-loaded MOF surface is presented to realize responsive iodine release along with intracellular reactive oxygen species(ROS) oxidation under near-infrared (NIR) exposure to achieve synergistic antibacterial effect. Iodine is successfully loaded using vapor deposition process onto zeolitic imidazolate framework-8(ZIF-8), which is immobilized onto micro arc oxidized titanium via a hydrothermal approach. The combination of NIR-triggered iodine release and ZIF-8 mediated ROS oxidative stress substantially augments the antibacterial efficacy of this approach both in vitro and in vivo. Furthermore, this composite coating also supported osteogenic differentiation of bone marrow stromal cells, as well as improved osseointegration of coated implants using an intramedullary rat model, suggesting improvement of antibacterial efficacy does not impair osteogenic potential of the implants. Altogether, immobilization of iodine via MOF on orthopedic implants with synergistic antibacterial effect can be a promising strategy to combat bacterial infections.

Identification of Serum miR-337-3p, miR-484, miR-582, and miR-3677 as Promising Biomarkers for Osteosarcoma.

BACKGROUND: The present study aimed to elucidate the clinical values of miR-337-3p, miR-484, miR-582, and miR-3677 in patients with osteosarcoma. METHODS: After extracting RNA from serum samples of healthy volunteers, OS patients, and periostitis patients, the real-time quantitative polymerase chain reaction (RT-qPCR) analysis was carried out. Afterwards, the receiver operating characteristic (ROC) assays were conducted in order to identify the area under the curves of certain microRNAs in OS. Finally, the log-rank survival analysis was used to analyze the five-year survival rate and disease-free survival rate of OS patients with aberrant microRNA expressions. RESULTS: From the results, miR-337-3p, miR-484, miR-582, and miR-3677 were remarkably decreased in OS cell lines, tumor tissues, and serum samples of OS patients. Furthermore, receiver operating characteristic (ROC) analysis verified that serum miR-337-3p, miR-484, miR-582, miR-711 and miR-3677 had favorable diagnostic values for identifying OS from periostitis patients with the area under the curves of 0.9434, 0.8760, 0.717,0 and 0.8705 and from healthy volunteers with the area under the curves 0.8218, 0.8358, 0.8008, and 0.7141, respectively. After surgery, serum miR-337-3p, miR-484, miR-582, and miR-3677 were dramatically increased. Meanwhile, lower expressions of miR-337-3p, miR-484, miR-582 and miR-3677 were strongly correlated with clinical stage and metastasis. Last but not the least, the log-rank survival analysis demonstrated that lower expressions of miR-337-3p, miR-484, miR-582, and miR-3677 were related to unfavorable prognosis in OS patients. CONCLUSIONS: Our study verified and illustrated the clinical values of miR-337-3p, miR-484, miR-582, and miR-3677 for the detection and prognosis of OS.

Sustained zinc release in cooperation with CaP scaffold promoted bone regeneration via directing stem cell fate and triggering a pro-healing immune stimuli.

Metal ions have been identified as important bone metabolism regulators and widely used in the field of bone tissue engineering, however their exact role during bone regeneration remains unclear. Herein, the aim of study was to comprehensively explore the interactions between osteoinductive and osteo-immunomodulatory properties of these metal ions. In particular, the osteoinductive role of zinc ions (Zn2+), as well as its interactions with local immune microenvironment during bone healing process, was investigated in this study using a sustained Zn2+ delivery system incorporating Zn2+ into ß-tricalcium phosphate/poly(L-lactic acid) (TCP/PLLA) scaffolds. The presence of Zn2+ largely enhanced osteogenic differentiation of periosteum-derived progenitor cells (PDPCs), which was coincident with increased transition from M1 to M2 macrophages (M[Formula: see text]s). We further confirmed that induction of M2 polarization by Zn2+ was realized via PI3K/Akt/mTOR pathway, whereas marker molecules on this pathway were strictly regulated by the addition of Zn2+. Synergically, this favorable immunomodulatory effect of Zn2+ further improved the osteogenic differentiation of PDPCs induced by Zn2+ in vitro. Consistently, the spontaneous osteogenesis and pro-healing osteoimmunomodulation of the scaffolds were thoroughly identified in vivo using a rat air pouch model and a calvarial critical-size defect model. Taken together, Zn2+-releasing bioactive ceramics could be ideal scaffolds in bone tissue engineering due to their reciprocal interactions between osteoinductive and immunomodulatory characteristics. Clarification of this synergic role of Zn2+ during osteogenesis could pave the way to develop more sophisticated metal-ion based orthopedic therapeutic strategies.

Spatiotemporal regulation of angiogenesis/osteogenesis emulating natural bone healing cascade for vascularized bone formation.

Engineering approaches for growth factor delivery have been considerably advanced for tissue regeneration, yet most of them fail to provide a complex combination of signals emulating a natural healing cascade, which substantially limits their clinical successes. Herein, we aimed to emulate the natural bone healing cascades by coupling the processes of angiogenesis and osteogenesis with a hybrid dual growth factor delivery system to achieve vascularized bone formation. Basic fibroblast growth factor (bFGF) was loaded into methacrylate gelatin (GelMA) to mimic angiogenic signalling during the inflammation and soft callus phases of the bone healing process, while bone morphogenetic protein-2 (BMP-2) was bound onto mineral coated microparticles (MCM) to mimics osteogenic signalling in the hard callus and bone remodelling phases. An Initial high concentration of bFGF accompanied by a sustainable release of BMP-2 and inorganic ions was realized to orchestrate well-coupled osteogenic and angiogenic effects for bone regeneration. In vitro experiments indicated that the hybrid hydrogel markedly enhanced the formation of vasculature in human umbilical vein endothelial cells (HUVECs), as well as the osteogenic differentiation of mesenchymal stem cells (BMSCs). In vivo results confirmed the optimal osteogenic performance of our F/G-B/M hydrogel, which was primarily attributed to the FGF-induced vascularization. This research presents a facile and potent alternative for treating bone defects by emulating natural cascades of bone healing.

Systemic evaluation of the relationship between psoriasis, psoriatic arthritis and osteoporosis: observational and Mendelian randomisation study.

OBJECTIVES AND METHODS: With 432 513 samples from UK Biobank dataset, multivariable linear/logistic regression were used to estimate the relationship between psoriasis/psoriatic arthritis (PsA) and estimated bone mineral density (eBMD)/osteoporosis, controlling for potential confounders. Here, confounders were set in three ways: model0 (including age, height, weight, smoking and drinking), model1 (model0 +regular physical activity) and model2 (model1 +medication treatments). The eBMD was derived from heel ultrasound measurement. And 4904 patients with psoriasis and 847 patients with PsA were included in final analysis. Mendelian randomisation (MR) approach was used to evaluate the causal effect between them. RESULTS: Lower eBMD were observed in patients with PsA than in controls in both model0 (ß-coefficient=-0.014, p=0.0006) and model1 (ß-coefficient=-0.013, p=0.002); however, the association disappeared when conditioning on treatment with methotrexate or ciclosporin (model2) (ß-coefficient=-0.005, p=0.28), mediation analysis showed that 63% of the intermediary effect on eBMD was mediated by medication treatment (p<2E-16). Patients with psoriasis without arthritis showed no difference of eBMD compared with controls. Similarly, the significance of higher risk of osteopenia in patients with PsA (OR=1.27, p=0.002 in model0) could be eliminated by conditioning on medication treatment (p=0.244 in model2). Psoriasis without arthritis was not related to osteopenia and osteoporosis. The weighted Genetic Risk Score analysis found that genetically determined psoriasis/PsA were not associated with eBMD (p=0.24 and p=0.88). Finally, MR analysis showed that psoriasis/PsA had no causal effect on eBMD, osteoporosis and fracture. CONCLUSIONS: The effect of PsA on osteoporosis was secondary (eg, medication) but not causal. Under this hypothesis, psoriasis without arthritis was not a risk factor for osteoporosis.

Survival predictors of metastatic angiosarcomas: a surveillance, epidemiology, and end results program population-based retrospective study.

BACKGROUND: Angiosarcomas (AS) have poor prognosis and often metastasize to distant sites. The potential predictors of metastatic angiosarcomas (MAS) have not been extensively investigated. The main objective of this study was to identify survival predictors of MAS. METHODS: Surveillance, Epidemiology, and End Results (SEER) datasets were used to identify patients with MAS from 2010 to 2016. Risk predictors were determined with the aid of Kaplan-Meier and Cox regression model analyses. RESULTS: A total of 284 MAS patients met the study entry criteria. Among these, 121 patients (42.6%) were diagnosed with metastasis in bone, 26 in brain (9.2%), 86 in liver (30.3%) and 171 in lung (60.2%). Overall, 96 patients (33.8%) had two or more metastatic sites. The 1- and 3-year overall survival (OS) rates were 20.8 and 3.8% while 1- and 3-year cancer-specific survival (CSS) rates were 22.0 and 5.2%, respectively. Cox regression analysis revealed chemotherapy, radiation treatment (RT) and tumor size ≤10 cm as independent favorable predictors of OS. In terms of CSS, tumor grade IV, tumor size > 10 cm and absence of chemotherapy were independent adverse predictors. Surgery did not prolong survival outcomes (both OS and CSS) in the current cohort. CONCLUSION: MAS is associated with extremely poor survival. Chemotherapy, RT, and tumor size are independent predictors of OS. Chemotherapy and tumor size are independent prognostic factors of CSS. Chemotherapy is therefore recommended as the preferred treatment option for MAS patients.

Intra-articular nodular fasciitis: a rare lesion case report and an updated review of the literature.

BACKGROUND: Nodular fasciitis is a benign proliferation of myofibroblasts that usually arises in subcutaneous tissues of the trunk, neck, head, and upper extremities of young adults. It is not reported to arise in the joints. CASE PRESENTATION: In this report, we describe a rare case where nodular fasciitis occurred in an intra-articular location in the right knee of a 20-year-old man. The patient presented with 3-months' duration of knee pain without history of trauma to the extremity. Physical examination revealed pain, joint effusion, and limited range of motion (ROM) of the affected knee. Magnetic resonance imaging (MRI) showed a 2.5 × 2 × 1 cm lesion in front of the posterior cruciate ligament. Arthroscopically, the soft tissue mass was removed and pathologically diagnosed as a rare, benign, intra-articular nodular fasciitis. Symptoms resolved 1 month after the operation and no recurrence was found at the 6 months follow-up. CONCLUSION: The present paper describes detailed characteristics of intra-articular nodular fasciitis and provides an updated comprehensive summary of 21 prior case reports.

Bone combined cement grafting in giant cell tumor around the knee reduces mechanical failure.

OBJECTIVES: The aims of our study are (1) to explore the risk factors of mechanical failure (MF), (2) to figure out an index to evaluate this risk, and (3) to select an optimal reconstruction strategy to reduce this risk. METHODS: We retrospectively reviewed 104 patients from Dec. 2008 to Mar. 2016, undergone extensive knee curettages in our institution. Radiographs and post-operative interviews were used to classified cases of MF. Relative factors (age, tumor location, the invaded area, etc.) were also collected and analyzed by SPSS software. RESULTS: Thick subchondral bony layer (p = 0.006) and combined grafting of the cement and bone (p = 0.006) had lower risk of mechanical failure. Mechanical failure appeared to happen in the femur (p = 0.012) more easily. The ROC curve (AUC = 0.722) reveals that less post-operative bony layer (≤ 3.3 mm) is more likely to cause mechanical failure. The Kaplan-Meier survival curve showing increased survival in those patients after a combination grafting surgery (HR, 3.799; p = 0.006). CONCLUSION: Based on our study results, combined grafting of the cement and bone reduced the risk of mechanical failure in the knee due to the thin subchondral bone layer (SCB), especially in the femur.

Upshifting the Ipsilateral Proximal Femur May Provide Satisfactory Reconstruction of Periacetabular Pelvic Bone Defects After Tumor Resection.

BACKGROUND: Pelvic ring reconstruction after resection of pelvic malignancies or aggressive benign tumors remains challenging, especially when the tumor invades periacetabular bone, resulting in a Type II resection as classified by Enneking and Dunham (removal of part or all of the acetabulum). Although numerous treatment approaches are in use, none is clearly superior to the others. An alternative involving use of the ipsilateral proximal femur as an autograft has not been well characterized, so we present our preliminary experience with this approach. QUESTIONS/PURPOSES: (1) What were the oncologic outcomes after using an ipsilateral proximal femur autograft for reconstruction after Type II pelvic resection in a small series of patients who underwent this reconstructive approach? (2) What were the Musculoskeletal Tumor Society (MSTS) scores after this reconstruction? (3) What complications were observed? METHODS: Between October 2006 and May 2016, we treated 67 patients with Type II malignant or aggressive benign tumors of the ilium. Of those, we used an ipsilateral proximal femur and a prosthesis as a reconstruction method for 11 patients with pelvic tumors. In general, we performed this approach in young or middle-aged patients with primary malignant or aggressive benign tumors involving pelvic area II and in whom the tumor did not invade the hip. The method used for resection of pelvic tumors included osteotomy of the femoral shaft, harvesting the proximal femur as a graft. The length of the femoral graft was determined by the extent of the pelvic defect. The proper placement was selected after a comparison of the proximal femur and the pelvic defect. A curved reconstruction plate and cancellous bone screws were used for pelvic fixation. The operative duration and total blood loss were recorded. Of the 11 patients who underwent this approach, all but one had at least 2 years of followup unless death occurred earlier, and all but one have been seen within the last year for evaluation. Functional outcomes were assessed using the MSTS scoring system. Local recurrence, metastases, and deaths were recorded as were complications including infection, bone nonunion, mechanical failure and sciatic nerve palsy. RESULTS: The followup was a mean of 37 months (range, 13-96 months). One patient was lost to followup. Three patients died of disease owing to local recurrence or lung metastasis. The other seven patients lived without evidence of tumor. The main complications included mechanical failure in two patients, nonunion in one patient, infection in two patients, and sciatic nerve palsy in one patient. The median MSTS function score was 70% (21 of 30 points; range, 11-25 points). CONCLUSIONS: Our preliminary results show that this technique of using the ipsilateral proximal femur may be an alternative method for reconstruction of pelvic bone defects after tumor resection. Even with this short followup, complications were common, but short-term function appears to be comparable to studies of other options. Longer term followup with more patients is necessary to confirm our results. LEVEL OF EVIDENCE: Level IV, therapeutic study.

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.

Malignant peripheral nerve sheath tumor in the paraspinal region mimicking a benign peripheral nerve sheath tumor: a case report.

PURPOSE: Malignant peripheral nerve sheath tumors are extremely rare in the general population and display a predilection for metastasis to the lungs. Here, we present a rare case of a malignant peripheral nerve sheath tumor located in the paraspinal region and highlight the importance of preoperative biopsy in diagnosis of spinal epidural peripheral nerve sheath tumors. METHODS: We describe the clinical course of the patient as well as the radiological and pathological findings of the tumor. RESULTS: A 14-year-old girl presented with a six-month history of sacral pain. Occasionally she experienced left leg pain and abnormal gait. General physical examination revealed sensorial loss in the L5-S1 regions. T1-weighted sagittal MRI showed a hypointense oval mass and the contrast-enhanced T1-weighted axial MRI image showed heterogeneous enhancement of the tumor. On CT imaging, this tumor characteristically appears as a dumbbell-like mass with punctate calcification and widening L5-S1 intervertebral foramen. Complete resection was performed using an anterior approach. Intraoperative pathological examination revealed evidence of malignancy and subsequent immunohistochemical analysis of the tumor confirmed the diagnosis of MPNST. The postoperative course was uneventful and the patient has had significant improvement in her symptoms 1 month postoperatively. CONCLUSIONS: Preoperative biopsy should be routinely performed for pathological differential diagnosis of spinal epidural PNSTs as well as surgical decision-making. Furthermore a combination of clinical manifestation, radiological findings and biopsy should also be pursued for diagnosing these tumors.