Foreword. Silver coatings, used in many surgical devices, have demonstrated good antimicrobial activity and low toxicity. Oncological musculoskeletal surgery have an high risk of infection, so in the last decades, silver coated mega-prostheses have been introduced and are becoming increasingly widespread. Material and methods. We performed a retrospective analysis of 158 cases of bone tumors, primary or metastatic, treated between 2002–2014 with wide margins resection and reconstruction with tumoral implants. The average age was 59 years (range 11–78 years), all patients were treated by the same surgeon, with antibiotic prophylaxis according to a standard protocol. In 58.5% of patients were implanted silver-coated prostheses, in the remaining part, standard tumor prosthesis. Patients were re-evaluated annually and were recorded complications, with particular attention to infectious diseases. Results. The mean follow-up was 39.5 months. 23.4% of patients died at a median time of 34.9 months after surgery. 18.4% develop complications that required a new surgery, in 12.6% of cases due to infectious problems. Patients treated with silver-coated implants developed early infection in 2.2% of cases against the 10.7% of the patients treated with standard tumor prosthesis. This different among the two groups was statistically significant, while the percentage of late infections, occurred from 6 months after surgery, was similar between groups. Assuming a reduction of antimicrobial silver activity in the time, it was carried out a microscopic analyses [Fig. 1] of silver-coated prostheses explanted 82 months and 27 months after surgery. It confirmed an important degradation of the coating surface with almost complete absence of silver. Silver blood level, taken in a sample of patients, at different time after surgery, always showed values well below the threshold of toxicity, and no patient has never shown any sign of local or general toxicity secondary to silver [Fig. 2]. Discussion. Our study demonstrates that tumor silver-coated implants have a rate of early infection significantly less than traditional implants, while there were no differences in the rate of late infections, as described also in the literature. This likely is related to wear of the silver coating, which occurs on average around 2 years after implantation. Conclusion. We recommend to use silver–coated prosthesis as primary implants for limb salvage surgery, in primary or metastatic bone tumors, considering the absence of signs of toxicity and the lower rate of early infection

Functional outcomes are commonly reported in studies of musculoskeletal oncology patients undergoing limb salvage surgery; however, interpretation requires knowledge of the smallest amount of improvement that is important to patients – the minimally important difference (MID). We established the MIDs for the Musculoskeletal Tumor Society Rating Scale (MSTS) and Toronto Extremity Salvage Score (TESS) in patients with bone tumors undergoing lower limb salvage surgery. This study was a secondary analysis of the recently completed PARITY (Prophylactic Antibiotic Regimens in Tumor Surgery) study. This data was used to calculate: (1) the anchor-based MIDs using an overall function scale and a receiver operating curve analysis, and (2) the distribution-based MIDs based on one-half of the standard deviation of the change scores from baseline to 12-month follow-up, for both the MSTS and TESS. There were 591 patients available for analysis. The Pearson correlation coefficients for the association between changes in MSTS and TESS scores and changes in the external anchor scores were 0.71 and 0.57, indicating “high” and “moderate” correlation. Anchor-based MIDs were 12 points and 11 points for the MSTS and TESS, respectively. Distribution-based calculations yielded MIDs of 16-17 points for the MSTS and 14 points for the TESS. The current study proposes MID scores for both the MSTS and TESS outcome measures based on 591 patients with bone tumors undergoing lower extremity endoprosthetic reconstruction. These thresholds will optimize interpretation of the magnitude of treatment effects, which will enable shared decision-making with patients in trading off desirable and undesirable outcomes of alternative management strategies. We recommend anchor-based MIDs as they are grounded in changes in functional status that are meaningful to patients

Impaired bone healing biology secondary to soft tissue deficits and chemotherapy contribute to non-union, fracture and infection following limb salvage surgery in Osteosarcoma patients. Approved bone healing augments such as recombinant human bone morphogenetic protein-2 (rhBMP-2) have great potential to mitigate these complications. rhBMP-2 use in sarcoma surgery is limited, however, due to concerns of pro-oncogenic signalling within the tumour resection bed. To the contrary, recent pre-clinical studies demonstrate that BMP-2 may induce Osteosarcoma differentiation and limit tumour growth. Further pre-clinical studies evaluating the oncologic influences of BMP-2 in Osteosarcoma are needed. The purpose of this study is to evaluate how BMP-2 signalling affects Osteosarcoma cell proliferation and metastasis in an active tumour bed. Two Osteosarcoma cell lines (143b and SaOS-2) were assessed for proliferative capacity and invasion. 143b and SaOS-2 cells were engineered to upregulate BMP-2. In vitro proliferation was assessed using a cell viability assay, motility was assessed with a scratch wound healing assay, and degree of osteoblastic differentiation was assessed using qRT-PCR of Osteoblastic markers (CTGF, ALP, Runx-2 and Osx). For in vivo evaluation, Osteosarcoma cells were injected into the intramedullary proximal tibia of immunocompromised (NOD-SCID) mice and local tumour growth and metastases were assessed using weekly bioluminescence imaging (BLI) and tumour volume measurements for 4–6 weeks. At the experimental end point we assessed radiographic tumour burden using ex-vivo micro-CT, as well as tibial and pulmonary gross and histologic pathology. SaOS-2 was more differentiated than 143b, with increased expression of Runx-2 (p = 0.009), Osx (p = 0.004) and ALP (p = 0.035). BMP-2 upregulation did not stimulate an osteoblast differentiation response in 143b, but stimulated an increase in Osx expression in SaOS-2 (p = 0.002). BMP-2 upregulation in 143b cells resulted in increased proliferation in vitro (p = 0.014), faster in vitro wound healing (p = 0.03), significantly increased tumour volume (p = 0.001) with enhanced osteolysis detected on micro-CT, but did not affect rates of lung metastasis (67% vs. 71%, BMP-2 vs. Control). BMP-2 over-expression in SaOS-2 cells reduced in vitro proliferation when grown in partial osteogenic-differentiation media (p < 0.001), had no effect on in vitro wound healing (p = 0.28), reduced in vivo SaOS-2 tumour burden at 6 weeks (photon counts, p < 0.0001), decreased tumour-associated matrix deposition as assessed by trabecular thickness (p = 0.02), and did not affect rates of lung metastasis (0% vs. 0%). Our results indicate BMP-2 signalling incites a proliferative effect on a poorly differentiated Osteosarcoma cell line (143b), but conditionally reduces proliferative capacity and induces a partial differentiation response in a moderately-differentiated Osteosarcoma cell line (SaOS-2). This dichotomous effect may be due to the inherent ability for Osteosarcoma cells to undergo BMP-2 mediated terminal differentiation. Importantly, these results do not support the clinical application of BMP-2 in Osteosarcoma limb salvage surgery due to the potential for stimulating growth of poorly differentiated Osteosarcoma cells within the tumour bed. Additional studies assessing the effects of BMP-2 in an immune-competent mouse model are ongoing

Impaired bone healing biology secondary to soft tissue deficits and chemotherapy contribute to non-union, fracture and infection following limb salvage surgery in Osteosarcoma patients. Approved bone healing augments such as recombinant human bone morphogenetic protein-2 (rhBMP-2) have great potential to mitigate these complications. rhBMP-2 use in sarcoma surgery is limited, however, due to concerns of pro-oncogenic signalling within the tumour resection bed. To the contrary, recent pre-clinical studies demonstrate that BMP-2 may induce Osteosarcoma differentiation and limit tumour growth. Further pre-clinical studies evaluating the oncologic influences of BMP-2 in Osteosarcoma are needed. The purpose of this study is to evaluate how BMP-2 signalling affects Osteosarcoma cell proliferation and metastasis in an active tumour bed. Two Osteosarcoma cell lines (143b and SaOS-2) were assessed for proliferative capacity and invasion. 143b and SaOS-2 cells were engineered to upregulate BMP-2. In vitro proliferation was assessed using a cell viability assay, motility was assessed with a scratch wound healing assay, and degree of osteoblastic differentiation was assessed using qRT-PCR of Osteoblastic markers (CTGF, ALP, Runx-2 and Osx). For in vivo evaluation, Osteosarcoma cells were injected into the intramedullary proximal tibia of immunocompromised (NOD-SCID) mice and local tumour growth and metastases were assessed using weekly bioluminescence imaging and tumour volume measurements for 4–6 weeks. At the experimental end point we assessed radiographic tumour burden using ex-vivo micro-CT, as well as tibial and pulmonary gross and histologic pathology. SaOS-2 was more differentiated than 143b, with significantly increased expression of the Osteoblast markers Osx (p = 0.004) and ALP (p = 0.035). BMP-2 upregulation did not stimulate an osteoblast differentiation response in 143b, but stimulated an increase in Osx expression in SaOS-2 (p = 0.002). BMP-2 upregulation in 143b cells resulted in increased proliferation in vitro (p = 0.014), faster in vitro wound healing (p = 0.03), significantly increased tumour volume (p = 0.001) with enhanced osteolysis detected on micro-CT, but did not affect rates of lung metastasis (67% vs. 71%, BMP-2 vs. Control). BMP-2 over-expression in SaOS-2 cells reduced in vitro proliferation when grown in osteogenic-differentiation media (p < 0.001), had no effect on in vitro wound healing (p = 0.28), reduced in vivo SaOS-2 tumour burden at 6 weeks (photon counts, p < 0.0001), decreased tumour-associated matrix deposition as assessed by trabecular thickness (p = 0.02), but did not affect rates of lung metastasis (0% vs. 0%). Our results indicate BMP-2 signalling incites a proliferative effect on a poorly differentiated Osteosarcoma cell line (143b), but conditionally reduces proliferative capacity and induces a partial differentiation response in a moderately-differentiated Osteosarcoma cell line (SaOS-2). This dichotomous effect may be due to the inherent ability for Osteosarcoma cells to undergo BMP-2 mediated terminal differentiation. Importantly, these results do not support the clinical application of BMP-2 in Osteosarcoma limb salvage surgery due to the potential for stimulating growth of poorly differentiated Osteosarcoma cells within the tumour bed. Additional studies assessing the effects of BMP-2 in an immune-competent mouse model are ongoing

Aims. Present the outcomes of those patients diagnosed with Ewing's Sarcoma of the foot within the past 10 years and treated at the Royal National Orthopaedic Hospital's Bone Tumour Unit, Stanmore. Methods. Retrospective study of the cases identified from the pathology database. Notes reviewed for presentation, treatment and follow up. TESS (Toronto Extremity Salvage Score) and MSTS (Musculoskeletal tumour score) were calculated. Results. 6 patients identified with positive diagnosis of Ewing's Sarcoma of the Foot. Male:Female ratio of 5:1. Age range 15–31 (Mode 25). 4 cases skeletal, 2 extra skeletal. All cases reviewed by supra-regional MDT and received adjuvant and neo-adjuvant chemotherapy. All except one patient underwent limb-salvage surgery. The MDT decision for the remaining patient was that amputation was the only viable surgical option but the patient and his parents requested radiotherapy without surgical treatment. Mean survival 40 months (15–107 months). All patients survive at time of submission. Mean MSTS/TESS scores 93% (80–100%) and 94.6% (85–100) respectively. Discussion. All patients reported a delay between first presentation and referral to the sarcoma unit. This experience is common across the literature for this rare pathology. Lowest scores were submitted by the two patients who had amputation of their great toe. All patients are happy with their outcome and decision to salvage their limb. All patients scored themselves as “not at all disabled” and two stated this would not have been their response if they had lost their foot. Conclusion. Amputation is psychologically difficult to accept and patients are more receptive to limb salvage surgery. Our patients demonstrate good functional outcome. Our experience at Stanmore suggests that limb salvage surgery with adequate MDT surveillance for Ewing's Sarcoma of the Foot can be a viable alternative to amputation

Ten to 15% of the pelvic girdle tumors are primary malignant bone tumors, while about 80% are osseous metastases. Due to improved function, enhanced quality of life, and acceptable local recurrence rates, limb salvage surgery has replaced external hemipelvectomies in many cases of primary malignancies. However, large segmental bony defects and poor bone quality due to the disease process itself and subsequent treatment (i.e. chemotherapy and radiation) can make stable implant fixation difficult when performing a total hip arthroplasty (THA) for oncologic periacetabular lesions with concurrent fractures. Various methods are available to reconstruct the hemipelvis, and include large structural allografts, allograft-prosthetic composites (APCs), custom-made endoprostheses, modular saddle prostheses, and modular hemipelvis endoprostheses. However, short- and mid-term results from our institution indicate that tantalum reconstructions with adjuvant screw fixation and supplemental reinforcement cages provide reasonable improvement in clinical outcomes and stable fixation in situations with massive bone loss and compromised bone quality. On the femoral side, cemented fixation remains a viable option (including proximal femoral replacements), but uncemented distal fixation with extensively-porous coated cylindrical stems or modular fluted tapered stems can be considered if the disease process (or subsequent treatment) primarily affects the proximal femur. In addition to long-term fixation, post-operative dislocations remain a significant concern given the often compromised abductor mechanism

Introduction. Advances in the management of open tibial fractures have reduced the incidence of long-term complications of these injuries. However, a number of patients continue to suffer from sequelae such as infection, non-union and malunion. Many orthopaedic surgeons believe a below-knee amputation with a well-fitted prosthesis is a better alternative to limb reconstruction surgery. There are few studies that evaluate the long-term functional outcomes of amputees against patients who have undergone limb salvage procedures, and their results are conflicting. The hypothesis of this study is that patients who have undergone limb salvage have as good or better outcomes than those who have had below-knee amputations. Methods. This is a retrospective case study. One group (n=12) had been treated with below-knee amputation following a variety of lower limb fractures. The other group (n=11) had developed complications following tibial fractures and undergone limb salvage surgery using the Ilizarov method. The groups were compared by means of a postal questionnaire, comprising the Oswestry Disability Index and the SF-36 Health Survey. Results. There were no statistically significant differences between the groups for any of the health scales measured. However, for the two scales in the SF-36 measuring functional health (Physical Functioning and Role-Physical) the differences were much lower than for any of the other scales (both p=0.13). The 95% confidence intervals for the difference between the means for each group were -6.4 to 45.4 for PF and -7.4 to 61.2 for RP. Discussion. This study provides evidence that limb conserving surgery offers a genuine improvement in long term functional health. The failure to reach statistical significance is a reflection of the relatively small numbers of patients affected and the difficulties in collecting data retrospectively

Purpose. The focus of current management of soft tissue sarcoma on limb preservation often necessitates that patients undergo multimodal treatment, including both surgery and external beam radiotherapy. Pathologic fracture is a serious, late complication of radiotherapy. In patients who have also undergone wide excision of soft tissue sarcoma, nonunion rates of 80–90% persist despite optimal internal fixationMany sequelae of the treatments for soft tissue sarcoma exhibit the potential to perpetuate failure of bony union. Limb salvage surgery is associated with extensive periosteal excision, disruption of vascular supply and eradication of local osteoprogenitor cells. External beam radiotherapy leads to obliterative endarteritis, decreased osteoblast proliferation and reduction in bone matrix production. We hypothesize that the combination of radiotherapy and surgical periosteal stripping leads to greater impairment in the fracture repair process than either intervention alone will produce. Method. We developed a method for creating a reproducible, low energy, simple femoral fracture in an animal model designed to proceed to nonunion. Female Wistar, retired breeder rats were separated into four treatment groups of 18 animals each: control, radiotherapy, surgery and combination radiotherapy and surgery. Animals were then further randomized to temporal end-points of 21, 28 and 35 days post-fracture. Designated animals first underwent external beam radiotherapy, followed by surgical stripping of the periosteum three weeks later and femoral fracture with fixation after another three weeks. Animals were sacrificed at their randomly assigned end-points. Results. The fracture device was shown to produce simple, transverse or short oblique femoral fractures using x-rays obtained immediately following fracture, validating the reliability of the model. No significant differences were observed in the force required for fracture between treatment groups. Mineralized callus was observed in control animals and those undergoing periosteal stripping alone, but was absent in all animals receiving radiotherapy. Reactive bone formation was observed in animals undergoing periosteal stripping alone, but was absent when preceded by radiotherapyMicroCT analysis confirmed the results visualized on plain x-ray. No callus formation was observed in animals undergoing radiotherapy and significantly less mineralized callus was produced in animals undergoing periosteal stripping when compared to control. Preliminary studies have shown an absence of cellular activity in animals undergoing radiotherapy, suggesting that fracture in these animals will proceed to nonunion. Conclusion. Early results suggest that this pre-clinical model of combined radiation and surgical periosteal stripping prior to controlled fracture reliably results in nonunion. We expect to utilize this model to examine interventions designed to improve fracture healing in this difficult clinical situation

Prior to the 1970s, almost all bone sarcomas were treated by amputation. The first distal femoral resection and reconstruction was performed in 1973 by Dr Kenneth C Francis at the Memorial Sloan-Kettering Cancer Centre in New York. Since that time, limb-sparing surgery for primary sarcoma has become the mainstay of sarcoma surgery throughout the world. Initially, the use of mega-prostheses of increasing complexity, involving all the major long bones and both pelvic and shoulder girdles, was popularised. In the early 1980s, wide use of massive allograft reconstructions became widespread in both Europe and in multiple centres in the USA and UK. Since that time, increasing complexity in the design of prostheses has allowed for increasing functional reconstructions to occur, but the use of allograft has become less popular due to the development of late graft failures of patients survive past ten years. Fracture rates approaching 50% at 10 years are reported, and thus, other forms of reconstruction are being sought. Techniques of leg lengthening, and bone docking procedures to replace segmental bone loss to tumour are now employed, but the use of biological vascularised reconstructions are becoming more common as patient survivorship increases with children surviving their disease. The use of vascularised fibular graft, composite grafts and re-implantation of extra-corporeally irradiated bone segments are becoming more popular. The improvement in survivorship brought about the use of chemotherapy is producing a population of patients with at least a 65% ten year survivorship, and as many of these patients are children, limb salvage procedures have to survive for many decades. The use of growing prostheses for children have been available for some 25 years, first commencing in Stanmore, UK, with mechanical lengthening prostheses. Non-invasive electro-magnetic induction coil mechanisms are now available to produce leg lengthening, with out the need for open surgery. Whilst many of these techniques have great success, the area of soft tissue attachment to metallic prostheses has not been solved, and reattachment of muscles is of great importance, of course, for return of function. There are great problems in the shoulder joints where sacrifice of rotator cuff muscles is necessary in obtaining adequate disease clearance at the time of primary resection, and a stable shoulder construct, with good movement, has yet to emerge. Similar areas of great difficultly remain the peri-acetabular and sacro-iliac resections in the pelvis. Perhaps the real future of the art of limb salvage will be in the reconstruction of failed major joint replacements where there is great loss of bone stock, and already massive tumour prostheses are providing a salvage pathway for failed standard joint replacement. The final future for limb salvage, however, may not rest with increasing surgical complexity and innovation, but with the development of molecular biology and specific targeted treatments, according to the cytogenetics of a particular tumour. We are on the threshold of yet another quantum change in the approach to cancer management; just as chemotherapy brought a tremendous change in the 1970s, molecular biology is the frontier to make much of the current limb salvage surgery that is performed redundant

CT and MRI scans are complementary preoperative imaging investigations for planning complex musculoskeletal bone tumours resection and reconstruction. Conventionally, tumour surgeons analyse two-dimensional (2-D) imaging information, mentally integrate and formulate a three-dimensional (3-D) surgical plan. Difficulties are anticipated with increase in case complexity and distorted surgical anatomy. Incorporating computer technology to aid in this surgical planning and executing the intended resection may improve precision. Although computer-assisted surgery has been widely used in cranial biopsies and tumour resection, only small case series using CT-based navigation are recently reported in the field of musculoskeletal tumor surgery. We investigated the results of CT/MRI image fusion for Computer Assisted Tumor Surgery (CATS) with the help of a navigation system. We studied 21 patients with 22 musculoskeletal tumours who underwent CATS from March 2006 to July 2009. A commercially available CT-based spine navigation system (Stryker Navigation; CT spine) was used. Of the 22 patients, 10 were males, 11 were females, and the mean age was 32 years at the time of surgery (range, 6–80 years). Five tumours were located in the pelvis, seven sacrum, eight femurs, and two tibia. The primary diagnosis was primary bone tumours in 16 (3 benign, 13 sarcoma) and metastatic carcinoma in four. The minimum follow-up was 17 months (average, 35.5 months; range, 17–52 months). Preoperative CT and MRI scan of each patient were performed. Axial CT slices of 0.0625mm or 1.25mm thickness and various sequences of MR images in Digital Imaging and Communications in Medicine (DICOM) format were obtained. CT and MR images for 22 cases were fused using the navigation software. All the reconstructed 2-D and 3-D images were used for preoperative surgical planning. The plane of tumour resection was defined and marked using multiple virtual screws sited along the margin of the planned resection. We also integrated the computer-aided design (CAD) data of custom-made prostheses in the final navigation resection planning for eight cases. All tumour resections could be carried out as planned under navigation guidance. Navigation software enabled surgeons to examine all fused image datasets (CT/MRI scans) together in two spatial and three spatial dimensions. It allowed easier understanding of the exact anatomical tumor location and relationship with surrounding structures. Intraoperatively, image guidance with the help of fusion images, provided precise visual orientation, easy identification of tumor extent, neural structures and intended resection planes in all cases. The mean time for preoperative navigation planning was 1.85 hours (1 to 3.8). The mean time for intraoperative navigation procedures was 29.6 minutes (13 to 60). The time increased with case complexity but lessened with practice. The mean registration error was 0.47mm (0.31 to 0.8). The virtual preoperative images matched well with the patients' operative anatomy. A postoperative superficial wound infection developed in one patient with sacral chordoma that resolved with antibiotic whereas a wound infection in another with sacral osteosarcoma required surgical debridement and antibiotic. After a mean follow-up of 35.5 months (17–52 months), five patients died of distant metastases. Three out of four patients with local recurrence had tumors at sacral region. Three of them were soft tissue tumour recurrence. The mean functional MSTS score in patients with limb salvage surgery was 28.3 (23 to 30). All patients (except one) with limb sparing surgery and prosthetic reconstruction could walk without aids. Multimodal image fusion yields hybrid images that combine the key characteristics of each image technique. Back conversion of custom prosthesis in CAD to DICOM format allowed fusion with navigation resection planning and prosthesis reconstruction in musculoskeletal tumours. CATS with image fusion offers advanced preoperative 3-D surgical planning and supports surgeons with precise intraoperative visualisation and identification of intended resection for pelvic, sacral tumors. It enables surgeons to reliably perform joint sparing intercalated tumor resection and accurately fit CAD custom-made prostheses for the resulting skeletal defect