In this study, we attempt to explore the differences between anatomical and non-anatomical tibial baseplates in terms of rotation and coverage. To achieve this, we divided 80 dry bones into groups, and examined them using anatomical and non-anatomical baseplates. The results of the study showed that anatomical baseplates provided better coverage and also yielded better results according to the rotational assessment. Surgeons make rotational mistakes by non-anatomic base plates, when trying to achieve best coverage. Anatomic base plates warrant better coverage according to non-anatomic base plates when both are placed at the same rotational axis. It is more possible to adjust size and rotation correctly with the anatomic tibial components

Aim. Current guidelines for the diagnosis of prosthetic joint infection (PJI) recommend collecting 4–5 independent tissue specimens, with isolation of indistinguishable organisms from two or more specimens. The same principle has been applied to other orthopaedic device-related infections (DRI) including fracture-related infections. However there are few published data validating this approach in DRI other than PJI. We evaluated the performance of different diagnostic cutoffs and varying numbers of tissue specimens for microbiological sampling in fracture-related infections. Method. We used standard protocols for tissue sample collection and laboratory processing, and a standard clinical definition of fracture-related infection. We explored how tissue culture sensitivity and specificity varied with the number of tissue specimens obtained; and with the number of specimens from which an identical isolate was required (diagnostic cutoff). To model the effect of the number of specimens taken we randomly sampled n specimens from those obtained at each procedure, excluding procedures from which less than n specimens were collected, and calculated sensitivity and specificity based on this sample. For each value of n we repeated this process 100 times to estimate the mean sensitivity and specificity for n specimens. Results. We analysed data for 246 cases of suspected fracture-related infection. 77 (31%) met the clinical definition of infection. A median of 4 independent tissue samples were obtained from each procedure (IQR 4–5). Culture sensitivity was highest and specificity lowest using a diagnostic cutoff of 1 specimen for isolation of an organism; specificity increased at the expense of sensitivity with diagnostic cutoffs of 2 or 3 specimens. Culture sensitivity increased as the number of tissue specimens obtained increased from 1 to 4. Although there was a corresponding decline in specificity with increasing numbers of tissue specimens obtained, this was negligible when a diagnostic cutoff of 2 or 3 specimens with identical organisms was used. Using a cutoff of 2 specimens with identical organisms, obtaining 4 specimens gave a sensitivity of 68% (55–78%) and a specificity of 95% (86–99%). Small numbers prevented meaningful analysis of the diagnostic performance of five or more specimens. Conclusions. These data are analogous to findings in prosthetic joint infections, and suggest similar principles may be applied to tissue sampling and culture interpretation in other orthopaedic DRI including fracture-related infection. A larger study is underway to evaluate the performance of greater numbers of tissue specimens

Backgrounds. The rigid fixation of glenoid base plate is essential for the prevention of dissociation of the construct in the reverse total shoulder arthroplasty. For the rigid fixation, ideal placement of fixation screw is crucial but it is difficult to determine the best direction and length of screws. The purpose of this study was to determine configuration of optimal screw in cadaveric scapulae and compare with that in patient who underwent reverse total shoulder arthroplasty. Materials and methods. Seven scapulae were used and implanted using a variable angle base plate with four directions screws. Optimal screw placement was defined as that which maximized screw length, accomplished far cortical purchase. Insertion angle and length of every screw was measured from AP and axial radiograph taken after the screws fixation. In a similar manner, the insertion angles of screws were measured from radiographs of 7 postoperative patients who underwent reverse total shoulder arthroplasty. The averages of length and insertion angle of 4 screws from two groups were compared. Result. The average lengths of screws were anterior 29.4 mm, posterior 15.0 mm, superior 36.0 mm, inferior 46.7 mm in the cadavers group and 22.2 mm, 22.3 mm, 28.0 mm, 29.1 mm each in the patient group. There was statistical significance of the difference of the insertion angle of superior and inferior screws between two groups. Conclusion. Trajectory angles of superior and inferior screw were smaller than those of optimal screws. Awareness of this tendency is helpful to insert the optimal screws intraoperatively

Introduction. Entry into orthopaedic higher surgical training remains extremely competitive, however little evidence exists regarding the validity of short-listing and interviewing for selection. This paper assesses the relative correlations of short-listing and interview scores in predicting subsequent performance as an orthopaedic trainee. Methods. We compared data from the selection process (short-listing and interview scores) to subsequent performance during training (academic output and an annual assessment score by Programme Director). Data was prospectively collected from 115 trainees on the South West Thames region of the U.K. during 2000–2010. Results. We found that trainees achieving an interview score within the top third subsequently produced a higher academic output and had a higher annual assessment score than their peers (MANOVA, p>0.05) see Figure 1. [Academic output vs interview score rank (thirds)]. The short-listing scores did not correlate with subsequent academic output or annual assessment score see Figure 2. [Academic output vs shortlist score rank (thirds)]. We found no statistical correlation between the short-listing and interview scores (r. 2. < 0.1). Discussion. This study provides an evidence base to support the value of interviews by senior surgeons in the selection of trainees. We support the following selection process for orthopaedic trainees: long listing followed by a competitive interview(s) of all remaining candidates

Metal on Metal hip resurfacing (MoM HR) can be an effective operation for the young arthritic hip population. However, errors in cup orientation have been associated with increased wear, circulating blood metal ions, and soft tissue abnormalities that can lead to premature failure of the bearing surface and subsequent revision surgery. While image free computer guidance has been shown to increase surgical accuracy in total hip arthroplasty, the role of image based technology in MoM HR is unclear. In this study, we compared the accuracy of cup orientation in MoM HR performed by either freehand technique or CT based navigation. Seventy five patients (81 hips) underwent either freehand (n=42) or navigation (n=39) surgery, both requiring a three dimensional (3D) CT surgical plan. Surgery was conducted by hip specialists blind to the method of cup implantation until the operation. Deviation in inclination and version from the planned orientation, as well as, number of cups within a 10° safe zone and 5° optimal zone of the target position was calculated using post operative 3D CT analysis. Error in inclination was significantly reduced with navigation compared to freehand technique (4° vs 6°, p=0.02). We could not detect a difference between the two groups for version error (5° vs 7°, p=0.06). There was a significantly greater number of hips within a 10° (87% vs 67%, p=0.04) and 5° (50% vs 20%, p=0.06) safe zone when navigated. Image based navigation can substantially improve accuracy in cup orientation. The results of our freehand group appear better than historic controls, suggesting the use of a 3D plan may help to reduce technical error and improve the learning curve in this technically demanding procedure. We advocate the use of image based navigation in MoM hip resurfacing arthroplasty

Aims

The aim of this study was to characterize the relationship between pre- and postoperative opioid use among patients undergoing common elective orthopaedic procedures

This study defines the patterns of perineal injury due to blast currently seen on operations. It refines our team-based surgical strategies of surgical resuscitation provides an evidence base for a perineal debridement - colonic diversion didactic on the Military Operational Surgical Training (MOST) course. The Joint Theatre Trauma Registry (JTTR) held at RCDM was examined from 1 January 2003 to 31 December 2010. Data abstracted included patient demographics, mechanism of injury, injury severity score (ISS), treatment, management, length of stay (LOS) and outcomes. Of 4807 military trauma patients, 118 (2.5%) had a recorded perineal injury, 56 died (48% all IED). Pelvic fractures were identified in 63 (53%) of which 17 (27%) survived. Mortality rates were significantly different between the combined perineal & pelvic fracture group compared to pelvic fracture & perineal injuries alone (41% & 18% respectively, p = 0.0001). Mean ISS for all patients was 41.03. Those with a pelvic fracture had a significantly higher ISS than those with perineal injuries alone (29.53 vs. 51.06, p = 0.0001). Recorded early antibiotic use was significantly more frequent in survivors (p = 0.0119). A literature review demonstrated the benefits of early feeding, emergent diversion, antibiotics, daily washouts and radical early debridement. Combined perineal injuries & pelvic fractures have the highest rate of mortality. Early aggressive management is essential to survival in this cohort. Our recommendations are immediate faecal diversion, aggressive initial debridement & early enteral feeding (in the deployed ITU after first surgery). These findings will enable the rapid provision of an evidence based training schedule to be incorporated into our pre-deployment surgical training program (MOST) to improve surgical team preparation and patient outcomes

Background. In our pursuit of surgical accuracy and precision we often neglect to evaluate our results objectively. With the use of Computerised Tomography (CT) in pre-operative planning we can use the same technology in order to evaluate surgical accuracy. Hypothesis. The use of Patient Specific Instrumentation (CT based) produces an accurate intra operative guide for precision cutting in knee arthroplasty. Method. A prospective study using Patient Specific Instrumentation (customized cutting blocks) was performed on 35 patients. The small cohort value is due to the high costs of post-operative CT. A CT based software was used to evaluate the pre-operative knee alignment. Surgery was planned and verified on a web based programme with the use of 3D models. Cutting blocks were custom made and used as intra operative guide to make the relevant cuts. Pre and post-operative CT scans were compared for AP and lateral alignment, femoral external rotation and flexion and tibial slope. Knee Society scores were also used to evaluate the clinical outcome. Results. The values for AP and lateral limb alignment, femoral external rotation and flexion were the same as the pre-operative values with no significant deviation (maximum 2 degree difference). The posterior tibial slope was the only value that showed significant deviation from the pre-planned values. Conclusion. There was a significant difference for the posterior tibial slope but otherwise we found no difference in pre and post-operative limb alignment measurements. Pre-operative planning with the use of CT based customised cutting blocks is a reliable and accurate option to obtain optimal alignment and prosthetic orientation in total knee arthroplasty. NO DISCLOSURES

To examine all open fractures presenting to Bundaberg Base Hospital—from January 2007 to January 2009—by monitoring the clinical course of the patients, with attention to the time intervals between injury, presentation and orthopaedic treatment. The complications of treatment and the implications for future practice were also examined. A search was performed of all open fractures and compound fractures during the period of January 2007 until January 2009. The eligible patients were selected and their charts reviewed. The time of the injury, the time they presented to the emergency department (ED) and the time to orthopaedic treatment were noted. The site of the fracture, the Gustillo classification and the number of days of admission were recorded. Complications of the fractures were investigated. The impact of time delays and fracture severity on subsequent infections were correlated. A total of 127 admissions were recorded, 38 were excluded and 89 open fractures were included in the study: 54 upper limb, 34 lower limb and 1 pelvic fracture. Thirty-six patients had Gustillo I, 34 II, 9 IIIa, and 11 IIIb classifications. Patient arrival times were as follows: less than one hour (19%), 1–3 hours (44%), 3–6 hours (26%), 6–12 hours (8%) and greater than 12 hours (2%). From presentation, 28% of patients received treatment in 1–3 hours, 3–6 hours (27%), 6–12 hours (22%) and greater than 12 hours (22%). 40.4% of patients received treatment within 6 hours of injury and 59.5% greater than 6 hours. 33% of patients stayed in hospital 24 hours, 1–3 days (44%), 3–7 days (15%) and for greater than one week (1%). There were a total of 17 complications (19%), of which 11 (12%) were associated with infections. Of these, six were superficial wound infections and five were deep infections. Of these deep infections, two were associated with non-unions and one with a mal-union. Four complications were associated with non-infectious non-unions, one non-infectious mal-union. One had a missing bone fragment. Complications were found to be more prevalent when there was delayed treatment of the fractures. The results demonstrate that the majority of open fractures treated are upper limb and Gustillo I in classification. The complication rate for open fractures during the two year period was 19%. These findings provide a base for continued monitoring of open fracture management at Bundaberg Base Hospital

Aim. The aim of this study is to assess the effectiveness of clinic based ultrasound screening by Orthopaedic surgeon for early diagnosis and treatment of developmental dysplasia of hip (DDH) in one stop clinic. Methods. This prospective study included 395 infants (185 male and 210 female) (5.2% of study population) who were referred for screening on the basis of abnormal findings or the presence of risk factors for DDH. Average age was 12.5 weeks (1 day to 15 months). All infants were assessed for risk factors of DDH. Clinical examinations were performed by the senior author followed by ultrasonography of both of the infant's hips, using the Graf's technique. Alpha and beta angles were calculated and hips were classified according to Graf's classification system. Results. Out of 790 hips examined 670 (84.8%) were labelled as normal. 120 (15.1%) hips in 84 patients were diagnosed as dysplastic or dislocated. Clinical examination only detected 39 patients out of 84, sensitivity of 46%. Average age of diagnosis was 12 weeks (3days-11 months). 79 patients were successfully treated with pavlic harness, 2 required traction and 3 were referred for surgical treatment. There were 14 cases of late diagnosis during one year period (> 4 months of age) (1.8/1000). Conclusion. Selective ultrasound screening is effective in early diagnosis of DDH and significantly reduces the duration of non operative treatment as well as the need for surgical intervention but does not completely eliminate late diagnosis of DDH. We find the concept of one stop DDH clinic highly effective and recommend that ultrasound training should be a part of orthopaedic curriculum

Introduction. The association of occupation and carpal tunnel syndrome (CTS) is unclear. Population based studies have failed to prove causal relationships between certain types of work and the onset of CTS. The aim of this study was to compare the incidence of CTS with the underlying regional occupational profile and assess differences in disease severity. Methods. The study took place from 2004 to 2010 in a regional hand unit that was the sole provider of hand services to a health board. Occupation was classified according to the SOC2000 classification as published by the Office for National Statistics and compared with the National Census 2000 statistics. 1564 patients were diagnosed with CTS during the study period of which 852 were aged 16 to 74, in full time employment. Results. CTS was less common among managers, directors and senior officials (< 0.001), associated professional and technical occupations (< 0.001), and process plant and machine operatives (p=0.013). It was higher than expected in professional occupations (p< 0.001), skilled trade occupations (p< 0.001) and caring and other service occupations and elementary occupations (p< 0.001). Bilateral disease was highest in the skill trades group (80%). Process, plant and machine operatives had the highest rate of compensation claims (15.2%, p=0.001), while the highest rate of exposure to vibration was in the skilled trades group (67%). There was a difference in preoperative grip strength (p< 0.001) and DASH score (p< 0.001). Conclusions. The incidence of CTS varied between occupational groups. This study demonstrated a higher incidence of CTS in skilled trades and elementary occupations. There was also a higher than expected rate of CTS observed in professional groups and caring, leisure and other service occupations, but lower in machine and plant operatives. Disease severity varied according to occupational group

Introduction. Rolando type base of thumb metacarpal fractures are potentially debilitating injuries, which can be difficult to manage because of their inherent instability. Malunion is associated with stiffness, pain and weakness of pinch grip. We aimed to assess the outcome of a simple technique for the treatment of this fracture using the principle of ligamentotaxis, with a static, 2-pin external fixator spanning the trapeziometacarpal joint. We present the results and functional outcomes of this technique. Methods. A consecutive series of 8 patients (7 males, 1 female) with Rolando type intra-articular fractures of the base of the first metacarpal was retrospectively reviewed. All cases were performed by the senior author using a static, 2-pin Mini-Hoffman external fixator. Case notes and radiographs were reviewed, and patients' functional outcome assessed using the Quick Disability of Arm, Shoulder and Hand (Quick DASH) scoring system. Mean age of the group was 32.8 years (range 18.1-52.3 years). Mean follow-up was 2.7 years (range 3.5 months to 6.0 years). Results. The mean delay between injury and surgery was 6.6 days (range 1-11). The mean time to frame removal was 28 days (range 15-41). There were 3 cases of superficial pin site infection all of which were treated satisfactorily with oral antibiotic therapy. Follow-up radiographs did not demonstrate any significant joint incongruity or malunion in any case. The mean Quick DASH score was 8 (range 0-23). Mean scores for the work and sport components were 10 (range 0-25) and 3 (range 0-6) respectively. Conclusion. The results of this study demonstrate that this simple method reliably gives excellent hand and thumb function with minimal impact upon work, sport or recreational activities. We recommend the use of spanning trapeziometacarpal external fixation for intra-articular fractures of the base of the first metacarpal

Aims. Several national studies have shown that the rates of joint replacement are rising and this increase may be greater than that expected by population ageing. The aim of this study was to assess local rates of joint replacement at a district general hospital (DGH) and to investigate whether there had been a change in pre-operative functional status of patients over the study period to account for any change in rates of arthroplasty. Methods. This was a DGH based local joint registry programme with independent functional assessment and follow up. All patients undergoing primary total hip replacement (THR) and total knee replacement(TKR) between 1 January 2000 and 31 December 2009 were eligible. Only after being listed for surgery were patients assessed with WOMAC and Oxford Hip or Oxford Knee scores. Catchment population data was obtained from the Office of National Statistics. Results. 5373 joint replacements were performed over the ten year period, 89% had preoperative scoring available. There was an 80% increase in numbers of THR performed and 95% increase in number of TKR performed between 2000 and 2009. This was a significant increase when compared to the local population aged between 60 and 80 years, the size of which increased just 28% over the same period. The average age of the patients remained static over the study period and there was no clinically significant change in any of the pre-operative functional scores. Conclusions. Whilst the incidence of joint replacement increased over the study period, this was not associated with a change in patients' ages or preoperative functional status. Our results suggest that the increases seen are not due to a change in functional threshold for surgery. This is of particular relevance during this time of austerity when funding for orthopaedic surgery may be threatened

Aim

To assess if immediate post-operative weight bearing has a negative influence on the results of osteotomy plus distal soft tissue repair to correct hallux valgus.

Purpose

The foam metal backed Advance BioFoam Knee Arthroplasty components utilize a porous titanium coating on the underside of the tibial baseplate, intended to promote bone in-growth and provide a more robust bone-implant interface without cement. There is also a version of the Biofoam Advance that incorporates screwed fixation that allows for augmented fixation with up to four titanium screws; however, it is not clear that this augmentation is necessary. The purpose of this study was to employ radiostereometric analysis (RSA) to compare implant migration in a randomized controlled trial of this implant design with or without screw fixation.

Treatment of segmental bone loss remains a major challenge in orthopaedic surgery. This study evaluated the healing potential of a series of highly porous tissue engineering scaffolds with the current clinical gold standard. We compare healing of collagen-glycosaminoglycan (CG) and collagen micro-hydroxyapatite (CHA) scaffolds, with and without recombinant bone morphogenetic protein-2 (BMP2), with autogenous bone graft (ABG) in the healing of a 15mm rabbit radius defect, which were filled with either CG scaffold, CHA scaffold, CG-BMP2, CHA-BMP2 or ABG. Serial radiographs and micro-computed tomography (µCT) at six week radiographs demonstrated complete defect bridging with callus using CHA and CG-BMP2 while the CHA-BMP2 was already in an advanced state of healing with cortical remodeling. By sixteen weeks CHA, CG-BMP2 and ABG all had advanced healing with cortical remodeling while CHA-BMP2 had complete anatomic healing. Quantitative histomorphometry values demonstrated similarly high healing levels of healing in CHA, CG-BMP2 and ABG with highest overall values in the CHA-BMP2 group. Thus, treatment of a critical sized, weight bearing, rabbit radius defect with a CHA scaffold can result in full cortical bridging with medullary cavity development. In addition, a CHA-BMP2 combination can result in fully mature, anatomic healing. The use of an off-the-shelf CHA scaffold for direct surgical placement into a defect site may be an effective bone graft substitute in the treatment of skeletal defects. The ease of manufacture, storage and peri-operative preparation may offer an alternative to traditional strategies, as well as to more recent BMP2 devices. This study provides clear evidence that CHA scaffolds can perform as well as autogenous bone grafts and supports their use as a viable alternative. Where the use of BMP2 may be desirable, these materials provide an ideal delivery mechanism and using a very low (near physiological) dose, healing superior to autogenous graft may be achieved.

Introduction

The correction of paediatric scoliosis is a surgical procedure in which substantial bleeding occurs, and which historically has been associated with high levels of blood transfusion. Transfusions are associated with risks of infection, allergic reactions, volume overload and immunosuppression.

The purpose of our study was to evaluate the efficacy of a care pathway implemented at St Thomas' hospital over ten years with a focus on minimising the need for blood transfusions. A Spinal Surgery Care Pathway was developed including: nurse-led clinics facilitating pre-operative haemoglobin optimisation; intra operative cell-salvage, the use of tranexamic acid, and a transfusion criteria awareness programme.

Introduction

Procedure Based Assessments (PBAs) were recently introduced for orthopaedic trainees and play an increasing role in assessment. The study aims to describe the attitudes of trainees to the educational benefit of PBAs and the factors which underlie these attitudes.

Symptomatic venous thromboembolism (SVTE) is a potentially significant complication which may occur following injury or surgery. Recent NICE guidelines, and clinical targets have all focused on decreasing in hospital death from acquired SVTE. Despite these guidelines there are no large studies investigating the risk factors for or incidence of SVTE in acute trauma admission.

Data from a prospective series of 9167 consecutive patients with a diagnosis of fractured neck of femur (NOF) at a single institution was used to construct a risk score for SVTE. Twenty three factors were screened with pairwise analysis. The cohort had an event rate of 1.4%. A multiple logistic regression model was used to construct a risk score and correct for confounding variables from nine significant factors identified by the pairwise analysis. Four factors; length of stay; chest infection; cardiac failure and transfusion were used to produce the final risk score. The score was statistically significant (p< 0.0001) and highly predictive (ROC analysis, AUC=0.76) of SVTE.

The score was separately validated in two cohorts from different Level 1 trauma centres. In one prospective consecutive cohort of 1000 NOF patients all components of the Nottingham SVTE score were found to be individually statistically significant (p< 0.0045). The score was further validated in a separate cohort of 3200 patients undergoing elective hip surgery. The score was found to be statistically significantly predictive of SVTE as a whole, and three of the four components were individually predictive in this patient cohort.

Balancing risks and benefits for thromboprophylaxis is key to reducing the risk of thromboembolic events, minimising bleeding and other complications associated with the therapy. Our study of 13,367 prospective patients is the largest of its type and we have successfully constructed and validated a scoring system that can be used to inform patient treatment decisions.

The poor prognosis of patients with soft-tissue sarcoma as not changed in the past several decades, highlighting the necessity for new therapeutic approaches. T-cell based immunotherapies are a promising alternative to traditional cancer treatments due to their ability to target only malignant cells, leaving benign cells unharmed. The development of successful immunotherapy requires the identification and characterization of targetable immunogenic tumor antigens. Cancer-testis antigens (CTA) are a group of highly immunogenic tumor-associated proteins that have emerged as potential targets for CD8+ T-cell recognition. In addition to identifying a targetable antigen, it is crucial to understand the tumor immune microenvironment. The level of immune infiltration and mechanisms of immune suppression within the tumor play important roles in the outcome of immunotherapy. The goal of this study is to identify targetable immunogenic antigens for T-cell based immunotherapy and to characterize the tumor immune microenvironment in human dedifferentiated liposarcoma (DDLS) by Nanostring and IHC. To assess the complexity of the human DDLS tumor immune microenvironment and to identify target antigens we used the nCounter NanoString platform to generate a gene expression profile for hundreds of genes from RNA obtained from 29 DDLS and 10 control fat FFPE samples. To classify inflammatory status of DDLS tumors, we performed hierarchical clustering based on expression levels of selected tumor inflammatory signature genes (CCL5, CD27, CD274, CD276, CD8A, CMKLR1, CXCL9, CXCR6, HLA-DQA1, HLA-E, IDO1, LAG3, PDCDILG2, PSMB10, STAT1, TIGIT). To confirm protein expression and distribution of identified antigens, we performed immunohistochemistry on human tissue micro-arrays encompassing DDLPS tumor tissues and matched normal control tissue from 63 patients. IHC for the cancer testis antigens PBK, SPA17, MAGE-A3, NY-ESO-1 and SSX2 was performed, and the staining results were scored by two authors based on maximal staining intensity on a scale of zero to three (absent=0, weak=1, moderate=2, or strong=3) and the percentage of tumor cells that stained. Hierarchical clustering of DDLS tumors based on expression of tumor inflammation signature genes revealed two distinct groups, consisting of 15 inflamed tumor and 14 non-inflamed tumors, demonstrating tumor heterogeneity within the DDLS sarcoma subtype. All antigens were found to be expressed in DDLS at an mRNA level. SPA17 was expressed at the highest levels in DDLS, however, this antigen was expressed at high levels in normal fat. Notably, antigens PBK and TTK had the largest fold change increase in expression in DDLS compared to normal fat controls. Immunohistochemical analysis of selected antigens revealed that PBK was found to be expressed in 96% (52/54) of DDLS samples at high levels. Other antigens were absent or expressed at low levels in DDLS; MAGEA3 in 15.87% (10/63) NY-ESO-1 in 6.35% (4/62) and SSX2 in 12.7% (8/63) and SPA17 in 5.5% (3/54). This data shows considerable inter-tumoral heterogeneity of inflammation, which should be taken into consideration when designing an immunotherapy for DDLS. To date, these results show promising expression of PBK antigen in DDLS, which may be used as a target in the future development of an immunotherapy for sarcoma