Controversies in orthopaedic oncology.

Chondrosarcoma is the second most common surgically treated primary bone sarcoma. Despite a large number of scientific papers in the literature, there is still significant controversy about diagnostics, treatment of the primary tumour, subtypes, and complications. Therefore, consensus on its day-to-day treatment decisions is needed. In January 2024, the Birmingham Orthopaedic Oncology Meeting (BOOM) attempted to gain global consensus from 300 delegates from over 50 countries. The meeting focused on these critical areas and aimed to generate consensus statements based on evidence amalgamation and expert opinion from diverse geographical regions. In parallel, periprosthetic joint infection (PJI) in oncological reconstructions poses unique challenges due to factors such as adjuvant treatments, large exposures, and the complexity of surgery. The meeting debated two-stage revisions, antibiotic prophylaxis, managing acute PJI in patients undergoing chemotherapy, and defining the best strategies for wound management and allograft reconstruction. The objectives of the meeting extended beyond resolving immediate controversies. It sought to foster global collaboration among specialists attending the meeting, and to encourage future research projects to address unsolved dilemmas. By highlighting areas of disagreement and promoting collaborative research endeavours, this initiative aims to enhance treatment standards and potentially improve outcomes for patients globally. This paper sets out some of the controversies and questions that were debated in the meeting.

Incidence of avascular necrosis of native femur following hip transposition surgery for periacetabular malignancies: a single-centre experience.

BACKGROUND: Hip transposition surgery after surgical resection of large pelvic tumours is a well-established alternate to endoprosthetic reconstruction. The major goals of surgery are to ensure adequate resection margins with limb salvation, albeit with acceptable levels of morbidity. While surveillance is aimed at diagnosing local recurrence or distant metastasis primarily, other complications may occasionally be seen.The aim of this study was to assess incidence of avascular necrosis (AVN) in the preserved native femoral heads after hip transposition surgery for periacetabular malignancies, also known as hanging hip surgery. PATIENTS AND METHODS: Patient records and follow-up imaging of 22 patients who had undergone hanging hip surgery from 1999 to 2020 were retrospectively analysed to assess for any probable causes of AVN. RESULTS: Of the 22 patients, 5 (22.7%) had developed AVN on follow-up with a mean time of onset of about 10.5 months from surgery (5 months-2 years). A review of the patient demographics, surgical notes, preoperative management did not offer any clues as to the cause of AVN in these patients. Osteopenia was the most common radiological finding (59%) in most patients, but this also did not herald AVN onset. CONCLUSIONS: The theory that loss of major vascular supply to the femoral head from capsular disruption during hip transposition surgery would lead to AVN in most patients did not hold true as AVN occurred in a small number of patients.

Chondrosarcoma of the Femur: Is Local Recurrence Influenced by the Presence of an Extraosseous Component?

BACKGROUND: Chondrosarcoma (CS) is the second most common surgically treated primary malignancy of the bone. The current study explored the effect of the margin and extraosseous tumor component in CS in the femur on local recurrence (LR), LR-free survival (LRFS), and disease-specific survival (DSS). METHODS: Among 202 patients, 115 were in the proximal extremity of the femur, 4 in the corpus of the femur, and 83 in the distal extremity of femur; 105 patients had an extraosseous tumor component. RESULTS: In the Kaplan-Meier analysis, factors significant for decreased LRFS were the extraosseous tumor component (p < 0.001), extraosseous tumor component arising from the superior aspect (p < 0.001), histological grade (p = 0.031), and narrow surgical margin < 3 mm (p < 0.001). Factors significantly affecting DSS were the histological grade (p < 0.001), extraosseous component (p < 0.001), LR (p < 0.001), metastases (p < 0.001), and surgical margin (p < 0.001). CONCLUSIONS: In CS of the femur, the presence of an extraosseous tumor component has a predictive role in LRFS, and extraosseous tumor component arising from the superior aspect was significant for decreased LRFS. Wide margins were more commonly achieved when the tumor had only an intraosseous component, and the rate of LR was significantly higher in cases with an extraosseous tumor component. When the extraosseous component arose from the superior aspect of the femur, LR occurred more frequently despite achieving adequate margins.

Controversies in Oncologic Pediatric Limb Salvage.

With advances in chemotherapy and radiation therapy, surgical treatment of patients with bone sarcomas has advanced from most patients undergoing an amputation to now most patients undergoing a limb salvage procedure. With the advances of limb salvage surgical techniques, reconstructive procedures have expanded to include autografts, allografts, endoprosthetic replacements, and rotationplasty. In a growing child, the decision to perform each of these reconstructive options is individualized and each needs to be considered to provide the patient with the optimal oncologic and functional outcome, while being durable to minimize the risk of complications and subsequent surgeries.

Frequent microbiological profile changes are seen in subsequent-revision hip and knee arthroplasty for prosthetic joint infection.

A proportion of patients with hip and knee prosthetic joint infection (PJI) undergo multiple revisions with the aim of eradicating infection and improving quality of life. The aim of this study was to describe the microbiology cultured from multiply revised hip and knee replacement procedures to guide antimicrobial therapy at the time of surgery. Patients and methods: Consecutive patients were retrospectively identified from databases at two specialist orthopaedic centres in the United Kingdom between 2011 and 2019. Patient were included who had undergone repeat-revision total knee replacement (TKR) or total hip replacement (THR) for infection, following an initial failed revision for infection. Results: A total of 106 patients were identified. Of these patients, 74 underwent revision TKR and 32 underwent revision THR. The mean age at first revision was 67 years (SD 10). The Charlson comorbidity index was ≤ 2 for 31 patients, 3-4 for 57 patients, and ≥ 5 for 18 patients. All patients underwent at least two revisions, 73 patients received three, 47 patients received four, 31 patients received five, and 21 patients received at least six. After six revisions, 90 % of patients had different organisms cultured compared with the initial revision, and 53 % of organisms were multidrug resistant. The most frequent organisms at each revision were coagulase-negative Staphylococcus (36 %) and Staphylococcus aureus (19 %). Fungus was cultured from 3 % of revisions, and 21 % of infections were polymicrobial. Conclusion: Patients undergoing multiple revisions for PJI are highly likely to experience a change in organism, with 90 % of patients having a different organism cultured by their sixth revision. It is therefore important to administer empirical antibiotics at each subsequent revision, taking into account known drug resistance from previous cultures. Our results do not support the routine use of empirical antifungals.

Intraosseous conventional central chondrosarcoma does not metastasise irrespective of grade in pelvis, scapula and in long bone locations.

Background: Histological grade has been regarded as the most important prognostic factor in conventional central chondrosarcoma. To evaluate whether the presence of an extraosseous tumour component is associated with a decreased metastasis-free survival or disease-specific survival and alternatively to develop a simple prognostic and clinical decision-making tool. Material and methods: We searched two prospectively maintained international sarcoma centre databases for primary non metastatic central conventional chondrosarcomas of all grades in pelvis, scapula or long bone location, undergoing curative treatment, diagnosed between 2000 and 2020. Pre-treatment MRI scans were reviewed for the presence of an extraosseous mass. The metastasis-free survival (MFS) and disease-specific survival (DSS) were estimated by the Kaplan-Meier method from surgery to event, death or last follow-up. Results: 336 patients were identified between 2000 and 2020, undergoing surgical treatment for conventional central chondrosarcoma. 111 patients (33 %) had grade 1 tumours, 149 patients (44 %) had grade 2, and 76 patient (23 %) had grade 3 chondrosarcomas determined as the highest grade in the final resected specimen. An extraosseous soft tissue component was more frequent in higher grade tumours (p < 0.001) and present in 200 cases (60 %). None of the patients with an intraosseous tumour developed metastases or died of the disease. For patients with extraosseous tumour component, MFS was 92 % (95 % CI, 96-100) at 2-years and 74 % (95 % CI, 67-81) at 10-years and DSS was 91 % (95 % CI, 87-95) at 2-years and 75 % (95 % CI, 68-82) at 10-years. The MFS and DSS was significantly different (p < 0.001) for those patients with or without an extraosseous tumour component, irrespective of grade or anatomical location. Discussion: The results of this study has shown that the metastatic potential of intraosseous conventional central chondrosarcoma is negligible. The presence of an extraosseous soft tissue component may be used for prognostication and to guide treatment pathways for patients with central cartilage tumours.

Effect of radiotherapy on local recurrence, distant metastasis and overall survival in 1200 extremity soft tissue sarcoma patients. Retrospective analysis using IPTW-adjusted models.

BACKGROUND AND PURPOSE: Neoadjuvant (NRTX) and adjuvant radiotherapy (ARTX) reduce local recurrence (LR) risk in extremity soft tissue sarcoma (eSTS), yet their impact on distant metastasis (DM) and overall survival (OS) is less well defined. This study aimed at analysing the influence of NRTX/ARTX on all three endpoints using a retrospective, multicentre eSTS cohort. MATERIALS AND METHODS: 1200 patients (mean age: 60.7 ± 16.8 years; 44.4 % females) were retrospectively included, treated with limb sparing surgery and curative intent for localised, high grade (G2/3) eSTS. 194 (16.2 %), 790 (65.8 %), and 216 (18.0 %) patients had received NRTX, ARTX and no RTX, respectively. For the resulting three groups (no RTX vs. NRTX, no RTX vs. ARTX, NRTX vs. ARTX) Fine&Gray models for LR and DM, and Cox-regression models for OS were calculated, with IPTW-modelling adjusting for imbalances between groups. RESULTS: In the IPTW-adjusted analysis, NRTX was associated with lower LR-risk in comparison to no RTX (SHR [subhazard ratio]: 0.236; p = 0.003), whilst no impact on DM-risk (p = 0.576) or OS (p = 1.000) was found. IPTW-weighted analysis for no RTX vs. ARTX revealed a significant positive association between ARTX and lower LR-risk (SHR: 0.479, p = 0.003), but again no impact on DM-risk (p = 0.363) or OS (p = 0.534). IPTW-weighted model for NRTX vs. ARTX showed significantly lower LR-risk for NRTX (SHR for ARTX: 3.433; p = 0.003) but no difference regarding DM-risk (p = 1.000) or OS (p = 0.639). CONCLUSION: NRTX and ARTX are associated with lower LR-risk, but do not seem to affect DM-risk or OS. NRTX may be favoured over ARTX as our results indicate better local control rates.

The Importance of Awaiting Biopsy Results in Solitary Pathological Proximal Femoral Fractures : Do We Need to Biopsy Solitary Pathological Fractures?

BACKGROUND: The optimal surgical treatment for patients presenting with (impending and complete) pathological proximal femoral fractures is predicated on prognosis. Guidelines recommend a preoperative biopsy to exclude sarcomas, however no evidence confirms a benefit. OBJECTIVE: This study aimed to describe the diagnostic accuracy, morbidity and sarcoma incidence of biopsy results in these patients. MATERIAL AND METHODS: All patients (n = 153) presenting with pathological proximal femoral fractures between 2000 and 2019 were retrospectively evaluated. Patients after inadvertent surgery (n = 25) were excluded. Descriptive statistics were used to evaluate the accuracy and morbidity of diagnostic biopsies. RESULTS: Of 112/128 patients who underwent biopsy, nine (8%) biopsies were unreliable either due to being inconclusive (n = 5) or because the diagnosis changed after resection (n = 4). Of impending fractures, 32% fractured following needle core biopsy. Median time from diagnosis to surgery was 30 days (interquartile range 21-46). The overall biopsy positive predictive value (PPV) to differentiate between sarcoma and non-sarcoma was 1.00 (95% confidence interval [CI] 0.88-1.00). In patients with a previous malignancy (n = 24), biopsy (n = 23) identified the diagnosis in 83% (PPV 0.91, 95% CI 0.71-0.99), of whom five (24%) patients had a new diagnosis. In patients without a history of cancer (n = 61), final diagnosis included carcinomas (n = 24, 39.3%), sarcomas (n = 24, 39.3%), or hematological malignancies (n = 13, 21.3%). Biopsy (n = 58) correctly identified the diagnosis in 66% of patients (PPV 0.80, 95% CI 0.67-0.90). CONCLUSION: This study confirms the importance of a preoperative biopsy in solitary pathological proximal femoral fractures due to the risk of sarcoma in patients with and without a history of cancer. However, biopsy delays the time to definite surgery, results can be inconclusive or false, and it risks completion of impending fractures.

Custom-Made Metaphyseal Sleeves in "Beyond" AORI III Defects for Revision Knee Arthroplasty-Proof of Concept and Short-Term Results of a New Technique.

BACKGROUND: While off-the-shelf cones and sleeves yield good results in AORI type 2 and 3 defects in revision knee surgery, massive longitudinal defects may require a proximal tibia replacement. To achieve the best anatomical as well as biomechanical reconstruction and preserve the tibial tuberosity, we developed custom-made metaphyseal sleeves (CMSs) to reconstruct massive defects with a hinge knee replacement. METHODS: Between 2019 and 2022, 10 patients were treated in a single-center study. The indication for revision was aseptic loosening in five cases and periprosthetic joint infection in five cases. The mean number of previous revisions after the index operations was 7 (SD: 2; 4-12). A postoperative analysis was conducted to evaluate the functional outcome as well as the osteointegrative potential. RESULTS: Implantation of the CMS in rTKA was carried out in all cases, with a mean operation time of 155 ± 48 (108-256) min. During the follow-up of 23 ± 7 (7-31) months, no CMS was revised and revisions due to other causes were conducted in five cases. Early radiographic evidence of osseointegration was recorded using a validated method. The postoperative OKS showed a significant increase (p < 0.001), with a mean score of 24 (SD: 4; range: 14-31). CONCLUSION: Custom-made metaphyseal sleeves show acceptable results in extreme cases. As custom-made components become more and more common, this treatment algorithm presents a viable alternative in complex rTKA.

Pelvic bone sarcomas, prognostic factors, and treatment: A narrative review of the literature.

Primary sarcomas of bone are rare malignant mesenchymal tumors. The most common bone sarcomas are osteosarcoma, Ewing's sarcoma, and chondrosarcoma. The prognosis has improved over the years, but bone sarcomas are still life-threatening tumors that need a multidisciplinary approach for diagnosis and treatment. Bone sarcomas arising in the pelvis present a unique challenge to orthopedic oncologists due to the absence of natural anatomical barriers, the close proximity of vital neurovascular structures, and the high mechanical demands placed on any pelvic reconstruction following the excision of the tumor. While radiotherapy has an important role especially in Ewing's sarcoma and chemotherapy for both Ewing's sarcoma and osteosarcoma, surgery remains the main choice of treatment for all three entities. While external hemipelvectomy has remained one option, the main aim of surgery is limb salvage. After complete tumor resection, the bone defect needs to be reconstructed. Possibilities to reconstruct the defect include prosthetic or biological reconstruction. The method of reconstruction is dependent on the location of tumor and the surgery required for its removal. The aim of this article is to give an insight into pelvic bone sarcomas, their oncological and surgical outcomes, and the options for treatment based on the authors' experiences.

Beyond type III Paprosky acetabular defects: are partial pelvic replacements with iliosacral fixation successful?

PURPOSE: Supra-acetabular bone loss close beyond the sciatic notch is one of the most challenging defect types for stable anatomical reconstruction in revision arthroplasty. Using reconstruction strategies from tumour orthopaedic surgery, we adapted tricortical trans-iliosacral fixation options for custom-made implants in revision arthroplasty. The aim of the present study was to present the clinical and radiological results of this extraordinary pelvic defect reconstruction. METHODS: Between 2016 and 2021, 10 patients with a custom-made pelvic construct using tricortical iliosacral fixation (see Fig. 1) were included in the study. Follow-up was 34 (SD 10; range 15-49) months. Postoperatively CT scans evaluating the implant position were performed. Functional outcome and the clinical results were recorded. RESULTS: Implantation was possible as planned in all cases in 236 (SD 64: range 170-378) min. Correct centre of rotation (COR) reconstruction was possible in nine cases. One sacrum screw crossed a neuroforamen in one case without clinical symptoms. During the follow-up period, four further operations were required in two patients. There were no individual implant revisions or aseptic loosening recorded. The Harris Hip Score increased significantly from 27 Pts. to 67 Pts. with a mean improvement of 37 (p < 0.005). EQ-5D developed from 0.562 to 0.725 (p = 0.038) as a clear improvement in quality of life. CONCLUSION: Custom-made partial pelvis replacement with iliosacral fixation offers a safe solution in "beyond Paprosky type III defects" for hip revision arthroplasty. Due to meticulous planning, precise implantation with good clinical outcome can be achieved. Furthermore, the functional outcome and patient satisfaction increased significantly showing promising early results with a relatively low complication rate.

Chondrosarcoma of the Proximal Humerus: Does the Margin Affect Survival?

Chondrosarcoma (CS) is the second most common primary malignant bone tumour and, in the absence of reliable chemotherapy and radiotherapy, is effectively a surgical disease. Overall disease specific survival (DSS) is affected by tumour grade, whilst resection margin contributes to local recurrence free survival (LRFS). The aim of this study was to investigate factors that affect the local and systemic prognoses for conventional central CSs arising from the proximal humerus. A multi-centre, retrospective study from three international collaborative sarcoma centres identified 110 patients between 1995 and 2020 undergoing treatment for a conventional central CS of the proximal humerus; 58 patients (53%) had a grade 1 tumour, 36 (33%) had a grade 2 tumour, and 16 patients (13%) had a grade 3 CS. The mean age of patients was 50 years (range 10-85). The incidence of local recurrence (LR) was 9/110 (8.2%), and the disease specific mortality was 6/110 (5.5%). The grade was a statistically significant factor for LRFS (p < 0.001). None of the grade 1 tumours developed LR. The DSS was affected by the grade (p < 0.001) but not by the LR (p = 0.4). Only one patient with a grade 2 tumour died from the disease. The proximal humeral grade 1 CS behaved as a benign tumour, having no cases of LR nor death due to disease. Grade 2 CSs of the proximal humerus behaved in a more indolent way when compared with comparable grade tumours elsewhere in the appendicular skeleton, being locally aggressive with a higher LR rate than grade 1 CSs but still having very low mortality and a high rate of DSS. The LR in grade 2 CSs did not affect the DSS; therefore, surgical management in proximal humeral grade 2 CSs should have a greater emphasis on preserving function whilst maintaining an adequate margin for resection. The proximal humeral grade 3 CS was, as elsewhere in the skeleton, an aggressive, high-grade tumour. Therefore, surgical management should include en bloc resection with clear margins to avoid LR.

Accuracy of MRI scans in predicting intra-articular joint involvement in high-grade sarcomas around the knee.

Aims: Intra-articular (IA) tumours around the knee are treated with extra-articular (EA) resection, which is associated with poor functional outcomes. We aim to evaluate the accuracy of MRI in predicting IA involvement around the knee. Methods: We identified 63 cases of high-grade sarcomas in or around the distal femur that underwent an EA resection from a prospectively maintained database (January 1996 to April 2020). Suspicion of IA disease was noted in 52 cases, six had IA pathological fracture, two had an effusion, two had prior surgical intervention (curettage/IA intervention), and one had an osseous metastasis in the proximal tibia. To ascertain validity, two musculoskeletal radiologists (R1, R2) reviewed the preoperative imaging (MRI) of 63 consecutive cases on two occasions six weeks apart. The radiological criteria for IA disease comprised evidence of tumour extension within the suprapatellar pouch, intercondylar notch, extension along medial/lateral retinaculum, and presence of IA fracture. The radiological predictions were then confirmed with the final histopathology of the resected specimens. Results: The resection histology revealed 23 cases (36.5%) showing IA disease involvement compared with 40 cases without (62%). The intraobserver variability of R1 was 0.85 (p < 0.001) compared to R2 with κ = 0.21 (p = 0.007). The interobserver variability was κ = 0.264 (p = 0.003). Knee effusion was found to be the most sensitive indicator of IA involvement, with a sensitivity of 91.3% but specificity of only 35%. However, when combined with a pathological fracture, this rose to 97.5% and 100% when disease was visible in Hoffa's fat pad. Conclusion: MRI imaging can sometimes overestimate IA joint involvement and needs to be correlated with clinical signs. In the light of our findings, we would recommend EA resections when imaging shows effusion combined with either disease in Hoffa's fat pad or retinaculum, or pathological fractures.

YBX1-interacting small RNAs and RUNX2 can be blocked in primary bone cancer using CADD522.

Primary bone cancer (PBC) comprises several subtypes each underpinned by distinctive genetic drivers. This driver diversity produces novel morphological features and clinical behaviour that serendipitously makes PBC an excellent metastasis model. Here, we report that some transfer RNA-derived small RNAs termed tRNA fragments (tRFs) perform as a constitutive tumour suppressor mechanism by blunting a potential pro-metastatic protein-RNA interaction. This mechanism is reduced in PBC progression with a gradual loss of tRNAGlyTCC cleavage into 5' end tRF-GlyTCC when comparing low-grade, intermediate-grade and high-grade patient tumours. We detected recurrent activation of miR-140 leading to upregulated RUNX2 expression in high-grade patient tumours. Both tRF-GlyTCC and RUNX2 share a sequence motif in their 3' ends that matches the YBX1 recognition site known to stabilise pro-metastatic mRNAs. Investigating some aspects of this interaction network, gain- and loss-of-function experiments using small RNA mimics and antisense LNAs, respectively, showed that ectopic tRF-GlyTCC reduced RUNX2 expression and dispersed 3D micromass architecture in vitro. iCLIP sequencing revealed YBX1 physical binding to the 3' UTR of RUNX2. The interaction between YBX1, tRF-GlyTCC and RUNX2 led to the development of the RUNX2 inhibitor CADD522 as a PBC treatment. CADD522 assessment in vitro revealed significant effects on PBC cell behaviour. In xenograft mouse models, CADD522 as a single agent without surgery significantly reduced tumour volume, increased overall and metastasis-free survival and reduced cancer-induced bone disease. Our results provide insight into PBC molecular abnormalities that have led to the identification of new targets and a new therapeutic.

Early radiographic osseointegration of a novel highly porous 3D-printed titanium collar for megaprostheses compared to a previous generation smooth HA-coated collar.

PURPOSE: Extracortical osseointegration at the collar-bone interface of megaprostheses is associated with improved implant stability, lower rates of stem fracture and loosening. The use of hydroxy-apatite (HA-) coated collars showed mixed results in previously published reports. A novel collar system has recently become available utilizing additive manufacturing technology to create a highly porous titanium collar with a calcium-phosphate coated surface. The aim of this study was to evaluate our early experience with this novel collar and compare it to the previously used HA-coated model. METHODS: Twenty patients who underwent megaprostheses implantation utilizing the novel collar system were case matched to 20 patients who had previously undergone a HA-coated collar. A minimum radiological follow-up of three months was available in all included patients. Osseointegration was evaluated using postoperative plain radiographs in two planes based on a previously published semi-quantitative score. RESULTS: Compared to the HA-coated collar the use of the novel highly porous collar was associated with a higher proportion of cases demonstrating osseointegration at the bone-collar interface (80% vs. 65%). Application of the highly porous collar led to a significantly shortened time to reach the final ongrowth score (173 ± 89 days vs. 299 ± 165 days, p < 0.05). At one year follow-up, 90% of the novel collars had reached their final osseoingration grade compared to 50% in the HA-coated collar group (p < 0.001). Radiological osseointegration was seen in 71% for highly porous collars where the indication was revision arthroplasty, compared to 27% in reported in the literature. CONCLUSION: These results indicate more reliable and accelerated osseointegration at the bone-collar interface of a novel highly porous collar system compared to a previously used HA-coated collar. Further studies are warranted to confirm these findings.

Anatomical distribution, the incidence of malignancy and diagnostic workup in the pathological lesions of the clavicle: a review of 410 cases.

BACKGROUND: The clavicle poses a diagnostic dilemma of the pathological lesions due to the wide range of pathologies seen at this site. This study aimed to identify and stratify various pathologies seen in the clavicle and to guide ways of investigation for diagnosis based on age, site and investigation findings. MATERIALS AND METHODS: Four hundred and ten cases with clavicle lesions were identified in our database. Data were collected about the patient's medical history, previous investigation, inflammatory markers radiological investigations and biopsy. All patients were worked up and managed after discussion in a multidisciplinary team meeting (MDT). RESULTS: Non-malignant lesions accounted for 79% of cases. Infection was the most common diagnosis (39%) and the commonest diagnosis in those less than 20 years of age. 73% of the lesions were found at the medial end of the clavicle. Malignant tumours were 21%, while primary benign bone tumours accounted for only 14%. 50% of the malignant lesions were due to metastatic disease. The risk of malignancy increases with advancing age. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were not sensitive as a diagnostic tool in cases of osteomyelitis confirmed by histology. Magnetic resonance imaging (MRI) was noted to have high sensitivity and specificity for identifying the nature of a lesion and diagnosis. CONCLUSION: We have identified age as a positive predictor of a malignant cause in pathological lesions of the clavicle. MRI should be considered in all these cases. CRP and ESR have poor predictive values in diagnosing infection in the clavicle. Patients presenting with clavicle lesions should be discussed in a specialist MDT and undergo a systemic diagnostic workup, still in some cases, diagnosis can be speculated based on the patient's age, location of the lesion within the clavicle and the features seen on the MRI scan. LEVEL OF EVIDENCE: IV.

Complete tumor necrosis after neoadjuvant chemotherapy defines good responders in patients with Ewing sarcoma.

BACKGROUND: Survival in patients who have Ewing sarcoma is correlated with postchemotherapy response (tumor necrosis). This treatment response has been categorized as the response rate, similar to what has been used in osteosarcoma. There is controversy regarding whether this is appropriate or whether it should be a dichotomy of complete versus incomplete response, given how important a complete response is for in overall survival of patients with Ewing sarcoma. The purpose of this study was to evaluate the impact that the amount of chemotherapy-induced necrosis has on (1) overall survival, (2) local recurrence-free survival, (3) metastasis-free survival, and (4) event-free survival in patients with Ewing sarcoma. METHODS: In total, 427 patients who had Ewing sarcoma or tumors in the Ewing sarcoma family and received treatment with preoperative chemotherapy and surgery at 10 international institutions were included. Multivariate Cox proportional-hazards analyses were used to assess the associations between tumor necrosis and all four outcomes while controlling for clinical factors identified in bivariate analysis, including age, tumor volume, location, surgical margins, metastatic disease at presentation, and preoperative radiotherapy. RESULTS: Patients who had a complete (100%) tumor response to chemotherapy had increased overall survival (hazard ratio [HR], 0.26; 95% CI, 0.14-0.48; p < .01), recurrence-free survival (HR, 0.40; 95% CI, 0.20-0.82; p = .01), metastasis-free survival (HR, 0.27; 95% CI, 0.15-0.46; p ≤ .01), and event-free survival (HR, 0.26; 95% CI, 0.16-0.41; p ≤ .01) compared with patients who had a partial (0%-99%) response. CONCLUSIONS: Complete tumor necrosis should be the index parameter to grade response to treatment as satisfactory in patients with Ewing sarcoma. Any viable tumor in these patients after neoadjuvant treatment should be of oncologic concern. These findings can affect the design of new clinical trials and the risk-stratified application of conventional or novel treatments.

Haemorrhagic soft-tissue sarcoma: Oncological outcomes and prognostic factors for survival.

INTRODUCTION: Haemorrhagic soft-tissue sarcomas (HSTS) are characterised by aggressive local growth and highly metastatic behaviour. We aimed to describe oncological outcomes and prognostic factors. MATERIALS AND METHODS: Retrospective review including 64 patients treated with palliation (n = 7), with limb salvage surgery (LSS) (n = 9), with neoadjuvant radiotherapy (RT) + LSS (n = 12), with LSS + adjuvant RT (n = 30) or amputation (n = 6). Kaplan-Meier survival analysis estimated overall survival (OS), metastasis-free survival (MFS) and local recurrence-free survival (LRFS). After uni- and multivariate analysis, prognostic factors affecting OS, MFS and LRFS were identified. RESULTS: Median age was 67 years (IQR 23 years) with median follow-up of 11 months (IQR 28 months). All cases were high grade. Eight (13%) had pulmonary metastases at presentation and another 40 (63%) developed metastases after median 9 months (IQR 19 months). Median OS was 12 months (IQR 38 months), and estimated OS after two-years was 15.9% and 52.9% for patients with and without metastatic disease at presentation, respectively. Improved OS was associated with negative resection margins (p = 0.031), RT (p = 0.045), neoadjuvant RT (versus adjuvant RT, p = 0.044) and amputation (versus LSS, p < 0.001). MFS was 35.1% after two-years. LR occurred in 18 of 51 (35.3%) patients with surgically treated localised disease. LRFS was 63.4% after two-years and significantly affected by a negative margin (p = 0.042) and RT (p = 0.001). CONCLUSION: Haemorrhagic soft-tissue sarcomas should be excised, either with amputation or LSS with a clear resection margin. If LSS is attempted, neoadjuvant RT reduces the risk of tumour spillage and early LR, enhances the feasibility of achieving clear resection margins, and offers superior overall survival compared to adjuvant RT.

Repeat revision TKR for failed management of peri-prosthetic infection has long-term success but often require multiple operations: a case control study.

BACKGROUND: Prosthetic joint infection (PJI) is associated with poor outcomes and catastrophic complications. The aim of this study was to present the outcomes of re-revision surgery for PJI of the knee following previous failed two-stage exchange arthroplasty. MATERIALS AND METHODS: A retrospective analysis was performed of 32 patients who underwent re-revision knee arthroplasty, having already undergone at least one previous two-stage exchange for PJI with a minimum follow-up of two-years for alive patients. Outcomes were compared to a matched control of two-stage revisions for PJI of a primary knee replacement also containing 32 patients. Outcomes investigated were eradication of infection, re-operation, mortality and limb-salvage rate. RESULTS: Successful eradication of infection was achieved in 50% of patients following re-revision surgery, compared with 91% following two-stage exchange of primary knee replacement for PJI (p < 0.001). Fourteen (44%) patients required further re-operation compared with three (9%) patients in the primary group (p = 0.006). Amputation was performed in one case (3%) with thirteen patients (92%) who had infection controlled by debridement, antibiotics and implant retention (DAIR), further revision surgery or arthrodesis. Two patients died with infection (6%) and the long-term rate for infection control was 91%. The mean number of procedures following surgery for the re-revision group was 2.8 (0-9) compared with 0.13 (0-1) for the primary two-stage group (p < 0.001). Five-year patient survival was 90.6% (95% CI 77.1-100). The limb-salvage rate for the re-revision cohort was 97%. CONCLUSION: Outcomes for re-revision knee arthroplasty for PJI have higher re-operation and failure rates, but no worse mortality than in revisions of primary knee replacements. Failures can successfully be managed by further operation.