Aneurysmal bone cysts: A UK wide tumor center experience.

BACKGROUND AND OBJECTIVES: This multicenter retrospective series of consecutive extra-spinal aneurysmal bone cysts aims to identify risk factors for treatment failure. METHODS: Aneurysmal bone cysts treated within seven collaborating centers with over 12-months follow-up were eligible for inclusion. Survival analyses were performed to identify variables associated with recurrence using log-rank tests and Cox proportional hazard regression. RESULTS: One hundred and fifteen (M:F 60:55) patients were included. Median age at presentation was 13 years and median follow-up was 27 months. Seventy-five patients underwent surgical curettage and 27% of these required further intervention for recurrence. Of the 30 patients who underwent biopsy with limited percutaneous curettage as initial procedure, 47% required no further treatment. Patients under 13 years (log-rank p = 0.006, HR 2.3, p = 0.011) and those treated who had limited curettage (log-rank p = 0.001, HR 2.7, p = 0.002) had a higher risk of recurrence/persistence. CONCLUSIONS: There is a high risk of recurrence following surgical treatment for aneurysmal bone cysts and this risk is higher in young patients. However, the cyst heals in a substantial number of patients who have a limited curettage at the time of biopsy.

Machine learning models based on routinely sampled blood tests can predict the presence of malignancy amongst patients with suspected musculoskeletal malignancy.

AIMS: This study explores the possibility of using routinely taken blood tests in the diagnosis and triage of patients with suspected musculoskeletal malignancy. METHODS: A retrospective study was performed on results of patients who had presented for assessment to a regional musculoskeletal tumour unit. Blood results of patients with a histologically confirmed diagnosis between 2010 and 2020 were retrieved. 33 distinct blood tests were available for model forming. Results were standardised by calculating z-scores. Data were split into a training set (70%) and a test set (30%). The training set was balanced by resampling underrepresented classes. The random forest algorithm performed best and was selected for model forming. Receiver operating characteristic curves were used to find the optimum threshold. Models were calibrated and performance metrics evaluated with confusion tables. RESULTS: 2371 patients formed the study population. 1080 had a malignant diagnosis in one of three categories: sarcoma, metastasis, or haematological malignancy. 1291 had a benign condition. Metastasis could be predicted with an accuracy of 79% (AUC 87%, sensitivity 79%, specificity 80% NPV 91%). Haematological malignancy accuracy 79% (AUC 81%, sensitivity 77%, specificity 79%, NPV 97%). Sarcoma accuracy 64% (AUC 73%, sensitivity 76%, specificity 61%, NPV 88%) and all malignancy accuracy 74% (AUC 80%, sensitivity 72%, specificity 75%, NPV 76%). CONCLUSION: Routinely performed blood tests can be useful in triage of musculoskeletal tumours and can be used to predict presence of musculoskeletal malignancy.

What Proportion of Patients with Bone and Soft Tissue Tumors Contracted Coronavirus-19 and Died From Surgical Procedures During the Initial Period of the COVID-19 Pandemic? Results From the Multicenter British Orthopaedic Oncology Society Observational Study.

BACKGROUND: Delivering uninterrupted cancer treatment to patients with musculoskeletal tumors has been essential during the rapidly evolving coronavirus 2019 (COVID-19) pandemic, as delays in management can be detrimental. Currently, the risk of contracting COVID-19 in hospitals when admitted for surgery and the susceptibility due to adjuvant therapies and associated mortality due to COVID-19 is unknown, but knowledge of these potential risks would help treating clinicians provide appropriate cancer care. QUESTIONS/PURPOSES: (1) What is the risk of hospital-acquired COVID-19 in patients with musculoskeletal tumors admitted for surgery during the initial period of the pandemic? (2) What is the associated mortality in patients with musculoskeletal tumors who have contracted COVID-19? (3) Are patients with musculoskeletal tumors who have had neoadjuvant therapy (chemotherapy or radiation) preoperatively at an increased risk of contracting COVID-19? (4) Is a higher American Society of Anesthesiologists (ASA) grade in patients with musculoskeletal tumors associated with an increased risk of contracting COVID-19 when admitted to the hospital for surgery? METHODS: This retrospective, observational study analyzed patients with musculoskeletal tumors who underwent surgery in one of eight specialist centers in the United Kingdom, which included the five designated cancer centers in England, one specialist soft tissue sarcoma center, and two centers from Scotland between March 12, 2020 and May 20, 2020. A total of 347 patients were included, with a median (range) age of 53 years (10 to 94); 60% (207 of 347) were men, and the median ASA grade was II (I to IV). These patients had a median hospital stay of 8 days (0 to 53). Eighteen percent (61 of 347) of patients had received neoadjuvant therapy (8% [27] chemotherapy, 8% [28] radiation, 2% [6] chemotherapy and radiation) preoperatively. The decision to undergo surgery was made in adherence with United Kingdom National Health Service and national orthopaedic oncology guidelines, but specific data with regard to the number of patients within each category are not known. Fifty-nine percent (204 of 347) were negative in PCR testing done 48 hours before the surgical procedure; the remaining 41% (143 of 347) were treated before preoperative PCR testing was made mandatory, but these patients were asymptomatic. All patients were followed for 30 days postoperatively, and none were lost to follow-up during that period. The primary outcome of the study was contracting COVID-19 in the hospital after admission. The secondary outcome was associated mortality after contracting COVID-19 within 30 days of the surgical procedure. In addition, we assessed whether there is any association between ASA grade or neoadjuvant treatment and the chances of contracting COVID-19 in the hospital. Electronic patient record system and simple descriptive statistics were used to analyze both outcomes. RESULTS: Four percent (12 of 347) of patients contracted COVID-19 in the hospital, and 1% (4 of 347) of patients died because of COVID-19-related complications. Patients with musculoskeletal tumors who contracted COVID-19 had increased mortality compared with patients who were asymptomatic or tested negative (odds ratio 55.33 [95% CI 10.60 to 289.01]; p < 0.001).With the numbers we had, we could not show that adjuvant therapy had any association with contracting COVID-19 while in the hospital (OR 0.94 [95% CI 0.20 to 4.38]; p = 0.93). Increased ASA grade was associated with an increased likelihood of contracting COVID-19 (OR 58 [95% CI 5 to 626]; p < 0.001). CONCLUSION: Our results show that surgeons must be mindful and inform patients that those with musculoskeletal tumors are at risk of contracting COVID-19 while admitted to the hospital and some may succumb to it. Hospital administrators and governmental agencies should be aware that operations on patients with lower ASA grade appear to have lower risk and should consider restructuring service delivery to ensure that procedures are performed in designated COVID-19-restricted sites. These measures may reduce the likelihood of patients contracting the virus in the hospital, although we cannot confirm a benefit from this study. Future studies should seek to identify factors influencing these outcomes and also compare surgical complications in those patients with and without COVID-19. LEVEL OF EVIDENCE: Level III, therapeutic study.

Bone biopsy results in patients with a history of malignancy: a case series of 378 patients.

OBJECTIVE: The value of a bone biopsy in patients who present with a bone lesion and past medical history of malignancy is uncertain. The objective of this study was to evaluate the outcome of bone biopsies in patients with a history of a malignancy undergoing bone biopsy of a lesion in a regional bone tumour unit. Secondary outcomes include the assessment of survival in the different outcome groups. MATERIALS AND METHODS: This was a retrospective study of patients, with a previous malignancy and suspicious bone lesions, who underwent bone biopsy for final diagnosis between March 2010 and September 2019. Results of the biopsy were summarized into 3 groups: confirmed original malignancy, confirmed benign diagnosis, and confirmed new malignancy. Survival analysis of each group was also undertaken. RESULTS: A total of 378 patients met the inclusion criteria (mean age 64 years, 216 females (57%)). In 250 cases (66%), the original malignancy was confirmed on the bone biopsy; in 128 cases, an alternative diagnosis was confirmed (benign diagnosis in 69 (18%)), and 59 had a new malignancy (16%). Survival was significantly greater for those in whom a benign diagnosis was confirmed (logrank test p = 0.0100). CONCLUSION: This study shows that for patients presenting with a suspicious bone lesion, together with a history of malignancy, in a third of cases, the bone biopsy will confirm an alternative diagnosis of a benign lesion or a new malignancy. Survival of these patients will vary significantly depending on the biopsy outcome.

Intraosseous lipomas originating from simple bone cysts.

PURPOSE: Fatty or part-fatty intraosseous lesions are occasionally encountered while imaging the skeletal system. A number of case reports have proposed involution of calcaneal bone cysts to intraosseous lipomas, but this has never been proven. This paper sets out to prove that simple bone cysts (SBCs) can involute to fatty lesions indistinguishable from intraosseous lipomas. MATERIALS AND METHODS: The pathology and PACS databases at 2 specialist orthopedic hospitals were retrospectively interrogated for all cases of intraosseous lipomas or SBCs with cross-sectional imaging follow-up for SBCs and precursor or follow-up imaging for intraosseous lipomas, in the time period from August 2007 to December 2016. For intraosseous lipoma cases, these were only included if change in imaging appearances was observed. RESULTS: There was no case of change in the appearance in intraosseous lipomas. Six cases of SBC with cross-sectional imaging follow-up were identified in one participating hospital and none in the other. The 6 cases were comprised of 4 male and 2 female patients. Two were located in the proximal humerus, one in the proximal tibia, and 3 in the os calcis. All cases demonstrated filling in of the cystic lesion with fat from the periphery, in 2 cases complete filling in, and in 4 cases partial fatty conversion. CONCLUSION: SBCs can heal with fatty conversion of the cystic cavity, with partly cystic remnants. It is proposed that at least part of the so-called intraosseous lipomas are healed simple bone cysts.

Synovial chondromatosis and soft tissue chondroma: extraosseous cartilaginous tumor defined by FN1 gene rearrangement.

A fusion between fibronectin 1 (FN1) and activin receptor 2A (ACVR2A) has been reported previously in isolated cases of the synovial chondromatosis. To analyze further and validate the findings, we performed FISH and demonstrated recurrent FN1-ACVR2A rearrangements in synovial chondromatosis (57%), and chondrosarcoma secondary to synovial chondromatosis (75%), showing that FN1 and/or AVCR2A gene rearrangements do not distinguish between benign and malignant synovial chondromatosis. RNA sequencing revealed the presence of the FN1-ACVR2A fusion in several cases that were negative by FISH suggesting that the true prevalence of this fusion is potentially higher than 57%. In soft tissue chondromas, FN1 alterations were detected by FISH in 50% of cases but no ACVR2A alterations were identified. RNA sequencing identified a fusion involving FN1 and fibroblast growth factor receptor 2 (FGFR2) in the case of soft tissue chondroma and FISH confirmed recurrent involvement of both FGFR1 and FGFR2. These fusions were present in a subset of soft tissue chondromas characterized by grungy calcification, a feature reminiscent of phosphaturic mesenchymal tumor. However, unlike the latter, fibroblast growth factor 23 (FGF23) mRNA expression was not elevated in soft tissue chondromas harboring the FN1-FGFR1 fusion. The mutual exclusivity of ACVR2A rearrangements observed in synovial chondromatosis and FGFR1/2 in soft tissue chondromas suggests these represent separate entities. There have been no reports of malignant soft tissue chondromas, therefore differentiating these lesions will potentially alter clinical management by allowing soft tissue chondromas to be managed more conservatively.

Patient factors affecting the Toronto extremity salvage score following limb salvage surgery for bone and soft tissue tumors.

BACKGROUND AND OBJECTIVES: The Toronto extremity salvage score (TESS) assesses physical function following limb salvage for bone and soft tissue sarcoma. In 2012, Clayer et al. showed increasing age affects the TESS score in normal individuals. The purpose of this study was to investigate what other patient factors affect outcome? METHODS: We reviewed the TESS scores, age, sex, BMI, diagnosis, smoking status, and social deprivation score of patients who have undergone limb salvage in our unit. Data were extracted from our tumor database and reviewed. Statistical analysis was performed using Wilcoxon pairwise test and linear regression analysis. RESULTS: Four hundred and ninety-eight TESS scores were found for 198 patients. Data were analyzed separating upper limb (UL) and lower limb (LL) tumors. In the UL group, being female (P = 0.01) and having a bone lesion (P < 0.001) were associated with a lower TESS score. In the LL group, being female (P = 0.04), increasing age (P = 0.002), having a bone lesion (P < 0.001), increasing BMI (P < 0.001), and smoking (P = 0.005) were associated with a lower TESS score. CONCLUSIONS: Analysis has shown that female sex, increasing age and BMI, smoking and having a bone lesion have an adverse effect on physical function following limb salvage, as indicated by the mean TESS score. J. Surg. Oncol. 2016;113:804-810. © 2016 Wiley Periodicals, Inc.

Accuracy of magnetic resonance imaging in planning the osseous resection margins of bony tumours in the proximal femur: based on coronal T1-weighted versus STIR images.

OBJECTIVE: Assessment of the extent of tumours using magnetic resonance imaging (MRI) is the basis for bone resection in limb-salvage surgery. We aimed to compare the accuracy of T1-weighted MRI and STIR sequences in measuring the extent of proximal femoral tumours, using the macroscopic specimens as the gold standard for comparison. MATERIALS AND METHODS: We compared single coronal T1-weighted with STIR sequences in 34 proximal femoral tumours, using bivalved resected macroscopic tumours for comparison. After randomisation, four observers measured longitudinal osseous tumour extent using MRI and specimen photographs on two separate occasions, 3 weeks apart. RESULTS: There were 25 metastatic tumours, 8 chondrosarcomas and 1 myeloma. Eight patients presented with pathological fractures. The Pearson's correlation coefficient for comparison of T1 with macroscopic tumours was 0.91 (95% confidence interval [CI]: 0.83 to 0.96) for all observers and 0.90 (95% CI: 0.81 to 0.95) for STIR images. This difference was not statistically significant, and T1 and STIR sequence measurements had similar precision and accuracy. Bland-Altman plots showed T1-weighted imaging to be unbiased, whereas STIR sequences were biased and had systematic error. Moreover, STIR measurements overestimated tumour size by 6.4 mm (95% CI: -26.9 to 39.7 mm) and 2 patients were outliers. T1 measurements were closer to the macroscopic measurements with a mean difference of 1.3 mm (95% CI: -28.9 mm to 31.5 mm), with 3 patients falling outside of this. The variance was greater for STIR measurements. This difference between T1 and STIR measurements was statistically significant (p = 0.000003). The intra-observer reliability between separate measurements for MRI and specimen photographs achieved interclass correlation coefficients of 0.97, 0.96 and 0.95 (T1, STIR and macroscopic tumour respectively). T1 had greater interobserver correlation than for STIR and macroscopic tumour measurements (0.88 vs 0.85 and 0.85 respectively). These differences in interclass correlation were not statistically significant. CONCLUSION: This study has shown T1-weighted MRI sequences to be unbiased compared with STIR sequences at determining intra-osseous tumour extent. STIR overestimates the length of bone tumours. T1 is therefore preferred for pre-operative planning for the resection of bone tumours.

Using nanopore sequencing to identify bacterial infection in joint replacements: a preliminary study.

This project investigates if third-generation genomic sequencing can be used to identify the species of bacteria causing prosthetic joint infections (PJIs) at the time of revision surgery. Samples of prosthetic fluid were taken during revision surgery from patients with known PJIs. Samples from revision surgeries from non-infected patients acted as negative controls. Genomic sequencing was performed using the MinION device and the rapid sequencing kit from Oxford Nanopore Technologies. Bioinformatic analysis pipelines to identify bacteria included Basic Local Alignment Search Tool, Kraken2 and MinION Detection Software, and the results were compared with standard of care microbiological cultures. Furthermore, there was an attempt to predict antibiotic resistance using computational tools including ResFinder, AMRFinderPlus and Comprehensive Antibiotic Resistance Database. Bacteria identified using microbiological cultures were successfully identified using bioinformatic analysis pipelines. Nanopore sequencing and genomic classification could be completed in the time it takes to perform joint revision surgery (2-3 h). Genomic sequencing in this study was not able to predict antibiotic resistance in this time frame, this is thought to be due to a short-read length and low read depth. It can be concluded that genomic sequencing can be useful to identify bacterial species in infected joint replacements. However, further work is required to investigate if it can be used to predict antibiotic resistance within clinically relevant timeframes.

Clinical outcome of open ankle fractures in patients above 70 years of age.

BACKGROUND: Open fractures of the ankle are complex injuries requiring multidisciplinary input and are associated with significant morbidity and mortality. However, data on the clinical outcomes of open ankle fracture management in patients older than 70 is minimal. AIM: To evaluate the clinical outcomes following open ankle fracture management in patients older than 70. Our secondary aim is to look at predictors of poor outcomes. METHODS: Following local research and audit department registration, 22 years of prospectively collated data from an electronic database in a district general hospital were assessed. All patients older than 70 years of age with an open ankle fracture requiring surgical intervention were identified. Demographic information, the nature, and the number of surgical interventions were collated. Complications, including surgical site infection (SSI), venous thromboembolic events (VTEs) during hospital stay, and mortality rate, were reviewed. RESULTS: A total of 37 patients were identified (median age: 84 years, range: 70-98); n = 30 females median age: 84 years, range: 70-97); n = 7 males median age: 74 years, range: 71-98)) who underwent surgical intervention after an open ankle fracture. Sixteen patients developed SSIs (43%). Superficial SSIs (n = 8) were managed without surgical intervention and treated with antibiotics and regular dressing changes. Deep SSIs (n = 8; 20%) required a median of 3 (range: 2-9) surgical interventions, with four patients requiring multiple washouts and one patient having metalwork removed. VTE incidence was 5% during the hospital stay. Eight patients died within 30 d, and mortality at one year was 19%. The 10-year mortality rate was 57%. The presence of a history of stroke, cancer, or prolonged inpatient stay was found to be predictive of lower survivorship in this population (log-rank test: cancer P = 0.008, stroke P = 0.001, length of stay > 33 d P = 0.015). The presence of a cardiac history was predictive of wound complications (logistic regression, P = 0.045). Age, number of operations, and diabetic history were found to be predictive of an increase in the length of stay (general linear model; age P < 0.001, number of operations P < 0.001, diabetes P = 0.041). CONCLUSION: An open ankle fracture in a patient older than 70 years has at least a 20% chance of requiring repeated surgical intervention due to deep SSIs. The presence of a cardiac history appears to be the main predictor for wound complications.

Genomic Sequencing to Diagnose Prosthetic Joint Infection in the Knee: A Case Report.

There is currently no "gold-standard" method to diagnose prosthetic joint infections (PJI), and the current practice of using microbiological cultures has many limitations. The identification of the bacterial species causing the infection is crucial to guide treatment; therefore, a robust method needs to be developed. Here, we attempt to use genomic sequencing with the MinION device from Oxford Nanopore Technologies to identify the species of bacteria causing PJI in a 61-year-old male. Genomic sequencing with the MinION presents an opportunity to produce species identification in real-time and at a smaller cost than current methods. By comparing results with standard hospital microbiological cultures, this study suggests that nanopore sequencing using the MinION could be a faster and more sensitive method to diagnose PJI than microbiological cultures.

The British Orthopaedic Oncology Management (BOOM) audit.

Aims: Most patients with advanced malignancy suffer bone metastases, which pose a significant challenge to orthopaedic services and burden to the health economy. This study aimed to assess adherence to the British Orthopaedic Oncology Society (BOOS)/British Orthopaedic Association (BOA) guidelines on patients with metastatic bone disease (MBD) in the UK. Methods: A prospective, multicentre, national collaborative audit was designed and delivered by a trainee-led collaborative group. Data were collected over three months (1 April 2021 to 30 June 2021) for all patients presenting with MBD. A data collection tool allowed investigators at each hospital to compare practice against guidelines. Data were collated and analyzed centrally to quantify compliance from 84 hospitals in the UK for a total of 1,137 patients who were eligible for inclusion. Results: A total of 846 patients with pelvic and appendicular MBD were analyzed, after excluding those with only spinal metastatic disease. A designated MBD lead was not present in 39% of centres (33/84). Adequate radiographs were not performed in 19% of patients (160/846), and 29% (247/846) did not have an up-to-date CT of thorax, abdomen, and pelvis to stage their disease. Compliance was low obtaining an oncological opinion (69%; 584/846) and prognosis estimations (38%; 223/846). Surgery was performed in 38% of patients (319/846), with the rates of up-to-date radiological investigations and oncology input with prognosis below the expected standard. Of the 25% (215/846) presenting with a solitary metastasis, a tertiary opinion from a MBD centre and biopsy was sought in 60% (130/215). Conclusion: Current practice in the UK does not comply with national guidelines, especially regarding investigations prior to surgery and for patients with solitary metastases. This study highlights the need for investment and improvement in care. The recent publication of British Orthopaedic Association Standards for Trauma (BOAST) defines auditable standards to drive these improvements for this vulnerable patient group.

A Rare Presentation of a Solitary Melanoma Bone Metastasis.

A 74-year-old woman presented with sudden onset pain and swelling in her right wrist. Plain radiographs showed a pathological fracture through a lytic lesion. The patient had a past medical history of melanoma on her right thigh, which had been excised two years previously. She was referred to the bone cancer unit to undergo a series of investigations that included a magnetic resonance imaging scan, bone scintigraphy and a computed tomography-guided biopsy. Collectively, all investigations revealed a solitary bone metastasis from her previous melanoma in the right distal radius. The patient was treated symptomatically and underwent internal fixation with cement augmentation for symptom control. With the incidence of melanoma increasing, this case demonstrates the importance of being vigilant of unusual presentations.

Mirels' score for upper limb metastatic lesions: do we need a different cutoff for recommending prophylactic fixation?

Hypothesis: The aim of this study was to investigate the reproducibility, reliability, and accuracy of Mirels' score in upper limb bony metastatic disease and validate its use in predicting pathologic fractures. Methods: Forty-five patients with upper limb bony metastases met the inclusion criteria (62% male 28/45). The mean age was 69 years (SD 9.5), and the most common primaries were lung (29%, 13/45), followed by prostate and hematological (each 20%, 9/45). The most commonly affected bone was the humerus (76%, 35/45), followed by the ulna (6.5%, 3/45). Mirels' score was calculated in 32 patients; with plain radiographs at index presentation scored using Mirels' system by 6 raters. The radiological aspects (lesion size and appearance) were scored twice by each rater (2 weeks apart). Intraobserver and interobserver reliability were calculated using Fleiss' kappa test. Bland-Altman plots compared the variances of both individual components and the total Mirels' score. Results: The overall fracture rate of upper limb metastatic lesions was 76% (35/46) with a mean follow-up of 3.6 years (range 11 months-6.8 years). Where time from diagnosis to fracture was known (n = 20), fractures occurred at a median 19 days (interquartile range 60-10), and 80% (16/20) occurred within 3 months of diagnosis.Mirels' score of ≥9 did not accurately predict lesions that fractured (fracture rate 11%, 5/46, for Mirels' ≥ 9 vs. 65%, 30/46, for Mirels' ≤ 8, P < .001). Sensitivity was 14%, and specificity was 73%. When Mirels' cutoff was lowered to ≥7, patients were more likely to fracture than not (48%, 22/46, vs. 28%, 13/46, P = .045); sensitivity rose to 63%, but specificity fell to 55%.Kappa values for interobserver variability were κ = 0.358 (fair, 95% confidence interval [CI] 0.288-0.429) for lesion size, κ = 0.107 (poor, 95% CI 0.02-0.193) for radiological appearance, and κ = 0.274 (fair, 95% CI 0.229-0.318) for total Mirels' score. Values for intraobserver variability were κ = 0.716 (good, 95% CI 0.432-0.999) for lesion size, κ = 0.427 (moderate, 95% CI 0.195-0.768) for radiological appearance, and κ = 0.580 (moderate, 95% CI 0.395-0.765) for total Mirels' score. Conclusions: This study demonstrates moderate to substantial agreement between and within raters using Mirels' score on upper limb radiographs. However, Mirels' score had a poor sensitivity and specificity in predicting upper extremity fractures. Until a more valid scoring system has been developed, based on our study, we recommend a Mirels' threshold of ≥7/12 for considering prophylactic fixation of impending upper limb pathologic fractures. This contrasts with the current ≥9/12 cutoff, which is recommended for lower limb pathologic fractures.

A genetic model for central chondrosarcoma evolution correlates with patient outcome.

BACKGROUND: Central conventional chondrosarcoma (CS) is the most common subtype of primary malignant bone tumour in adults. Treatment options are usually limited to surgery, and prognosis is challenging. These tumours are characterised by the presence and absence of IDH1 and IDH2 mutations, and recently, TERT promoter alterations have been reported in around 20% of cases. The effect of these mutations on clinical outcome remains unclear. The purpose of this study was to determine if prognostic accuracy can be improved by the addition of genomic data, and specifically by examination of IDH1, IDH2, and TERT mutations. METHODS: In this study, we combined both archival samples and data sourced from the Genomics England 100,000 Genomes Project (n = 356). Mutations in IDH1, IDH2, and TERT were profiled using digital droplet PCR (n = 346), whole genome sequencing (n=68), or both (n = 64). Complex events and other genetic features were also examined, along with methylation array data (n = 84). We correlated clinical features and patient outcomes with our genetic findings. RESULTS: IDH2-mutant tumours occur in older patients and commonly present with high-grade or dedifferentiated disease. Notably, TERT mutations occur most frequently in IDH2-mutant tumours, although have no effect on survival in this group. In contrast, TERT mutations are rarer in IDH1-mutant tumours, yet they are associated with a less favourable outcome in this group. We also found that methylation profiles distinguish IDH1- from IDH2-mutant tumours. IDH wild-type tumours rarely exhibit TERT mutations and tend to be diagnosed in a younger population than those with tumours harbouring IDH1 and IDH2 mutations. A major genetic feature of this group is haploidisation and subsequent genome doubling. These tumours evolve less frequently to dedifferentiated disease and therefore constitute a lower risk group. CONCLUSIONS: Tumours with IDH1 or IDH2 mutations or those that are IDHwt have significantly different genetic pathways and outcomes in relation to TERT mutation. Diagnostic testing for IDH1, IDH2, and TERT mutations could therefore help to guide clinical monitoring and prognostication.

The outcome of locking plate fixation for the treatment of periarticular metastases.

Periarticular bone metastasis may be treated with endoprosthetic reconstruction. The extensive surgery required may not, however, be appropriate for all patients. Our aim was to establish whether locking plates provide good functional outcomes and a durable construct when used in the management of metastatic disease. Prospective data collection was performed. Twenty one patients underwent surgery for periarticular metastatic tumours. The median duration of followup for surviving patients is one year. There have been no cases of implant failure and no requirement for revision surgery. Pain relief was excellent or good in the majority of patients. Patients who had sustained a fracture prior to fixation had restoration of their WHO performance status. All patients had a dramatic improvement in their MSTS scores. The median pre-operative score was 15% (0%-37%) improving to a median score of 80% (75%-96%) post operatively. Locking plates were found to provide reliable fixation and excellent functional restoration in selected patients suffering from periarticular metastatic bone disease.

Distal femoral replacement - Does length matter? Mid-term results for distal femoral replacements.

BACKGROUND: Review of mid-term results (five years) for tumour and revision arthroplasty surgery using the Stanmore METS® distal femoral replacement. METHODS: Data were collected retrospectively for 90 patients for procedures performed between 2002 and 2019. Kaplan-Meier survivorship for implant was estimated at five years post-op. Endpoints for survivorship analysis included revision for any cause and as per Henderson classification. Log rank test was used to compare implant survival for different categorical variables. Musculo-Skeletal Tumour Society (MSTS) score was used to estimate function. RESULTS: Overall implant survival at five years was 76% (95% CI 66-86). Implants with a short body (<= 45 mm) had significantly better implant survival [87% (95% CI 78-99)] compared to those with larger bodies [63% (95% CI 48-82)] (logrank test, p = 0.031). There was no significant difference in implant survival for tumour and revision arthroplasty patients (logrank test, p = 0.61). Mean MSTS scores (median follow-up = 3.5 years) for tumour and revision arthroplasty patient were 71% and 63% respectively (Wilcoxon rank test, p < 0.05). Higher total number of surgeries was a significant predictor of patient mortality [HR = 0.7 (95% CI 0.49-0.99)]. Longer bodies were a significant predictor of implant failure [HR = 3.2 (95% CI 1.05-10.53), p < 0.05]. CONCLUSION: Overall outcome of Stanmore METS® distal femoral replacement at five years following tumour and revision arthroplasty reconstruction is comparable to the other implants.

Bone Tumours of the Talus: 18-Year Cohort of Patients With Rare Osteoid Lesions.

Background Bone tumours of the talus are a rare cause of ankle pain. This study aims to provide additional clinical clarity regarding the presentation and management of a minimally researched topic. Methods Sixteen patients were diagnosed with bone tumour of the talus between 2002 and 2020 following referral for ankle pain. Symptoms, diagnosis, and management were retrospectively reviewed. Patients were actively followed up until consistently symptom-free and consenting to discharge (mean of 2.9 years). An open appointment was offered to all patients to reattend the unit if symptoms recurred. Results The most common diagnosis was osteoid osteoma/osteoblastoma (nine patients), chondroblastoma (four patients), a giant cell tumour of bone, a chondral lesion in Ollier's disease and a rare metastatic renal cancer case. The mean age of onset was 29 years. Thirteen patients experienced ankle pain without a clear precipitating cause. Night pain was less common in osteoid osteoma/osteoblastoma than usually observed in the literature. The mean delay in diagnosis was two years, often due to an incorrect diagnosis of soft tissue injury. Plain radiographs are insufficient to identify most lesions. Ten patients underwent computed tomography (CT)-guided radiofrequency ablation and five patients had open surgical curettage. Ollier's disease was managed with orthotics. The five cases of recurrence across four patients were managed operatively. Conclusions Patients are usually young and healthy with benign disease, but talus tumours can cause significant functional impairment. Unexplained ankle pain should be extensively examined and be further investigated with magnetic resonance imaging (MRI) and CT scanning to avoid missing these rare tumours.

Joint replacement surgery for elbow tumours: a systematic review of outcomes.

BACKGROUND: Tumour resection followed by joint reconstruction is a surgical option in the appropriate patient. The evidence for such reconstructive surgery of the elbow joint is limited. The aim of this study is to review the literature to evaluate the outcomes of joint replacement surgery in tumours of the elbow. METHODS: A systematic review of PUBMED and EMBASE databases was conducted. Case series and comparative studies reporting results after total elbow arthroplasty, modular endo-prosthetic replacement and custom prosthesis were eligible for inclusion. RESULTS: Eleven eligible studies were identified (n = 134). At mean follow-up of 44 months, the overall revision rate was 14% and complication rate was 28%. The mean Mayo Elbow Performance Score was 75, with 56% of patients reporting good or excellent outcomes. The mean post-operative range of motion was 97°. DISCUSSION: Elbow prosthesis reconstruction after tumour resection can provide good functional outcomes at mid-term follow-up. The complication and revision rates are comparable to other indications for elbow replacement surgery. Further prospective studies are required to compare outcomes between different elbow arthroplasty options after tumour resection.