Obesity increases the risk of major wound complications following pelvic resection for bone sarcoma.

BACKGROUND: Given the paucity of data, the objective of this study is to evaluate the association between obesity and major wound complications following pelvic bone sarcoma surgery specifically. METHODS: Patients who underwent pelvic resection for bone sarcoma from 2005 to 2021 with a minimum 6-month follow-up were reviewed. Patients with benign tumors, primary soft tissue sarcomas, local recurrence at presentation, pelvic metastatic disease, and underweight patients were excluded. A major wound complication was defined as the need for a secondary debridement procedure. Differences in baseline demographics, surgical factors, postoperative complications, and functional outcomes were compared between obese and nonobese patients. A multivariate logistic regression was performed to identify independent risk factors for major wound complications, and a Kaplan-Meier analysis to estimate overall survival between both groups. RESULTS: Of the 93 included patients, 21 were obese (body mass index ≥ 30 kg/m2). The obesity group had a significantly higher rate of major wound complication (52% vs. 26%, p = 0.034) and a lower Toronto Extremity Salvage Score at 1-year postoperatively (47.5 vs. 71.4, p = 0.025). Obesity was the only independent risk factor in the multivariate analysis. No differences in overall survival were demonstrated between groups. CONCLUSIONS: Obesity is a significant risk factor for major wound complications in pelvic bone sarcoma treatment. This highlights the importance of careful perioperative optimization and wound management.

Intralesional leiomyosarcoma malignant transformation from a biopsied benign angioleiomyoma of the proximal anterior tibia.

We present a novel case of a malignant transformation of an extremity soft tissue angioleiomyoma to leiomyosarcoma in a man in his late 70s who presented with a painful and increasing lump on his anterior tibia. Initial imaging and biopsy showed a benign angioleiomyoma which was excised for symptomatic reasons. An analysis of the resulting specimen revealed a 50×42×15 mm smooth muscle neoplasm consistent with angioleiomyoma with a 22×11 mm entirely intralesional nodular component in keeping with a grade 1 leiomyosarcoma. The malignant constituent of the lesion was entirely encased in benign angioleiomyoma negating the need for further surgery. Systemic staging investigation revealed no evidence of metastatic disease spread final staging as per the eighth edition of the American Joint Committee on Cancer (AJCC) Staging T1N0M0 R0 Stage 1 a.

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.

Intermuscular extremity myxoid liposarcoma can be managed by marginal resection following neoadjuvant radiotherapy.

BACKGROUND: Compared with other soft tissue sarcomas, myxoid liposarcoma (MLS) occurs in younger patients, has a propensity for intermuscular locations and is highly radiosensitive. With pre-operative radiotherapy, intermuscular MLS demonstrates substantial volume reduction and can be easily separated from surrounding tissues during resection. However, it is unclear whether marginal excision of MLS is oncologically safe. This study aimed to assess the association between margins and survival in irradiated, intermuscular MLS. METHODS: The study identified 198 patients from seven sarcoma centres with a first presentation of localized, extremity, intermuscular MLS that received pre-operative radiotherapy and was diagnosed between 1990 and 2017. Patient and treatment characteristics, radiological and histological responses to neoadjuvant treatment and clinical surveillance were recorded. RESULTS: Margins were microscopically positive in 11% (n = 22), <1.0 mm in 15% (n = 29) and ≥1.0 mm in 72% (n = 143). There was no association between margin status and local recurrence-free, metastasis-free or overall survival. This finding held true even in patients at higher risk of worse overall survival based on multivariable analysis (% round cell≥5%, percentage ellipsoid tumour volume change ≤ -60.1%). CONCLUSION: Irradiated, extremity, intermuscular myxoid liposarcoma can safely undergo marginal resection without compromising oncologic control.

Apparent trends in the use of femoral megaprostheses: an analysis from the National Joint Registry.

BACKGROUND: Megaprosthetic replacement (MPR) of the femur is typically reserved for salvage or oncological reconstruction. Presently little is known about the provision of femoral MPRs performed nationally, the trends in indications for their use, and their outcomes beyond published unit-level data. Although the National Joint Registry (NJR) collects data as part of a mandatory arthroplasty audit process, MPR data entry on this platform is thought to be inconsistent. The aim of this study is to determine current trends for femoral MPR procedures as submitted to the NJR. METHODS: Data for all procedures submitted to the NJR using the following implants were extracted: METS (Stanmore/Stryker), MUTARS (Implantcast), Segmental (Zimmer), GMRS (Stryker) and MEGA C (LINK). Pseudoanonymized data were analyzed through the NJR's research Data Access Portal and are reported using descriptive statistics. RESULTS: A total of 1781 procedures were identified. Submitted cases increased for primary and revision hip and knee categories over the study period, although they plateaued in recent years. MPR implants were most commonly used in revision hip arthroplasty procedures. MPR use for the management of peri-prosthetic fractures has increased and now represents the most commonly reported indication for MPR use in both hip and knee revision categories. Few centers submitted large MPR case volumes (which were noted to be lower than published unit case series, indicating NJR under-reporting), and the vast majority of centers submitting MPR cases did so in low volume. CONCLUSIONS: Due to the limitations identified, reported case volumes must be interpreted with caution. An MPR-specific NJR data entry form has been developed to allow more accurate and tailored reporting of MPR procedures, to support specialist service provision, and to provide meaningful data for future research.

The importance of the early appropriate management of foot and ankle soft tissue sarcomas - experiences of a regional sarcoma service.

INTRODUCTION: Soft tissue sarcomas (STS) are a group of rare malignant tumours that can occur at almost any anatomical location in patients of any age, which often present to health care professional working outside a recognised sarcoma service. A review of foot and ankle STSs was conducted, reporting on patient and tumour characteristics, and patient outcome following surgery performed within and outside our sarcoma service. PATIENTS AND METHODS: A retrospective review of all foot and ankle STSs managed by our sarcoma service over a 14 year period was performed. Patient demographics, tumour characteristics, management and patient outcomes including recurrence rates and survival were analysed. RESULTS: Twenty-six patients were analysed (16F:10M) with a mean age of 57.7 years (range 17-87). The mean follow-up was 6.3 years (range 1-16). Sixteen tumours involved the foot, nine the ankle, and one spanned the foot and ankle. Mean tumour size was 4.3 cm (range 0.8-15), although 61% of cases were smaller than 4 cm, and almost one third of cases smaller than 1 cm. Seven of 26 (27%) cases were diagnosed after an unplanned excision performed by non sarcoma surgeons. These patients were more likely to undergo an incomplete tumour excision (p < 0.001), suffer local recurrence (p = 0.001), and eventually undergo a secondary amputation (p = 0.034) than those patients managed exclusively by a sarcoma service. Overall, 12 (46%) patients died of their disease during follow up, equating to a five-year survival rate of 69%. CONCLUSION: Our data shows that unplanned excisions continue to be performed on foot and ankle STSs, and that these have detrimental effects on patients. Despite this, our results also show that these complex patients can be managed successfully when referred appropriately to a sarcoma service, prior to any surgical treatment. This highlights the importance of vigilance amongst all health care professionals managing any foot or ankle lumps, regardless of their size.

Intra-articular steroid injections in large joint arthritis: A survey of current practice.

INTRODUCTION: Intra-articular corticosteroid injections are widely used as a management modality for mild large joint osteoarthritis (OA). In contrast, there is little guidance or consensus on the use of steroids in moderate to severe disease. The aim of this study is to explore the current practice of surgeons in relation to the use of therapeutic intra-articular steroid injections in patients awaiting large joint arthroplasty for OA. METHODS: An anonymous questionnaire was distributed to consultants performing large joint arthroplasty in four National Health Service Trusts. Participants were questioned on their use of intra-articular therapeutic steroid injections in patients listed for elbow, shoulder, hip or knee arthroplasty. Data was collected over 6 months and analysed using Microsoft Excel. RESULTS: A total of 42 surgeons were included in the study with the majority performing lower limb arthroplasty (73%). About 21 (50%) surgeons indicated they would perform injections in the patient group of interest. Two would perform an unlimited number of injections, whilst the remainder would perform between one and three injections. Respondents most commonly indicated they would tell patients that an injection would provide between 6 and 12 weeks of benefit (14 of 39 surgeons, 36%). Most injecting surgeons (88%) leave 4 months between an injection and subsequent arthroplasty due to increased risk of infection if surgery is performed sooner. CONCLUSION: This study demonstrates variation in practice in the use of intra-articular steroids in the analysed patient group, and the way surgeons council their patients. National or specialist society guidelines may help to reduce this variation in practice.

The Circulating Nucleic Acid Characteristics of Non-Metastatic Soft Tissue Sarcoma Patients.

Soft tissue sarcomas (STS) are rare, malignant tumours with a generally poor prognosis. Our aim was to explore the potential of cell free DNA (cfDNA) and circulating tumour DNA (ctDNA) analysis to track non-metastatic STS patients undergoing attempted curative treatment. The analysed cohort (n = 29) contained multiple STS subtypes including myxofibrosarcomas, undifferentiated pleomorphic sarcomas, leiomyosarcomas, and dedifferentiated liposarcomas amongst others. Perioperative cfDNA levels trended towards being elevated in patients (p = 0.07), although did not correlate with tumour size, grade, recurrence or subtype, suggesting a limited diagnostic or prognostic role. To characterise ctDNA, an amplicon panel covering three genes commonly mutated in STSs was first trialled on serial plasma collected from nine patients throughout follow-up. This approach only identified ctDNA in 2.5% (one in 40) of the analysed samples. Next custom-designed droplet digital PCR assays and Ion AmpliSeq™ panels were developed to track single nucleotide variants identified in patients' STSs by whole exome sequencing (1-6 per patient). These approaches identified ctDNA in 17% of patients. Although ctDNA was identified before radiologically detectable recurrence in two cases, the absence of demonstrable ctDNA in 83% of cases highlights the need for much work before circulating nucleic acids can become a useful means to track STS patients.

Circulating tumour-derived DNA in metastatic soft tissue sarcoma.

Following treatment 40% of soft tissue sarcoma (STS) patients suffer disease recurrence. In certain cancers circulating cell free DNA (cfDNA) and circulating tumour-derived DNA (ctDNA) characteristics correlate closely with disease burden, making them exciting potential sources of biomarkers. Despite this, the circulating nucleic acid characteristics of only 2 STS patients have been reported to date. To address this we used an Ion AmpliSeq™ panel custom specifically designed for STS patients to conduct a genetic characterisation of plasma cfDNA, buffy coat (germline) DNA and where available Formalin-Fixed Paraffin-Embedded (FFPE) primary STS tissue DNA in a cohort of 11 metastatic STS patients. We found that total cfDNA levels were significantly elevated in the STS patients analysed, and weakly correlated with disease burden. Using our Ion AmpliSeq™ panel we also successfully detected ctDNA in 4/11 (36%) patients analysed with a wide variety of STS subtypes and disease burdens. This evidence included the presence of cancer associated TP53 / PIK3CA mutations in 2 patients' plasma and matched primary STS tumour tissue, and in the plasma alone for 2 patients. We also identified 2 potential examples of allelic loss of heterozygosity in an additional patient's STS DNA and cfDNA. This is the largest study performed characterising STS patient cfDNA/ctDNA and confirms that the field remains an attractive potential source of novel STS biomarkers. Further work is required to investigate the circulating nucleic acid characteristics of individual STS subtypes, and the potential prognostic or therapeutic roles that cfDNA/ctDNA may hold for patients with these complex tumours.

Telomere maintenance in soft tissue sarcomas.

Soft tissue sarcomas (STS) are a diverse group of heterogeneous malignant tumours derived from mesenchymal tissues. Over 50 different STS subtypes are recognised by WHO, which show a wide range of different biological behaviours and prognoses. At present, clinicians managing this complex group of tumours face several challenges. This is reflected by the relatively poor outcome of patients with STSs compared with many other solid malignant tumours. These include difficulties securing accurate diagnoses, a lack of effective systemic treatments and absence of any sensitive circulating biomarkers to monitor patients throughout their treatment and follow-up. In order to progress STS's cells must evade the usual cellular proliferative checkpoints, and then activate a telomere maintenance mechanism in order to achieve replicative immortality. The purpose of this review is to provide an overview of STS genetics focusing particularly on these mechanisms. We will also highlight some of the key barriers to improving outcome for patients with STS, and hypothesise how a better understanding of these genetic characteristics may impact on future STS management.

A Prospective Randomized Control Study on Patient's Recall of Consent after Hand Surgery: How Much They Want to Know?

Informed consent implies that the person undergoing an intervention thoroughly understands its pros and cons. We conducted a randomized control trial to evaluate patients' recall of complications after day case hand surgery and how this can be influenced by age and/or socioeconomic factors. Patients' wishes on the extent and type of provided information were also evaluated. A total of 124 cases were recruited. Ten cases were excluded because they presented for follow up more than 2 weeks after surgery. The other patients were randomized into 2 groups: the first one (48) received only verbal information, while the second one (66) also received written information sheets. No statistically significant difference was noted in the recall between the two groups. No difference among gender, age or socioeconomic status was noted. Most patients preferred both written and verbal information. Preference for knowledge of rates of complications increased when surgery was dangerous. Our results don't show any significant difference in patients' recall depending on the type of consenting method. Nevertheless, we still propose that patients should receive as much information as possible before undergoing any intervention.

Radiographs late in the follow up of uncomplicated distal radius fractures: are they worth it? Clinical outcome and financial implications.

Fractures of the distal radius are common. Displacement can quickly lead to secondary osteoarthritis. Early follow up radiographs are subsequently paramount to facilitate for early attempts at reduction. Developing callus eventually makes this impractical. In the absence of complications we propose that radiographs may become obsolete at the later stages of follow up. We investigate whether clinical deformity, range of wrist movement and grip strength are independent of radiographs taken later than 2 weeks into the follow up of uncomplicated cases. Local cases between May 2009 and December 2011 were reviewed. Devised criteria regulated case selection. Data was collected from radiological software and occupational therapy clinical notes. Fractures were placed in short or term follow up groups dependant on whether they were imaged later than 2 weeks into follow up. T-tests compared our outcomes measures between these groups. 138 cases were included; 77 short term; 61 long term. No cases reported visible clinical deformity. There were no significant differences between grip strength or range of wrist movement for the short and long term groups. No cases required intervention for late displacement. Although complications may justify delayed imaging, our results suggest radiographs late in the follow up of uncomplicated distal radius fractures have no impact on our outcome measures. Further studies are required to confirm this. Financial regulation means any potential benefits from the removal of these unnecessary radiographs should be recognised. Established radiological follow up regimes need to be devised.

Skeletal metastases - the role of the orthopaedic and spinal surgeon.

Developments in oncological and medical therapies mean that life expectancy of patients with metastatic bone disease (MBD) is often measured in years. Complications of MBD may dramatically and irreversibly affect patient quality of life, making the careful assessment and appropriate management of these patients essential. The roles of orthopaedic and spinal surgeons in MBD generally fall into one of four categories: diagnostic, the prophylactic fixation of metastatic deposits at risk of impending fracture (preventative surgery), the stabilisation or reconstruction of bones affected by pathological fractures (reactive surgery), or the decompression and stabilisation of the vertebral column, spinal cord, and nerve roots. Several key principals should be adhered to whenever operating on skeletal metastases. Discussions should be held early with an appropriate multi-disciplinary team prior to intervention. Detailed pre-assessment is essential to gauge a patient's suitability for surgery - recovery from elective surgery must be shorter than the anticipated survival. Staging and biopsies provide prognostic information. Primary bone tumours must be ruled out in the case of a solitary bone lesion to avoid inappropriate intervention. Prophylactic surgical fixation of a lesion prior to a pathological fracture reduces morbidity and length of hospital stay. Regardless of a lesion or pathological fracture's location, all regions of the affected bone must be addressed, to reduce the risk of subsequent fracture. Surgical implants should allow full weight bearing or return to function immediately. Post-operative radiotherapy should be utilised in all cases to minimise disease progression. Spinal surgery should be considered for those with spinal pain due to potentially reversible spinal instability or neurological compromise. The opinion of a spinal surgeon should be sought early, as delays in referral directly correlate to worse functional recovery following intervention. Patients who suffer a slowly progressive deficit, present within hours of complete neurological deficit, or have compression caused by bone alone are those most likely to benefit from surgery. Back pain in the presence of MBD should be regarded as impending spinal cord compression, and investigated urgently to allow intervention prior to the development of neurological compromise.

Ischemia is not required for arteriogenesis in zebrafish embryos.

OBJECTIVE: The role of ischemia in collateral vessel development (arteriogenesis) is a contentious issue that cannot be addressed using mammalian models. To investigate this, we developed models of arteriogenesis using the zebrafish embryo, which gains sufficient oxygenation via diffusion to prevent ischemia in response to arterial occlusion. METHODS AND RESULTS: We studied gridlock mutant embryos that suffer a permanently occluded aorta and show that these restore aortic blood flow by collateral vessels. We phenocopied gridlock mutants by laser-induced proximal aortic occlusion in transgenic Fli1:eGFP/GATA1:dsRED embryos. Serial imaging showed these restore aortic blood flow via collateral vessels by recruitment of preexisting endothelium in a manner similar to gridlocks. Collateral aortic blood flow in gridlock mutants was dependent on both nitric oxide and myeloid cells. Confocal microscopy of transgenic gridlock/Fli1:eGFP mutants demonstrated no aberrant angiogenic response to the aortic occlusion. qPCR of HIF1alpha expression confirmed the absence of hypoxia in this model system. CONCLUSIONS: We conclude that NO and myeloid cell-dependent collateral vessel development is an evolutionarily ancient response to arterial occlusion and is able to proceed in the absence of ischemia.