Background

Impaction bone grafting with milled human allograft is the gold standard for replacing lost bone stock during revision hip surgery. Problems surrounding the use of allograft include cost, availability, disease transmission and stem subsidence (usually due to shear failure of the surrounding allograft). Aims. To investigate various polymers for use as substitute allograft. The ideal graft would be a composite with similar mechanical characteristics as allograft, and with the ability to form de novo bone.

Aims

Disease transmission, availability and economic costs of allograft have resulted in significant efforts into finding an allograft alternative for use in impaction bone grafting (IBG). Biotechnology offers the combination of skeletal stem cells (SSC) with biodegradable polymers as a potential solution. Recently polymers have been identified with both structural strength and SSC compatibility that offer the potential for clinical translation.

The aim of this study was to assess whether increasing the porosity of one such polymer via super critical CO₂ fluid foaming (SCF) enhanced the mechanical and cellular compatibility characteristics for use as an osteogenic alternative to allograft in IBG.

Aims

Impaction bone grafting with milled human allograft is the gold standard for replacing lost bone stock during revision hip surgery. Problems surrounding the use of allograft include cost, availability, disease transmission and stem subsidence (usually due to shear failure of the surrounding allograft).

The aim of this study was to investigate various polymers for use as substitute allograft. The ideal graft would be a composite with similar mechanical characteristics as allograft, and with the ability to form de novo bone.

Disease transmission, availability and economic costs of allograft have resulted in significant efforts into finding an allograft alternative for use in impaction bone grafting (IBG). Biotechnology offers the combination of skeletal stem cells (SSC) with biodegradable polymers as a potential solution. Recently polymers have been identified with both structural strength and SSC compatibility that offer the potential for clinical translation.

The aim of this study was to assess whether increasing the porosity of one such polymer via super critical CO2 dissolution (SCD) enhanced the mechanical and cellular compatibility characteristics for use as an osteogenic alternative to allograft in IBG.

High molecular weight PLA scaffolds were produced via traditional (solid block) and SCD (porous) techniques, and the differences characterised using scanning electron microscopy (SEM). The polymers were milled, impacted, and mechanical comparison between traditional vs SCD created scaffolds and allograft controls was made using a custom shear testing rig, as well as a novel agitation test to assess cohesion. Cellular compatibility tests for cell number, viability and osteogenic differentiation using WST-1 assays, fluorostaining and ALP assays were determined following 14 day culture with SSCs.

SEM showed increased porosity of the SCD produced PLA scaffolds, with pores between 50-100 micrometres. Shear testing showed the SCD polymer exceeded the shear strength of allograft controls (P<0.001). Agitation testing showed greater cohesion between the particles of the SCD polymer (P<0.05). Cellular studies showed increased cell number, viability and osteogenic differentiation on the SCD polymer compared to traditional polymer (P<0.05) and allograft (P<0.001).

The use of supercritical C02 to generate PLA scaffolds significantly improves the cellular compatibility and cohesion compared to traditional non-porous PLA, without substantial loss of mechanical shear strength. The improved characteristics are critical for clinical translation as a potential osteogenic composite for use in impaction bone grafting.

Impaction bone grafting with milled human allograft is the gold standard for replacing lost bone stock during revision hip surgery. Problems surrounding the use of allograft include cost, availability, disease transmission and stem subsidence (usually due to shear failure of the surrounding allograft).

The aim of this study was to investigate various polymers for use as substitute allograft. The ideal graft would be a composite with similar mechanical characteristics as allograft, and with the ability to form de novo bone.

High and low molecular weight (MW) forms of three different polymers (polylactic acid (PLA), poly (lactic co-glycolic) acid (PLGA) and polycaprolactone (PCL)) were milled, impacted into discs, and then tested in a custom built shear testing rig, and compared to allograft.

A second stage of the experiment involved the addition of skeletal stem cells (SSC) to each of the milled polymers, impaction, 8 days incubation, and then tests for cell viability and number, via fluorostaining and biochemical (WST-1) assays.

The shear strengths of both high/ low MW PLA, and high/low MW PLGA were significantly higher than those of milled allograft (P<0.001, P<0.001, P<0.005 and P<0.005) but high and low MW PCL was poor to impact, and had significantly lower shear strengths (P<0.005, P<0.001). Fluorostaining showed good cell survival on high MW PLA, high MW PCL and high MW PLGA. These findings were confirmed with WST-1 assays.

High MW PLA as well as high MW PLGA performed well both in mechanical testing and cell compatibility studies. These two polymers are good contenders to produce a living composite for use as substitute human allograft in impaction bone grafting, and are currently being optimised for this use via the investigation of different production techniques and in-vivo studies.

When transferring tissue regenerative strategies involving skeletal stem cells to human application, consideration needs to be given to factors that may affect the function of the cells that are transferred. Local anaesthetics are frequently used during surgical procedures, either administered directly into the operative site or infiltrated subcutaneously around the wound. The aim of this study was to investigate the effects of commonly used local anaesthetics on the morphology, function and survival of human adult skeletal stem cells.

Cells from three patients who were undergoing elective hip replacement were harvested and incubated for two hours with 1% lidocaine, 0.5% levobupivacaine or 0.5% bupivacaine hydrochloride solutions. Viability was quantified using WST-1 and DNA assays. Viability and morphology were further characterised using CellTracker Green/Ethidium Homodimer-1 immunocytochemistry and function was assessed by an alkaline phosphatase assay. An additional group was cultured for a further seven days to allow potential recovery of the cells after removal of the local anaesthetic.

A statistically significant and dose dependent reduction in cell viability and number was observed in the cell cultures exposed to all three local anaesthetics at concentrations of 25% and 50%, and this was maintained even following culture for a further seven days.

This study indicates that certain local anaesthetic agents in widespread clinical use are deleterious to skeletal progenitor cells when studied in vitro; this might have relevance in clinical applications.

Abstract

Displaced mid-shaft clavicle fractures have traditionally been treated non-operatively. New evidence supports the use of operative treatment with better functional results although with some risk of adverse complications. The patient's opinion in choosing one or the other option of treatment is important especially when a new therapeutic philosophy is introduced.

We aimed to obtain the patients' preference based on their opinion of various possible outcomes of each treatment method. A clinical decision tree was constructed based on probabilities for various outcomes from the current literature. We used clinical decision analysis based on Bayesian logic. A similar clinical decision analysis was done for a cohort of orthopaedic surgeons.

We interviewed 20 patients to obtain their health preferences on a numerical rating scale for each of the six possible outcomes for the conservative and operative treatments. Similar health preferences were obtained from 20 orthopaedic surgeons.

The cohort of patients were young (age range: 13 – 21, mean: 16 years) males involved in active sport. The results of the decision analysis demonstrated a strong preference for operative management in this cohort of patients (combined probability of 0.81 for operative treatment versus 0.61 for non-operative).

The cohort of orthopaedic surgeons were either career orthopaedic trainees or qualified orthopaedic surgeons with an age range of 28 – 41 years (mean age: 35 years). The results of the decision analysis demonstrated a weak preference for operative management in this cohort of surgeons (combined probability of 0.84 for operative treatment versus 0.77 for non-operative management).

Overall the young active patient is eight times more likely to prefer operative treatment over non-operative management compared to the well informed orthopaedic surgeon. Patient education is the key to a better informed patient who can make a balanced decision. Clinical decision analysis can be a useful tool in this process.

In order to define the optimum timing of surgery for a hip fracture, we undertook a systematic review of all previously published studies on this topic. Data from the retrieved studies were extracted by two independent reviews and the methodology of each study assessed. In total, 43 studies involving 265,137 patients were identified. Outcomes considered were mortality, post-operative complications, length of hospital stay and return of patients back home.

There were no randomised trials on this topic. Six studies of 8535 patients have the most appropriate methodology, which was prospective collection of data with adjustment for confounding variables. These studies found no effect on mortality for any delays in surgery. One of these studies found fewer complications for those operated on early but this was not found in the other study to report on these outcomes. Two of these studies reported on hospital stay, which was reduced for those operated on early. Six studies of 229,418 patients were retrospective reviews of patient administration databases with an attempt at adjusting for confounding factors. They reported a reduced mortality, hospital stay and complications for those operated on early. Thirty-one other studies of variable methodology reported similar findings of reduced complications with early surgery, apart from one study of 399 patients which reported an increased mortality and morbidity for those operated on within 24 hours of admission.

In conclusion those studies with more careful methodology were less likely to report a beneficial effect of early surgery, particularly in relation to mortality. But early surgery (within 48 hours of admission) does seem to reduce complications such as pressure sores and reduces hospital stay.

Aim

To identify patient, tumour or treatment factors that influence outcome in patients with radiation induced sarcoma of bone.

The Oxford unicompartmental knee replacement gives good results in patients with symptomatic osteoarthritis of the medial compartment. Previous studies have suggested that the presence of radiolucent lines (RLLs) does not reflect a poor outcome in such patients. However, the reliability and validity of this assessment have not been determined. Our aim was to assess the intra- and interobserver reliability and the sensitivity and specificity of the assessment of RLLs around both tibial and femoral components using standard radiographs.

Two reviewers assessed the radiographs of 45 patients who had loosening of the tibial or femoral component confirmed at revision surgery and compared them with those of a series of 45 asymptomatic patients matched for age and gender.

The results suggested that, using standard radiographs, tibial RLLs were 63.6% sensitive and 94.4% specific and femoral RLLs 63.9% sensitive and 72.7% specific for loosening. Overall intra- and interobserver reliability was highly variable, but zonal analysis showed that lucency at the tip of the femoral peg was significantly associated with loosening of the femoral component.

Fluoroscopically guided radiographs may improve the zonal reliability of the assessment of RLLs, but further independent and comparative studies are required. In the meantime, the innocence of the physiological RLLs detected by standard radiographs should be viewed with caution.

Mortality after hip fractures in the elderly is one of the most important patient outcome measures. Sub-clinical thyroid dysfunction is common in the elderly population. This is a prospective study of 131 elderly patients with a mean (SD) age of 82.0 (8.9) years (range: 61–94) admitted consecutively to our trauma unit. The aim of the study was to determine the prevalence of sub-clinical thyroid dysfunction in an elderly cohort of patients with hip fracture and to determine if this affects the one year mortality.

There were three times more women (n=100) than men (n=31) in this cohort. All patients underwent surgical treatment for the hip fracture. The prevalence of sub-clinical hypothyroidism (TSH > 5.5 mU/L) was15% (n=20) and of sub-clinical hyperthyroidism (TSH < 0.35 mU/L) was 3% (n=4). Overall 18% (n=24) of patients had a subclinical thyroid dysfunction. The twelve month mortality was 27% (n=36).

Age, gender, heart rate at admission, pre-existing Coronary Heart Disease, ASA grade and presence of overt or subclinical thyroid dysfunction were analysed for association with twelve month mortality using a forward stepwise logistic regression analysis. Only ASA grade was found to significantly affect mortality at twelve months (c2 = 3.98, df = 1, p =.046). The presence of sub-clinical hypo or hyper – thyroidism was not associated with a higher mortality (p = 0.278).

We conclude that sub-clinical thyroid dysfunction does not affect the one year mortality in elderly patients treated surgically for hip fracture.

In order to define the optimum timing of surgery for a hip fracture, we undertook a systematic review of all previously published studies on this topic. Data from the retrieved studies was extracted by two independent reviews and the methodology of each study assessed. In total, 43 studies involving 265137 patients were identified. Outcomes considered were mortality, post-operative complications, length of hospital stay and return of patients back home.

There were no randomised trials on this topic. Six studies of 8535 patients have the most appropriate methodology, which was prospective collection of data with adjustment for confounding variables. These studies found no effect on mortality for any delays in surgery. One of these studies found fewer complications for those operated on early but this was not found in the other study to report on these outcomes. Two of these studies reported on hospital stay, which was reduced for those operated on early. Six studies of 229418 patients were retrospective reviews of patient administration databases with an attempt at adjusting for confounding factors. They reported a reduce mortality, hospital stay and complications for those operated on early. Thirty-one other studies of variable methodology reported similar findings of reduced complications with early surgery apart from one study of 399 patients, which reported an increased mortality and morbidity for those operated on within 24 hours of admission.

In conclusion those studies with more careful methodology were less likely to report a beneficial effect of early surgery, particularly in relation to mortality. But early surgery (within 48 hours of admission) does seem to reduce complications such as pressure sores and reduces hospital stay.

Introduction: The population of the UK is getting older. Patients over the age of 80 (the older old) are increasingly presenting with musculoskeletal tumours that require major surgery. We have investigated the success or otherwise of endoprosthetic replacements after tumour excision in this population.

Methods: We looked at an oncological database to identify patients over the age of 80 who had an endprosthetic replacement after tumour excision. We reviewed the records of all patients over the age of 80 who had an endoprosthetic replacement to assess the oncological and functional outcomes of the procedure.

Results: 17 patients over the age of 80 had an endoprosthesis over the past 10 years. The main indication was for metastatic disease (9 patients) but 6 had primary malignant bone tumours. The most common site was the distal femur in 9 followed by the proximal femur in 5. Most of the patients had associated co-morbidity (12 were ASA 2 or 3). There were no perioperative deaths but 2 patients had early complications with one having a paralytic ileus and one a chest infection. The median survival of the patients was 2 years with death being due to progressive metastases in most. 3 had late complications to do with the prosthesis including one infection in a proximal tibial replacement and a late dislocation at 2 years in a proximal femoral replacement. Two patients developed local recurrence treated by local excision and radiotherapy. There were no amputations or revisions.

Conclusions: Endoprosthetic replacements have a useful role to play in the surgical management of elderly patients. Although they have significant comorbidity most do well. Functional results are less good than in the younger population but most patients regain their independence and are free of pain.

Synovial sarcoma is a morphologically well-defined neoplasm that most commonly occurs in soft tissue accounting for 5% to 10 % of all soft tissue sarcomas. We reviewed 156 patients with synovial sarcoma of soft tissues treated at a supra-regional centre to determine survival and prognostic factors.

There were 77men and 79 women with mean age at presentation of 38 years (3 to 84). Follow-up periods ranged from 3 to 494 months (median 43 months). Tumor was located in lower extremities in 111patients, upper extremities in 34 patients, and trunk and pelvis in 11 patients. Overall survival was 66% at 5 years and 48% at 10 years. The 5 and 10 year survival for the 23 patients who had metastases at the time of diagnosis was 13% and 0% respectively compared to 75% and 54% for those without metastases at diagnosis. Local recurrence occurred in 18 patients (13%). The significant prognostic factors for survival included presence of metastases at diagnosis and development of local recurrence. Tumour size and depth, age of patients and use of chemotherapy did not significantly influence survival.

We conclude that the clinical factors which influence survival of patients with synovial sarcoma are different from those of soft tissue sarcomas in general. Biological factors may better predict prognostic survival than the usual clinical factors.

Aim: To identify patient, tumour or treatment factors that influence outcome in patients with radiation induced sarcoma of bone.

Method: A retrospective review of an oncology database supplemented by referral back to original records.

Results: We identified 42 patients who presented to our Unit over a 25 year period with a new sarcoma of bone following previous radiotherapy. The age of the patients at presentation ranged from 10 to 84 years of age (mean: 17 years) and the time interval from previous radiotherapy ranged from 4 to 50 years (median: 14 yrs; mean: 17 years). The median dose of radiotherapy given had been 50 Gy but there was no correlation of radiation dose with time to development of sarcoma. The pelvis was the most common site for development of sarcoma (14 cases) but breast cancer was the most common primary tumour (8 cases). 9 of the patients had metastases at the time of diagnosis of the sarcoma. Osteosacoma was the most common diagnosis (30). Treatment was by surgery and chemotherapy when indicated and 30 of the patients had treatment with curative intent. The survival rate was 41% at 5 years for those treated with curative intent but in those treated palliatively median survival was only 6 months and all had died by one year. The only factor found to be significant for survival was the ability to completely resect the tumour, thus limb sarcomas had a better prognosis (66% survival at 5 years) than central ones (12%)(p=0.009).

Conclusion: Radiation induced sarcoma is a rare complication of radiotherapy. Both surgical and oncological treatment is likely to be compromised by previous treatment the patient has received. Despite this 40% of patients will survive more than 5 years with aggressive modern treatment.

Background: Limb preserving surgery in patients with tumours involving the whole femur present a formidable challenge.

Results: We present our experience of treating such patients with total femur endoprostheses over the last 30 years (1975 to 2005). There were twenty six consecutive patients including 14 males and 12 females. Average age was 40 years (14 – 82 years) at the time of surgery. Eleven patients were still alive of which nine were free of disease at the time of review. The mean follow-up was 57 months (3 to 348). Using Kaplan Meier estimates, the long-term patient survival at 10 years was 37%. The survival of patients with primary localised tumour was 50% at 10 years.

Revision of the prostheses was necessary in two patients at 110 and 274 months after surgery because of recurrent dislocation in one and aseptic loosening of the acetabular cup and tibial stem in the other. Amputation was necessary in two patients, one due to deep infection and the other due to local recurrence. The long-term limb survival being 92% at 10 years. Nine patients who were alive with no evidence of disease were assessed for function of the salvaged limbs using the musculoskeletal tumour society (MSTS) rating system. The mean functional score was 72%.

Conclusion: We conclude that total femur endoprosthetic replacement offers an excellent method of limb reconstruction following excision of the whole femur either for primary or metastatic tumours. However, patients survival after such operation is poor due to disease related factors.

99 patients with new diagnosed soft tissue sarcomas involving the pelvic region were studied to determine the outcome and prognostic factors for survival and local recurrence.

The mean age at diagnosis was 57 years. There were 55 males and 44 females. The mean tumor size was 12cm. The tumor was deep in 79 patients and superficial in 20. Surgical treatment was excision in 93 patients and hindquarter amputation in 6 patients. Histological grade was low grade in 23 and high grade in 75 patients. 7% of the patients had metastases at presentation.

The 5 year overall survival was 57% and local recurrence occurred in 22% of the patients. The risk of inadequate surgical margins in patients with tumors within the pelvic brim was 50% compared to 18% for those with tumors located outside the pelvic brim. The significant predictors of local recurrence were inadequate margins and location of the tumor within the pelvic brim. Tumor size, grade and depth did not influence development of local recurrence. Significant predictors of survival included metastases at presentation, tumor grade and depth. The cumulative 5 year survival for patients with deep high grade tumors, deep low grade tumors, superficial high grade and superficial low grade tumors were 45%, 74%, 63% and 100% respectively (p=0.01). The 5-year overall survival was 66% in those patients without local recurrence compared to 37% in those who develop local recurrence (p=0.005). Multivariate analysis revealed that development of local recurrence was the most important determinant of overall and metastases free survival.

We conclude that patients with pelvic soft tissue sarcoma who develop local recurrence have an extremely poor prognosis. Patients with high grade and inadequate surgical margins represent a particular group with very high risk of metastases and death even with radiotherapy and perhaps should be considered for other adjuvant treatment.

We identified 42 patients who presented to our unit over a 27-year period with a secondary radiation-induced sarcoma of bone. We reviewed patient, tumour and treatment factors to identify those that affected outcome. The mean age of the patients at presentation was 45.6 years (10 to 84) and the mean latent interval between radiotherapy and diagnosis of the sarcoma was 17 years (4 to 50). The median dose of radiotherapy given was estimated at 50 Gy (mean 49; 20 to 66). There was no correlation between radiation dose and the time to development of a sarcoma. The pelvis was the most commonly affected site (14 patients (33%)). Breast cancer was the most common primary tumour (eight patients; 19%). Metastases were present at diagnosis of the sarcoma in nine patients (21.4%). Osteosarcoma was the most common diagnosis and occurred in 30 cases (71.4%). Treatment was by surgery and chemotherapy when indicated: 30 patients (71.4%) were treated with the intention to cure. The survival rate was 41% at five years for those treated with the intention to cure but in those treated palliatively the mean survival was only 8.8 months (2 to 22), and all had died by two years. The only factor found to be significant for survival was the ability to completely resect the tumour. Limb sarcomas had a better prognosis (66% survival at five years) than central ones (12% survival at five years) (p = 0.009).

Radiation-induced sarcoma is a rare complication of radiotherapy. Both surgical and oncological treatment is likely to be compromised by the treatment received previously by the patient.

Peri- and sub-prosthetic fractures, or pathological fractures below an existing well-fixed femoral component, with or without an ipsilateral knee replacement, present a difficult surgical challenge.

We describe a simple solution, in which a custom-made prosthesis with a cylindrical design is cemented proximally to the stem of an existing, well-fixed femoral component. This effectively treats the fracture without sacrificing the good hip. We describe five patients with a mean age of 73 years (60 to 81) and a mean follow-up of 47 months (6 to 108).

The mean overlap of the prosthesis over the femoral component was 7.5 cm (5.5 to 10). There have been no mechanical failures, no new infections and no re-operations. We suggest that in highly selected cases, in which conventional fixation is not feasible, this technique offers a durable option and avoids the morbidity of a total femoral replacement.