Metastatic osteosarcoma is seen in 10-20% of patients at initial presentation with the lung the most common site of metastasis. Historically, prognosis has been poor. We studied trends in survival in our small developed nation and aimed to identify correlations between the survival rate and three factors: newer chemotherapy, advances in radiological imaging and a more aggressive approach adopted by cardiothoracic surgeons for lung metastases.

Our national bone tumour registry was used to identify patients at the age of 18 or under, who presented with metastatic disease at initial diagnosis between 1933 and 2006. There were 30 patients identified. Kaplan-Meier analysis was used to determine survival rates and univariate analysis was performed using the Cox regression proportional hazards model.

Median survival has improved over the last 50 years; highlighted by the ‘Kotz’ eras demonstrating incremental improvement with more effective chemotherapy agents (p=0.004), and a current 5-year survival of 16%. Aggressive primary and metastatic surgery also show improving trends in survival. Three patients have survived beyond 5 years. The introduction of computerised tomography scanning has led to an increase in the prevalence of metastases at initial diagnosis.

Metastatic osteosarcoma remains with a very poor prognostic factor, however, aggressive management has been shown to prolong survival.

Background

High re-rupture rates following repairs of rotator cuff tears (RCTs) have resulted in the increased use of repair grafts to act as temporary scaffolds to support tendon healing. It has been estimated that thousands of extracellular matrix repair grafts are used annually to augment surgical repair of rotator cuff tears. The only mechanical assessment of the suitability of these grafts for rotator cuff repair has been made using tensile testing only, and compared grafts to canine infraspinatus. As the shoulder and rotator cuff tendons are exposed to shearing as well as uniaxial loading, we compared the response of repair grafts and human rotator cuff tendons to shearing mechanical stress. We used a novel technique to study material deformation, dynamic shear analysis (DSA).

Improved understanding of the biomechanics and biology of rotator cuff tendons (RCT) may help reduce high re-rupture rates following repairs, particularly amongst larger tears. This study aims to use novel methods for quantitatively determining differences in the mechanical and thermal properties of intact healthy RCTs compared to torn ‘diseased’ tendons. A common problem in the mechanical testing of small tendon samples is that stress risers at the clamp-tendon interface can obscure measurements. As the shoulder is subject to shear, tension and compression, we developed a novel solution using Dynamic Shear Analysis (DSA), a form of rheology which studies material deformation. As collagen is the main component of RCT, the structure and mechanical properties may be affected by collagen conformational changes. Both dermis and rat tail tendon with increased collagen cross-linking exhibit stronger mechanical properties. Thermal changes detected by differential scanning calorimetry (DSC) can help to quantify collagen structural differences in torn RCT, and has been previously used to study muscle, cartilage and vertebral discs.

There were 79 tears (mean age 65.2 years), which were classified according to the size of the tear as small, medium, large and massive. Two separate 3mm-sized biopsy samples were taken and subjected to DSA using oscillatory deformation under compression. The storage modulus (G') was calculated and used as an indicator of mechanical integrity. 18 control tendon specimens were obtained from patients aged between 22-89 years (mean age 58.8 years) during shoulder hemiarthroplasties and stabilisations. Additionally 7 normal, 7 small and 7 massive frozen specimens were thermally characterized. 3 samples per patient were heated between 20-80oC in hermetically sealed vessels. Useful thermal parameters were measured such as the melting temperature (TM) which apparently represents breaking of the amide-amide bonds and protein chains mobility, the denaturation temperature (TD) which supposedly corresponds to proteins falling out of solution and the denaturation enthalpy (ΔH) which reflects the relative amount of triple helical structure.

Healthy tendons had a significantly higher modulus than torn tendons, indicating that torn tendons are mechanically weaker than normal tendons (p = 0.032). Normal tendons had significantly higher mean shear modulus than tendons with small and massive tears (p<0.01). Overall there was a negative correlation between moduli and severity of tendon tear (r = −0.698, p=0.189). The moduli did not significantly correlate with age, sex, hand dominance, or length of preservation in formalin. Massive RCT tears had significantly higher TM and TD when compared to normal RCT (p < 0.05), unlike small RCT tears. No significant difference was detected between the denaturation enthalpy of the different RCT groups. This case control study has demonstrated that normal RCTs have a significantly higher modulus than torn tendons, indicating that torn tendons have less mechanical integrity. Our study further demonstrated a trend between increasing tear size and decreasing mechanical integrity. This study has also demonstrated differences in some of the thermal properties of normal and torn RCTs. These are likely due to collagen structural changes. A decrease in the denaturation temperature of torn tendons, suggests that the material is intrinsically less stable. Torn tendons with reduced storage modulus and collagen integrity may be less able to withstand mechanical loads following repair. This pilot study provides some preliminary insight into the mechanisms that may contribute to, or represent adaptations to high rates of failure of RCT repairs.