Fifty-six patients with stage II-B osteosarcoma around the knee were followed-up for a minimum of 92 months. The percentage of tumour cells expressing VEGF/MMP-9 was assessed using immunohistochemistry. The relationship between VEGF/MMP-9 expression and survival was assessed using Kaplan-Meier and Cox regression models. Patients with tumours expressing VEGF in >25% of their cells had shorter overall (p=0.019) and disease-free survival (p=0.009). Patients with tumours expressing MMP-9 had shorter overall (p=0.0042) and disease-free survival (p=0.0004). There was an association between VEGF and MMP-9 expression (p=0.021). The negative effects of VEGF/MMP-9 expression on survival were independent of traditional prognostic factors.

Our study sets out to show whether vascular endothelial growth factor (VEGF) expression in stage 2B osteosarcomas around the knee influences disease-free and overall survival.

Fifty-two such patients treated in out unit were identified and followed-up for for a minimum of 92 months. All were treated according to the current MRC protocol and had resection of their tumour. Tissue from their resected tumours was stained for VEGF using immunohistochemical methods and the percentage of tumour cells staining for VEGF was assessed. The relationship between VEGF expression and survival was assessed using the log-rank test and Kaplan-Meier survival curves.

At follow-up 32 (62%) patients were dead, all from metastatic disease. Twenty-six (50%) tumours showed expression of VEGF. Statistical analysis showed that patients with tumours with VEGF expression in more than 25% of the cells had significantly shorter overall survival (p=0.019) and disease free intervals (p=0.009). Expression of VEGF also correlated with expression of the proteolytic enzyme MMP9 (p=0.02).

VEGF is peptide which acts as a stimulator of new blood vessel growth in normal tissues, as well as in some solid tumours and their metastases. A tumour which is able to induce a blood supply has an increased ability to grow, seed metastases and threaten life. Our study is the first to look at VEGF expression in the tumour cells surviving after chemotherapy. It is this population of cells which is important as it is these cells which may go on to develop into metastatic or locally recurrent tumours. The over-expression of VEGF by osteosarcoma cells is thought to be associated with a worse prognosis due to a number of mechanisms. This study shows that VEGF expression is an important prognostic factor in osteosarcomas and suggests that the mechanisms by which VEGF and MMP9 expression produce a poor prognosis may be linked. Suppression of tumour angiogenesis by inhibition of the action of VEGF has shown promise in animal models as a potential new treatment for osteosarcoma, and warrants further study.

Introduction and Aims: The clavicle has several important functions each of which may be affected after fracture and malunion of the bone. The aim is to establish any association between shortening of the clavicle, following successful conservative management and clinical outcome.

Method: 132 patients with history of an acute fracture of the clavicle were reviewed. None of them had previous pathology affecting shoulder function, prior to injury. Men accounted 93 with average age 25.4 years, and women 39 with average age 34.2 years. All underwent conservative management with standard protocols and the fracture was united. The length and relative shortening of the united clavicle were assessed on a standardised posteroanterior chest x-ray. Intra- and Inter-observer reliability of measurements were assessed. Clinical outcome was evaluated with the Constant score. Mean follow-up was 30 months.

Results: Clavicular shortening following fracture union was 11.4 mm on average (range 3–25 mm), and was encountered in 120 patients. Intra- and inter-observer variability of measurements were not significant. Fracture healing time averaged 10 weeks (range 6–20 weeks) and 5.3% of patients presented delayed union. Thirty-four patients (25.8%) were unsatisfied with the result. The mean Constant score was 84 (range 62–100). Forty patients were having pain, and 21 had shoulder function impairment. Shortening > 14mm was statistically associated with unsatisfactory results.

Conclusion: Clavicle is an important element in the integral functional mobility of the shoulder and malunion after fracture could lead to unsatisfactory results. We describe a simple, reliable method of Clavicular length-shortening evaluation and we report the results following successful conservative management. Identification of those patients likely to have poor results after conservative treatment, would give the opportunity for alternative treatment modalities. Further prospective randomised trials are necessary.

Aims: The purpose of this study is to investigate whether the expression of MMP-9 (matrix metalloproteinase-9) is a potentially useful marker in osteosarcomas. Methods: 55 patients with stage IIB knee osteosarcomas were treated in our unit and had a median follow-up of 68 months. In addition to clinical data, MMP-1, MMP,-2, MMP-3, MMP-7, MMP-9 and MMP-13 were studied in the resection specimens, using immunohistochemical methods. The importance of all factors was studied using the log-rank test, and the overall survival of patients was calculated using Kaplan-Meier survival curves. Multiple variable analysis was carried out using Cox regression models with variables chosen forward and backward stepwise methods with deviance statistics. Signiþcance was set at p< 0.05. Results: On multiple variable analysis only the MMP-9 status of the tumour cells had a signiþcant effect on overall (p=0.032) and disease free survival (p=0.014). Conclusions: Our study shows that some post-chemotherapy osteosarcoma specimens express MMP-9 in the surviving tumour cells after chemotherapy. We believe that MMP-9 in the osteosarcoma cells which survive chemotherapy, contributes to recurrence because of the ability of these cells, to stimulate a new vascular network. The relationship between osteosarcomas and MMP-9 is worthy of further study.