TRAIL/Apo2L is a member of the tumour necrosis factor (TNF) family of cytokines that induces death of cancer cells but not normal cells. Its potent apoptotic activity is mediated through its cell surface death domain containing receptors, DR4 and DR5. TRAIL binds also to three “decoy” receptors, DcR1, DcR2 and osteoprotegerin (OPG), which lack functional death domains, and do not induce apoptosis. The aim of this study was to investigate the cytotoxic activity of TRAIL as a single agent or in combination with clinically relevant anti-sarcoma drugs on human soft tissue sarcomas that are traditionally resistant to chemotherapy. Human soft tissue sarcomas known to be resistant to chemotherapy were taken at the time of biopsy and cultured to produce a cell line. This cell line was then tested against TRAIL, standard chemotherapeutic agents (including doxorubicin, cis platinum, etoposide, methotrexate and cyclophosphamide) and in combination. When used alone, TRAIL and/or the standard chemotherapeutic agents produced minimal tumour necrosis and this was mirrored in the clinical results. In combination, however, up to 60% necrosis was seen, with doxorubicin the most effective chemotherapeutic agent used. These results indicate that chemotherapy and TRAIL act synergistically to kill sarcoma cells and potentially opens up a new area of cytotoxic treatment for these difficult malignancies.

The humerus is a common site for metastasis. Intramedullary nail fixation has been reported to be the best form of fixation for this disease but complications with this procedure have been reported. This study reports on the results of using a new humeral nail for the treatment of pathological fracture or impending fracture of the humerus. Twenty nine patients had 31 Austofix humeral nails, 25 for pathological fracture and 6 for impending fracture. Twenty-four nails were inserted anterograde and 7 retrograde. Cement augmentation was used in 4 patients. Adjuvant therapy was used in 26 patients. One patient was lost to follow-up. Fixation failed in six patients, two due to intra-operative fractures during retrograde insertion, one due to fracture through screw holes postoperatively, and three due to local progression of disease. Difficulties in locking the nail distally were encountered in an additional 3 patients. In conclusion, in the majority of patients, nailing of the humerus with metastatic disease resulted in a stable humerus. Retrograde nailing of the humerus was associated with an increased risk of intra-operative fracture. Adjuvant therapy cannot be relied upon to prevent loss of fixation due to local progression of disease. The longest possible nail should be inserted through the antegrade route and locked to minimise the risk of loss of fixation.