R. M. Tillman

We studied 153 patients with non-metastatic chondrosarcoma of bone to determine the risk factors for survival and local tumour control. The minimum follow-up was for five years; 52 patients had axial and 101 appendicular tumours. Surgical treatment was by amputation in 27 and limb-preserving surgery in 126. The cumulative rate of survival of all patients, at 10 and 15 years, was 70% and 63%, respectively; 40 patients developed a local recurrence between 3 and 87 months after surgery and 49 developed metastases. Local recurrence was associated with poor survival in patients with concomitant metastases but not in those without. On multivariate analysis independent risk factors for rates of survival include extracompartmental spread, development of local recurrence and high histological grade. Independent risk factors for local recurrence include inadequate surgical margins and tumour size greater than 10 cm. Location within the body, the type of surgery and the duration of symptoms are of no prognostic significance. Surgical excision with an oncologically wide margin provides the best prospect both for cure and local control in these patients.

BACKGROUND: Prosthetic replacement following excision of a bone tumor can be complicated by infection because patients who undergo surgery for a neoplastic condition often are subjected to extensive soft-tissue dissection and long operating times and are immunosuppressed. The aim of this study was to investigate the rate of periprosthetic infection, identify possible predisposing factors, and assess treatment efficacy in such patients. METHODS: Prosthetic reconstruction was performed in 1264 patients over a thirty-seven-year period in a single hospital by four surgeons. Twenty-four patients were excluded because of incomplete follow-up, leaving 1240 patients who had been followed for a mean of 5.8 years. Infection was identified in 136 patients (11.0%). The management and outcome of the infections in all of these patients were analyzed. RESULTS: Coagulase-negative Staphylococcus was the most common organism isolated. Two-stage revision successfully treated the infection in 72% (forty-two) of the fifty-eight patients in whom it was performed. Local surgical debridement with or without antibiotic implants was successful in only 6% (four) of sixty-eight patients. Amputation to treat the infection was performed in fifty (37%) of the 136 patients. The factors that were associated with a significant risk of infection (p <or= 0.05) included tibial and pelvic prosthetic replacements, radiation therapy, and the use of a pediatric expandable prosthesis. CONCLUSIONS: Patients treated with an orthopaedic procedure for an oncological condition have high infection rates. The treatment of infection in these patients is arduous and lengthy, with a substantial risk of amputation.

BACKGROUND: Excision of a bone tumor requires reconstruction if limb salvage is a priority. Reconstruction with an endoprosthetic implant is preferred in our unit, as the patient typically can return rapidly to full weight-bearing and functional activities. Long-term complications, such as deep infection, aseptic loosening, and mechanical failure of the implants, have led to concerns about the efficacy of reconstruction and the ability to revise failed implants while maintaining limb salvage in the longer term. The purpose of this study was to investigate the survival of endoprosthetic reconstructions in the medium to long term in order to determine the factors associated with their failure. METHODS: A consecutive series of 776 patients underwent endoprosthetic reconstruction following resection of a bone tumor at a minimum of ten years prior to this investigation. One hundred and nine children with a so-called growing endoprosthesis were excluded as they often require revision to an adult prosthesis near skeletal maturity. Six patients were excluded because of a lack of adequate follow-up data, leaving 661 patients for analysis. Kaplan-Meier survival analysis of the implant was performed, with implant revision for any cause (infection, local recurrence, and mechanical failure), mechanical failure alone, and amputation used as the end points. RESULTS: The mean duration of follow-up was fifteen years for patients who survived the original disease. Two hundred and twenty-seven patients (34%) had revision surgery because of mechanical failure (116 patients), infection (seventy-five patients), and locally recurrent disease (thirty-six patients). Implant survival at ten years was 75% with mechanical failure as the end point and 58% with failure from any cause as the end point. The limb salvage rate was 84% at twenty years. CONCLUSIONS: We believe these medium to long-term results with first-generation endoprostheses are encouraging and justify the continued use of endoprostheses for reconstruction following the excision of a bone tumor.

We investigated whether improvements in design have altered the outcome for patients undergoing endoprosthetic replacement of the distal femur after resection of a tumour. Survival of the implant and 'servicing' procedures have been documented using a prospective database, review of the design of the implant and case records. In total, 335 patients underwent a distal femoral replacement, 162 having a fixed-hinge design and 173 a rotating-hinge. The median age of the patients was 24 years (interquartile range 17 to 48). A total of 192 patients remained alive with a mean follow-up of 12 years (5 to 30). The risk of revision for any reason was 17% at five years, 33% at ten years and 58% at 20 years. Aseptic loosening was the main reason for revision of the fixed-hinge knees while infection and fracture of the stem were the most common for the rotating-hinge implant. The risk of revision for aseptic loosening was 35% at ten years with the fixed-hinge knee, which has, however, been replaced by the rotating-hinge knee with a hydroxyapatite collar. The overall risk of revision for any reason fell by 52% when the rotating-hinge implant was used. Improvements in the design of distal femoral endoprostheses have significantly decreased the need for revision operations, but infection remains a serious problem. We believe that a cemented, rotating-hinge prosthesis with a hydroxyapatite collar offers the best chance of long-term survival of the prosthesis.

Ewing's tumors are rare pediatric neoplasms that are characterized by specific chromosomal translocations and gene rearrangements. All of the fusion genes reported to date in Ewing's tumors juxtapose the EWS gene at 22q12 to an ETS-related gene, the most common of which are FLI1 at 11q24 and ERG at 21q22. We present here four cases of Ewing's tumor, which showed no evidence of a EWS gene rearrangement, but instead contained translocations involving 16p11 and 21q22. A rearrangement involving the same chromosome bands, t(16;21)(p11;q22), is found in rare cases of acute myeloid leukemia and fuses the FUS gene at 16p11 to the ERG gene at 21q22. In two of our Ewing's tumor cases, we were able to show at the sequence level that the translocation between chromosomes 16 and 21 similarly results in a FUS/ERG fusion. In one case, exons 1-5 and most of exon 6 of FUS were fused in-frame to exon 9 of ERG; in the other case, FUS exons 1-7 were fused in-frame to ERG exons 8-9. The functional fusion transcript is expected to be expressed from the der(21)t(16;21) derivative. In the two other t(16;21)-positive Ewing's cases, we performed bacterial artificial chromosome fluorescence in situ hybridization analysis on metaphases and interphase nuclei to demonstrate colocalization of bacterial artificial chromosomes containing FUS and ERG genes, also highly suggestive of fusion gene formation. These represent the first four cases where FUS, rather than EWS, is rearranged with an ETS-family transcription factor in Ewing's tumors. Our data provide additional evidence that the transactivation domains of the TET family of RNA-binding proteins (such as EWS and FUS) are interchangeable, and suggests a novel mechanism of oncogenesis in Ewing's tumors.