L. Jeys

Periprosthetic infection in patients treated for an orthopaedic oncological condition.

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.

Endoprosthetic Reconstruction for the Treatment of Musculoskeletal Tumors of the Appendicular Skeleton and Pelvis

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.

Prognostic factors and outcomes for osteosarcoma: an international collaboration

We aimed to evaluate the prognostic significance of traditional clinical predictors in osteosarcoma through an international collaboration of 10 teams of investigators (2680 patients) who participated. In multivariate models the mortality risk increased with older age, presence of metastatic disease at diagnosis, development of local recurrence when the patient was first seen, use of amputation instead of limb salvage/wide resection, employment of unusual treatments, use of chemotherapeutic regimens other than anthracycline and platinum and use of methotrexate. It was also influenced by the site of the tumour. The risk of metastasis increased when metastatic disease was present at the time the patient was first seen and also increased with use of amputation or unusual treatment combinations or chemotherapy regimens not including anthracycline and platinum. Local recurrence risk was higher in older patients, in those who had local recurrence when first seen and when no anthracycline and platinum were used in chemotherapy. Results were similar when limited to patients seen after 1990 and treated with surgery plus combination chemotherapy. This large-scale international collaboration identifies strong predictors of major clinical outcomes in osteosarcoma.

Post operative infection and increased survival in osteosarcoma patients: are they associated?

Despite neo-adjuvant chemotherapy osteosarcomas having significant mortality, recent studies have shown survival advantages following infections for some tumour types. This study investigates the effect of post-operative infection in patients treated for osteosarcoma using endoprosthetic replacement and neo-adjuvant chemotherapy. A consecutive series of 547 patients underwent surgery between 1981 and 2001 for osteosarcoma. Patients were excluded from the study if over 60 years old at diagnosis (n = 14) as they would not routinely receive chemotherapy. Studies showed that 70% of deep infections occur within one year from reconstruction. Therefore landmark analysis was performed; all patients infected after 12 months of reconstruction were excluded (15 patients, 2.7%) and those who died within 12 months from diagnosis due to metastases were excluded (105 patients, 19.2%), leaving 412 patients. Any survival advantage of early infection was analysed by Kaplan-Meier survival analysis from this landmark point. Overall population survival was 65% at 10 years after landmarking. There were 41 patients (10%) who developed an infection within one year of implantation. These patients had significantly better survival (p = 0.017). The 10-year survival for patients with osteosarcoma with infection was 84.5% compared to 62.3% in the non-infected group after landmarking. There was no significant difference in the percentage post-chemotherapy specimen necrosis between the two groups (p = 0.36). Infection was an independent prognostic factor on cox regression analysis. There was evidence for increased survival after deep post-operative infection in osteosarcoma patients, in keeping with other research. The authors feel this warrants further investigation.

Chondroblastoma of bone

We undertook this retrospective study to determine the rate of recurrence and functional outcome after intralesional curettage for chondroblastoma of bone. The factors associated with aggressive behaviour of the tumour were also analysed. We reviewed 53 patients with histologically-proven chondroblastoma who were treated by intralesional curettage in our unit between 1974 and 2000. They were followed up for at least two years to a maximum of 27 years. Seven (13.2%) had a histologically-proven local recurrence. Three underwent a second intralesional curettage and had no further recurrence. Two had endoprosthetic replacement of the proximal humerus and two underwent below-knee amputation after aggressive local recurrence. One patient had the rare malignant metastatic chondroblastoma and eventually died. The mean Musculoskeletal Tumour Society functional score of the survivors was 94.2%. We conclude that meticulous intralesional curettage alone can achieve low rates of local recurrence and excellent long-term function.

Can computer navigation-assisted surgery reduce the risk of an intralesional margin and reduce the rate of local recurrence in patients with a tumour of the pelvis or sacrum?

We hypothesised that the use of computer navigation-assisted surgery for pelvic and sacral tumours would reduce the risk of an intralesional margin. We reviewed 31 patients (18 men and 13 women) with a mean age of 52.9 years (13.5 to 77.2) in whom computer navigation-assisted surgery had been carried out for a bone tumour of the pelvis or sacrum. There were 23 primary malignant bone tumours, four metastatic tumours and four locally advanced primary tumours of the rectum. The registration error when using computer navigation was < 1 mm in each case. There were no complications related to the navigation, which allowed the preservation of sacral nerve roots (n = 13), resection of otherwise inoperable disease (n = 4) and the avoidance of hindquarter amputation (n = 3). The intralesional resection rate for primary tumours of the pelvis and sacrum was 8.7% (n = 2): clear bone resection margins were achieved in all cases. At a mean follow-up of 13.1 months (3 to 34) three patients (13%) had developed a local recurrence. The mean time alive from diagnosis was 16.8 months (4 to 48). Computer navigation-assisted surgery is safe and has reduced our intralesional resection rate for primary tumours of the pelvis and sacrum. We recommend this technique as being worthy of further consideration for this group of patients.

Retrospective evaluation of the incidence of early periprosthetic infection with silver-treated endoprostheses in high-risk patients

We conducted a case-control study to examine the merit of silver-coated tumour prostheses. We reviewed 85 patients with Agluna-treated (silver-coated) tumour implants treated between 2006 and 2011 and matched them with 85 control patients treated between 2001 and 2011 with identical, but uncoated, tumour prostheses. In all, 106 men and 64 women with a mean age of 42.2 years (18.4 to 90.4) were included in the study. There were 50 primary reconstructions (29.4%); 79 one-stage revisions (46.5%) and 41 two-stage revisions for infection (24.1%). The overall post-operative infection rate of the silver-coated group was 11.8% compared with 22.4% for the control group (p = 0.033, chi-square test). A total of seven of the ten infected prostheses in the silver-coated group were treated successfully with debridement, antibiotics, and implant retention compared with only six of the 19 patients (31.6%) in the control group (p = 0.048, chi-square test). Three patients in the silver-coated group (3.5%) and 13 controls (15.3%) had chronic periprosthetic infection (p = 0.009, chi-square test). The overall success rates in controlling infection by two-stage revision in the silver-coated group was 85% (17/20) compared with 57.1% (12/21) in the control group (p = 0.05, chi-square test). The Agluna-treated endoprostheses were associated with a lower rate of early periprosthetic infection. These silver-treated implants were particularly useful in two-stage revisions for infection and in those patients with incidental positive cultures at the time of implantation of the prosthesis. Debridement with antibiotic treatment and retention of the implant appeared to be more successful with silver-coated implants.

The long-term risks of infection and amputation with limb salvage surgery using endoprostheses.

Endoprostheses are now an established technique to reconstruct defects following bone tumour resection. The long-term durability of the reconstruction is excellent, with limb salvage being maintained in the long-term in 91% of patients at 20 years from surgery. The main reasons for secondary amputation were locally recurrent disease and deep periprosthetic infection. Infection remains one of the biggest threats to early failure of reconstructions with endoprostheses. Most series of reconstructions show a periprosthetic infection rate of approximately 10%. Infection most frequently occurs within 12 months from the last surgical procedure; however, the risk of infection is life-long. The commonest pathogenic organism is coagulase-negative Staphylococcus. The most effective treatment for deep infection is two-stage revision, with local treatments having little chance of curing deep infection. Research is on-going into surface treatments with silver and other materials to help to reduce the infection rates.

Prognostic factors and metastatic patterns in primary myxoid/round-cell liposarcoma.

Background. This study aimed to investigate prognostic factors for patients with myxoid/round-cell liposarcoma (MRCLS), in particular the significance of the round cell component, and to identify metastatic patterns as well as possibly suggest a suitable strategy for followup. Methods. Clinical, morphologic, and follow-up data from 160 patients with MRCLS was reviewed and statistically analysed. Results. Of 130 tumours with the round cell component evaluated, 61 had no round cell component, 27 had <5% round cell component, and 42 had >5%. All patients underwent surgical excision, 15 requiring amputation. 107 patients received adjuvant radiotherapy. Local recurrence occurred in 19 patients (12%), predominantly in patients with marginal or intralesional margins and a round cell component. Overall disease specific survival was 75% at 5 years and 56% at 10 years and was related to the proportion of round cell component. Of 52 patients who developed metastases, 38 (73%) had purely extrapulmonary metastases. We could not identify any factors predicting the site of metastases developing. Conclusions. The occurrence of any round cell component is the most important adverse prognostic factor for patients with MRCLS; patients with >5% round cell component are at higher risk of local recurrence, metastasis and tumour-related death and should be considered for adjuvant radiotherapy and possibly chemotherapy. The best method of monitoring extrapulmonary metastases remains to be established.

Mesenchymal chondrosarcoma: prognostic factors and outcome in 113 patients. A European Musculoskeletal Oncology Society study.

BACKGROUND Mesenchymal chondrosarcoma (MCS) is a distinct, very rare sarcoma with little evidence supporting treatment recommendations. PATIENTS AND METHODS Specialist centres collaborated to report prognostic factors and outcome for 113 patients. RESULTS Median age was 30 years (range: 11-80), male/female ratio 1.1. Primary sites were extremities (40%), trunk (47%) and head and neck (13%), 41 arising primarily in soft tissue. Seventeen patients had metastases at diagnosis. Mean follow-up was 14.9 years (range: 1-34), median overall survival (OS) 17 years (95% confidence interval (CI): 10.3-28.6). Ninety-five of 96 patients with localised disease underwent surgery, 54 additionally received combination chemotherapy. Sixty-five of 95 patients are alive and 45 progression-free (5 local recurrence, 34 distant metastases, 11 combined). Median progression-free survival (PFS) and OS were 7 (95% CI: 3.03-10.96) and 20 (95% CI: 12.63-27.36) years respectively. Chemotherapy administration in patients with localised disease was associated with reduced risk of recurrence (P=0.046; hazard ratio (HR)=0.482 95% CI: 0.213-0.996) and death (P=0.004; HR=0.445 95% CI: 0.256-0.774). Clear resection margins predicted less frequent local recurrence (2% versus 27%; P=0.002). Primary site and origin did not influence survival. The absence of metastases at diagnosis was associated with a significantly better outcome (P<0.0001). Data on radiotherapy indications, dose and fractionation were insufficiently complete, to allow comment of its impact on outcomes. Median OS for patients with metastases at presentation was 3 years (95% CI: 0-4.25). CONCLUSIONS Prognosis in MCS varies considerably. Metastatic disease at diagnosis has the strongest impact on survival. Complete resection and adjuvant chemotherapy should be considered as standard of care for localised disease.