Philipp T. Funovics

Failure Mode Classification for Tumor Endoprostheses: Retrospective Review of Five Institutions and a Literature Review

BACKGROUND Massive endoprostheses provide orthopaedic oncologists with many reconstructive options after tumor resection, although failure rates are high. Because the number of these procedures is limited, failure of these devices has not been studied or classified adequately. This investigation is a multicenter review of the use of segmental endoprostheses with a focus on the modes, frequency, and timing of failure. METHODS Retrospective reviews of the operative databases of five institutions identified 2174 skeletally mature patients who received a large endoprosthesis for tumor resection. Patients who had failure of the endoprosthesis were identified, and the etiology and timing of failure were noted. Similar failures were tabulated and classified on the basis of the risk of amputation and urgency of treatment. Statistical analysis was performed to identify dependent relationships among mode of failure, anatomic location, and failure timing. A literature review was performed, and similar analyses were done for these data. RESULTS Five hundred and thirty-four failures were identified. Five modes of failure were identified and classified: soft-tissue failures (Type 1), aseptic loosening (Type 2), structural failures (Type 3), infection (Type 4), and tumor progression (Type 5). The most common mode of failure in this series was infection; in the literature, it was aseptic loosening. Statistical dependence was found between anatomic location and mode of failure and between mode of failure and time to failure. Significant differences were found in the incidence of failure mode Types 1, 2, 3, and 4 when polyaxial and uniaxial joints were compared. Significant dependence was also found between failure mode and anatomic location in the literature data. CONCLUSIONS There are five primary modes of endoprosthetic failure, and their relative incidences are significantly different and dependent on anatomic location. Mode of failure and time to failure also show a significant dependence. Because of these relationships, cumulative reporting of segmental failures should be avoided because anatomy-specific trends will be missed. Endoprosthetic design improvements should address failure modes specific to the anatomic location.

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.

Reconstruction of the Pelvis After Resection of Malignant Bone Tumours in Children and Adolescents

The predominant tumour of the pelvic region in children and adolescents is Ewings sarcoma followed by osteosarcoma. Both tumours are treated by chemotherapy and the best chance of survival is offered by wide tumour resection. Compared to surgical treatment on the extremities, the resection and reconstruction of pelvic sarcomas remains challenging. Surgery of pelvic sarcomas shows higher rates of local recurrence and complications and a lower functional outcome than other localisations. Especially in children and adolescents the reconstruction methods have to focus additionally on the growing skeleton. According to the different types of pelvic resections and therefore the need of different reconstruction methods, the following article is based on Ennekings surgical classification of pelvic resections. Type I resections are best reconstructed with autografts implanted between the supracetabular osteotomy and the sacrum. Patients show the best functional results after this reconstruction. Periacetabular resections (type II) in small children do best with iliofemoral arthrodesis or pseudarthrosis; in larger adolescents the use of the pedestal Schoellner cup showed superior results over the prior saddle prosthesis. Type III resections are not reconstructed. Complete internal hemipelvectomy represents the most difficult situation, in children as well as in adults. High complication rates after allograft and endoprosthetic reconstruction have recently favoured the renaissance of a flail hip reconstruction or the hip transpositionplasty.

Modular Prosthetic Reconstruction of Major Bone Defects of the Distal End of the Humerus

BACKGROUND Bone defects of the distal end of the humerus require complex reconstructions, for which standard prostheses may be insufficient. We investigated the outcomes of distal humeral reconstruction with use of a modular prosthesis. METHODS Fifty-three elbows in fifty-two patients underwent reconstruction with a modular prosthesis (twelve total humeral replacements and forty-one distal humeral replacements) after tumor resection (thirty-eight elbows) or because of massive joint degeneration (fifteen elbows). In the tumor group, twenty-three patients (twenty-four elbows) had metastatic disease and fourteen had a primary tumor. Degenerative defects of the distal end of the humerus were caused by pseudarthrosis (six elbows), prosthetic failure (five), trauma (two), osteomyelitis (one), and supracondylar fracture (one). The mean duration of follow-up for all patients was twenty-eight months (median, thirteen months; range, one to 219 months). RESULTS The mean Inglis-Pellicci score in the tumor group was 84 points, and the mean Musculoskeletal Tumor Society score was 78%. Patients with total humeral reconstruction had worse scores than those with distal humeral reconstruction. Twenty-four patients died of disease at a mean of thirteen months after surgery. Local tumor control was achieved in all patients. In the revision group, the mean Inglis-Pellicci score was 76 points. The Inglis-Pellicci score was significantly better for patients in the tumor group. Eight patients (15%) had a deep periprosthetic infection, requiring amputation in one patient (2%) and prosthetic removal in two patients (4%). Four patients (8%) had the implants revised for aseptic loosening. CONCLUSIONS Modular prostheses of the distal end of the humerus provide a stable reconstruction of the elbow with satisfactory function and disease control in patients with a tumor, but careful patient selection is required when the prostheses are used for revision surgery in patients without a tumor.

Vascularised or non-vascularised autologous fibular grafting for the reconstruction of a diaphyseal bone defect after resection of a musculoskeletal tumour

Resection of a primary sarcoma of the diaphysis of a long bone creates a large defect. The biological options for reconstruction include the use of a vascularised and non-vascularised fibular autograft. The purpose of the present study was to compare these methods of reconstruction. Between 1985 and 2007, 53 patients (26 male and 27 female) underwent biological reconstruction of a diaphyseal defect after resection of a primary sarcoma. Their mean age was 20.7 years (3.6 to 62.4). Of these, 26 (49 %) had a vascularised and 27 (51 %) a non-vascularised fibular autograft. Either method could have been used for any patient in the study. The mean follow-up was 52 months (12 to 259). Oncological, surgical and functional outcome were evaluated. Kaplan-Meier analysis was performed for graft survival with major complication as the end point. At final follow-up, eight patients had died of disease. Primary union was achieved in 40 patients (75%); 22 (42%) with a vascularised fibular autograft and 18 (34%) a non-vascularised (p = 0.167). A total of 32 patients (60%) required revision surgery. Kaplan-Meier analysis revealed a mean survival without complication of 36 months (0.06 to 107.3, sd 9) for the vascularised group and 88 months (0.33 to 163.9, sd 16) for the non-vascularised group (p = 0.035). Both groups seem to be reliable biological methods of reconstructing a diaphyseal bone defect. Vascularised autografts require more revisions mainly due to problems with wound healing in distal sites of tumour, such as the foot.

Impact of RANK signalling on survival and chemotherapy response in osteosarcoma.

Summary The receptor activator of NF-&kgr;B (RANK) signalling pathway represents a promising target for the therapy of bone-related tumours. In the present study we evaluated the impact of the expression of RANK and its ligand (RANKL) on survival and response to chemotherapy in osteosarcoma patients. Expression of RANK and RANKL was examined in 91 human osteosarcomas by immunohistochemistry using formalin fixed, paraffin embedded (FFPE) tumour samples. Results of the stainings were correlated with clinicopathological parameters and patient survival. Sixty-three osteosarcomas (69.2%) expressed RANK, whereas only eight cases (8.8%) showed expression of RANKL. Expression of RANK was significantly associated with shorter disease-free survival by Kaplan–Meier analysis (p = 0.031). We further observed worse response to chemotherapy in RANK expressing tumours, which was statistically not significant (p = 0.099). RANKL expression was significantly more frequent in osteosarcoma of the lower extremity than in any other location. Analysis of RANKL expression did not reveal any statistically significant correlation with disease-free or osteosarcoma-specific survival. In our study, we identified RANK expression as a negative prognostic factor regarding disease-free survival in osteosarcoma. Moreover, RANK might modulate response of human osteosarcoma to chemotherapy. Therefore, RANK signalling cascade is likely to provide a novel alternative to targeted therapy of osteosarcoma and deserves further investigation.

The impact of re‐excision of inadequately resected soft tissue sarcomas on surgical therapy, results, and prognosis: A single institution experience with 682 patients

Due to their rare incidence soft tissue sarcomas (STS) are often resected without clear margins. The aim of this study was to investigate the impact of re‐excision of STS on survival.

Outcome after Reconstruction of the Proximal Tibia--Complications and Competing Risk Analysis.

Background and Objectives The proximal tibia (pT) is a common site for bone tumors. Improvements in imaging, chemotherapy and surgical technique made limb salvage surgery the treatment of choice. Yet, reconstructions of the pT have been associated with less favorable outcome compared to other parts of the extremities. The aim of this study was to evaluate the outcome of patients with a modular endoprosthetic reconstruction of the pT. Methods Eighty-one consecutive patients with an average age of 29 years underwent endoprosthetic reconstruction of the pT. Postoperative complications were categorized according to the ISOLS classification, and revision-free survival until first complication (any Type 1–5), soft tissue failure (Type 1), aseptic loosening (Type 2), structural failure (Type 3), infection (Type 4), and local tumor progression (Type 5) was estimated by using a Fine-Gray model for competing risk analyses for univariate and multivariable regression with Firth’s bias correction. Results A total of 45 patients (56%) had at least one complication. Cumulative incidence for complication Types 1 to 5 at 5 years with death and amputation as competing events revealed a risk of 41% for the first complication, 14% for Type 1, 16% for Type 2, 11% for Type 3, 17% for Type 4, and 1% for Type 5. Conclusion Despite inclusion of amputation and death as strong competing events, pT replacements are still associated with a high risk of postoperative failures. The results suggest that infection and soft tissue failures (Type 1 and 5) seem to depend from each other. Sufficient soft tissue reconstruction and closure allow better function and reduce the risk of infection as the most prominent complication. The use of a rotating hinge design has significantly reduced structural failures over time.

Hemoglobin, alkalic phosphatase, and C-reactive protein predict the outcome in patients with liposarcoma

Data on prognostic biomarkers in soft tissue sarcomas are scarce. The aim of the study was to define prognostic markers in patients with a liposarcoma, a subtype of sarcoma derived from adipose tissue. We restrospectively reviewed 85 patients with liposarcoma treated at our department from May 1994 to October 2011. Kaplan–Meier curves, uni‐, and multivariable Cox proportional hazard models and competing risk analysis were performed to evaluate the association between putative biomarkers with disease‐specific and overall survival. We observed a significant association between both alkalic phosphatase (ALP; subhazard ratio [SHR] per 1 unit increase: 1.35; 95%CI 1.10–1.65; p = 0.005) and C‐reactive protein (CRP; SHR per 1 mg/dl increase: 2,57; 95%CI 1.36–4,86; p = 0.004) with disease‐specific survival. Hemoglobin (Hb) (HR per 1 g/dl increase: 065; 95%CI 0.48–0.87; p = 0.003) was associated with overall survival. These associations prevailed after multivariable adjustment for AJCC tumor stage. This study identifies CRP and ALP as novel independent predictors of disease‐specific survival in patients with liposarcoma.

Treatment and outcome of parosteal osteosarcoma: biological versus endoprosthetic reconstruction.

Due to its good prognosis despite local recurrence, more and less invasive methods for surgical treatment of parosteal osteosarcoma (POS) have been described. Aim of this retrospective single‐center study was to investigate differences in outcome after biological and prosthetic reconstruction.