Carsten Gebert

Endoprosthetic reconstruction in 250 patients with sarcoma

We assessed the clinical results and complications associated with a new endoprosthetic replacement system (Mutars®) used in 250 patients with a malignant bone or soft tissue tumor. The key features of the system are its cementless, hexagonal-shaped stem (titanium alloy), the possibility of torsion adjustments in 5°-increments, and the Trevira® tube for soft tissue attachment. The mean age of the patients was 30.7 years, and the mean followup was 45 months. Prosthetic survival at 5 years was 89.7% for the upper extremity and 68.5% for the lower extremity. Prosthetic survival without any reoperation was 73.4% at 3 years postoperatively and 60.4% at 5 years postoperatively. Prosthetic failure was caused by deep infection in 12% (30 patients) of patients and aseptic loosening in 8% (20 patients) of patients. Stem fracture occurred in only 1.6% (four patients) of patients. Dislocation rates were reduced by using the Trevira® tube. Limb survival was achieved in 82.6% to 93.1% of patients depending on the endoprosthetic replacement site, and functional results ranged between 63% to 83% according to the Tumor Society score. Our results suggest limb salvage with the Mutars® endoprosthesis is successful with good functional results.Level of Evidence: Therapeutic study, Level IV (case series). See the Guidelines for Authors for a complete description of levels of evidence.

Bisphosphonate treatment of aggressive primary, recurrent and metastatic Giant Cell Tumour of Bone

BackgroundGiant cell tumour of bone (GCTB) is an expansile osteolytic tumour which contains numerous osteoclast-like giant cells. GCTB frequently recurs and can produce metastatic lesions in the lungs. Bisphosphonates are anti-resorptive drugs which act mainly on osteoclasts.MethodIn this study, we have examined clinical and radiological outcomes of treatment with aminobisphosphonates on 25 cases of aggressive primary, recurrent and metastatic GCTB derived from four European centres. We also analysed in vitro the inhibitory effect of zoledronic acid on osteoclasts isolated from GCTBs.ResultsTreatment protocols differed with several different aminobisphosphonates being employed, but stabilisation of disease was achieved in most of these cases which were refractory to conventional treatment. Most inoperable sacral/pelvic tumours did not increase in size and no further recurrence was seen in GCTBs that had repeatedly recurred in bone and soft tissues. Lung metastases did not increase in size or number following treatment. Zoledronic acid markedly inhibited lacunar resorption by GCTB-derived osteoclasts in vitro.ConclusionOur findings suggest that bisphosphonates may be useful in controlling disease progression in GCTB and that these agents directly inhibit GCTB - derived osteoclast resorption. These studies highlight the need for the establishment of standardised protocols to assess the efficacy of bisphosphonate treatment of GCTB.

Reconstruction of the proximal humerus after wide resection of tumours

In 45 patients we assessed the functional results and complications for three different reconstructive procedures after resection of primary tumours of the proximal humerus. An osteoarticular allograft was used in 11, a clavicula pro humero operation in 15 and a tumour prosthesis in 19. The glenoid was resected with the proximal humerus in 25 patients. The axillary nerve was resected in 42 patients. The complication rate was lowest after reconstruction with a tumour prosthesis. The clavicula pro humero operation resulted in the most revisions. Cumulative survival rates for all the reconstructive procedures were similar. At follow-up at two years the functional results for the three reconstructive procedures were the same with a mean functional rating of 79% (Musculoskeletal Tumor Society). Excision of the glenoid had no influence on the functional result. Our findings indicate that the use of a tumour prosthesis is the most reliable limb-salvage procedure for the proximal humerus. The clavicula pro humero is an appropriate procedure if a prosthesis cannot be used.

Functional Results and Quality of Life After Treatment of Pelvic Sarcomas Involving the Acetabulum

BACKGROUND Limb salvage after resection of a pelvic sarcoma that involves the acetabulum represents a surgical challenge. The ideal method of reconstruction after acetabular resection remains a subject of controversy, and the outcome in terms of the impact of therapy is still unknown. The purpose of this study was to determine the impact of surgery on health-related quality of life and function after acetabular resection. METHODS Eighty-one patients with a pelvic sarcoma underwent acetabular resection at a single institution. Functional evaluation and quality-of-life examination were performed in forty-five patients, and these patients comprised the study group. Quality of life was assessed with use of the European Organization for Research and Treatment of Cancer core quality-of-life questionnaire. Function was assessed with use of the Musculoskeletal Tumor Society system. RESULTS The median age of the patients was 30.4 years at the time of the acetabular resection and 35.7 years at the time of follow-up. The median time interval from the index operation to the latest follow-up was sixty-nine months. At the latest follow-up evaluation, the mean functional status score was 14.5 points of a maximum of 30 points. In a comparison of endoprosthetic replacement and hip transposition following resection, significantly better functional results (p = 0.017) and a lower number of complications were found in patients who had a hip transposition. Quality-of-life assessment results were also better in patients with a hip transposition, especially in role functioning (p = 0.043). CONCLUSIONS On the basis of the low complication rate and the good functional and quality-of-life results, hip transposition after acetabular resection seems to be the optimal technique for treating patients with a pelvic sarcoma involving the acetabulum.

Expression of β-catenin and p53 are prognostic factors in deep aggressive fibromatosis

Aims:  To determine the prognostic significance of β‐catenin in aggressive fibromatosis and to identify potential molecular markers for new targeted therapies.

Morphologic characterization of osteosarcoma growth on the chick chorioallantoic membrane

BackgroundThe chick chorio-allantoic membrane (CAM) assay is a commonly used method for studying angiogenic or anti-angiogenic activities in vivo. The ease of access allows direct monitoring of tumour growth by biomicroscopy and the possibility to screen many samples in an inexpensive way. The CAM model provides a powerful tool to study effects of molecules, which interfere with physiological angiogenesis, or experimental tumours derived from cancer cell lines. We therefore screened eight osteosarcoma cell lines for their ability to form vascularized tumours on the CAM.FindingsWe implanted 3-5 million cells of human osteosarcoma lines (HOS, MG63, MNNG-HOS, OST, SAOS, SJSA1, U2OS, ZK58) on the CAM at day 10 of embryonic development. Tumour growth was monitored by in vivo biomicroscopy at different time points and tumours were fixed in paraformaldehyde seven days after cell grafting. The tissue was observed, photographed and selected cases were further analyzed using standard histology.From the eight cell lines the MNNG-HOS, U2OS and SAOS were able to form solid tumours when grafted on the CAM. The MNNG-HOS tumours showed the most reliable and consistent growth and were able to penetrate the chorionic epithelium, grow in the CAM stroma and induce a strong angiogenic response.ConclusionsOur results show that the CAM assay is a useful tool for studying osteosarcoma growth. The model provides an excellent alternative to current rodent models and could serve as a preclinical screening assay for anticancer molecules. It might increase the speed and efficacy of the development of new drugs for the treatment of osteosarcoma.

Hip transposition as a limb salvage procedure following the resection of periacetabular tumors

One of the most difficult problems in tumor surgery is the treatment of pelvic tumors, particularly those in the periacetabular region. This retrospective study serves to analyze clinical and functional outcome of the new surgical technique of hip transposition.

Hip transposition as a universal surgical procedure for periacetabular tumors of the pelvis

Surgical treatment of pelvic tumors represents one of the most challenging problems in musculoskeletal oncology, especially in the periacetabular region. Because of the complex anatomy and demanding biomechanical situation, surgery leads to a considerable disability while all possible types of reconstruction are often associated with high complication rates. Nevertheless, it is known that wide resection of the tumor is one of the key points for long‐term survival in sarcoma therapy. Therefore, hip transposition was established in our clinic as a universal tool for periacetabular tumors excelling in small foreign parts and resulting in acceptable complication rates with good functional outcome. The following article gives an overview of the technique and the indications of different types of hip transposition, which were developed from the first procedure, described and published by Winkelmann in 1988. J. Surg. Oncol. 2009;99: 169–172.

The influence of elementary silver versus titanium on osteoblasts behaviour in vitro using human osteosarcoma cell lines.

Purpose. The antimicrobial effect of a silver-coated tumor endoprosthesis has been proven in clinical and experimental trials. However, in the literature there are no reports concerning the effect of elementary silver on osteoblast behaviour. Therefore, the prosthetic stem was not silver-coated because of concerns regarding a possible inhibition of the osseointegration. The aim of the present study was to investigate the effect of 5–25 mg of elementary silver in comparison to Ti-6Al-4V on human osteosarcoma cell lines (HOS-58, SAOS). Methods. Cell viability was determined by measuring the MTT proliferation rate. Cell function was studied by measuring alkaline phosphatase (AP) activity and osteocalcine production. Results. In the HOS-58 cells, the AP activity was statistically significant (P < 0.05) higher at a supplement of 5–10 mg of silver than of Ti-6 Al-4V at the same doses. For both cell lines, a supplement above 10 mg of silver resulted in a reduced AP activity in comparision to the Ti-6 Al-4V group, but a statistically significant difference (P < 0.05) was observed at a dose of 25 mg for the SAOS cells only. At doses of 20–25 mg in the HOS-58 cells and 10–25 mg in the SAOS cells, the reduction of the proliferation rate by silver was statistically significant (P < 0.05) compared to the Ti-6 Al-4V supplement. Discussion. In conclusion, elementary silver exhibits no cytotoxicity at low concentrations. In contrast, it seems to be superior to Ti-6 Al-4V concerning the stimulation of osteogenic maturation at these concentrations, whereas at higher doses it causes the known cytotoxic properties.

Epidermal Growth Factor Receptor Expression in High-Grade Osteosarcomas Is Associated with a Good Clinical Outcome

Purpose: The expression of the epidermal growth factor receptor (EGFR) in osteosarcomas has repeatedly been described. With the introduction of anti-EGFR–targeted therapies in clinical practice, these findings regain increased attention. Experience with anti-EGFR–targeted therapies in other cancers has made clear that besides the expression status of EGFR, a detailed knowledge about gene mutations is of major predictive power. We therefore aimed to explore the EGFR expression and gene mutation status in high-grade osteosarcomas. Experimental Design: We investigated tumor samples of osteosarcoma patients of all age groups by means of immunohistochemistry (n = 111) and egfr fluorescence in situ hybridization (n = 39). Sixty-three patients were treated according to the Cooperative Osteosarcoma Study Group protocols and complete clinical follow-up was available in these cases. Results: Ninety-one of 111 (81%) of osteosarcomas revealed an expression of EGFR. EGFR expression showed a dose-response relation with improved event-free and overall survival. This was independent of the degree of tumor regression due to neoadjuvant chemotherapy. Nine of 39 (23%) osteosarcomas showed egfr amplifications by means of fluorescence in situ hybridization. All these cases expressed EGFR. When comparing EGFR expression between primary biopsy and resection specimen (n = 19), viable residual tumor cells in resection specimens revealed a lower EGFR expression and a tendency toward membranous staining compared with the initial biopsy. Conclusions: In conclusion, expression and amplification of EGFR are frequently observed in high-grade osteosarcomas and are associated with improved prognosis in a dose-responsive way. This implies that low EGFR expression possibly predicts lack of response to conventional treatment in high-grade osteosarcomas and may warrant a more intensive therapeutic approach, although not based on EGFR targeting.