[Growing prostheses after sarcoma resection in children and adolescents]. / Wachstumsprothesen nach Sarkomresektionen im Kindes- und Jugendalter.

BACKGROUND: Growing prostheses are regarded as a valuable alternative to amputation and rotationplasty for the treatment of primary malignant bone and soft-tissue sarcomas in childhood. During the last three decades different devices have been introduced and technically improved from invasively to non-invasively extendable prostheses. THE CURRENT SITUATION OF STUDIES: Despite the long period, only 21 peer-reviewed publications could be detected containing relevant numbers and results. In these papers, 590 patients with mean follow-up times of 81.1 months were reported who had been fitted with growing prostheses at the age of 12.6 years. Besides satisfactory functional results (78.3 out of 100 MSTS points) there was a high complication rate of 27.3% infections and 22.4% mechanical failure. COMPLICATIONS: This increasing risk of infection over a long follow-up period, represents the biggest drawback of this method and, therefore, needs to be discussed extensively with the patients and parents when considering this procedure as an alternative to ablative surgery.

Rapid and reliable healing of critical size bone defects with genetically modified sheep muscle.

Large segmental defects in bone fail to heal and remain a clinical problem. Muscle is highly osteogenic, and preliminary data suggest that autologous muscle tissue expressing bone morphogenetic protein-2 (BMP-2) efficiently heals critical size defects in rats. Translation into possible human clinical trials requires, inter alia, demonstration of efficacy in a large animal, such as the sheep. Scale-up is fraught with numerous biological, anatomical, mechanical and structural variables, which cannot be addressed systematically because of cost and other practical issues. For this reason, we developed a translational model enabling us to isolate the biological question of whether sheep muscle, transduced with adenovirus expressing BMP-2, could heal critical size defects in vivo. Initial experiments in athymic rats noted strong healing in only about one-third of animals because of unexpected immune responses to sheep antigens. For this reason, subsequent experiments were performed with Fischer rats under transient immunosuppression. Such experiments confirmed remarkably rapid and reliable healing of the defects in all rats, with bridging by 2 weeks and remodelling as early as 3-4 weeks, despite BMP-2 production only in nanogram quantities and persisting for only 1-3 weeks. By 8 weeks the healed defects contained well-organised new bone with advanced neo-cortication and abundant marrow. Bone mineral content and mechanical strength were close to normal values. These data demonstrate the utility of this model when adapting this technology for bone healing in sheep, as a prelude to human clinical trials.

Matrix-associated autologous chondrocyte transplantation in a compartmentalized early stage of osteoarthritis.

OBJECTIVE: Cartilage restoration in joints with an early stage of osteoarthritis (OA) is an important clinical challenge. In this study, a compartmentalized, early-stage OA was generated surgically in sheep stifle joints, and this model was used to evaluate a matrix-associated cell transplantation approach for cartilage repair. METHOD: Eighteen sheep were operated twice. During the first operation, a unicompartmental OA in a stable joint was induced by creating a critical-size defect. The second operation served as a regeneration procedure. The eighteen sheep were divided into three groups. One group was treated with spongialization (SPONGIO), while the two others had spongialization followed by implantation of a hyaluronan matrix with (MACT) or without chondrocytes (MATRIX). The follow-up took place 4 months after the second operation. Gross Assessment of Joint Changes score and Brittberg score were used for the macroscopic evaluation, Mankin score, O'Driscoll score, and immunohistochemistry for collagen type I and type II for histological evaluation. RESULTS: The MACT group achieved significantly better results in both macroscopic and histological examinations. In the regeneration area, a Mankin score of 7.88 (6.20; 9.55) [mean (upper 95% confidence interval; lower 95% confidence interval)] was reached in the MACT group, 10.38 (8.03; 12.72) in the MATRIX group, and 10.33 (8.80; 11.87) in the SPONGIO group. The O'Driscoll score revealed a highly significant difference in the degree of defect repair: 15.92 (14.58; 17.25) for the MACT group compared to the two other groups [5.04 (1.21; 8.87) MATRIX and 6.58 (5.17; 8.00) SPONGIO; P < 0.0001]. CONCLUSION: This study demonstrates promising results toward the development of a biological regeneration technique for early-stage OA.

Extendible Prostheses for Children After Resection of Primary Malignant Bone Tumor: Twenty-seven Years of Experience.

BACKGROUND: Endoprosthetic replacement in children following resection of a malignant bone tumor still is controversial because of the high number of reoperations. The aim of this study was to evaluate the long-term outcome with respect to limb-lengthening potential, satisfaction rate, and complications after implantation of extendible devices. METHODS: Seventy-one patients with a sarcoma in an extremity who had been followed for more than twenty-four months (mean, 131.6 months; range, 27.2 to 281.8 months) after tumor resection and prosthetic reconstruction with an extendible device were analyzed. The mean age at the time of the operation was ten years (range, four to sixteen years). The complication-free survival rate was evaluated with competing-risk analysis. Clinical outcomes and complications were rated with use of the Musculoskeletal Tumor Society (MSTS) score and a failure mode classification for segmental tumor endoprostheses, respectively. RESULTS: Twelve of seventy-one patients died of their disease. The overall MSTS score averaged 87.8% (range, 23.3% to 100%). The most common mode of failure was soft-tissue failure (46%), followed by structural failure (28%), infection (17%), and aseptic loosening (8%); only 2% of the children had local recurrence. An average of 4.4 lengthening operations per patient were required for an average limb elongation of 70.8 mm (range, 0 to 224 mm). An average of 2.5 operations (range, zero to eleven) per patient were performed for complications. CONCLUSIONS: Although limb lengthening with an extendible endoprosthesis seems to be effective, many children have related complications. These data will be a source of preoperative information for children and parents, and will provide a benchmark for further clinical improvements.

[Growing prostheses for reconstruction of lower limb defects in children]. / Wachstumsprothesen zur Rekonstruktion von Defekten der unteren Extremitäten beim Kind.

OBJECTIVE: Bone defect reconstruction with growing prostheses after resection of malignant bone tumors using the technique of extendable prostheses. INDICATIONS: Limb salvage surgery after resection of primary malignant bone tumors in the growing skeleton for expected leg length deficiencies > 4 cm. CONTRAINDICATIONS: Palliative tumor resection, infection, systemic metastases at the time of diagnosis, social contraindications, lack of compliance of the patient and/or family. SURGICAL TECHNIQUE: Wide resection of the tumor with resection of the biopsy location. Reconstruction with the growing prosthesis. Planned lengthening operations. POSTOPERATIVE MANAGEMENT: Mobilization with crutches, weight bearing or partial weight bearing according the prosthesis' fixation. Chemotherapy as defined in the chemotherapy protocol. Planned minimally invasive lengthening or noninvasive lengthening according to the type of growing module. RESULTS: Since 1969, more than 8,632 patients have been registered in the Vienna Bone and Soft Tissue Tumor Registry. Of these, 691 patients suffered from osteosarcoma and 243 from Ewing's sarcoma. A total of 513 patients were < 18 years of age (54.4%). Since 1987, 71 patients have been treated with growing prostheses: 13 patients died of disease, and 44 patients reached maturity. The overall 5- and 10-year survival were 84% and 77%, respectively. The patient group consisted of 26 girls and 18 boys, mean age at surgery 10 ± 3 years. The diagnosis was 34 osteosarcoma and 10 Ewing's tumors. The patients had a mean of 4 ± 3 elongation procedures to reach an elongation of 72.5 ± 53.45 mm. The average elongation per procedure was 14.83 ± 4.6 mm.