The working hypothesis of guided bone regeneration (GBR) is that the membrane physically excludes non-osteogenic tissues from interfering with bone healing. However, the underlying mechanisms are insufficiently explained. This study aimed to investigate the molecular and structural pattern of bone healing in trabecular bone defects, with and without naturally derived resorbable membrane. Defects were created in rat femurs and treated with the membrane or left empty (sham). After 3d, 6d and 28d, the defect sites and membranes were harvested and analyzed with histology, histomorphometry, quantitative-polymerase chain reaction (qPCR), Western blot (WB) and immunohistochemistry (IHC). Histomorphometry demonstrated that the presence of the membrane promoted bone formation in early and late periods. This was in parallel with upregulation of cell recruitment and coupled bone remodeling genes in the defect. Cells recruited into the membrane expressed signals for bone regeneration (BMP-2, FGF-2, TGF-β1 and VEGF). Whereas the native membrane contained FGF-2 but not BMP-2, an accumulation of FGF-2 and BMP-2 proteins and immunoreactive cells were demonstrated by WB and IHC in the in vivo implanted membrane. The results provide cellular and molecular evidence suggesting a novel role for the membrane during GBR, by acting as a bioactive compartment rather than a passive barrier.
Background. A retrospective study of long term outcome after the development of metastases from osteosarcoma was performed, with emphasis on the impact of different treatment strategies and the identification of prognostic factors.
Methods. From 1975 to 1993, a population‐based series of 60 patients with distant metastases (relapse) from high grade, extremity‐localized osteosarcoma was treated at The Norwegian Radium Hospital. Six patients relapsed after surgery alone, 28 patients relapsed after primary chemotherapy of low potency, and 26 patients after modern, intensive chemotherapy. Lung metastases were present in 88% of the patients, 52% had bilateral lesions, and the median number of lesions was three (range, 1‐25 lesions). Forty‐seven percent of patients had complete surgical excision of all identifiable metastatic nodules and 54% of these had additional second line chemotherapy defined as adequate. Adequate chemotherapy included further dose escalations of methotrexate in approximately half of the patients, usually from 8 to 12 g. The rest were exposed to novel agents such as cisplatin, etoposide, and ifosfamide. Of the operated patients, 43% had additional thoracotomies after subsequent relapses.
Results. The projected 5‐year survival rate from the first metastatic event was 24% for all patients and 50% for patients who underwent complete metastasectomy. In a multivariate analysis, the factors with independent predictive value for improved overall survival were the presence of a solitary metastasis, the accomplishment of complete metastasectomy, and the administration of adequate salvage chemotherapy.
Conclusions. Complete metastasectomy is mandatory for long term survival of patients with metastatic osteosarcoma, and repeated lung resections are necessary in nearly half the patients. Second line chemotherapy and following primary treatment with modern intensive chemotherapy protocols may improve survival further. Cancer 1995;75:1084–93.
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