Efficacy and Safety of Microsurgery in Interdisciplinary Treatment of Sarcoma Affecting the Bone

Background: Sarcomas are tumors of mesenchymal origin with high variation in anatomical localization. Sarcomas affecting the bone often require an interdisciplinary resection and reconstruction approach. However, it is critical that microsurgical reconstruction strategies do not negatively impact tumor safety and overall survival, as limb salvage is only the secondary goal of tumor surgery. Here, we analyzed the efficacy and safety of microsurgery in interdisciplinary treatment of sarcoma affecting the bone. Patients and Methods: We performed a retrospective chart review of all patients treated for soft-tissue and bone sarcoma at the senior author's institution with a focus on bone affection and microsurgical reconstruction between 2000 and 2019. This particular subgroup was further investigated for tumor resection status, 5-year survival rate, length of hospital stay, as well as overall complication and amputation rates. Results: Between 2000 and 2019, 803 patients were operated for sarcoma resection and reconstruction by the Department of Plastic and Hand Surgery. Of these, 212 patients presented with sarcoma of the extremity affecting the bone. Within this subgroup, 40 patients required microsurgical reconstruction for limb salvage, which was possible in 38 cases. R0 resection was achieved in 93.8%. The 5-year survival was 96.7%, and the overall complication rate was 25%, of which 40% were microsurgery associated complications. Conclusion: Safe and function-preserving treatment of soft-tissue and bone sarcoma is challenging. Primary reconstruction with microsurgical techniques of sarcoma-related defects enables limb-sparing and adequate oncosurgical cancer treatment without increasing the risk for local recurrence or prolonged hospital stay. The treatment of sarcoma patients should be reserved to high-volume centers with experienced plastic surgeon embedded in a comprehensive treatment concept

Development and Retranslational Validation of an In Vitro Model to Characterize Acute Infections in Large Human Joints

Bacterial infections can destroy cartilage integrity, resulting in osteoarthritis. Goal was to develop an in vitro model with in vivo validation of acute joint inflammation. Inflammation in cocultivated human synovial fibroblasts (SFB), chondrocytes (CHDR), and mononuclear cells (MNC) was successively relieved for 10 days. Articular effusions from patients with (n=7) and without (n=5) postoperative joint infection in healthy patients (ASA 1-2) were used as model validation. Inflammation in vitro resulted in an enormous increase in IL-1 and a successive reduction in SFB numbers. CHDR however, maintained metabolic activity and proteoglycan synthesis. While concentrations of bFGF in vivo and in vitro rose consistently, the mRNA increase was only moderate. Concurring with our in vivo data, cartilage-specific IGF-1 steadily increased, while IGF-1 mRNA in the CHDR and SFB did not correlate with protein levels. Similarly, aggrecan (ACAN) protein concentrations increased in vivo and failed to correlate in vitro with gene expression in either the CHDR or the SFB, indicating extracellular matrix breakdown. Anabolic cartilage-specific BMP-7 with highly significant intra-articular levels was significantly elevated in vitro on day 10 following maximum inflammation. Our in vitro model enables us to validate early inflammation of in vivo cell- and cytokine-specific regulatory patterns. This trial is registered with MISSinG, DRKS 00003536

Immunohistological Localization of BMP-2, BMP-7, and Their Receptors in Knee Joints with Focal Cartilage Lesions

Introduction. Although it is well known that BMP-2 and BMP-7 play significant roles in cartilage metabolism, data about intra-articular expression and localization of these proteins and their receptors in humans are rare. Methods. Biopsies of synovia and debrided cartilage were taken in patients undergoing autologous chondrocyte implantation. Expression of BMP-2, BMP-7, and their receptors BMPR-1A, BMPR-1B and BMPR-2 were semiquantitatively evaluated by immunohistological staining. Results. BMP-7 was equally highly expressed in all cartilage and synovial biopsies. Increased levels of BMPR-1A, but not of BMPR-1B, and BMPR-2, were found in all synovial and 47% of all cartilage samples (P=0.002). BMP-2 was positively scored in 47% of all cartilage and 40% of all synovial specimens. Defect size, KOSS, Henderson or Kellgren-Lawrence score did not statistically significant correlate with the expression of the analyzed proteins or Mankin and Pritzker scores. Duration of symptoms and localization of lesions were associated with KOSS (P<0.02), but there was no influence of these parameters on protein expression. Conclusions. BMP-2, BMP-7, and BMPR-1A were expressed in cartilage and synovia of knees with focal cartilage lesions. Although defect localization and duration of symptoms decisively influence KOSS, there was no associated alteration of protein expression observed