A major challenge in reconstructive surgery is flap ischemia, which might benefit from induction of therapeutic angiogenesis. Here we demonstrate the effect of an adeno-associated virus (AAV) vector delivering vascular endothelial growth factor (VEGF)165 in two widely recognized in vivo flap models. For the epigastric flap model, animals were injected subcutaneously with 1.5 x 10(11) particles of AAV-VEGF at day 0, 7, or 14 before flap dissection. In the transverse rectus abdominis musculocutaneous flap model, AAV-VEGF was injected intramuscularly. The delivery of AAV-VEGF significantly improved flap survival in both models, reducing necrosis in all treatment groups compared to controls. The most notable results were obtained by administering the vector 14 days before flap dissection. In the transverse rectus abdominis musculocutaneous flap model, AAV-VEGF reduced the necrotic area by >50% at 1 week after surgery, with a highly significant improvement in the healing process throughout the following 2 weeks. The therapeutic effect of AAV-VEGF on flap survival was confirmed by histological evidence of neoangiogenesis in the formation of large numbers of CD31-positive capillaries and alpha-smooth muscle actin-positive arteriolae, particularly evident at the border between viable and necrotic tissue. These results underscore the efficacy of VEGF-induced neovascularization for the prevention of tissue ischemia and the improvement of flap survival in reconstructive surgery.

In this study we performed 77 procedures on 65 patients fulfilling the oncological criteria for skin-sparing mastectomy and presenting with large or medium size breasts. All the operations were performed as a single-stage procedure with an anatomical prosthesis allocated into a compound pouch, made up of the pectoralis major, serratus anterior fascia, and a lower dermal adipose flap. The medium size of the anatomical implants employed was 444.3 cc. The implant removal rate was 14.2%. At a median follow-up of 36 months we reported a 0.5% local recurrence rate per year. The overall specific survival rate was 98.2%. This study confirms the safety and effectiveness of this technical variation of skin and nipple-sparing mastectomies. All breast, irrespective of mammary shape and size, can be reconstructed with medium size implants and, if required, contralateral adjustments. The overall complication rate is in keeping with previous studies.

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