Faculty Bibliography

BACKGROUND/AIMS: Neovascularization involves angiogenesis and vasculogenesis mediated by cytokines and soluble chemokines. The predominant stimulus is ischemia, however, recent data suggest that ionizing radiation (IR) has angiogenic potential. In this study we evaluated whether IR increases vascularity and perfusion in vivo. METHODS: In wild-type mice, a full-thickness, pedicled skin flap was created and isolated for localized irradiation at a dose of 5 Gy. Serial Doppler analysis of the flap was performed. The skin flaps were then harvested at various time points for vascularity and histologic analysis. Blood was concurrently harvested for serum and hematopoietic progenitor cell population analysis. RESULTS: IR to an ischemic flap augmented the angiogenic cytokines SDF-1 and VEGF. Serum MMP-9 and s-kit levels, which are critical for progenitor cell mobilization, were also increased. When hematopoietic progenitor cells were evaluated by Sca1+/Flk1+ cells, a correlate 2-fold increase was seen compared to controls. When the flaps were examined, both vascularity and perfusion were increased. CONCLUSION: In this study we demonstrate that local, low-dose IR upregulates angiogenic chemokines and results in progenitor cell mobilization to the systemic circulation. There is a resultant increase in the vascularity of the irradiated flap, suggesting that the pro-angiogenic effects of IR can be harnessed locally

BACKGROUND: Composite tissue allotransplantation may have different immunosuppressive requirements and manifest different complications compared with solid organ transplantation. We developed a non-human primate facial composite tissue allotransplantation model to investigate strategies to achieve prolonged graft survival and immunologic responses unique to these allografts. METHODS: Composite facial subunits consisting of skin, muscle, and bone were heterotopically transplanted to mixed lymphocyte reaction-mismatched Cynomolgus macaques. Tacrolimus monotherapy was administered via continuous intravenous infusion for 28 days then tapered to daily intramuscular doses. RESULTS: Five of the six animals treated with tacrolimus monotherapy demonstrated rejection-free graft survival up to 177 days (mean, 113 days). All animals with prolonged graft survival developed posttransplant lymphoproliferative disorders (PTLD). Three animals converted to rapamycin after 28 days of rejection of their allografts, but did not develop PTLD. Genotypic analysis of PTLD tumors demonstrated donor origin in three of the five analyzed by short-tandem repeats. Sustained alloantibodies were detected in rejecting grafts and absent in nonrejecting grafts. CONCLUSIONS: Tacrolimus monotherapy provided prolonged rejection-free survival of composite facial allografts in a non-human primate model but was associated with the development of a high frequency of donor-derived PTLD tumors. The transplantation of a large volume of vascularized bone marrow in composite tissue allografts may be a risk factor for PTLD development.

BACKGROUND:: The authors assessed the safety and efficacy of a novel cleft rhinoplasty procedure that combines an open rhinoplasty with the Dibbell and Tajima techniques. METHODS:: A single-surgeon, 10-year, retrospective review was conducted of all unilateral cleft lip rhinoplasties (n = 157). Nonsyndromic patients undergoing a combined open incision/Dibbell/Tajima procedure and who had follow-up of greater than 8 months were included. Thirty-five patients were identified. Standardized patient photographs were studied in 18 patients who had both preoperative and 1-year postoperative photographs. Farkas normal values were applied to the medial canthal distance; from this value, metric measurements of changes in alar base width, columellar height, and nostril apex height were derived. RESULTS:: There were no complications secondary to skin envelope ischemia or cartilage graft infection. The revision rate was 11 percent for alar base position, 3 percent for depressed lower lateral cartilage, and 3 percent for nostril apex overhang. After the procedure, there was a statistically significant decrease in alar base width (19.9 mm versus 18.2 mm; p < 0.01) and an increase in columellar height (8.37 mm versus 9.59 mm; p = 0.02) and nostril apex height (4.70 mm versus 5.44 mm; p = 0.02) on the affected side. The differences in alar base width, columellar height, and nostril apex height between the affected and nonaffected sides all decreased significantly postoperatively. CONCLUSIONS:: The combined open rhinoplasty/Dibbell/Tajima procedure is safe, has a low revision rate, and is associated with a statistically significant decrease in alar base width, an increase in columellar height and nostril apex height, and a greater symmetry of nasal form