Faculty Bibliography

BACKGROUND: Gustilo IIIB fractures involve high-energy tibial fractures for which there is inadequate soft tissue coverage. In addition to orthopedic fixation, these injuries require soft tissue reconstruction, often in the form of a microvascular free flap. Although the majority of orthopedic literature favorably compares intramedullary rod fixation to external fixation in open tibial fractures, these studies have not focused on the role of either method of fixation in relation to the soft tissue reconstruction. METHODS: Because we had noted numerous complications after providing free-flap coverage over intramedullary rodded fractures, we sought to investigate whether there were differences in outcomes between free flap-covered lower-extremity fractures which were fixated by external fixation versus intramedullary rods. A retrospective chart review was performed on all patients in our institution who had lower-extremity free flaps for coverage of Gustilo IIIB fractures from 1995-2005 in relation to the type of bony fixation. RESULTS: Of the 38 patients studied, 18 underwent external fixation of the tibial fracture, and 20 had intramedullary rodding. Overall flap survival was 95%, with 1 failure in each group. However, the intramedullary rod group had higher incidences of wound infection, osteomyelitis, and bony nonunion (25%, 25%, and 40%, respectively) than the external fixation group (6%, 11%, 17%, respectively). CONCLUSIONS: For Gustilo IIIB fractures that require free-flap coverage, the added bony and soft tissue manipulation required for intramedullary rodding may disrupt the surrounding blood supply and lead to higher rates of complications that threaten the overall success of the reconstruction. Plastic and orthopedic surgeons should discuss the optimal method of bony fixation for complex tibial fractures when a free flap will likely be needed for soft tissue coverage. This integrated team approach may help minimize complications

BACKGROUND: Lower-extremity reconstruction with microvascular free flap coverage is often the only option for limb salvage. Flap failure rates, however, continue to have higher complication rates than those to other anatomic sites; a significant number of flaps that fail result in amputation. This study retrospectively analyzed patients treated at a single institution who underwent attempted lower-extremity limb salvage with microsurgical techniques over a 25-year period. Of particular interest are the outcome data for patients who had initial free flap failure. PATIENTS AND METHODS: A prospectively maintained database was used to identify patients who satisfy criteria. Every patient who was treated with a microvascular free flap to their lower extremities was identified and included in this analysis. All records were reviewed from 1980 through 2004. Patients who had free flaps to the lower extremity fail after the initial operation were identified and selected for further analysis. RESULTS: Five hundred eighty-eight patients who underwent microsurgical reconstruction of lower extremity wounds had a failure rate of 8.5%. Trauma patients (83%) had a failure rate of 9%. On subset analysis, the failure rate for trauma patients decreased from 11% (1980-1992) to 3.7% (1993-2004). Of patients who had a failed free flap, 18% went on to limb amputation; the remainder was salvaged with secondary free flaps, local flaps, or skin grafting. CONCLUSION: This single institutional experience spanning 25 years represents the longest continual series of lower-extremity free flaps reported in the literature. The improved success rate seen in the second half of the study period is attributed to a more critical selection of free-flap candidates, improved understanding of the physiology surrounding acute trauma and a more sophisticated multidisciplinary team organization

Successful nonextremity replantations, particularly of the facial anatomy and testicles, are rare procedures, and only a handful of cases have been reported. This article reviews the current literature in nonextremity replantations and representative cases performed at the authors' institution. Certain underlying themes and problems are consistently encountered in the surgical management of these cases. These are identified and reviewed. Although the replantation of these body parts remains technically challenging, all efforts should be made, when indicated, to repair these injuries microsurgically, because it currently offers the best reconstructive solution for these patients

Calreticulin (CRT), an intracellular chaperone protein crucial for the proper folding and transport of proteins through the endoplasmic reticulum, has more recent acclaim as a critical regulator of extracellular functions, particularly in mediating cellular migration and as a requirement for phagocytosis of apoptotic cells. Consistent with these functions, we show that the topical application of CRT has profound effects on the process of wound healing by causing a dose-dependent increase in epithelial migration and granulation tissue formation in both murine and porcine normal and impaired animal models of skin injury. These effects of CRTare substantiated, in vitro, as we show that CRT strongly induces cell migration/wound closure of human keratinocytes and fibroblasts, using a wound/scratch plate assay, and stimulates cellular proliferation of human keratinocytes, fibroblasts, and vascular endothelial cells, providing mechanistic insight into how CRT functions in repair. Similarly, in both animal models, the histology of the wounds show marked proliferation of basal keratinocytes and dermal fibroblasts, dense cellularity of the dermis with notably increased numbers of macrophages and well-organized collagen fibril deposition. Thus, CRT profoundly affects the wound healing process by recruiting cells essential for repair into the wound, stimulating cell growth, and increasing extracellular matrix production

BACKGROUND: Gene therapy for cancer holds enormous therapeutic promise, but its clinical application has been limited by the inability to achieve targeted, high-level transgene expression with limited systemic toxicity. The authors have developed a novel method for delivering genes to microvascular free flaps (commonly used during reconstructive surgery) to avoid these problems. METHODS: During the finite period in which a free flap is separated from the host (ex vivo), it can be perfused with extremely high titers of genetic material through the afferent artery, resulting in efficient transduction of the tissue. Before reanastomosis, unincorporated genetic material is flushed from the flap, minimizing systemic toxicity. RESULTS: In a rodent model using an adenoviral vector containing the lacZ reporter gene, high regional expression of beta-galactosidase was achieved in all the different cells in a microvascular free flap. Moreover, no beta-galactosidase staining was observed outside of the transduced flap, and viral sequence was undetectable by polymerase chain reaction analysis in other tissues. Further analysis confirmed that high-level transgene expression was precisely localized to the explanted tissue, with no collateral transduction. CONCLUSIONS: Targeting gene delivery with minimal systemic toxicity is essential for successful gene therapy. This form of 'biological brachytherapy' provides a new opportunity to deliver targeted therapeutic transgenes to patients undergoing reconstructive surgery and allows microvascular free flaps to perform therapeutic and reconstructive functions

BACKGROUND: Although microvascular coupling devices are used routinely and successfully for venous anastomosis, there are few published reports demonstrating their efficacy for performing arterial anastomosis. It has been the senior author's (C.Y.A.) preference to perform arterial anastomosis using the microvascular coupling device when feasible. METHODS: All microsurgical breast reconstructions performed by the senior author at the New York University Medical Center between 1998 and 2004 were retrospectively reviewed. A total of 60 patients underwent microsurgical breast reconstruction, of which 20 were bilateral, for a total of 80 flaps. RESULTS: Of the 80 flaps performed, there were 47 muscle-sparing TRAM and 22 deep inferior epigastric perforator (DIEP) flaps, and 11 were superior gluteal flaps. Arterial coupling was successfully performed in 60 of 69 flaps based on the deep inferior epigastric artery (87%) and 2 of 11 gluteal flaps (18%); arterial coupling was performed successfully 62 of 74 times (83.9%) when the thoracodorsal artery was the recipient vessel and never performed when the internal mammary artery was the recipient vessel. The overall flap success rate was 100%. CONCLUSIONS: In our large series, we were able to perform a coupled arterial anastomosis in nearly 80% of the cases, without the loss of any flaps. With proper vessel selection and sufficient experience using the microvascular coupler, arterial coupling may be performed in an expeditious, safe, and reliable fashion with minimal morbidity. Though not commonly practiced, use of the coupling device for arterial anastomosis can provide significant time savings, especially in bilateral breast reconstructions

BACKGROUND: Long-term survival of a skin graft is dependent on eventual revascularization. The authors' aim in the present study was to determine whether skin graft vascularization occurs by (1) simple reconnection of vessels, (2) ingrowth of recipient vasculature, (3) outgrowth of donor-derived vessels, and/or (4) recruitment of bone marrow-derived endothelial progenitor cells. METHODS: Full-thickness skin grafts (1 x 1 cm) were transferred between wild-type FVB/N mice (n = 20) and transgenic tie2/lacZ mice (n = 20), where lacZ expression is controlled by the endothelial specific tie2 promoter, allowing differentiation of recipient and donor endothelial cells. The contribution of endothelial progenitor cells to skin graft neovascularization was determined using a bone marrow transplant model where tie2/lacZ bone marrow was transplanted into wild-type mice (n = 20). RESULTS: Vascular regression in the graft was observed at the periphery starting on day 3 and moving centrally through day 21, sparing graft vessels in the absolute center of the graft. At the same time, vascular ingrowth occurred from the wound bed to replace the regressing vessels. Furthermore, bone marrow-derived endothelial progenitor cells contributed to these new vessels starting as early as day 7. Surprisingly, the contribution of bone marrow-derived vessels to the overall process was approximately 15 to 20 percent of new endothelial cells. CONCLUSIONS: Replacement of the donor graft vasculature by endothelial and endothelial progenitor cells from the recipient along preexisting channels is the predominant mechanism for skin graft revascularization. This mechanism is likely similar for all nonvascularized free grafts and suggests novel strategies for optimizing the vascularization of tissue constructs engineered in vitro