Justin M. Sacks

Intraoperative laser angiography using the SPY system: review of the literature and recommendations for use

Inadequate tissue perfusion is a key contributor to early complications following reconstructive procedures. Accurate and reliable intraoperative evaluation of tissue perfusion is critical to reduce complications and improve clinical outcomes. Clinical judgment is the most commonly used method for evaluating blood supply, but when used alone, is not always completely reliable. A variety of other methodologies have been evaluated, including Doppler devices, tissue oximetry, and fluorescein, among others. However, none have achieved widespread acceptance. Recently, intraoperative laser angiography using indocyanine green was introduced to reconstructive surgery. This vascular imaging technology provides real-time assessment of tissue perfusion that correlates with clinical outcomes and can be used to guide surgical decision making. Although this technology has been used for decades in other areas, surgeons may not be aware of its utility for perfusion assessment in reconstructive surgery. A group of experts with extensive experience with intraoperative laser angiography convened to identify key issues in perfusion assessment, review available methodologies, and produce initial recommendations for the use of this technology in reconstructive procedures.

Co-infusion of donor bone marrow with host mesenchymal stem cells treats GVHD and promotes vascularized skin allograft survival in rats.

We investigated the effect of autologous mesenchymal stem cells (MSC) on multiple unmodified donor bone marrow (BM) infusions and vascularized skin graft outcome. BM-derived rat MSC were examined for phenotype and function. MSC/MSC-conditioned-medium suppressed IFN-gamma production by T cells and modified DC function. Infusions of MSC with one-time BM improved vascularized skin graft survival, while with one-two-times BM reversed graft versus host disease (GVHD). Mixed chimerism was enhanced in recipients given two-four-times BM with MSC infusions. Interestingly, four-times BM infusions with MSC delayed GVHD onset, reduced host tissue damage and enhanced vascularized skin allograft survival compared to four-times BM alone. These data demonstrate that, the co-infusion of MSC with unmodified BM limit the toxicity of allogeneic BM transplantation, enhance mixed chimerism and improve vascularized skin graft survival. These findings provide insights for the development of autologous MSC-based BM transplantation and prevention of graft rejection or treatment of autoimmunity.

Reconstructive outcomes in patients undergoing contralateral prophylactic mastectomy

Background: As the rate of contralateral prophylactic mastectomy in breast cancer patients increases, more women are seeking immediate bilateral breast reconstruction. The authors evaluated complication rates in the index and prophylactic breasts in patients undergoing bilateral immediate reconstruction. Methods: The authors retrospectively reviewed the outcomes of all consecutive patients undergoing immediate postmastectomy bilateral reconstruction for an index breast cancer combined with a contralateral prophylactic mastectomy between 2005 and 2010. Patient, tumor, reconstruction, and outcome characteristics were compared between the index and prophylactic breasts in the same patient. Patients were classified by reconstruction method: implant, abdominal flap, or latissimus dorsi flap/implant. Regression models evaluated patient and reconstruction characteristics for potential predictive or protective associations with postoperative complications. Results: Of 497 patients included, 334 (67.2 percent) underwent implant reconstruction, 142 (28.6 percent) had abdominal flap reconstruction, and 21 (4.2 percent) had latissimus dorsi flap/implant reconstruction. Index reconstructions had a complication rate (22.5 percent) equivalent to that of contralateral prophylactic mastectomy reconstructions (19.1 percent; p = 0.090). Overall, 101 patients (20.3 percent) developed a complication in one reconstructed breast, and 53 (10.7 percent) developed complications in both breasts. Of the 154 patients who developed complications, 42 (27.3 percent) developed a complication in the prophylactic breast. Conclusions: Immediate index and contralateral prophylactic breast reconstructions appear to have equivalent outcomes, both overall and across reconstruction classifications. Together, patients, reconstructive surgeons, and extirpative surgeons should carefully consider the oncologic benefits of a contralateral prophylactic mastectomy in light of the risk of increased surgical morbidity of this type of mastectomy and reconstruction. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Prolongation of composite tissue allograft survival by immature recipient dendritic cells pulsed with donor antigen and transient low-dose immunosuppression.

Background: Composite tissue allograft transplantation is limited by risks of long-term immunosuppression. The authors investigated whether short-term immunosuppression combined with recipient immature dendritic cells pulsed with donor antigens promotes composite tissue allograft survival. Methods: Orthotopic hind-limb transplants were performed (day 0) from Wistar-Furth (RT1u) to Lewis (RT1l) rats. Recipient dendritic cells were propagated from bone marrow with granulocyte-macrophage colony-stimulating factor (bone marrow–derived dendritic cells) and pulsed with or without donor splenic cell lysate. Recipients were as follows: group I, control; group II, cyclosporine (10 mg/kg/day, days 0 through 6, intraperitoneally); group III, antilymphocyte serum plus cyclosporine (days −4 and +1, intraperitoneally); and groups IV and V, cyclosporine plus antilymphocyte serum, combined with 7 × 106 untreated or donor cell lysate-pulsed bone marrow–derived dendritic cells (days +7 and +14, intravenously), respectively. Epidermolysis/desquamation of donor skin defined rejection. Mixed leukocyte reaction determined recipient T-cell reactivity to donor. Tissue samples were obtained at 3 weeks and on the day of rejection. Groups comprised six or seven rats. Results: Donor alloantigen-pulsed bone marrow–derived dendritic cells (group V) significantly prolonged median composite tissue allograft survival time (32.0 days) compared with groups II (18.0 days, p = 0.0012), III (22.5 days, p = 0.0043), and IV (26.5 days, p = 0.0043). Splenic T cells in group V exhibited hyporesponsiveness to donor alloantigen in mixed leukocyte reaction. Interestingly, the graft muscle component in the bone marrow–derived dendritic cell–treated group (group V) showed significant reduction in mononuclear cell infiltration relative to group II (p = 0.0317). Conclusions: Donor alloantigen–pulsed recipient bone marrow–derived dendritic cells combined with transient T-cell–directed immunosuppression significantly prolonged composite tissue allograft survival across a full major histocompatibility complex barrier. This may represent the basis for a novel, clinically applicable strategy to promote composite tissue allograft survival with reduced systemic immunosuppression.

Long-Term Survival of Limb Allografts Induced by Pharmacologically Conditioned, Donor Alloantigen-Pulsed Dendritic Cells Without Maintenance Immunosuppression

Background. We showed recently that limb allograft survival could be enhanced by administration of alloantigen (Ag)-pulsed immature dendritic cells (DC) after transplantation. Since indefinite graft survival was not achieved, we have further modified the DC by pharmacologic (rapamycin; Rapa) conditioning and ascertained their influence on graft survival, without continued immunosuppressive therapy. Methods. We compared the ability of donor Ag-pulsed, Rapa-conditioned rat myeloid DC (Rapa DC) and control DC (CTR DC) to inhibit alloreactive T-cell responses after limb transplantation in antilymphocyte serum (ALS)-treated recipients given a short postoperative course of cyclosporine (CsA). Results. Both DC populations expressed similar levels of major histocompatibility complex (MHC) II, CD40 and CD54, but Rapa DC expressed lower CD86. After toll-like receptor activation, both populations produced minimal interleukin (IL)-12p70, but Rapa DC secreted lower levels of IL-6 and IL-10. The capacity of DCs to stimulate T-cell proliferation in mixed leukocyte reactions was very low. Pulsing of the DC with donor Ag did not alter their phenotype or function. Interestingly, posttransplant administration of donor Ag-pulsed Rapa DC to rats given perioperative ALS and 21 days CsA significantly delayed graft rejection and promoted long-term (>125 days) graft survival. AlloAg-pulsed Rapa DC induced T-cell hyporesponsiveness and promoted the generation of IL-10-secreting CD4+ T cells upon ex vivo challenge. Conclusions. Infusion of donor Ag-pulsed, Rapa-conditioned DC after composite tissue transplantation can prevent rejection of the grafts, including skin, across a full MHC mismatch and in the absence of continued immunosuppressive therapy.

Daily topical tacrolimus therapy prevents skin rejection in a rodent hind limb allograft model.

Background: Skin is the most immunogenic component of a composite tissue allograft. Topical immunotherapy is an attractive therapeutic modality with which to provide local immunosuppression, with minimal systemic toxicity. The present study was performed to investigate the potential of topical tacrolimus to prolong survival of the skin component of a composite tissue allograft. Methods: Wistar Furth–to-Lewis rat orthotopic hind limb transplants were performed. Group I consisted of rats treated with topical tacrolimus; group II, antilymphocyte serum plus 21 days cyclosporine; and group III, antilymphocyte serum plus 21 days of cyclosporine plus topical tacrolimus. In group IV, tacrolimus levels in blood, skin, and muscle were measured in an autograft control group. Results: All animals in group I (n = 8) developed grade III clinical rejection by postoperative day 9. In group II (n = 9), the median onset of grade III rejection was postoperative day 40 (range, postoperative days 34 to 44). In group III (n = 6), two animals developed focal grade III rejection on postoperative days 35 and 56. The remaining four animals reached the 100-day endpoint without grade III rejection. In group IV, tacrolimus levels were low or undetectable in blood, whereas skin levels were 100-fold higher than underlying muscle. Conclusions: Topical tacrolimus therapy has the potential to prevent skin rejection in a composite tissue allograft. Preoperative depletion of T cells with antilymphocyte serum, along with a short course of systemic immunosuppression, prevents acute rejection, whereas topical tacrolimus inhibits immune cell function in the skin. Concentrations of tacrolimus are substantially higher in skin compared with underlying muscle and peripheral blood. Topical immunotherapy could reduce the morbidity associated with systemic immunosuppression in clinical composite tissue allografts.

Anatomical Relationships among the Median Nerve Thenar Branch, Superficial Palmar Arch, and Transverse Carpal Ligament

Background: A possible complication of open, limited incision or endoscopic carpal tunnel release is transection of the thenar branch of the median nerve or the superficial palmar arch. Knowledge of the anatomy of these structures in relationship to the transverse carpal ligament is critical in preventing these complications. The authors investigated these anatomical relationships using cadaveric dissections. Methods: Forty-eight fresh cadaver hands were analyzed. The distance between the distal transverse carpal ligament and the superficial palmar arch, the distance between the distal transverse carpal ligament and the origin of the thenar branch of the median nerve, and the length of the transverse carpal ligament were measured. Results: In the 48 specimens, the thenar branch of the median nerve was extraligamentous in 44 (92 percent), subligamentous zero (0 percent), and transligamentous in four (8 percent). The thenar branch of the median nerve contained one branch in 28 (58 percent) and multiple branches in 20 specimens (42 percent). The average distance from the distal transverse carpal ligament to the superficial palmar arch was 18.8 ± 0.6 mm (95 percent CI, 17.6 to 20.1 mm) and that to the thenar branch of the median nerve was 6.9 ± 0.4 mm (95 percent CI, 6.0 to 7.8 mm) (p < 0.0001). The average length of the transverse carpal ligament was 28.5 ± 0.8 mm (95 percent CI, 26.9 to 30.1 mm). Conclusions: The anatomical relationships among the superficial palmar arch, thenar branch of the median nerve, and distal transverse carpal ligament were found to be consistent. This will assist the hand surgeon in preventing specific complications regardless of the method of carpal tunnel release chosen.

Omental transposition flap for salvage of ventricular assist devices.

Background: The use of ventricular assist devices for patients with end-stage cardiac failure awaiting heart transplantation has become increasingly common. Ventricular assist devices improve the longevity and the quality of life for these patients. In addition, they serve as a bridge to cardiac allograft transplantation until a donor heart is found. However, ventricular assist device–related infections remain a major problem complicating their long-term use. Clinical infection and sepsis can critically threaten these patients with ventricular assist devices. Infection can delay immediate transplantation and potentially require the removal of the device for definitive treatment of the problem. Methods: Patients who underwent insertion of a ventricular assist device at the University of Pittsburgh Medical Center were identified through accessing the medical records archives of the hospital. Review of patients’ medical records was conducted to obtain patient demographics, preoperative diagnosis and disease state, type of ventricular assist device inserted, postoperative day of ventricular assist device infection onset, infectious organism identified, timing of omental flap procedure after the initial insertion, duration of ventricular assist device support before cardiac transplantation, and patient follow-up. Results: There were 76 patients who underwent a ventricular assist device insertion procedure during the 4-year period between January of 2000 and January of 2004. Of the 76 patients who received a device, 11 (14 percent) had evidence of clinical infection secondary to insertion. Two of these 11 patients died before surgical intervention, four had their devices explanted, and the remaining five underwent omental flap transposition with bilateral pectoralis major advancement flaps in surgically addressing their infections. Of the five patients with infections who received omental transposition flaps, two went on to undergo successful transplantation, two continue to await cardiac allograft transplantation, and one died as a result of an unknown cause. Conclusions: The authors present their experience with five patients who received omental transposition flaps to cover infected ventricular assist device pumps and the associated tubing in large, open sternoabdominal wounds. Treatment included the direct application of an omental transposition flap over the infected device with use of a bilateral pectoralis advancement flap to aid in complete sternal and skin closure of the sternal wound defect. In each of these cases, the use of the omental flap was followed by resolution of the mediastinal infection. In addition, the treatment with an omental flap prevented the removal of infected devices in patients who were otherwise pump dependent during their waiting periods for transplantation. The use of omental transposition flaps can be an effective technique in salvaging infected ventricular assist devices and preserving this valuable device for patients awaiting a cardiac transplant.

Using the dorsal, cavernosal, and external pudendal arteries for penile transplantation: technical considerations and perfusion territories.

Background: Penile transplantation may provide improved outcomes compared with autogenous phalloplastic reconstruction. The optimal approach to vascularizing penile allografts is unknown. In penile replantation, typically only the dorsal arteries are repaired, but using the cavernosal and external pudendal arteries may improve erectile function and shaft skin perfusion, respectively. The authors sought to demonstrate the technical feasibility of using the dorsal, cavernosal, and external pudendal vessels for penile transplantation and to assess differences in their perfusion territories. Methods: Cadaveric penile transplantation was performed. Different colored dyes were injected at physiologic pressure into the dorsal, cavernosal, and external pudendal arteries, and tissue perfusion territories were assessed visually. Results: Cavernosal artery exposure and repair required minimal dissection of the corpora cavernosa; extra length taken from the donor compensated for resultant shortening of the proximal shaft stump. The external pudendal system was easily accessed in the groin. Dye injected into the cavernosal artery strongly perfused the corpora cavernosa, with minimal communication to skin. The dorsal artery principally perfused the glans and corpus spongiosum. The external pudendal artery perfused the shaft and surrounding skin. Conclusions: Anastomosing the cavernosal arteries may augment corporal inflow, which is necessary for erection. Although the dorsal arteries are critical for distal penile skin perfusion, the external pudendal artery should be used in proximal transplantation to ensure adequate shaft skin perfusion. Each of these arteries has a distinct and seemingly important perfusion territory that should be considered in the setting of penile transplantation.

A Model for Functional Recovery and Cortical Reintegration after Hemifacial Composite Tissue Allotransplantation

Background: The ability to achieve optimal functional recovery is important in both face and hand transplantation. The purpose of this study was to develop a functional rat hemifacial transplant model optimal for studying both functional outcome and cortical reintegration in composite tissue allotransplantation. Methods: Five syngeneic transplants with motor and sensory nerve appositions (group 1) and five syngeneic transplants without nerve appositions (group 2) were performed. Five allogeneic transplants were performed with motor and sensory nerve appositions (group 3). Lewis (RT1l) rats were used for syngeneic transplants and Brown-Norway (RT1n) donors and Lewis (RT1l) recipients were used for allogeneic transplants. Allografts received cyclosporine A monotherapy. Functional recovery was assessed by recordings of nerve conduction velocity and cortical neural activity evoked by facial nerve and sensory (tactile) stimuli, respectively. Results: All animals in groups 1 and 3 showed evidence of motor function return on nerve conduction testing, whereas animals in group 2, which did not have nerve appositions, did not show electrical activity on electromyographic analysis (p < 0.001). All animals in groups 1 and 3 showed evidence of reafferentation on recording from the somatosensory cortex after whisker stimulation. Animals in group 2 did not show a cortical response on stimulation of the whiskers (p < 0.001). Conclusion: The authors have established a hemiface transplant model in the rat that has several modalities for the comprehensive study of motor and sensory recovery and cortical reintegration after composite tissue allotransplantation.