Faculty Bibliography

BACKGROUND: Although fat deposition is a defining clinical characteristic of lymphedema, the cellular mechanisms that regulate this response remain unknown. The goal of this study was to determine how lymphatic fluid stasis regulates adipogenic gene activation and fat deposition. METHODS: Adult female mice underwent tail lymphatic ablation and were euthanied at 1, 3, or 6 weeks postoperatively (n = 8 per group). Samples were analyzed by immunohistochemistry and Western blot analysis. An alternative group of mice underwent axillary dissections or sham incisions, and limb tissues were harvested 3 weeks postoperatively (n = 8 per group). RESULTS: Lymphatic fluid stasis resulted in significant subcutaneous fat deposition and fibrosis in lymphedematous tail regions (p < 0.001). Western blot analysis demonstrated that proteins regulating adipose differentiation including CCAAT/enhancer-binding protein-alpha and adiponectin were markedly up-regulated in response to lymphatic fluid stasis in the tail and axillary models. Expression of these markers increased in edematous tissues according to the gradient of lymphatic stasis distal to the wound. Immunohistochemical analysis further demonstrated that adiponectin and peroxisome proliferator-activated receptor-gamma, another critical adipogenic transcription factor, followed similar expression gradients. Finally, adiponectin and peroxisome proliferator-activated receptor-gamma expression localized to a variety of cell types in newly formed subcutaneous fat. CONCLUSIONS: The mouse-tail model of lymphedema demonstrates pathologic findings similar to clinical lymphedema, including fat deposition and fibrosis. The authors show that lymphatic fluid stasis potently up-regulates the expression of fat differentiation markers both spatially and temporally. These studies elucidate mechanisms regulating abnormal fat deposition in lymphedema pathogenesis and therefore provide a basis for developing targeted treatments.

We propose the profunda femoris artery perforator (PAP) flap for autologous breast reconstruction. We provide an anatomic basis for this flap. Ten cadaveric thighs were dissected. A perforator was dissected to its origin. The lengths of pedicle, vessel diameters, and weights were measured. The average distance inferior to the gluteal crease was 3.5 cm (1 to 5 cm). The average distance from the midline was 6.2 cm (3 to 12 cm). The average pedicle length was 10.6 cm. Diameters of the artery and vein averaged 2.3 mm and 2.8 mm. The flaps averaged 28 x 8 cm. The average weight was 206 g (100 to 260 g). Computed tomography angiograms of 20 thighs were examined. Measurements were taken from the gluteal crease and midline to the perforator. The average distance caudal to the gluteal crease was 4.4 cm (1.1 to 7.2 cm). The average distance lateral to the midline was 5.1 cm (2.5 to 9 cm). The data presented in this article provide an anatomic basis for the PAP flap.

BACKGROUND: Transplantation of a facial vascularized composite allograft is a highly complex procedure that requires meticulous planning and affords little room for error. Although cadaveric dissections are an essential preparatory exercise, they cannot simulate the true clinical experience of facial vascularized composite allograft recovery. METHODS: After obtaining institutional review board approval to perform a facial vascularized composite allograft research procurement, a 66-year-old, brain-dead donor was identified. The family graciously consented to donation of a total face, double jaw, and tongue allograft and multiple solid organs. RESULTS: A craniofacial computed tomographic angiogram was obtained preoperatively to define the vascular anatomy and facilitate virtual computerized surgical planning. The allograft was procured in 10 hours, with an additional 2 hours required for an open tracheostomy and silicone facial impression. The donor was coagulopathic throughout the recovery, resulting in an estimated blood loss of 1500 ml. Fluorescence angiography confirmed adequate perfusion of the entire allograft based on lingual and facial arterial and external jugular and thyrolinguofacial venous pedicles. The solid organ transplant team initiated abdominal organ isolation while the facial allograft procurement was in progress. After completion of allograft recovery, the kidneys and liver were recovered without complication. CONCLUSIONS: Before conducting a clinical face transplant, adequate preparation is critical to maximize vascularized composite allotransplantation outcomes and preserve solid organ allograft function. As more centers begin to perform facial transplantation, research procurement of a facial vascularized composite allograft offers a unique educational opportunity for the surgical and anesthesia teams, the organ procurement organization, and the institution.

BACKGROUND: With the transplantation of more extensive facial vascularized composite allografts, fundamental craniofacial and aesthetic principles become increasingly important. In addition, computer-assisted planning and intraoperative navigation may improve precision and efficiency in these complex procedures. METHODS: Ten mock face transplants were performed in 20 cadavers. The vascularized composite allograft consisted of all facial skin, mimetic muscles, the tongue, the midface by means of a Le Fort III osteotomy, and the mandible by means of sagittal split osteotomies. Craniofacial computed tomographic scans were obtained before and after the mock transplants. Surgical planning software was used to virtually plan the osteotomies, and a surgical navigation system guided the osteotomies intraoperatively. Cephalometric analyses were compared between the virtually planned transplants and the actual postoperative results. RESULTS: The combination of preoperative computerized planning and intraoperative guidance consistently produced a vascularized composite allograft that could be easily fixated to the prepared recipient, with only minimal burring of osteotomy sites necessary. Satisfactory occlusion was maintained, and postoperative computed tomography confirmed accurate skeletal fixation. Insignificant differences with regard to cephalometric analyses were noted when predicted and actual postoperative data were compared. CONCLUSIONS: The authors' experience treating severe craniofacial injury allowed consistent transfer of facial vascularized composite allografts, maintaining proper occlusion. Preoperative computer planning and intraoperative navigation ensured precise osteotomies and a good donor-recipient skeletal match, which greatly reduced the need for intraoperative adjustments and manipulation. This total facial vascularized composite allograft represents one of the most extensive described and is intended to represent a typical central facial demolition pattern.

BACKGROUND: Current literature describes the forehead as one aesthetic subunit of the face. We argue for the usefulness of aesthetic forehead subunits when microvascular flap reconstruction is required. Key to utilization of microvascular flaps for restoration of forehead subunits is an understanding of the patient population and defect characteristics most amiable to treatment. METHODS: We conducted an International Review Board-approved retrospective chart review of nine consecutive patients who had undergone free flap reconstruction for large forehead defects. RESULTS: The patients' foreheads included one paramedian defect; one central and paramedian defect; four central, paramedian, and lateral defects; and three lateral defects. Seven patients had ulnar forearm flaps and two had anterolateral thigh flaps. The success rate was 100%. CONCLUSION: A forehead subunit classification system has been devised that provides a suitable option for cases that benefit from distant tissue replacement in a single stage, while preserving the principles of aesthetic replacement.

BACKGROUND: Clinical vascularized composite allografts (VCA), although performed with good success, have been characterized by rejection episodes and postoperative graft edema. We investigated lymphatic donor-recipient reconstitution and lymphatic regeneration in a nonhuman primate facial VCA model. METHODS: Heterotopic partial face (n = 9) VCAs were performed in cynomolgus macaques. Grafts were monitored for rejection episodes and response to immunosuppressive therapies as previously described. Donor and recipient lymphatic channels were evaluated using a near-infrared handheld dual-channel light-emitting diode camera system capable of detecting fluorescence from indocyanine green injections. Graft lymphatic channels were serially evaluated from postoperative day 0 to 364. RESULTS: Preoperative imaging demonstrated superficial lymphatic anatomy similar to human anatomy. Initial resolution of facial allograft swelling coincided with superficial donor-recipient lymphatic channel reconstitution. Reconstitution occurred despite early acute rejection episodes in 2 animals. However, lymphatic channels demonstrated persistent functional and anatomic pathology, and graft edema never fully resolved. No differences in lymphatic channels were noted between grafts that developed transplant vasculopathy (n = 3) and those that did not (n = 6). Dynamic changes in patterns of lymphatic drainage were noted in 4 animals following withdrawal of immunosuppression. CONCLUSIONS: Donor-recipient lymphatic channel regeneration following VCA did not result in resolution of edema. Technical causes of graft edema may be overcome with alternative surgical techniques, allowing for direct investigation of the immunologic relationship between VCA graft edema and rejection responses. Mechanisms and timing of dynamic donor-recipient lymphatic channel relationships can be evaluated using fluorescent imaging systems to better define the immunologic role of lymphatic channels in VCA engraftment and rejection responses, which may have direct clinical implications.

BACKGROUND: This study was to evaluate the sensory recovery in the lower lip and chin in patients who underwent segmental mandibulectomy involving inferior alveolar nerve and simultaneous reconstruction with fibular osteoseptocutaneous flap and interposition sural nerve graft. MATERIAL AND METHOD: From 1993 to 2004, a total of 20 patients underwent segmental mandibulectomy, simultaneous fibula osteoseptocutaneous flap reconstruction and interpositional sural nerve graft. Twelve patients were available for the study. There were seven male and five female patients with average age of 35.8 years (16-52 years). The sense at the lower lip and chin was measured by two-point discrimination both at the operated and non-operated side at an average of 64.3 months (12-146 months). RESULT: The operated side revealed an average of 13.7 mm for static (STPD) and 13.3 mm for moving two-point discrimination (MTPD) at the lower lip and 13.7 mm for static and 13.4 mm for MTPD at the chin. Data from the non-operated side averaged 3.4 mm for static and 3.2 mm for MTPD at lower lip and 5.1 mm for static and 4.5 mm for moving discrimination at the chin. All patients recovered better than protective sensation on the operated side, which was sufficient to prevent self-mutilation, preserve comprehensible speech and maintain oral competence. No patient complained of significant donor site morbidity. CONCLUSION: Simultaneous reconstruction of a segmental mandibulectomy involving inferior alveolar nerve with a fibula osteoseptocutaneous flap and interpositional sural nerve graft offers simultaneous replacement of mandibular architecture and restoration of protective perioral sensation.

BACKGROUND: Adjuvant chemotherapy is often required for the treatment of bone cancers after tumor resection, which often results in a large continuity defect. The immunosuppressive side effects could instead be exploited to allow immediate reconstruction with a composite tissue allograft (CTA) that would provide for replacement of tissues. We used a short course of doxorubicin to achieve a novel method of immunosuppression in a rat model undergoing CTA to create an immunological environment for allograft survival. MATERIALS & METHODS: The Institutional Animal Care and Use Committee-approved protocol consisted of 3 experimental groups. Groups 2 and 3 consisted of Brown Norway rats (n = 5) as allograft donors and Lewis rats (n = 5) as transplant recipients. An abdominal wall CTA was harvested off the superficial inferior epigastric vessels. Doxorubicin therapy was administered in group 3 animals. Survival of the CTA was assessed by physical examination and histological analysis. RESULTS: Allotransplant without treatment showed complete clinical and histologic rejection by day 7. Allotransplant rats treated with doxorubicin had clinically and histologically normal grafts through day 10. Kaplan-Meier survival analysis showed a statistically significant difference, with increased CTA survival time to end point with doxorubicin treatment, from a mean of 8.8 days in group 2 to 16.4 days in group 3. CONCLUSIONS: Allotransplant flaps without treatment developed complete clinical and histological rejection. The allotransplant group which received doxorubicin showed a delay of allograft rejection with an 86% increased CTA graft survival time. This demonstrates the feasibility of the immunosuppression side effect caused by chemotherapy to prevent rejection of a CTA.

The role of vascularized bone marrow in promoting composite allograft survival can be assessed by intrinsically chimeric flaps. In this study, we introduce a significant modification to a previously described rat model of combined superficial inferior epigastric artery (SIEA) myocutaneous/vascularized femur transplantation. We previously noted autocannibalization in orthotopic myocutaneous SIEA allotransplants, which complicated clinical and histologic evaluation of rejection. We therefore designed syngeneic experiments in eight Lewis (RTl(1) ) rat pairs to explore the feasibility of tunneling the SIEA component of chimeric SIEA myocutaneous/vascularized femur flaps to the recipient dorsum. Vascularized SIEA myocutaneous/femur transplants survived in their entirety to POD 63 study endpoint with patent anastomoses in seven of eight (87.5%) transplants as confirmed clinically, histologically, and via near-infrared fluorescent angiography. Tunneling of the SIEA component of SIEA myocutaneous/vascularized femur flaps to the recipient dorsum can be achieved with high success rate and acceptable operative times, and is a technically easy method to study the role of vascularized bone marrow in composite allografts. This modification facilitates SIEA component monitoring, removes it from constant contact with cage bedding, and places it in a location where autocannibalization is unlikely.

Craniofacial defects are often associated with 3-dimensional volumetric contour deficiencies. The free groin flap was historically popular though technical limitations subsequently caused its use to fall from favor. We sought to determine if a role remained for the free groin flap in aesthetic craniofacial reconstruction. From May 2005 to July 2010, 15 patients had 18 consecutive free groin flaps performed by the senior surgeon at the R Adams Cowley Shock Trauma Center and the Johns Hopkins Medical Institute. Data collected included age, sex, operative date, etiology, defect size, recipient vessels, complications, donor-site closure, and follow-up time. Eighteen groin flaps were used for the patient cohort consisting of 10 males and 5 females (mean age, 26 years; range, 18-40 years) who underwent reconstruction necessitated by various oncologic, traumatic, infectious, and congenital etiologies. The average defect size was 7.3 x 6.3 cm (range, 3-10 x 1-10 cm). Seventeen flaps were based on the superficial circumflex iliac vessels and 1 on the superficial inferior epigastric vessels. Seventeen flaps used the superficial temporal artery and vein as the recipient vessels, and the remaining flap used the superior thyroid artery and retromandibular vein. Of the 18 flaps, 17 survived (94% survival rate). All donor sites were closed primarily. Follow-up time ranged from 6 to 60 months. The free groin flap is generally underused in the reconstruction of complex craniofacial facial defects. Its unique characteristics and minimal donor-site morbidity should prompt the reconstructive surgeon to retain the free groin flap in his or her armamentarium.