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Infrared fluorescence imaging of lymphatic regeneration in nonhuman primate facial vascularized composite allografts
Mundinger, Gerhard S; Narushima, Mitsunaga; Hui-Chou, Helen G; Jones, Luke S; Ha, Jinny S; Shipley, Steven T; Drachenberg, Cinthia B; Dorafshar, Amir H; Koshima, Isao; Bartlett, Stephen T; Barth, Rolf N; Rodriguez, Eduardo D
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.
PMID: 22356782
ISSN: 0148-7043
CID: 631002
Repair of recurrent cleft palate with free vastus lateralis muscle flap
Christiano, Jose G; Dorafshar, Amir H; Rodriguez, Eduardo D; Redett, Richard J
A 6-year-old girl presented with a large recalcitrant oronasal fistula after bilateral cleft lip and palate repair and numerous secondary attempts at fistula closure. Incomplete palmar arches precluded a free radial forearm flap. A free vastus lateralis muscle flap was successfully transferred. No fistula recurrence was observed at 18 months. There was no perceived thigh weakness. The surgical scar healed inconspicuously. Free flaps should no longer be considered the last resort for treatment of recalcitrant fistulas after cleft palate repair. A free vastus lateralis muscle flap is an excellent alternative, and possibly a superior option, to other previously described free flaps.
PMID: 21787238
ISSN: 1055-6656
CID: 631072
Short-term application of doxorubicin chemotherapy immunosuppressive side effects for composite tissue allotransplantation
Hui-Chou, Helen G; Olenczak, J Bryce; Drachenberg, Cinthia B; Shea, Sofia M; Rodriguez, Eduardo D
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.
PMID: 22270570
ISSN: 0148-7043
CID: 631022
Tunneled superficial inferior epigastric artery (SIEA) myocutaneous/vascularized femur chimeric flaps: a model to study the role of vascularized bone marrow in composite allografts
Mundinger, Gerhard S; Kelamis, Joseph A; Kim, Soon H; Magarakis, Michael; Jones, Luke S; Ha, Jinny S; Rodriguez, Eduardo D
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.
PMID: 22113953
ISSN: 0738-1085
CID: 631032
A reappraisal of the free groin flap in aesthetic craniofacial reconstruction [Case Report]
Muresan, Claude; Dorafshar, Amir H; Rodriguez, Eduardo D
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.
PMID: 21734535
ISSN: 0148-7043
CID: 631082
Ocular injury, visual impairment, and blindness associated with facial fractures: a systematic literature review
Magarakis, Michael; Mundinger, Gerhard S; Kelamis, Joseph A; Dorafshar, Amir H; Bojovic, Branko; Rodriguez, Eduardo D
BACKGROUND: Injuries to the face can potentially lead to destruction of vital structures, with devastating sequelae to the patient. Facial fractures, especially of the midface, are often complicated by ocular injuries. The purpose of this study was to systematically review the literature to better understand specific fracture patterns associated with ocular injuries, including visual impairment and blindness. METHODS: The PubMed, EMBASE, and Cochrane databases from January of 2004 to April of 2010 were systematically reviewed to identify relevant studies. Only those that investigated facial fractures with concomitant ocular injuries, visual impairment, and/or blindness were included. Studies that described nonfacial fractures or those that only focused on the function of extraocular muscles were excluded. Case reports, nonsystematic reviews, and studies with fewer than 10 patients were also excluded. RESULTS: Eleven articles met study criteria and were included for analysis. There were a total of 14,535 patients, with an average of 1211 patients (range, 39 to 4426) per study. Level of evidence included levels II (n = 1 study), III (n = 1), and IV (n = 9). The mean reported rate of acute visual loss was 1.7 percent. Periorbital and orbital blowout fractures were more often complicated by ocular injuries compared with other facial fracture patterns. High-impact zygomatic fractures were most commonly associated with blindness. CONCLUSIONS: Existing studies exploring ocular injuries, visual impairment, and blindness associated with facial fractures offer conflicting data. Specifically directed studies are required so that significant correlations between specific fracture patterns and specific ocular injuries can be drawn. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, IV.
PMID: 21915081
ISSN: 1529-4242
CID: 631052
The prevalence of cervical spine injury, head injury, or both with isolated and multiple craniomaxillofacial fractures [Letter]
Mithani, Suhail Kamrudin; Kelamis, Joseph A; Mundinger, Gerhard S; Brooke, Benjamin S; Smith, Ian M; Bluebond-Langner, Rachel; Rodriguez, Eduardo
PMID: 22186532
ISSN: 1529-4242
CID: 631642
The component separation index: a standardized biometric identity in abdominal wall reconstruction
Christy, Michael R; Apostolides, John; Rodriguez, Eduardo D; Manson, Paul N; Gens, David; Scalea, Thomas
Objective: Reconstruction of traumatic ventral hernias often requires additional techniques to the abdominal wall component separation, such as the use of interpositional reconstruction with an acellular dermal matrix or other mesh to bridge the defect. Methods: We have developed a new value termed the "Component Separation Index" to evaluate ventral hernia defects. Choosing a fixed point on a preoperative axial computed tomographic scan (aorta) and the medial leading edges of the rectus abdominus muscles, we determined the angle of diastasis of the hernia. This angle is divided by 360 degrees giving a relative value of the transverse defect size as compared to the estimated circular body habitus for that specific patient. A retrospective review of 36 cases of ventral hernia repairs was performed. The Component Separation Index was calculated from the preoperative computed tomographic scans obtained before repair. Group 1 (n = 18) required component separation for closure. Group 2 (n = 18) required component separation and placement of interpositional mesh to span the hernia defect. Results: The Component Separation Index values were then compared using the student t test for each group. The mean Component Separation Index for group 1 was 0.11 with standard deviation of 0.06. The mean Component Separation Index for group 2 was 0.21 with standard deviation of 0.04 (P < .0001). As this value approaches 0.21, the likelihood of an interpositional repair in addition to component separation becomes much greater. Conclusions: While there is no substitute for clinical acumen when evaluating these defects, objective measurements can provide a valuable additional tool for the surgeon facing these challenging cases.
PMCID:3312684
PMID: 22461951
ISSN: 1937-5719
CID: 630992
Nonhuman primate model of fibula vascularized composite tissue allotransplantation demonstrates donor-recipient bony union
Mundinger, Gerhard S; Nam, Arthur J; Hui-Chou, Helen G; Stanwix, Matthew G; Jones, Luke S; Drachenberg, Cinthia B; Kukuruga, Debra; Shipley, Steven T; Dorafshar, Amir H; Panda, Aruna; Bartlett, Stephen T; Barth, Rolf N; Rodriguez, Eduardo D
BACKGROUND: Vascularized composite tissue allotransplantation has demonstrated clinical success with standard immunosuppression in hand and upper extremity transplantation. The authors developed a fibular vascularized composite tissue allotransplantation model in nonhuman primates to investigate healing and rejection patterns of bone and associated tissues. METHODS: Five fibular vascularized composite tissue allotransplantations were performed between mismatched cynomolgus macaques (Macaca fascicularis). Vascularized fibular segments with associated muscle and skin were transplanted to recipient forearm radius defects. Recipients were treated with either tacrolimus monotherapy or tacrolimus plus co-stimulatory blockade with a novel anti-CD28 antibody. Animals were followed for 6 months with serial radiographs, blood sample collection, and biopsies. At the study endpoint, angiographic, biomechanical, histologic, and immunologic assays were performed. RESULTS: All animals survived to the experimental endpoint of 180 days. Rapid or immediate skin loss was evident secondary to vascular compromise (n = 3) or rejection (n = 1) in four animals. Despite loss of nonbony segments and the development of transplant arteriopathy consistent with chronic rejection in two animals, serial radiologic imaging and histology demonstrated bone healing and donor-recipient bony union by 10 weeks in all animals. Histology confirmed the presence of viable cortical and marrow elements. Biomechanical analysis supported donor-recipient bony union. Short-tandem repeated genotypic analysis revealed that donor marrow had been completely replaced by recipient marrow. CONCLUSIONS: In contrast to successes in extremity vascularized composite tissue allotransplantation, the authors' nonhuman primate fibular vascularized composite tissue allotransplantation model showed early skin loss, replacement of donor bone marrow, and chronic rejection. Donor-recipient bone union did occur and supports the potential for reconstruction of bony continuity defects using isolated vascularized bone allotransplants.
PMID: 21841529
ISSN: 1529-4242
CID: 631062
Isolated bilateral zygomatic arch fractures of the facial skeleton are associated with skull base fractures
Kelamis, Joseph A; Mundinger, Gerhard S; Feiner, Jeffrey M; Dorafshar, Amir H; Manson, Paul N; Rodriguez, Eduardo D
BACKGROUND: To date, only limited case reports involving isolated bilateral zygomatic arch fractures exist. This fracture pattern is defined by the presence of bilateral zygomatic arch fractures and the absence of any other facial fractures. The purpose of this study was to systematically review a large trauma database to determine whether this fracture pattern exists and, if so, to elucidate the mechanism of injury and associated concomitant injuries. METHODS: A retrospective review of all patients admitted to the R Adams Cowley Shock Trauma center from February of 1998 to December of 2009 was conducted. International Classification of Diseases, Ninth Revision coding of computed tomographic scans was used to identify patients with zygoma fractures. The facial computed tomographic scans of all patients coded with bilateral zygoma fractures were reviewed to determine whether any had isolated bilateral zygomatic arch fractures. Medical charts were reviewed extensively. RESULTS: Five patients (0.24 percent of all zygoma fractures, 3.18 percent of bilateral zygoma fractures) were found to have isolated bilateral zygomatic arch fractures. All five patients had evidence of skull impact with at least one skull fracture and one skull base fracture. Glasgow Coma Scale scores (range, 6 to 14; average, 8.2) were significantly lower (t test, two-sided, p=0.01) compared with all patients (average, 12.2) with facial trauma during the study period. CONCLUSIONS: Isolated bilateral zygomatic arch fractures do exist. The authors' findings suggest skull impacts as the inciting mechanism of injury and an intimate link with skull base force transmission. The severe nature of this injury warrants a search for concomitant injuries to the head, brain, and spinal cord.
PMID: 21921771
ISSN: 1529-4242
CID: 631042