RESUMO
ABSTRACT: Vascularized composite allotransplantation of the face is an exceedingly complex procedure, requiring extensive planning and surgical precision in order to successfully manage patients with facial disfigurements. This review aims to present an overview of the salient anatomic considerations in facial transplantation, as well as give attention to unique patient populations and special considerations.A literature review was performed in search of articles pertaining to considerations in facial transplantation using the databases PubMed, Web of Science, and Cochrane. Articles selected for further review included full-text articles with an emphasis on specific anatomic defects and how they were addressed in the transplant process, as well as management of special patient populations undergoing facial transplantation. In total, 19 articles were deemed appropriate for inclusion.The use of computer-assisted technologies for the planning portion of the procedure, as well as intraoperative efficiency, has yielded favorable results and can be considered as part of the operative plan. The ultimate outcome is dependent upon the synchronization of subunits of the allograft and the desired functional outcomes, including osseous, ocular, oral, and otologic considerations. Management of specific pathology and subgroups of patients are critical aspects. Although pediatric face transplantation has not yet been performed, it is a likely a future step in the evolution of this procedure.When performing a face transplantation, many components must be considered pre-, intra-, and post-operatively. This systematic review presents specific anatomic considerations, as well as information about special patient populations within this crosssection of multidisciplinary microsurgery, psychiatry, and transplant immunology.
Assuntos
Transplante de Face , Alotransplante de Tecidos Compostos Vascularizados , Criança , Transplante de Face/métodos , Humanos , Microcirurgia , Transplante Homólogo , Alotransplante de Tecidos Compostos Vascularizados/métodosRESUMO
BACKGROUND: Cellular therapies for immunomodulation in vascularized composite allotransplantation (VCA) have gained importance due to their potential for minimization of immunosuppression. Adipose-derived (AD) mesenchymal stem cells (MSCs) especially have shown encouraging potential. We investigated the influence of timing and frequency of AD-MSC treatment on immunologic and graft survival as well as graft vasculopathy outcomes after VCA. METHODS: Lewis rats received full-mismatched Brown Norway rat hindlimb transplants. Recipient animals were assigned to groups receiving donor-derived AD-MSCs (10 cells/animal) either on postoperative day (POD) 1, POD 4, or repeatedly on POD 4, 8, and 15, and compared to untreated controls. RESULTS: Although AD-MSC administration on POD 1 or POD 4, 8, and 15 resulted in 50% long-term graft acceptance, recipients treated on POD 4, and controls rejected before POD 50. All treated animals revealed peripheral blood chimerism (4 weeks), most pronounced after repetitive cell administration (12.92% vs 5.03% [POD 1] vs 6.31% [POD 4]; P < 0.05; all P < 0.01 vs control 1.45%). Chimerism was associated with the generation of regulatory T cells (CD4CD25FoxP3). In vitro mixed lymphocyte reactions revealed modulation of the recipient immune response after AD-MSC treatment. Graft arteries at end point revealed significant differences of arterial intimal thickness between rejecting and AD-MSC-treated animals (P < 0.01). CONCLUSIONS: Taken together, our results point to the potential for repetitive AD-MSC administration in improving outcomes after VCA. Future studies are warranted into optimization of the dosing and frequency of AD-MSC therapy, either alone or used in, combination with other cell therapies (such as hematopoietic stem cells or bone marrow-derived MSC or dendritic cells) for optimization of appropriate conditioning or maintenance regimens.
Assuntos
Tecido Adiposo/citologia , Aloenxertos Compostos/irrigação sanguínea , Aloenxertos Compostos/transplante , Sobrevivência de Enxerto , Membro Posterior/irrigação sanguínea , Membro Posterior/transplante , Imunoterapia/métodos , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/imunologia , Alotransplante de Tecidos Compostos Vascularizados/métodos , Animais , Proliferação de Células , Células Cultivadas , Aloenxertos Compostos/imunologia , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/prevenção & controle , Membro Posterior/imunologia , Imunoterapia/efeitos adversos , Ativação Linfocitária , Masculino , Transplante de Células-Tronco Mesenquimais/efeitos adversos , Modelos Animais , Ratos Endogâmicos BN , Ratos Endogâmicos Lew , Linfócitos T Reguladores/imunologia , Fatores de Tempo , Quimeras de Transplante , Tolerância ao Transplante , Doenças Vasculares/imunologia , Doenças Vasculares/prevenção & controle , Alotransplante de Tecidos Compostos Vascularizados/efeitos adversosRESUMO
BACKGROUND: Vascularized composite allotransplantation of the eye is an appealing, novel method for reconstruction of the nonfunctioning eye. The authors' group has established the first orthotopic model for eye transplantation in the rat. With advancements in immunomodulation strategies together with new therapies in neuroregeneration, parallel development of human surgical protocols is vital for ensuring momentum toward eye transplantation in actual patients. METHODS: Cadaveric donor tissue harvest (n = 8) was performed with orbital exenteration, combined open craniotomy, and endonasal approach to ligate the ophthalmic artery with a cuff of paraclival internal carotid artery, for transection of the optic nerve at the optic chiasm and transection of cranial nerves III to VI and the superior ophthalmic vein at the cavernous sinus. Candidate recipient vessels (superficial temporal/internal maxillary/facial artery and superficial temporal/facial vein) were exposed. Vein grafts were required for all anastomoses. Donor tissue was secured in recipient orbits followed by sequential venous and arterial anastomoses and nerve coaptation. Pedicle lengths and calibers were measured. All steps were timed, photographed, video recorded, and critically analyzed after each operative session. RESULTS: The technical feasibility of cadaveric donor procurement and transplantation to cadaveric recipient was established. Mean measurements included optic nerve length (39 mm) and caliber (5 mm), donor artery length (33 mm) and caliber (3 mm), and superior ophthalmic vein length (15 mm) and caliber (0.5 mm). Recipient superficial temporal, internal maxillary artery, and facial artery calibers were 0.8, 2, and 2 mm, respectively; and superior temporal and facial vein calibers were 0.8 and 2.5 mm, respectively. CONCLUSION: This surgical protocol serves as a benchmark for optimization of technique, large-animal model development, and ultimately potentiating the possibility of vision restoration transplantation surgery. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, V.
Assuntos
Olho/transplante , Coleta de Tecidos e Órgãos/métodos , Alotransplante de Tecidos Compostos Vascularizados/métodos , Estudos de Viabilidade , HumanosRESUMO
Vascularized composite allotransplantation represents a potential shift in approaches to reconstruction of complex defects resulting from congenital differences as well as trauma and other acquired pathology. Given the highly specialized function of the eye and its unique anatomical components, vascularized composite allotransplantation of the eye is an appealing method for restoration, replacement, and reconstruction of the nonfunctioning eye. Herein, we describe conventional treatments for eye restoration and their shortcomings as well as recent research and events that have brought eye transplantation closer to a potential clinical reality. In this article, we outline some potential considerations in patient selection, donor facial tissue procurement, eye tissue implantation, surgical procedure, and potential for functional outcomes.
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Cegueira/cirurgia , Olho/transplante , Alotransplante de Tecidos Compostos Vascularizados/métodos , Animais , Humanos , Seleção de Pacientes , Cuidados Pós-Operatórios/métodos , Ratos , Coleta de Tecidos e Órgãos/métodos , Obtenção de Tecidos e Órgãos/métodosRESUMO
BACKGROUND: The restoration of complex tissue deficits with vascularized composite allotransplantation is a paradigm shift in reconstructive surgery. Clinical adoption of vascularized composite allotransplantation is limited by the need for systemic immunosuppression, with associated morbidity and mortality. Small-animal models lack the biological fidelity and preclinical relevance to enable translation of immunologic insights to humans. Large-animal models have been described; however, limitations persist, including the inability of heterotopic models to evaluate functional nerve regeneration, and the sensitivity of primates to toxicity of immunosuppressive drugs. The authors' novel orthotopic porcine limb transplant model has broad applicability and translational relevance to both immunologic and functional outcomes after vascularized composite allotransplantation. METHODS: Recipients underwent amputation at a level corresponding to the mid forearm. Replantation or transplantation of grafts was performed by plate fixation of the radio-ulna, microsurgical repair of brachial artery and median nerve, and extensor and flexor tendon repairs. Viability of replants was monitored clinically and radiologically. Transplants were monitored for clinicopathologic signs of rejection. Animals mobilized freely postoperatively. RESULTS: Replantations remained viable until the endpoint of 14 days. Transplants developed Banff grade 4 acute rejection by postoperative day 7. Doppler sonography and angiography confirmed vascular patency. Serial biopsy specimens of skin and histopathology of replants at endpoint confirmed tissue viability and bone healing. CONCLUSIONS: An orthotopic load-bearing porcine forelimb vascularized composite allotransplantation model was successfully established. Technical, procedural, and logistic considerations were optimized to allow model use for immunologic, bone healing, functional nerve regeneration, and other translational studies.
Assuntos
Membro Anterior/transplante , Pesquisa Translacional Biomédica , Alotransplante de Tecidos Compostos Vascularizados/métodos , Animais , Animais Endogâmicos , Regeneração Óssea/fisiologia , Rejeição de Enxerto/patologia , Rejeição de Enxerto/fisiopatologia , Sobrevivência de Enxerto/fisiologia , Haplótipos , Teste de Histocompatibilidade , Suínos , Coleta de Tecidos e Órgãos/métodos , Suporte de Carga/fisiologiaRESUMO
With the limitations of surgical reconstructive procedures, the growing number of gunshot wounds, burns, and work accidents in Mexico that result in complex facial deformities leaves only 1 option-face transplantation. The National Institute of Medical Sciences and Nutrition "Salvador Zubiran" (INCMNSZ) has performed transplants since 1971. We at INCMNSZ undertook the 1st bilateral upper-limb transplantation in Latin America in 2012. We are willing to continue in this manner toward conducting face transplantation at our institute. To this end, we identified and solved various challenges. The 1st challenge was acceptance and inclusion of vascularized composite allotransplantation (VCA) within general Mexican health law and approval of the face transplantation procedure. Subsequently, the health ministry provided a license to INCMNSZ to perform the procedure. The 2nd challenge concerned who would pay for the procedure. The costs will be paid by the patient (1st-party payer), social security institutions (2nd-party payers), and the health ministry (3rd-party payer). The 3rd challenge was to maintain ongoing surgical training of the team using cadavers. The fourth challenge was to locate donors; toward this end, we developed a campaign for promoting face donation in social media, making a comic book, and training organ and tissue coordinators to further VCA. Thus, INCMNSZ has the legal, administrative, medical, and surgical wherewithal to accomplish face transplantation.
Assuntos
Face/cirurgia , Traumatismos Faciais/cirurgia , Transplante de Face/métodos , Doadores de Tecidos , Cadáver , Traumatismos Faciais/epidemiologia , Humanos , Incidência , México/epidemiologia , Alotransplante de Tecidos Compostos Vascularizados/métodosRESUMO
Vascularized composite allotransplantation (VCA) has emerged as a treatment option for treating nonlife-threatening conditions. Therefore, in order to make VCA a safe reconstruction option, there is a need to minimize immunosuppression, develop tolerance-inducing strategies and elucidate the mechanisms of VCA rejection and tolerance. In this study we explored the effects of hIL-2/Fc (a long-lasting human IL-2 fusion protein), in combination with antilymphocyte serum (ALS) and short-term cyclosporine A (CsA), on graft survival, regulatory T cell (Treg) proliferation and tolerance induction in a rat hind-limb transplant model. We demonstrate that hIL-2/Fc therapy tips the immune balance, increasing Treg proliferation and suppressing effector T cells, and permits VCA tolerance as demonstrated by long-term allograft survival and donor-antigen acceptance. Moreover, we observe two distinct types of acute rejection (AR), progressive and reversible, within hIL-2/Fc plus ALS and CsA treated recipients. Our study shows differential gene expression profiles of FoxP3 versus GzmB, Prf1 or interferon-γ in these two types of AR, with reversible rejection demonstrating higher Treg to Teff gene expression. This correlation of gene expression profile at the first clinical sign of AR with VCA outcomes can provide the basis for further inquiry into the mechanistic aspects of VCA rejection and future drug targets.
Assuntos
Membro Posterior/transplante , Interleucina-2/química , Proteínas Recombinantes de Fusão/química , Tolerância ao Transplante/efeitos dos fármacos , Alotransplante de Tecidos Compostos Vascularizados/métodos , Animais , Proliferação de Células , Ciclosporina/química , Fatores de Transcrição Forkhead/metabolismo , Regulação da Expressão Gênica , Rejeição de Enxerto , Sobrevivência de Enxerto , Granzimas/metabolismo , Humanos , Sistema Imunitário , Tolerância Imunológica , Masculino , Proteínas Citotóxicas Formadoras de Poros/metabolismo , Ratos , Ratos Endogâmicos Lew , Ratos Wistar , Transplante HomólogoRESUMO
Queimaduras de segundo grau são especialmente dolorosas em crianças. A cada dia que passa, a pele queimada tende a cicatrizar, mas há momentos em que a área lesada fica pior devido a curativos inadequados ou à infecção. A utilização de substitutivos dérmicos deve ser considerada. Relatamos a utilização de aloenxerto de pele como um substitutivo dérmico transitório, a fim de diminuir a dor e promover a reepitelização em queimaduras dolorosas de segundo grau. A redução da dor foi completa após o uso do aloenxerto de pele. A criança obteve reepitelização completa da área lesada, não necessitando de internação e enxerto autólogo. Aloenxertos podem representar uma possibilidade de cobertura temporária para queimaduras dolorosas de segundo grau em crianças.
Second-degree burns are especially painful in children. With each passing day, the burned skin tends to heal, but there are times when the injured area gets worst due to inadequate dressing or infection. The use of dermal substitutes must be considered. We report the use of skin allograft as a transitory dermal substitute in order to decrease pain and promote re-epithelialization in painful second-degree burns. The child got complete re-epithelialization of the injured area, not requiring hospitalization and skin grafts. The pain reduction was complete after using skin allograft. Allografts may represent a possibility of temporary coverage in painful second-degree burns in children.
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Humanos , Lactente , Queimaduras/terapia , Manejo da Dor , Alotransplante de Tecidos Compostos Vascularizados/métodos , Infecções/etiologia , Obtenção de Tecidos e ÓrgãosRESUMO
Vascularized bone marrow transplantation (VBMT) appears to promote tolerance for vascularized composite allotransplantation (VCA). However, it is unclear whether VBMT is critical for tolerance induction and, if so, whether there is a finite amount of VCA that VBMT can support. We investigated this with a novel VCA combined flap model incorporating full-thickness hemiabdominal wall and hindlimb osteomyocutaneous (HAW/HLOMC) flaps. Effects of allograft mass (AM) and VBMT on VCA outcome were studied by comparing HAW/HLOMC VCAs with fully MHC-mismatched BN donors and Lewis recipients. Control groups did not receive treatments following transplantation. Treatment groups received a short course of cyclosporine A (CsA), antilymphocyte serum, and three doses of adipocyte-derived stem cells (POD 1, 8, and 15). The results showed that all flaps in control allogeneic groups rejected soon after VCAs. Treatment significantly prolonged allograft survival. Three of eight recipients in HLOMC treatment group had allografts survive long-term and developed donor-specific tolerance. Significantly higher peripheral chimerism was observed in HLOMC than other groups. It is concluded that the relative amount of AM to VBMT is a critical factor influencing long-term allograft survival. Accordingly, VBMT content compared with VCA mass may be an important consideration for VCA in humans.
Assuntos
Parede Abdominal/cirurgia , Transplante de Medula Óssea/métodos , Aloenxertos Compostos , Membro Posterior/cirurgia , Retalhos Cirúrgicos , Alotransplante de Tecidos Compostos Vascularizados/métodos , Animais , Medula Óssea/irrigação sanguínea , Medula Óssea/imunologia , Estudos de Viabilidade , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto , Tolerância Imunológica , Imunossupressores/uso terapêutico , Teste de Cultura Mista de Linfócitos , Subpopulações de Linfócitos/imunologia , Masculino , Tamanho do Órgão , Ratos , Ratos Endogâmicos BN , Ratos Endogâmicos Lew , Transplante de Pele , Cauda , Quimeras de TransplanteRESUMO
The field of vascularized composite allotransplantation has developed for more than a decade. Investigators are defining patient selection criteria, transplant indications, immunologic regimens, and tolerance. The majority of the current reported hand transplantations have been for treatment of distal forearm or hand amputations. In more proximal amputees, the functional outcome of the transplanted arm has some unique variables that require a different surgical approach. We present a single case of bilateral proximal forearm transplantation in effort to describe the unique technical considerations in this complex procedure. The surgical procedure is described in detail. At 19 months, our patient had 4/5 strength of finger and thumb flexors and protective extensor as well as 4/5 wrist flexors and extensors. Our patient had recovery of sensation. Our patient now lives independently and does her lower extremity prosthesis independently using her hands. These results are expected to continue to improve with more time. In hand transplantation, functional results have been very promising. The described approach of forearm transplantation allows the transfer of the entire functional unit, which should optimize the ultimate outcome for these more proximal injuries.