Facial transplantation.

PURPOSE OF REVIEW: Twenty-one face transplants have been performed to date. This review provides an overview of the clinical outcomes and the lessons learned from these initial cases. RECENT FINDINGS: Facial transplantation has progressed over the past 10 years from an experimental possibility to a clinical reality. The most recent transplants performed in the USA, Spain and Turkey involve the full face. Good sensory recovery of the allograft has been consistently reported, even in the absence of nerve repair. As predicted, motor recovery has been slower than re-innervation of sensation. Dramatic improvements to functional status have been seen, with recipients regaining the ability to smile, smell, eat, drink and speak. Episodes of acute rejection have been common and controlled with increases in systemic immunosuppression. The first face transplant recipient is now over 5 years after surgery. Chronic rejection has not been seen in her or any other case. Despite the encouraging outcomes, complications because of immunosuppression, including malignancy, have occurred. SUMMARY: The outcomes of facial transplantation thus far have been very encouraging. The development of standardized tools to measure functional and psychological outcomes is required as more cases are performed. We recommend that facial transplantation is still only to be performed by experienced multidisciplinary teams.

Face transplantation: outcomes, concerns, controversies, and future directions.

BACKGROUND: Since 2005, 17 facial allotransplantations have been performed worldwide. The brief summary of current cases with ongoing concerns is presented in this article. METHODS: Fifteen publications were reported for 10 facial allotransplantations. For the remaining 7 transplantations, information was gathered from scientific meeting presentations and media releases. The summary of current cases in terms of etiology, indications, results, complications, and outcomes are based on these data. The discussion of ongoing concerns, controversies, and overview of future implications is accomplished by reviewing the literature of ethical debates, experimental studies, clinical studies, and personal opinion. RESULTS: Two of the 17 face transplant recipients died. Overall survival rate was 88%. No early graft loss due to technical failure was reported. All reported cases that have more than 1-year follow-up had at least 1 acute rejection episode, which was reversible with treatment. Opportunistic infections and metabolic complications were observed as adverse effects. Motor recoveries were slower than the sensorial recoveries, as expected. Functional and aesthetic outcomes were satisfactory. Concerns and controversies about concomitant face and hand transplantation, recipient blindness, recipient age, primary reconstruction option in facial trauma cases, funding, graft failure risks, and future treatment options are discussed. CONCLUSIONS: Because of uncertainty about long-term outcomes, immunosuppression-related concerns and ethical debates limit worldwide application of facial allotransplantation. However, in selected group of patients, it is a unique reconstruction method with promising outcomes. Further research and investigation in transplant immunology and treatment hold the key to advance this treatment option.

Human facial allotransplantation: patient selection and pertinent considerations.

Devastating facial deformities can cause significant functional and psychosocial injury. Significant facial disfigurement can preclude meaningful human interaction. Allotransplantation of facial tissues for reconstruction of devastating deformities has become a clinical reality, with 15 transplants performed at various centers around the world. Restoration of aesthetics and functionality has been superior to that achieved by conventional reconstruction, without the morbidity of multiple surgeries. Unlike solid organ transplantation which can be life saving, facial transplantation is considered by many to be life enhancing, highlighting the ethical argument against justification of these procedures given the risks of lifelong immunosuppression. Meticulous patient selection is mandatory, and a multidisciplinary team approach is key for the program's success. The overriding goal of screening for candidacy is to identify and select subjects who have the best chance for a positive immunologic, functional, and quality-of-life outcome. This article reviews the pertinent considerations and screening approach for appropriate patient selection in facial tissue transplantation.

First human face transplantation: 5 years outcomes.

BACKGROUND: The first human facial allotransplantation, a 38-year-old woman, was performed on November 27, 2005. The aesthetic aspect and functional recovery and the risk-to-benefit ratio are evaluated 5 years later. MATERIALS AND METHODS: The facial transplantation included nose, chin, part of cheeks, and lips. The immunosuppressive protocol included tacrolimus, mycophenolate mofetil, prednisone, and antithymocyte globulins. In addition, donor bone marrow cells were infused on days 4 and 11 after transplantation. RESULTS: The aesthetic aspect is satisfying. The patient has normal protective and discriminative sensibility. She showed a rapid motion recovery, which has remained stable for 3 years posttransplantation. She can smile, chew, swallow, and blow normally whereas pouting and kissing is still difficult. Phonation recovery was impressive therefore the patient can talk normally. Two episodes of acute rejection developed during the first year. Donor-specific anti-human leukocyte antigen antibodies were never detected. Five-year mucosal biopsy showed a slight perivascular inflammatory infiltrate while skin biopsy was normal. The main side effect of the immunosuppressive treatment was a progressive decrease in renal function, which improved after switching from tacrolimus to sirolimus. Moreover, she developed arterial hypertension, an increase in lipid levels, and in situ cervix carcinoma treated by conization. Since 2008, she showed mild cholangitis possibly caused by sirolimus. In September 2010, bilateral pneumopathy occurred and was successfully treated with antibiotics. CONCLUSION: Despite some long-term complications, which are similar to those reported after solid organ transplantation, the patient is satisfied of her new face and has normal social interaction.

Feasibility, reproducibility, risks and benefits of face transplantation: a prospective study of outcomes.

Composite tissue allotransplantations can be indicated when autologous transfers fail to restore human appearance. We report the reproducibility, difficulties, serious adverse events and outcomes of our patients. Five patients were included in a registered clinical research protocol after thorough screenings assessed by an independent expert committee systematically discussing the alternative options. One patient suffered from plexiform neurofibromas, two from third degree burns and two from gunshot injuries. They were included on a national waiting list with a dedicated face procurement procedure. Transplants were harvested from heart beating brain-dead donors before other tissues and organs. Induction immunosuppressive therapy included antithymocyte globulins, steroids, mycophenolate mophetil and tacrolimus. Maintenance therapy included the last three ones associated with extracorporeal-photopheresis. Four patients were transplanted with 7- to 38-month follow-up. One could not due to multiple panel reactive antibodies after 18 months on waiting list. Acute cellular rejections were controlled by conventional treatment. Opportunistic infections affected all patients and lead one patient to die two month after the transplantation. Voluntary facial activity appeared from 3 to 5 month. Face transplantation has been reproducible under conventional immunosuppression. Major improvements in facial aesthetic and function allowed patients to recover social relations and improved their quality of life.

Restoration of facial form and function after severe disfigurement from burn injury by a composite facial allograft.

Composite facial allotransplantation is emerging as a treatment option for severe facial disfigurements. The technical feasibility of facial transplantation has been demonstrated, and the initial clinical outcomes have been encouraging. We report an excellent functional and anatomical restoration 1 year after face transplantation. A 59-year-old male with severe disfigurement from electrical burn injury was treated with a facial allograft composed of bone and soft tissues to restore midfacial form and function. An initial potent antirejection treatment was tapered to minimal dose of immunosuppression. There were no surgical complications. The patient demonstrated facial redness during the initial postoperative months. One acute rejection episode was reversed with a brief methylprednisolone bolus treatment. Pathological analysis and the donor's medical history suggested that rosacea transferred from the donor caused the erythema, successfully treated with topical metronidazol. Significant restoration of nasal breathing, speech, feeding, sensation and animation was achieved. The patient was highly satisfied with the esthetic result, and regained much of his capacity for normal social life. Composite facial allotransplantation, along with minimal and well-tolerated immunosuppression, was successfully utilized to restore facial form and function in a patient with severe disfigurement of the midface.

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 (RT1) rats were used for syngeneic transplants and Brown-Norway (RT1) donors and Lewis (RT1) 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.

Outcomes 18 months after the first human partial face transplantation.

BACKGROUND: We performed the first human partial face allograft on November 27, 2005. Here we report outcomes up to 18 months after transplantation. METHODS: The postsurgical induction immunosuppression protocol included thymoglobulins combined with tacrolimus, mycophenolate mofetil, and prednisone. Donor hematopoietic stem cells were infused on postoperative days 4 and 11. Sequential biopsy specimens were taken from a sentinel skin graft, the facial skin, and the oral mucosa. Functional progress was assessed by tests of sensory and motor function performed monthly. Psychological support was provided before and after transplantation. RESULTS: Sensitivity to light touch, as assessed with the use of static monofilaments, and sensitivity to heat and cold had returned to normal at 6 months after transplantation. Motor recovery was slower, and labial contact allowing complete mouth closure was achieved at 10 months. Psychological acceptance of the graft progressed as function improved. Rejection episodes occurred on days 18 and 214 after transplantation and were reversed. A decrease in inulin clearance led to a change in immunosuppressive regimen from tacrolimus to sirolimus at 14 months. Extracorporeal photochemotherapy was introduced at 10 months to prevent recurrence of rejection. There have been no subsequent rejection episodes. At 18 months, the patient is satisfied with the aesthetic result. CONCLUSIONS: In this patient who underwent the first partial face transplantation, the functional and aesthetic results 18 months after transplantation are satisfactory.