First human face allograft: early report

doi:10.1016/S0140-6736(06)68935-6

The Lancet

Volume 368, Issue 9531, 15–21 July 2006, Pages 203-209

https://doi.org/10.1016/S0140-6736(06)68935-6 Get rights and content

Summary

Background

Extended soft tissue defects of the face are difficult to reconstruct, and autologous tissue transfers usually lead to poor cosmetic and functional outcomes. We judged that composite tissue transplantation could be valuable in facial reconstructive surgery.

Methods

We transplanted the central and lower face of a brain-dead woman onto a woman aged 38 years who had suffered amputation of distal nose, both lips, chin, and adjacent parts of the cheeks. Transplantation consisted of revascularisation of right and left facial arteries and veins (ischaemic time 4 h), mucosal repair of oral and nasal vestibules, bilateral anastomoses of infraorbital and mental sensitive nerves, joining of mimic muscles with motor nerve suture on mandibular branch of the left facial nerve, and skin closure. Immunosuppressive treatment was with thymoglobulin, tacrolimus, mycophenolate mofetil, and prednisone. Two infusions of donor bone-marrow cells were given. Follow-up included routine tests, biopsies, physiotherapy, and psychological support.

Findings

The initial postoperative course was uneventful. No surgical complication occurred. Bone-marrow graft and immunosuppression were well tolerated. Mild clinical signs of rejection were seen at day 20. Increased corticoids initially did not reverse rejection, but signs of rejection disappeared after three boluses of prednisone. Anatomical and psychological integration and recovery of sensation were excellent. At the end of the first postoperative week, the patient could eat, and speech improved quickly. Passive transmission of muscle contractions to the graft already exists; physiotherapy is being done to restore dynamic motions around the lips.

Interpretation

The 4-month outcome demonstrates the feasibility of this procedure. The functional result will be assessed in the future, but this graft can already be deemed successful with respect to appearance, sensitivity, and acceptance by the patient.

Introduction

For several decades, plastic and maxillofacial surgeons have tried to promote the transplantation of autologous tissues to reconstruct patients who have been severely disfigured by burns, ballistic trauma, tumours, or congenital deformities. Despite their quest to find the ideal method to restore simultaneously the aesthetic appearance and expressive function of the face, all conventional techniques—including skin grafts, local flaps, free tissue transfers, and skin expansion—have failed up to now to reach this goal.1, 2, 3 Similarly, attempts to prefabricate autologous tissue transfers had disappointing results with poor motor function and unsatisfactory cosmetic appearance, because of the technical difficulty faced by the even most inventive surgeon to restore inside a flap the structure complexity that exists in each anatomical component of the face.4, 5, 6 However, sporadic reports of successful total face and scalp implantations suggested that, because of their dense anastomotic vascular network, the whole facial tissues could overcome a relative ischaemia and survive entirely after a single arterial repair.7, 8 The idea that face allotransplantation could be used in reconstructive surgery was supported by some studies in rats.9, 10 Furthermore, clinical experience with composite tissue allografts, such as human hand allograft,¹¹ showed that the immunological obstacle of composite tissue transplantation could be overcome with usual immunosuppressive regimens.¹² Consequently, the remaining question in face transplantation was an ethical issue. After reviewing this question, the French National Consultation Ethics Committee allowed a partial functional allotransplantation to reconstruct the central part of the face, including the nose, both lips, and chin. On Nov 27, 2005, we undertook facial allotransplantation on a young female patient with an extended soft tissue defect corresponding exactly to these conditions. We report the results of this face allograft for the first 4 months after surgery.

Section snippets

The patient

The patient, a 38-year-old woman, was admitted to the maxillofacial surgery department of the University hospital in Amiens, France, after a severe dog bite that completely amputated her distal nose, upper and lower lips, the whole chin, and adjacent parts of right and left cheeks. The injury involved all soft tissues of the face, down to the skeleton and teeth, and was largest in the right buccal and zygomatic areas. Since conventional autologous tissue reconstruction would have required at

Results

The initial postoperative course was uneventful. No microsurgical complications occurred and no ischaemic or congestive area was observed on the graft, or on the sentinel flap. Wound healing occurred normally. Minor oedema of both grafts was observed in the early postoperative period, but quickly disappeared and did not delay the immediate start of the rehabilitation programme. The patient's general condition remained excellent. During the second postoperative week, she developed a transient

Discussion

The early outcome of this human face transplantation confirms what was known from studies in animals14, 15 and from the retrospective multicentre clinical experience with human hand transplantation.¹² The technical feasibility of the procedure has been clearly demonstrated, with no surgical complication. Compared with conventional techniques using serial autologous tissue transfers, face allografting is an advantageous possibility for the reconstruction of severely disfigured patients in a

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Vascularized Composite Allografts (VCA) are usually performed in a full major histocompatibility complex mismatch setting, with a risk of acute rejection depending on factors such as the type of immunosuppression therapy and the quality of graft preservation. In this systematic review, we present the different immunosuppression protocols used in VCA and point out relationships between acute rejection rates and possible factors that might influence it.
This systematic review was performed according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. We systematically searched Medline (PubMed), Embase, and The Cochrane Library between November 2022 and February 2023, using following Mesh Terms: Transplant, Transplantation, Hand, Face, Uterus, Penis, Abdominal Wall, Larynx, and Composite Tissue Allografts. All VCA case reports and reviews describing multiple case reports were included.
We discovered 211 VCA cases reported. The preferred treatment was a combination of antithymocyte globulins, mycophenolate mofetil (MMF), tacrolimus, and steroids; and a combination of MMF, tacrolimus, and steroids for induction and maintenance treatment, respectively. Burn patients showed a higher acute rejection rate (P = 0.073) and were administered higher MMF doses (P = 0.020).
In contrast to previous statements, the field of VCA is not rapidly evolving, as it has encountered challenges in addressing immune-related concerns. This is highlighted by the absence of a standardized immunosuppression regimen. Consequently, more substantial data are required to draw more conclusive results regarding the immunogenicity of VCAs and the potential superiority of one immunosuppressive treatment over another. Future efforts should be made to report the VCA surgeries comprehensively, and muti-institutional long-term prospective follow-up studies should be performed to compare the number of acute rejections with influencing factors.
Long-term outcomes and future challenges in face transplantation
2024, Journal of Plastic, Reconstructive and Aesthetic Surgery
Face transplant (FT) has emerged as a groundbreaking option for patients with severe facial deformities, resulting from congenital disorders, trauma, or tumor ablation. Although reconstructive surgery has made significant strides, the challenges of restoring both form and function remain, particularly in centrally located defects. This review explored the long-term outcomes of FT, addressing its challenges and potential pitfalls. A systematic review following the PRISMA guidelines was conducted, encompassing articles published in English from November 2005 to January 2023, which were searched across PubMed, MEDLINE, and EMBASE databases. Keywords included “face transplant,” “face transplant outcomes,” and “face transplant long-term.” Data on surgical teams, patient demographics, transplant specifics, rejection episodes, additional surgeries, and patient-reported outcomes were extracted and analyzed. In total, 34 articles met the inclusion criteria. Over the 2 decades, 48 FT procedures were performed, with 23 patients followed for at least 3 years. Predominantly, patients were men (80%), averaging 31 years in age. Ballistic trauma (44.6%) and burns (25.5%) were common causes of injury. Chronic rejection emerged as a significant concern, leading to graft loss and necessitating retransplantation in 2 patients. Additional surgical procedures were often required. FT offers a remarkable solution for individuals with extensive facial disfigurement. Successful outcomes depend on factors, such as patient selection, multidisciplinary collaboration, psychiatric evaluation, and post-operative care. Nevertheless, challenges persist, including the need for lifelong immunosuppression and risk of chronic rejection. Although FT has transformed lives, continued success in this evolving field hinges on the ongoing research and vigilant patient management.
International consensus recommendations on face transplantation: A 2-step Delphi study
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Face transplantation is a viable reconstructive approach for severe craniofacial defects. Despite the evolution witnessed in the field, ethical aspects, clinical and psychosocial implications, public perception, and economic sustainability remain the subject of debate and unanswered questions. Furthermore, poor data reporting and sharing, the absence of standardized metrics for outcome evaluation, and the lack of consensus definitions of success and failure have hampered the development of a “transplantation culture” on a global scale. We completed a 2-round online modified Delphi process with 35 international face transplant stakeholders, including surgeons, clinicians, psychologists, psychiatrists, ethicists, policymakers, and researchers, with a representation of 10 of the 19 face transplant teams that had already performed the procedure and 73% of face transplants. Themes addressed included patient assessment and selection, indications, social support networks, clinical framework, surgical considerations, data on patient progress and outcomes, definitions of success and failure, public image and perception, and financial sustainability. The presented recommendations are the product of a shared commitment of face transplant teams to foster the development of face transplantation and are aimed at providing a gold standard of practice and policy.
18 years of face transplantation: Adverse outcomes and challenges
2023, Journal of Plastic, Reconstructive and Aesthetic Surgery
Since the first procedure performed in 2005, face transplantation has been debated as viable approach for the treatment of severe craniofacial defects. Despite the benefits provided, the experience in face allotransplantation has brought to light a significant risk of complications, including allograft removal or loss, and mortality. The present study is intended to provide an updated review on complications and major challenges witnessed over 18 years of experience in the field.
A systematic review of PubMed, MEDLINE, Cochrane, Google, and Google Scholar databases on face transplantation was conducted according to PRISMA guidelines up to April 2023. Articles providing details on cases of face allograft loss, removal, and patient death were included. Online articles and media reports were assessed to include information not disclosed in peer-reviewed literature. Face transplant centers were contacted to have updated follow-up information on single-face transplant cases.
The search yielded 1006 reports, of which 28 were included. On a total of 48 procedures performed in 46 patients, adverse outcomes were gleaned in 14 cases (29%), including seven allograft losses (14.6%), and the death of ten patients (21.7%). Chronic rejection was the leading cause of allograft loss, with a median time from transplant to irreversible rejection of 90 months (IQR 88.5–102). The main causes of death were infectious complications, followed by malignancies, non-compliance to immunosuppression, and suicide. The median time to death was 48.5 months (IQR 19–122).
To the best of our knowledge, this is the first study providing a comprehensive review of adverse outcomes in face transplantation. Considering the high rate of major complications, the heterogeneity of cases and single-center approaches, and the absence of published standards of care, the development of a consensus by face transplant teams holds the key to the field’s advancement.
Comprehensive outcome analysis in two composite face transplants in Helsinki: Have we succeeded?
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There is a need to define what is success after face transplantation (FT). We have previously created a four-component criteria tool to define indications for FT. In this study, we used the same criteria to evaluate the overall outcome of our first two patients after FT.
Preoperative analysis of our two bimaxillary FT patients was compared to the results at four and six years post-transplantation. The facial deficiency impact was divided into four categories: (1) anatomical regions, (2) facial functions (mimic muscles, sensation, oral functions, speech, breathing, periorbital functions), (3) esthetics, and (4) impact on health-related quality of life (HRQoL). Immunological status and complications were also evaluated.
For both patients, near-normal anatomical restoration of almost all the facial regions (except the periorbital and intraoral regions) was achieved. The majority of the facial function parameters improved in both patients (patient 2 to a near-normal level). The esthetic score improved from severely disfigured to impaired (patient 1) and to near to normal (patient 2). Quality of life was severely lowered prior to FT and improved after FT but was still affected. Neither patient has experienced acute rejection episodes during follow-up.
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A Systematic Review of the Reported Complications Related to Facial and Upper Extremity Vascularized Composite Allotransplantation
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Fast track — ArticlesFirst human face allograft: early report

Summary

Background

Methods

Findings

Interpretation

Introduction

Section snippets

The patient

Results

Discussion

Lancet

Int J Oral Maxillofac Surg

Lancet

Clin Plast Surg

Lancet

J Thorac Cardiovasc Surg

Transpl Immunol

Transplant Proc

Total face reconstruction: skin graft versus skin flap

Plast Reconstruct Surg

Total face reconstruction with one free flap

Plast Reconstruct Surg

Tissue expansion in facial reconstruction

Plast Reconstruct Surg

Flap prefabrication in head and neck: a ten-year experience

Plast Reconstruct Surg

Total face and scalp replantation

Plast Reconstruct Surg

Fast track — Articles
First human face allograft: early report