Face transplantation: the view from Paris, France.

During the night of November 27, 2005, a 36-year-old woman disfigured by a dog was reconstructed by a transplantation of the lower part of the face including the nose and the lips. This first "facial transplantation" was a true medical performance. It answers the question that some had raised of the feasibility of such a transplant. However, the real scientific question of the usefulness of such a transplant is too far away to be answered.

Together with hand transplants, these transplants composed of different tissues like bone, skin, muscle, nerves and vessels are the most expressive version of composite tissue allotransplantation. Composite Tissue Allotransplantation (CTA) was performed as early as the fourth century by Saint Cosmos and Saint Damian who are reported to have replaced the limb of a parishioner with that of a recently deceased moor. With the rise of immunosuppressive drugs in the 80s, the concept of CTA came progressively to clinical practice. Before that era the only reported hand transplant was a case in Ecuador in 1963 and could only be supported for 3 weeks. Several anatomic parts such as vascularized flexor digit tendons, knee joints and a larynx were transplanted with various results. However, the modern era of CTA started in September 1998 when an international team performed a hand allograft in Lyon, France. To date, 18 patients have received hand transplants including 6 bilateral hand allografts. The impetus of these events rested in the confidence of the surgeons that such a surgery could technically be performed. As W. P. Andrew Lee reported, "the early experience of hand transplantation has yielded a mixture of successes and failure. (1)" Early results of these first clinical cases demonstrated partial functional recovery while the immunosuppressive treatment could prevent graft rejection (except in two cases) with no major life threatening adverse events. Long-term graft survival depends upon adequate and indefinite immunosuppression. Thus, the postoperative follow up of the recipient must ensure that the immunosuppressive treatment is not over- or under-dosed. Compliance of the patient with his/her treatment must be assessed with blood concentrations and should be repeated at each visit. Signs of rejection should be investigated, especially in the first 6 months postoperatively. All the patients who received a hand transplant have encountered at least one episode of acute rejection. The earliest signs of rejection are visible on the skin surface as erythema, rash and pinpoint swelling. If present, skin biopsies, an increase in systemic immunosuppression and the use of topical Tacrolimus and steroids should be done. Long-term side effects of the immunosuppressants fall into 3 categories: opportunistic infections (cutaneous, fungal and tinea infections, and CMV and herpes virus recurrences), metabolic disorders (diabetes, Cushing syndrome), and malignancies (basal cell and squamous cell carcinomas and Epstein Barr virus B cell lymphoproliferative disorders). These side effects are a major limiting factor in tissue allotransplantation for correcting physical or functional disabilities. They have led many surgeons to oppose using CTA to "only" improve the recipient's quality of life. Also, current immunosuppressive treatments do not prevent the long term functional deterioration of some organ allografts, a process called "chronic rejection". It is still too early to know if composite tissue allografts will be subjected to this phenomenon, but this is a serious threat for the long term functional recovery of these allografts.

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Successful development of strategies reducing the risks associated with immunosuppression is critical for composite tissue and face transplantation. Various approaches in research are currently being evaluated. One of them is the transplantation of hematopoietic stem cells which result in hematopoietic chimerism and central tolerance created by peripheral-tolerance induction. These protocols can be done with or without myeloablative conditioning. Although these new approaches hold great promises, any clinical application awaits further progress in the field. In the case of the face transplant of Lyon's team, a nonmyeloablative protocol has been established.

With the longest surviving hand transplant just passing its sixth anniversary, it is clear that these operations will need to be evaluated in the long term. However, as time and experience evolves, it becomes clearer that CTA extends the boundaries of reconstructive surgery for patients with tissue defect that cannot be adequately reconstructed with autologous tissues. P. Butler, from London, opened the debate of human face transplantation at the November 2002 meeting of the British Association of Plastic Surgeons, when he announced that his team was working on and would be able to do this within the next six to nine months. He claimed that the issue was not "Can we do it?" but rather "Should we do it?"

But a face is not a hand. Hand transplantation was an immunologic but not a surgical challenge, since surgeons have mastered microsurgery and refined the technique of limb replant through experience for nearly 40 years. Facial transplantation paints a rather different picture. The vascular anatomy of the face is well known but its surgical application, the harvesting of a free facial flap, remains uncertain. In clinical practice only two cases of total face (ie, facial skin with scalp) replant have been reported for traumatic defects. This shows the necessity of an anatomic model before performing such surgery. Most of the authors have considered total face transplant mainly for burn deformity. But for total face transplant to be reliable and to be sure to create movement would necessitate harvesting the musculature also. The main concerns are then vascular reliability of the facial flap, donor-host tissue discrepancy, and nerve regeneration across the transplanted face. Any vascular compromise could lead to large necrosis of the transplanted face. That would be the case also in the case of rejection or if immunosuppressive treatment should be stopped. In that case necrosis would be life threatening and the exit strategy would be very difficult to elaborate. Such risk may be decreased by transplanting only part of the face. We advocate this position as it presents for us several advantages. It destroys the "face off" fantasy of seeing the face of a dead person on a living one. It brings down the risks in case of failure and allows easier exit strategy. One can advocate that our reconstructive procedures combining the use of local and free flap are sufficient and that there is no place for such surgery. In French history more than 500,000 veterans of the First World War had benefits from facial reconstruction which could lead a vast majority to social reintegration. But in facial reconstruction, the reconstruction of circular muscle (ie, orbicularis oculi and orbicularis la-biali) are very difficult and in most of the cases the reconstruction tends to be lacking in terms of function and violates Sir Harold Gillies reconstructive dictum of replacing "like with like." Central facial tissue defects are sometimes observed after suicide attempts with guns. The defect commonly involves the nose, the superior maxilla, the lips, the mandible, and the chin. Its coverage usually requires the free transfer of autologous tissues such as fibular and forearm flaps. Despite many revision procedures for shaping the flap, the functional and aesthetical results of the reconstruction usually remain poor. Bilateral eyelid total destruction is very uncommon but can occur in a carbonized patient. The reconstruction is very difficult, leading in some cases to cornea ulcers and loss of vision. For such major and complex tissue defects, allotransplantation offers a unique and preeminent advantage by restoring "like with like."

We addressed a question to the French National Ethics Committee in 2002 on the possibility of partial or total face transplant. The answer in 2004 was "In conclusion, a full facial CTA does not make much sense for the time being. The possibility of partial CTA for a reconstruction of the mouth-nose triangle to regain some morphologic identity for the face is still in the realm of research and high-risk experimentation. It cannot be presented as an early, accessible and ideal solution for the distressing problem of facial disfigurement. Should such procedures be considered, then they should be contained within the bounds of precise multidisciplinary and multicentric protocols. (2)" We conducted anatomic research and deposed a protocol on partial face transplant and obtained ethical and technical approval to pursue such research. Until now, our team has not been willing to race because none of our patients are urgent. Recent announcement of total face transplant in the next six months does not represent a safe attitude neither for the patients nor for science.

Two months after its announcement, the first case of face transplantation is still stirring up an inflamed debate in the medical community. For doctors, the rationale of this debate falls into different questions: the scientific interest and challenge carried out by the procedure (Have we led modern science far enough to perform it now?); the expected benefit for the patient (Could this procedure improve this patient's life?); and the repercussions of people's consideration for this kind of medicine (Is the procedure going to affect people's opinion of doctors in general, and the practice of transplantation in particular?). In answering these questions, little help should be expected from the media. The first case of face transplantation has been turned into sensationalism by mass media. Photos of the patient and of the surgery have been negotiated. The mutilated face reinforced by the dreary story revealed with tearful details was published in a French tabloid in an article entitled "The woman with two faces: a new miracle of surgery." This kind of "scientific reality-show" with exhibition of patients diminishes the potential values of these procedures.

Face transplantation should be considered a potential medical solution to provide relief to suffering for a few numbers of patients. This suffering comprises physical distortions and functional disabilities that lead to social exclusion and psychological repercussions. We consider that plastic surgeons are the right doctors to evaluate and be in charge of these kinds of patients, who might look at face transplantation as a cosmetic surgery procedure. Thanks to their experience with similar situations like congenital malformations, breast removal, or distal limb amputations, plastic surgeons are less likely to deny or despise this suffering in the name of futile cosmetic reasons. However, consideration and compassion for these patients are not enough to justify the procedure. The prospect of a face allotransplantation carries high risks with an uncertain benefit for the recipient, and this unbalanced equation still hampers the first attempt. While risks of the immunosuppressive treatment are better known now, from the experience with other composite tissue allografts, many pitfalls threaten the surgical aspects of the procedure. Chances for a successful procedure, quality of the functional recovery, aesthetic result, long term outcome of the graft, and psychological impact on the patient remain unanswered questions.

In conclusion, we believe that Lister's position "the surgeon is an armed savage that obtains by force what a civilized man would obtain by negotiation" is history. Surgical research should be now more than ever in our free market society full of mass media conducted with careful approach guided with ethics and science.

References

1. Andrew Lee WP. Perspectives on hand transplantation. Clinical Plast Surg 2005;32:463-470.

2. National Consultative Ethics Committee for Health and Life Sciences Opinion No 82, Composite tissue allotransplantation (CTA) of the face. Available at: http://www.ccne-ethique.fr/english/start.htm.

"The world is a book and those who do not travel, read only a page."
--St. Augustine

Laurent A. Lantieri, MD

From the Department of Plastic Surgery, Hopital Henri Mondor Assistance, Publique Hopitaux de Paris, Paris, France.

Reprint requests to Laurent A. Lantieri, MD, Head of the Department of Plastic Surgery, Hopital Henri Mondor Assistance, Publique Hopitaux de Paris, 94000 Creteil, Paris, France. Email: [e-mail]