Facial Transplantation Surgery Introduction

The history of facial reconstructive surgery has progressed slowly and naturally and is punctuated by highlights from sudden profound changes. Facial transplantation has only recently become possible through the discovery of innovative drugs and the courage of innovative surgeons. Facial allotransplantation is a new surgical technique that could be considered a new paradigm in facial reconstruction. Facial transplantation is among the most prominent areas of composite tissue allotransplantation (CTA) or vascular composite allograft (VCA), along with hand transplantation. Since the first facial allograft transplantation was reported in France in 2005, 25 cases have been performed worldwide with encouraging results (1). As with any novel and previously developed procedure, many questions have been posed and many concerns have emerged. For example, what is an acceptable risk-benefit ratio, and what are the indications for transplantation? Today, the number of facial transplantations remains small; however, the total number of allograft recipients, including those receiving hands, faces, bones, joints, and abdominal walls, has surpassed 150, and more than 10 yr of follow-up data are available for some of these patients (2).

The indications for facial transplantation require considerable discussion. Although many superb techniques and solutions exist, all reconstructive surgeons agree that specific unmet needs and limitations also exist. Bullet injuries and severe burn trauma seem to be definite and primary indications for transplantation, as these injuries include severe skin damage, tissue loss, and disfigurement (3). However, reconstructive options, multiple conventional surgical reconstructive procedures, and even very sophisticated supermicrosurgical techniques cannot facilitate recovery and thus reveal the limits of autologous tissue. Facial composite tissue allotransplantation is the best currently available option for such cases. Full or partial facial transplantation can be selected as the surgical strategy according to the anatomic deficiencies.

Inequitable patient characteristics such as immunosensitization or mental illness can present hurdles to such surgeries (4). The transplantation team should thoroughly examine the previous medical histories of blood transfusions or cadaveric skin grafts. Human leukocyte antigen screening is mandatory for the detection of presensitized patients. Psychological issues such as major depressive, psychotic, cognitive, and behavioral disorders represent another contraindication because of problems with a postoperative loss of control and cooperation. A comprehensive psychological evaluation should be conducted prior to transplantation surgery. Postoperative immune therapy is associated with many harmful complications such as renal toxicity, malignancy, diabetes, and metabolic disorders. Ultimately, patients should decide whether the benefits of facial transplantation outweigh the risks of surgery and immunosuppression. Each practicing physician has the duty and responsibility to provide his/her patients with the best treatment options available, and patients should be allowed to decide for themselves whether to accept these risks and proceed with CTA. In most Asian countries, patients and their families may experience feelings of guilt regarding the procedure of facial harvesting from the donor patient. This guilt acts as another major hurdle that is not as prominent in the USA and European countries. After donor facial harvesting is completed, a prefabricated facial mask should be applied to the facial deficit area (5). The recipient might experience problems with identity because of the expected transformation resulting from the transplantation surgery. A follow-up psychological consultation should be conducted.

Anesthesia for the long facial transplantation procedure requires advanced planning for airway management, vascular access, anesthetic technique, and fluid management. The preparation and grafting phases are highly hemorrhagic (>1 blood volume) and therefore massive transfusion is required (6). During facial allograft transplantation, the anesthesiologist must be prepared for a long period of anesthesia with rapid blood loss following graft reperfusion. Severe postoperative graft edema is present in most patients. In the intensive care unit (ICU), most patients encounter complications such as renal insufficiency, acute respiratory distress syndrome, and jugular thrombosis. Opportunistic bacterial infections are also an issue in these highly immunosuppressed patients during the postoperative period. The anesthesia team should be involved in the early planning phase and should have access to the donor's detailed medical history; alternative anticoagulation treatments for the donor and recipient have been suggested to avoid possible complications.

Craniofacial and orthognathic considerations should be emphasized with respect to functional effects when planning and executing facial transplants that include both bone and soft tissue elements. These steps are taken to restore the normal anatomy by fixing the face in a proper relationship with the skull base. Traditional orthognathic planning via cephalometric parameters yields the most anatomical restoration of occlusion, speech, and airway function (7). Typical candidates have extremely complex vascular anatomies due to severe injury and/or multiple prior reconstructive attempts; therefore, each procedure is uniquely determined according to the candidate's defects and vascular anatomy. CT angiography vascular mapping has demonstrated the clinical relevance of imaging, the angiosome concept, and noninvasive key vessel delineation as well as the current controversies related to the vascular anastomoses. The facial artery is the main arterial supply to the facial skin envelope and serves as the main pedicle for a number of facial flaps, including the facial transplant graft (8). Facial arterial dominance in the facial blood supply is common but unpredictable. A careful vascular workup prior to facial transplantation and a unipedicled flap procedure are therefore essential. Previously, surgical planning software was used to create specific facial defects (Mandibular, Midface, or Large) in recipient models, followed by restoration using allografts extracted from the donor models.

Most immunosuppression protocols are triple-therapy regimens, which comprise tacrolimus (FK-506), mycophenolate mofetil, and prednisolone. The initial functional and aesthetic outcomes have been very encouraging, and good motor and sensory recovery and improved important facial functions have been observed. Phonation recovery has been impressive and has allowed patients to talk, smile, chew, swallow, and blow normally (9). As predicted, episodes of acute rejection have been common but are easily controlled with increased systemic immunosuppression treatments. All candidates are fully informed with regard to the risks of cytomegalovirus/infection transmission and the institution of aggressive anti-viral, bacterial, and fungal prophylaxis. Despite some long-term complications, which are similar to the complications reported after solid organ transplantation, the patients have been generally satisfied with their new faces, and the results have led to the recovery of some social interactions. The psychological improvements have been remarkable and have resulted in the reintegration of patients into the outside world, social networks, and even the workplace (10). Cellular therapy in the context of transplantation can significantly benefit the allograft survival and reduce the healing time. The molecular characterizations of these cells and the mechanisms associated with their participation in allograft acceptance and rejection will contribute to the future of modern transplantology.

Anatomical research, immunosuppression, and immune tolerance are important topics in CTA research. Before initiating human facial transplantation in any country, the preclinical laboratory results should be determined and animal surgeries performed for 2 reasons: first, to develop an immune tolerance strategy and second, to provide surgical simulation opportunities. Because these fields do not target life-saving organs, there have been many debates regarding immunosuppression therapy. However, without this presurgical preparation, it is difficult to obtain appreciation and compassion from other scientists and the population. Review articles about transplantation immunology as well as a few research papers about topical immunosuppressive agents, immune tolerance strategies that incorporate cell culture, and pretreatments have been published (11, 12, 13). Additionally, a few preclinical animal allotransplantation studies using rat, rabbit, dog, and cadaver models have been published (14, 15, 16, 17, 18, 19). Surgical simulation opportunities in medium to large-sized animals are very important for transplantation surgeons. Although the facial transplantation technique has been described as similar to the currently used surgical methods, this is not true in reality. Experience with large animal transplantation research can lead to an understanding of the considerable existing differences.

In any country, it is very difficult and challenging to establish a facial transplantation program. The development of such a program in Korea would involve a successful collaboration between a strong project leader with a vested clinical research interest, a multidisciplinary team of investigators, an Institutional Review Board (IRB), the Korean Network For Organ Sharing (KONOS), and a special fundraiser (20) as this program far exceeds the presently occurring tasks in plastic surgery departments. There had been intense debate regarding the risks and benefits of this type of experimental surgery prior to the start of the facial transplant program. A sound research protocol, solid infrastructure, expert personnel, and adequate funding will be required before launching human applications. To date, only a few active facial transplantation programs have been implemented worldwide in areas with growing interests. The members of the facial transplantation team responsible for carrying out the protocol will include a team leader, a program manager/coordinator, clinical and rehabilitation specialists, social workers, bioethicists, nurses, and administrative staff. The demonstrated experience of this team indicates that patients will receive optimal care both before and after facial transplantation via the collaborations, creativity, and unique multidisciplinary approaches of the members. The establishment of this process can be slow and lengthy; therefore, the project leader must strive to maintain the enthusiasm and continue to drive the project forward (21).

Many Korean surgeons expected that this program would begin at an earlier time point; however, there remain a few hurdles to overcome. First, facial transplantation should be categorized as a new medical technology and protected under the organ transplantation law with respect to facial harvesting from a brain-dead patient. Second, during the donor harvest, close and intimate coordination is necessary between the teams harvesting the face and those harvesting other organs such as the heart, liver, kidney, and cornea. The related situations and circumstances differ between countries; therefore, each program must find its own way. The risk/benefit balance must be weighed carefully by each program and individually for each patient. Our duty as doctors and scientists is to collect and report the informative data and knowledge needed to develop a social consensus regarding these important issues. This will only be possible through candid discussions and presentations of the strategic protocols among many interested stakeholders.

The costs associated with facial transplantation are higher than those associated with heart or any other solid organ transplantation and are 2-fold higher than the costs associated with liver transplantation (22). This cost might decrease as the surgical teams gain experience, which might also reduce the requirement for postoperative intensive care and the overall hospital stay durations. The 2 largest areas of cost utilization are surgery and nursing, followed by anesthesia and pharmacy. The cost of facial transplantation is similar to that of multiple conventional reconstructions (23). Although the cost of facial transplantation is considerable, the alleviation of psychological and physiological suffering, exceptional functional recovery, and fulfillment of long-lasting hopes for social reintegration may be priceless. The overall early outcomes of the facial transplant program have been generally more positive than many had predicted. Dissemination of the outcomes and ongoing refinement of the process might eventually allow facial transplantation to become a first-line reconstructive option for patients with extensive facial disfigurements.

Facial transplantation has the unique potential to restore the facial form and function in patients with severe facial defects. This procedure represents the most comprehensive type of transplantation performed to date. To effectively address this challenging surgery, a comprehensive multidisciplinary approach should be devised. The establishment of a facial transplantation program is complicated by multiple problems concerning the various involved medical fields, administration, society, ethics, and laws; however, if we cooperate, this paradigm change in facial reconstruction can deliver new hope to the few patients with no other alternatives. The establishment strategy involves the foundation of a basic science laboratory, the cultivation of a supportive institutional clinical environment, and the innovative application of technologies. Patients should be extensively educated about the risks and benefits of facial transplantation and then allowed to act as the primary decision-makers. Improving patients' quality of life is a major goal of plastic surgery, and facial transplantation can help us to accomplish this goal.