CME Facial Transplantation: Principles and Evolving Concepts Rami S. Kantar, M.D., M.P.H. Learning Objectives: After studying this article, the participant should be able to: Allyson R. Alfonso, B.S., B.A. 1. Appreciate the evolution and increasing complexity of transplanted facial Gustave K. Diep, M.D. allografts over the past two decades. 2. Discuss indications and contraindications Zoe P. Berman, M.D. for facial transplantation, and donor and recipient selection criteria and con- William J. Rifkin, M.D. siderations. 3. Discuss logistical, immunologic, and cost considerations in facial J. Rodrigo Diaz-Siso, M.D. transplantation, in addition to emerging technologies used. 4. Understand sur- Michael Sosin, M.D. gical approaches and anatomical and technical nuances of the procedure. 5. Bruce E. Gelb, M.D. Describe aesthetic, functional, and psychosocial outcomes of facial transplanta- Daniel J. Ceradini, M.D. tion reported to date. Eduardo D. Rodriguez, M.D., Summary: This CME article highlights principles and evolving concepts in D.D.S. facial transplantation. The field has witnessed significant advances over the past New York, N.Y. two decades, with more than 40 face transplants reported to date. The proce- dure now occupies the highest rung on the reconstructive ladder for patients with extensive facial disfigurement who are not amenable to autologous recon- structive approaches, in pursuit of optimal functional and aesthetic outcomes. Indications, contraindications, and donor and recipient considerations for the procedure are discussed. The authors also review logistical, immunologic, and cost considerations of facial transplantation. Surgical approaches to allograft procurement and transplantation, in addition to technical and anatomical nuances of the procedure, are provided. Finally, the authors review aesthetic, functional, and psychosocial outcomes that have been reported to date. (Plast. Reconstr. Surg. 147: 1022e, 2021.) he first face transplant in 2005 introduced injuries in the United States lies between 32.1 and a paradigm shift in craniofacial reconstruc- 58.1 per 100,000.7 These figures, combined with Ttive surgery.1 Since then, facial transplan- recent encouraging reports of face transplant cost tation has evolved into an effective solution for coverage by third-party payers, suggest a high like- patients with extensive facial disfigurement when lihood that an increasing number of patients with autologous approaches fail or are inappropriate extensive facial injuries who are not amenable in restoring optimal facial form and function.2 to conventional reconstruction will seek evalu- Growing international experience with the proce- ation and undergo facial transplantation when dure has revealed overall satisfactory results and appropriate.8 shifted the focus of the field from demonstrating Facial transplantation is complex, requires feasibility, to refining approaches, outcomes, and extensive preparation, and relies on a multidis- addressing new challenges.2,3 ciplinary approach to achieve optimal outcomes. Over the past 15 years, a total of 48 face trans- Despite the growing number of procedures per- plants have been performed in 46 patients.2,4–6 formed around the world, consensus regarding Moreover, data suggest that the annual incidence a number of perioperative considerations is lack- rate of individuals aged 20 to 64 years who suf- ing. This is further exacerbated by limited data fer from preventable nonfatal severe craniofacial regarding long-term outcomes given the recent From the Hansjörg Wyss Department of Plastic Surgery and Disclosure: The authors have no disclosures to the Transplant Institute, New York University Langone declare in relation to the content of this article. Health. Received for publication June 15, 2020; accepted January 20, 2021. Related digital media are available in the full-text Copyright © 2021 by the American Society of Plastic Surgeons version of the article on www.PRSJournal.com. DOI: 10.1097/PRS.0000000000007932 1022e www.PRSJournal.com Volume 147, Number 6 • Facial Transplantation advent of the field. With these issues in mind, the debates and discussions regarding the appropri- goal of this CME article is to provide an overview ateness of performing the procedure in pediatric of current and evolving concepts in facial trans- patients.20 plantation, and review important preoperative, Extensive facial disfigurement involving the intraoperative, and postoperative principles. majority of the surface area of the face in associa- tion with significant damage to or loss of central SURGICAL INDICATIONS AND facial structures that are critical to facial func- tion and appearance, and that are challenging RECIPIENT SELECTION to reconstruct through autologous techniques Surgical indications and patient selection (e.g., the nose, lips, and eyelids), is the most criteria in facial transplantation are closely widely accepted indication for facial transplanta- related, and determining the appropriate candi- tion.2,17 The most common mechanism of injury date for the procedure requires rigorous evalua- in patients who have undergone facial transplan- tion. Candidate evaluation should be performed tation is trauma, including ballistic injury, burns, through a collaborative and multidisciplinary animal attacks, and others.2 The procedure has team-based approach between reconstructive sur- also been performed to treat benign tumors geons, psychologists, speech therapists, dentists, such as neurofibromas, and facial defects result- 9 transplant specialists, and others. Face transplant ing from oncologic resections.2,17,19,21–23 Although teams must also thoroughly assess a candidate’s immediate facial transplantation following injury social support system to ensure favorable con- has been performed successfully with encouraging ditions for the lengthy postoperative recovery, outcomes, the viability of this approach, especially adaptation to psychological repercussions, and when considering donor shortages and matching adherence to lifelong immunosuppression that criteria, remains to be determined.24 Table 1 high- 2,10 accompany the procedure. Psychosocial factors lights surgical and nonsurgical indications, and are particularly important in candidates who have contraindications to facial transplantation based sustained self-inflicted injuries and have a history on the experience of the senior author (E.D.R). of substance abuse or suicidality. Facial transplan- tation has been reported to be successful in these patients, but resolution of suicidal tendencies and DONOR SELECTION AND substance abuse must be ensured before perform- CONSIDERATIONS ing the procedure.2 Facial transplantation in blind Donor selection and matching in facial trans- patients remains controversial, with opponents plantation are more challenging than in solid organ suggesting that recipients will not be able to per- transplantation. The donor and recipient must be ceive the outcomes of the procedure or allograft appropriately matched based on blood type and changes that may indicate immunologic rejec- immunologic criteria in addition to demographic tion, whereas supporters argue that it is unethi- factors, hair and skin color, and cephalometric cal to exclude blind patients, especially in light of parameters.2 These considerations have made donor favorable reported aesthetic and functional out- shortages more pronounced in facial transplanta- comes.11–15 Immunologic risk factors also need to tion, and have often resulted in prolonged candi- be considered when weighing the risks and bene- date wait times before transplantation. Moreover, fits of the procedure in potential candidates. This discrepancies exist between organ procurement is particularly relevant for patients with a history of organization involvement in solid organ and vas- burns and extensive transfusions that can lead to cularized composite allograft donation, including immunosensitization, human immunodeficiency facial allografts, in favor of solid organ donation.25 syndrome infection, presence of donor-specific Strong collaborations between face transplant cen- antibodies, and other immunomodulatory con- ters and organ procurement organizations can ditions that can complicate finding matching alleviate candidate wait times by expanding dona- donors and postoperative recovery.16–18 The risk of tion service areas.25 Furthermore, opt-out donation de novo malignancies associated with the manda- systems have been shown to significantly reduce tory use of lifelong immunosuppression should candidate wait time.24 Lastly, educational initiatives also be taken into consideration, especially in targeting the general public can provide insight immunosuppressed candidates and in patients into functional and aesthetic outcomes of the pro- with facial defects resulting from oncologic resec- cedure and reduce misconceptions, and have been tions.17,19 To date, facial transplantation has been shown to increase the willingness to donate facial limited to adult patients, with ongoing ethical tissue by almost 20 percent.26 1023e Plastic and Reconstructive Surgery • June 2021 Table 1. Surgical and Nonsurgical Indications and Contraindications to Facial Transplantation Based on the Senior Author’s Experience Strong Strong Relative Considerations Indications Contraindications Contraindications Surgical Extensive defects involving the Sufficient tissue of the central face majority of the surface area subunits (upper/lower eyelids, upper/ of the face lower lips, nose) to complete