Transformation of Face Transplants: Volumetric and Morphologic Graft Changes Resemble Aging After Facial Allotransplantation.

Facial allotransplantation restores normal anatomy to severely disfigured faces. Although >30 such operations performed worldwide have yielded promising short-term results, data on long-term outcomes remain scarce. Three full-face transplant recipients were followed for 40 months. Severe changes in volume and composition of the facial allografts were noted. Data from computed tomography performed 6, 18 and 36 months after transplantation were processed to separate allograft from recipient tissues and further into bone, fat and nonfat soft tissues. Skin and muscle biopsies underwent diagnostic evaluation. All three facial allografts sustained significant volume loss (mean 19.55%) between 6 and 36 months after transplant. Bone and nonfat soft tissue volumes decreased significantly over time (17.22% between months 6 and 18 and 25.56% between months 6 and 36, respectively), whereas fat did not. Histological evaluations showed atrophy of muscle fibers. Volumetric and morphometric changes in facial allografts have not been reported previously. The transformation of facial allografts in this study resembled aging through volume loss but differed substantially from regular aging. These findings have implications for risk-benefit assessment, donor selection and measures counteracting muscle and bone atrophy. Superior long-term outcomes of facial allotransplantation will be crucial to advance toward future clinical routine.

Codominant Role of Interferon-γ- and Interleukin-17-Producing T Cells During Rejection in Full Facial Transplant Recipients.

Facial transplantation is a life-changing procedure for patients with severe composite facial defects. However, skin is the most immunogenic of all transplants, and better understanding of the immunological processes after facial transplantation is of paramount importance. Here, we describe six patients who underwent full facial transplantation at our institution, with a mean follow-up of 2.7 years. Seum, peripheral blood mononuclear cells, and skin biopsy specimens were collected prospectively, and a detailed characterization of their immune response (51 time points) was performed, defining 47 immune cell subsets, 24 serum cytokines, anti-HLA antibodies, and donor alloreactivity on each sample, producing 4269 data points. In a nonrejecting state, patients had a predominant T helper 2 cell phenotype in the blood. All patients developed at least one episode of acute cellular rejection, which was characterized by increases in interferon-γ/interleukin-17-producing cells in peripheral blood and in the allograft's skin. Serum monocyte chemotactic protein-1 level was significantly increased during rejection compared with prerejection time points. None of the patients developed de novo donor-specific antibodies, despite a fourfold expansion in T follicular helper cells at 1 year posttransplantation. In sum, facial transplantation is frequently complicated by a codominant interferon-γ/interleukin-17-mediated acute cellular rejection process. Despite that, medium-term outcomes are promising with no evidence of de novo donor-specific antibody development.

Guillain-Barré syndrome associated with resistant cytomegalovirus infection after face transplantation.

A 39-year-old male, who received a facial allograft (cytomegalovirus [CMV] donor-seropositive, recipient-seronegative), developed multidrug-resistant CMV infection despite valganciclovir prophylaxis (900 mg/day) 6 months post transplantation. Lower extremity weakness with upper and lower extremity paresthesias developed progressively 11 months post transplantation, coinciding with immune control of CMV. An axonal form of Guillain-Barré syndrome was diagnosed, based on electrophysiological evidence of a generalized, non-length-dependent, sensorimotor axonal polyneuropathy. Treatment with intravenous immunoglobulin led to complete recovery without recurrence after 6 months.

Functional outcomes of face transplantation.

In this study we provide a compilation of functional impairments before and improvements after face transplantation (FT) of five FT recipients of our institution and all FTs reported in current literature. Functional outcome included the ability to smell, breath, eat, speak, grimace and facial sensation. Before FT, all our patients revealed compromised ability to breath, eat, speak, grimace and experience facial sensation. The ability to smell was compromised in two of our five patients. Two patients were dependent on tracheostomy and one on gastrostomy tubes. After FT, all abilities were significantly improved and all patients were independent from artificial air airways and feeding tubes. Including data given in current literature about the other 24 FT recipients in the world, the abilities to smell, eat and feel were enhanced in 100% of cases, while the abilities of breathing, speaking and facial expressions were ameliorated in 93%, 71% and 76% of cases, respectively. All patients that required gastrostomy and 91% of patients depending on tracheostomy were decannulated after FT. Unfortunately, outcomes remain unreported in all other cases and therefore we are unable to comment on improvements.

The management of antibody-mediated rejection in the first presensitized recipient of a full-face allotransplant.

We report on the management of the first full-face transplantation in a sensitized recipient with a positive preoperative crossmatch and subsequent antibody-mediated rejection (AMR). The recipient is a 45-year-old female who sustained extensive chemical burns, with residual poor function and high levels of circulating anti-HLA antibodies. With a clear immunosuppression plan and salvage options in place, a full-face allotransplant was performed using a crossmatch positive donor. Despite plasmapheresis alongside a standard induction regimen, clinical signs of rejection were noted on postoperative day 5 (POD5). Donor-specific antibody (DSA) titers rose with evidence of C4d deposits on biopsy. By POD19, biopsies showed Banff Grade III rejection. Combination therapy consisting of plasmapheresis, eculizumab, bortezomib and alemtuzumab decreased DSA levels, improved clinical exam, and by 6 months postop she had no histological signs of rejection. This case is the first to demonstrate evidence and management of AMR in face allotransplantation. Our findings lend support to the call for an update to the Banff classification of rejection in vascularized composite tissue allotransplantation (VCA) to include AMR, and for further studies to better classify the histology and mechanism of action of AMR in VCA.

Vascular communications between donor and recipient tissues after successful full face transplantation.

The vascular reorganization after facial transplantation has important implications on future surgical planning. The purpose of this study was to evaluate blood flow (BF) after full face transplantation using wide area-detector computed tomography (CT) techniques. Three subjects with severe craniofacial injury who underwent full face transplantation were included. All subjects underwent a single anastomosis bilaterally of the artery and vein, and the recipient tongue was preserved. Before and after surgery, dynamic volume CT studies were analyzed for vascular anatomy and blood perfusion. Postsurgical CT showed extensive vascular reorganization for external carotid artery (ECA) angiosome; collateral flows from vertebral, ascending pharyngeal or maxillary arteries supplied the branches from the recipient ECAs distal to the ligation. While allograft tissue was slightly less perfused when the facial artery was the only donor artery when compared to an ECA-ECA anastomosis (4.4 ± 0.4% vs. 5.7 ± 0.7%), allograft perfusion was higher than the recipient normal neck tissue. BF for the recipient tongue was maintained from contralateral/donor arteries when the lingual artery was sacrificed. Venous drainage was adequate for all subjects, even when the recipient internal jugular vein was anastomosed in end-to-end fashion on one side. In conclusion, dynamic CT identified adequate BF for facial allografts via extensive vascular reorganization.

Multidisciplinary experience in the selection of patients for tubal sterilization.

Results of the use of a special protocol for evaluation of patients requiring tubal ligation is presented after applied by a multidisciplinary group. The authors conclude that the use of defined parameters of age, parity, marital union duration, number of children alive and the presence of maternal clinical pathology are useful to identify patients with smaller chances of regret after surgery.

PIP: 27% of reproductive-age women in Brazil have chosen surgical sterilization as their contraceptive method. Most of these women who have undergone tubal sterilization opted for cesarean surgery. However, given the young ages of many of these women, many regret having been sterilized. This paper summarizes the experience of a multidisciplinary group in evaluating women who apply for surgical sterilization at the Department of Tocogynecology, Faculdade de Ciencas Medicas, Universidade Estadual de Campinas in Sao Paulo. Detailed descriptions are presented of the medical and social characteristics of cases seen between June 1988 and July 1989. The authors conclude that the use of the defined parameters of age, parity, marital union duration, number of living children, and the presence of maternal clinical pathology are useful in identifying the patients who are least likely to regret undergoing surgical sterilization.

Abdominal wall reconstruction using a non-cross-linked porcine dermal scaffold: a follow-up study.

PURPOSE: In a previous study, we have shown that non-cross-linked porcine dermal scaffolds (NCPDS) are a safe and effective alternative to prosthetic mesh in the reconstruction of complicated abdominal wall defects. Here, we report the long-term outcomes of abdominal wall reconstruction using NCPDS in a larger patient population. METHODS: Patients who underwent abdominal wall reconstruction with NCPDS between May 2006 and December 2010 were retrospectively reviewed. Analysis of demographics, indications for NCPDS placement, surgical technique, complications, and follow-up data was performed. RESULTS: NCPDS was used for abdominal wall repair in 40 patients. In all patients, NCPDS was positioned using an intraperitoneal technique. At a mean follow-up time of 40.1 months, most patients had successful outcomes. Complications included seroma (21 %), recurrence (7.9 %), and infection (5.2 %); these rates are comparable to our initial report. Two patients died from multi-organ failure unrelated to NCPDS placement. CONCLUSIONS: This study shows that complex abdominal wall defects can be successfully reconstructed using NCPDS with a low rate of recurrence and complications.

CT angiography for surgical planning in face transplantation candidates.

SUMMARY: Facial allotransplantation replaces missing facial structures with anatomically identical tissues, providing desired functional, esthetic, and psychosocial benefits far superior to those of conventional methods. On the basis of very encouraging initial results, it is likely that more procedures will be performed in the near future. Typical candidates have extremely complex vascular anatomy due to severe injury and/or multiple prior reconstructive attempts; thus, each procedure is uniquely determined by the defects and vascular anatomy of the candidate. We detail CT angiography vascular mapping, noting the clinical relevance of the imaging, the angiosome concept and noninvasive delineation of the key vessels, and current controversies related to the vascular anastomoses.

Evolution of indications for facial transplantation.

Face transplantation has the unique potential to restore facial form and function in patients with severe facial defects. Current indications for face transplantation remain limited by unknown long-term outcomes and the requirements for lifelong immunosuppression and substantial plans for reconstruction in case of failure. We initially obtained Institutional Review Board approval for partial face transplantation in patients with defects comprising 25% of the face and/or loss of one or more major facial features. We launched an outcome-oriented face transplantation study and screened 13 potential patients between February 2008 and January 2011. Experience gained during screening motivated the expansion of indications to include full facial defects and the consideration of patient-specific complex issues on a case-by-case basis. Although our programme focuses on restoring absent or severely compromised motor and sensory functions, we recognise aesthetic appearance as a crucial facial function. Patients are extensively educated on the risks and benefits of facial transplantation and then allowed to play the main role in the decision-making process, as long as no absolute exclusion criteria are present. As we learn more about the long-term outcomes of face transplantation and safe reduction of immunosuppression, face-transplant indications may expand from major unreconstructable defects towards potentially minor defects.

A multidisciplinary protocol for face transplantation at Brigham and Women's Hospital.

Face transplantation introduces an unprecedented potential to restore form and function in patients with severe facial disfigurement. A successful face transplantation programme requires a sound research protocol, a solid infrastructure, expert personnel and adequate funding. There are only a few active face transplant programmes in the world and interest in the development of new such programmes continues to grow. After 2 years of working on the development of the face transplant programme, in 2009 the team at Brigham and Women's Hospital (BWH) performed the 2nd face transplant in the United States. Since then, the team has continued to evaluate several possible face transplant candidates and performed three additional facial transplants. These experiences have helped refine a highly effective multidisciplinary protocol that carries a patient through recruitment, informed consent, screening, preoperative planning, face transplantation surgery and postoperative long-term follow-up. The members of the BWH face transplantation team responsible for carrying out this protocol include a team leader, a programme manager/coordinator, clinical and rehabilitation specialists, social workers, bioethicists, nurses and administrative staff. The roles of each team member during the various stages of the face transplant process are presented here. Additional insight into the interaction between the face transplant team, the Institutional Review Board and the regional Organ Procurement Organization is given. The BWH team's experience has shown that true collaboration, creativity and a unique approach to each candidate translate into the optimal care of the face transplant patient both before and after surgery.