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.

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.

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.

Intraoral features and considerations in face transplantation.

Face transplantation (FT) is a unique and novel addition to the field of reconstructive surgery, which offers new hope to facially disfigured individuals. This review provides an overview of FT, including clinical indications, immunological principles, and functional outcomes, as well as an in-depth characterization of the intraoral hard and soft tissue findings in the six patients transplanted to date at Brigham and Women's Hospital in Boston, MA, USA. Six FT recipients underwent comprehensive clinical and radiographic evaluation to assess their intraoral status, function, and overall health. The extra- and intraoral soft tissue was assessed via quantitative sensory testing. The vitality of the transplanted dental hard tissue was evaluated with clinically available testing methods. Native teeth and prostheses were also assessed. Sensation of transplanted oral mucosa varied based on time elapsed from FT, ranging from minimal at 3 months post-FT, to nearly complete recovery by approximately 24 months. There was mixed success with the integration of donor teeth (Patients 1, 4 and 6), including associated occlusal discrepancies. Mucosal complications included constriction at the donor/recipient interface (Patients 2 and 5) and solitary episodes of mucosal rejection presenting as lichenoid inflammation (Patients 2 and 4). Face transplantation represents a pivotal moment in the history of reconstructive surgery and transplant medicine, providing new optimism to patients with gross facial deformities. This report highlights the successes of FT, but also the challenges of transplanting hard and soft tissues to restore complex stomatognathic function. Further attention directed toward comprehensive oral rehabilitation in FT will contribute to improved outcomes, with the ultimate goal of restoring and optimizing patient quality of life.

Initial experience of dual maintenance immunosuppression with steroid withdrawal in vascular composite tissue allotransplantation.

Current immunosuppression in VCA is largely based on the experience in solid organ transplantation. It remains unclear if steroids can be reduced safely in VCA recipients. We report on five VCA recipients who were weaned off maintenance steroids after a median of 2 months (mean: 4.8 months, range 2-12 months). Patients were kept subsequently on a low dose, dual maintenance consisting of tacrolimus and mycophenolate mofetil/mycophenloic acid with a mean follow-up of 43.6 months (median = 40 months, range 34-64 months). Early and late acute rejections responded well to temporarily augmented maintenance, topical immunosuppression, and/or steroid bolus treatment. One late steroid-resistant acute rejection required treatment with thymoglobulin. All patients have been gradually weaned off steroids subsequent to the treatment of acute rejections. Low levels of tacrolimus (<5 ng/mL) appeared as a risk for acute rejections. Although further experience and a cautious approach are warranted, dual-steroid free maintenance immunosuppression appears feasible in a series of five VCA recipients.

Management of steroid-resistant late acute cellular rejection following face transplantation: a case report.

Face transplants have been clinically established, and early acute rejections have been reported. Late acute rejections have been less common. Immediate and accurate diagnosis along with successful treatment is critical to prevent graft damage. This case report describes the successful treatment of a severe, steroid-resistant rejection 2 years after a full face transplant.

Early postoperative imaging and image-guided procedures on patients with face transplants.

Face transplantation is being performed with increasing frequency. Facial edema, fluid collections, and lymphadenopathy are common postoperative findings and may be due to various etiologies, some of which are particular to face transplantation. The purpose of this study was to demonstrate how postoperative imaging and image-guided minimally invasive procedures can assist in diagnosing and treating complications arising from face transplantation. Retrospective evaluation of 6 consecutive cases of face transplantation performed at Brigham and Women's Hospital between April 2009 and March 2014 was performed with assessment of postoperative imaging and image-guided procedures, including aspiration of postoperative fluid collection, lymph node biopsy, and treatment of salivary gland leak. Through these cases, we demonstrate that early postoperative imaging and image-guided procedures are key components for the management of complications following face transplantation.

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.

[Progress in face transplantation]. / Fortschritte in der Gesichtstransplantation.

Vascularised composite allotransplantation (VCA) is utilised for restoration of complex defects. In this context, restoration describes the replacement of destroyed tissue by identical anatomic structures. Up to date, over 150 VCAs including 31 face transplantations have been performed worldwide. Face transplantation is a life giving, rather than life saving procedure that is intended to significantly improve the patient's quality of life. Safe revascularisation as well as aesthetic and functional reintegration are the ultimate goals of face transplantation. The necessary lifelong immunosuppression with potentially life-threatening side effects imposes the need for a very strict risk-benefit ratio assessment and currently limits the indications of face transplantation. Different transplant centres use different protocols for induction and maintenance immunosuppression. Skin is the most immunogenic part of the vascularised composite allograft and has been the focus of intensive research efforts in order to replicate the success of immunosuppressive regimens for solid organ transplantation. Organ preservation during transfer from donor to recipient is another important field of research within VCA. The general public's originally rejecting attitude towards non-lifesaving VCA procedures has changed towards a general acceptance following the publication of promising results after the first cases of face transplantation. Further improvements of surgical techniques and immunosuppressive strategies will be important to drive these young and exciting procedures forward in the future.

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.

Infections following facial composite tissue allotransplantation--single center experience and review of the literature.

We reviewed medical records of all patients (n = 4) who underwent facial composite tissue allotransplantation (FCTA) at our center between April 2009 and May 2011; data were censored in June 2012. We searched for FCTA publications and reviewed them for infectious complications and prophylaxis strategies. Three patients received full and one partial FCTA at our institution. Two recipients were cytomegalovirus (CMV) Donor (D)+/Recipient (R)- and two CMV D+/R+. Perioperative prophylaxis included vancomycin, cefazolin and micafungin and was adjusted based on peritransplant cultures. Additional prophylaxis included trimethoprim-sulfamethoxazole and valganciclovir. Two recipients developed surgical site infection and two developed pneumonia early after transplantation. Both CMV D+/R- recipients developed CMV disease after discontinuation of prophylaxis, recovered with valganciclovir treatment and did not experience subsequent rejection. Other posttransplant infections included bacterial parotitis, polymicrobial bacteremia, invasive dermatophyte infection and Clostridium difficile-associated diarrhea. Nine publications described infectious complications in another 9 FCTA recipients. Early posttransplant infections were similar to those observed in our cohort and included pulmonary, surgical-site and catheter-associated infections. CMV was the most frequently described opportunist. In conclusion, infections following FCTA were related to anatomical, technical and donor/recipient factors. CMV disease occurred in D+/R- recipients after prophylaxis, but was not associated with rejection.

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.