In June 2014, the Organ Procurement and Transplantation Network (OPTN) and United Network for Organ Sharing (UNOS) Board of Directors unanimously approved the first national policies and standards for vascularized composite allografts (VCA). These policies have encouraged creative new approaches employing VCA for a variety of functional and reconstructive dilemmas. Recently our group reported the first vascularized tracheal transplantation for a patient with a life- threatening 9.0 cm combined cricoid- tracheal airway stenosis. This surgical innovation along with face, laryngeal, abdominal wall, uterus, and penile VCA transplantation, is expanding the frontiers of functional and reconstructive surgery.
For nearly a century, it was scientific dogma that the human tracheal airway was not amenable to revascularization and therefore transplantation was not possible. The proof of principle established with the recent tracheal transplantation was based on extensive basic science research and expands the limits of advanced airway reconstruction. Our basic science and clinical research suggest that a segment of the esophagus may also be transplanted with the tracheal allograft and this combination may provide an option for management of tracheoesophageal fistula, a universally fatal communication between the tracheal airway and the esophagus.
Twenty months after tracheal transplantation, the patient has resumed a normal life, re-entering the work force and, for the first time in 6 years, she is able to speak with her family without a tracheostomy or stent. However, vascularized composite allograft transplantation is not without risk. Rejection rates remain unacceptably high. Some estimates suggest approximately 80% of recipients undergo acute rejection and 50% undergo chronic rejection. Interestingly, the tracheal allograft recipient has not demonstrated evidence of acute or chronic rejection. Like hand or face VCA, the trachea is composed of a composite of muscle, epithelium, cartilage, and vasculature. Yet, the allograft continues to persist without evidence of rejection on standard immunotherapy. Interestingly, the tracheal allograft has undergone a transition wherein recipient- derived epithelium has repopulated the allograft resulting in an epithelial chimera. This is important because the epithelium has been identified as the target of rejection. Epithelial migration is an observation that we observed experimentally, and we theorize may impact the risk of rejection. Tolerance has been reported in patients who underwent a kidney or liver transplant combined with bone marrow transplantation, a state where the donor hemopoietic cells engraft into the recipient's bone marrow. The role of epithelial and endothelial chimerism is less clear.
Tracheal transplantation has raised as many questions as it has answered. We are now left to determine the impact of epithelial chimerization on cell- mediated rejection. Does the chimeric state provide an opportunity to deescalate immunosuppression? Is combined tracheoesophageal transplantation possible and does a similar epithelial chimerization occur in the esophagus? And finally, who is a candidate for this procedure; can this procedure be applied to the approximately 400 newborns afflicted with congenital tracheoesophageal abnormalities? This is an exciting area of study that may impact our understanding of VCA transplantation and reveal new approaches to evading immune- mediated rejection.
By Eric M. Genden, MD, MHCA, FACS
Mount Sinai Health System
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