Vascularized Tracheal Transplantation: A Twenty Month Follow Up

Abstract

Background: Tracheal transplantation has been considered the ideal option for the reconstruction of long-segment circumferential tracheal defects. Our group developed a technique for vascularized single-staged tracheal transplantation. Twenty months ago, we performed the first-in-human tracheal transplantation. Herein, we report a twenty-month follow-up.Methods: The recipient presented with a 9.0 cm airway tracheal stenosis and complete cricoid stenosis. The patient previously failed six major conventional surgical procedures. Prior to transplantation, the patient's airway was maintained with an extended tracheostomy and stent. The patient experienced repeated life-threatening airway obstruction because of mucous plugging and obstructive granulation tissue. In January 2020 the patient underwent a single-staged tracheal transplantation treated with triple-therapy immunosuppression. Organ rejection was monitored with endoscopic tracheoscopy, narrow-band imaging, free-cell DNA assessment, and histological and cytogenetic analysis of tracheal biopsies. Mucociliary function was assessed with dye motility studies.Results: Twenty months following transplantation, there has been no evidence of acute or chronic rejection. Since day 60, there has been no detectable free cell DNA, a surrogate marker for immune-mediated allograft rejection. Fluorescence in situ hybridization (FISH) cytogenetics demonstrated that the donor trachea was repopulated with recipient epithelium establishing a chimeric allograft. Narrow-band imaging demonstrates a well-vascularized epithelial mucosa and bronchoscopic biopsies demonstrate normal ciliated epithelial architecture and viable epithelial lining with functional ciliated epithelium. The patient has resumed a normal life without a stent or tracheostomy and has returned to work.Conclusions: Twenty months after single-staged vascularized tracheal transplantation, the trachea is functional and the patient breathes without the need for a tracheostomy or stent. Single-staged long-segment tracheal transplantation is a viable option for tracheal defects that are not amenable to conventional reconstructive techniques.

Human tracheal transplantation: A systematic review of case reports

“…Interestingly, FISH cytogenetic assays demonstrated initially a rapid increase in recipient‐derived cells, which represented 98.9% of epithelial cells by day 111 from transplantation. However, the percentage of recipient‐derived epithelial cells declined to only .8% after 455 days from transplantation 31 . FISH cytogenetic assay was also reported by Delaere et al.…”

“…However, the percentage of recipient-derived epithelial cells declined to only .8% after 455 days from transplantation. 31 FISH cytogenetic assay was also reported by Delaere et al in their first patient, after withdrawal of immunosuppressive therapy. At the time of orthotopic transplantation, the allograft was trimmed to the desired length, and redundant tissue was used for cytogenetic analysis, which demonstrated that the respiratory epithelium in the anterior part of the graft was of donor's origin.…”

Case Report: Human Tracheal Transplantation Undergoes Progressive Reepithelialization Over Time

“…5 The patient has subsequently been decannulated and remains breathing and phonating without difficulty 2 years after surgery. 6 We have shown previously that after an initial epithelial injury there was a degree of epithelial repopulation that provided functional mucociliary clearance on a blue dye test. 5 Fascinatingly, as seen in animal models, the epithelial repopulation was in part recipient-derived.…”

“…Indeed, this would coincide with the drop in recipient-derived epithelium seen by POD 111. 6 Additionally the ciliated epithelial cells present contained some serous granules which suggest that some of the ciliated epithelium were derived from serous cells precursors as well. Ultimately 200-400 days after surgery, normal ciliated epithelium and mucous cells appear without signs of chronic inflammation.…”

“…Prior work has demonstrated that upon transplantation, after an initial loss of luminal epithelium, the donor graft will ultimately be repopulated by functional ciliated epithelium. 5,6 Although these histologic changes have been studied extensively in mouse [7][8][9][10][11] and canine 12,13 models of tracheal transplantation, this has not been examined in depth in humans. Such an understanding is critical to improving outcomes of tracheal transplantation, as it is now clear that functional mucociliary clearance is a critical component for long-segment airway reconstruction.…”