Laryngeal Transplantation and 40-Month Follow-up

Abstract

OTAL laryngectomy and total occlusion of the larynx with tracheostomy are associated with an impaired sense of taste and smell, an increased incidence of tracheobronchial infections, stomal encrustations, loss of nasal respiration, and loss of a human-sounding voice. A fundamental consideration in treating a patient whose larynx has been irreparably damaged is whether the goals of surgery should include replacement of the larynx to improve the patient's quality of life. An early attempt to treat laryngeal cancer with a partial laryngeal transplant 1 was accompanied by rapid recurrence of the tumor, an outcome that quashed interest in the procedure for nearly two decades. Similarly, tracheal transplantation has had only limited success. 2,3 In 1987, we initiated a program to explore the potential of laryngeal transplantation. The program addressed four issues critical to successful transplantation: revascularization, reinnervation, rejection, and the ethics of transplanting an organ considered by some to be nonvital. In rats, the rate of success of laryngeal transplantation was nearly 100 percent. 4,5 In these studies in animals, we classified the histologic features of laryngeal rejection 6 ; determined the maximal tolerable period of ischemia; evaluated preservative solutions 5 ; determined doses of cyclosporine, 7 prednisone, and adjunct in vitro radiation 8 ; and studied the use of sirolimus and tacrolimus. 9 In 1998, we performed a total laryngeal transplantation in a man who had sustained a severe traumatic injury to the larynx and pharynx. 10 We describe the procedure and report the results in detail here. CASE REPORT The Patient and the DonorThe patient was a 40-year-old man who had been in a motorcycle accident 20 years earlier. His larynx and pharynx had been T crushed, leaving him aphonic. He lost his sense of smell and taste a year after the injury. He used an external device (Cooper-Rand Electrolarynx) to speak. Despite attempts at another institution to reconstruct his larynx, it was totally stenotic and shortened, with immobile arytenoid cartilages and a fragmented cricoid cartilage. A barium swallow revealed narrowing of the pharynx and upper esophagus and a pharyngolaryngeal fistula. The supraglottis was bathed in oropharyngeal secretions.Other than mild essential hypertension that was treated with valsartan and hydrochlorothiazide, the patient was healthy. Although he had mild dysphagia, his nutritional status was normal. He did not smoke. Serologic tests for cytomegalovirus and Epstein-Barr virus were negative, and his serum creatinine concentration was normal. With the exception of the tracheal stoma and the aforementioned laryngeal, tracheal, and pharyngeal abnormalities, the results of a physical examination were normal.After surgery was proposed, the patient was interviewed once by a psychiatrist and four times by members of the surgical team and a speech pathologist. All those involved agreed that the patient understood the risks and agreed that his motivation was appropriate. The procedure...

A new mouse laryngeal transplantation rejection grading system

“…Mice were euthanized at six separate time points (1,3,5,7,9, and 15 days post-transplant). Six mice were euthanized on post-transplant day 1.…”

“…1 To date, the patient continues to speak with a good voice and swallow without difficulty. Success of this procedure was largely based upon the development of a reliable rat transplantation model.…”

Early immunological changes associated with laryngeal transplantation in a major histocompatibility complex-matched pig model

“…However, recent advances have made laryngeal transplantation an increasingly viable proposition for patients with irreversible laryngeal disease [5]. One successful human laryngeal transplant has been performed and the 40-month follow-up report was encouraging [6].…”

Tracheal Tissue Engineering

“…Arterial, venous, and neural anastomoses was accomplished and perfusion was established. 40 months after surgery,the patient was healthy with functional vocal chords [118]. This one off success has not been repeatable and led to further work assessing the immunosupressive therapeutics and tissue pre-treatment.…”