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Bronchoscopic Image

Laryngeal Transplant

Choure, Arti J MD*; Hicks, Douglas PhD; Strome, Marshall MD; Mehta, Atul C MB, BS*

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doi: 10.1097/01.lab.0000131031.58156.87
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A 40-year-old, lifelong nonsmoking man sustained a motor vehicle accident 20 years ago during which his larynx and pharynx were crushed leaving him aphonic. Within 1 year, he also lost his sense of taste and smell and developed mild dysphagia. He used an external device (an electrolarynx) to speak and had a permanent tracheal stoma. Multiple attempts to reconstruct the larynx at another institution did not yield positive results and he was referred to our institution for further evaluation. With the exception of a tracheal stoma and the laryngotracheopharyngeal abnormality, the remainder of the physical examination was within normal limits. Examination with the flexible laryngoscope revealed an intact epiglottis with a totally stenotic and shortened larynx, with the stenosis extending to within half a centimeter above the stoma. The posterior commissure was scarred together with immobile arytenoid cartilages and a fragmented cricoid cartilage. The barium swallow revealed narrowing of the pharynx and upper esophagus and a pinhole pharyngolaryngeal fistula. Cervical endoscopy revealed 2 strictures below the cricopharyngeus and little granular area corresponding with the fistula seen radiographically. The patient was receiving losartan and hydrochlorothiazide for mild hypertension. Total laryngectomy and total occlusion of the larynx with tracheostomy is 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.1 The role of surgery to replace the larynx to improve the quality of life of the patient was weighed against that of palliative treatment.

Previous attempts at partial laryngeal transplantation and tracheal transplantation had met with limited success, plummeting the interest of otolaryngologists in the procedure.2,3 After nearly 100% success rate of laryngeal transplantation in animal studies, a total laryngeal transplant was proposed for this patient.3–7

It addressed 4 critical issues: revascularization, reinnervation, rejection, and the ethics of transplanting an organ considered by some to be nonvital.

After approval by the Institutional Review Board of our institution and written informed consent was obtained, the patient underwent laryngeal transplant. The donor was a 40-year-old man who died of a ruptured cerebral aneurysm, had no coexisting illnesses, and was a nonsmoker. HLA matching between the donor and recipient was complete and the viral serologic markers were negative. The donor had been incubated for less than 48 hours before his death. Before surgery, the recipient received cyclosporine, azathioprine, and methylprednisolone. The donor tissue, which included the entire pharyngolaryngeal complex with the 6 tracheal rings and the thyroid and parathyroid glands, was removed and stored in University of Wisconsin solution and ice for 10 hours before the surgery. The duration of ischemia was well within the acceptable 20-hour window. The patient underwent transplantation of the larynx, trachea, pharynx, and the thyroid and parathyroid glands. A stoma was created in the transplanted trachea and the tracheostomy tube was placed. He was placed on aggressive immunosuppressive therapy with responses monitored by measurements of plasma drug concentrations and biopsies of the transplanted tracheal mucosa. The patient had 1 episode of rejection 15 months after transplantation. There was laryngeal edema, which subsided with high doses of prednisone. Tacrolimus was then substituted for cyclosporine with no further episode of rejection during the 40-month follow up. Flexible endoscopy performed 3 weeks after the procedure revealed slowly resolving edema of the vocal cords and their movement from a paramedian to an intermediate position. His tracheal as well as laryngeal mucosa appeared to be well vascularized. After approximately 14 weeks, the indirect laryngoscopy performed was particularly fascinating with the overall impression of the transplanted larynx being as if it was the patient’s own larynx with no irregularities. There was bilateral true vocal cord immobility in close approximation, right virtually at the midline with the left in a paramedian position. The right fold’s medial edge was almost straight, whereas the left medial edge was obviously bowed (Fig. 1).

FIGURE 1.
FIGURE 1.:
Image of the injured larynx prior to transplant.

During his third postoperative week, the patient had uttered his first laryngeal speech in 20 years. His voice quality further improved toward almost normal by 36 months with reinnervation of both his vocal cords and cricothyroid muscles, as confirmed by electromyography. The patient’s sense of taste and smell returned too along with purposeful swallowing.

He had few episodes of infections, which were successfully contained. The transplant remained viable for 40 months and continues to do so.

The patient now has a normal human-sounding voice and can swallow normally.

DISCUSSION

Transplantation of the larynx and trachea is not a new concept. Studies were initiated by several investigators in canine and other animal models from the 1960s to date.4–7 Technical limitations, nonselective immunosuppression, and ethical concerns regarding the transplantation of nonvital organs resulted in a 20-year investigational hiatus.8 However, with the advent of numerous advances in immunobiology and the increasing stress on the improvement of quality of life, it will not be long enough because these procedures are performed as routinely as we perform the vital organ transplantation. The case will hold a source of inspiration for more successful procedures to be undertaken in the future.

Figure.
Figure.:
Image of the injured larynx prior to transplant.

REFERENCES

1. Strome M, Stein J, Esclamado R, et al. Laryngeal transplantation and 40-month follow-up. N Engl J Med. 2001;344:1676–1679.
2. Kluyskens P, Ringoir S. Follow-up of a human larynx transplantation. Laryngoscope. 1970;80:1244–1250.
3. Rose KG, Sesterhenn K, Wustrow F. Tracheal allotransplantation in man. Lancet. 1979;1:433.
4. Alonso WA, Bridger GP, Bordley JE. Tracheal transplantation in dogs. Laryngoscope. 1972;82:204–209.
5. Strome S, Sloman-Moll E, Samonte BR, et al. Rat model for a vascularized laryngeal allograft. Ann Otol Rhinol Laryngol. 1992;101:950–953.
6. Strome S, Brodsky G, Darrell J, et al. Histopathologic correlates of acute laryngeal allograft rejection in a rat model. Ann Otol Rhinol Laryngol. 1992;101:156–160.
7. Strome M, Wu J, Strome S, et al. A comparison of preservation techniques in a vascularized rat laryngeal transplant model. Laryngoscope. 1994;104:666–668.
8. Genden EM, Urken ML. Laryngeal and tracheal transplantation: ethical limitations. Mt Sinai J Med. 2003;70:163–165.
© 2004 Lippincott Williams & Wilkins, Inc.