Larynx Transplant Survivors

To date, only two laryngeal transplants have been completed in the United States. Tim Heidler first received his new larynx in 1998 when he was 40 years old. Heidler suffered trauma to the larynx in a motorcycle accident nearly 20 years before his surgery. He was using an ElectroLarynx at the time, but was hopeful to regain vocal function following a laryngeal transplant. Ten months following his surgery, Heidler was able to speak with near normal voicing, was eating an oral diet, and had a functioning thyroid gland. Heidler suffered vocal fold paralysis following the surgery, though, and required a tracheostomy. He breathes normally through the stoma and is able to produce a voice.  Nearly 10 following the surgery, Heidler reported that being able to speak again has changed his life (1,2).

Tim Heidler

Brenda Jensen was the second patient to receive a laryngeal transplant in 2010 at the UC Davis Medical Center in California. Jensen damaged her larynx when she repeatedly pulled out a ventilation tube during a hospital stay 12 years before her surgery. Following this incident, Jensen required a tracheostomy to breathe and used an electronic device to talk.  Thirteen days after the transplant, Jensen was able to produce a voice through her own structures. It was much lower in pitch and harsh, but still intelligible. Jensen still relies on the tracheostomy for breathing as she still has difficulty inhaling. She still receives nutrition through a feeding tube as she still aspirates while eating and drinking. However, she receives swallowing therapy and her sensation and laryngeal function has improved since the surgery. Her surgeons report that Jensen smiles every time she hears her voice (3).

Brenda Jensen

These two cases provide hope and inspiration for future patients who wish to have a laryngeal transplant. Both of these patients served as case studies for future research in the field as well.

Resources:

1. Whitley, M.A. (2009). Tim Heidler, world's first larynx transplant recipient at Cleveland Clinic, is doing well: Whatever happened to . . .? Retrieved from http://blog.cleveland.com/metro/2009/06/tim_heidler_worlds_first_laryn.html

2. Iskowitz, M. (1998). Transplanting the Larynx.  Retrieved from http://speech-language-pathology-audiology.advanceweb.com/Article/Transplanting--the-Larynx.aspx

3. Larynx: Q&A. (2013). Retrieved from http://www.ucdmc.ucdavis.edu/welcome/features/2010-2011/01/20110126_larynx_transplant_qa.html

Larynx Transplant on California Woman Successful

Check out this story from NPR:
http://www.npr.org/2011/01/20/133082678/larynx-transplant-on-california-woman-successful

Case Study of Laryngotracheal Transplant

Introduction

•   Loss of laryngeal function impacts communication, swallowing, and respiration and affects overall quality of life (QOL).
•  Laryngeal transplantation has been proposed as an option for patients not amenable to alternative treatment options.
• Challenges in microvascular reconstruction and re-innervations, as well as ethical considerations for the transplantation of a non vital organ, have limited the acceptance of this procedure.

Subject (Case History)

• 51 year old female with a prolonged history of traumatic, tracheotomy tube- dependent, benign, and complete laryngotracheal stenosis (stenosis extended to the second tracheal ring).
•  Failed endoscopic restoration of laryngeal quality. Patient was determined by a multidisciplinary team to be not amenable for nontransplant alternatives for restoration of laryngeal function.
• Patient underwent psychological assessment, counseling, and informed consent. Clearance to perform the transplant surgery was obtained. In addition a research protocol, and informed consent were approved by the University of California Review Board.

Preoperative Evaluation and Preparation

• Patient underwent preoperative laryngeal electromyography (EMG) and comprehensive videofluoroscopic swallow study from lips to stomach.
• Patient was extensively counseled and prepared for a laryngectomy and tracheoesophageal puncture as a fallback procedure if the transplant failed.

Results of Transplant

• No signs of clinical or pathologic rejection of transplant to this date. Multiple biopsies were taken (6 hours, 1, 14, 30, and 137 days) post- transplant. All of which showed a normal appearing larynx with no detection of rejection.

• Airway: The larynx and trachea were inspected on a frequent basis post-transplant (everyday day for 8 days, 10, 14, 20 days).
• Voice: The patient was able to speak 14 days after she received the transplant. Three months after surgery, sensory testing of the larynx revealed a typical laryngeal adductor response bilaterally but limited, primarily paradoxical vocal fold movement noted. Botox injections were given to the patient which induced extreme lateralization of the vocal folds. Two months later her voice and tone was back to normal and her vocal folds remained minimally mobile in a median position.
• Acoustic measures: acoustical recordings from standardized speech tasks were measure. The patient’s fundamental frequency range measured was considered within normal limits.
• Swallowing: Recovery of swallowing function was prolonged.

1. Evidence of pharyngeal motor integrity and epiglottic inversion was present after 4 months.
2. Botox injections were performed 2 months postoperatively due to management of pooled secretions.
3. A mild stenosis at the pharyngeal site was identified at 5 months postoperatively. Stenosis dilated in clinic.
4. Patient underwent daily dysphagia therapy after surgery and was transitioned to three days a week at home. She was cleared to eat a pureed diet at 7 months, a general diet at 11 months, and her gastrointestinal tube was removed at 13 months. At 18 months she denied any difficulties with dysphagia and no signs or symptoms of aspiration pneumonia.

• A multidisciplinary approach resulted in a successful transplant without evidence of rejection to this date.
•  This case study demonstrates successful transplantation of a larynx with a long segment of trachea. Many refinements and advances are described in this report: successful revascularization and transplant of larynx and trachea, and first attempt at selective innervations of the left vocal fold. Challenges to this patients swallowing may have been due to her extensive history of diabetes and associated neuropathy, however, this must be a part of pre-operative counseling for future patients receiving laryngeal transplant surgery.

Resource:

Farwell, G.D., Birchall, M.A., Macchiarini, P., Luu, Q.C., de Mattos, A.M.,  Gallay, B.J.,

Richard, V.P., Grow, M.P., Ramsamooj, R., Salgado, M.D., Brodie, H.A., Belafsky, P.C. (2013). Laryngotracheal Transplantation: Technical Modifications and Functional Outcomes, The Laryngoscope, 123, 2502-2508. 

Psychological and Social Issues

Psychological assessments should be completed on potential candidates of laryngeal transplantations. Most importantly, patients must demonstrate self-interest in obtaining a transplant rather than being externally motivated by family members or a significant other. The patient’s cognitive function should be at or near baseline in order to fully understand the complexity of the surgery, weighing the risks and benefits in order to make the best-educated decision for oneself. Potential candidates need to understand that the potential complications include lifelong immunosuppression for the potential possibility of improved communication. Immunosupression is needed in a transplant to decrease the risk of organ rejection. This requires compliance with drug regiments by the recipient indefinitely. The patient should be prepared for the possibility of a transplant rejection as well as unpredictable outcomes.  During the post-operative period, patients may experience similar symptoms other transplant patients have reported such as anxiety, depression, and stress reactions.

A patient may consider his/her voice to be an integral part of his/her identity. Therefore, a new laryngeal mechanism (voice box) may cause some self-identification problems that the patient will need to work through following surgery.  More research is needed in this area, with such a new surgical procedure.  There has also been little to no research on the psychological effects of transplantation in regards to the families of the recipient. However, families will benefit from advice given by the multidisciplinary team on how to help the patient and the best ways to encourage the patient.  Families should also be aware of the potential risks and lifelong consequences of such an invasive procedure (Narula, Bradley, Carding, Hakim, Rumsey & Sokol, 2011).

Resource:

Narula, T., Bradley, P., Carding, P., Hakim, N., Rumsey, N., & Sokol, D. (2011). Laryngeal transplantation . London: The Royal College of Surgeons of England.

Role of the Speech-Language Pathologist

A multidisciplinary team should be compiled in advance to assist with both the preoperative and postoperative education and treatment.  The functional outcomes of a laryngeal transplantation include breathing, vocal, and swallowing functions. A speech and language pathologist (SLP) will be involved in the swallowing and voicing treatment of the patient. The evaluations completed pre and post operative by the SLP should include the GRABS, Vocal handicap index, basic acoustic analysis, Flexible endoscopic evaluation of swallowing, and a videofluoroscopic swallow study. These evaluations may also be given at regular intervals until the patient’s voice and swallowing functions are stabilized.

Counseling and education prior to the surgery is a crucial role for the SLP. The SLP must explain potential outcomes of voicing, swallowing, and breathing.  This includes explaining  what the voice could sound like post-surgery, consequences of failed nerve reinnervation, potential need of a tracheostomy for breathing and speaking (including use of a Passy-Muir valve if needed), possible need for a feeding tube, and any speech therapy that may be necessary to return the laryngeal functioning to near-normal.

For swallowing function, the larynx provides glottal closure so that food and liquids do not enter into the trachea. It also allows for the timely opening of the crico-pharyngeal sphincter so that food can easily pass into the esophagus.  Research continues to develop comparing normal laryngeal excursion to that of a transplant. Swallowing therapy will likely be needed in order to focus on coordination of laryngeal closure with the pharyngeal stage of the swallow. It should be noted that treatment would be intense, occurring on a daily basis during the recovery period.

Looking at voice function in terms of speaking quality, transplantation allows the vocal folds to phonate again. In theory, the resonating chamber such as the pharynx, nasopharynx, and oral cavity are not changing; therefore the sounds of the vocalizations should not dramatically change. This theory continues to be looked at as new transplants begin to occur. A person’s accent is formed by the articulators (lips, cheeks, tongue, and palate), therefore the patient’s accent will remain the same.

It is not realistic to think that upon transplantation that the larynx will immediately begin functioning normally, allowing for easy speech. Voice therapy to help restore function may work on aspects such as coordination of breathing in conjunction with vibratory phonation. Achieving mastery of pitch and volume can take time (Narula, Bradley, Carding, Hakim, Rumsey & Sokol, 2011).

Dr. Douglas Hicks was the SLP who treated Tim Hiedler, the first patient to receive a laryngeal transplant.  Prior to the surgery, Dr. Hicks and other members of the team provided counseling and education regarding the procedure and possible outcomes, especially since this was the first laryngeal transplant. Following the surgery, Dr. Hicks performed voice and swallowing therapy. Hiedler’s vocal folds were paralyzed, so he required a tracheostomy to breath. Dr. Hicks trained Hiedler to use the tracheostomy to speak. In addition, swallowing therapy was performed and Hidler now eats an oral diet. After the surgery, Dr. Hicks continued to conduct subjective and object assessments, aerodynamic tests of airflow and volume, and videoendoscopy to monitor the functioning of the larynx.

Resources:

Iskowitz, M. (1998). Transplanting the Larynx.  Retrieved from http://speech-language-pathology-audiology.advanceweb.com/Article/Transplanting--the-Larynx.aspx

Narula, T., Bradley, P., Carding, P., Hakim, N., Rumsey, N., & Sokol, D. (2011). Laryngeal transplantation . London: The Royal College of Surgeons of England.

Women Receives Larynx Transplant

Check out this video about the first woman to receive a larynx transplant! 

http://www.cbsnews.com/videos/woman-receives-larynx-transplant/

Human Larynx: Innervation

According to Stavroulaki and Birchall (2001), transplantation is being viewed as a means of increasing both the quality of life (QOL) and quantity of life (pg. 257). The notion of returning phonation and respiratory function via transplantation has fascinated laryngologists since the 1950’s. Strome performed the first true human laryngeal transplantation in 1998 and the patient continues to do well. However, according to Stravroulaki and Birchall (2001) re-innervation of the transplanted larynx is crucial for a successful functional outcome

The human larynx receives innervation from the vagus nerve via the superior laryngeal nerve (SLN) and recurrent laryngeal nerve (RLN). The SLN travels from the back of the larynx to the front initially under and then medial to the internal carotid artery (pg. 258). The SLN divides two branches: the large internal branch (InSLN) and the small external branch (ExSLN).

The InSLN descends above the superior laryngeal artery on the thyroid membrane. It then pierces through a hiatus at the upper edge of the inferior pharyngeal constrictor (IPC) muscle (pg. 258). Within the thyroid membrane, it divides into multiple branches descending along the aryepiglottic fold. The most superior branches supply the mucosa of the valleculae and the epiglottis (sensory fibers).

The ExSLN passes to the back of the larynx (posterior) to the sternothyroid muscle, which is deeper to the superior thyroid artery. The ExSLN descends within the inferior pharyngeal constrictor muscle sending branches to the pharyngeal plexus. Just under the lower edge of the thyroid cartilage or level of the “oblique line”, it curves to the front and middle of the larynx and reaches the cricothyroid (CT) muscle. Prior to entering the CT muscle the nerve splits and supplies both the oblique and rectus bellies of the CT muscle (motor fibers).

The recurrent laryngeal nerve (RLN) also derives from the vagus nerve. On the right side of the larynx the RLN winds around the subclavian artery, running closer to the trachea as it travels upward towards the tracheo-esophageal groove. On the left it passes lateral to the ligamentum arteriorsum behind the aortic arch and enters the trachea-esophageal groove in the chest. Branches on the left are distributed to the esophagus, trachea, and IPC muscles as they ascent towards the larynx. In the majority of cases, the RLN divides outside the larynx into an anterior motor branch and medial sensory branch. The anterior RLN carries adductor and abductor fibers which supply the PCA and Interarytenoid (IA) muscles of the larynx.

The posterior cricoarytenoid (PCA) muscle is frequently innervated by two or three compartmental nerve branches that arise of the main trunk of the AnRLN. In some cases, the nerve is innervated by a single nerve branch, which splits as soon as it enters the muscle. The inferior and superior branches innervate bellies of the PCA muscle.

         Reinnervation of the transplanted larynx is important for a successful outcome. A major step towards achieving the goal of successful innervation has been the use of appropriate animal models (dogs, cats, and rats). According to Stavroulaki and Birchall (2001), these animals have been widely used as preclinical models and a thorough understanding of the larynx structure and function. 

Resource:

Stavroulaki, P., Birchall, M.(2001). Comparative study of the laryngeal innervations in humans

and animals employed in laryngeal transplantation research, The Journal of Laryngology & Otology, 115, 257-266