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New therapies offer improved quality of life for patients who need laryngectomy

May 18, 2021

New options available in the U.S. only at Mayo Clinic's campus in Phoenix/Scottsdale, Arizona — larynx transplant program and 3D-printed prosthetic larynx — appear promising for improved quality of life for patients undergoing laryngectomy.

Cancer is the major reason for laryngectomy, according to David G. Lott, M.D., an otolaryngologist leading the research into these surgical options and associate medical director of the Center for Regenerative Biotherapeutics at Mayo Clinic in Arizona. "Watchful waiting is not an option for these patients with laryngeal cancer," says Dr. Lott. "You have to remove everything."

Other laryngectomy indications include damage from throat radiation in cancer treatment and laryngeal trauma. Currently, 10,000 people in the U.S. live with laryngectomy.

Challenges with standard surgical therapeutic options

To date, physicians have faced a dilemma when discussing laryngectomy options with patients: removal of part of the voice box (partial laryngectomy) or removal of all of the voice box (total laryngectomy).The cancer itself doesn't always dictate the need for a total laryngectomy, but the functions of swallowing, breathing and speaking are typically better with a total laryngectomy. However, the thought of living without one's voice box can be quite devastating, and patient acceptability has been poor. At worst, patients mention suicide or choose not to proceed with the surgery, opting to die of cancer.

Dr. Lott says that in the past, he typically reviewed the list of what life would be like without a larynx with patients before surgery and tried to be positive. After laryngectomy, patients would have a permanent hole in their necks, often causing social embarrassment, and could no longer breathe through the mouth and nose. Blowing the nose was out of the question, and swimming and showers were dangerous because of drowning risk. "What hurts most people is the inability to communicate," says Dr. Lott. "They become reclusive, a shell of themselves."

One option after total laryngectomy has been electrolarynx, a battery-operated voice box. Patients who use these devices usually prefer to use them only when absolutely necessary, says Dr. Lott, as they create a robot-like sound.

The other standard therapy after laryngectomy has been tracheoesophageal puncture (TEP), a voice prosthesis that enables patients to create sounds by expiration through the esophagus. Though TEP helps 90% of patients speak effectively, the new voice can be unpleasant.

"Vocal quality with a prosthesis is inhuman," says Dr. Lott. "It makes the esophagus vibrate — essentially it's burp talking."

Beyond creating unusual sounds when speaking, patients who receive prostheses after laryngectomy need replacements every three to six months and may have to contend with leakage and aspiration.

Dr. Lott's goal is to offer improved surgical options for patients with damaged larynges, restoring the three major laryngeal functions: swallowing, breathing — especially through the nose — and speaking. His laboratory, which is researching the therapies, serves as the flagship lab for the head and neck region in Mayo Clinic's Center for Regenerative Biotherapeutics. He and his team have two options not otherwise available in the U.S. for normalizing laryngeal functions.

Transplant option

Two U.S. medical centers have performed laryngeal transplants with the patients faring well, according to a 2017 article in Laryngoscope. Yet, the field hasn't advanced quickly, and these centers have since ceased operations. Dr. Lott says he doesn't see this as a technological failure, but instead as a therapy requiring significant infrastructure.

Mayo Clinic has taken up the mantle of laryngeal transplant, establishing the Larynx and Trachea Transplantation Program, a first-of-its-kind program approved by the United Network for Organ Sharing (UNOS).

Transplant benefits are significant, allowing patients to swallow, taste and smell. A transplanted larynx results in a voice that may be a little rough, but essentially a normal voice, says Dr. Lott. He says one of the first patients to undergo laryngeal transplant did well enough that he became a motivational speaker.

Laryngeal transplant also presents disadvantages, such as:

Organ shortage is an issue. Insufficient larynges are available for all U.S. patients who might benefit from transplant.
Eligibility constraints impact many patients who might elect laryngeal transplant but don't meet eligibility criteria. For instance, those who've recently experienced cancer are ineligible for immunosuppression, which is crucial after transplant.
Cost may be prohibitive. Payers don't currently cover laryngeal transplant, as it's considered an elective procedure akin to a hand or face transplant. Beyond surgical bills, ongoing medication needs are costly. The clinical trial that Dr. Lott's team started aims to make laryngeal transplantation a covered procedure.
Lifelong immunosuppression therapy is required. Not only do patients who undergo laryngeal transplant have to take regular immunosuppressants to avoid organ rejection, but these medications also put patients at higher risk of infection and some cancers.

3D-printed larynx implant option

Mayo Clinic is the first medical center to develop an image-guided, 3D-printed laryngeal implant. With this implant, the patient needs only a partial laryngectomy — removal of part of the voice box. For many patients, having the implant as an option may prevent the need for total laryngectomy. Investigators create a replica scaffold for the resected part of the larynx. Then, they treat the scaffold with stem cells from the patient's fat tissue plus growth factors to promote laryngeal tissue regrowth into the scaffold. The research team inserts the construct into a bioreactor for 14 days. Then the construct is ready for implantation. This is a National Institutes of Health grant-funded project.

A tremendous advantage of implants is that they don't require immunosuppression. Thus, a patient who's recently had cancer isn't precluded from getting an implant. An implant is also less expensive and faster than a transplant.

Other methods to reconstruct a partial laryngectomy are not patient specific. This results in swallowing, breathing and voice results that may not be functional. Early findings with this new implant have shown promising results with excellent functional outcomes.

Referring patients for these therapies

Currently, Dr. Lott and colleagues lead a clinical trial examining laryngeal transplant safety and efficacy. They are accruing additional patients. Patients who have not undergone laryngectomy and are five years out from cancer are eligible. Though criteria are more stringent currently, investigators plan to expand the study later to patients who've had a laryngectomy.

The lab is preparing for a Food and Drug Administration-approved human clinical trial to evaluate efficacy of the tissue-engineered technologies.

Dr. Lott says physicians interested in these options for their patients may email hnrm@mayo.edu or call 480-342-6611.

The future dream

Dr. Lott feels encouraged about developments with the transplant and implant post-laryngectomy therapies. "We've come close to repairing functions," he says. "They are night and day better in terms of voice than standard therapies. Others wouldn't guess our patients had a procedure without them sharing that information. Socially, what we offer now comes a long way."

Dr. Lott says he envisions a day when tissue engineering will fulfill all the needs of patients undergoing laryngectomy, making transplant unnecessary.