April 7, 2021

Why doctors are calling a direct trachea transplant the 'holy grail'

Daily Briefing

    After breathing through a tracheal tube for years, Sonia Sein, a 56-year-old woman, was considering ending her life. But after reaching out to a doctor at Mount Sinai, she underwent a groundbreaking surgery to become the first person to directly—and successfully—receive a donor trachea.

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    'You need to do this for me or I'm going to end my life'

    Sein's trachea issues began in 2014, when she was hospitalized and intubated following a severe asthma attack. "I was intubated too long so the trachea was damaged," she said, "so I went through surgery after surgery trying to repair it."

    Eventually, doctors cut a hole in her throat and inserted a tracheostomy tube. However, Sein's day-to-day life with the tube was uncomfortable, and she found her ability to work and speak limited. She spent years looking for alternatives until—in 2017—yet another hospital informed her that everything had already been tried.

    At that point, Sein decided to do her own research. "I researched trachea transplant because I figured they do transplants for everything else," she said. "There should be something for tracheas."

    She discovered that researchers at Mount Sinai were researching how to make such a procedure viable and started to call them every other day for help. "I kept calling back until somebody called me back and gave me an appointment," Sein said. "I think they got tired of me calling!"

    However, it took several years for the surgeons at Mount Sinai to reach the point in their work where they were ready to try the procedure on a patient. Finally, on Jan. 12, Sein received a call from Eric Genden, a surgeon at Mount Sinai and a researcher at the Icahn School of Medicine. Genden was finally ready to try the procedure.

    A surprisingly complex transplant

    According to Genden, trachea transplants may seem "like a pretty straightforward thing, because at first sight it seems just like a tube, [but] it turns out it's a highly complex organ system." In fact, according to the New York Times, "the trachea has defied decades of transplantation attempts."

    Perhaps the biggest hurdle in a trachea transplant is getting blood to the trachea, NPR's "Shots" reports. Doctors for decades thought the trachea's blood supply was supported by a network of small vessels that couldn't be surgically reconnected—an idea that, according to Genden, originated in a research paper from the 1960s.

    "This dogma kind of stuck, and so if you look at the literature, you'll see hundreds and hundreds of articles that start out 'here's how we are going to reconstruct the trachea because we can't transplant it,'" he said.

    However, efforts to reconstruct the trachea—such as developing synthetic tubes, using a donor aorta, or even temporarily transplanting tracheas into people's arms to develop a new network of blood vessels before moving them to the throat—have been largely unsuccessful or applicable only in cases of partial transplants.

    Then, Genden in his own research discovered that the 1960s paper was wrong; some of the arteries that pass through the thyroid gland provide blood to the trachea, as do some blood vessels that connect to the esophagus. "This wasn't a discovery we made," Genden said. "It was a discovery that had been documented all the way back in the 1800s" but then largely forgotten.

    Genden temporarily abandoned his research in 2008, when Paolo Macchiarini, a surgeon at the Karolinska Institute in Italy, made headlines after he said he transplanted a trachea grown from stem cells. That sort of development made Genden's work "obsolete," he said. "You can't justify doing experimental surgery and immunosuppression when you see something else that looks perfect."

    But Garden resumed his work after Macchiarini came under fire for research misconduct. Many of his patients had passed away, and Macchiarini himself was ultimately dismissed from the Karolinska Institute.

    By mid-January, Genden was ready to try his innovative technique in person. He would transplant from an eligible donor into Sein not just the trachea, but also the attached esophagus, thyroid gland, and thyroid arteries—an approach that ensured the donated trachea came with a blood supply that could attach to Sein's blood vessels.

    Ultimately, Sein's surgery lasted 18 hours, including a surgery to remove the trachea and related materials from the donor and hours of surgery connecting veins and arteries to the organ in Sein.

    'The holy grail'

    Months later, Sein is tolerating the new trachea well, Genden said, and her cells are starting to grow inside it. "It's kind of the holy grail of what we've all been after," Genden said.

    G. Alexander Patterson, a surgeon at Washington University in St. Louis said the transplant "is promising. I really think it's exciting." However, he said he doesn't think trachea transplants will become a routine surgery.

    "I don't think it's a practical option for patients who have a tracheal tumor, for example," he said. According to NPR's "Shots," while cancer is a common reason people require tracheal repair, transplant patients must take immunosuppressants, which poses risks for cancer patients.

    Nor did Patterson think it would be easy to perform the surgery in newborns with tracheal defects, since they have far smaller blood vessels than adults. However, Patterson said patients who, like Sein, have damaged tracheas will be good candidates.

    Pierre Delaere, a professor of head and neck surgery at University Hospital Gasthuisberg in Belgium, added that the transplant is "very significant," but cautioned that long-term results need to be observed before the technique is fully embraced. "Let's see how it works and how you can do it in more patients," he said.

    For Sein's part, she said she was excited she had the energy to cook food for the first time and plan a trip to visit to relatives in Puerto Rico soon. Next month, Sein will turn 57.

    "We would have been planning my funeral," she said, "but now we're planning a birthday party" (Harris, "Shots," NPR, 4/6; Belluck, New York Times, 4/6).

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