or decades, transplant surgeons have treated organs as if they were beers for a camping trip: You just pack them in a cooler and hit the road.
But livers, it turns out, aren’t much like lagers, and might benefit from a different sort of travel. The alternative that researchers have come up with is a machine designed to mimic the environment of the human body, keeping the organ warm and breathing as it’s being shuttled from donor to recipient. Now, after comparing the two, a team has shown that this contraption not only kept livers safer for longer than cold storage, but also allowed surgeons to transplant organs that might otherwise have been thrown out.
“It’s a landmark paper. It’s truly a breakthrough in organ preservation,” said Dr. Markus Selzner, surgical director of the liver transplant program at Toronto General Hospital, who was not involved in the study. “Over the last decades we have put livers on ice, put them to sleep, and have basically slowed down the dying process by cooling. This new technology does the opposite: It keeps them warm, alive, and happy.”
The paper, published Wednesday in Nature, comes weeks after the Food and Drug Administration approved a similar device for lungs. Taken together, the developments underline a shift in thinking about how best to handle organs for transplants.
The idea of keeping organs working outside the body dates back to Lucky Lindy himself. In the early ’30s, a few years after his famous transatlantic flight, Charles Lindbergh was dismayed to hear that his sister-in-law couldn’t get heart surgery because the organ wouldn’t survive outside of her body long enough for the doctors to fix what they needed to fix. So he set about designing a glass contraption that might make the procedure possible. He ended up publishing an unsigned paper in Science about his “artificial heart,” which cycled liquid into the chambers to keep the organ pumping.
But when transplantation took off in the 1960s, surgeons used a different tack, preserving organs by keeping them cold, and the technique hasn’t changed much since then. There have been new liquids added into the mix, to help cells maintain their shape, but the concept remains the same: Slow down the organ’s metabolism as much as possible, and rush it into the recipient before too much damage occurs.
Damage occurs anyway, though. Deprived of blood, the organ has no source of oxygen, and so uses up its stores of energy without replenishing them, and injures itself in the process. That can cause problems when the actual transplant happens, because the recipient’s body responds with inflammation, sometimes causing the patient’s blood pressure to plummet.
In the 1990s, a team at Oxford University tried out something reminiscent of Lindbergh’s idea, but with pig livers instead of hearts.
“What was clear was that organs functioned remarkably well and for a remarkably long time,” recalled Dr. Peter Friend, a professor of transplantation at Oxford. “We demonstrated that they worked for three days, at which point, we thought, ‘Well actually this is so much more natural and logical, we should be looking at this to replace cold storage because you avoid most of the damage.’”
In 2008, he and his colleague Constantin Coussios spun their research into a medical device company called OrganOx. But if they wanted hospitals to lease their liver machines, they’d have to do a randomized study comparing their doohickeys to plain old iceboxes.
Those are the results they published on Wednesday, with data collected in the U.K., Germany, Belgium, and Spain. When a liver was matched to a patient, it was randomly assigned to be transported either in a cooler filled with melting ice or in the relative luxury of an OrganOx contraption, which looks a little like a rolling Rube Goldberg machine, with liquids flowing in and out of the box where the organ is kept. Then, the researchers measured the level of damage to the organ by testing for an enzyme that gets released into the blood when liver cells die. They found that there was significantly less injury in the livers that had been moved while they were being warmed and pumped full of donated blood.
Yet many experts were also excited about something else. The researchers saw that surgeons were much less likely to reject the organs that arrived in the OrganOx box. Of the livers taken out of the cooler, medical teams turned down 32 and ended up performing 101 successful transplants. Among those taken out of the machine, only 16 were discarded, and 121 were put inside patients.
Why the difference?
When the organ is in a device that mimics the body, doctors can see it taking in blood and letting out bile, and can better tell how it might work in a patient. By lessening injury, the machine might also allow them to use organs that wouldn’t be in good enough shape for the breathless, bloodless rush of an icebox transplant.
“That should translate into saving lives of people who are waiting for a transplant,” said Dr. James Markmann, chief of the transplant surgery division at Massachusetts General Hospital, who was not involved in the study.
The new technology could also potentially give teams a window during which to treat an organ — trimming off fat or giving high doses of antibiotics — before it gets slotted into a new abdominal home.
These kinds of machines might not be standard of care, but they are already in use for a few different organs. TransMedics, based north of Boston, makes them, as does the Dutch company Organ Assist. From their headquarters in the U.K., OrganOx leases out its devices around the world; in Europe, it costs somewhere between $6,000 and $9,000 for each organ that gets hooked up, according to Friend. The devices tend to hit the market in Europe and Australia while they’re still being tested in the U.S.
To Friend, this study could be part of a large-scale change in transplantation. “It no longer has to be done in a big hurry in the middle of the night. It may well be that transplant could become a daytime activity,” he said. “Daytime operating is associated with better results and lower costs.”
But there’s still plenty of research to do before anything like that.
“Incorporating technology like this really changes how organs are procured, how they are handled, how they are transplanted. It potentially changes the allocation system,” said Dr. David Klassen, chief medical officer of the United Network for Organ Sharing, which coordinates transplantation across the U.S. “There are training requirements, there are major costs. Decisions of this kind of consequence aren’t done based on one single trial.”