Pulse of Longwood takes you inside one of the nation’s largest hubs of hospitals and biomedical research.
It sounds too crazy to work: To ward off diabetes in patients after they’ve had their pancreas removed, blenderize the organ while they’re lying on the operating table, and then infuse the mixture into their livers.
The procedure isn’t done too often — at most 200 times a year across the United States. Now doctors at Brigham and Women’s Hospital, who have treated six patients in the past few years, are starting to see their first successful cases.
The technique, called total pancreatectomy with islet autotransplantation, was pioneered by doctors at the University of Minnesota back in 1977. It’s slowly catching on to treat patients who have a chronically inflamed pancreas removed — a surgery that eases their pain, but leaves them with brittle diabetes, bringing dangerous swings in blood sugar, because they can no longer produce insulin. Infusing a slurry made from their pancreas cells helps at least some of these patients produce insulin again.
“It still seems like magic to me,” said Dr. Gregory Beilman, deputy chair of the surgery department at University of Minnesota, “and I’ve been doing it 20 years.”
It felt pretty magical to Karen Grippen, too. Now 53, she had been living with “gut-wrenching” abdominal pain from an inflamed pancreas for years before getting the treatment at the Brigham last year. Grippen is now pain-free and is able to manage her diabetes with just one dose of insulin per day.
“I’m a very lucky lady,” she said.
Here’s how the procedure works: Starting early in the morning, Dr. Thomas Clancy, a surgical oncologist at the Brigham, removes the patient’s pancreas, gallbladder, and duodenum, a section of the small intestine. Then Dr. Sayeed Malek, clinical director of transplant surgery, cuts the pancreas away from the other organs, flushes out the blood, and places the pancreas into a jar inside a cooler full of ice. He grabs the cooler by the handle and heads to Massachusetts General Hospital, which has the equipment and expertise to handle the hardest part of the procedure: isolating the islet cells, which produce insulin.
To get there, he usually hails a cab: “You want to get there as soon as possible,” Malek said.
Inside the Mass. General lab, Malek covers up from head to toe in a protective gown and enters a sterile inner sanctum, where a four-person team takes the organ. They use an enzyme to digest the pancreas and isolate the islets.
Once the cells are isolated, he said, “they’re basically blenderized into a shake.”
The islets get mixed with a blood thinner called heparin and placed into a bag. That goes back into the jar, into the cooler — and back in a taxi cab.
Meanwhile at the Brigham, Clancy has been working to reconnect the digestive system after the surgery. He said the timing usually works out so that when Malek returns, the patient is ready for the next step: accepting the blenderized pancreas back into the body.
Malek hangs an IV bag and lets the cells drip into the portal vein that leads to the liver. That’s a crucial moment: If the solution is highly viscous, the patient risks getting a blood clot and requiring long-term anticoagulation, he said.
If all goes well, the islet cells enter the liver, set up shop there, and begin producing insulin again.
In early experiments in Minnesota, researchers tried to implant the islets in different spots — the lung, muscle, skin, and even the testicles — but none proved to be as effective in humans as the liver, Beilman said.
That could be because the liver is large, with a ready blood supply. When the portal vein flows into the liver, it branches into tiny capillaries, widely distributing the islets throughout the organ. And the liver is well-placed for the job of producing insulin because it’s “downstream of the gastrointestinal tract, which is where all of the glucose is coming from as you eat,” Beilman said.
The University of Minnesota has now performed over 600 such procedures, he said.
They’re fairly successful, but not universally so: Three years after the operation, a third of patients live free of insulin because their islets are working so well, Beilman and fellow researchers found. A third have partial function of islets, needing some insulin, and a third are insulin-dependent, the study found.
The University of Minnesota and Mass. General also transplant islets from dead donors to patients with diabetes. Dr. James Markmann, transplant chief at Mass. General, said those procedures are in the trial stage.
Grippen had the operation after five years of debilitating abdominal pain, coupled with vomiting, fevers, and sweat. The pain felt like being gouged through the stomach by a metal chair leg, she said. The first time it happened to her, it knocked her down so hard she couldn’t call 911.
Doctors couldn’t figure out what was wrong, except that it got worse when she ate, Grippen said. She had several surgeries that didn’t help much. At times, she relied on narcotics such as oxycodone and morphine to make it through.
Grippen spent over three years carrying around an IV bag hooked up to a peripherally inserted central catheter, or PICC line, because she couldn’t eat. At one point, the PICC line got infected, and she was rushed to the hospital with a life-threatening case of sepsis.
Visiting the doctor’s office was a continual letdown, she said, because it seemed like nothing could be done. “I didn’t think I was going to live.”
So when Grippen heard about the islet cell transplant program, she jumped at the chance. Not everyone can have the procedure: Patients have to be able to produce insulin in the first place, and they have to have exhausted other options, such as a partial removal of the pancreas, said Clancy. A team at the Brigham, including a social worker, gastroenterologist, endocrinologist, pain psychiatrist, and case manager, helps surgeons screen patients and manage each case.
Grippen passed the screening. She said she knew about the risk of blood clot, but she felt “anything was better” than what she was living with. So in January 2015, she rolled into an operating room at the Brigham for a 15-hour operation.
She said she felt good about the surgery — though she was worried about Dr. Malek taking her pancreas through Boston traffic in a taxi: “What if it gets in an accident?”
“I wanted him to take the duck boat,” she quipped.
Grippen said the surgery wasn’t easy — she had lingering surgical pain for four months, and had to take seven months off from work. But now she’s back on the job as a manager at a state agency, and is able to eat without pain. Last year, she ate a Thanksgiving dinner complete with turkey, mashed potatoes, and green beans — her first in five years.
“I feel like I have a new life,” she said.