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Islet transplant helps control diabetes after pancreas removal

June 30, 2014


PITTSBURGH ó Extreme, persistent pain can lead a person to make dramatic decisions, including getting rid of the painful body part.

Thatís what Vincent Nasser, 28, of Squirrel Hill decided to do last summer.

Entering his senior year at Penn State University six years ago, Nasser began feeling pain and discomfort in his mid- and upper back and his stomach, especially after eating.

In time, doctors diagnosed him with idiopathic pancreatitis ó inflammation of the pancreas with no known cause. After graduation, he took an information-technology position. But sharp, stabbing pain in the back and torso, sometimes radiating to the legs, required heavy-duty pain medications each day such as morphine, oxycodone, Percocet, Vicodan and Dilaudid.

Early last summer, ever-progressing levels of pain persuaded Nasser to undergo surgery to remove the entire pancreas. "My life is amazing now compared to having chronic pancreatitis," he said. "Iím living a pretty good life."

The clearly successful surgery did have two drawbacks.

Itís a given that once the pancreas is removed, the person must take digestive enzymes orally for the remainder of his or her life. But the larger challenge involves the potential of developing diabetes from the loss of insulin-producing beta cells in the pancreas.

To counter that loss, the pancreatectomy includes saving as many islets from the removed pancreas as possible. Islets are groups of cells consisting mostly of beta cells. The preserved islets then are injected into the portal vein leading to the liver, with the hope that a solid percentage will take refuge in the liver, where they can continue producing insulin and prevent diabetes.

In Nasserís case, the process fell a bit short. He now takes a small daily dose of insulin, but retains some islet function, which makes his diabetes easier to control.

Now thereís hope that a new drug can increase islet survival

Univerity of Pittsburgh Medical Centerís new Islet Transplantation Center, led by director Martin N. Wijkstrom, is participating in a human clinical trial to test whether the drug, Reparixin, or REP0112, produced by the Italian company Dompť, will increase islet survival following a pancreatectomy.

The drug in previous clinical trials improved outcomes in donor islets transplanted into patients with type 1 diabetes, with better glucose control and insulin independence for three of four patients. The current trial also could advance the knowledge and outcomes in transplants using islets from brain-dead donors, Dr. Wijkstrom said.

UPMC joins four other medical centers nationwide in the Reparixin clinical trial to measure islet survival and insulin production, following about 100 patients who undergo pancreas removal in the next two years. Dr. Wijkstrom said his center is seeking participants but will accept referrals only from gastroenterologists.

Medical centers at the University of Minnesota (leading the trial), Baylor University, the University of South Carolina and the University of Chicago also are participating.

Removal of the pancreas causes consequences that must be addressed.

Currently, 60 to 80 percent of the islets injected into the portal vein en route to the liver are thought to be destroyed in the process. That can lead to diabetes known as type 3C, which is a more brittle, or hard to treat, form of the disease involving not only insufficient insulin but also the loss of other pancreatic cells and enzymes beneficial to maintaining normal blood glucose levels by interfering with the absorption of nutrients.

Dr. Wijkstrom said only one third of the patients who currently undergo pancreas removal emerge with enough insulin production to prevent diabetes, which helps explain Nasserís results. UPMC does about 12 pancreatectomies a year.

With Reparixin, the hope is that 50 to 70 percent of islets will survive in the liver, making a larger percentage of patients insulin-independent.

Research has long been underway worldwide to develop the procedure to cure type 1 diabetes with islet-cell transplantation in the liver. But in those cases, the islet cells come from a donor, which means the patient must take immunosuppressant drugs to prevent destruction of the foreign islets.

"So many people with type 1 potentially will benefit," Dr. Wijkstrom said. "If we improve outcomes, we could in the future transplant two patients with one donor, which would be fantastic"

Another advantage is that the procedure doesnít require surgery, as would a pancreas transplant. Both pancreas and islet transplants show similar results with 60 percent success rate after five years.

The U.S. Food and Drug Administration and the Centers for Medicare & Medicaid Services must approve Reparixin as a safe and effective treatment, which in turn would prompt private health insurers to pay for the procedure, Dr. Wijkstrom said

"You should go to your gastroenterologist and ask the doctor if you would benefit from the operation," he said. "Potentially this could have a big impact. The drug REPO112 could be key because it is designed to help rescue islet cells from being destroyed."

Islet transplants for type 1 diabetes are not yet available as the National Institutes of Health analyzes data from a series of clinical trials for patients who received the transplants.

"Success rates are improving," Dr. Wijkstrom said. "After five years, 60 percent are working, which makes the results similar to whole-organ (pancreas) transplants. Itís not necessarily cheaper, though," due to the cost of organ procurement and the processing necessary to provide islets for transplantation.

Dr. Wijkstomís own research focuses on using pig islets for implantation to avoid the long wait for donor islets. About 2 million people in the United States have type 1 diabetes.

Benefits might be widespread

"This is a pretty exciting area of study," said Gregory G. Ginsberg, director of endoscopic services at the University of Pennsylvania School of Medicine. "Pittsburgh has been a leader in understanding genetic difference in the forms of inherited and spontaneous mutations in acute and recurrent chronic pancreatitis. The (combined symptoms) can be disruptive and lethal."

Dr. Ginsberg also said the trial now underway will provide parallel learning opportunities on refining the process of isolating islets and administering them into the liver, which can improve outcomes, with additional benefits for other processes involving cell transplantation. That could aid in genetic engineering of stem cells to create cells necessary to prevent or treat all kinds of diseases.

"Honestly, itís a pretty dramatic thing to recommend that a patient undergo total pancreatectomy because historically it has involved diabetes and brittle diabetes," Dr. Ginsberg said. "So this is a fairly revolutionary thing, and it has taken time to get this going."

The most common causes of pancreatitis, Dr. Ginsberg said, are gallstones and excessive alcohol consumption, with others developing the problem as the result of inherited genes.

Nasser said gallstones were not discovered, nor did he abuse alcohol. Genetic tests also revealed no signs that his pancreatitis was hereditary.

Approaching one year after his pancreas was removed, he said others might not have experienced the level of success he has.

"Itís not even comparable, before and after the surgery," he said, adding that he suffers no pain, takes no pain medications and credits his wife, Bree, with supporting him throughout his health crisis. "Itís a different life now. Itís 100 percent better ó the highest percentage you can go."

It could get even better with Reparixin.

"You do see people who have bad reactions to the surgery, and I donít know the percentages," he said. "It was good for me and UPMC was fantastic. If you are at witís end like I was and you have no other options, you should at least check it out."

(David Templeton is at dtempleton@post-gazette.com )

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