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When the first pancreas transplant was performed in 1966 at the University of Minnesota, doctors considered it a risky venture at best. Three decades later and over a 1,000 people in the United States undergo a pancreas or simultaneous pancreas/kidney transplant every year. Still, a cloud of misinformation surrounds the procedure.
Robert Stratta, MD, a professor of surgery at the University of Tennessee at Memphis, has been performing both pancreas and pancreas/kidney transplants since the late '80s and has had significant success with both. Still, he feels that most people with diabetes know little about transplantation.
"I think we could do a lot more," says Stratta. "But many endocrinologists and diabetes specialists don't believe in pancreas transplants. Most aren't aware of the new advancements in surgical techniques and immunosuppressants that have been made in recent years."
Stratta also points out that often a negative stigma is associated with transplantation.
"Historically it has been offered as a last resort for people at death's door," he says. Stratta believes that a pancreas transplant could be offered to some people with diabetes before the onset of deadly complications like kidney failure.
"If transplants became more widely accepted, they could be utilized by those who have reached stages where it's certain that serious complications are going to occur in the future," he adds.
David Sutherland, MD, PhD, director of the University of Minnesota's Diabetes Institute of Immunology and Transplantation, also agrees that pancreas transplants can be performed on those with diabetes who are not so ill.
"If someone would rather take their chances with immunosuppressants instead of diabetes, that's perfectly logical," says Sutherland.
Who Qualifies for a Transplant?
The majority of candidates for a transplant are people with type 1 diabetes between the ages of 20 to 50 years old who have advanced complications such as retinopathy, kidney disease or neuropathy. People with extremely brittle diabetes who are prone to severe bouts of hypoglycemia and people who have frequent cases of diabetic ketoacidosis also qualify.
Marjorie Hunter had suffered end stage renal disease, a heart attack and lost nearly all of her eyesight by the age of 29. A successful patent attorney at the time, Hunter found herself unable to work and desperately ill.
Her doctor said she needed a kidney transplant. After being evaluated, Hunter decided she'd have a pancreas transplant too.
Those waiting for a kidney or a pancreas can wait anywhere from six months to two years depending on where they live and what donor program they are enrolled in. According to the United Network for Organ Sharing (UNOS), a nationwide organization that matches organs with donors, the average wait for a pancreas or a pancreas/kidney transplant is a little under a year. This can mean agonizing days and months waiting for the phone to ring with the news that a healthy donor organ has been found.
Marjorie Hunter was one of the lucky ones. Her brother offered his kidney and 40 percent of his pancreas, and four months later the transplant was successfully performed at the University of Minnesota.
"I didn't even feel fear over the surgery, just anticipation," says Hunter. "I was so sick that all I could think of was the new organs working."
For those considering having a pancreas transplant, one of the biggest concerns is the risk of taking immunosuppressants versus taking insulin.
Which is worse?
Immunosuppressants are critical to survival in transplant recipients, yet harmful to the body since they suppress the immune system so that the donor organ won't be attacked or rejected by the body. They also produce a host of side effects including a higher susceptibility to cancer and infection.
"Taking immunosuppressants is considered by many a disease in itself or a chronic medical condition," says Stratta. "Getting a transplant is definitely not a quick fix. You have to be on these medications for the rest of your life."
Marjorie Hunter hasn't taken an insulin shot for 12 years. Still, after her transplant she took 11 different medications eight times a day and averaged 40 pills a day for nearly a year. Currently, she takes three immunosuppressants which she will have to continue taking until the end of her life, or the life of her transplant organ.
This vast array of medications is not uncommon. After a transplant, patients take an average of 10 to 15 different kinds of pills.
Side effects are also a constant worry. In the 12 years Hunter has been on immunosupressants she has developed osteoporosis, "the shakes," short- term memory loss and bruising. "From my knees down is a solid bruise," says Hunter.
For those on immunosuppressants, the chances of getting cancer range between one percent and 16 percent (with the mean of four percent). This is a good deal higher than in the general population. And there is an 80 percent chance of contracting an infection after a transplant. Forty percent of deaths after transplants are due to infection alone or infection combined with organ rejection and its treatment.
The good news is that because of new advancements in transplantation, especially in immunosuppressants, the rejection rate for a kidney/pancreas transplant at one year is three percent compared to seven just a few years ago. There is a nine percent rejection rate for a pancreas only or a pancreas after a kidney transplant
Doctors are especially excited about a combination of the newest immunosuppressants, Prograf (FK506) and CellCept. When used together they are 100 times more effective than the commonly used antirejection drug cyclosporin. Of all the antirejection drugs, they have provided the most impressive results with a 92 percent patient survival rate 12 months after transplantation. They also allow doctors to prescribe fewer steroids which can, in some cases, cause diabetes.
A New Pancreas Procedure
Many aren't aware that doctors have also been performing pancreas transplants alone without a kidney for the last ten years. Nearly 90 percent receive a simultaneous kidney/pancreas transplant, but the remaining 10 percent receive a pancreas after a kidney transplant or a pancreas transplant alone.
The pancreas can come from a cadaver or part of a pancreas can be donated from a living donor. However, according to Peter Stock, MD, transplant surgeon at University of California at San Francisco, there are only a handful of hospitals in the United States who will transplant part of a pancreas from a living donor since it is an extremely risky and difficult procedure.
A transplant from a living donor is performed by taking the tail end of the pancreas and placing it in the pelvis area. Ducts are then fashioned so that the pancreatic enzymes are either drained through the bladder or the bowels.
Stock says there is a small chance that the person who donates part of his pancreas can develop diabetes as a result.
"Of course, it's a very low likelihood, but the risks are still there," says Stock.
A pancreas transplant has about a 70 percent success rate after a year (success means the recipient does not have to inject insulin) and pancreas/kidney transplants have an 88 percent success rate. Stock explains this is because it is much easier to detect rejection in two organs than in one. "People with renal failure have very thin blood also," says Stock. "This makes it easier to detect when the organs have been rejected in a pancreas/kidney transplant."
How Long Will it Last?
If a pancreas transplant is successful, how long will it produce insulin?
Since the procedure is relatively young it's still difficult to predict with any certainty. According to Deborah Butterfield, who runs an organization called the Insulin-Free World Foundation, an information service on pancreas transplants, the longest functioning donor pancreas to date survived 17 years in a Massachusetts woman who unfortunately died in a horseback riding accident a few years ago.
Marjorie Hunter has not needed to inject insulin for 12 years, and Butterfield, who had a pancreas transplant in 1994, has not had to take any insulin since her transplant. According to UNOS statistics, approximately 60 percent of transplant recipients do not need to inject insulin five years after the procedure.
The Future of Transplantation
Last year over a 1,000 pancreas transplants were performed in the United States. And the odds are good that with the advent of even newer and safer technology, the number waiting for pancreas transplants will increase. Doctors have already begun to work on solutions for this impending crunch. Currently, islet transplantation and the artificial pancreas offer the most hope.
Several institutes worldwide have devoted millions of dollars to the research and development of islet transplantation. (Islets are the cells in the pancreas that produce insulin.) Doctors hope that if healthy donor islets are injected into a person with diabetes, they will start to produce insulin again. If islet transplantation becomes a reality, the procedure could be performed in about 15 minutes in a doctor's office under local anesthetic.
While several important steps have been made in this technology, most doctors believe that people with diabetes may have several more years to wait.
"Ten years ago people said I'd be out of business in three to five years because of islet transplantation," says Stratta, who performs numerous whole pancreas transplants every year. "I think we'll see it become a reality in our lifetime - maybe in 15 to 20 years to be more realistic."
Sutherland is more hopeful. He estimates that islet transplantation will be a reality in five to 10 years.
There are still several hurdles to overcome before it can become a viable option, however. Immunosuppressants are still needed in order to prevent the body from rejecting the foreign islets. As a result, researchers are trying a variety of techniques to get around the use of antirejection drugs such as gene therapy, islet encapsulation and induced body tolerance.
The impending shortage of pancreases is yet another challenge. Many researchers have turned to xenotransplantation (cross-species transplantation) as an answer. Some have begun experimenting with pig islets raised in a sterile, pathogen-free environment. This has raised some debate, however, over such weighty topics as animal cruelty and the possibility of animal viruses transferring to human hosts. These conflicts will have to be ironed out before the technology can be fully utilized.
The Artificial Pancreas
Scientists have worked for years to develop an artificial device that could sense blood sugar levels and release the proper amount of insulin automatically. The artificial pancreas would be about the size of a human fist and implanted in the stomach area. It would consist of an insulin pump, a blood glucose monitor and a control system.
Working implantable insulin pumps have already been manufactured. Currently, the biggest hurdle seems to be the construction of a long-term implantable glucose sensor that gives reliable glucose readings. John F. Patzer II, PhD, of the McGowan Center for the Artificial Organ in Pittsburgh, has been working on a microchip glucose sensor for over five years. He thinks a working artificial pancreas is still several years away, however.
"Technology hasn't changed in the last 10 years," says Patzer. "It's going to take a breakthrough and, after that, probably another five years of FDA clinical trials."
When and if the artificial pancreas becomes a reality, Patzer estimates it will cost in the range of $2,000 to $2,500 and last about two years.
A Void of Information
Deborah Butterfield says she started her web site The Insulin- Free World Foundation to fill a void in pancreas transplant information. Five years ago, after developing kidney disease as a result of her diabetes, Butterfield knew next to nothing about the possibility of getting a pancreas transplant. Only through luck and her own mother's tenacity did she find out about the procedure.
For weeks she held onto the phone number for the transplant center her mother had given her, but was afraid to make the call.
"I had always equated transplants with people who were dying," says Butterfield. "I kept telling myself, 'I'm 32 years old and I'm not dying.' "
Eventually Butterfield did make the call and had a pancreas/kidney transplant in 1993. The pancreas was rejected, however, and she had to have another pancreas transplant in 1994.
Now she devotes her days to spreading the news about the surgical procedure that saved her life. Some in the diabetic community worry that she makes pancreas transplants sound too good to be true. The name of her web site alone, "Insulin-Free," causes skepticism in some.
Butterfield is aware of this. Still, she claims she presents both the pros and cons of the procedure on her web site so that readers can make an informed decision for themselves. And more importantly, she points out, the information is there so that others are not left in the dark like she was.
"I've been as far as you can go on this side of the grave with a transplant and with diabetes," she says. "And I'm aware of both the risks of diabetes and of pancreas transplants."
One thing for certain, many transplant recipients have been given a new lease on life.
"It's wonderful," says Hunter. "I never expected I'd get this far."
0 comments - Jun 1, 1998