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Living donor islet cell transplant called a success.

The world's first living donor islet cell transplantation is being called a success, with the recipient weaned completely off insulin therapy just 4 weeks after the procedure.

James Shapiro, M.D., the University of Alberta surgeon who pioneered cadaveric islet cell transplantation in 1999, performed the procedure with a team of Japanese surgeons in Kyoto on Jan. 19. By the middle of February, he said, the 27-year-old female recipient was no longer taking any form of exogenous insulin. She had been a brittle diabetic as a result of childhood pancreatitis and was C-peptide negative. The donor was her 56-year-old mother.

"The recipient has been weaned completely from her insulin and has good glucose control," Dr. Shapiro told FAMILY PRACTICE NEWS. "The donor had an uncomplicated recovery and has been tested and does not have diabetes."

He sees the living donor transplantation as a breakthrough that could change the lives of many patients. "I'm very enthusiastic about this. It will allow more patients to be treated, but we do have to think about the serious potential risks for donors. It's not something to be taken lightly."

The procedure was a "logical next step" from cadaveric islet cell transplantations, Dr. Shapiro said. Since 1999, close to 500 patients have received the cadaveric cells through variations of the Edmonton Protocol, a procedure developed in Canada for transplanting cadaveric islet cells into people with type 1 diabetes. With this procedure, patients usually receive the purified cells from two entire cadaveric pancreases. Although the procedure has a high success rate--88% of the grafts retain at least partial function beyond 5 years--it is not practical in Japan, where the concept of cadaveric organ transplantation is only now gaining public support. In 1997, Japan became the last industrialized nation to create a legal definition of brain death, opening the way for transplantations.

Because of the lack of donor organs, Japanese surgeons Koichi Tanaka, M.D., and Shinichi Masumoto, M.D., former colleagues of Dr. Shapiro's, decided to attempt a living donor transplantation. Instead of two entire cadaveric pancreases, this procedure would require only half a living pancreas. The mother and daughter shared the same blood type and had a haploidentical tissue match.

At the Kyoto University Hospital, Dr. Shapiro and Dr. Tanaka performed a distal pancreatectomy and splenectomy on the donor, removing half of her pancreas. The pancreas was flushed and a cannula placed in the pancreatic duct.

Dr. Masumoto then isolated the islet cells. He perfused the pancreas with collagenase enzyme. The islets were separated, and to maintain the integrity of the living cells, the tissue was not purified, as is cadaveric tissue, Dr. Shapiro said.

This procedure resulted in 9.5 cc of tissue, which was mixed in 200 mL of transplant medium. This was infused into the recipient's liver through a catheter in the portal vein. The islet cells began producing insulin within minutes of entering the liver, Dr. Shapiro said.

The recipient must now take a daily immunosuppressive regimen, consisting of the nonglucocorticoid antirejection drugs used in the Edmonton Protocol: sirolimus and low-dose tacrolimus, along with short-term dacluzimab.

Although the recipient's new independence from insulin therapy is obviously positive, it's too soon to predict how long, and at what level, the islets will continue to function. Among the current Edmonton Protocol patients, 85% were completely insulin independent at i year, but only 50% remained insulin independent by 5 years.

The cadaveric cells could lose function for a number of reasons, Dr. Shapiro said. They may be initially damaged by cold storage before transplantation, and some could be lost through unrecognized rejection. But he hopes that the cells transplanted in this new procedure will have a longer life. "Because they were not purified, and because they were alive, they are much more potent," he said.

The surgery itself is relatively uncomplicated, but the donor is at risk of possibly developing a pancreatic fistula or diabetes secondary to the pancreatectomy, he said. "That has occurred in some living donor pancreatic transplants, but the risks can be mitigated by careful donor screening."

Recipients must also weigh the risks of lifelong immunosuppressive therapy against the benefits of being able to discontinue insulin for an undetermined period. This decision is complicated by the time-dependent decrease in cadaveric islet cell function, said James Markmann, M.D., director of the pancreatic transplantation program at the University of Pennsylvania.

"The new procedure is very exciting and it will certainly be part of the future of islet cell transplantation, but we have to proceed cautiously," Dr. Markmann said in an interview. "Is the benefit for the recipient, to be off insulin for 5 years, worth the risk to the donor? We don't know the answer to that. It would be much clearer if we knew the islets were going to last 10 or 15 years, but if it's only 5 years, there is still a question."


Mid-Atlantic Bureau
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Author:Sullivan, Michele G.
Publication:Family Practice News
Geographic Code:1USA
Date:Mar 15, 2005
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