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June 23, 2011

Shapiro traces transplantation career in provost’s lecture

“Our goal in life is really not to avoid death — that’s not possible — but to try to cheat death as much as possible,” said professor of surgery Ron Shapiro as he celebrated his appointment as the Robert J. Corry Chair in Transplantation Surgery.

Shapiro came to Pitt in 1986 as a clinical fellow in transplant surgery under Thomas E. Starzl. He now directs the kidney, pancreas and islet transplant programs at the Thomas E. Starzl Transplantation Institute.

Shapiro, whose career has focused in particular on the development of improved immunosuppression protocols, credited the collective efforts of many scientists and medical professionals as he outlined advances in the field over recent decades.

His June 9 talk, “A Life in Transplantation,” was presented as part of the Provost’s Inaugural Lecture series.

Before the development of the first anti-rejection regimens, successful transplants were limited to identical twins, Shapiro said. “Sixty years ago if you had end-stage renal disease it was pretty easy — you just died. There was no dialysis; there was no transplantation.”

As anti-rejection treatments were developed, they came at a price.

“The history of immunosuppression is to a large extent the history of all the terrible things we’ve done to our patients in terms of infections, weight gain and growth retardation in children as a result of steroids,” Shapiro noted. In spite of their value, many immunosuppressant drugs are toxic.

In the 1960s and 1970s the first anti-rejection regimes used azathioprine — a failed cancer drug — with steroids and anti-lymphocyte preparations, Shapiro recounted.

In the 1980s, cyclosporine — discovered by researchers seeking a new antifungal agent — “revolutionized transplantation,” Shapiro said. It improved survival in kidney transplant recipients and made liver and heart transplantation possible. It also brought about the start of successful pancreas and lung transplants. However, cyclosporine is toxic to the kidneys and comes with side effects including hypertension and cosmetic and metabolic problems, Shapiro noted.

The first immunosuppressive agent not discovered by accident was tacrolimus, or FK506, which was discovered in 1982 and found its first clinical use in 1989 in liver and kidney recipients. The new drug improved survival and resulted in fewer side effects, although it too was toxic to the kidneys.

It enabled doctors to withdraw or nearly withdraw the steroid prednisone in a large number of patients. “This was a new phenomenon,” Shapiro said, noting that tacrolimus and mycophenolate mofetil — a successor to azathia-prine — have become the dominant immunosuppressants over the years in kidney transplants.

Newer treatments — including the use of bone marrow infusions — have enabled doctors to wean some patients off steroids, but work in that area continues as doctors and scientists seek new ways of avoiding or reducing complications in transplant recipients.

In addition to being instrumental in the development of tacrolimus, Shapiro said his group’s work over the past two decades has included reducing and avoiding complications such as infections and lymphoma. Another area Shapiro said his group has been involved in is finding matches for patients who need transplants via paired donations and donor chains.

Shapiro said the University’s progress in the field was a “huge group effort,” crediting close relations between nephrologists and surgeons, the dedication of pathologists and scientists, team members including nurses and research coordinators, and fellows of the Starzl Institute program.

“And at the end of the day, it kind of doesn’t matter how many papers you wrote or how many talks you gave, but what really matters is who did you train and how did they do?” he said, adding that many former fellows now are running transplant programs all over the world. “It’s been a privilege to be involved in their training,” he said.

Shapiro credited his own mentors, including former chief of surgery Richard Simmons, who was recruited to Pitt by Starzl and was chief of surgery when Shapiro was a young faculty member.

In addition to being “a great surgeon and a very thoughtful and analytical individual,” Shapiro said, “he was one of the greatest mentors that one could possibly have.” He added that Simmons and Starzl formed a formidable team.

Starzl’s list of accomplishments is lengthy but his most interesting aspect as a mentor is that he is never satisfied, Shapiro said. “We can always do it better, we can always come up with some sort of better way of taking care of patients, better immunosuppression,” is what Starzl insists. “This lack of complacency, I think, is perhaps his most enduring legacy to us so that we are taught never to really be satisfied with what we’ve accomplished in the care of our patients and are always trying to improve what it is we are trying to do,” Shapiro said.

Shapiro also paid respect to the memory of Robert J. Corry, professor of surgery and director of pancreas transplantation at the Starzl Institute.

Shapiro, who studied under Corry, credited him with helping to establish Pitt as a major center for pancreatic transplantation. “In addition to being a fabulous surgeon and clinician, [Corry] was a great mentor and wonderful friend, really a role model for a great academic surgeon,” Shapiro said.

“He went out of his way to help many people in the field, really just to do it, just because he thought it was the right thing to do.

Corry died in 2002 at the age of 67. “We miss him still,” Shapiro said. “We still think about him every day and we still think about what he would do.”

—Kimberly K. Barlow

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