Pancreas-Kidney Transplantation: Background

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Background

Although they could not be called "successful" in the modern meaning of "successful transplant," individuals carried out experiments in transplantation as early as the late 18th century. John Hunter (England) experimented with transplanting organs from a male into a female chicken. Samuel Bigger (Ireland) successfully transplanted a full cornea into the blind eye of a pet gazelle. Thompson, in 1890, experimented with the excision of canine and feline frontal lobes from the brain, replacing these with allografts; some animals and allografts survived for as long a seven weeks, although there was no evidence that any neural activity occurred in the grafts.(1) Dr. Edward Zim pioneered human corneal transplants in 1906; the non-vascularized cornea avoids most of the rejection problems associated with organs that are directly connected to the blood or lymphatic systems. Various bone, joint, and vascular transplants followed, again with widely varying outcomes.

Dr. Joseph E. Murray of Brigham & Women's Hospital in Boston performed the first successful kidney transplant (from a living identical twin) in 1954. Drs. Richard Lillehei and William Kelly performed the first simultaneous kidney-pancreas transplant (SKPT) in 1966 at the University of Minnesota, Minneapolis, MN. The 1966 procedure survived for two months before being rejected by the body's immune system. 1967 brought the first successful liver transplant by Dr. Thomas Starzl at U. Colorado in Denver. The first pancreas-only transplant, again by Lillehei in Minneapolis, occurred during 1968, as well as the first successful heart transplant, performed by Dr. Norman Shumway at Stanford University.(2)

Between 1954 and 1970, the major immunosuppressant drugs used to control rejection were 6-mercaptopurine, a related drug azathioprine, and corticosteroids; all of these drugs suffered from a lack of specificity in suppression, leaving the organ recipient very, very susceptible to infections, while not entirely controlling rejection.

In 1970, the discovery of a new anti-rejection agent named cyclosporine, isolated from a Norwegian soil fungus (Beauveria nivea), accelerated transplant activity. With the advent of a more effective anti-rejection drug and improved surgical techniques, the number and variety of transplant procedures increased, and graft survival rates and length of graft survival times increased dramatically.

1981 brought the advent of the heart-lung transplant by Dr. Bruce Reitz at Stanford. In 1983, Dr. Joel Cooper in Toronto performed the first single-lung transplant, followed by the first double lung transplant in 1986.(2)

Living, related donor liver transplants (segmented), and living, related donor single-lung transplants followed, as well as living, related donor transplant of a segmented pancreas.

Advances in the immunosuppressant drugs, as well as technical improvements in surgery and postoperative monitoring make transplants initially more successful and the longevity of the grafts much greater.

Even procedures that in the past were strictly forbidden, such as transplanting recipients with HIV or Hepatitis C virus are being explored. As of January 31, 2000, the University of California San Francisco began a kidney and liver transplant program for HIV infected individuals.

In what seems to us today a classic piece of understatement, Thompson said:

I think the main fact of this experiment - namely, that brain tissue has sufficient vitality to survive for seven weeks the operation of transplantation without wholly losing its identity as brain substance - suggests an interesting field for further research, and I have no doubt that other experimenters will be rewarded by investigating it. (Thompson WG, Successful brain grafting. NY Med J. 1890; 51: 701-702).(1)