Fig. 7.11. Histopathology of acute pancreas allograft rejection demonstrating a dense inflammatory infiltrate involving septa and extending in to acinar tissue. (Reprinted with permission from: Solid Organ Transplant Rejection, Editor Solez, Publisher Marcel Dekker, Inc., 1996).

rapamycin in 19%. Therefore, in 2001, the most frequently used combination of maintenance therapy at discharge was tacrolimus, mycophenolate mofetil, and corticosteroids.

The dominant use of tacrolimus today represents a marked shift from earlier eras. In 1992-93 cyclosporine accounted for virtually 100% of the calcineurin inhibitor use in pancreas transplantation. In 2001, 92% of SPK transplant recipients received corticosteroids, 86% tacrolimus (14% cyclosporine), 82% mycophenolate mofetil, and 19% rapamycin. Based on these data, one can extrapolate that the most common maintenance immunosuppressive regimen used in SPK transplant recipients included corticosteroids, tacrolimus, and mycophenolate mofetil.

Trends in the uses of maintenance therapies over the past 7 years for SPK transplant recipients are depicted in Figures 7.12 and 7.13.5 The use of tacrolimus rose to 86% in 2001. Because tacrolimus is used as a replacement for cyclosporine, cyclosporine usage has dropped from nearly 100% of cases in 1992 to only 14% of cases in 2001. Similar trends in the use of antimetabolites are seen with respect to azathioprine and mycophenolate mofetil. In the early 1990s azathioprine was used in nearly 100% of cases, dropping to 1% in 2001; mycophenolate mofetil usage grew from 25% in 1995 to 82% in 2001. From 2000 to 2001, sirolimus usage rose from 13% to 19% of cases.

Similar trends were observed for recipients of a solitary pancreas allogaft. The use of tacrolimus has increased yearly aince 1995 and reached 91% in 2001. The FDA approved mycophenolate mofetil for marketing for kidney transplantation in 1995, and it was used in only 14% of solitary pancreas transplant cases that year (azathioprine was used in 72% of cases). However, within one year nearly 80% of solitary pancreas transplant recipients received mycophenolate mofetil, with only 12% receiving azathioprine. The use of azathioprine has diminished yearly and dropped to 1% usage in 2001. In 1999, the FDA approved the use of sirolimus for marketing for kidney transplantation. For pancreas transplantation, this agent is usually used in combination with a calcineurin inhibitor, and as a substitute for an antimetabolite. The use of sirolimus has been relatively slow to penetrate the market, compared to the rapid spread of tacrolimus and mycophenolate mofetil usage. In 2000 and 2001, sirolimus was used for 10% and 19% of solitary pancreas cases, respectively.

B. Pancreas Allograft Rejection

The early clinical presentation of pancreas allograft rejection is much different than that of kidney rejection. An understanding of the kinetics of the tissue injury during acute rejection of the pancreas allograft is essential to making a timely diagnosis. Destruction of the (beta cells occur relatively late following initial injury of the acinar tissue. Therefore, the diagnosis of pancreas graft rejection by hyperglycemia is a late and often irreversible situation. Detection of changes in acinar cell function is the basis for early suspicion of pancreas graft rejection. The graft is usually inflamed and patients experience pain and discomfort around the graft due to peritoneal irritation. This, coupled with elevation in the serum amy-lase or lipase, and if bladder-drained, reduction in urinary amylase, may be the

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