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Findings of Several Studies to be Presented by University of Pittsburgh Researchers at Transplant 2000 Meeting

CHICAGO, May 13, 2000 — With nearly 70 presentations on clinical and basic science research findings, University of Pittsburgh transplant researchers will have a strong showing at Transplant 2000, the first combined scientific sessions of the American Society of Transplant Surgeons and the American Society of Transplantation. The meeting is being held

May 13 - 17 at the Sheraton Chicago Hotel and Towers. Highlights of findings include:

  • Patients prone to rejection could be screened and their immunosuppression tailored to prevent serious episodes, according to a study that classified heart transplant patients by their genetic profiles of key hormone substances involved in immune response. (Sunday)
  • A life-long regimen of anti-rejection drugs may not be necessary for some patients, especially children, say researchers who have weaned a number of adults and children completely off drugs, some for as long as eight years. (Sunday)
  • There are far fewer repeat transplants in recent years and organ rejection is now rarely the indication for retransplantation, according to a 20-year study of 4,000 liver transplants performed at the University of Pittsburgh, the largest series from a single center. (Tuesday)
  • Last year, there was a 19-percent increase in deaths on national transplant waiting lists, due in large part to the shortage of organs. Based on their results, researchers say the use of nonheart-beating donors is a feasible way to increase the donor pool of organs. (Tuesday)

Following is a summary of these and other presentations. Please note embargo times:

SUNDAY, May 14

Analysis points to possible screening tool for patients who are "rejecters"

EMBARGO 2 PM CENTRAL

Patients prone to rejection could be screened and their immunosuppression tailored to prevent serious episodes that could result in graft loss, according to a study that classified pediatric heart transplant patients by their genetic profiles of certain hormones involved in the immune response. Using a polymerase chain reaction method that detects unique profiles of genes, 81 heart recipients, 29 organ donors and 50 control patients were cytokine-genotyped. Cytokines are hormone-like substances that cells use to communicate with each other and that modulate immune activity. Those who had multiple acute rejection episodes -- referred to as rejecters -- had a markedly different profile of cytokines (lower levels of Interleukin-10, or IL-10) than did those who experienced few episodes (higher levels of IL-10 and low levels of Tumor Necrosis Factor-alpha, or TNF-a ). Donor cytokine genotype had little correlation with rates of rejection. According to Adriana Zeevi, Ph.D., professor of pathology and surgery at the Thomas E. Starzl Transplantation Institute, these profiles could be used by the transplant team to help determine the best immunosuppressant regimen for their patients. (Abstract #35)

Weaning of drugs feasible for some liver transplant patients, long-term results show

EMBARGO 2:30 PM CENTRAL

A life-long regimen of anti-rejection drugs may not be necessary for some patients, say researchers who have weaned a number of patients completely off drugs. According to a study of 120 patients who entered a physician-controlled protocol between June 1992 and November 1999, nearly a third (32.5 percent) of the 52 children and 68 adults have been drug-free for a mean of 6.2 years. Drug withdrawal typically took about a year and was more successful in children. Weaning was stopped in 38 patients with acute rejection. All were successfully treated, most often with previous levels of immune suppression with or without steroids, and no grafts were lost. Patients currently being weaned have had daily doses of cyclosporine, tacrolimus or prednisone significantly decreased. According to George Mazariegos, M.D., assistant professor of surgery at the Thomas E. Starzl Transplantation Institute, the long-term study indicates that not only is weaning feasible, but that patients can remain drug-free for a relatively long time. Researchers will be exploring whether cytokine gene profile screening (see above) can help identify which patients might be the best candidates for successful weaning. (Abstract #29)

Study points to need for policy reforms: Patients with liver cancer have little time to wait

EMBARGO 5 PM CENTRAL

While a United Network for Organ Sharing (UNOS) policy allows patients with Stage I and II hepatocellular carcinoma (HCC) to be upgraded on the UNOS waiting list from status 3 to status 2B, this decreases the average waiting time by only 18 days, from 341 days to 323. According to a University of Pittsburgh analysis, the mean waiting time of nearly a year for patients of either status is sufficient time for their tumors to go through 1.5 to three doublings, which may render the tumors too large to cure. These patients ought to be listed in the more urgent category -- status 2A, which has a mean waiting time of 116 days, equivalent to one tumor doubling time, says lead author Wallis Marsh, M.D. Dr. Marsh, associate professor of surgery at the Thomas E. Starzl Transplantation Institute, examined 344 HCC patients transplanted at the University of Pittsburgh. All tumor Stage I patients were alive and tumor-free at five years; tumor Stage II patients had a 93 percent five-year tumor-free survival rate. Stage I is defined by the American Liver Tumor Study Group as a cancer that involves one nodule less than 2 cm in size; Stage II is characterized by either one nodule of 2 to 5 cm or two to three nodules less than 3 cm. Stage III patients (those with one nodule greater than 5 cm or two to three nodules, one of which is greater than 3 cm) and stage IV-A1 patients (with four or more nodules of any size) had five-year tumor-free survival rates of 64 percent and 52 percent, respectively. Modifying the staging system to select a subgroup of Stage IV patients with four or more nodules all less than 3 cm results in an 80 percent five-year survival rate, outcomes that justify a change in policy to allow these patients to be upgraded as well, but to status 2A, not status 2B, Dr. Marsh argues. (Abstract # 104)

MONDAY, May 15

Two lungs are not better than one: Surgeon debates merits of single lung transplants

EMBARGO 7:30 AM CENTRAL

Are two lungs better than one? Not necessarily, argues a University of Pittsburgh transplant surgeon in a scheduled debate. Considering the fact that more than 25 percent of all wait-listed lung patients die before a second chance at life, more surgeons should embrace the idea that one donor can in many instances save the lives of two patients awaiting life-saving lung transplantation. Bartley P.Griffith, M.D., the Henry Bahnson Professor of Surgery and chief, division of cardiothoracic surgery at the University of Pittsburgh, will argue his points against Bruce Reitz, M.D., of Stanford University. Nearly twice as many single-lung transplants are performed at the Pittsburgh program, which in 1999 performed 22 single-lung transplants and 12 double-lung transplants. In 1998, 486 single-lung transplants and 376 double-lung transplants were performed in the United States. At Stanford that year, surgeons performed 11 single- and 10 double-lung transplants.

TUESDAY, May 16

Study of 4,000 liver transplants yields clues about causes and rates of retransplantation

EMBARGO 8 AM CENTRAL

There are far fewer repeat liver transplants in recent years and organ rejection is now rarely the indication for retransplantation, according to a 20-year study of 4,000 liver transplants performed at the University of Pittsburgh, the largest series from a single center. Overall, about one in five liver transplant patients needed a second transplant, but the rates of retransplantation were significantly less in the last decade (13 percent) with the advent of the immunosuppressant tacrolimus compared to the early 80s (33 percent), said John J. Fung, M.D., Ph.D., professor of surgery and chief, division of transplantation at the Thomas E. Starzl Transplantation Institute. With a median follow-up of 15 years, researchers found the most common reasons for retransplantation were primary nonfunction, hepatic artery thrombosis and chronic and acute rejection, which collectively, accounted for 80 percent of the retransplants. But while rejection accounted for 13 percent of rejections in the cyclosporine era (1981-85), rejection accounted for just 1 percent in the tacrolimus era (1991-98). Disease recurrence, cancers and age-related complications are now the major factors related to graft loss. (Abstract # 800)

HIV-positive patients receiving liver transplants at few centers

EMBARGO 12:30 PM CENTRAL

New drugs are halting the progression of HIV and AIDS and prolonging the lives of those with HIV, yet patients with HIV and hepatitis face certain death without a liver transplant, and few centers are willing to transplant such patients. John Fung, M.D., Ph.D., professor of surgery and chief of transplantation at the Thomas E. Starzl Transplantation Institute, will lead a discussion on the controversial issue with Peter Stock, M.D., of the University of California, San Francisco. Surgeons at these two programs are among the few willing to accept HIV patients on their liver transplant waiting lists.

Patients do well with livers from nonheart-beating donors

EMBARGO 2:30 PM CENTRAL

Based on results of the largest study of its kind, researchers at the University of Pittsburgh say the use of nonheart-beating donors (NHBDs) is a feasible way to increase the number of available organs for transplantation. Last year, there was a 19-percent increase in waiting-list deaths, due in large part to the shortage of organs. In most cases, cadaveric organ donors are brain dead, meaning they meet neurological criteria for complete cessation of brain activity. In contrast, NHBDs do not have complete cessation of brain activity but neurological damage is irreversible. These donors are declared dead when the heart stops beating. Between January 1997 and December 1999, surgeons at the University of Pittsburgh's Thomas E. Starzl Transplantation Institute identified 21 NHBDs. Twelve of the 21 livers were suitable for transplantation. With a median 23-month follow-up, there is 92 percent patient survival. According to David Geller, M.D., Samuel P. Harbison Assistant Professor of Surgery, graft survival is 83 percent. Two grafts failed for reasons unrelated to the source of the donor.

(Abstract #985)

WEDNESDAY, May 17

Antibiotic-resistant infections on the rise in liver transplant patients

EMBARGO 11 AM CENTRAL

A review of the types of infections and antimicrobial susceptibility seen in liver transplant patients over a 10-year period has shown an alarming increase in Gram-positive infections that are multiply antibiotic resistant. According to a study of 162 liver transplants performed at the VA Medical Center in Pittsburgh, Nina Singh, M.D., associate professor of medicine, reports about a third of the patients had at least one multiply antibiotic-resistant bacterial infection. While resistance has been common with Gram-negative bacteria, there has been a trend through the decade toward a significant increase in the number of infections resistant to multiple antibiotic therapies, which she says is due largely to an increase in Gram-positive bacteria. (Abstract # 1127)

Pig virus not detected in patients treated with artificial liver containing pig cells

EMBARGO 11:40 AM CENTRAL

No evidence of a pig retrovirus was found in five patients with end-stage liver disease who were treated with an extracorporeal liver assist device that uses healthy pig liver cells to remove toxins in the liver. Using various assays, researchers examined the blood serum and peripheral blood cells of patients who underwent treatment with the Excorp Liver Assist System and found no evidence of transmission of porcine endogenous retrovirus (PERV) or the presence of circulating cells of pig origin. Ruhul H. Kuddus, Ph.D., research instructor of surgery working in the laboratory of Abdul Rao, M.D., D.Phil., says the preliminary study indicates the device's hollow glass fibers that separate a patient's blood from the pig cells can protect patients against PERV transmission. Longer patient follow-up and further investigation is required, however, to adequately assess the potential risk of disease transmission associated with the use of animal tissue in humans. (Abstract # 1131)

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