Developing Best Practices for Organ Transplantation
Elizabeth A. Pomfret, MD, PhD, is the chair of the Department of Transplantation and Hepatobiliary Diseases at Lahey Clinic Medical Center and a professor of surgery at Tufts University School of Medicine. She earned her MD and PhD from Boston University School of Medicine and did postdoctoral training at New England Deaconess Hospital (surgery) and at Beth Israel Deaconess Medical Center (multiorgan transplantation). “We transplant liver and kidney at Lahey Clinic Medical Center, and we’ll be starting pancreas transplantation in the near future,” says Pomfret. “We also have a very large practice of nontransplant surgery for patients with liver, bile duct and pancreas disorders and/or cancer. The primary research that we have here is related to transplantation, patient safety, and liver diseases, especially hepatitis C.”
The structure of Pomfret’s department integrates medical and surgical people under one roof, a model that not only improves patient care but also aids in research “because you have the integrated pieces of the puzzle, instead of the traditional silo approach” she says. One NIH-sponsored multicenter research project the department is involved in is called A2ALL (Adult to Adult Living Donor Liver Transplantation). “Ours is the largest program in the U.S. for live donor liver transplantation,” says Pomfret. “This involves surgically removing approximately 60% of the healthy donor’s liver, taking out the entire diseased liver of the patient who needs the transplant, and replacing it with that portion (60%) from the donor. The liver is the only organ that is able to regenerate itself and so it’s the only organ where you can transplant part of it, have it grow to the appropriate size for the recipient, and function like the whole organ.”
The A2ALL study collects and analyzes information about the outcomes, risks, complications, and surgical techniques used for both the donor and recipient. The first part of A2ALL (now completed) established the safety and effectiveness of living donor liver transplantation. The second part (now underway) is focused on donor safety and donor quality of life. A2ALL has generated several spin-off projects involving Pomfret. One is an NIH-sponsored multicenter study that involves the same tools that are used in federal aviation and nuclear power plants to avert disaster. “It’s designing systems to determine where weaknesses may exist along the spectrum of the live liver donor process, from preoperatively through intraoperatively and postoperatively,” she says. “Determining where the Swiss cheese holes line up to potentially result in a catastrophic event.” The study started with a retrospective review of the entire transplantation protocol and then moved on to anonymous questionnaires sent to randomly chosen members of the transplant team. “We’ve identified common themes irrespective of institution and have now put these in a hierarchical grid of the most commonly cited areas of potential weakness,” says Pomfret. “The next phase of the study is to videotape the entire process experienced by a donor–recipient pair, including pre- and postoperative care as well as the actual surgery.” The videos will be analyzed by system safety experts. The last part of the study will be to develop a checklist of potential problems and corrections, prospectively test them, and see if the checklist makes a difference in patient safety.
Pomfret is involved with several studies of organ imaging, an essential aspect of transplantation. One study will compare MRI and CT scan assessments of liver cancers in patients awaiting a liver transplant with the actual liver removed during transplantation. Assessment accuracy is important because patients with liver cancer diagnosed by imaging alone are eligible to receive increased priority on the liver transplant waiting list without having a liver biopsy to confirm cancer pathologically. Since the waiting list is usually three times greater than the number of livers available, this higher priority could create an unfair advantage for patients with a liver cancer diagnosis. “This study will go on for several years and will be the definitive study for determining whether there is a superior imaging modality (MRI versus CT) and whether preoperative imaging accurately reflects the extent of cancer found at the time of transplantation. This will help to inform the design of an allocation and distribution scheme that more accurately reflects the true risk for a transplant candidate with cancer on the waiting list as compared to a patient who does not have cancer, and how to appropriately prioritize these patients on the list,” says Pomfret.
Lahey Clinic is one of a few centers that use state-of-the-art software that provides 3-D renderings of CT scans with accurate volume measurements. “For me as the surgeon, to be able to divide this person’s liver safely while leaving the blood supply intact, we have to really know the blood vessel anatomy like a road map,” says Pomfret. “This is one of the ways I determine whether the person is technically suitable to be a liver donor. Can I divide that liver and preserve what I need to preserve so that the donor has enough left—I need to leave them with at least 30% of their original liver volume—and still have an adequate amount of liver to transplant into the recipient? Since this is just a part of a liver, we often have to do extensive reconstruction of the liver blood vessels in order to make it ‘fit’ the recipient’s anatomy.”
Hepatitis C (HCV) treatment is also a major focus of research in Pomfret’s department. Studies of various treatment options are underway, including regimens that combine newly available protease inhibitors with standard therapy. Collaborative studies focusing on patient genotypes associated with treatment success or failure are also in progress, as are studies regarding safe dosing strategies in liver transplant patients who must also take immunosuppression. “Approximately 40% of our patients have HCV, and it recurs with varying degrees of severity following liver transplantation” says Pomfret. “Control and/or cure of hepatitis C is very important for liver transplant programs so that this scarce resource is used responsibly.”
Pomfret collaborates extensively with Christiane Ferran of Beth Israel Deaconess Medical Center. “She is looking at the different genomic patterns of what turns regeneration on and what stops it,” Pomfret says. “We know for instance from our clinical data that there are two totally different patterns of regeneration. You would think that the donor would be the one who would regenerate most quickly—the healthy person. Actually, the recipient has explosive growth during the first 30 days.” The growth of the donor’s remaining liver starts off quickly then slows over time. “We hypothesized that since the recipient’s liver had been damaged, the recipient’s body has been trying to repair this damage for years, so everything’s upregulated,” says Pomfret. “Now we’re actually seeing the very first genomic and proteomic data.”
“We always love to cooperate with other groups of people who are interested in the things that we’re doing,” says Pomfret. “I understand the basic science, and know what clinically relevant questions need to be answered, but I don’t have the time or the facilities to do the basic science. I enjoy working with people in totally different fields—that type of collaboration creates innovation. I would like to be able to work with engineers—like what we’re doing with the nuclear regulatory and federal aviation people—so maybe biomedical engineers or other people who devise system models for decision making.”
For more information, please see http://www.lahey.org.