Basic Concepts of Organ Transplants - Report Example

Transplants COVER PAGE ORGAN TRANSPLANTS Transplants #2 An organ transplant is the transplantation of a whole or partial organ from one body to another (or from a donor site on the patient's own body), for the purpose of replacing the recipient's damaged or failing organ with a working one from the donor site. Organ donors can be living, or deceased (previously referred to as cadaveric). Successful inter-human allotransplants have a relatively long history; the operative skills were present long before the necessities for post-operative survival were discovered. Rejection and the side effects of preventing rejection (especially infection and nephropathy) were, are, and may always be the key problem. Several apocryphal accounts of transplants exist well prior to the scientific understanding and advancements that would be necessary for them to have actually occurred. The Chinese physician Pien Ch-iao reportedly exchanged hearts between a man of strong spirit but weak will with one of a man of weak spirit but strong will in an attempt to achieve balance in each man. Roman Catholic mythology reports the third-century saints Damian and Cosmas as replacing the gangrenous leg of the Roman deacon Justinian with the leg of a recently deceased Ethiopian. Most accounts have the saints performing the transplant in the fourth century A.D., decades after their death; some accounts have them only instructing living surgeons who performed the procedure. More likely accounts exist in the area of skin transplantation. The first reasonable account is of the Indian surgeon Sushruta in the second century B.C., who used autografted skin transplantation in nose reconstruction rhinoplasty. Success or failure of these procedures is not well documented. Centuries later, the Italian surgeon Gaspare Tagliacozzi performed successful skin autografts; he also failed consistently with allografts, offering the first suggestion of rejection centuries before that mechanism could possibly be understood. He attributed it to the "force and power of individuality" in his 1596 work De Curtorum Chirurgia per Insitionem. Transplants #3 The first successful corneal allograft transplant was performed in 1837 in a gazelle model; the first successful human corneal transplant, a keratoplastic operation, was performed by Eduard Zirm in Austria in 1905. Pioneering work in the surgical technique of transplantation was made in the early 1900s by the French surgeon Alexis Carrel, with Charles Guthrie, with the transplantation of arteries or veins. Their skillful anastomosis operations, the new suturing techniques, laid the groundwork for later transplant surgery and won Carrel the 1912 Nobel Prize for Medicine or Physiology. From 1902 Carrel performed transplant experiments on dogs. Surgically successful in moving kidneys, hearts and spleens, he was one of the first to identify the problem of rejection, which remained insurmountable for decades. Major steps in skin transplantation occurred during WW I, notably in the work of Harold Gillies at Aldershot. Among his advances was the tubed pedicle graft, maintaining a flesh connection from the donor site until the graft established its own blood flow. Gillies' assistant, Archibald McIndoe, carried on the work into WW II as reconstructive surgery. In 1962 the first successful replantation surgery was performed - re-attaching a severed limb and restoring (limited) functioning and feeling. The first attempted human deceased-donor transplant was performed by the Ukrainian surgeon Yu Yu Voronoy in the 1930s; rejection resulted in failure. Joseph Murray performed the first successful transplant, a kidney transplant between identical twins, in 1954, successful because no immunosuppression was necessary in genetically identical twins. In the late 1940s Peter Medawar, working for the National Institute for Medical Research, improved the understanding of rejection. Identifying the immune reactions in 1951 Medawar suggested that immunosuppressive drugs could be used. Cortisone had been recently discovered and the more effective azathioprine was identified in 1959, but it was not until the discovery of cyclosporine in 1970 that transplant surgery found a sufficiently powerful immunosuppressive. (Brook & Nicholson, 2003) Transplants #4 Dr. Murray's success with the kidney led to attempts with other organs. There was a successful deceased-donor lung transplant into a lung cancer sufferer in June 1963 by James Hardy in Jackson, Mississippi. The patient survived for eighteen days before dying of kidney failure. Thomas Starzl of Denver attempted a liver transplant in the same year, but was not successful until 1967. The heart was a major prize for transplant surgeons. But, as well as rejection issues the heart deteriorates within minutes of death so any operation would have to be performed at great speed. The development of the heart-lung machine was also needed. Lung pioneer James Hardy attempted a human heart transplant in 1964, but a premature failure of the recipient's heart caught Hardy with no human donor, he used a chimpanzee heart which failed very quickly. The first success was achieved December 3rd 1967 by Christiaan Barnard in Cape Town, South Africa. Louis Washkansky, the recipient, survived for eighteen days amid what many saw as a distasteful publicity circus. The media interest prompted a spate of heart transplants. Over a hundred were performed in 1968-69, but almost all the patients died within sixty days. Barnard's second patient, Philip Blaiberg, lived for 19 months (Finn, 2000). As mentioned, it was the advent of cyclosporine that altered transplants from research surgery to life-saving treatment. In 1968 surgical pioneer Denton Cooley performed seventeen transplants including the first heart-lung transplant. Fourteen of his patients were dead within six months. By 1984 two-thirds of all heart transplant patients survived for five years or more. With organ transplants becoming commonplace, limited only by donors, surgeons moved onto more risky fields, multiple organ transplants on humans and whole-body transplant research on animals. On March 9th 1981 the first successful heart-lung transplant took place at Stanford University Hospital. The head surgeon, Bruce Reitz, credited the patient's recovery to cyclosporine-A. Transplants #5 History of successful transplants: 1954: First successful kidney transplant by Joseph Murray (Boston) 1966: First successful pancreas transplant by Richard Lillehei and William Kelly (Minnesota) 1967: First successful liver transplant by Thomas Starzl (Pittsburgh) 1967: First successful heart transplant by Christiaan Barnard (South Africa) 1981: First successful heart/lung transplant by Bruce Reitz (Stanford) 1983: First successful lung lobe transplant by Joel Cooper (Toronto) 1986: First successful double-lung transplant (Ann Harrison) by Joel Cooper (Toronto) 1987: First successful whole lung transplant by Joel Cooper (St. Louis) 1995: First successful laparoscopic live-donor nephrectomy by Lloyd Ratner and Louis Kavoussi (Baltimore) 1998: First successful live-donor partial pancreas transplant by David Sutherland (Minnesota) 1998: First successful hand transplant (France) 2005: First successful partial face transplant (France) Types of Transplant Autograft A transplant of tissue from one to oneself. Sometimes this is done with surplus tissue, or tissue that can regenerate, or tissues more desperately needed elsewhere (examples include skin grafts, vein extraction for CABG, etc.) Sometimes this is done to remove the tissue and then treat it or the person, before returning it (examples include stem-cell autograft and storing blood in advance of surgery.) Transplants #6 Allograft An allograft is a transplanted organ or tissue from a genetically non-identical member of the same species. Most human tissue and organ transplants are allografts. (Morris, 2004) Isograft A subset of allografts in which organs or tissues are transplanted from one to a genetically identical other (such as an identical twin). This is differentiated because it is anatomically identical to an allograft, but closer to autograft in terms of immunology. Xenograft A transplant of organs or tissue from one species to another. Examples include porcine heart valves, which are quite common and successful, a baboon-to-human heart (failed), and piscine-primate (fish to non-human primate) islet, the latter's research study directed for potential human use if successful (http://www.uncaged.co.uk/xeno.htm). Types of Donor In living donors, the donor remains alive and donates a renewable tissue, cell, or fluid (e.g. blood, skin); or donates an organ or part of an organ in which the remaining organ can regenerate or take on the workload of the rest of the organ (primarily single kidney donation, partial donation of liver, small bowel, or pancreas). Living related donors donate to family members or friends in whom they have an emotional investment. The risk of surgery is offset by the psychological benefit of not losing someone related to them, or not seeing them suffer the ill effects of waiting on a list. "Good Samaritan" or "altruistic" donation is living donation to someone not well-known to the donor. Some people choose to do this out of a need to donate. Some donate to the next person on the list; others use some method of choosing a recipient based on criteria important to them. Web sites are being developed that facilitate such donation. Transplants #7 Each year, impoverished people sell their kidneys to be used in transplants. Additionally, some authorities may mandate organ donation from unwilling donors such as prisoners (Cherry, 2005). The size and scope of these problems are not well-documented and is probably not known. The National Organ Transplant Act of 1984 made illegal any profit from organ donation in the United States; careful regulation by the OPTN has probably eliminated organ sales in the United States. Recent development of web sites such as MatchingDonors.com and personal advertisements for organs among listed candidates has raised the possibility of selling organs once again, as well as sparking significant ethical debates over directed donation, "good-Samaritan" donation, and the current U.S. organ allocation policy. Deceased donors are donors who have been declared brain-dead and whose organs are kept alive by ventilators or other mechanical mechanisms until they can be excised for transplantation. Apart from brain-stem dead donors, who have formed the majority of deceased donors for the last twenty years, there is increasing use of non-heart beating donors to increase the potential pool of donors as demand for transplants continues to grow. These organs have inferior outcomes to organs from a brain-dead donor; however given the scarcity of suitable organs and the number of people who die waiting, any potentially suitable organ must be considered. The overwhelming majority of deceased-donor organs in the United States are allocated by federal contract to the Organ Procurement and Transplantation Network (OPTN), held since it was created by the Organ Transplant Act of 1984 by the United Network for Organ Sharing. This allocates organs based on the method considered most fair by the scientific leadership in the field. For kidneys, for instance, that is by waiting time; for livers, it is by MELD (Model of End-Stage Liver Disease), an empirical score based on lab values indicative of the sickness of the patient from liver disease (Tuttle-Newhall et al., 2005). Transplants #8 Experiencing somewhat increased popularity, but still very rare, is directed or targeted donation, in which the family of a deceased donor (often honoring the wishes of the deceased) requests an organ be given to a specific person. If medically suitable, the allocation system is subverted, and the organ is given to that person. One of the more publicized cases of this type was the 1994 Chester and Patti Szuber transplant. This was the first time that a parent had received a heart donated by one of their own children. Although the decision to accept the heart from their recently killed child was not an easy decision, the Szuber family agreed that giving Patti's heart to her father would have been something that she would have wanted. (Taylor, 2005) As successful transplants and modern immunosuppression make transplants more common, the need for more organs has become critical. Advances in living-related donor transplants have made that increasingly common. Additionally, there is substantive research into xenotransplantation or transgenic organs; although these forms of transplant are not yet being used in humans, clinical trials involving the use of specific cell types have been conducted with promising results, such as using porcine islets of Langerhans to treat type one diabetes. However, there are still many problems that would need to be solved before they would be feasible options in patients requiring transplants (Martinez & Rosen, 2005). Recent Developments Steroid-free immunosuppression is being pioneered on large scale with use of Campath-1H (a humanized monoclonal antibody developed at Cambridge Pathology Laboratories) induction at Northwestern University in Chicago and the University of Wisconsin at Madison. This would avoid the side-effects of steroids. While short-term outcomes are outstanding, long-term outcomes are still unknown. Transplants #9 Calcineurin-Inhibitor-Free Immunosuppression is currently undergoing extensive trialing, the result of which would be to allow sufficient immunosuppression, without the nephrotoxicity associated with standard regimens that include calcineurin inhibitors. Positive results have yet to be demonstrated in any trial. Paired-donor exchange, led by work in the New England OPO region as well as at Johns Hopkins University and the Ohio OPOs may more efficiently allocate organs and lead to more transplants. References: Brook N.R., Nicholson M.L. Kidney transplantation from non heart-beating donors. Surgeon 1 (6): 311-22, 2003. Cherry, Mark (2005). Kidney for Sale By Owner. Georgetown University Press. Finn, R. (2000). Organ Transplants: Making the Most of Your Gift of Life. Sebastopol: O'Reilly & Associates. Martinez O.M., Rosen H.R. Basic concepts in transplant immunology. Liver Transplantation 11 (4): 370-81, 2005. Morris P.J. Transplantation - A Medical Miracle of the 20th Century. New England Journal of Medicine 2004; 351:26 78-80. Online . Accessed 12 Feb 2006. Taylor, James (2005). Stakes and Kidneys: Why markets in human body parts are morally imperative. Ashgate Press. Tuttle-Newhall J.E., Collins B.H., Desai D.M., Kuo P.C., Heneghan M.A. The current status of living donor liver transplantation. Current Problems of Surgery 42 (3): 144-83, 2005. Read More