Organ transplantation

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).

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).

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.

Isograft
A subset of allografts in which organs or tissues are transplanted from a donor to a genetically identical recipient (such as an identical twin). Isografts are differentiated from other types of transplants because while they are anatomically identical to allografts, they are closer to autografts in terms of the recipient's immune response.

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 (i.e. pancreatic or insular tissue), the latter's research study directed for potential human use if successful.

Thoracic Organs

 * Heart (Deceased-donor only)
 * Lung (Deceased-donor and Living-Donor)
 * En bloc Heart/Lung (Deceased-donor only)

Abdominal Organs

 * Liver (Deceased-donor and Living-Donor)
 * Kidney (Deceased-donor and Living-Donor)
 * Pancreas (Deceased-donor and rarely Living-Donor)
 * Small bowel (Small Intestine) (Deceased-donor and Living-Donor)
 * Kidney-Pancreas (Sometimes simultaneous, sometimes in separate procedures) (Deceased-donor, Living-Donor, and combined deceased/living (e.g. kidney from living donor, pancreas from deceased donor))
 * Combined Liver-Kidney (Generally Deceased-donor only)
 * Combined Liver-Small Bowel (Deceased-donor only)

Other Organs

 * Hand (Deceased-donor only)
 * Cornea (Deceased-donor only)
 * Skin graft including Face transplant (almost always autograft)
 * Penis (Deceased-donor only)

Tissues, Cells, and Fluids

 * Islets of Langerhans (Pancreas Islet Cells) (Deceased-donor and Living-Donor)
 * Bone marrow/Adult stem cell (Living-Donor and Autograft)
 * Blood transfusion/Blood Parts Transfusion (Living-Donor and Autograft)
 * Blood vessels (Autograft and Deceased-Donor)
 * Heart valve (Deceased-Donor, Living-Donor and Xenograft[Pig])
 * Bone (Deceased-Donor, Living-Donor, and Autograft)
 * Skin (Deceased-Donor, Living-Donor, and Autograft)

Living
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
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.

Paired-Exchange
A "paired-exchange" is a technique of matching willing living donors to compatible recipients. For example a spouse may be more than willing to donate a kidney to their partner but cannot since there is not a biological match. Willing spouse's kidney is donated to a matching recipient who also has an incompatible but willing spouse. The second donor must match the first recipient to complete the pair exchange. Typically the surgeries are scheduled simultaneously in case one of the donors decides to back out and the couples are kept anonymous from each other until after the transplant.

Paired exchange programs were popularized in the New England Journal of Medicine article "Ethics of a paired-kidney-exchange program" in 1997 by L.F. Ross. It was also proposed by Felix T. Rapport in 1986 as part of his initial proposals for live-donor transplants "The case for a living emotionally related international kidney donor exchange registry" in Transplant Proceedings. A paired exchange is the simplest case of a much larger exchange registry program where willing donors are matched with any number of compatible recipients. A transplant exchange programs have been suggested as early as 1970: "A cooperative kidney typing and exchange program.". The first pair exchange transplant in the U.S. was in 2001 at John Hopkins hospital.

"Good Samaritan"
"Good Samaritan" or "altruistic" donation is giving 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. It has been featured in recent television journalism that over half of the members of the Jesus Christians, an Australian religious group, have donated kidneys in such a fashion.

Compensated / coerced
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. The size and scope of these events 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 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. Recently, two books have been published that advocate using markets to increase the supply of organs available for transplantation. The first is by Mark Cherry: Kidney for Sale By Owner (Georgetown University Press, 2005). The second is by James Stacey Taylor: Stakes and Kidneys: Why markets in human body parts are morally imperative (Ashgate Press, 2005).

Deceased (formerly cadaveric)
Deceased donors are donors who have been declared brain-dead and whose organs are kept viable 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 Donation after Cardiac Death - DCD- Donors (formerly 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.

In China a notable category of donors is that of executed prisoners, including members of Falun Gong, the practice which has been suppressed in China.

Allocated
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.

Directed
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. In other countries such as the UK, only medical factors and the position on the waiting list can affect who receives the organ. If this is not the desired person, it is noted that this puts them higher on the list.

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.

Body-snatching
Illegal dissection of corpses is a form of body-snatching and may have taken place to obtain allografts. 

Split Liver Transplants
Sometimes, a deceased-donor liver may be divided between two recipients, especially an adult and a child. This is uncommon, as the outcomes are worse for both patients than had they received the whole organ.

Domino Transplants
This operation is usually performed for cystic fibrosis as both lungs need to be replaced and it is a technically easier operation to replace the heart and lungs en bloc. As the recipient's native heart is usually healthy, this can then itself be transplanted into someone needing a heart transplant. That term is also used for a special form of liver transplant, in which the recipient suffers from familial amyloidotic polyneuropathy in which the liver (slowly) produces a protein that damages other organs; their liver can be transplanted into an older patient who is likely to die from other causes before a problem arises.

History
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.

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.

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.

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.

History of successful transplants:
 * 1905: First successful cornea transplant by Eduard Zim
 * 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 (Cape Town, South Africa)
 * 1970: First successful monkey head transplant by Robert White (Cleveland, U.S.A.)
 * 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)
 * 2006: First successful penis transplant (China)

As successful transplants and modern immunosuppression such as Tacrolimus (Prograf) in 1994, Mycophenolic acid (Cellcept or Myfortic) and Prednisone unsually used in conjunction with Ciclosporin make transplants more common and have improved the survival rate as these drugs are more effective in many patients than the previous generation of immunosuppression drugs. A new form of Ciclosporin is in clinical trials it is an Inhaled Cyclosporine and is being developed by Chiron Corp., 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.

Demographics
Despite efforts of international transplantation societies, it is not possible to access an accurate source on the number, rates and outcomes of all forms of transplantation globally; the best that we can achieve is estimations. This is not a sound basis for the future and thus one of the crucial strategies for the Global Alliance in Transplantation is to foster the collection and analysis of global data.

Transplantation of organs in different continents/regions year 2000 Source:
 * All numbers per million population

In addition to the citizens waiting for organ transplants in the US and other developed nations, there are astounding waiting lists in the rest of the world. More than 2 million people need organ transplants in China, 50,000 waiting in Latin America (90% of which are waiting for kidneys), as well as thousands more in the less documented continent of Africa. Donor bases vary in developing nations.

In Latin America the donor rate is 40-100 per million per year, similar to that of developed countries. However, in Uruguay, Cuba, and Chile, 90% of organ transplants came from cadaveric donors. Cadaveric donors represent 35% of donors in Saudi Arabia. There is continuous effort to increase the utilization of cadaveric donors in Asia, however the popularity of living, single kidney donors in India yields India a cadaveric donor prevalence of less than 1 pmp. China’s organ source statistics are still shrouded and controversial, but close relative donations are known to represent only 2% of transplants, 50% less than that in the United States.

Comparative Costs
One of the driving forces for illegal organ trafficking and “transplantation tourism” is the price differences for organs and transplant surgeries in different areas of the world. According the New England Journal of Medicine, a human kidney can be purchased in Manila for $1000- $2000, but in urban Latin America a kidney may cost more than $10,000. Kidneys in South Africa have sold for as high as $20,000. Price disparities based on donor race are a driving force of attractive organ sales in South Africa, as well as in other parts of the world. The Voluntary Health Association of India reports the prospect of such a small fortune has enticed about 2,000 impoverished Indians to sell a kidney every year. In China, a kidney transplant operation runs for around $70,000, liver for $160,000, and heart for $120,000. Although these prices are still unattainable to the poorer citizens of the world, especially those whose governments offer little or no financial health care support, compared to the fees of the United States, where a kidney transplant may demand $100,000, a liver $250,000, and a heart $860,000, Chinese prices have made China a major provider of organs and transplantation surgeries to other countries.

Transplantation Safety
Inadequate precaution, illegal organ trade, and higher presence of diseases such as HIV, hepatitis, and malaria present greater health safety dangers to both organ donors and recipients in developing countries. In Latin American countries that do not screen blood and organ donations for Chagas disease, the risk of infection may be as high as 20%. Indian doctors fear that for every HIV-positive potential kidney donor caught, another 5 may slip through screening. Compensation for donors also increases the risk of introducing diseased organs to recipients because these donors often yield from poorer populations unable to receive health care regularly and organ dealers may evade disease screening processes. The majority of such deals include one major payment and no follow up care for the donor. Some cases argue that there is a possibility of 1:18 to acquire HIV from such transplants.

Organ Transplant Legislation
Developing countries have forged various policies to try to increase the safety and availability of organ transplants to their citizens. Poland and Brazil have ruled all adults potential donors with the “opting out” policy, unless they attain cards specifying not to be. However, whilst potential recipients in developing countries may mirror their more developed counterparts in desperation, potential donors in developing countries do not. The Indian government has had difficulty tracking the flourishing organ black market in their country and have yet to officially condemn it. Other countries victimized by illegal organ trade have implemented legislative reactions. Moldova has made international adoption illegal in fear of organ traffickers. China has made selling of organs illegal as of July 2006 and claims that all prisoner organ donors have filed consent. However, doctors in other countries, such as the United Kingdom, have accused China of abusing its high capital punishment rate. Despite these efforts, illegal organ trafficking continues to thrive and can be attributed to corruption in healthcare systems, which has been traced as high up as the doctors themselves in China, Ukraine, and India, and the blind eye economically strained governments and health care programs must sometimes turn to organ trafficking. Some organ deals are also insulated: Japanese citizens living in China can take advantage of Japan’s strict organ transplant laws and sell Chinese organs to Japanese citizens at home.

Ethical Concerns
The existence and distribution of organ transplantation procedures in developing countries, while often beneficial to those receiving them, raise many ethical concerns. Both the source and method of obtaining the organ to transplant are major ethical issues to consider, as well as the notion of distributive justice. The World Health Organization argues that transplantations promote health, but the notion of “transplantation tourism” has the potential to violate human rights or exploit the poor, to have unintended health consequences, and to provide unequal access to services, all of which ultimately may cause harm. Regardless of the “gift of life”, in the context of developing countries, this is coercive. The practice of coercion could be considered exploitative of the poor population, violating basic human rights according to Articles 3 and 4 of the Universal Declaration of Human Rights.

Steroid-Free Immunosuppression
Steroid-free immunosuppression is being pioneered on large scale at Northwestern University in Chicago and other smaller institutions, while steroid minimization is being employed at the University of Wisconsin at Madison and other smaller institutions. This would avoid the side-effects of steroids. While short-term outcomes are outstanding, long-term outcomes are still unknown.

Calcineurin-Inhibitor-Free Immunosuppression
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
Paired-donor exchange, led by work in the New England Program for Kidney Exchange as well as at Johns Hopkins University and the Ohio OPOs may more efficiently allocate organs and lead to more transplants.

Notable people having had organ transplants

 * George Best (1946–2005); British football player and alcoholic (liver, 2002).
 * Aron Eisenberg (b. 1969); Actor Star Trek: Deep Space Nine (kidney)
 * Jimmy Little (b. 19XX); Australian country/rock artist (kidney, 2004).
 * Jonah Lomu (b. 1975); New Zealand rugby union player (Kidney, 2004).
 * Charles Perkins (1936–2000); Australian soccer player, Aboriginal activist and government minister; on his death was the world's longest surviving kidney transplant survivor (kidney, 1972).
 * George Lopez (b. 1961); Actor-Comedian received kidney transplant from his wife, Ann Lopez.
 * Robert Altman; Director of films, received a heart transplant mid-1990s (announced at the 2006 Academy Awards).
 * Jim Nabors; Actor-singer-comedian, best known for playing Gomer Pyle in the sitcom of the same name (liver).
 * David Crosby (b. 1941); Rock-folk singer (liver).
 * Mickey Mantle (1931-1995); Hall of Fame baseball player, notorious alcoholic (liver, 1995; Mantle died a couple of months later of liver cancer, which had spread to his new liver).
 * Larry Hagman (b. 1931); Actor, best known for playing J.R. Ewing on the soap opera Dallas (liver).
 * Gary Coleman (b. 1968); Actor who played Arnold on Diff'rent Strokes (two kidney transplants).
 * Shelley Fabares (b. 1944); Actress and singer who starred on the sitcom Coach (liver, 2000).
 * Alonzo Mourning (b. 1970); NBA basketball star (kidney, 2003; Mourning made history by returning to play in the NBA following his surgery).

Fictitious
 * In Season 5 of Curb Your Enthusiasm, Larry David is reluctant to be a kidney donor for comedian Richard Lewis.

Scientific/Academic Societies

 * American Society of Transplant Surgeons
 * American Society of Transplantation
 * International Society of Heart and Lung Transplantation
 * American Society for Histocompatibility and Immunogenetics
 * International Transplant Society
 * Chicago Transplant Ethics Consortium
 * International Liver Transplant Society
 * American Transplant Congress

Journalism

 * What is a Kidney Worth? (Christian Science Monitor)

Philanthropy/Support

 * Students for Organ Donation
 * International Association of Living Organ Donors
 * (U.S.) National Kidney Foundation
 * (U.S.) American Liver Foundation
 * Kidney Foundation of Canada
 * Second Wind Lung Transplant Association, Inc

Cellular memory

 * Cellular memory

United States Federally Contracted Services

 * United Network for Organ Sharing
 * Organ Transplant survival rates from the Scientific Registry of Transplant Recipients
 * TransWeb (partly outdated)

Websites critical of legislation prohibiting organ selling

 * Deadly Shortage - How the federal ban on profit incentive is killing those awaiting organ transplants
 * Organ Donations, Egalitarian Envy, and the High Cost of Busybodies - by Thomas Sowell [Capitalism Magazine]

Transplantation Trasplante Greffe (médecine) Trapianto d'organi השתלת איברים Transplantatie 移植 (医療) Transplantasjon Transplantasjon Przeszczepianie narządów Transplantação de órgãos Трансплантология Transplantácia Elinsiirto Transplantation