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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [8]
An organ transplant is the moving 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). Organ transplants can be categorized as "life-saving", while tissue transplants are "life-enhancing".
Organs that can be transplanted are the heart, kidneys, liver, lungs, pancreas, and intestine. Tissues include bones, tendons, cornea, heart valves, veins, and skin.
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).
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. This however will result in the receiver of organs to take immunosuppressive drugs to prevent their body's antibodies rejecting and destroying the new organ. This dramatically effects the entire immune system making the body vulnerable to pathogens.
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.
A transplant of organs or tissue from one species to another. Xenotransplantion is often an extremely dangerous type of transplant. 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. See: xenotransplantation.
Sometimes, a deceased-donor organ (specifically the liver) may be divided between two recipients, especially an adult and a child.
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.[1]
Successful 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 Chi'ao 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 accounts report 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, decades after their deaths; some accounts have them only instructing living surgeons who performed the procedure.
The more likely accounts of early transplants deal with skin transplantation. The first reasonable account is of the Indian surgeon Sushruta in the second century BC, 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 World War 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 World War II as reconstructive surgery. In 1962 the first successful replantation surgery was performed - re-attaching a severed limb and restoring (limited) function 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.
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.
As the rising success rate of 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.
Recently, researchers have been looking into steroid-free immunosuppression. This type of immunosupporession 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.
In addition, 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.
An FDA approved immune function test from Cylex has shown effectiveness in minimizing the risk of infection and rejection in post-transplant patients[4] by enabling doctors to tailor immunosuppressant drug regimens. By keeping a patient's immune function within a certain window, doctors can adjust drug levels to prevent organ rejection while avoiding infection. Such information could help physicians reduce the use of immunosuppressive drugs, lowering drug therapy expenses while reducing the morbidity associated with liver biopsies, improve the daily life of transplant patients, and could prolong the life of the transplanted organ.
Many other new drugs are under development for transplantation.[5]
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). Deceased (formerly cadaveric) 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.
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.
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[9]. It was also proposed by Felix T. Rapport[10] 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[11]. 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[12]. A transplant exchange programs have been suggested as early as 1970: "A cooperative kidney typing and exchange program."[13]. The first pair exchange transplant in the U.S. was in 2001 at Johns Hopkins hospital[14].
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.
"Good Samaritan" or "altruistic" donation is giving a 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 [15].
In compensated donation, donors get money or other compensation in exchange for their organs.
In the United States, The National Organ Transplant Act of 1984 made organ sales illegal; regulation by the OPTN has probably eliminated organ sales. In the United Kingdom, the Human Tissue Act 1961 made organ sales illegal.
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.
Two books, Kidney for Sale By Owner by Mark Cherry (Georgetown University Press, 2005); and Stakes and Kidneys: Why markets in human body parts are morally imperative by James Stacey Taylor: (Ashgate Press, 2005); advocate using markets to increase the supply of organs available for transplantation.
In 2006, Iran became the only country to allow individuals to sell their kidneys, and the market price is US$2,000 to US$4,000. The Economist[16], and the Ayn Rand Institute[17] approve, and advocated a legal market elsewhere. They argued that if 0.06% of Americans between 19 and 65 were to sell one kidney, the national waiting list would disappear (which, the Economist wrote, happened in Iran). The Economist argued that donating kidneys is no more risky than surrogate motherhood, which can be done legally for pay in most countries.
Two European conferences in 2007 recommended against the sale of organs[8]. In Pakistan, 40 percent to 50 percent of the residents of some villages have only one kidney because they have sold the other for a transplant into a wealthy person, probably from another country, said Dr. Farhat Moazam of Pakistan, at a World Health Organization conference. Pakistani donors are offered $2,500 for a kidney but receive only about half of that because middlemen take so much[9]. In Chennai, southern India, poor fishermen and their families sold kidneys after their livelihoods were destroyed by the Indian Ocean tsunami two years ago. about 100 people, mostly women, sold their kidneys for 40,000-60,000 rupees ($900-$1,350)[10]. Thilakavathy Agatheesh, 30, who sold a kidney in May 2005 for 40,000 rupees said, "I used to earn some money selling fish but now the post-surgery stomach cramps prevent me from going to work." Most kidney sellers say that selling their kidney was a mistake[11].
This is organ donation that is done against the will of the donor. There have been various accusations that certain authorities are harvesting organs from those the authorities deem undesirable, such as prison populations. The World Medical Association stated that individuals in detention are not in the position to give free consent to donate their organs [12]. Illegal dissection of corpses is a form of body-snatching and may have taken place to obtain allografts. [18]
According to the Chinese Deputy Minister of Health, Huang Jiefu, [13] approximately 95% of all organs used for transplantation are from executed prisoners. The lack of public organ donation program in China is used as a justification for this practice. However reports in Chinese media raised concerns if executed criminals are the only source for organs used in transplants.
In October 2007, bowing to international pressure, the Chinese Medical Association agreed on a moratorium of commercial organ harvesting from condemned prisoners, but did not specify a deadline. China agreed to restrict transplantations from donors to their immediate relatives.[14][15]
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 or UNOS. UNOS does not handle donor cornea tissue. Corneal donor tissue is usually handled by various eye banks. 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. 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 the United States, there are various lengths of waiting due to the different availabilities of organs in different UNOS regions. 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.[16]
Access to organ transplantation is one reason for the growth of medical tourism.
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
Kidney
(pmp*) |
Liver
(pmp) |
Heart
(pmp) | |
USA | 52 | 19 | 8 |
Europe | 27 | 10 | 4 |
Turkey | 11 | 3.5 | 1 |
Asia | 3 | 0.3 | 0.03 |
Latin America | 13 | 1.6 | 0.5 |
The Spanish Transplant Organization led by Dr Rafael Matesanz claims the highest worldwide rate of 35.1[17] donors per million population in 2005 and 33.8[18] in 2006.
In addition to the citizens waiting for organ transplants in the US and other developed nations, there are long 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 does 10,000 transplants a year, and experts say that at least 90% of organs are taken from executed prisoners, without signed consent, since Chinese have taboos against donating organs of deceased family members.[19][20] Amnesty International has criticized this practice, and accused the Chinese of executing people without fair trials.[21] Close relative donations represent only 2% of transplants.
In Israel, there is a severe organ shortage due to religious objections by some rabbis, some of whom oppose all organ donations and others who advocate that a rabbi participate all decision making regarding a particular donor. This shortage has resulted in one-third of all heart transplants performed on Israelis being done in the Peoples' Republic of China; others are done in Europe. Dr. Jacob Lavee, head of the heart-transplant unit, Sheba Medical Center, Tel Aviv, believes that "transplant tourism" is unethical and Israeli insurers should not pay for it.[22]
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 to 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 [21]. Although these prices are still unattainable to poor, 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.
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.
In November 2007, the CDC reported the first-ever case of HIV and Hepatitis C being simultaneously transferred through an organ transplant. The donor was a 38-year-old gay male, considered "high-risk" by donation organizations, and his organs transmitted HIV and Hepatitis C to four organ recipients, none of whom had been told he was "high-risk." Experts say that the reason the diseases didn't show up on screening tests is probably because they were contracted within three weeks before the donor's death, so antibodies wouldn't have existed in high enough numbers to detect. The crisis has caused many to call for more sensitive screening tests, which could pick up anitbodies sooner. Currently, the screens cannot pick up on the small number of anitbodies produced in HIV infections within the last 90 days or Hepatitis C infections within the last 18-21 days before a donation is made.
Both developing and developed countries have forged various policies to try to increase the safety and availability of organ transplants to their citizens. Brazil, Italy, Poland and Spain have ruled all adults potential donors with the “opting out” policy, unless they attain cards specifying not to be. Iran is the only country in the world where it is lawful for one citizen to sell an organ to another for transplantation. 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.
Starting on May 1, 2007, doctors involved in commercial trade of organs will face fines and suspensions in China. Only a few certified hospitals will be allowed to perform organ transplants in order to curb illegal transplants. Harvesting organs without donor's consent was also deemed a crime.[23]
The existence and distribution of organ transplantation procedures in developing countries, while almost always 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 might be 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. There is also a powerful opposing view, that trade in organs, if properly and effectively regulated to ensure that the seller is fully informed of all the consequences of donation, is a mutually beneficial transaction between two consenting adults, and that prohibiting it would itself be a violation of Articles 3 and 29 of the Universal Declaration of Human Rights.
Even within developed countries there is concern that enthusiasm for increasing the supply of organs may trample on respect for the right to life. The question is made even more complicated by the fact that the "irreversibility" criterion for legal death cannot be adequately defined and can easily change with changing technology [24].
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