Transplant, Surgical

views updated

Transplant, surgical

A surgical transplant involves the removal of body parts, organs, or tissues from one person and implanting them into the body of another person. Although the idea of transplantation to cure disease dates back several centuries, transplantation has been considered a viable therapy for only a few decades. The relatively recent growth in transplantation stems primarily from expanding knowledge about the body's immune system and the ability to suppress its natural response to attack foreign tissue . Another advance has been the ability to preserve organs out of the body for longer periods of time until they can be transplanted. Although most transplants involve the transference of tissues or organs between two humans, research is rapidly advancing toward using animal organs for transplantation into humans. Unfortunately donor organs are scarce, which has led to ethical questions concerning what patients would most benefit from receiving a transplant. For example, some believe that alcoholics suffering from cirrhosis of the liver should not receive a liver transplant that they may eventually destroy again because of alcohol abuse.

The history of transplants

The idea of transplanting animal or human parts dates back for many centuries. The mythical Chimera, animals made up of different animal parts, was believed to be the work of the gods. Perhaps the most famous chimera is the Sphinx in Egypt, which has the head of a man and the body of a lion.

The first viable transplantation occurred in the sixteenth century when a technique was developed for replacing noses lost during battle or due to syphilis. The technique involved using skin from the upper inner arm and then grafting and shaping it onto the nose area. In the eighteenth century, Scottish surgeon John Hunter successfully transplanted a cock's claw to the animal's comb. Corneal transplants between two gazelles were also successfully performed in the latter part of the century.

During the nineteenth century, advances in surgery (like the development of antiseptic surgery to prevent infection and anesthetics to the lessen the pain ) increased the success rates of most surgical procedures. However, transplantation of organs languished as surgeons had no knowledge of how to "reconnect" the organ to the new body. It was not until techniques for vascular anastomosis, or the ability to reconnect blood vessels, was developed near the twentieth century that transplant surgery began to move ahead. The first long-lasting renal transplant was performed in Germany in 1902, when a dog kidney was transplanted into another dog by using tube stents (a slender tube used to support the structural integrity of the artery during an operation) and ligatures (wires used to tie off the blood vessels) to make the vascular connections.

The next major advance in transplantation would not occur for more than 40 years. Although renal and kidney transplants were attempted, the transplant recipient's body always rejected the organ. In 1944, Peter Medawar

showed that the rejection was due to the immune system, which attacked the foreign tissues or organs as foreign invaders, much the same way it works to ward of viruses and other disease. Although short-term successful renal transplants from donor to recipient were achieved in the early 1950s, these transplants usually were rejected by the patient's immune system. As a result, scientists began to focus on manipulating the immune system so it would accept the transplant.

By the early 1960s radiation and drugs were being used to suppress the immune system, in effect, shutting it down to prevent rejection. As a result, that decade saw the first bone marrow transplant, kidney transplant, and kidney/pancreas transplant. In 1967, Christiaan Barnard, a South African surgeon, received world wide notoriety for achieving the first successful heart transplant.

The next major advance came in 1978 with the development of the extremely effective antirejection (also called immunosuppressant) drug cyclosporin. Continued research on how to selectively control the immune system has grown to the point that transplantation is now a relatively common operation with more than 35,000 surgical transplants performed in medical centers throughout the world each year.

Transplantation and the immune system

Once surgeons acquired the ability to sever and reconnect arteries , the ability to control the immune system has been the primary concern in transplant surgery. The immune system is a complex biological network intricately linked to cells found in the blood. Many individuals share similar antigens, (small molecular proteins found on the surface of tissues that can stimulate an immune response,) and one of the first goals is to match antigens between organ donors and the recipients. The idea is to increase the likelihood that the patient's immune system will not attack because it recognizes a foreign antigen in the donor tissue.

Scientists have identified six primary types of antigens, called histocompatibility-locus antigens. Transplantation between people whose tissues and organs share all of these antigens generally is successful. For example, family members, particularly identical twins, usually have the same antigens. (In fact, the first successful kidney transplant was performed in 1955 when a young man received one of the kidneys of his twin brother.) As a result, relatives are often the source of donor tissues for patients who need kidneys and bone marrow transplants because one kidney or some bone marrow can be donated without causing harm to the donor.

As the number of matching antigens between donor and recipient decreases, the need to suppress the immune system with drugs becomes increasingly important. Unfortunately, many of these drugs have side effects and can suppress the immune system to the point that the patient becomes susceptible to other infections and diseases, which can cause the transplant to be rejected and lead to the patient's death. The advantage of cyclosporin is that it can be targeted somewhat to work in specific tissues and organs of the body, thus keeping the patient from becoming entirely immunocompromised, which can lead to death from any number of diseases and infections not directly related to the transplanted organ's functioning.

The immune responses

Although there are probably many types of immune responses, scientists have only identified a few associated with organ rejection. Hyperacute rejection occurs when the patient's body has already produced a large number of antibodies (proteins manufactured by the immune system to battle disease and infection) that immediately recognize the antigens from the donor organ. This type of rejection, which usually occurs because of incompatible blood types, is often instantaneous, sometimes causing the patient to die even before the surgery is completed.

Acute rejection usually takes several days to occur because the immune system's white blood cells called lymphocytes, which are integral to its functioning because they initiate the production of antibodies, are lying dormant until the patient receives the organ. As the immune system initiates a response to the antigens in the donor organ, specific immune cells in the blood begin to attack. Acute rejection is combated by the use of immunosuppressive drugs. The longer the patient survives without a immune response attacking the organ, the greater the chances for keeping the immune system under control and for long-term survival.

However, chronic rejection can occur several months or years later. Although this type of rejection is rare, when it occurs, the donor organ slowly deteriorates despite all efforts at immunosuppression. Scientists do not fully understand why the immune response may kick in months or years after an organ has been successfully transplanted.

Types of transplants

There are many types of transplant surgeries, from specific cell and tissue transplants to entire organs. Cornea tissue transplants for the eye were one of the first successful transplants routinely performed. A thin transparent membrane found in front of the eye, the cornea can cause blindness or clouded vision if it is scarred by injury or infection. The transplant procedure involves cutting out part of the damaged cornea and replacing it with cornea from a donated eye. Cornea transplants are relatively simple procedures because they require no reconnection of blood supplying arteries, thus removing the danger of an adverse immune response. These procedures are successful 90% of the time.

The transplantation of bone tissue was first performed in the 1890s and involved replacing diseased or injured bone with pieces of bone from donors. The modern procedure involves using donor bone as a type of scaffolding built over metal nails that immobilizes and connects the patient's remaining bone sections.

Unlike bones and the cornea, most other transplants are more difficult to achieve because they involve circulating blood and the immune system. Skin grafts for burn patients, for example, are often achieved using autografts (meaning from the self), in this case, segments of skin from other areas of the patient's own body. A flap graft begins with the partial separation of skin from its original site until adequate blood circulation is achieved, then it is completely severed and grafted onto the transplant site. This technique has a high success rate for curing scars or deformities. A full thickness autograft entails removing small pieces of all the layers of skin for transplantation; these types of skin grafts are particularly suitable for the face to achieve the least amount of scarring. A split-thickness autograft removes tissue-thin layers of skin that heal easily when transplanted. The one drawback to this type of skin graft is that the transplanted tissue usually appears reddish, which makes them more noticeable. Some skin grafts come from the skin of human donors or other animals, like pigs , and are used when large areas must be covered. Unlike the cosmetic goals of other grafts, these grafts are used primarily to stop the patient from losing fluids through the burned area and to prevent infection. Research is also underway to grow skin for grafting from a few donated skin cells.

Bone marrow transplants are often used to treat patients with blood diseases, like leukemia . The transplant procedure involves taking the tissue from the center of bones through a needle, a technique called bone marrow aspiration. The marrow may be an autograft taken from a patient while the disease is in remission and stored until they need the healthy blood cells. Bone marrow taken from other donors of the same species are called allografts. Unlike most immune responses in transplantation in which the donor's body rejects the transplant, in bone marrow allografts it is often the transplanted marrow that reacts against the host. This is known as graft-versus-host disease.

Organ transplants

By far, organ transplantation has received the most attention in the popular press. People who would be severely debilitated or die because of failing organs are the recipients of organ transplants. The primary organ transplants are heart, liver, pancreas, lung, and kidney transplants. Under certain circumstances, a patient may receive more than one transplant, the most common multiple transplant procedure is the dual heart/lung transplant.

Kidney transplants are designed to treat patients whose kidneys are failing, making them unable to process body waste products. These transplants have approached a 90% success rate. If the transplant fails, the patient may be put on dialysis until a new donor kidney can be found. Dialysis uses a machine to artificially remove blood from the body, clean the waste products by filtering the blood, and then return the blood to the body.

Other transplantable organs include the liver, the heart, and the lungs. With the development of immunosuppressive drugs, liver transplants have been growing in their success rates, although many patients still die because of organ rejection or from infections. Heart and lung transplants are often performed simultaneously since they share an interrelated vascular system and survival rates are higher for lung transplant patients when they also receive a new heart.

Organ transplants are delicate and complex procedures that require a well trained staff and usually take several hours or much longer to perform. As the surgeon removes the organ, sutures (wire or some other material) are used to close or tie off arteries and other connections to the organ. The new organ is then placed in position and the painstaking task of reconnecting the organ begins. Although the techniques, like vascular anastomosis, for making these connections are well established, they can be difficult procedures. For example, many of the connections to the liver lie underneath the liver and out of the surgeons' immediate view.

Organ preservation

Unlike tissues or cells, which can be maintained in functioning condition by placing them in life sustaining cultures (specially prepared nourishing fluids places in a dish or a bowl), organs that have been donated for transplantation require a more complex approach for their preservation. Perfusion is the process of using a pump or other mechanical device to circulate specific electrolyte solutions through the organ's vascular system.

These solutions may support the organ's metabolic (or chemical and physical) functioning. Some solutions are used, in effect, to freeze the organ. For instance, in cornea, skin, kidney, liver, heart, and pancreas transplants, some solutions are designed to cause hypothermia (subnormal body temperatures) in the organ. Organ tissues maintain their ability to function 10 or more times longer when kept at a temperature of 32–39°F (0–4°C), and kidneys have been preserved for more than 50 hours using this approach.

Donor organ and tissue networks

Most organs and tissues used for transplantation come from nationwide networks designed to provide quick access to organs when they become available. For example, the United Network for Organ Sharing (UNOS) provides access to organs and tissues throughout North America . The more than 70 organ procurement agencies in the United States are crucial to the success of transplants since they facilitate access to and transportation of organs and tissues that remain viable for transplanting for only a limited amount of time after they are removed from the donor's body.

The procurement begins when a hospital notifies a local organ bank that a seriously ill or dying patient (who is willing to donate his or her organ or whose family has given permission) is under their care. Organ bank staff will go to the hospital to assess the patient to determine whether their organs are healthy enough for transplantation. For example, most donor organs are harvested from people under age 65, and organs from someone who was an intravenous drug user may also be precluded from use since the organs may be infected with the AIDS disease or hepatitis . Once the patient is pronounced dead, a team of surgeons begin to remove the eyes, heart, liver, and kidneys. The next step is to determine who receives the organ. This is usually done on a geographic basis with those patients in the same general geographic area as the donor receiving first consideration to receive the organ.

However, since these organs are a precious commodity, a nationwide computer list of potential transplant recipients is also maintained. The National Organ Procurement and Transplantation Network was established by the National Organ Transplant Act of 1984. Potential donor recipients are prioritized to receive organs according to the length of time they have been on the UNOS list and on the compatibility to the donor organ in terms of blood types, body sizes, and genetic similarities.

The future of transplantation

Although many transplants, especially organ transplants, would not be needed if people took better care of their bodies by exercising and not smoking or drinking alcohol, the number of organ transplants performed each year is likely to continue to grow as long as donor organs can be obtained. In addition, new kinds of transplants are being pioneered.

One of the more exciting advances is the transplantation of tissues and cells from the central nervous system (CNS). These cells have been transplanted into the brains of people suffering from neurological (or nervous system) diseases, like Parkinson disease. CNS cells and tissues have the unique ability to regenerate, or grow back. In the case of Parkinson's patients, the substantia nigra area of the brain can no longer produce the neuro-transmitter (chemical messenger) dopamine , which usually results in the progressive loss of many motor skills to the point where patients can no longer walk or feed themselves. One of the surgical treatments under investigation is to transplant adrenal medullary tissue in hopes that the transplanted tissue will permanently regenerate new cells in the brain.

Artificial organs and xenografts

Due to the lack of available organs for transplantation, researchers are constantly experimenting with developing new sources of organs and tissues for transplantation. Artificial organs, for example, are being developed. These include electronic devices to make the heart beat and pumps implanted into the body that can supply necessary substances like insulin . Many of these devices are used as "bridges" to transplantation. In other words, they are temporary therapies to keep the patient alive while a suitable donor organ can be found. Artificial skin is also under development as are mechanical implants to help cure deafness.

Although current transplantation deals primarily in allografts, or transplantation within the same species, transplantation between species, called xenografts, is also a rapidly advancing area of study. The first partially successful xenografts were performed over a quarter of a century ago when surgeons transplanted organs from chimpanzees to humans.

But since the use of primates , which are closer to humans in nature, raises certain ethical questions, recent research has focused on non-primate animals. Pigs, for example, are relatively easy to breed and have large litters. They also share with humans many similar anatomical structures, like the heart, that function in similar ways in the body. Although pig organ transplants have, to date, been unsuccessful, advances in the development of immunosuppressive drugs have led some transplant scientists to think that success in this area can be achieved. Another advance in medical science, the ability to manipulate genes (hereditary components found in cells), has led to genetic engineering . This process involves manipulating and combining specific genetic components to achieve desirable traits or effects. In the case of pig organs, the goal is to make them more compatible to humans. However, the primary obstacle to xenografts remains rejection by the host's immune system. Even using immunosuppressant drugs does not guarantee the immune system will not eventually recognize and destroy the non-human organ.

Ethical issues surrounding transplantation

The primary ethical issue associated with transplanted is the extreme shortage of available donors. Nearly 20,000 people die in the United States each year who would have been suitable organ donors. But only about 3,000 of these organs are ever donated and harvested. Questions surrounding the limited supply of donor organs include who should get the donor. For example, should the organ go to someone who is poor and on welfare or someone who can afford to pay for the operation. There is also concern over buying organs from people before they have died or from their families after the person has died. Some organs, like kidneys, corneas, bones, and bone marrow could even be bought and removed before death since they would not fatally harm the donor if removed.

Another ethical issue surrounding transplantation is the high costs associated with obtaining and transplanting an organ. Some transplant procedures can cost more than $200,000. Since most people cannot afford such operations, the burden falls on society in the form of higher insurance premiums and government subsidies. Even after the surgery is over, it can cost tens of thousands of dollars each year to keep the person alive because of the high cost of antirejection drugs.

Despite the difficulty of obtaining organs, the high costs, and the many ethical concerns, transplantation will continue to thrive since it is the only hope for many terminally ill patients. Society's mandate is to develop ethical regulations to ensure that growing demands are met fairly and humanely.

Resources

books

Gutkind, L. Many Sleepless Nights. Pittsburgh: The University of Pittsburgh Press, 1990.

Keyes, C.D. New Harvest: Transplanting Body Parts and Reaping the Benefits. Clifton, NJ: Humana Press, 1991.

periodicals

Fox, Mark D. "The Transplantation Success Story." Journal of the American Medical Association (December 7, 1994): 1704.

"National Registry Creation Helps Assess Donor Risk." Transplant & Tissue Weekly (June 4, 2000).

Pace, Brian. "Suppressing the Immune System for Organ Transplants." JAMA 283 no. 18 (May 10, 2000): 2484.

Starzl, T.E. "The Early Days of Transplantation." Journal of the American Medical Association (December 7, 1994): 1705.

White, D., and J. Wallork. "Xenografting: Probability, Possibility, or Pipe Dream?" The Lancet (October 9, 1993): 879-880.

other

Current Science and Technology Center. "Robotic Surgery" [cited April 2003]. <http://www.mos.org/cst/article/1623/>.

David Petechuk

KEY TERMS

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Allografts: —Tissues and organs used for transplantation that come from donors of the same species.
Autografts: —Tissues and organs used for transplantation that come from the patients themselves.
Bone marrow: —A spongy tissue located in the hollow centers of certain bones, such as the skull and hip bones. Bone marrow is the site of blood cell generation.
Graft: —Bone, skin, or other tissue that is taken from one place on the body (or, in some cases, from another body), and then transplanted to another place where it begins to grow again.
Immunocompromised: —A condition in which the immune system suppressed so that it is not functioning completely.
Immunosuppressant: —Something used to reduce the immune system's ability to function, like certain drugs or radiation.
Lymphocytes: —White blood cells that play a role in the functioning of the immune system.
Vascular anastomosis: —A technique for reconnecting blood vessels.
Xenografts: —Tissues and organs used for transplantation that come from different animal species, like pigs or baboons.