Eleven different organs or human body parts can be trans planted—blood vessels, bone, bone marrow or stem cells, cornea, heart, kidneys, liver, lung, middle ear, pancreas, and skin. Successful organ transplants have increased since the advent of the immunosuppressive drug cyclosporine (cyclosporin A).
Living donor transplants have attracted significant media attention. According to the United Network for Organ Sharing and the Health Resources and Services Administration of the U.S. Department of Health and Human Services, a living donor may donate a single kidney, segment of the liver, portion of the pancreas, or the lobe of a lung.
Bone
Bone matrix autografts or allografts are common. Transplantation of bone matrix is used after certain limb-sparing tumor resections and to correct congenital bone abnormalities. The major criteria for bone donation are a lack of infection, no history of IV drug use, and no history of prolonged steroid therapy or human growth hormone treatment. Bone can be easily harvested and frozen. Freezing not only preserves the bone but offers the additional benefit of concomitant diminution of histocompatibility antigens.
The major technical requirement for allograft transplantation is maintaining the periosteal sheath of the recipient bone to strip the donor bone completely of all periosteal elements. Transplantation of bone is an easy procedure. Processed bone lacks significant quantities of immunogenic substances; therefore, the need for immunosuppression is almost completely eliminated.
Cornea
Corneal transplants have been a common form of therapy for many years. The first human corneal eye bank was established in New York City in 1944. This type of transplantation has an extremely high success rate because of the ease in obtaining and storing viable corneas.
Corneal grafts are generally performed to replace nonhealing corneal ulcerations. Graft rejection is minimal because of the following: (1) the avascularity (lack of blood vessels) of this tissue; (2) a reasonably low concentration of class I trans plantation antigens; and (3) an essential absence of class II antigens. To prevent rejection, grafts are made as small as possible and are placed centrally to avoid contact with the highly vascularized limbic region. Eccentrically placed grafts are subject to a high rate of immunologic failure because vascularity will allow for lymphocyte contact. Immunosuppressive agents are not routinely administered.
Heart
The first successful allograft cardiac transplantation was per formed in 1967 by Dr. Christian Barnard in Cape Town, South Africa. The criteria for selecting the donor and recipient com bination for cardiac transplantation are essentially the same as those used for cadaveric renal transplantation. The most significant exclusion for cardiac transplantation, however, is the presence of an active infection. Cardiac transplant donors must have sustained irreversible brain death, but near-normal cardiac function must be maintained. Prophylactic antibiotics and cytotoxic drugs are given to the donor just before harvesting of the heart. Because of the urgency of most situations, most grafts are performed despite multiple HLA incompatibilities. Transplant recipients are maintained on immunosuppressive therapy, anticoagulants, and antithrombotic agents, as well as on a low-lipid diet.
Due to advances in immunosuppression following heart transplantation, there has been an increase in the rate of 1-year survival among recipients to almost 90%, but acute cellular rejection is still observed during the first year after transplantation and at lower rates after the first year. Endomyocardial biopsy remains the primary method for monitoring organ rejection for heart transplants. An alternative method for detecting the rejection of a heart transplant, aside from endo myocardial biopsy, is quantitative assessment of mononuclear cell gene expression in peripheral blood specimens. A study conducted with 602 patients to compare the two methods for monitoring patients for rejection has shown that the overall rate of survival does not differ significantly according to the method of monitoring.
Heart Valves
Xenogenic valve replacement is a standard modality for the treatment of aortic and mitral valve defects. Sources of these xenogenic valves are bovine (cow) or porcine (pig); the valves are chemically or physically modified to reduce antigenicity.
Patients receiving xenoallografts of heart valves are not immunosuppressed after surgery because only minimal or non existent graft rejection reactions take place in these modified valves.
Intestine
The first successful intestine transplantation was performed at the University of Toronto in 1986, although the patient only survived for 10 days. The first intestinal transplant recipient to survive for an extended amount of time was a 3½-year-old girl who lived for 192 days in 1987. Intestinal transplantation has improved over the past decade along with the number of intestinal transplantations performed in North America. In 2008, 185 intestinal transplantations were performed. With recent surgical advances, control of acute cellular rejection, and decrease in lethal infections, the rate of patient survival for the first year now exceeds 90%.
When the small intestine is transplanted alone it is referred to as an isolated intestinal transplant, but intestinal transplantations are usually performed with other organs with a composite allograft or with organs implanted separately from the same donor. Suitable intestinal organ donors have stable cardiopulmonary status and liver function. Potential organ trans plant recipients with systemic infection and malignancy are excluded.
After a donor is accepted, selective decontamination of the gastrointestinal tract is begun through a nasogastric tube using polyethylene glycol. Generally, the recipient of the transplant is a person suffering from short gut syndrome, in which the intestine had been resected for a variety of reasons.
Kidney
The first successful human kidney transplantation was per formed in 1954 between monozygotic twins. Induction of tolerance (see later) was attempted through the use of sublethal total body irradiation and allogeneic bone marrow transplantation, followed by renal transplantation. By 1960, renal transplantation was firmly established as a viable treatment for end-stage renal disease. Because of the continuing problems associated with total-body irradiation, chemical immunosuppression became the mode of treatment. The criteria for recipients of renal allografts generally exclude older patients and patients with a history of malignancy. In addition, patients with active sepsis or patients in whom chronic infection may be reactivated by treatment with steroids or immunosuppressive therapy are also not considered transplantation candidates.
Traditionally, kidney donations are not accepted from individuals older than 65 years because of a decreased likelihood of recipient survival. Donors are excluded if chronic renal disease or sepsis is present. Transplant donations are usually not accepted from those with generalized or systemic diseases such as diabetes mellitus, hypertension, and tuberculosis. Because of the severe shortage of donor kidneys, organs from donors older than 55 years or from donors with a history of hypertension or diabetes mellitus have been used with increasing frequency. Young trauma victims are the most desirable source of cadaveric organ transplants, including the kidneys. Cadaveric organs are not accepted from donors with a history of any malignancy other than that involving the central nervous system.
In addition to tissue compatibility, newer methods of harvesting kidneys have reduced the sensitizing effect related to passenger leukocytes against transplantation antigens borne on these cells. HLA-A and HLA-B loci matches have the best chance for long-term survival of the graft and recipient. The increased survival rate with HLA-A and HLA-B matches is determined not as much by class I compatibility as by the HLA-D region–related antigens associated with these regions. The strongest association between transplantation survival and tissue antigens is with the D region–related antigens (DR, MB, MT). Lewis antigens on the erythrocytes and H-Y antigens associated with X and Y chromosomes are among the other antigen systems that demonstrate a reasonably significant association with graft survival.
Liver
Potential liver transplant recipients must have no extrahepatic disease or infection present. The largest group of transplant recipients has been those with congenital biliary atresia. Patients with cirrhosis may also be good candidates. HLA crossmatching appears to increase the rate of graft survival, but the influence of tissue typing is somewhat unclear. Immunosuppressive regimens such as azathioprine and corticosteroids or cyclosporin A increase survival. Major complications of this procedure have been biliary tract fistulae or leaks, which have occurred in 30% to 50% of patients.
Lung Successful lung transplantation has been difficult to achieve because of technical, logistic, and immunologic problems. Technically, the lung donor and recipient must have essentially identical bronchial circumferences to obtain a good match. An additional technical problem is that the lungs are extremely sensitive to ischemic damage, and successful preservation after harvesting has been unsuccessful. Occasionally, lung-heart combination transplantation has been attempted. The combined procedure is less difficult than single-organ transplantation.
The lungs are susceptible to infection; sepsis is very common among potential donors. Severe rejection is common because of the high density of Ia-positive cells in the vasculature and the high concentration of passenger leukocytes trapped in the alveoli and blood vessels. Intensive immunosuppressive therapy is needed to maintain the graft. Many lung recipients have died from massive infection and sepsis.
Pancreas
Newer modes of transplantation include full pancreatic or isolated islet cell transplantation. Pancreatic grafts have been successful for only a short period because of a high rate of technical failure or irreversible rejection. Transplantation of small quantities of isolated islet cells into the retroperitoneal space, however, has demonstrated a reasonably good success rate.
Pancreatic islet transplants are risky and experimental, with about 50% of patients achieving insulin dependency after 1 year. From December 16, 1966 to December 31, 2008, more than 30,000 pancreas transplants were reported to the International Pancreas Transplant Registry (IPTR). There are three types of pancreatic transplantations that can be done: pancreas-kidney transplantation (SPK, the most common; 73%); pancreas trans plantation after kidney transplantation (PAK; 18%); and pancreas transplantation alone (PTA; 9%).
Skin
The development of nonimmunogenic skin replacement mate rials has lowered the demand for skin allografts. Skin allografts elicit the rejection phenomenon because skin has an extremely high density of MHC class I antigens. Therefore, sensitization and recognition of antigenic differences are likely, with resultant rejection of the grafted skin. If done, skin allografts are performed and supported with immunosuppressive therapy.
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