Professor Arye Durst, M.D.
Head of Surgical Dept. B, Hadassah Hospital
and Professor of Surgery at the Medical School
An Overview on Organ Transplantation
First of all I would like to express my appreciation for the invitation to lecture here at this colloquium. I have attempted to prepare my material in such a way as to make it relatively easy for all those present to understand, keeping in mind that the audience is comprised of representatives of various professions and different branches of medicine.
Preconditions for Organ Transplantation
What are the conditions required for organ transplantation to be carried out?
Firstly, it must be surgically possible to disconnect the whole organ, and to transfer it from the body of one person to another in its entirety. Secondly, a critical factor (and the one that causes the most problems, even today) is rejection of the transplanted organ by the recipient. Thirdly, and no less important, is the location of a suitable organ, from a live or deceased donor, in a state that will allow it to be transplanted. I emphasize, "in a state that will allow it to be transplanted," for this is a point of much ethical debate and discussion. Organs obtained for transplant can be unsuitable for various reasons and can often harm the patient receiving the transplant.
The history of organ transplantation is lengthy. In the Middle Ages the possibility of organ transplants had already been considered, and evidence for it exists in the literature, particularly Christian texts which describe attempts by various monks to exchange organs. A famous illustration from the fifteenth century shows a patient undergoing “transplantation” of a leg in which decomposition has spread. But real organ transplantation began only in 1902, when Karl, a French surgeon working in the United States, demonstrated a technique for connecting blood vessels. This represented the first serious basis for transplants.
In 1936 a first attempt was made by a Russian surgeon, Varonoy, to transplant a kidney in a person who was about to die of kidney failure. The transplant held for thirty-six hours, and then the patient died. The concept of rejection was as yet unknown, as were other problems with which we are familiar today. It is important to note the breakthrough by Sir Peter Midber, who was the first to note the process of rejection (first and second set rejection), introducing the study and understanding of organ rejection.
In 1951 a French surgeon, Kuss, was the first to describe the place in the groin where the kidney is transplanted, and in 1954 David Hume (in Boston) performed the first transplant between identical twins, thus overcoming the problem of rejection, and the kidneys actually functioned. In 1955 it was once again Hume who transplanted kidneys from one person to another, carrying out nine such transplants which lasted a number of months. At that time steroids were already in use, but they caused numerous infections: the kidneys were rejected, and most of the patients died. Hume admitted that kidney transplants were still in their early stages, and supported the view that steroids are of no benefit in these transplants.
In 1959 Hamburge, from the Keer Hospital in Paris, applied total body radiation on patients in order to prevent rejection. Indeed, following his transplantation of kidney, his patients functioned very well as long as he kept them in total isolation. As soon as the patients were taken out of isolation, they contracted infections.
The real move towards clinical transplants took place in 1962, when Tom Sterszal began transplanting organs with the help of immunosuppressives, using a method similar to that which we use today. In 1966 the HLA system was discovered, assisting in the determination of organ compatibility, and in 1980 a new breakthrough was achieved: following studies by a Swiss researcher named Borel (from the Sandoz company) a new immunosuppressive substance preventing rejection was discovered - Cyclosporin A, which is still widely used.
Dangers of Organ Transplants
What dangers are associated with organ transplants? Firstly, there can be a technical failure with the connection of the actual organ. Whether it be obstruction of the veins or arteries or whether it involve connection of a kidney and ureter there are problems related to the surgical technique on one hand, and problems related to rejection of the transplanted organ on the other.
It is important to note that the organs which are regularly transplanted can be divided into two types. The first type consists of organs which have no mechanical replacement, such as the liver or the heart. In the event of the transplant failing, a repeat transplant is immediately required. This poses a very serious problem as there is no “dialysis” for a liver or heart. If someone undergoes a heart or liver transplant and the organ does not function, a new transplant is immediately required. Hence for every transplant of this type, planning is required as to where another heart or liver will be obtained for a repeat transplant. Transplantation of the second type of organ, for example kidneys, is easier, for if the new kidney is rejected, the possibility exists of returning to dialysis.
An additional problem in organ transplantation is the issue of the serious infections which attack patients receiving immunosuppressive treatment. The most important issue today, and one which is constantly debated, is the question of choosing organs which will be compatible and which will not be damaged as a result of being removed from the donor's body. There are cases of serious infection following transplants, a phenomenon which occurs principally in patients receiving immunosuppressive therapy. The infection is likely to attack specifically those patients who receive damaged organs when the attending surgeons and doctors use strong immunosuppressive treatment to suppress rejection and to combat the problem of the damaged organ.
Which organs are transplanted today? Clinical transplants of the following have been carried out for many years: kidneys (since 1962), liver (since 1963), heart and lungs (since 1968), and in recent years pancreas and intestines. I have not mentioned skin transplants or corneas since these do not require connection of blood vessels.
Kidney Transplants and Trade in Organs
I shall begin with kidney transplants, which are routinely carried out almost worldwide. The kidney may come from a living relative, a live donor who is not related, or from a dead donor.
Let us concentrate on the second category: a live donor who is not related. We have here a person who, from the point of view of the result of the transplant, is comparable to a dead donor since he is not related to the recipient of the organ. Owing to the huge shortage of organs, an organ trade exists in the world today and it is well known that kidneys may be bought from live donors not related to the patient. In India, for example, there is a lively trade in organs. People from all over the world travel to India in order to buy kidneys, and even undergo the transplants there. An organ trade also exists in Egypt.
There are well-founded rumors from South America concerning the kidnapping of children, particularly from the poorer sectors, supposedly with the purpose of taking them to resorts for treatment and support. These children disappear, and it is believed that their organs are removed and sold to people who are prepared to pay for them. With evidence of such trade going on worldwide, we are particularly careful in Israel to avoid reaching a similar situation. But we do treat Israeli patients who have undergone organ transplants in India, particularly kidney transplants, and who come back to us for continued treatment following the operation.
A review of the results of kidney transplants shows that there is 90% success during the first year for kidneys from live relatives, and 75% success during the first year from dead donors. Currently there are approximately one hundred transplants carried out each year in Israel, with the demand reaching around two hundred and fifty. It must be pointed out that the organ-demand curve in recent years has continually risen, while the supply of organs has remained constant since the source for organs remains more or less the same. The demand curve rises exponentially, and the discrepancy between demand and supply is continually growing, giving rise to various phenomena which are entirely unethical.
Following the transplant, an angiograph may be carried out in order to show the artery of the leg on one side and the artery of the kidney on the other. The artery of the kidney is attached to the artery of the leg, and the angiograph shows the kidney very clearly, with the different branches of the artery feeding it.
A kidney removed from the body too long after death may be damaged, and will not function following transplantation.
Let us turn our attention to liver transplants. The first was carried out in 1963 by Professor Tom Sterszal in Denver, Colorado. Thereafter he continued to transplant livers, together with very few others (one surgeon in South Africa, and Prof. Kilna in Cambridge, for instance). A number of problems were encountered, many of which have been solved with progress in surgical procedure. In a liver transplant there are several blood vessels which have to be connected, including the bile ducts. There are problems associated with the size-compatibility of the organ, particularly when an adult's liver is transplanted into a child.
In the event of definitive rejection of the organ which cannot be suppressed by immunosuppressive treatment, a new organ must immediately be transplanted, and any available source is approached for this purpose since without a liver the patient will die.
Owing to the shortage of organs from dead donors, attempts are being made to use live donors - a relative of the patient, most often parents to children - and to remove just a portion of the liver. In the case of dead donors, the liver is divided into two in order that one organ can be used for two patients, even though this is much
more complicated and presents a certain level of danger to the recipients.
Liver transplants are still carried out only in large medical centers, unlike kidney transplants which are much simpler and are executed routinely in most hospitals, even the smaller ones.
Cyclosporin A and Heart Transplants
Now for a completely different topic, that of Cyclosporin A. Until 1980, transplants, especially of kidneys, were a subject taken mostly for granted probably because the success rate for transplants involving heart, liver, pancreas and other organs was not all that high. The turning point occurred with the discovery of Cyclosporin A, a more potent immunosuppressive substance, which was put into use during 1980-1. Since then transplant results have improved dramatically, and even the curves for heart, liver, pancreas and other organs have become exponential.
Heart transplants began in 1968. This first was carried out in South Africa by Christiaan Barnard, although there are those who insist that the road was already paved for him by the laboratory work of Dr. Kantrowitz in California. In any event, following that operation, many attempted heart transplants, but owing to the continuing high rate of failure, enthusiasm waned considerably. Few centers made further attempts at heart transplants. This was, as mentioned, until the beginning of the 1980's, when Cyclosporin began to be used, and since then heart transplants have become "routine" and are carried out in many medical centers.
As mentioned, the problem with a heart transplant is that if there is rejection, we attempt to control it using immunosuppressives. But if this is unsuccessful, a repeat transplant needs to be carried out immediately.
The life expectancy today for one year after a heart transplant is about 50% - 60%.
A lung transplant is required in the case of chronic lung failure. The number of patients requiring such a procedure is constantly rising. The transplant is complicated, since the lung is very sensitive owing to various factors in the lung tissue, and hence the failure rate is high. There are only a few medical centers in the world where lung transplants are carried out. At first the practice was to transplant the heart and lung as one unit, but today sufficient experience exists for the transplant of a lung alone to be performed.
Pancreas transplants, too, are becoming increasingly common. The indication for a pancreas transplant is severe diabetes, especially juvenile diabetes, which affects the kidneys. (Hence some patients undergo transplant of kidney and pancreas.) The organ can come from a dead donor or from a live relative. Experiments have been carried out at the University of Minnesota, where a good procedure has been developed for transplantation of a portion of the pancreas from a living relative.
Some fairly serious technical problems continue to complicate the connection of the transplanted portion of the pancreas into the body of the recipient. The pancreas must also be connected to the bladder, into which its secretions must flow.
During the 1980's a revolution occurred in the area of pancreas transplants, as with other organs, and the number of transplants started rising exponentially, as did the life expectancy figures for the organs transplanted. This was due not only to the introduction of Cyclosporin, but also to the increased skill of the surgeons. With a growing number of such operations their experience in pancreas transplants increased, and the results improved accordingly.
The transplant of intestines is also an important development. There are many patients whose intestines cease to function as a result of obstruction in the arteries or other damage. Such patients live permanently on intravenous nutrition, as we investigate ways to transplant intestines. This operation is still very complicated, the results are not yet satisfactory. Consequently, there are only a small number of centers which perform the procedure. This procedure could be said to be still in its experimental stages.
Life Expectancy and Future Aspirations
With regard to the subject of life expectancy, at the end of the first year and after five years following the transplant we see the best results from kidney transplants from live relative donors. Even after five years the results in these patients are excellent. Results of kidney transplants from dead donors are also excellent after a year, and after five years the figure still remains higher than 75%. Liver transplants also yield excellent results today: five years following the operation the recipient's life-expectancy is the same as that of the transplanted organ. Except for rare cases where repeat transplants are required, the success rate stands above 50%.
The figures for heart transplants are even better. In recent years we have also seen a considerable improvement in transplants of heart and lungs, although the five-year prognosis is not as good as that of the first year. Here the results refer not to the patients but rather to the transplanted organs. In other words, the number of transplanted organs which continue to function after one year and after five years. All in all the results are excellent, signaling a positive forecast for future transplants.
One of the factors that will help to advance the success of transplants is an intensified fight against rejection using immunosuppressives. New substances are continuously being sought, and a long list of substances are being studied. 506FK, 61443RS, Refermicin and Cytocasein are among those being investigated today for their possible toxic effects, in order to ascertain whether they may be used in transplants for improved results.
Another important area, of course, is that of encouraging organ donation after death. The approach to this subject remains very cautious and slow, especially here in Israel. But even elsewhere, many countries face severe problems in this regard.
A further possibility for advancing transplants is gathering organs from animals, xenografting. Experiments have been carried out by Prof. Sterszal, including some involving hearts. Such experiments have yet to show signs of success, but there are those who attach considerable hope to such a solution, at least for some cases.
Today attempts are being made to increase the use of organs from live donors. Kidneys, liver, pancreas and large intestine are taken from live donors, relatives who are prepared to donate part of their organs to a loved one, most often parents to children, or between siblings.
I have attempted to summarize the current situation of organ transplants. We hope that in the future, with the further development of immunosuppressive substances, and with increased awareness in the area of organ donation, we shall continue to progress.