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Presidential Address at the 9th Congress of the Polish Transplantation Society, Krakow, May 16th, 2009
Presidential Address at the 9th Congress of the Polish Transplantation Society, Krakow, May 16th, 2009 ear Members of the Polish Transplantation Society. Ladies and Gentlemen: I would like to extend my appreciation and thanks for allowing me to be the President of our Society for the last 2 years. The nomination was of great significance to me, especially that in the same period I retired from the chairmanship of the Department of General and Transplantation Surgery of the Medical University of Warsaw, which ended my long lasting involvement in the professional activity in the field of clinical organ transplantation. In most scientific societies the Presidential Addresses are usually considered necessary presentations, which are listened to politely, not being, however, an important part of the meeting. The possibility to prepare this presidential address has allowed me to deliver a reflection regarding my professional life, as well as recent developments in the field of organ transplantation in Poland. Professor Leszek Kułakowski, a famous Polish philosopher, in his last interview said “a man is not getting old as long as he has a passion or hobby.” During my lifetime I did not ski or sail (as a number of associates used to do). My passion was the life of the academic surgeon, which included not only performing surgery (a number of my associates were technically better surgeons than me), but also taking care of the seriously ill surgical patients, facilitation of the scientific promotion of my associates, developing my department and teaching. In addition, for a number of years I was fighting with the Health Care providers in Poland for proper understanding of the place of transplantation medicine in the health care system. So I still have something to do and therefore feel young. My talk will include three aspects. The past, where I shall mention my Mentors, Jan Nielubowicz, a surgeon, and Tadeusz Orłowski, a nephrologist, who made a great impact on my professional life; the present problems of organ transplantation medicine in Poland; and finally, I would like to briefly mention a few aspects of the future of organ transplantation. Foreseeing of the future is difficult. The future developments can be fascinating or terrifying, but one has to be prepared to face them. In January 1966, Jan Nielubowicz performed the first successful deceased donor kidney transplantation. The patient, a young student of the nursing school suffering from chronic renal failure, was prepared for the surgery by a nephrologist, Tadeusz Orlowski, who also took care of the patient after transplantation. The intellectual impact of
D
Professor Orlowski (who died at the age of ninety in September 2008) on the development of organ transplantation in Poland cannot be overestimated. Preparatory steps to the human kidney transplantation taken by Jan Nielubowicz and his associates in the Surgical Research Laboratory of the Polish Academy of Sciences had stirred emotions, recognition, but also a number of critical comments. One of the then-eminent Polish immunologists said “What is he expecting? This cannot end with a success.” Kidney transplantation performed in 1966 in Warsaw had been preceeded by only 600 such operations in the whole world. Not much was known at that time about pathologic mechanisms of rejection; immunosuppression consisted of azathioprine and steroids. Posttransplant care of the recipient had nothing in common with evidencebased medicine, which at that time did not exist. The Surgical Research Laboratory alike the 1st Surgical Department as well as the 1st Medical Department of the Medical School (called “cadet corps” and “first in best dressed”, respectively by unfriendly and jealous colleagues from other medical schools). do not exist any more. However, special words of recognition should be addressed to Jan Nielubowicz and Tadeusz Orlowski, the real Pioneers of transplantation medicine in Poland. The results of the preliminary kidney transplantations performed in Warsaw (and soon after in Wroclaw, Krakow and Katowice) were similar to those obtained in other world centers. Approximately 10% of patients survived for over 1 year after transplantation. In the next two years, nine such transplants were performed in the Surgical Department of Warsaw Medical School. Three of these patients died soon after surgery, but six of them survived for over two years. The first kidney transplantations from a living donor were done in 1968 by Józef Gasin ´ski in Bytom and Wiktor Bross in Wroclaw. In 1969, two years after Christiaan Barnard, Jan Moll performed the first heart transplantation in Poland, although the patient survived only a few hours and died due to pulmonary hypertension. At the time it seemed to us that this method of treatment would soon be well developed in Poland. However, that was not the case. There were no legal regulations. Kidney recovery from a deceased donor was considered to be the beginning of a postmortem examination, which at that time was obligatory for all patients who died in hospitals. The diagnosis of brain death was not
© 2009 Published by Elsevier Inc. 360 Park Avenue South, New York, NY 10010-1710
0041-1345/09/$–see front matter doi:10.1016/j.transproceed.2009.09.047
Transplantation Proceedings, 41, 2949 –2951 (2009)
2949
2950
possible, so kidneys were always recovered after cardiac arrest. Public attitude toward organ recovery from deceased donors was negative and the attitude of the medical profession was neutral. In such situations, the development of kidney transplantation program was slow. Transplantation research at that time was performed in a few centers. It is understandable that I am describing what was going on in Warsaw in the 1st Surgical Department of the Medical School and in the Surgical Research Laboratory, both directed by Jan Nielubowicz. A number of physicians who are presently involved in clinical transplantation worked at that time in the Surgical Research Laboratory of the Polish Academy of Sciences. Our group consisted of young trainee surgeons, immunologists, pathologists, biochemists, anesthesiologists and medical students. It was a time of active cooperation among a group of friends. In the mornings we would perform our clinical duties and in the afternoons (and often nights) we would spend our time in the laboratory doing experiments on mice, rats, dogs and pigs. Despite problems, resulting from socio-economic conditions, which hampered access to the world scientific literature and international congresses, we were trying to follow the new developments in the field of transplantation. Studies were performed on the mechanisms of rejection of kidney, liver, spleen and intestinal grafts in experimental animals. As early as 1967, we began to raise anti-lymphocyte sera in horses, rabbits and goats for experimental use in animals and, in 1970, for humans. In 1972, using a rabbit anti-rat serum raised with the use of “sensitized” lymphocytes from inbred animals, we observed very marked prolongation (over 100 days) in a heterotopic heart transplant model. These results were presented at one of the European Surgical Research Society Congresses. It is understandable, for the reasons mentioned above, that this achievement went unnoticed in the world scientific literature. As early as the 1969/1970 period, Waldemar Olszewski and Jan Nielubowicz, together with a group of coworkers, performed studies on extracorporeal perfusion of pig livers for patients with acute hepatic coma. These were one of the first xenogeneic studies. In experimental studies they documented the role of natural antibodies and complement to mediate the endothelial injury. The mechanisms of ischemic injury of kidney and methods of preservation have been important parts of our interest. In the mid-1980s we showed experimentally that administration of lidocaine hydrochloride to the donor before organ recovery ameliorated the results of warm ischemia, results that were later confirmed in human deceased donor kidney transplantation. The results of our studies at that time were published mainly in the Polish scientific literature, since access to world journals was for us rather difficult. Our studies were not known among western transplantation professionals – no surprises here. Our contacts with Dr Nicholas L. Tilney, which started in 1975, were helpful to promote our studies. From 1984 to 2000, six Polish scientists completed fellow-
ROWIN´SKI
ships in the Surgical Research Laboratory directed by Nick Tilney. We owe him great appreciation and thanks for this help and attitude. In the subsequent years, clinical studies in the Department of General and Transplantation Surgery of the Medical University of Warsaw, which I was chairing from 1982 until 2006, reflected our continued interest in ischemic injury to and preservation of deceased donor organs which were recovered for transplantation. A retrospective analysis of over 250 kidney transplants confirmed the value of lidocaine hydrochloride administration to the donor (before recovery) and continuous dopamine infusions in the recipient to decrease the extent of ischemic damage, as evidenced by a reduced incidence of delayed graft function. As early as 1994, we started in the prospective study to use hypothermic machine perfusion for storage of kidneys recovered from unstable donors. Implementation of this preservation method ameliorated ischemic damage. A retrospective analysis showed that the long term function of kidneys stored with the use of machine perfusion was better than that of organs that were cold stored. Studies in brain dead donors showed upregulation of proinflammatory cytokines in donor sera and gene expressions in kidneys after revascularization that correlated with delayed graft function and mid-term renal function. At the beginning of the 1980s kidney transplantation programs functioned in a few centers – Wroclaw, Krakow, Katowice and Szczecin. The first successful heart transplantation performed by Zbigniew Religa (Zabrze) in 1986 was a real breakthrough. It gave real impetus for the development of transplantation of other organs. In 1987, Zielinski in Szczecin and Szmidt in Warsaw performed the first pancreatic transplantations. Liver, lung and pancreas transplantation program were started at the beginning of the 1990s. In 1993, a small group of transplant physicians and surgeons founded The Polish Transplantation Society. The activity of Mietek Lao, a nephrologist and the director of the Transplantation Institute at The Medical University of Warsaw, should be acknowledged. In 1996, The Polish Parliament enacted the Directive on the Recovery and Transplantation of Cells, Tissues and Organs. This act regulated all legal and medical aspects of organ transplantation. Organs from deceased (brain dead) donors could be recovered if the person during his/her lifetime had not objected to this (the so called “presumed consent”) The directive also established the National Registry of Objections. The brain death had to be recognized by three physicians who were not taking part in the recovery or transplantation processes. The Act legalized transplantation of kidneys and other organs from live donors who were genetically or emotionally related (excluding minors). It also allowed kidney transplantation from unrelated persons who were closely related to the recipient, In later instances, however, the decision was examined by the Ethical Committee of the National Transplantation Council and the court. The directive strongly prohibited any form of payment or trade in organ transplantation. Within the next few
PRESIDENTIAL ADDRESS
months the directive will be updated, due to the necessity to implement the European Directive on Tissue and Cell Transplantation. In addition, organs can be recovered after a cardiac arrest. From 1966 until the end of 2008, over 15 000 kidneys, more than 1600 livers and over 1500 hearts had been transplanted in 24 centers in the whole country. The results of these procedures were similar to those obtained in the USA and European countries. However, the number of transplantations was much lower than the need. In addition, for reasons that remain unclear, the numbers of living donor kidney transplantations are extremely low (1.5% of all transplants per year). In the last 2 years we have observed increasing activity of new programs. Lung transplantations are being performed in the Silesian Heart Center, two cases of upper limb transplantation, in the Plastic and Reconstructive Surgery Center in Trzebnica (near Wroclaw) and the first two cases of pancreatic islet transplantations in Warsaw. During my term, a number of new activities have been undertaken by the Board of our Society. A Polish – German workshop was held in Wroclaw, dedicated to Ischemia – Reperfusion Injury. It is our hope that such workshops will be held annually in Germany or in Poland. The Annals of Transplantation, a Quarterly Journal of our Society has become included in the Philadelphia List of Citations. The Polish Union of Transplantation Medicine, an NGO founded by the members of our Society and the Polish Nephrological Society has been actively promoting the significance of transplantation medicine in the health care system. We have founded the Postgraduate School for Transplant Coordinators; its lectures and seminars are held in the Medical University of Warsaw. Each course lasts 3 months. So far, 120 physicians and experienced nurses have completed the training. In addition, a number of educational activities have been carried out. Members and Guests, Excellent results of organ transplantation have caused waiting lists to grow. The lack of organs has become an important problem in the whole world. There is no transplantation without organ procurement. But also no transplantation can be performed without patients. A multidisciplinary approach is important for the development and proper function of a transplant program. Surgeons used to consider themselves to be the core group of the team. Obviously, this is true, but we should remember that the whole process of transplantation would not be possible without the participation of physicians who prepare the patients for surgery and perform long term care, or without anesthesiologists, transplant coordinators and specialized nurses. Such is the multidisciplinary character of our Society.
2951
So, what awaits us? In near future, the lack of organs will inevitably lead to a large-scale increase in the use of living donors. This is an excellent solution, since the number of waiting recipients-to-be is so high that we are using more and more often the so called “not ideal”, “complex” or “marginal donor”. Are we not crossing the ethical principle primum non nocere? Are we modifying the ethical code to suit our needs? Do we have the right to do so? In the future, more altruistic unrelated donors will be used. Is this not hypocrisy, accepting such a situation, remembering at the same time that no form of payment is allowed? Finally, maybe such donors should receive some sort of compensation? But what are the long term prospects for transplantation medicine? In 1932, Aldous Huxley in his science-fiction book called “Brave New World” predicted that, using the fictitious “Bokanowski’s process”, it should be possible to create (by cloning) 100 human-like robots from one egg. Let us hope that this not be the case, despite the fact that the regenerative medicine can partially replace organ transplantation. Whether we like it or not, stem cells will be used for the treatment of several diseases. Will embryonic stem cells have to be used? Ethical problems may become solved by the use of adult somatic cells and the process of nuclear reprogramming. First experimental trials are underway in patients with spinal cord injury or Parkinson’s disease. Achievements of regenerative medicine are allowing us, even now, to prepare two- and three-dimensional structures containing various cell types which are seeded into a biocompatible skeleton. Ex vivo formation of organs may become possible in this way. Finally, organogenesis may become real. Such considerations in certain aspects may seem to be unethical. However, I would like to remind everyone that the famous beekeeper Monsignore Dzierzon, at the end of 19th century discovered that parthenogenesis exists in bees. He was excommunicated, only to be rehabilitated after 100 years. So I would like to end and to leave you with this quote from Einstein: “Progress requires an imagination and knowledge. Imagination without knowledge creates beauty, Knowledge without imagination leads to perfection, [. . .] But real product has to be tested by the time.”
I would like to extend my appreciation to the Board Members with whom I have been working for the last two years. Also, I would like to wish the newly elected President, Professor Magda Durlik, every possible success with her new task. Wojciech Rowin ´ ski
D
Professor Orlowski (who died at the age of ninety in September 2008) on the development of organ transplantation in Poland cannot be overestimated. Preparatory steps to the human kidney transplantation taken by Jan Nielubowicz and his associates in the Surgical Research Laboratory of the Polish Academy of Sciences had stirred emotions, recognition, but also a number of critical comments. One of the then-eminent Polish immunologists said “What is he expecting? This cannot end with a success.” Kidney transplantation performed in 1966 in Warsaw had been preceeded by only 600 such operations in the whole world. Not much was known at that time about pathologic mechanisms of rejection; immunosuppression consisted of azathioprine and steroids. Posttransplant care of the recipient had nothing in common with evidencebased medicine, which at that time did not exist. The Surgical Research Laboratory alike the 1st Surgical Department as well as the 1st Medical Department of the Medical School (called “cadet corps” and “first in best dressed”, respectively by unfriendly and jealous colleagues from other medical schools). do not exist any more. However, special words of recognition should be addressed to Jan Nielubowicz and Tadeusz Orlowski, the real Pioneers of transplantation medicine in Poland. The results of the preliminary kidney transplantations performed in Warsaw (and soon after in Wroclaw, Krakow and Katowice) were similar to those obtained in other world centers. Approximately 10% of patients survived for over 1 year after transplantation. In the next two years, nine such transplants were performed in the Surgical Department of Warsaw Medical School. Three of these patients died soon after surgery, but six of them survived for over two years. The first kidney transplantations from a living donor were done in 1968 by Józef Gasin ´ski in Bytom and Wiktor Bross in Wroclaw. In 1969, two years after Christiaan Barnard, Jan Moll performed the first heart transplantation in Poland, although the patient survived only a few hours and died due to pulmonary hypertension. At the time it seemed to us that this method of treatment would soon be well developed in Poland. However, that was not the case. There were no legal regulations. Kidney recovery from a deceased donor was considered to be the beginning of a postmortem examination, which at that time was obligatory for all patients who died in hospitals. The diagnosis of brain death was not
© 2009 Published by Elsevier Inc. 360 Park Avenue South, New York, NY 10010-1710
0041-1345/09/$–see front matter doi:10.1016/j.transproceed.2009.09.047
Transplantation Proceedings, 41, 2949 –2951 (2009)
2949
2950
possible, so kidneys were always recovered after cardiac arrest. Public attitude toward organ recovery from deceased donors was negative and the attitude of the medical profession was neutral. In such situations, the development of kidney transplantation program was slow. Transplantation research at that time was performed in a few centers. It is understandable that I am describing what was going on in Warsaw in the 1st Surgical Department of the Medical School and in the Surgical Research Laboratory, both directed by Jan Nielubowicz. A number of physicians who are presently involved in clinical transplantation worked at that time in the Surgical Research Laboratory of the Polish Academy of Sciences. Our group consisted of young trainee surgeons, immunologists, pathologists, biochemists, anesthesiologists and medical students. It was a time of active cooperation among a group of friends. In the mornings we would perform our clinical duties and in the afternoons (and often nights) we would spend our time in the laboratory doing experiments on mice, rats, dogs and pigs. Despite problems, resulting from socio-economic conditions, which hampered access to the world scientific literature and international congresses, we were trying to follow the new developments in the field of transplantation. Studies were performed on the mechanisms of rejection of kidney, liver, spleen and intestinal grafts in experimental animals. As early as 1967, we began to raise anti-lymphocyte sera in horses, rabbits and goats for experimental use in animals and, in 1970, for humans. In 1972, using a rabbit anti-rat serum raised with the use of “sensitized” lymphocytes from inbred animals, we observed very marked prolongation (over 100 days) in a heterotopic heart transplant model. These results were presented at one of the European Surgical Research Society Congresses. It is understandable, for the reasons mentioned above, that this achievement went unnoticed in the world scientific literature. As early as the 1969/1970 period, Waldemar Olszewski and Jan Nielubowicz, together with a group of coworkers, performed studies on extracorporeal perfusion of pig livers for patients with acute hepatic coma. These were one of the first xenogeneic studies. In experimental studies they documented the role of natural antibodies and complement to mediate the endothelial injury. The mechanisms of ischemic injury of kidney and methods of preservation have been important parts of our interest. In the mid-1980s we showed experimentally that administration of lidocaine hydrochloride to the donor before organ recovery ameliorated the results of warm ischemia, results that were later confirmed in human deceased donor kidney transplantation. The results of our studies at that time were published mainly in the Polish scientific literature, since access to world journals was for us rather difficult. Our studies were not known among western transplantation professionals – no surprises here. Our contacts with Dr Nicholas L. Tilney, which started in 1975, were helpful to promote our studies. From 1984 to 2000, six Polish scientists completed fellow-
ROWIN´SKI
ships in the Surgical Research Laboratory directed by Nick Tilney. We owe him great appreciation and thanks for this help and attitude. In the subsequent years, clinical studies in the Department of General and Transplantation Surgery of the Medical University of Warsaw, which I was chairing from 1982 until 2006, reflected our continued interest in ischemic injury to and preservation of deceased donor organs which were recovered for transplantation. A retrospective analysis of over 250 kidney transplants confirmed the value of lidocaine hydrochloride administration to the donor (before recovery) and continuous dopamine infusions in the recipient to decrease the extent of ischemic damage, as evidenced by a reduced incidence of delayed graft function. As early as 1994, we started in the prospective study to use hypothermic machine perfusion for storage of kidneys recovered from unstable donors. Implementation of this preservation method ameliorated ischemic damage. A retrospective analysis showed that the long term function of kidneys stored with the use of machine perfusion was better than that of organs that were cold stored. Studies in brain dead donors showed upregulation of proinflammatory cytokines in donor sera and gene expressions in kidneys after revascularization that correlated with delayed graft function and mid-term renal function. At the beginning of the 1980s kidney transplantation programs functioned in a few centers – Wroclaw, Krakow, Katowice and Szczecin. The first successful heart transplantation performed by Zbigniew Religa (Zabrze) in 1986 was a real breakthrough. It gave real impetus for the development of transplantation of other organs. In 1987, Zielinski in Szczecin and Szmidt in Warsaw performed the first pancreatic transplantations. Liver, lung and pancreas transplantation program were started at the beginning of the 1990s. In 1993, a small group of transplant physicians and surgeons founded The Polish Transplantation Society. The activity of Mietek Lao, a nephrologist and the director of the Transplantation Institute at The Medical University of Warsaw, should be acknowledged. In 1996, The Polish Parliament enacted the Directive on the Recovery and Transplantation of Cells, Tissues and Organs. This act regulated all legal and medical aspects of organ transplantation. Organs from deceased (brain dead) donors could be recovered if the person during his/her lifetime had not objected to this (the so called “presumed consent”) The directive also established the National Registry of Objections. The brain death had to be recognized by three physicians who were not taking part in the recovery or transplantation processes. The Act legalized transplantation of kidneys and other organs from live donors who were genetically or emotionally related (excluding minors). It also allowed kidney transplantation from unrelated persons who were closely related to the recipient, In later instances, however, the decision was examined by the Ethical Committee of the National Transplantation Council and the court. The directive strongly prohibited any form of payment or trade in organ transplantation. Within the next few
PRESIDENTIAL ADDRESS
months the directive will be updated, due to the necessity to implement the European Directive on Tissue and Cell Transplantation. In addition, organs can be recovered after a cardiac arrest. From 1966 until the end of 2008, over 15 000 kidneys, more than 1600 livers and over 1500 hearts had been transplanted in 24 centers in the whole country. The results of these procedures were similar to those obtained in the USA and European countries. However, the number of transplantations was much lower than the need. In addition, for reasons that remain unclear, the numbers of living donor kidney transplantations are extremely low (1.5% of all transplants per year). In the last 2 years we have observed increasing activity of new programs. Lung transplantations are being performed in the Silesian Heart Center, two cases of upper limb transplantation, in the Plastic and Reconstructive Surgery Center in Trzebnica (near Wroclaw) and the first two cases of pancreatic islet transplantations in Warsaw. During my term, a number of new activities have been undertaken by the Board of our Society. A Polish – German workshop was held in Wroclaw, dedicated to Ischemia – Reperfusion Injury. It is our hope that such workshops will be held annually in Germany or in Poland. The Annals of Transplantation, a Quarterly Journal of our Society has become included in the Philadelphia List of Citations. The Polish Union of Transplantation Medicine, an NGO founded by the members of our Society and the Polish Nephrological Society has been actively promoting the significance of transplantation medicine in the health care system. We have founded the Postgraduate School for Transplant Coordinators; its lectures and seminars are held in the Medical University of Warsaw. Each course lasts 3 months. So far, 120 physicians and experienced nurses have completed the training. In addition, a number of educational activities have been carried out. Members and Guests, Excellent results of organ transplantation have caused waiting lists to grow. The lack of organs has become an important problem in the whole world. There is no transplantation without organ procurement. But also no transplantation can be performed without patients. A multidisciplinary approach is important for the development and proper function of a transplant program. Surgeons used to consider themselves to be the core group of the team. Obviously, this is true, but we should remember that the whole process of transplantation would not be possible without the participation of physicians who prepare the patients for surgery and perform long term care, or without anesthesiologists, transplant coordinators and specialized nurses. Such is the multidisciplinary character of our Society.
2951
So, what awaits us? In near future, the lack of organs will inevitably lead to a large-scale increase in the use of living donors. This is an excellent solution, since the number of waiting recipients-to-be is so high that we are using more and more often the so called “not ideal”, “complex” or “marginal donor”. Are we not crossing the ethical principle primum non nocere? Are we modifying the ethical code to suit our needs? Do we have the right to do so? In the future, more altruistic unrelated donors will be used. Is this not hypocrisy, accepting such a situation, remembering at the same time that no form of payment is allowed? Finally, maybe such donors should receive some sort of compensation? But what are the long term prospects for transplantation medicine? In 1932, Aldous Huxley in his science-fiction book called “Brave New World” predicted that, using the fictitious “Bokanowski’s process”, it should be possible to create (by cloning) 100 human-like robots from one egg. Let us hope that this not be the case, despite the fact that the regenerative medicine can partially replace organ transplantation. Whether we like it or not, stem cells will be used for the treatment of several diseases. Will embryonic stem cells have to be used? Ethical problems may become solved by the use of adult somatic cells and the process of nuclear reprogramming. First experimental trials are underway in patients with spinal cord injury or Parkinson’s disease. Achievements of regenerative medicine are allowing us, even now, to prepare two- and three-dimensional structures containing various cell types which are seeded into a biocompatible skeleton. Ex vivo formation of organs may become possible in this way. Finally, organogenesis may become real. Such considerations in certain aspects may seem to be unethical. However, I would like to remind everyone that the famous beekeeper Monsignore Dzierzon, at the end of 19th century discovered that parthenogenesis exists in bees. He was excommunicated, only to be rehabilitated after 100 years. So I would like to end and to leave you with this quote from Einstein: “Progress requires an imagination and knowledge. Imagination without knowledge creates beauty, Knowledge without imagination leads to perfection, [. . .] But real product has to be tested by the time.”
I would like to extend my appreciation to the Board Members with whom I have been working for the last two years. Also, I would like to wish the newly elected President, Professor Magda Durlik, every possible success with her new task. Wojciech Rowin ´ ski