Preface

Replacement of diseased tissue with new, healthy tissue is not a new dream. Mankind entertained this idea since even before written history, the concept of repair and replacement of body portions being quite prevalent in the lore of primitive people. Legend speaks of the saints, Cosmas and Damian, transplanting a gangrenous leg from one human to another. In medieval times, belief in magical powers began to decline as resurgence in the investigative spirit took precedence. In the nineteenth century, John Hunter performed ample experiments in autograft-ing solid organ fragments. At the same time, a renewed interest in plastic surgical procedures led to several key discoveries, such as the temperature and neo-vascularization dependence of grafts.

The development of vascular surgery in the early 1990s paved the way for successful organ revascularization. Jaboulay and Unger were the first to attempt vascularized xenografts in humans. Alexis Carrel further developed modern vascular techniques and established the need for core cooling of grafts. Simultaneously, work had begun earlier in the field of immunology on the theories of histocompatibility. Rejection mechanisms were more clearly understood after the classic observations of Medawar and Gibson in the 1940s, which gave way to the discovery of the cellular component of the rejection mechanism, paved the way for immunologic tolerance theories and studies, and brought the role of the lymphocyte to the forefront as an immunocompetent cell. In the 1950s, Hume in Boston, and Kuss in Paris, further developed kidney transplantation, which would see a large-scale resurgence in 1960. In 1952, Jean Dausset described the major histocompatibility complex genes in humans, and in 1954, Joseph Murray performed the first successful human kidney transplant, which later won him the Nobel Prize. However, the rate of graft loss was still very high due to rejection, which led to attempts to modify the immune response to promote graft acceptance. The discovery and use of 6-mercaptopurine (6-MP) and its derivatives by Calne vii and Murray gave poor results until combined later with steroids by Starzl and others. The results of kidney transplantation slowly improved and technical advances were made, along with the discovery of transplant-associated complications, such as hyperacute rejection from preformed antibodies, emergence of infections and tumors, and the long-term effects of steroids. Tissue typing also developed during the 1960s, with further clarification of the role of human leukocyte antigens (HLAs). Also in this decade, brain death criteria were established and newer preservation solutions were developed, specifically, the solution by Folkert Belzer in 1967 at the University of Wisconsin. This stimulated the first attempts at transplant of other organs, such as liver (Starzl, 1963), lung (Hardy, 1963), heart (Barnard, 1967) and pancreas (Lillehei, 1966). The 1970s brought about a flurry of curiosity and maturation in the kidney transplant arena, followed by further developments in the other organ transplant systems (heart, liver, lung, and pancreas). Though considerable ethical issues remained, work on the definition of brain death, which had started in 1968, led to practical use of guidelines in the mid-1970s. Azathioprine, a 6-MP derivative, and steroids were the unchallenged standard combination of immunosuppressive drugs used until cyclo-sporine emerged in 1979, making transplantation safer and more successful. The 1980s brought about an immense growth in transplantation thanks to cyclosporine, and, as experience was gained in its use, results improved. Concomitant advances in detection of rejection and infections such as cytomegalovirus (CMV) were also substantial. More recent developments that have brought us into the 21st century include newer immunosuppressive agents, such as tacrolimus, receptor-aimed monoclonal and polyclonal antibodies, mycophenolate, and sirolimus. The latest approaches being evaluated include the search for consistent tolerance induction, the Holy Grail of transplantation. In summary, within the last four decades, transplantation of solid organs has evolved from an experimental surgical tour de force to an accepted, scientifically sound modality of treatment for a selected group of patients with end-stage organ disease.

At a growing number of centers in the United States and worldwide, transplant procedures now achieve 1-year survival rates greater than 80% with many long-term survivors. Many patients so transplanted lead a high-quality, economically productive life in lieu of near certain death or disability. This growth has brought about the development of transplantation programs.

While cost considerations have played a role in slowing the activation of programs (costs are in the range of $60,000 to $250,000, depending on the specific organ), these figures do not accurately reflect the cost of this procedure to society. Management of end-stage organ disease is far more costly and does not yield a viable patient in the end. Optimal comparative data are not available for liver transplants. However, kidney transplantation is more cost-efficient than dialysis. The net cost of a strategy that attempts to save lives and rehabilitate patients to a level of economic viability may be only marginally greater than the current costs of terminal care, and offset by the return of the patient to society and gainful employment.

The major constraint to meeting the demand for transplants is the availability of donated (cadaver) organs. Several steps have been taken, nationally and locally, to alleviate the organ shortage. National required request laws mandate that families of every medically suitable potential donor be offered the option to donate organs and tissues. In addition, laws such as Act 102, enacted in Pennsylvania, that require all deaths to be reported to organ procurement organizations (OPOs), resulting in increased organ donations, will soon be adopted nationwide. Rising public awareness about organ transplantation should continue to reduce the organ shortage. Finally, aggressive use of extended donors, reduced-size, split, and living-related liver transplantation continue to expand the organ donor pool. These efforts, however, still fail to meet the need.

In terms of procurement, allocation, and distribution, major improvements are being made nationally to optimize distribution and ensure good matches. Entry into the waiting list is being standardized by the recent development of listing criteria for all degrees of sickness. The United Network for Organ Sharing (UNOS, Richmond, Virginia) maintains a computerized registry of all patients waiting for organ transplants, and allocation is based upon degree of illness and waiting time. This organization develops and maintains the national Organ Procurement and Transplantation Network (OPTN), which in turn, is funded by the Health Resources and Services Administration (HRSA), an agency of the U.S. Department of Health and Human Services (DHHS).

As this brief historical synopsis illustrates, intra-abdominal organ transplantation has experienced vertiginous growth over the last two decades. When I first became involved in transplantation in 1989, as the first multiorgan transplant fellow of the Mount Sinai Hospital in New York City, the experience was one of the highlights of my existence. I still vividly remember my interview with my mentor, Charles Miller, a great surgeon to whom I am indebted, and my wonderful experience there. Over the years, this enthusiasm has not declined; in fact, it continues to grow strong. Perhaps motivated by this drive, I noticed that in those early times there was a need for a general, academically oriented, standardized introduction manual for those health care professionals involved with these very complex patients. This need became even more evident as I developed the multiorgan transplant program at Inova Fairfax Hospital, Virginia, from 1991 to 1995. I noticed that many physicians and nursing staff were new to intraabdominal transplantation, and no readily available concise references existed. Though this problem had been partially overcome at the time of my move to the Albert Einstein Medical Center in Philadelphia, I resolved to develop a standard manual that could grow and develop along with the specialty, one that was large enough to be really useful and small enough to be easily portable for residents and fellows alike. Thus, this manual was born as a quick, reasonably comprehensive reference for the residents, fellows, medical students, nurses physician assistants, practicing physicians, and any other ancillary health care personnel who may interact with organ transplant recipients or simply want to enhance their knowledge of the subject.

This manual covers not only the basic concepts but also addresses other controversial and ethical topics in detailed, albeit succinct manner. Strict attention to detail and protocols, a sound clinical and surgical base, and a strong sense of teamwork will continue to make improvements in the teaching of our fellows and the success in the management of our patients. We only hope that incorporating the principles outlined herein will benefit us as well as our patients. This manual systematically goes through the same steps these patients experience, namely, workup and evaluation, management during the waiting period, the process of organ allocation, the surgical procedure, early and late complications, immuno-suppression medications and side effects, and outcomes. In addition, diagnostic techniques used in the specialty are discussed. We believe that such a concise approach is beneficial in providing the reader with a practical approach to the topic, and if further in-depth analysis is required, a suggested reading section can be found at the end of this manual. Transplantation is an ever-growing, dynamic, and exciting field that offers cure possibilities to those patients suffering from endstage organ disease. Developments continue to flourish and the only frontier at the present time seems to be the availability of transplantable cadaver organs. Once this is conquered and costs are made reasonable, the possibilities are endless.

The purpose of this manual is to familiarize the user with the most current protocols and practical issues arising in the day-to-day management of abdominal organ transplant recipients, including, but not limited to, liver, kidney, and pancreas transplantation. For an in-depth review of any given topics, the journals and textbooks listed should be consulted. Finally, practitioners should always keep in mind that no protocol is meant to be a substitute for sound clinical judgment and should exercise their own discretion for any given patient.

We are in deep gratitude to all our colleagues who have contributed to this manual, and we look forward to expanding the topics and editions as the specialty evolves in the new millennium.

ACKNOWLEDGMENTS

An old Castilian proverb translates as follows:

To be a man, one has to do three things in life: Plant a tree, have a child, and write a book.

It is therefore only right that I thank all those responsible for who I am today.

My parents, for planting the tree of wisdom and giving me the strength and means to succeed in life.

My wife, JoAnn, for her faith, patience, and care of our children, Robert Daniel, and Aaron Joseph, who make life worth living.

My friends and colleagues, for nurturing, teaching, and helping me from my early days in Madrid to the present times.

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