Table Of ContentPathology of Solid Organ Transplantation
Helen Liapis • Hanlin L. Wang
(Editors)
Pathology of Solid
Organ Transplantation
Editors
Helen Liapis, MD Hanlin L. Wang, MD, PhD
Washington University Cedars-Sinai Medical Center
School of Medicine Department of Pathology and Laboratory
Department of Pathology & Immunology Medicine
660 S. Euclid Avenue 8700 Beverly Blvd.
Campus Box 8118 Los Angeles, CA 90048
Saint Louis, Missouri 63110-1093 USA
USA [email protected]
[email protected]
ISBN 978-3-540-79342-7 e-ISBN 978-3-540-79343-4
DOI 10.1007/978-3-540-79343-4
Springer Heidelberg Dordrecht London New York
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To my husband Athanasios and my daughters Anastasia and Katerina,
for time taken from them.
Helen Liapis
To Michelle, Sean, and Jason for their tremendous support and
encouragement.
Hanlin L. Wang
v
Preface
Solid organ transplantation is now the treatment of choice for end-stage kidney, heart,
liver, pancreas, and lung diseases and increasingly so for intestinal disease.
Experimental transplantation in animals provided the impetus for transplantation in
humans, first with the kidney [1–3]. A brief account of successful human “experi-
ments” in the time frame of the last 50 years is given in the Table 1 below. These
successes were preceded by multiple failures or short-lived grafts. It is through the
combined efforts of many researchers, surgeons, and the development of successful
immunosuppressive drugs that graft survival and patient outcomes improved [4, 5].
More than a dozen Nobel prices since 1901 were awarded to those who worked on
the fundaments of transplantation [6]. Currently, the search for agents that perfect
induction of tolerance is intensified and transplant services and organ sharing con-
tinue to improve [7]. In this remarkable journey of pioneer surgeons, transplant
immunologists, and chemists, pathologists were instrumental in recognizing allograft
rejection, and more recently, defining the criteria that distinguish acute from chronic
rejection, rejection from drug toxicity, and recurrent from de novo disease. Pathology
has also been in the forefront of the endeavor of new therapies participating in the
evaluation of the effects of drugs on tissue, thus maintaining clear and ethical views
in the search for better treatments. Pathologic interpretation of the transplanted organs
in humans was first described for the kidney in the 1960s by Gustav Dammin at
Harvard and Kendick Porter at St. Mary’s Hospital in London [8, 9]. It soon became
the most reliable tool to distinguish rejection from other complications of transplan-
tation such as drug toxicity, recurrent/de novo disease, and infection. Transplantation
pathology is now an indispensable guide to prompt therapy. As the field of transplan-
tation advances, so is transplant pathology. New criteria for donors and the effective-
ness of alternative immunosuppression drugs are better understood by histopathologic
study of the tissue immune response in the graft, short- and long-term. Innovative
approaches of immune tolerance, such as mixed allogeneic chimerism, monoclonal
antibodies, and fusion proteins and stem cells for immune modulation, may in the
next decade become a reality, therefore changing the pathology of grafted organs
[10–12]. Finally, new molecular mechanisms to explain early dysfunction or late
graft loss may eventually become diagnostic tools.
This book aims to present a thorough account of the pathology of solid organ trans-
plantation in the down of the twenty-first century. The book is organized in a detailed
practical diagnostic approach which we hope the reader will find didactic and clear.
Molecular studies are discussed when relevant to diagnosis. Introductory chapters are
written by our clinical colleagues who describe the immune response from their per-
spective on treatment and management issues. A chapter on xenotransplantation and
vii
viii PrPfafP
Table 1 Human transplantation: a brief account
1902 Alexis Carrel Technique to join blood vessels
1943 Willem J. Kolf First artificial kidney
1944 Peter Medawar Rejection is an immune-related phenomenon
1954 Joseph Murray First kidney transplant in identical twins
1958 Georges Mathé First bone marrow transplantation
1960 Renè Kuss First living related ABO compatible kidney transplant
1966 William D. Keyy First kidney/pancreas transplant
Richard Lillehei
1967 Christian Barnard First heart transplant
1967 Thomas Starzl First liver transplant
1983 Joel Cooper First successful lung transplant
1986 The Southeast Organ Scientific organization for transplant professionals
Procurement foundation Predecessor of the “United Network for Organ Sharing
(SEOPF) is formed “UNOS”
1981 Bruce Reitz First heart–lung transplant
Norman Shumway
1983 Santoz Ltd. (Basel) Cyclosporine A was FDA approved
1984 NOTA National Organ Transplant Act establishes national
system of matching donors to recipients
UNOS separates from SEOPF
1986 Alexander Patterson First bilateral lung transplant
1987 Pittsburgh surgeons team First successful intestinal transplant
1982 William C. DeVries First artificial heart transplant
1989 Fujisawa Tacrolimus was introduced
1991 Ray V. Rajotte Islet transplantation with insulin independence
1997 Antonio Secchi Islet transplantation with insulin independence
1998 Jean Michel Dubernard First hand transplant
2005 Duvauchelle, Dubernard First face transplantation
2007 Transplant Growth and Assessment of nationwide transplant center capacity
Management
Collaborative Group
organogenesis is a forecast for possible solutions in organ transplantation and one
that will, if successful, may change the field and patient care.
We would like to thank with gratitude all our colleagues who contributed their
invaluable time and experience. We hope that the book will be useful to our col-
leagues, also in countries around the world, where transplantation is becoming
increasingly more available and frequently the only organ replacement modality
within financial reach.
St. Louis, MO, USA Helen Liapis
Hanlin L.Wang
PrPfafP ix
References
1. Groth, C.G., Longmire Jr., W.P. (eds.): Historical Landmarks in Clinical Transplantation.
Springer, New York (2000)
2. Cinqualbre, J., Kahan, B.D., Küss, R.: Fifty years of retroperitoneal placement of renal trans-
plants. Transplant Proc. 34, 3019–3025 (2002)
3. Cooper, J.D.: The history of surgical procedures for emphysema. Ann Thorac Surg. 63, 312–319
(1997)
4. Murray, J.E., Merrill, J.P., Harrison, J.H., Wilson, R.E., Dammin, G.J.: Prolonged survival of
human-kidney homografts by immunosuppressive drug therapy. N Engl J Med. 268, 1315–1323
(1963)
5. Stähelin, H.F.: The history of cyclosporin A (Sandimmune) revisited: another point of view.
Experientia 52, 5–13 (1996)
6. Starzl, T.E.: Liver transplantation. Gastroenterology. 112, 288–291 (1997)
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Organ donation and utilization in the United States, 1997–2006. Am J Transplant. 8(4 Pt 2),
922–934 (2008)
8. Glassock, R.J., Feldman, D., Reynolds, E.S., Dammin, G.J., Merrill, J.P.: Human renal isografts:
a clinical and pathologic analysis. Medicine (Baltimore). 47, 411–454 (1968)
9. Kincaid-Smith, P.: Histological diagnosis of rejection of renal homografts in man. Lancet.
21(7521), 849–852 (1968)
10. Atala, A.: Advances in tissue and organ replacement. Curr Stem Res Ther. 3, 21–31 (2008)
11. Kawai, T., Cosimi, A.B., Spitzer, T.R., et al.: HLA-mismatched renal transplantation without
maintenance immunosuppression. N Engl J Med. 358, 353–361 (2008)
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Contents
Part I Immunology, Clinical, and Laboratory Aspects of Organ
Transplantation
1 Immunology of Organ Transplantation......................... 3
Sevgi Gurkan, Bernd Schröppel, and Barbara Murphy
2 Current Concepts of Immunosuppression and Side Effects ........ 11
Anand Khurana and Daniel C. Brennan
3 Clinical Aspects of Infection.................................. 31
Rouba Ghoussoub and Daniel C. Brennan
4 Clinical Evaluation of Alloantibodies in Solid
Organ Transplantation ...................................... 45
Gerald P. Morris and T. Mohanakumar
5 Frontiers in Organ Transplantation............................ 57
Marc R. Hammerman
Part II Transplant Pathology of Organ Systems
6 Kidney.................................................... 77
Helen Liapis, Matthew J. Koch, and Michael Mengel
7 Lung ..................................................... 171
Anja C. Roden and Henry D. Tazelaar
8 Liver ..................................................... 199
Hanlin L. Wang, Christopher D. Anderson, Sean Glasgow,
William C. Chapman, Jeffrey S. Crippin, Mathew Augustine,
Robert A. Anders, and Andres Roma
xi
xii ContPnts
9 Heart ..................................................... 315
Dylan V. Miller, Hannah Krigman, and Charles Canter
10 Small Intestine ............................................. 347
Frances V. White and Sarangarajan Ranganathan
11 Pancreas .................................................. 371
Raghava M. Munivenkatappa, John C. Papadimitriou,
and Cinthia B. Drachenberg
12 Vascularized Composite Allotransplantation .................... 393
Linda C. Cendales, Jean Kanitakis, and Carolyn Burns
Index ......................................................... 401
