Pancreas Transplantation

300 Pages·1988·13.125 MB·English

by  Luis H. Toledo-Pereyra (auth.), Luis H. Toledo-Pereyra M.D., Ph.D., Ph.D. (eds.)

PANCREAS TRANSPLANTA TION
PANCREAS
TRANSPLANTATION
edited by
Luis H. Toledo-Pereyra
Kluwer Academic Publishers
BOSTON DORDRECHT LONDON
~.
"
DISTRIBUTORS
for the United States and Canada: Kluwer Academic Publishers, 101 Philip Drive,
Assinippi Park, Norwell, MA 02061
for the UK and Ireland: Kluwer Academic Publishers, Falcon House
Queen Square, Lancaster LAI lRN, UK
for all other countries: Kluwer Academic Publishers Group, Distribution Centre,
P.O. Box 322, 3300 AH Dordrecht, The Netherlands
Library of Congress Cataloging in Publication Data
Pancreas transplantation.
Includes bibliographies and index.
1. Pancreas-Transplantation. I. Toledo-Pereyra, Luis H.
[DNLM: 1. Pancreas-transplantation. WI 800 P18845]
RD546.P354 1988 617'.557 87-35025
ISNB-13: 978-1-4612-8976-0 e-ISNB-13: 978-1-4613-1735-7
DOl: 10.1007/978-1-4613-1735-7
© 1988 by Kluwer Academic Publishers
Softcover reprint of the hardcover 1st edition 1988
All rights reserved. No part of this publication may be reproduced,
stored in a retrieval system, or transmitted in any form or by any means,
mechanical, photocopying, recording, or otherwise,
without the prior written permission of the publishers,
Kluwer Academic Publishers, 101 Philip Drive, Assinippi Park, Norwell, MA 02061
To those who saw the need for
helping the diabetic patient through
pancreas transplantation.
To the pioneers, at the University
of Minnesota, who have persistentlY
searched for a better understanding
of the diabetic quandary:
Richard C. Lillehei
Frederick C. Goetz
John S. Nqjarian
David E.R. Sutherland
All of them, in multiple ways,
have been able to make significant
contributions to solving the diabetic
dilemma.
CONTENTS
Contributing Authors ix
Foreword by Frederick C. Goetz xi
Preface XU1
1. Experimental Pancreas 10. Complications 167
Transplantation 1 Luis H. Toledo-Pereyra and Vij~ K. Mittal
Luis H. Toledo-Pereyra
11. Immunosuppression 189
2. Indications for Pancreas
Paul McMaster
Transplantation 41
Frederick C. Goetz
12. Diagnosis and Management of
3. Pancreas Harvesting and Preservation Rejection 203
Techniques 47
Luis H. Toledo-Pereyra
Luis H. Toledo-Pereyra
13. Pathology of Pancreatic
4. Anesthesia Management 61
Transplants 227
Willard S. Holt and Luis H. Toledo-Pereyra
Theodore A. Reyman
5. Surgical Techniques 73
Vijay K. Mittal and Luis H. Toledo-Pereyra 14. Duct-Occluded Pancreas
Transplants 251
6. Cadaver Transplant Results 99
Rino Munda
Luis H. Toledo-Pereyra
7. Living Related Pancreas 15. Bowel-Drained Pancreas
Transplantation 109 Transplants 261
Luis H. Toledo-Pereyra Dai D. Nghiem and Robert J. Corry
8. Clinical Posttransplant Followup 123
16. Urinary-Drained Pancreas
I.G.M. Brons and R~ Y. Caine Transplants 271
Luis H. Toledo-Pereyra
9. Endocrine and Metabolic Response:
Effect of Pancreas Transplantation on
Diabetes Mellitus and Its Secondary 17. Future Prospects of Pancreas
Complications 131 Transplantation 291
Luis H. Toledo-Pereyra Luis H. Toledo-Pereyra
Index 295
vii
CONTRIBUTING AUTHORS
LG.M. Brons, Ph.D. Queen Elizabeth Hospital
Department of Surgery Edgbaston, Birmingham, England
University of Cambridge Clinical School
Vijay K. Mittal, M.D.
Cambridge, England
Transplant Surgeon
Roy Y. CaIne, M.D. Department of Surgery
Professor of Surgery Mount Carmel Mercy Hospital
Department of Surgery Detroit, Michigan
University of Cambridge Clinical School
Rino Munda, M.D.
Cambridge, England
Associate Professor of Surgery
Robert J. Corry, M.D. University of Cincinnati Medical Center
Professor of Surgery Cincinnati, Ohio
University of Iowa
Dai D. Nghiem, M.D.
Iowa City, Iowa
Head, Transplantation Service
Frederick C. Goetz, M.D. Allegheny General Hospital
Professor, Pittsburgh, Pennsylvania
Department of Medicine
Theodore A. Reyman, M.D.
University of Minnesota
Chief, Pathology
Minneapolis, Minnesota
Mount Carmel Mercy Hospital
Willard S. Holt, M.D. Detroit, Michigan
Medical Director
Luis H. Toledo-Pereyra, M.D., Ph.D., Ph.D.
Department of Anesthesia
Chief, Transplantation
Mount Carmel Mercy Hospital
Director, Research
Detroit, Michigan
Department of Surgery
Paul McMaster, M.D. Mount Carmel Mercy Hospital
Professor of Surgery Detroit, Michigan
ix
FOREWORD
In December, 1966, two patients dying of months after the transplants had been per
uremia as a result of diabetic kidney disease formed. This was long enough, however, to
were offered a small chance of survival. Ac establish unequivocally in both patients
cording to the thinking of the time, it was that an endocrine organ, the pancreas, could
inappropriate-and perhaps even unethical function normally and for many days as a
to offer them either chronic hemodialysis or human-to-human graft. The patients had
kidney transplantation. These were considered become normoglycemic independent of insulin
a waste of effort because it was believed that injections.
scarce medical resources should not be spent The possible long-term benefits of restoring
on patients, uremic or not, whose chances of insulin function were hotly argued then, and
surviving for more than a few months were they have not been fully determined 20 years
thought to be very small. Reduced to its later. It seems to me now, however, that the
essence, the idea was that diabetic patients basic premise is sounder than I realized in
were terrible risks and would remain so even if 1966: if one could restore an effective, norm
the uremia were corrected. ally regulated insulin supply to an insulin
What the two patients were offered was a deficient diabetic patient, and do it early
double transplant: simultaneous grafting of enough in the course of the diabetes, there is
pancreas and kidney from the same donor. To now reason to believe that the whole course of
our knowledge this had never been carried out diabetes and diabetic vascular disease might be
in a human being. The rationale-again re prevented.
duced to its essence-was that if diabetes was That all-important point remains to be
the barrier that kept patients from receiving a settled by direct testing. Meanwhile, the in
kidney transplant, then the diabetes could be direct effects of the beginning of pancreas
eliminated most directly by grafting a pancreas transplantation continue to be as significant as
as well as a kidney. Two groups of surgeons the direct effects. One early and critical result
at the University of Minnesota had been was to bring the diabetic patient into the
encouraged-separately-by Owen Wangen bounds of acceptability for consideration for
steen, head of their department, to develop kidney transplant alone. From this almost
pancreas transplant techniques in the labora inadvertant beginning, kidney transplantation
tory. They pooled their knowledge to devise a for diabetics has become a major effort in the
combination of pancreas transplantation with United States and in some other countries.
already established human kidney transplant Furthermore, as the data on HLA typing in
techniques, including use of current immuno diabetic patients accumulated, they provided
suppressive medication. a rich source for investigation of associa
W. Kelly, R.C. Lillehei, F. Merkel, and Y. tions between the human histocompatibility
Idezuki were the four surgeons who carried complex and the risk for insulin-dependent
out the transplants; I had the great privilege of diabetes. Much of the current explosion of
observing the patients with them. They were knowledge concerning the pathogenesis of
both terribly sick; the surgery and added this form of diabetes has been intimately
immunosuppression were a major added bur connected with this research.
den; and they did not live more than a few In this volume, Dr. Toledo-Pereyra pro-
xi
Xll
vides a comprehensive and up-to-date view of benefit from increasing skill in restoring their
the present state of pancreas transplantation, endocrine deficit, and for the even larger
much of it from his own extensive experience. group of patients and investigators who will
Clearly the field is one of the greatest im share the fruits of future discoveries that will
portance, both for the patients who will assuredly derive from this work.
Frederick C. Goetz, M.D.
PREFACE
Pancreas transplantation is one of the emerg and tissue typing was not felt to be necessary,
ing technologies in the ever-developing area because numerous books on transplantation
of organ transplantation. Since 1966, when the have already discussed these issues.
first human pancreas transplant was performed Two other works on pancreas transplanta
at the University of Minnesota Hospitals, the tion, which began concurrently with ours,
interest in this new field of medicine has will soon be published. They will provide
progressively increased. Obstacles to the com additional perspectives on this exciting field.
plete acceptance of this modality of treatment Their texts and ours will make up a comple
have been more technical than immunological. mentary set for the serious student in this area.
The Achilles heel of this procedure has been As more work is accumulated in the years to
the appropriate drainage of the pancreatic come, studies such as ours will have to be
secretions, varying from simple polymer expanded to include this new body of know
occlusion to drainage into the small bowel or ledge. It is not hard to believe that in a few
bladder. years down the road, we will be looking at
In this work, we attempt to present the pancreatic transplantation in the same way as
necessary arsehal to complete whatever is left we are currently viewing kidney transplanta
of this fascinating story to the student of tion. If in our quest for knowledge, in this
pancreatic transplantation. We can learn from rather stimulating endeavor, we can improve
this book the when, how, who, and what of the quality of life of even a few patients with
pancreatic transplantation. In a systematic the sometimes devastating diabetic compli
way, our text reviews the beginnings and cations, our aim will be more than accom
experimental aspects of this procedure with plished. The freedom from insulin dependency
the indications, harvesting, preservation and is the dream of every diabetic.
transplantation techniques. The results of In the Foreword of this book, we have
cadaver and living related pancreas transplanta asked Dr. F. Goetz to tell the story of the
tion, clinical followup, diagnosis and man beginnings of pancreas transplantation so
agement of rejection, and immunosuppression that we can appreciate the great significance of
are all considered separately. Special chapters those moments.
for the complications, transplant pathology, I would like to thank the Department of
endocrine and metabolic response, and the Surgery of our institution for providing an
effect of the procedure on the progression of environment conducive to the development of
the secondary complications are all presented this work. The staff of Transplantation and
individually. Separate descriptions and analy Surgical Research were highly supportive of
sis of the most important transplantation tech our academic pursuits. The editorial assistance
niques used clinically are discussed in the last of Debra A. Gordon, Research Coordinator,
part of the book, future prospects are also and Mona L. Chapman, Research Associate,
considered. A chapter on histocompatibility are also greatly appreciated.
xiii
1. EXPERIMENTAL PANCREAS
TRANSPLANTATION
Luis H. Toledo-Pereyra
Experimental work in the field of pancreas decades. In addition, an attempt has been
transplantation has been hindered by the small made to concentrate on controversial areas of
number of animal models with naturally debate and to highlight potential develop
occurring diabetes mellitus. As a result, the ments. This initial section will present work
diabetic state must therefore be induced either done between 1957 and 1967 in chronological
pharmacologically, with streptozotocin or al sequence.
loxan, or surgically by means of pancreatec The first canine pancreas transplant employ
tomy. In addition, it has become quite difficult ing true vascular anastomoses was performed
to differentiate between technical and immun by Lichtenstein and Barschak in 1957 [2].
ological problems, especially because allograft Their technique involved preservation of the
models are so commonly used. Nevertheless, donor's arterial supply and venous drainage by
substantial information in the field of ex transplantation of the uncinate lobe, with
perimental pancreas transplantation has been direct anastomoses to the iliac artery and vein
produced regarding surgical techniques, pre of the recipient. The transplants were reported
servation, the management of exocrine secre as being technically successful; however, when
tions, rejection, and immunosuppression. all dogs were sacrificed six to eight weeks
A selected review of these topics will be later, histological evidence of surviving pan
detailed in this chapter, begining with the creatic tissue was not seen.
contributions made in the area of experimental In 1959, Brooks and Gifford [3], using
surgical techniques. vascular anastomoses, allotransplanted the en
tire canine pancreas into the abdomens of
recipients. The recipient's iliac vein and aorta
Surgical Techniques
were used for attachments to the graft. None
Attempts at pancreas transplantation have of the grafts were able to function in any of the
been made since the early 1890s [1]. Since recipients due to tissue necrosis, thrombosis,
then, numerous reviews have been written on and hemorrhagic pancreatitis, which occurred
the historical aspects of pancreas transplant shortly after transplantation. In subsequent
ation. Therefore, this section will contain a experiments, the authors attempted to pre
balanced overview of only those experiments serve the exocrine functions in four dogs by
that have been conducted in the last three cannulating the pancreatic duct and allowing it