Practical Manual ofAbdominal OrganTransplantation

Practical Manual ofAbdominal OrganTransplantation

Edited by

Cosme Manzarbeitia, M.D.Albert Einstein Medical CenterPhiladelphia, Pennsylvania

KLUWER ACADEMIC PUBLISHERS NEW YORK, BOSTON, DORDRECHT, LONDON, MOSCOW

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0-306-47627-4

Contributors

Sergio Alvarez, Albert Einstein Medical Center, Philadelphia, Pennsylvania19141

Victor Araya, Albert Einstein Medical Center, Philadelphia, Pennsylvania 19141

Ierachmiel Daskal, Albert Einstein Medical Center, Philadelphia, Pennsylvania19141

Sukru Emre, Mount Sinai Medical Center, New York, New York 10029

Javid Fazili, Albert Einstein Medical Center, Philadelphia, Pennsylvania 19141

Arthur J. Geller, Freehold, New Jersey 07728

Kevin Hails, Albert Einstein Medical Center, Philadelphia, Pennsylvania 19141

Steven-Huy Han, UCLA School of Medicine, Los Angeles, California 90095

Vivek Kaul, Albert Einstein Medical Center, Philadelphia, Pennsylvania 19141

Jan Kramer, Albert Einstein Medical Center, Philadelphia, Pennsylvania 19141

Laurel Lerner, Albert Einstein Medical Center, Philadelphia, Pennsylvania 19141

Michael K. McGuire, Albert Einstein Medical Center, Philadelphia, Pennsylva-nia 19141

Cosme Manzarbeitia, Albert Einstein Medical Center, Philadelphia, Pennsylva-nia 19141

Paul Martin, UCLA School of Medicine, Los Angeles, California 90095

Rohit Moghe, Albert Einstein Medical Center, Philadelphia, Pennsylvania 19141

M. Catherine Morrison, Albert Einstein Medical Center, Philadelphia, Pennsyl-vania 19141

v

vi Contributors

Santiago J. Munoz, Albert Einstein Medical Center, Philadelphia, Pennsylvania19141

Juan Oleaga, Albert Einstein Medical Center, Philadelphia, Pennsylvania 19141

Jorge A. Ortiz, Albert Einstein Medical Center, Philadelphia, Pennsylvania 19141

Lloyd E. Ratner, Johns Hopkins University School of Medicine, Baltimore,Maryland 21287

David J. Reich, Albert Einstein Medical Center, Philadelphia, Pennsylvania 19141

Jonathan V. Roth, Albert Einstein Medical Center, Philadelphia, Pennsylvania19141

Kenneth D. Rothstein, Albert Einstein Medical Center, Philadelphia, Pennsylva-nia 19141

Sammy Saab, UCLA School of Medicine, Los Angeles, California 90095

Henkie P. Tan, Johns Hopkins University School of Medicine, Baltimore, Mary-land 21287

Shuin-Lin Yang, Albert Einstein Medical Center, Philadelphia, Pennsylvania19141

Nayere Zaeri, Albert Einstein Medical Center, Philadelphia, Pennsylvania 19141

Radi Zaki, Albert Einstein Medical Center, Philadelphia, Pennsylvania 19141

Preface

Replacement of diseased tissue with new, healthy tissue is not a new dream. Man-kind entertained this idea since even before written history, the concept of repairand replacement of body portions being quite prevalent in the lore of primitivepeople. Legend speaks of the saints, Cosmas and Damian, transplanting a gan-grenous leg from one human to another. In medieval times, belief in magicalpowers 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 surgicalprocedures 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 forsuccessful organ revascularization. Jaboulay and Unger were the first to attemptvascularized xenografts in humans. Alexis Carrel further developed modern vas-cular techniques and established the need for core cooling of grafts. Simul-taneously, work had begun earlier in the field of immunology on the theories ofhistocompatibility. Rejection mechanisms were more clearly understood after theclassic observations of Medawar and Gibson in the 1940s, which gave way to thediscovery of the cellular component of the rejection mechanism, paved the wayfor immunologic tolerance theories and studies, and brought the role of thelymphocyte to the forefront as an immunocompetent cell. In the 1950s, Hume inBoston, and Kuss in Paris, further developed kidney transplantation, which wouldsee a large-scale resurgence in 1960. In 1952, Jean Dausset described the majorhistocompatibility complex genes in humans, and in 1954, Joseph Murray per-formed the first successful human kidney transplant, which later won him theNobel 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

viii Preface

and Murray gave poor results until combined later with steroids by Starzl andothers. The results of kidney transplantation slowly improved and technicaladvances were made, along with the discovery of transplant-associated complica-tions, such as hyperacute rejection from preformed antibodies, emergence ofinfections and tumors, and the long-term effects of steroids. Tissue typing alsodeveloped during the 1960s, with further clarification of the role of humanleukocyte antigens (HLAs). Also in this decade, brain death criteria were estab-lished and newer preservation solutions were developed, specifically, the solutionby Folkert Belzer in 1967 at the University of Wisconsin. This stimulated the firstattempts at transplant of other organs, such as liver (Starzl, 1963), lung (Hardy,1963), heart (Barnard, 1967) and pancreas (Lillehei, 1966). The 1970s broughtabout a flurry of curiosity and maturation in the kidney transplant arena, followedby further developments in the other organ transplant systems (heart, liver, lung,and pancreas). Though considerable ethical issues remained, work on the defini-tion of brain death, which had started in 1968, led to practical use of guidelines inthe mid-1970s. Azathioprine, a 6-MP derivative, and steroids were the un-challenged standard combination of immunosuppressive drugs used until cyclo-sporine emerged in 1979, making transplantation safer and more successful. The1980s brought about an immense growth in transplantation thanks to cyclosporine,and, as experience was gained in its use, results improved. Concomitant advancesin detection of rejection and infections such as cytomegalovirus (CMV) were alsosubstantial. More recent developments that have brought us into the 21st centuryinclude newer immunosuppressive agents, such as tacrolimus, receptor-aimedmonoclonal and polyclonal antibodies, mycophenolate, and sirolimus. The latestapproaches 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 deforce to an accepted, scientifically sound modality of treatment for a selectedgroup of patients with end-stage organ disease.

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

While cost considerations have played a role in slowing the activation ofprograms (costs are in the range of $60,000 to $250,000, depending on the specificorgan), 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 aviable patient in the end. Optimal comparative data are not available for livertransplants. However, kidney transplantation is more cost-efficient than dialysis.The net cost of a strategy that attempts to save lives and rehabilitate patients to alevel of economic viability may be only marginally greater than the current costs

Preface ix

of terminal care, and offset by the return of the patient to society and gainfulemployment.

The major constraint to meeting the demand for transplants is the availabilityof donated (cadaver) organs. Several steps have been taken, nationally and locally,to alleviate the organ shortage. National required request laws mandate thatfamilies of every medically suitable potential donor be offered the option todonate organs and tissues. In addition, laws such as Act 102, enacted in Pennsylva-nia, 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 theorgan 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 improvementsare being made nationally to optimize distribution and ensure good matches. Entryinto the waiting list is being standardized by the recent development of listingcriteria for all degrees of sickness. The United Network for Organ Sharing(UNOS, Richmond, Virginia) maintains a computerized registry of all patientswaiting for organ transplants, and allocation is based upon degree of illness andwaiting time. This organization develops and maintains the national Organ Pro-curement and Transplantation Network (OPTN), which in turn, is funded by theHealth 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 transplan-tation has experienced vertiginous growth over the last two decades. When I firstbecame involved in transplantation in 1989, as the first multiorgan transplantfellow of the Mount Sinai Hospital in New York City, the experience was one ofthe highlights of my existence. I still vividly remember my interview with mymentor, Charles Miller, a great surgeon to whom I am indebted, and my wonderfulexperience there. Over the years, this enthusiasm has not declined; in fact, itcontinues to grow strong. Perhaps motivated by this drive, I noticed that in thoseearly times there was a need for a general, academically oriented, standardizedintroduction manual for those health care professionals involved with these verycomplex patients. This need became even more evident as I developed themultiorgan transplant program at Inova Fairfax Hospital, Virginia, from 1991 to1995. I noticed that many physicians and nursing staff were new to intra-abdominal transplantation, and no readily available concise references existed.Though this problem had been partially overcome at the time of my move to theAlbert Einstein Medical Center in Philadelphia, I resolved to develop a standardmanual that could grow and develop along with the specialty, one that was largeenough to be really useful and small enough to be easily portable for residents andfellows alike. Thus, this manual was born as a quick, reasonably comprehensive

x Preface

reference for the residents, fellows, medical students, nurses physician assistants,practicing physicians, and any other ancillary health care personnel who mayinteract with organ transplant recipients or simply want to enhance their knowl-edge of the subject.

This manual covers not only the basic concepts but also addresses othercontroversial and ethical topics in detailed, albeit succinct manner. Strict attentionto detail and protocols, a sound clinical and surgical base, and a strong sense ofteamwork will continue to make improvements in the teaching of our fellows andthe success in the management of our patients. We only hope that incorporatingthe principles outlined herein will benefit us as well as our patients. This manualsystematically goes through the same steps these patients experience, namely,workup and evaluation, management during the waiting period, the process oforgan allocation, the surgical procedure, early and late complications, immuno-suppression medications and side effects, and outcomes. In addition, diagnostictechniques used in the specialty are discussed. We believe that such a conciseapproach is beneficial in providing the reader with a practical approach to thetopic, and if further in-depth analysis is required, a suggested reading section canbe 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 end-stage organ disease. Developments continue to flourish and the only frontier at thepresent time seems to be the availability of transplantable cadaver organs. Oncethis is conquered and costs are made reasonable, the possibilities are endless.

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

We are in deep gratitude to all our colleagues who have contributed to thismanual, and we look forward to expanding the topics and editions as the specialtyevolves 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.

Preface xi

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

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

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

Contents

I. PRETRANSPLANT EVALUATION AND MANAGEMENT

1. Indications for Liver Transplantation 3

344455667889

Victor Araya, Javid Fazili, Vivek Kaul, Kenneth D. Rothstein, andSantiago J. Munoz

1.1. General Indications for Liver Transplantation1.2. Disease-Specific Indications for Liver Transplantation

1.2.1. Acute Liver Failure1.2.2. Primary Biliary Cirrhosis1.2.3. Primary Sclerosing Cholangitis1.2.4. Chronic Viral Hepatitis1.2.5. Alcoholic Liver Disease1.2.6. Hepatic Malignancy

1.3. Uncommon Indications for Liver Transplantation1.4. Contraindications to Liver Transplantation

1.4.1. Absolute Contraindications1.4.2. Relative Contraindications

2. Evaluation of Candidates for Liver Transplantation 11

11121417

Vivek Kaul, Kenneth D. Rothstein, Santiago J. Munoz, Jorge A.Ortiz, and Cosme Manzarbeitia

2.1. Organ Matching2.2. Candidate Selection

2.2.1. Workup of Candidates2.2.2. Waiting Lists and Waiting Period

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xiv Contents

18192124

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27272829303031313233343739

41

4141414244444445464646

51

51

2.3. Optimal Timing of Liver Transplantation2.3.1. Fulminant Hepatic Failure2.3.2. Chronic Liver Disease2.3.3. Retransplantation: Whether or Not?

3. Management of the Patient Awaiting Liver Transplantation

Sammy Saab, Steven-Huy Han, and Paul Martin

3.1. Introduction3.2. Ascites

3.2.1. Refractory Ascites3.2.2. Spontaneous Bacterial Peritonitis (SBP): Treatment3.2.3. Spontaneous Bacterial Peritonitis: Prophylaxis3.2.4. Hepatorenal Syndrome

3.3. Encephalopathy3.3.1. Treatment3.3.2.

3.4.3.5.3.6.3.7.

PruritusEsophageal VaricesMalnutritionSummary

4. Pretransplant Evaluation: Kidney and Pancreas

Jorge A. Ortiz, Cosme Manzarbeitia, and Radi Zaki

4.1. Evaluation of the Kidney Transplant Recipient4.1.1.4.1.2.4.1.3.4.1.4.

General IndicationsContraindicationsEvaluation of CandidatesWaiting Lists and Waiting Period

4.2. Evaluation and Modalities of Pancreas Transplantation4.2.1.4.2.2.4.2.3.4.2.4.

Indications and TestingSimultaneous Pancreas–Kidney Transplantation (SPK)Pancreas after Kidney Transplantation (PAK)Pancreas Transplant Alone (PTA)

4.3. Timing of Kidney and Pancreas Transplantation

5. Psychiatric and Social Workup of the Abdominal OrganRecipient

Kevin Hails

5.1. Psychological and Psychiatric Evaluation of the TransplantRecipient

Benefits

Contents xv

5.1.1.5.1.2.5.1.3.

ScreeningPerioperative PeriodPostoperative Period

5.2. Social Evaluation

515656575859595960

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6364

69

6969707070

71717172

73

73757676

78

5.2.1.5.2.2.5.2.3.5.2.4.5.2.5.

Pretransplant ScreeningNontransplantation CandidatesWaiting PhaseHospitalization PostsurgeryDischarge Planning

6. The Role of the Transplant Coordinator

Laurel Lerner and M. Catherine Morrison

6.1.6.2.

Pretransplant Coordinator’s RolePosttransplant Coordinator’s Role

II. ORGAN PROCUREMENT AND PRESERVATION

7. Organ Donation and the Allocation System

Cosme Manzarbeitia

7.1. Introduction7.1.1.7.1.2.

NOTA, OPTN, and UNOSDeath by Neurologic Criteria

7.2. Organ Procurement Organizations (OPOs)7.2.1.7.2.2.

Donor Evaluation and ManagementAdministrative Coordination of Multiorgan, Long-Distance Retrieval

7.3. Waiting Lists and Organ Allocation7.3.1.7.3.2.

Allocation of Kidneys and PancreasAllocation of Livers

8. Surgical Techniques for Liver Procurement

Sukru Emre and Cosme Manzarbeitia

8.1.8.2.

Whole Liver ProcurementReduced-Size and Split-Liver Transplantation8.2.1.8.2.2.8.2.3.

In situ Split-Liver ProcurementLiving Donor Liver ProcurementComplications and Ethical Concerns of Living DonorLiver Procurement

xvi Contents

9. Surgical Techniques for Kidney and Pancreas Procurement 81

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104105106106106109

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112

115

115116116116116117

Henkie P. Tan and Lloyd E. Ratner

9.1.9.2.

Cadaveric Donor NephrectomyLiving Donor Nephrectomy

9.2.1.9.2.2.9.2.3.

Traditional Open Donor NephrectomyLaparoscopic Donor NephrectomyComplications and Ethics of Living Donor KidneyProcurement

9.3. Cadaveric Donor Pancreatectomy9.3.1.9.3.2.

Pancreas without Liver ProcurementPancreas with Liver Procurement

9.4. Living Donor Pancreatectomy

III. RECIPIENT OPERATIVE TECHNIQUES AND STRATEGIES

10. The Liver Transplant Procedure

Cosme Manzarbeitia and Sukru Emre

10.1.10.2.

IntroductionWhole Organ Implantation10.2.1.10.2.2.

Orthotopic Transplantation (OLT)Piggyback Techniques

10.3.10.4.

Heterotopic/Auxiliary TransplantationPartial/Segmental Organ Implantation10.4.1.10.4.2.10.4.3.10.4.4.

Reduced-Size Liver TransplantationSplit-Liver TransplantationLiving Donor Liver TransplantationRecipient Operation for Split-Liver and LivingDonor Grafts

10.4.5. Special Considerations in Pediatric LiverTransplantation

11. The Kidney Transplant Procedure

Shuin-Lin Yang

11.1.11.2.

Backtable Graft PreparationRecipient Surgery11.2.1.11.2.2.11.2.3.11.2.4.

Position and PreparationIncision at Lower Quadrant of AbdomenRetroperitoneal Space DissectionIsolation of Iliac Vessels

Contents xvii

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121

121124

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125126126129131134136

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141143144144145146147148148148149150150150151

11.2.5.11.2.6.

Vascular AnastomosisUreteric Reconstruction and Closure

The Pancreas Transplant Procedure12.

Jorge A. Ortiz

12.1.12.2.

Backtable PreparationImplantation Procedure

13. Anesthesia in Abdominal Organ Transplantation

Jonathan V. Roth and Jan Kramer

13.1.13.2.

Anesthetic Management of the Organ DonorManagement of the Liver Transplant Recipient13.2.1.13.2.2.13.2.3.

Preoperative EvaluationPerioperative ManagementIntraoperative Management

13.3.13.4.

Management of the Kidney Transplant RecipientManagement of the Pancreas Transplant Recipient

IV. IMMEDIATE POSTOPERATIVE CARE AND COMPLICATIONS

14. Postoperative Care in Liver Transplantation

Jorge A. Ortiz

14.1.14.2.14.3.14.4.14.5.14.6.14.7.14.8.14.9.

14.10.14.11.14.12.14.13.14.14.14.15.

General Intensive Care IssuesRenal DysfunctionNeurologic IssuesCardiovascular IssuesHematologic AlterationsInfections in the Immediate Postoperative PeriodPrimary Graft Nonfunction (PNF)Hemorrhagic NecrosisInduction ImmunosuppressionHepatic ArteryPortal VeinInferior Vena Cava (IVC) and Hepatic VeinsBiliary SystemRejectionIntra-Abdominal Bleeding

xviii Contents

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153153154154154155155155157158

161

161162162163164

167

167168169169170171171171172172173173174174175

15. Postoperative Care in Kidney Transplantation

Radi Zaki and Shuin-Lin Yang

15.1.15.2.15.3.15.4.15.5.15.6.15.7.15.8.15.9.

15.10.

ImmunosuppressionFluid ManagementHemodialysisHyper- and HypotensionHyperglycemiaFoley Catheter ManagementViral ProphylaxisSurgical ComplicationsComplications Manifesting in Allograft DysfunctionVascular Complications

16. Postoperative Care in Pancreas Transplantation

Jorge A. Ortiz

16.1.16.2.

General ICU CareImmediate Complications of Pancreas Transplantation16.2.1.16.2.2.16.2.3.

Complications of Bladder DrainageVascular ComplicationsGeneral Complications

17. Immunosuppression, Rejection Prophylaxis, and OtherPharmacotherapy of the Transplant Recipient

Cosme Manzarbeitia, Michael K. McGuire, and Rohit Moghe

17.1.17.2.17.3.

IntroductionGlucocorticoidsCalcineurin Inhibitors17.3.1.17.3.2.

Cyclosporine A (CyA)Tacrolimus (Fk506,Prograf®)

17.4. Antimetabolites17.4.1.17.4.2.

Azathioprine (Imuran®)Mycophenolate Mofetil (Cellcept®)

17.5. Antilymphocyte Antibody Preparations17.5.1.17.5.2.17.5.3.

Muromonab-CD3 (Orthoclone OKT3®)Antithymocyte (Atg) GlobulinsInterleukin 2 (IL-2) Receptor Antagonists

17.6.17.7.17.8.

Sirolimus (Rapamune®)Immunosuppressive RegimensOther Medications

Contents xix

175178179179180180180

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183183184184185185185186186

187187187188

189

189189192192194194196196196196

17.8.1.17.8.2.17.8.3.17.8.4.17.8.5.17.8.6.17.8.7.

AntiviralsAntibacterialsAntifungalsAntihypertensivesHypoglycemic AgentsLipid-Lowering AgentsSupplements

V. LAST POSTOPERATIVE COMPLICATIONS AND OUTCOMES

18. General Late Complications in Transplantation

David J. Reich

18.1. Complications of Immunosuppression18.1.1.18.1.2.18.1.3.18.1.4.18.1.5.18.1.6.18.1.7.18.1.8.

Renal DysfunctionHypertensionDiabetes MellitusHyperlipidemiaObesityOsteoporosisPosttransplant MalignanciesPosttransplant Infections

Disease Recurrence, Chronic Rejection, and Technical18.2.Problems18.2.1.18.2.2.18.2.3.

Disease RecurrenceChronic RejectionTechnical Problems

19. Organ-Specific Late Complications in Transplantation

David J. Reich, Cosme Manzarbeitia, Radi Zaki, Jorge A. Ortiz,and Sergio Alvarez

19.1. Liver Transplantation19.1.1.19.1.2.19.1.3.

Technical ComplicationsChronic Hepatic RejectionRecurrent Disease after Transplantation

19.2. Kidney Transplantation19.2.1.19.2.2.19.2.3.

Surgical ComplicationsChronic RejectionDisease Recurrence

19.3. Pancreas Transplantation19.3.1. Rejection

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199199200202202202203203204

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219219

221

221221223224224227229

19.3.2.19.3.3.

Urologic ComplicationsOther Complications

20. Results of Abdominal Organ Transplantation

David J. Reich, Jorge A. Ortiz, and Cosme Manzarbeitia

20.1. Liver Transplantation20.1.1.20.1.2.20.1.3.20.1.4.

Overall SurvivalFactors Affecting SurvivalQuality of LifePregnancy after Liver Transplantation

20.2.20.3.

Kidney TransplantationPancreas Transplantation20.3.1.20.3.2.

Graft Loss and ImmunosuppressionSurvival Rates and Results

VI. DIAGNOSTIC TOOLS IN ABDOMINAL TRANSPLANTATION

21. Pathology of Transplantation

Nayere Zaeri and Ierachmiel Daskal

21.1.21.2.

Liver TransplantKidney Transplant21.2.1.21.2.2.21.2.3.21.2.4.21.2.5.

21.2.6.

Organ SelectionImmune-Mediated RejectionScoring RejectionImmunosuppressive Drug ToxicityPosttransplantation Lymphoproliferative Disorders(PTLD)Other Causes for Graft Loss

22. Radiology in Transplantation

Juan Oleaga

22.1. Pretransplant Evaluation22.1.1.22.1.2.

LiverKidney

22.2. Posttransplant Evaluation and Management22.2.1.22.2.2.22.2.3.

LiverKidneyPancreas

Contents xxi

23. Endoscopy in Liver Transplantation 231

231

232232232233

239

251

Arthur J. Geller

23.1.23.2.

Upper and Lower Gastrointestinal EndoscopyRole of Endoscopic Retrograde Cholangiography (ERCP)in Liver Transplantation23.2.1.23.2.2.23.2.3.

Preoperative Evaluation and TreatmentPostoperative Biliary ComplicationsManagement of Biliary Complications

Suggested Reading

Index