TRANSPLANT SURGERY

from Immunology to Surgery

Department of Surgery
Faculty of Medicine and Surgery
University of Santo Tomas

Renato M. Reyes MD

Landmarks on Transplantation in the

PHILIPPINES
The first successful Renal Transplant was done at UST
Hospital in1968 by Dr. Domingo Antonio and Renal
Transplant Team). A small series of patients were done
and later the program was abandoned.
Establishment of a National Health Center: National
Kidney & Transplant Institute being the main training
program in the country
General Surgeons & Urologist and Fellowship Program
overseas contributed to the Training Program of local
Transplant Surgeons
Renal Transplantation was the mainstay. Small series of
Liver, Pancreas and Heart Transplants were done.

Transplant Immunobiology
unlike surgery in general which was born out
of the discovery of knife, needle and
thread TRANSPLANT SURGERY evolved
from understanding of the complex process
of self none self Immunobiology and the
ability to trick this process with elegant
Pharmacological Intervention

Transplant Immunobiology
(MHC) & Minor
Histocompatibility Antigens: Class I, II & III
Antigens on Human Chromosome 6 expressed as HLA
Molecules (A,B,C,DP,DQ,DR,DZ etc.)
Recognition of ALLOANTIGEN: T Cell Recognition of
MHC (HLA) or Antigen Presenting Cell
(APC)

Major Histocompatibility Complex

Transplant Immunobiology
T and B Cells: T cells recognize alloantigen
thru the T Cell Receptor (TCR) either as intact

Activation of

molecules (Direct Recognition) or processed allopeptides

(Indirect Recognition). Resting B cells bind antigen by

immunoglobulin (Ig) that serves as B Cell

Receptor (BCR)
Adhesion Molecules: The central event of rejection
process is increased expression of Adhesion Molecules on
both Endothelial Cells and Leucocytes: Selectins, Integrins,
ICAM (immunoglobulin cell), VCAM (vascular cell) etc.

Transplant Immunobiology
Cytokine Networks: Autocrine and Paracrine
mediators of Rejection Inflammatory Response and
Transplantation Tolerance. Based on their origin

(macrophages, T and B lymphocytes, fibroblast) and location

IL,
interferons, TNF, CSF and TFGF.
Transplantation Tolerance: Deletion, Anergy,
Suppression and Ignorance
on chromosomes they are divided into

Tissue Typing & Cross Matching

Human Lymphocyte
& Identified Typing Sera
MHC Transplant Antigens: Class I (HLA A and B) and
Class II (HLA DR)

Microlymphocytotoxicity Test:

HLA (Human Leukocyte Antigen) exhibits great degree of

polymorphism and co dominant allelic

expression

Tissue Typing & Cross Matching

Two Surface Antigens are expressed for each of the MHC

HLA-A, HLA-B and HLA-DR

6 Antigen Match for HLA-A, HLA-B and HLA-DR is a
Full House Match or 0 Antigen MisMatch
As a rule, the siblings will inherit 1 Haplotype from
each of the Parents. Siblings therefore are 1
Haplotype, 3 Antigen Match & 3 Antigen
Mismatch to their Parents

Tissue Typing & Cross Matching

HLA-DR Antigens are the strongest transplantation
antigens followed by HLA-B and HLA-A

Recipient Current
Serum to Donors Peripheral
Lymphocyte. A positive cross match is an Absolute

Tissue Cross Matching:

Contraindication to Transplantation.
A poor HLA
Transplantation

Match is NOT a contraindication to

Steps in the Clinical Diagnosis of

BRAINSTEM DEATH:
Ascertain that certain PRECONDITIONS has been met:

COMATOSE and VENTILATOR DEPENDENT

EXCLUDE reversible causes of non functioning Brainstem:
HYPOTHERMIA, DRUG INTOXICATION and
SEVERE METABOLIC DISTURBANCE
Establish that comatose patient is APNEIC and that BRAINSTEM
REFLEXES are absent: NO PUPILLARY, CORNEAL,
VESTIBULO-OCULAR, MOTOR RESPONSE,GAG
REFLEX, RESPONSE TO TRACHEOBRONCHIAL
CATHETER STIMULATION

Recommended Criteria for Screening

Potential Cadaver Donors
Maximum Age: 65 years with Compatible Blood Type
No History of: HPN, DM, Malignancy and Drug Abuse
No Evidence of: Renal Disease and Generalized Viral or
Bacterial Infection
Acceptable Urinalysis
Preterminal Urine Output above .5mL per/Kg/Hr
Normal BUN, Creatinine and Liver Function Tests
Warm Ischemia Time < 60 Minutes
Negative Serology: HIV, HBV & HCV

Cadaveric Organ Donation

Republic Act No. 7170: Organ Donation Act of
1991 and subsequent DOH pronouncements on the
conduct of transplantation.
Brainstem Dead Donors
Heart Beating Cadaveric Donors
Excluded are History of Cardiac Arrest or Witnessed
Cardiopulmonary Arrest (optional)
Surgical Explantation will result in Exsanguination
and Cessation of Cardiac Activity

Living Organ Donor

Living Related and Living Non Related
Donation
Living Emotionally Related Donation
Living Liver Donor: Segmental Organ
Donation
Legal and Illegal, Moral and Immoral
Commercial Donation and Rewarded Gifting

Routine Evaluation of a Potential

Living Related Donor

Blood Typing, HLA Typing & Cross Matching

CBC, Serum Electrolytes, Coagulation Studies
Hepatitis Profile, HIV and CMV Studies
Liver Function Test, Cholesterol & Triglycerides
Urinalysis, Creatinine Clearance, Uric Acid
VDRL, Pregnancy Test
Glucose Tolerance Test
CP and Medical Clearance

Routine Evaluation of a Pretransplant Patient

Blood Typing and Tissue Typing

Hepatitis Profile: HBV and HCV
Viral Titers: EBV and CMV
CBC, Electrolytes, Coagulation Profile
Liver Function Tests, Cholesterol,
Triglycerides, FBS, Renal Function Tests
HIV and VDRL
CP and Medical Clearance

Organ Retrieval and Preservation

Living Donor Harvesting:
Systematic Vascular & Ductal / Drainage Isolation,
Transection & Ex Vivo Cooling and Perfusion
Cadaveric Organ Harvesting:
Arterial and Venous Cannulation
In Situ Arterial Perfusion and Core / Topical and
Venous Exsanguination
Sequential Organ Evisceration and Bench Surgery
Preparation

Organ Retrieval and Preservation

Hypothermic Preservation ( approx. 4 degrees
Centigrade ) by In Situ or Ex Vivo Perfusion & Core and
Topical Cooling
Perfusion w/ Chilled LRS, Collins, euroCollins or UW
(University of Wisconsin ), Custodiol HTK Soln. (Histidine
Tryptophan Ketoglutarate) Preservative Solution
Injury During Preservation due to Mitochondrial Damage
(loss of ATP precursors), Oxygen Free Radicals, Activation
of Catabolic Enzymes from the Lysozomes
(phospholipases & proteases) and Cytotoxic Products
(thromboxane & leukotrienes)

Immunosuppressive Agents
STEROID: blocks Ca ionophore induced
lymphocyte proliferation
Lymphokine Synthesis Inhibitors: CYCLOSPORINE
and TACROLIMUS (FK506)
Nucleoside Synthesis Inhibitor: AZATHIOPRINE &
MYCOPHENOLATE MOFETIL (RS61443)
Cytokine Signal Transduction Inhibitors:
SIROLIMUS & LEFLUNOMIDE
MONOCLONAL & POLYCLONAL ANTIBODIES:
for induction and reversal or rescue of acute
rejection episode

The Clinical Immunosuppressive Matrix

Prevention and Prophylaxis of Acute Rejection
Episode: Positive cross match is absolute
contraindication. Identification of immunologically
reactive recipients with PRA (panel of reactive
antibodies)
Induction Immunosuppression: Two (2) weeks
after transplant using sequential or standard
immunosupression
Short Term Maintenance
Immunosuppression: First 90 days after
transplant characterized by delicate balancing of
CyA or Tacrolimus, Mofetil and Steroids

The Clinical Immunosuppressive Matrix

Anti Rejection Immunosuppression: Period of
Acute Rejection Episode within the first year of
transplant. Treated with pulse steroid therapy (IV
methylprednisolone) for 3 to 5 days. Steroid
resistant episode is treated with OKT3 or with
polyclonal antibodies
Long Term Maintenance Immunosuppression:
Progressive reduction of immunosuppressive drugs.

The Risks of Immunosuppression

NEOPLASIA
The Risk for Cancer is 1% to 16%
Most Common are Non Melanotic Skin & Lip Cancer,
Lymphoproliferative Diseases (LPD) and Cervical
Carcinoma
OKT3 Treatment Poses a Particular Risk for LPD
Therapy is Based on Surgical Extirpation with
Reduction of Immunosuppressive Therapy

The Risk of Immunosuppression

INFECTIONS
80% Develop at Least One Infection After
Transplantation
40% of Death are Due to Infectious Complications
55% are Bacterial, 30% Viral and 15% Fungal
Most Infection Arise in the Urinary Tract, Plastic
Venous Catheters, Surgical Wound and
IntraAbdominal Site

The Risk of Immunosuppression

INFECTION
Bacterial Infections are Polymicrobial
Most Common Viral Infection are DNA Viruses of
the Herpes Virus Family (CMV, EBV, HSV & VZV)
Use of Polyclonal Antibodies and Monoclonal
Antibodies for Acute Rejection Episodes are
Associated with Increased Risk for Viral Infections
Candida Albicans and Pneumocystic Carinii are
Most Common Fungal and Protozoal Agents
Respectively

Solid Organ TRANSPLANTATION:

An Overview
Renal Transplantation: ESRF
Liver Transplantation: Cirrhosis, Biliary Atresia,
Acute Liver Failure & Inborn Errors of Metabolism
Heart Transplantation: Ischemic Disease,
Cardiomyopathy, Valvular Disease, Congenital
Disease, Drug Induced Myocardial Destruction
Pancreas Transplantation: Insulin Dependent
Diabetes Mellitus
Small Bowel Transplantation: Short Bowel from
vascular and congenital conditions

 dont bring your ORGANS to Heaven, God Knows

We Need Them Here

TRANSPLANT
is Good,
Let Us Talk About It