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TRANSPLANTATION

DR. ELOISE ANA SUAN


DEFINITION

TRANSPLANTATION Process of transferring an organ, tissue or cell from one place to another

ORGAN TRANSPLANT Surgical procedure in which a failing organ is replaced by a functioning one

May be ORTHOTOPIC or HETEROTROPIC

3 MAIN CATEGORIES:

AUTOTRANSPLANT In the same person

ALLOTRANSPLANT One person to another of the same species

XENOTRANSPLANT From one organism to another of a different specied


TRANSPLANT ANTIGENS
• HUMAN LEUKOCUE ANTIGEN (HLA) SYSTEM – responsible for rejection

• 2 major classes

• Cass I antigen (HLA-A, HLA-B, and HLA-C)

• Class II antigen (HLA-DR, HLA-DP, and HLA-DQ)


• Principal function is to present the fragments of foreign proteins to T lmphocytes

• 2 different mechanisms:

• Cellular Rejection

• Humoral Rejection
ALLORECOGNITION AND LYMPHOCYTE
ACTIVATION

ALLORECOGNITION – discriminate between self


and nonself cells and tissues
T cells plays a crucial role
Activated T cells attack transplanted organ

HLA antigen processed by B cells interacts with


activated helper T cells → proliferation and
antibody production
CLINICAL REJECTION

HYPERACUTE ACUTE CHRONIC


Triggered by preformed Most common type Occurs slowly and is
antibodies again the Further divided into usually progressive
donor’s HLA or ABO blood Cellular (T-cell mediated) Eventually leads to tissue
group antigens rejection, Humoral fibrosis and loss of graft
(antibody-mediated), function
rejection or Both
CLINICAL IMMUNOSUPPRESSION

INDUCTION PHASE
Starting immediately posttransplant, when
the risk of rejection is highest

To prevent acute rejection

MAINTENANCE
Usually starting within days posttransplant
and usually continuing for the life of the
graft and the recipient
INDUCTION PHASE

DEPLETING ANTIBODIES
• Rabbit antithymocyte globulin (Thymoglobulin)
• Total dose of 6mg/kg
• Causes a cytokine release syndrome
• Principal SE: fever, chills, arthralgia,
thrombocytopenia, leukopenia, and an increased
incidence of variety of infection
• Atgam – purified gamma globulin obtained by
immunizing horses with human thymocytes
• Results in rapid depletion of peripheral lymphocytes
INDUCTION PHASE
NONDEPLETING ANTIBODIES
• Basilximab (Simulect) – anti-CD25 monoclonal
antibody
• Powerful induction agent without added risk of
infection, malignanices, or other major side effects
• Alemtuzumab (Campath, Lemtrada) – anti-CD25
monoclonal antibody
• Causes cell death by complement-mediated cytoclysis,
antibody-mediated cytotoxicity, and apoptosis
• 1 dose (30mg) – depletes 99% of lymphocytes
• Causes significant cytokine release
• Risk of infection and posttransplant
lymphoproliferative disorders
CORTICOSTEROIDS

MAINTENANCE • Often the first-line agents in he treatment of


acute rejection
• Most common maintenance immunosupression
PHASE regimen: triple-drug therapy (prednisone,
calcineurin inhibitor, and antimetabolite)
• Given in large doses preoperatively and
immediate post-op
• Tapered to an adult dose of roughly 5 to
15mg daily or completely stopped
AZATHIOPRINE
• Converted to 6-mercaptopurine and inhibits both
MAINTENANCE the de novo purine synthesis and salvage purine
synthesis
• Preferred in recipients who are considering
PHASE conceiving a child
• SE (dose related): bone marrow suppression,
leukopenia, hepatotoxicity, pancreatitis,
neoplasia, anemia and pulmonary fibrosis
• Drug interaction
• Allopurinole – blocks AZA metabolism,
increasing the risk of pancytopenia
MYCOPHENOLATE MOFETIL (MMF)
• Prodrug of mycophenolate acid, derived from
MAINTENANCE Penicillium fungi
• Inhibitor of IMPDH
• Starting dose: 1g BID
PHASE • SE: GI (most common), diarrhea, nausea,
dyspepsia, and bloating
• Esophagitis and Gastritis in 5% → CMV or
herpes virus infection
• Leukopenia, anemia, and
thrombocytopenia
SIROLIMUS
• Mammalian target of Rapamycin (mTOR) inhibitor
• SE: hypertriglyceridemia, impaired wound
healing, thrombocytopenia, leukopenia, and

MAINTENANCE anemia

CYCLOSPORINE (CALCINEURIN INHIBITOR)


PHASE • Binds with cyclophilin and inhibits calcineurin
activity → T-cell activation suppression (IL-2)
• Ex: Sandimune, Gengraf and Neoral
• Can be given IV or orally to maintain trough levels
Of 250 to 350ng/mL for the first 3 months
posttransplant
• SE: nephrotoxicity, hyperkalemia and
hypomagnesemia, neurological complications,
hirsutism and gingival hyperplasia, hypertension
and hyperlipidemia
TACROLIMUS
• Calcineurin inhibitor tacrolimus (Prograf)
• Can be given IV or orally, or sublingual to

MAINTENANCE maintain levels of 8 to 12 ng/mL for the first 3


months posttransplant
• SE: new-onset diabetes, alopecia, nephrotoxicity,
PHASE hypertension, hyperkalemia, hypomagnesemia,
infection

BELATACEPT
• Also known as LEA29Y
• SE: posttransplant lymphoproliferative disorder,
metabolic disorders, hypertension, neurotoxicity,
glucose abnormalities and adverse cosmetic
effects
RITUXIMAB
• Chimeric anti-CD25 (anti-B cells) monoclonal
HUMORAL REJECTION antibody
• Used as treatment of antibody-mediated
rejection and use in desentization protocols

BORTEZOMIB
• Proteasome inhibitor, approved for treating
multiple myeloma

ECULIZUMAB
• Blocks the activation of the terminal
complement cascade
• Useful to treat antibody-mediated rejection
and to desensitized patients pretransplant
• SE: infection (N. meningitides)
• Should be immunized at least 2 weeks before
INFECTION AND
MALIGNANCIES
EARLY
INFECTION • Occuring within 1 month posttransplant
• Differentiate between medical and surgical
infections
• Surgical infections – most common and
require expedient surgical intervention
• Liver and Pancreas recipient, most severe
• S/Sx: peritonitis, fever, hypotension, ileus,
abdominal pain
• Treatment: prompt return to the OR
• Localized infection or abscess – Percutaneous
drainage an antibiotics
• Medical infections – respiratory, urinary tract
and bloodstream infection
• Treatment should be aggressive
LATE
INFECTION • Primarily due to chronic immunosupression
• Etilogic agents:
• Herpesvirus – most common
• CMV – can be transmitted or reactivated
• Usually occur 3 to 6 months posttransplant or
during treatment for rejection
• Treatment: IV ganciclovir, reduction of
immunosuppression
• EBV – first line of treatment is to reduce
immunosuppresion
• Rituximab – advanced PTLD
• Invasive fungal infections – high risk after 6 months
posttransplant
• Blastomyces dermatidis
• Coccidoides immitis
• Histoplasma capsulatum
• Opportunistic infections
• Pneumocystis jiroveci
MALIGNANCIES
• 5-fold increased risk
• Kaposi’s sarcoma, nonmelanoma, skin cancer, non-
Hodgkin’s lymphoma, and cancer of the liver, anus, vulva
and lip
• Increased risk for melanoma, Hodgkin’s lymphoma, cancer of the
lung, kidney, colon, rectum, and pancreas
ORGAN PROCUREMENT AND
PRESERVATION
(DECEASED AND LIVING
DONORS)
DECEASED DONORS – determined by the cessation of both cardiac
and respiratory function

DONATION AFTER BRAIN DEATH


• Brain Death – defined as the irreversible cessation of
brain functions, including brainstem
• 4 essential steps in the clinical diagnosis of brain death
• Establishment of the proximate cause of
neurologic insult
• Medical and social history obtained from
available family history
• Serologic test or molecular detection of HIV and
viral hepatitis
GOALS FOR BRAIN-DEAD DONORS
• Maintain core temperature between
36C to 3.5C
• MAP >70mmHg or systolic pressure
>100mmHg
• Hemoglobin level between 7 and
10g/dL
• Hormonal therapy
• Aggressive treatment of arrhythmias
and metabolic derangements
SURGICAL TECHNIQUE
• Long incision to provide wide
exposure of all thoracic and
abdominal organs
• Cattell-Braasch maneuver
• Identify Distal aorta, iliac
bifurcation and IVS
Identify INFRARENAL AORTA – site of cannulation for flushing organs with
cold preservation solution
• Administer systemic heparin (300U/kg) prior
Clamp SUPRACELIAC AORTA
Identify root of SUPERIOR MESENTERIC ARTERY – temporarily occluded at
time of flushing
• GB is incised and flushed with ice-cold saline to
clear bile and sludge
• If pancreas is to be procured – duodenum is
flushed with antimicrobial solution
• Thoracic organs, liver, pancreas and kidneys
then removed
DECEASED DONORS – determined by the cessation of both cardiac
and respiratory function

DONATION AFTER CARDIAC DEATH


• Warm ischemic injury to organs can occur during the
period between circulatory cessation and rapid core
cooling
• Liver grafts – warm ischemic time >25 minutes
develop ischemic cholangiopathy and fail
• ECMO – minimize ischemic injury to organs
LIVING DONORS
• 3 guiding principles of ethical framework
• Beneficence to the recipient
• Nonmalificence to the donor
• Donor’s right to autonomy
• Advantages of living donors
• Availability of lifesaving organs
• Shorter waiting time
• Transplants are planned – allows for better
preoperative preparation of the recipient
• Immunologic benefits
• Disadvantage
• Risk of the living donor
LIVING DONORS
• Kidney
• Avoid extensive dissection of the ureter
• Preserve as much length of the renal artery
and vein as possible
• Liver – preserve integrity of vascular structure
• Pancreas – vascular inflow and outflow from
splenic artery and vein
• Intestine – 200cm of donor’s ileum
• Inflow and outflow from ileocolic vessels
• Lung – one lobe of one lung each from 2 donors
ORGAN TRANSPLANTATION
Hypothermia and
01
pharmacologic inhibition
Preservation solution – contains
lactobionate, raffinose and
02 hydroxyethyl starch
Histidine-tryptophan-ketoglutarate
solution
Kidney – ischemic time >24
03 hours necessitate temporary
dialysis
Heart and Lung – ischemic
04 time should be <6 hours
KIDNEY
TRANSPLANT
PRETRANSPLANT EVALUATION
MEDICAL SURGICAL
EVALUATION EVALUATION

IMMUNOLOGIC PSYCHOSOCIAL
EVALUATION EVALUATION
ABSOLUTE
CONTRAINDICATION
• Active Infection
• Presence of Malignancy
• Active substance abuse
• Poorly controlled
psychiatric illness
MEDICAL EVALUATION
• Cardiovascular evaluation
• Diabetes and Hypertension
• Screen for presence of significant cardiac
conditions, prior history of CHF and coronary
interventions or valcular surgery
• Resting 12L-ECG
• Echocardiography
• Stress Test – for patients with no active cardiac
conditions but with risk factors
• Troponin T levels
MEDICAL EVALUATION
• Malignancies
• Untreated and/or active malignancies are absolute
contraindications, except:
• Nonmelanocytic skin cancer
• Incidental Renal cell CA at time of concurrent
nephrectomy and renal transplantation
• Undergone treatment
• low-grade tumors with low risk of recurrence –
wait at least 2 years after successful treatment
• Advanced stage or with high risk of recurrence –
delay at least 5 years
MEDICAL EVALUATION
• Infections
• Thorough history of infections and immunizations
• Vaccinations completed at least 4-6 weeks before kidney
transplant
• Splenectomy anticipated – immunize against encapsulated
organisms
• With history or residing in endemic areas serologic screening
with chest roentgenogram (fungal infections)
• Acute Viral Hepatitis – contraindication to kidney transplant
• Chronic viral hepatitis
• Obtain liver biopsy
• Consider combined liver-kidney transplant
MEDICAL EVALUATION
• Kidney Disease
• 3rd most common cause of graft loss – recurrence
of glomerular disease
• FSGS – investigate for posttransplant nephrotic
proteinuria
• Rescue plasmapheresis should be instituted
• Adjuvant therapy with Rituximab
• Hypercoagulability
• History of thrombotic events, repeated
miscarriage, family history of thrombophilia
SURGICAL EVALUATION
UROLOGIC EVALUATION
• VCUG and complete lower urinary tract evaluation

VASCULAR EVALUATION
• Potential implant sited for kidney graft: iliac vessels, aorta, and vena cava
• Abdominal CT scan or ultrasound
• Pulsatile intra-abdominal mass
• Diminished or absent peripheral pulses
• Claudication
• Rest pain
• Tissue loss in LE
IMMUNOLOGIC EVALUATION
• ABO blood typing and HLA typing required
• Panel-reactive antibody (PRA) assal – higher PRA level, higher risk
for a positive cross-matching
• Luminex technology – use HLA-coated fluorescent microbead and
flow cytometry
• Considered gold standard
PSYCHOSOCIAL EVALUATION
• Patients with uncontrolled psychiatric disorders are at a high risk for
concompliance with drug treatment, impaired cognitive function, and the
development of substance abuse
RECIPIENT OPERATION
• Usually transplanted heterotropically
• Right iliac fossa (retroperitoneal) –
ideal position
• Left iliac fossa – if pancreas transplant
is anticipated or if previous failed left
iliac kidney grafts
RECIPIENT OPERATION

• Exposure: curvilinear skin incision, 1 or 3 fingerbreadth above


the midline pubic bone and the lateral edge of the rectus
sheath
• donot’s renal artery and vein are anastomosed to the
recipient’s external iliac vessels in an end-to-side fashion
RECIPIENT OPERATION
• Exposure: curvilinear skin incision, 1 or 3 fingerbreadth above
the midline pubic bone and the lateral edge of the rectus
sheath
• donot’s renal artery and vein are anastomosed to the
recipient’s external iliac vessels in an end-to-side fashion
• Urinary continuity estabilished
Leadbetter-Politano Ureteroneocystostomy
• Large cystostomy created in the dome of the bladder
• Donor ureter spatulated is brought through a lateral
and somewhat inferior 1-cm submucosal tunnel into
the bladder
Lich (Extravesical)
Ureteroneocystostomy
• Careful dissection of a 1-cm
portion of the muscular layers on
the anterolateral portion of the
bladder until a “bubble” of mucosa
is exposed
• mucosa-to-mucosa anastomosis
over a temporary ureteral stent
• Mucosal layers of the bladder are
then carefully approximated over
the anastomosis to prevent reflux
Grafts with Multiple Renal Arteries
• Fare as well as those with single vessels
• Vascular reconstruction options:
• Implanting the donor’s arteries separately
• Reconstructing the multiple arteries into a common channel
• Combining multiple arteries in a common Carrell patch
En bloc Grafts
• Donor aorta and vena cava are used as the vascular inflow and
outflow conduits
• Color of 2 kidneys look different after reperfusion → attempt
repositioning to rule out torsion
PREOPERATIVE CARE PREOPERATIVE CARE
• Thorough history and PE
• Negative PRA levels who have undergone blood
transfusion → tissue cross-match is necessary
• Emergency dialysis – patients with hyperkalemia
over fluid overload
• dialysis-dependent transplant candidates – catheter
site should be examined preop
• Vascular evaluation is mandatory
• Routine preoperative evaluation: CXR, 12L ECG,
blood typing, cross-match tests, and prophylaxis
against surgical site infection
PREOPERATIVE CARE
INTRAOPERATIVE
• Recipients should be kept well hydrated to avoid
acute tubular necrosis
• Heparin prior to vascular occlusion
• Before reperfusion – CVP should be maintained
around 10mmHg, and SBP should be above
120mmHg
• Often Administered before reperfusion
• Mannitol
• Diuretics (e.g. Furosemide)
POSTOPERATIVE
PREOPERATIVE CARE
• CRUCIAL ELEMENT:
• Hemodynamic stability
• Euvolomic status – fluid replacement of recipient’s
UO
• Hypotension
• Posttransplant hypertension
• Fluid and Electrolyte balance
• Brisk diuresis – aggressive replacement of
electrolytes
• With ATN, fluid overload or hyperkalemia – fluid
restriction for hyperkalemia or hemodialysis

• Postoperative urine output – surrogate marker to


monitor graft function
PREOPERATIVE CARE • Sudden decreased or minimal UO – require
immediate attention
• Most common cause – change in volume status
• Diagnostic studies: doppler ultrasound, nuclear
renogram, biopsy
• Postoperative bleeding – uncommon
• s/sx: expanding hematoma over the surgical site,
increased pain over the surgical site, increased pain
over the graft, falling hemoglobin level, hypotension,
and tachycardia
• Dx: Doppler ultrasound
• Indication for surgical exploration:
• Ongoing transfusion requirement
• Hemodynamic instability
• Graft dysfunction from hematoma compression
PREOPERATIVE CARE
• Graft thrombosis – rare, Occuring in fewer than 1%
of recipients
• Recipient factors: history of recipient
hypercoaguloathy, severe peripheral vascular disease
• Donor-related risk factors – use of en-bloc or pediatric
donor kidney, procurement damage, technical factors,
hyperacute rejection
• Dx: Doppler ultrasound
• Tx: urgent thrombectomy (rarely results in graft
salvage)
PREOPERATIVE CARE • Urologic complications – up tp 5%
• Symptoms: urine leak (fever, pain, swelling at graft
site, increased creatinine levels, decreased UO and
Cutaneous drainage)
• Dx: combination of US, nuclear renography, drainage
of perinephric fluid collection, and comparison of
serum and fluid creatinine levels
• Tx: Surgical treatment and repair, percutaneous
placement of nephrostomy, ureteral stenting
• Early urinary obstruction
• Late → related to ischemia
• Hydronephrosis on US
• Tx: Percutaneous placement of nephrostomy, ureteral
stenting, surgical intervention (ureteral
reimplantation or ureteropyelostomy)
Results
Most common cause of organ loss:
● Recipient death (usually from CV causes) with a functioning graft
● Chronic allograft nephroparhy – slow, unrelenting deterioration of graft function
● Surgical technique – 1% to 2%
PANCREAS
TRANSPLANTATION
PANCREAS TRANSPLANTATION
• Only Definitive long-term treatment for patients with Insulin-Dependent
Diabetes Mellitus
• Performed in 3 recipient categories
• Simultaneous Pancreas and Kidney transplant – diabetic and uremic
patients
• Pancreas after kidney (PAK) transplant – diabetic and posturemic patients
(15%)
• Pancrease transplant alone – non uremic patients with brittle diabetes
Mellitus (5)%
DONOR OPERATION DONOR OPERATION
• Contraindications to donation:
• History of Type I Diabetes
• Relative contraindication: previous pancreatic
prodecure(s), pancreatic disorders (chronic
pancreatitis and IPMN)
• “no-touch” technique in Pancreas procurement is
preferred
• Pancreas should not be extensively flushed at the
end of procurement
• Splenic artery and SMA can be temporarily clamped at
their origin
BACK TABLE PREPARATION OF THE PANCREAS
GRAFT
• Consists of 4 steps:
• Removal of the spleen
• Shortening, restapling, and/or suture reinforcement of the mesenteric
root
• Trimming of any excess distal and proximal duodenum, along with
reinforcement of the proximal staple line
• Arterial reconstruction

• Arterial inflow – Y-graft reconstruction


• end-to-end anastomosis: external iliac-SMA; internal iliac-
splenic artery

• Venous outflow – portal vein kept relatively short


RECIPIENT OPERATION
MANAGEMENT OF EXOCRINE PANCREATIC SECRETION
Drainage of duodenal segment to bladder
• Advantage:
• rejection of the exocrine Pancrease precedes rejection of the
endocrine Pancrease by 5 to 7 days
• Avoids the bacterial contamination that occurs with enteric
drainage

Drainage to the small bowel (enteric drainage)


• more physiologic
• Antimesenteric side of the donot’s duodenum is anastomosed to
the an times enteric portion of the recipient’s duodenum in a
side-to-side fashion
COMPLICATION
• Technical complication rate is higher

MOST COMMON SURGICAL COMPLICATIONS:


• THROMBOSIS (5%-15%)
• Usually occurs within the first week posttransplant
• Venous thrombosis more common than arterial thrombosis
• Clinical symptoms: swollen and tender graft, hematuria, lower
extremity edema, and deep vein thrombosis
• Diagnosis: Doppler Ultrasonography
• Treatment: Surgical exploration, possible graft pancreatectomy
COMPLICATION

MOST COMMON SURGICAL COMPLICATIONS:


• INTRA-ABDOMINAL ABSCESSES (5%-15%)
• Interventional radiologic procedure to drain abscess
• broad-spectrum antimicrobial agents for the first 7 days
posttransplant
• BLEEDING (6%-8%) – frequently requires relaparotomy
• PANCREAS-SPECIFIC COMPLICATIONS: graft pancreatitis, pancreatic
fistulas, and pancreatic pseudocysts
• ANASTOMOTIC LEAK
• ARTERIAL PSEUDOANEUYSM, AV FISTULAS, AND WOUND
DEHISCENCE
COMPLICATIONS
NONSURGICAL COMPLICATIONS
• REJECTION – most common, 30% within the first year
• Diagnosis:
• Should be confirmed by Pancreas graft biopsy
• increase in serum amylase and lipase plus:
• bladder-drained recipients – decrease in urinary amylase level >25%
from baseline
• enteric-drained – increase in serum amylase and Lipe levels
• S/Sx: Tenderness over the graft, unexplained fever, and hyperglycemia (late finding)
• INFECTIONS – CMV, HCV, or extra-abdominal bacteria or fungi
• MALIGNANCIES – PTLD
• GRAFT-VS-HOST DISEASE
COMPLICATION
UROLOGIC COMPLICATIONS
• Irritating nature of pancreatic enzyme on the urothelium
• Dehydration and metabolic acidosis – loss of bicarbonate from pancreatic
secretions
• Complications are usually chronic – 20%-30% require conversion to enteric
drainage
LIVING DONOR PANCREAS TRANSPLANTS
• Ideal for patients with an identical twin
• Patients with high PRA levels should be considered for a living
donor transplant
• Reduce the risk of graft rejection
• Donor splenic artery and vein are anastomosed to the recipient’s
external iliac artery and vein in an end-to-side fashion
• Exocrine drainage to bladder or bowel
• Immunosuppressive protocols: antibody induction therapy,
followed by administration of tacrolimus and MMF for maintenance
ISLETS VERSUS PANCREAS TRANSPLANTS
• Islet transplant are less invasive
• 2 types of transplant are complementary
• Pancreas transplant remains the treatment of choice for β
• 10,000 islets per kilogram of body weight needed to achieve insulin
independence
• Needs up to 4 donor pancreas for one islet recipient
• Primary goal:
• Reduction in the incidence and severity of hypoglycemic event
• Reduction in exogenous insulin requirements
• Amelioration of HbA1c levels
ISLET TRANSPLANTATION
• Pancreas harvested from donor is enzymatically digested then
purified using density gradients
• Infused into the portal vein of a diabetic recipient
• Advantage:
• Restoring β-cell secretory capacity
• Improving glucose counter-regulation
• Restoring hypoglycemia awaireness
• Providing perfect or near-perfect glucose hemostasis, and potentially, preventing secondary
diabetic complication
• Does not involve a major surgical procedure
• Complication:
• Portal hypertension
• Portal vein
• Hepatic abscess
• bactermia
LIVER
TRANSPLANTATION
INDICATIONS
• Any form of irreversible liver disease is an indication
• Alcoholic Liver Cirrhosis
• 4 to 8 ounces of liquor daily for 10 to 15 years – increased risk for developing
cirrhosis
• General requirement for acceptance as a transplant candidate – 6 months of
abstinence
• Transplant for HCV – prone to recurrence
• Viral levels reach pretransplant levels as early as 72 hours posttransplant
• Viral infection often accelerated posttransplant
• Primary biliary cirrhosis – excellent posttransplant outcomes
• Primary sclerosing cholangitis
• Significant risk factor for cholangiocarcinoma –
annual screening (imaging and measurement of
serum Ca19-9)
INDICATIONS
• Hemochromatosis – careful cardiac evaluation is necessary pretransplant
• α1-Antitrypsin deficiency – careful pulmonary evaluation is necessary
• Wilsons’s disease – leads to copper accumulation in the liver, brain and
cornea
• Advanced/Unresectable HCC or HCC with significant cirrhosis
• Meet’s the Milan Criteria:
• Single tumor <5cm in diameter
• 3 tumors; <3cm in diameter
• No vascular invasion
• Cholangiocarcinoma
• Acute Fulminant Hepatic Failure
• Highest priority for the next available liver in their
UNOS region
INDICATIONS
• Acute Fulminant Hepatic Failure
• Highest priority for the next available liver in their UNOS region
• Cerebral edema – serious complication of acute liver failure
causing brain herniation
• Irreversible brain damage is transplant is not performed
• Transplant according to the King’s College Criteria:
• Acetaminophen-induced disease
• pH <7.3 or grade III/IV encephalopathy
• Prothrombin time >100 seconds
• Serum creatinine >3.4mg/dL
RECIPIENT
• Diagnosis itself is not an indication
OPERATION • Hepatic encephalopathy →
Hyperammonemia
• Ascites
• Transudate with high serum-ascites
gradient (<1.1g/dL)
• Refractory ascites – necessitates large-
volume paracentesis and eventually TIPS
procedure
• Spontaneous bacterial peritonitis
• First line empiric treatment: third-
generation cephalosporin
RECIPIENT
OPERATION • Portal Hypertensive bleeding cirrhosis
• Initial medical treatment: vasopressin and
ocreotide
• Initial intervention: endoscopy with
sclerotherapy
• Initial attempts fail: balloon tamponade
(Sengstaken-Blakemore tube) and
emergent TIPS placement
• Last line of treatment: emergency
surgery, Suguira procedure
• Prevention of variceal bleeding: β-
blockers
RECIPIENT
OPERATION • Hepatorenal syndrome
• Characterized by oliguria (<500ml of urine/day)
and low urine sodium levels (<10mEq/L)
• Initial medical therapy: ocreotide, midodrine,
and vasopressing analogs
• Reversed by liver transplant, even after dialysis
dependence
• Model for End-Stage Liver Disease (MELD)
• Minimum MELD score of 18 – have survival
benefit posttransplant
• MELD score between 15 and 18 – does not
confer a survival advantage
RECIPIENT • Acute Liver Failure itself is an indication
OPERATION for a liver transplant
• Status 1 (first priority UNOS) – must meet
the following criteria
• Onset of hepatic encephalopathy
within 8 weeks after the first
symptoms of liver disease
• Absence of preexisting liver
disease
• Ventilator dependence, dialysis,
or an INR >2.0
ABSOLUTE CONTRAINDICATIONS
• Insufficient cardiopulmonary reserve
• Severe COPD with oxygen dependence
• Severe pulmonary hypertension with mean
pulmonary artery pressure >35mmHg
• Uncontrolled malignancy or infection
• Refractory compliance
RELATIVE CONTRAINDICATIONS
• Older age
• Alcoholic liver disease – require 6 months of abstinence from drugs and
alcohol
• Uncontrolled infection pretransplant
• Fungal and multidrug-resistant bacterial infections
• HIV infection
• History of malignancy other than HCC
SURGICAL PROCEDURE
ANHEPATIC PHASE – begins after the liver
is removed
• Characterized by the absece of inferior
vena caval return to the heart and by
portal congestion due to clamping of
the portal vein
• Unable to tolerate → venovenous
bypass
SURGICAL PROCEDURE
• Donor liver placed in orthotopic
position
• Suprahepatic vena caval anastomosis
performed first in end-to-end fashion,
followed by infrahepatic vena caval
and portal anastomosis (both end-to-
end)
• Liver reperfused – arterial anastomosis
between donor hepatic or celiac trunk
with the recipient CHA in an end-to-
end fashion
• Bile duct anastomosis (end-to-end)
SURGICAL PROCEDURE
PIGGYBACK TECHNIQUE
• Recipient’s IVC is preserved
• Increases hepatectomy time and blood loss
• Allows venous return from the lower body
to the heart during anhepatic phase and
improve renal perfusion
PEDIATRIC TRANSPLANT
Indications
• Biliary atresia – most common indication
• Kasai Procedure – RNY loop of bowel
is directly anastomosed to the hilum of
the liver
• Allows time for children to grow in
size, reducing the risk of a
transplant when it is required
• Metabolic Disorders
• PELD (Pediatric End-Stage Liver
Disease) score used
PEDIATRIC TRANSPLANT

• Surgical procedure similar to adult


• Complications more common
• Donor size matching very important
• Deceased donor split-liver transplant and
living donor transplants developed
DECEASED DONOR SPLIT-LIVER TRANSPLANT
• Deceased donor allograft can be split into 2 grafts
• Child – left lateral segment
• Adult – extended right segment
LIVING DONOR
TRANSPLANTS
• Donation by an adult living donor to an
adult recipient – right or left lobe of the
liver
• Donation by an adult living donor to a
pediatric recipient – left lateral lobe
• Overall donor mortality rate after
donation – 0.4%
• Overall complication rate – 40%
• Rate of serious complications resulting in
lasting disability – 1.1%
• Absolute contraindication for recipient –
critical illness
POSTOPERATIVE CARE
- First goal immediate posttransplant – stabilize major organ systems
- Essential to maintain acid-base equilibrium and hemodynamic stability
- Appropriated hemoglobin levels should be maintained
o Ongoing bleeding mandates a return trip to the OR
- Transfusion of platelets must be done prudently – can increase risk of hepatic artery
thrombosis
- Evaluate graft function frequently
o If impaired – urgent ultrasound to assess for the presence of vascular complications
EVALUATION OF GRAFT FUNCTION
• Begins in the operating room – overall appearance,
presence of swelling, and quantity and quality of bile
production after perfusion
• Monitor at ICU
• Transaminase levels usually peak by post-op day 2
• AST >2500IU/L – suggestive of significant injury
• Cholestasis – peaks from post-op day 7 to 12
• INR – improve shortly after reperfusion
EVALUATION OF GRAFT FUNCTION
• Primary Non-function – seen in 3% to 4% of patients
• Graft does not function for any identifiable reason
• Peak AST level of 5000IU/L – predictive of primary
nonfunction graft
• Factors associated:
• Donor macrosteatosis
• Prolonged cold and warm ischemic times
• Prolonged donor hospital stay
COMPLICATIONS
VASCULAR COMPLICATIONS
• Occur in about 8% to 12% of recipients
• Include thrombosis, stenosis and pseudoaneurysm formation
• Hepatic Artery Thrombosis – most common vascular complication
• Mortality rate 50%, even after definitive therapy
• Early presentation can be dramatic
• Late presentation can be asymptomatic or subtle
• Portal Vein Thrombosis – liver dysfunction, ascites and variceal bleeding
• Tx: Operative Thrombectomy
COMPLICATIONS
BILIARY COMPLICATIONS
• “Achille’s heel” of liver transplantation
• Signs: fever and abdominal pain, with bilious drainage from surgical drains
• Dx: Cholangiography
• Manifest as Leaks or Strictures
• Leak – require a reoperation and surgical correction
• Strictures – can be managed with radiologic or endoscopic intervention
COMPLICATIONS
INFECTION
• Early infectious complications – often associated with initial graft function and pretransplant factors
• Intra-abdominal infections – possible leak
• Fungal infection – associated with poor graft function

ACUTE REJECTION
• Occurs in approximately 20%
• First line treatment: high dose corticosteroids → antilymphocyte therapy
• Maintenance immunosuppression: corticosteroid, tacrolimus, and mycophenolate
INTESTINAL AND
MULTIVISCERAL
TRANSPLANTATION
OBSTACLES:
• High immunogenicity caused by
its abundant lymphoid tissue
• Microbial colonization of the
intestine – risk of translocation
of pathogenic microorganisms
into the recipient’s circulation
INDICATIONS AND RECIPIENT SELECTION
• Irreversible intestine failure in combination with TPN
failure
• Intestinal failure, variables include:
• What part of the SI is absent
• Ileocecal valve involvement
• Previous ostomy
• Length of remaining colon
• TPN Failure
INDICATIONS AND RECIPIENT SELECTION
• Liver Failure
• Combined Liver-Intestine Transplant (Treatment of Choice)
• Multivisceral transplant (liver, pancreas, stomach,
duodenum, and/or SI)
• Child: Diffuse intestinal dysmotility syndrome
• Adult: Diffuse portomesenteric thrombosis, extensive intra-
abdominal desmoid disease encasing the main visceral
vascular structures with concurrent short gut
syndrome or massive abdominal trauma
INDICATIONS AND RECIPIENT SELECTION
SURGICAL
PROCEDURES
ISOLATED INTESTINE
TRANSPLANT
• Blood supply based on the arterial inflow
from the SMA and venous outflow from
the SMV
• Living Donor: 150 to 200 cm of donor’s
ileum on a vascular pedicle comprising the
ileocolic artery and vein
• Recipient Operation:
• Aterial inflow to the graft from recipient’s
infrarenal aorta
• Venous drainage – vis systemic or
portomesenteric drainage
COMBINED LIVER-INTESTINE
TRANSPLANT

• Blood supply based on the arterial inflow


from the celiac axis and SMA
• Venous drainage achieved by anastomosis
of the hepatic vein to the recipient’s vena
cava
• Performed almost exclusively for pediatric
patients
• Living donor: Segments II and III of the
donor’s liver are used, in addition to the
intestine
MULTIVISCERAL
TRANSPLANT
• Stomach is part of the graft
• Transection of the Gi tract
occurs at the distal esophagus
POSTOPERATIVE CARE
• Cardiopulmonary and Renal Function closely monitored
• Broad-spectrum antibiotic
• Intestine transplants have the highest rate of rejection
• Induction: polyclonal T-cell antibody and high dose of
corticosteroid
• Maintenance: corticosteroid and calcineurin inhibitor Tacrolimus
• Monitor for systemic infections
• TPN immediate posttransplant
COMPLICATION
• Complication rate high
• Most common: intra-abdominal abscesses, enteric
leaks, intra-abdominal sepsis, graft thrombosis, life-
threatening bleeding, and central line problems
• Immunosuppression-specific complications: rejection,
PTLD, graft-versus-host disease, infections and
malignancies
HEART
TRANSPLANTATION
INDICATIONS
Ischemic dilated
01
cardiomyopathy

02 Idiopathic dilated
myopathy

03 Congenital Heart Disease


EVALUATION Recipient – Echocardiography, Right and
left heart catheterization, evaluation for
any undiagnosed malignancies,
laboratory testing

Donor – serologic testing,


echocardiography, chest X-ray,
hemodynamic testing, coronary artery
evaluation
• Determine wheter donor’s heart can
withstand up to 4 hours of cold ischemic
time
PROCEDURE
• Most often performed
orthotopically
• Recipient’s native heart is
removed, leaving the SVC, IVC, Left
atrial cuff, aorta, and the
pulmonary artery in situ
• Left atrial cuff anastomosed first –
provide left heart inflow
PROCEDURE
• Right Heart inflow
• Bicaval technique by directly sewing
the donor’s SVC and IVC to the
recipient’s vena cavae
• Anastomosis of the Right Atrium to a
Right atrial cuff
• Donor’s main pulmonary artery
connected to the recipient’s
pulmonary artery
• Inotropic support
• Isoproterenol, Dobutamine or
Epinephrine
• Often required for 3-5 days
• Heterotropic or ”piggyback”
transplant – heart can be transplante,
leving the native heart in place
POSTTRANSPLANT CARE
• Must be monitored for both early and late
complications

Early complications
• Pulmonary graft dysfunction
• Acute cellular or antibody-mediated rejection
• Right heart failure secondary to pulmonary
hypertension
• Infection
• Hemodynamic values monitored
POSTTRANSPLANT
• Immunosuppression to prevent CARE
rejection
• Both T-cell-mediated (cellular) and B-cell-
mediated (antibody-mediated) rejection
monitored
• Consists of 3 categories of medication
• Calcineurin inhibitor – usually Tacrolimus
or Cyclosporine
• Antiproliferative agent – MMF or AZA
• Corticosteroid – prednisone
• Assess for infection
POSTTRANSPLANT CARE
Late complications
• Acquired transplant vasculopathy
• Progressive renal failure
• Malignancies – skin cancer and PTLD
• Accelerated CAD – 3rd most common cause of
death posttransplant
• Can begin to develop as early as 1-year posttransplant
• Screening tests and recipient examination
annually after first year
LUNG
TRANSPLANTATION

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