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Solid Organ Transplantation
Daniel Maluf, MDAssistant Professor of SurgeryVCU School of Medicine
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Basic Immunology
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Basic Immunology
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Basic Immunology
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History of organ transplantation
First successful heart transplantDr. Norman Shumway, Stanford University Hospital, Stanford, CA
1968
First isolated pancreas transplantDr. Richard Lillehei, University of Minnesota, Minneapolis, MN
1968
First successful liver transplant*Dr. Thomas Starzl, University of Colorado Health Sciences Center, Denver, CO
1967
First successful pancreas/kidney transplantDrs. Richard Lillehei, William Kelly, University of Minnesota, Minneapolis, MN
1966
First successful kidney transplant*Dr. Joseph E. Murray, Brigham & Women's Hospital, Boston, MA
1954
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History of organ transplantation
*Transplant was the first of its kind in the world
First successful living-related lung transplantDr. Vaughn A. Starnes, Stanford University Medical Center, Stanford, CA
1990
First successful living-related liver transplantDr. Christoph Broelsch, University of Chicago Medical Center, Chicago, IL
1989
First successful double lung transplant*Dr. Joel Cooper, Toronto Lung Transplant Group, Toronto General Hospital, Toronto Canada
1986
First successful single lung transplant*Dr. Joel Cooper, Toronto Lung Transplant Group, Toronto General Hospital, Toronto Canada
1983
First successful heart-lung transplantDr. Bruce Reitz, Stanford University Hospital, Stanford, CA
1981
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7
Cadaveric Donors, Cadaveric Transplants,and Number on Waiting List
0
10,000
20,000
30,000
40,000
50,000
60,000
70,000
80,000
1990 1991 1992 1993 1994 1995 1996 1997 1998 1999
Source: Donors from OPTN data as of 9/5/00; transplants from Scientific Registry data as of 9/5/00; snapshot of OPTN waiting list on the last day of each year.
Donors
Transplants
Waiting List at Year’s End
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Waiting List Additions 1994-2003: U.S.
0
10,000
20,000
30,000
40,000
50,000
60,000
1994 1995 1996 1997 1998 1999 2000 2001 2002 2003Year
Num
ber
of R
egis
trat
ions
Kidney Liver
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Waiting List Additions 1994-2003: U.S.
0
1000
2000
3000
4000
5000
1994 1995 1996 1997 1998 1999 2000 2001 2002 2003Year
Num
ber o
f Reg
istra
tions
Heart Lung Pancreas Heart-Lung Kidney-Pancreas10
Patients waiting for transplantation
Type of Transplant Patients Waitingkidney 52,216liver 17,546pancreas 1,317pancreas islet 295kidney-pancreas 2,540
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Organ Donor and Recovery
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Percent of Cadaveric DonorsContributing to Each Organ Type
Source: OPTN data as of 9/5/00.
0
1,000
2,000
3,000
4,000
5,000
6,000All Donors N = 5,849
2%
40%
28%
85%92%
KidneyN=5,396
LiverN=4,954
PancreasN=1,627
HeartN=2,316
IntestineN=97
LungN=781
13%
3
13
Recovered and Transplanted Cadaveric Organs
1,451
5,012
10,710
2,3161,6271,333
2,2381,298
4,496
9,233
02,0004,0006,000
8,00010,00012,000
Recovered OrgansTransplanted Organs
Kidney Liver Pancreas Heart Lung
Note:Each liver and pancreas segment is counted as an individual organ in this figure.Source:OPTN data as of 9/5/00.
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Organ Disposition (N=21,213) Cadaveric Donors
Not Used9%
Transplanted (Shared)
28%
Used Research3%
Transplanted (Local)
60%
Note: Disposition is shown for 21,213 organs which includes liver and pancreas segments. Source: OPTN data as of 9/5/00.
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Need more organs for transplant!!! Living Donor:
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Deceased and Living Donors1993 - 2003
0
1,000
2,000
3,000
4,000
5,000
6,000
7,000
1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003
Year
Num
ber o
f Don
ors
Deceased DonorLiving Donor
6455
6802
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Using Live-donor Organs:Considerations
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Kidney Transplantation
4
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Kidney Transplantation
1997 National Wait Time– 1099 days
2001 MCVH Wait Time– 845 days
2001 Length of Stay– 7 days
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Kidney Transplantation: Etiology
Europe US Australiaglomerulonephritis 25 17 37diabetes 12 33 13cystic disease 8 4 7HTN 10 29 8analgesic 2 1 11interstitial nephritis 17 ? 11UNK 26 15 13
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Kidney Transplantation:Severity of renal failure
Severity GFR (ml/min) Signsmild 30-50 HTNmoderate .10-29 HTN, anemiasevere <10 pericarditis, osteodystrophyend-stage <5 pruritis,edema, dyspnea
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Kidney TransplantationMCV Evaluation: The Listing process– history and physical, financial and social
support system evaluation– blood typing, CXR, EKG, TB, Hep C, Hep
B, HIV testing and dental clearance – Women must have a pap smear &
mammogram– Diabetics:VCUG & gallbladder u/s &
cardiac clearance – Colonoscopy mandatory for age>50
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Kidney Transplantation
Contraindications– Active Infection– Cancer w/in 5 years– Morbid Obesity– Active Substance Abuse– Severe Coronary Artery or Peripheral
Vascular Disease– Medical Non-Compliance
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Kidney transplant Operation
5
25
Kidney transplant Operation
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Kidney transplant Operation
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National Data. UNOS.ORG
(83.2, 86.5)84.913175 YearAB
(84.2, 86.2)85.235365 YearB
(84.3, 85.4)84.9113935 YearA
(84.9, 85.9)85.4131175 YearO
(88.4, 91.0)89.717833 YearAB
(90.0, 91.5)90.748313 YearB
(90.3, 91.1)90.7150953 YearA
(90.5, 91.3)90.9172323 YearO
(94.4, 96.4)95.417951 YearAB
(95.1, 96.3)95.747651 YearB
(95.1, 95.8)95.4147861 YearA
(95.4, 96.0)95.7174511 YearO
95% ConfidenceIntervalSurvival Rate# AliveYears Post TransplantBlood Type
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Kidney Graft SurvivalOne- and Five-Year by Level of HLA Mismatch
91% 92% 90% 85%
68% 64% 61%55%
0
20
40
60
80
100
0 MM 1 MM 3 MM 6 MM
Perc
enta
ge
One-YearFive-Year
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Renal Transplant Patient Survival VCUHS vs National Average
0
0.2
0.4
0.6
0.8
1
0 365 730 1095
Days
PatientSurvival
United States VCUHS
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Using Live-donor Organs: Considerations
6
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Living-Donor Liver Transplantation in the U.S.
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Kidney Transplantation At VCUHS Living Donor Transplants
0
5
10
15
20
25
30
1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002
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Kidney Transplantation: Complication - rejection
T cell
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Kidney Transplantation: Complication - infection
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Post-Transplantation Cancer
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Post-Transplantation Cancer (by age)
7
37
Incidence of Skin Cancer in Organ Transplant Recipients
Squamous cell carcinoma– 65-fold
Squamous cell carcinoma of the lip– 20-fold
Basal cell carcinoma– 10-fold
Melanoma– 3.4-fold
Kaposi’s sarcoma– 8.4-fold
Other: – lung, – prostate, – colon, – PTLD, etc.
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Kidney-Pancreas Transplantation
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0
20
40
60
80
100
Kidney-Pancreas
Kidney-Liver Kidney-Heart Intestine-Liver
Perc
ent
1st Organ Graft 2nd Organ Graft Patient
1-Year Graft and Patient Survival RatesMultiple Organ Transplants1997-1998 Transplant Cohort
Source: Scientific Registry data as of 9/5/00.
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5-Year Graft and Patient Survival Rates1990-1998 Transplant Cohort
0
20
40
60
80
100
CadavericKidney
Living DonorKidney
Liver Pancreas Heart Lung Heart-Lung
Perc
ent
Graft Patient
Source: Scientific Registry data as of 9/5/00.
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Pancreas TransplantationIndications– Pancreas alone
• Retransplant/Graft Failure • Diabetes Mellitus – Type I• Diabetes Mellitus – Type II Diabetes
– Chronic Pancreatitis – Cystic Fibrosis
– Pancreas after kidney• DM
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Pancreas Transplantation
Arterial inflow provided by ‘y graft’Splenic attachment preserved to decrease graft hyperperfusionSpleen is removed and exocrine secretions drained via duodeno-ileostomy or duodeno-cystostomy
8
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Kidney-Pancreas Transplantation
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Kidney-Pancreas Transplantation
Success rates– Patient Survival (1995-1999)
MCV National• 30 day 100% 98.4%• 1 year 95.6% 94.5%• 5 years 83.8% 90%
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Kidney-Pancreas Transplantation: success rates
82.5%82.5%90.2%75.7%5 years
91.4%91.4%95.7%82.6%1 year
96.2%95.8%97.9%90%30 day
KidneyPancreasKidneyPancreas
NationalMCV
Graft Survival (1995 – 1999)
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Kidney-Pancreas Transplantation
1997 National Wait Time - 335 days 2000 MCVH Wait Time - 238 days 2000 MCV Length of Stay- 9 days
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Kidney-Pancreas Transplantation
Etiology of early renal graft dysfunction– Donor issues
• Hypotension/pressor agent usage• age• oliguria
– Preservation issues• prolonged warm ischemia• prolonged cold ischemia
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Kidney-Pancreas Transplantation
Etiology of early renal graft dysfunction– Immunologic issues
• ABO incompatibility• high PRA• african-american descent• hyperacute rejection (preformed antibodies)• accelerated rejection (second set exposure)• Acute and chronic rejection
– Drug toxicity
9
49
Kidney-Pancreas Transplantation
Early complications– Vascular thrombosis
• venous/ arterial– Ureteral issues
• leakage/stenosis– Lymphocele– Incisional issues
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Kidney-Pancreas Transplantation
Contraindications– Active Infection– Cancer w/in 5 years– Morbid Obesity/Type II diabetes– Active Substance Abuse– Severe Coronary Artery or Peripheral
Vascular Disease– Medical Non-Compliance– age >50 years
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Liver Transplantation
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Liver TransplantationSeverity, Signs and Symptoms
• quality of life issues– recurrent cholangitis, intractable ascites or
pruritis, severe lethargy or bone disease• severe hepatic dysfunction & complications
– hyperbilirubinemia / jaundice– severe coagulopathy– marked hypoalbuminemia / ascites– variceal hemorrhage– spontaneous bacterial peritonitis
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Liver Transplantation
Etiology– Hepatitis C 23%– Alcohol 20%– Cryptogenic 12%– PSC 10%– PBC 11%– Autoimmune 5%– Fulminant failure 5%
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Liver Transplantation
Contraindications– HIV– Extrahepatic malignancy– Uncontrolled sepsis– On going substance abuse– Advanced cardiopulmonary disease– Severe pulmonary hypertension– Noncompliance
10
55
Liver TransplantationMCV evaluation– multidisciplinary team assessment
• surgical (alternative or adjunct procedures)• hepatologist (intensive medical management)• cardiologist (catheterization/stenting/ P-Thal)• pulmonologist (PFT, bubble echo, ABGs)• psychologist (organic brain
syndromes/dependency)• social work (support system analysis)• financial (can it be done)
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Liver Transplantation
Cadaveric liver– National 1997 Wait Time - 439 days– MCVH 2000 Wait Time - 178 days– Average 2000 Length of Stay- 9 days
57
Liver Transplantation
Success rates– Cadaveric liver patient survivals
MCV National• 30 day 93.2% 94%• 1 year 83.8% 85.6%• 5 years 78.5% 75.9% (3yr)
58
Liver Transplantation
Success rates– Cadaveric liver graft survivals
MCV National• 30 day 89.8% 90%• 1 year 79.5% 79.8%• 5 years 73.7% 68.8% (3yr)
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Liver Transplantation
60
Liver Transplantation
11
61
Liver Transplantation
62
Liver Transplantation
63
Liver Transplantation
64
Liver Transplantation
65
Liver Transplants by Donor Type1997-1999
0500
10001500200025003000350040004500
Cadaveric 3929 4270 4367Living 76 86 219
1997 1998 1999
Source: Scientific Registry data as of 9/5/00. 66
Living Donor Relationship To Recipient1990, 1995, 1999
2 511
53
29
126
15
45
23 20
7
18
37
18
0
10
20
30
40
50
60
Parent Sibling Offspring OtherRelated
Unrelated
Perc
ent
199019951999
Source: OPTN data as of 9/5/00.
12
67
Liver Transplantation
Live donor liver– 2000 Wait Time- 108 days– Recipient Length of Stay- 10.5 days– Donor Length of Stay- 6.5 days
68
Liver Transplantation
Live donor liver-Survival 1999-2000
Patient Graft 30 day 95% 92%1 year 83% 81%
69
Liver Transplantation
70
Liver Transplantation
71
Liver Transplant
72
Liver Transplant
13
73
Liver Transplantation
Graft loss etiology– Sepsis– MI– CVA– Recurrent disease
74
Liver Transplantation
Early complications– primary graft dysfunction– hepatic artery thrombosis– bile duct leakage– rejection
• acute cellular• chronic
– infection
75
Liver Transplant Graft SurvivalVCUHS vs National Average
0
0.2
0.4
0.6
0.8
1
0 365 730 1095
Days
GraftSurvival
United States VCUHS
Source: www.ustransplant.org 76
Liver Transplant Patient SurvivalVCUHS vs National Average
0
0.2
0.4
0.6
0.8
1
0 365 730 1095
Days
PatientSurvival
United States VCUHS
Source: www.ustransplant.org
77
Living Donor Liver Transplant At VCUHS Graft Survivals
0
0.2
0.4
0.6
0.8
1
0 365 730 1095
Days
GraftSurvival
Living Cadaveric
78
Living Donor Liver Transplant At VCUHS Patient Survivals
0
0.2
0.4
0.6
0.8
1
0 365 730 1095
Days
PatientSurvival
Living Cadaveric
14
79
Solid Organ Transplantation
Daniel Maluf, MDAssistant Professor of SurgeryVCU School of Medicine
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