Upload
dr-lewis-teperman
View
300
Download
1
Tags:
Embed Size (px)
Citation preview
UPDATE AND INNOVATIONS IN
LIVER TRANSPLANTATION
Lewis Teperman, M.D.
Director of Transplantation
Vice Chairman of Surgery
NYU School of Medicine
Annual Presentation to Nurses
June 28, 20131
2
Sources: (1) 2007 OPTN/SRTR Annual Report Tables 1.3 and 1.7; and (2) http://optn.transplant.hrsa.gov/ar2009/
Number of Patients on UNOS Liver Waiting List (as of 3/14/2011 = 16,853)
Transplants
3
Causes of Death in 262 Causes of Death in 262 DonorsDonors
5
41
27
74
51
15
10
8
5
6
4
4
4
4
3
2
2
2
1
0 10 20 30 40 50 60 70 80
MOTOR VEHICLE ACCIDENT
GUN SHOT WOUND
SUBARACHNOID BLEED/CVA
HEAD INJURY
FALLING
INTRACRANIAL ANEURYSM
ASPIRATION
MENINGITIS
BRAIN TUMOR
IATROGENIC
CHILD ABUSE
DROWNING
DRUG INTOXICATION
SUDDEN INFANT DEATH
SEIZURE
DIABETES
CHOKING
SPORTS ACCIDENT
New York Organ Donor New York Organ Donor NetworkNetwork
4
New York is saferNew York is safer Crime is downCrime is down Vehicular accidents are downVehicular accidents are down
Organ Donation
Living Donation 20%
Deceased Donation 10%
Import Organ Offers 75%
5
Doctors Confirm West Nile in a 4th Doctors Confirm West Nile in a 4th Transplant PatientTransplant Patient
Doctors have confirmed that a woman in Florida is the fourth Doctors have confirmed that a woman in Florida is the fourth person to have contracted West Nile virus after receiving an person to have contracted West Nile virus after receiving an organ transplanted from a single donor who had the virus, a organ transplanted from a single donor who had the virus, a federal health official said last night.federal health official said last night.
Finding the virus in all four organ recipients "very strongly Finding the virus in all four organ recipients "very strongly suggestssuggests”” that the disease was transmitted by the organs that the disease was transmitted by the organs rather than by mosquito bites, said the official, Dr. Lyle rather than by mosquito bites, said the official, Dr. Lyle Petersen, a West Nile expert at the Centers for Disease Petersen, a West Nile expert at the Centers for Disease Control and Prevention.Control and Prevention.
--- --- The New York TimesThe New York Times
6
6
WEST NILE VIRUS
• West Nile, a flavivirus, is a relatively
new pathogen to the U.S.
• Other flaviviruses include:
- Yellow fever
- Dengue
- Saint Louis Encephalitis
LW Teperman, MD, T Diflo, MD, A Fahmy, MB, GR Morgan, MD, et al. “West Nile Virus Infections in Organ Transplant Recipients---New York and Pennsylvania, August---September, 2005.” MMWR Disptach of CDC October 5, 2005: 54 (Dispatch); 1-3. 7
West Nile VirusWest Nile VirusApproximate Geographic Range in 1998Approximate Geographic Range in 1998
8
9
2005
• 2,949 cases
• 628 counties
• 42 states
10
0
20
40
60
80
100
120
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30
Tem pCurveNeurologic
Neurologic
Temp Curve
OLTX T 105° Weakness
Seizures Flaccid Paralysis
68 days
expired
PATIENT COURSE
OMR-IgG-am IgG
300
Treatment
AST
FK/SM/ZENEPAX
CELLCEPT FK / DC’d
40.6° C 40.3° C
37.6° C
311
35
400
1137
43
DC’d Cellcept
WNV
11
Tumor ConveyanceTumor Conveyance
““Teen Organ Donor's Gift Turns Teen Organ Donor's Gift Turns TragicTragic””11
““Transmission of Anaplastic Large Transmission of Anaplastic Large Cell Lymphoma via Organ Cell Lymphoma via Organ
Donation After Cardiac DeathDonation After Cardiac Death””22
1. SAG HARBOR, N.Y., April 1, 2008, Nancy Cordes, CBS News Correspondent2. JW Harbell, TB Dunn, M Faudia, DG John, AS Goldenberg and LW Teperman.. American Journal of Transplantation,
January 2008; Vol. 1; Issue I; 238-244.
12
Transmission of Anaplastic Large Cell Lymphoma via Organ
Donation After Cardiac Death
J.W. Harbell, T.B. Dunn, M. Fauda, D.G.John, A.S. Goldenberg, L.W. Teperman; AJT:2008; 8, pps 238-244.
14
Donor-Derived Disease Transmission Donor-Derived Disease Transmission Events in the United States: Data Events in the United States: Data
ReviewedReviewedby the OPTN/UNOS Disease by the OPTN/UNOS Disease
TransmissionTransmissionAdvisory CommitteeAdvisory Committee
M. G. Ison,*, J. Hager, E. Blumberg,M. G. Ison,*, J. Hager, E. Blumberg,
J. Burdick, K. Carney, J. Cutler, J. M. DiMaio,J. Burdick, K. Carney, J. Cutler, J. M. DiMaio,
R. Hasz, M. J. Kuehnert, E. Ortiz-Rios,R. Hasz, M. J. Kuehnert, E. Ortiz-Rios,
L. Teperman and M. NalesnikL. Teperman and M. Nalesnik
American Journal of Transplantation 2009; 9: 1–7American Journal of Transplantation 2009; 9: 1–7
15
Table 5: Reports made to DTAC regarding a potential donor-derived malignancy transmission
2005-2007
Malignancies Donor Reports1
Confirmed
Recipients2
Recipient Deaths3
Renal Cell Carcinoma
25 3 0
Lung adenocarcinoma
5 2 2
Glioblastoma multiforme
4 1 1
Lymphoma 3 4 2
Metastatic Melanoma
3 2 1
Prostate adenocarcinoma
2 0 0
OTHERS X X X
TOTALS 55 15 6
1. Number of donors reported possible donor-derived disease transmission. 2. Number of recipients with confirmed (proven, probable or possible) donor-derived disease. 3. Number of recipients who died as the result of a donor-derived disease transmission.
““The liver does The liver does not undergo not undergo senescence.senescence.””
-Hans Popper, MD-Hans Popper, MD
7
The Successful Use of The Successful Use of Older Donors for Liver Older Donors for Liver
TransplantationTransplantationL. Teperman, L. Podesta, L. Mieles, T. L. Teperman, L. Podesta, L. Mieles, T.
Starzl JAMA 1989; 262:2837Starzl JAMA 1989; 262:2837
8
Donor FactorsDonor Factors
Age BarrierAge Barrier > 80 Years> 80 Years Fat Content:Fat Content: macro vs. macro vs.
micromicro Length of stay Length of stay > 10 days> 10 days HypernatremiaHypernatremia
19
Expanded Criteria Expanded Criteria DonorDonor
Define Relative Risk(RR) of FailureDefine Relative Risk(RR) of Failure RR 1.7: 70% greater risk of failureRR 1.7: 70% greater risk of failure
FactorFactor RRRR P-ValueP-Value
Donor Age 40 to 49Donor Age 40 to 49 1.161.16 0.00060.0006
Donor Race BlackDonor Race Black 1.191.19 0.00010.0001
DCD LiverDCD Liver 1.521.52 0.00060.0006
Partial / Split LiverPartial / Split Liver 1.531.53 0.00010.0001
Donor Age 70 or AboveDonor Age 70 or Above 1.631.63 0.00010.0001
20
19961991
Obesity Trends* Among U.S. AdultsBRFSS, 1991, 1996, 2004
(*BMI 30, or about 30 lbs overweight for 5’4” person)
No Data <10% 10%–14% 15%–19% 20%–24% ≥25%
2004
Source Mokdad A.H., et all JAMA 2003,289-1 21
Obesity Trends* Among U.S. AdultsBRFSS, 2011
http://feww.files.wordpress.com/2011/07/obesity-2011-feww1.png22
23
Retransplant Rates in Retransplant Rates in Region vs. the USRegion vs. the US
13.4
10.3
6.7
4.9
8.4
5.6
0
2
4
6
8
10
12
14
ECD Non ECD Overall
Region 9 Rest of Country
Ret
rans
plan
t Rat
es (
%)
NYU
5%
24
Utility vs. EquityUtility vs. Equity
12
Old Allocation SystemOld Allocation SystemChild-Turcotte-Pugh Scoring System to Assess
the Severity of Liver Disease
* For cholestatic liver diseases, these values for bilirubin are to be submitted for the values above.
Points 1 2 3
Encephalopathy None 1-2 3-4
Ascites Absent Slight or At least controlled moderate
by diuretics despite diuretics
Bilirubin(mg/dL) <2 2-3 >3
Albumin >3.5 2.8-3.5 <2.8
Prothrombin time <1.7 1.7-2.3 >2.3(seconds prolonged) or INR
For PBC, PSC or other <4 4-10 >10cholestatic liver diseases:Bilirubin (mg/dL)*
16
26
Problems with CTP ScoreProblems with CTP Score
Limited number Limited number ofof categories categories Limited Limited discriminating abilitydiscriminating ability Uses Uses subjective parameters subjective parameters -- gaming gaming Laboratory Laboratory variabilityvariability (protime, (protime,
albumin)albumin) Never validatedNever validated CreatinineCreatinine not included not included
18
27
Q: What is Q: What is MELD?MELD?
A: Disease Severity ScoreA: Disease Severity Score
90% Survival Probability on the 90% Survival Probability on the waitlistwaitlist
VariablesVariables BilirubinBilirubin CreatinineCreatinine INRINR
““ CHANGE REAGENTCHANGE REAGENT”” Liver disease etiology (deleted)Liver disease etiology (deleted)
MELD MODEL:MELD MODEL: Predicts Survival in TIPS Patients
21
?
29
Creatinine Bilirubin INR Dialysis? HCC? MELD
Person #1 0.8 0.3 1.04 N N 6
Person #2 1.1 1.4 1.14 N N 10
Person #3 3.2 1.0 1.03 N N 18
Person #6 8.9 0.6 1.01 Y N 20
Person #4 1.8 1.6 2.00 N N 22
Person #5 0.9 1.7 1.26 N 2 – 5 cm* 22
Person #7 3.5 12.0 1.56 N N 33
MELD EquationMELD Equation MELD = (0.957 x LN (creatinine) + 0.378 x MELD = (0.957 x LN (creatinine) + 0.378 x
LN (bilirubin) + 1.12x LN(INR) + 0.643) x 10LN (bilirubin) + 1.12x LN(INR) + 0.643) x 10 Capped at 40Capped at 40
30
HCC: Extra CreditHCC: Extra Credit
Patients meeting criteria receive Patients meeting criteria receive 2222 points. points.
After a three-month reevaluation After a three-month reevaluation patients receive additional points.patients receive additional points.
Thereafter they receive additional Thereafter they receive additional points every three months.points every three months.
31
Indications for Indications for TransplantationTransplantation
NYUC Txps 2007 32
Hepatitis C Tumor Hepatitis C Tumor BurdenBurden
4 million US Patients4 million US Patients 1 million Cirrhotics (10 years)1 million Cirrhotics (10 years) 1/4 million HCC1/4 million HCC (10 years) (10 years)
25
33
Lewis Teperman, M.D.
Abdominal Organ Cluster Abdominal Organ Cluster Transplantation for the Transplantation for the
Treatment of Upper Abdominal Treatment of Upper Abdominal MalignanciesMalignancies
Thomas E Starzl MD, PHD; Satoro Todo MD; Andreas Tzakis MD; Luis Podesta MD; Luis Mieles MD, Anthony Demetris MD, Lewis Teperman MD; Rick Selby MD; William Stevensen MD; Andre Steiber MD; Robert Gordon MD; Shunzaburo Iwatzuki MD
35
35
36
OLT Survival Milan OLT Survival Milan CriteriaCriteria
60 1812 3024 4236 48
20
0
40
60
100
80
Months
Pro
bab
ilit
y (%
)
Mazzaferro, V. N Engl J Med 1996
37
HCCHCC
While we wait, the tumor grows!While we wait, the tumor grows! Treatment is appropriateTreatment is appropriate Are 6 cm lesions really more deadly Are 6 cm lesions really more deadly
than 5 ?than 5 ? Exceptional case review (RRB)Exceptional case review (RRB)
John Roberts, UCSF, AJT 2006;
Yao, et al. Am J Transplant. 2007;7:2587-2596.38
HCC Recurrence after HCC Recurrence after OLTOLT
5040 6010 3020
.2
0
.4
.6
1.
.8
Months
Recu
rren
ce
.3
.5
.7
.9
.1No Vascular
Invasion
Vascular Invasion
Hemming, A. Ann Surg 2001
0
39
HepatomasHepatomas
Initial MELD ExceptionInitial MELD Exception 29 points29 points ~ 20% of transplants~ 20% of transplants 20-24 points20-24 points Excellent SurvivalExcellent Survival MELD is Evolving!MELD is Evolving! Consider living donationConsider living donation
40
Strategies for Long Strategies for Long Waiting TimeWaiting Time
TACE TACE
Living Donor TransplantLiving Donor Transplant
41
Chemoembolization Chemoembolization (CE) for HCC(CE) for HCC
Femoral artery CatheterizationFemoral artery Catheterization 3 Elements3 Elements
LipiodolLipiodol Chemotherapeutic agent(adriamycin, Chemotherapeutic agent(adriamycin,
cisplatinum)cisplatinum) Embolizing Agent(Gelform, Avitene)Embolizing Agent(Gelform, Avitene)
Selective hepatic arterial localizationSelective hepatic arterial localization ““KillKill”” Rates Rates Without significant complicationsWithout significant complications*Neo adjuvant: Thalidomide (-)*Neo adjuvant: Thalidomide (-)
(+) NEXAVAR MULTI-CENTER(+) NEXAVAR MULTI-CENTER TRIAL 2012TRIAL 2012
36
42
43
44
Chemoembolization Chemoembolization Random Effects ModelRandom Effects Model
6395
503
807379
112
Favors Treatment
Favors Control
0.10.01
10.5 2 10010
Lin, Gastroenterology 1988
Overall
GETCH NEJM 1995
Bruix, Hepatology 1998
Pelletier, J Hepatology 1998
Lo, Hepatology 2002
Lovett, Lancet 2002
OR (95% CI)
P=0.017
Llovet, J Hepatology 2003
45
Patient Survival after liver Patient Survival after liver transplantation:transplantation:
Benign vs. Malignant diseaseBenign vs. Malignant disease
Months after transplantation
33
46
TRANSPLANTATION FOR TRANSPLANTATION FOR HEP B HBIG TREATMENTHEP B HBIG TREATMENT
Months
HBIG HBIG HBIG
31
47
There is NO consensus on There is NO consensus on optimal duration of HBIG, dose, optimal duration of HBIG, dose, or mode of administration.or mode of administration.
-- Lewis TepermanLewis Teperman 10/15/200610/15/2006
48
Viral DNA Chain Viral DNA Chain TerminatorsTerminators
GanciclovirGanciclovir FamciclovirFamciclovir LamivudineLamivudine AdefovirAdefovir EntecevirEntecevir TenofovirTenofovir EmtricitabineEmtricitabine
28
49
A Randomized Trial of HBIG A Randomized Trial of HBIG Withdrawal Using Withdrawal Using
Emtricitabine/Tenofovir DF Emtricitabine/Tenofovir DF in Post-Liver Transplant in Post-Liver Transplant
RecipientsRecipients L TepermanL Teperman11, J Spivey, J Spivey22, F Poordad, F Poordad33, T Schiano, T Schiano44, N Bzowej, N Bzowej55,,
S PungpapongS Pungpapong66, P Martin, P Martin77, D Coombs, D Coombs88, K Hirsch, K Hirsch88, J Anderson, J Anderson88 and F and F RousseauRousseau88
11The Mary Lea Johnson Richards Organ Transplantation Center, The Mary Lea Johnson Richards Organ Transplantation Center, New York University Medical Center, New York, NY; New York University Medical Center, New York, NY; 22Emory Healthcare, Atlanta, GA; Emory Healthcare, Atlanta, GA;
33Cedars-Sinai Medical Center, Los Angeles, CA; Cedars-Sinai Medical Center, Los Angeles, CA; 44Recanati/Miller Transplantation Institute, Recanati/Miller Transplantation Institute, Mount Sinai Hospital, New York, NY; Mount Sinai Hospital, New York, NY; 55California Pacific Medical Center, San Francisco, CA;California Pacific Medical Center, San Francisco, CA;
66Mayo Clinic Jacksonville, Jacksonville, FL; Mayo Clinic Jacksonville, Jacksonville, FL; 7 7 Schiff Liver Institute,Schiff Liver Institute, University of Miami,University of Miami,Miller School of Medicine, Miami, FL; Miller School of Medicine, Miami, FL; 88Gilead Sciences Inc., Durham, NCGilead Sciences Inc., Durham, NC
BackgroundBackground
HBIG prophylaxis is routinely prescribed to HBIG prophylaxis is routinely prescribed to prevent HBV recurrence post-orthotopic prevent HBV recurrence post-orthotopic liver transplantation (OLT) liver transplantation (OLT)
HBIG prevents recurrence by HBIG prevents recurrence by neutralizingneutralizing HBsAgHBsAg
Long-term prophylaxis with HBIG is Long-term prophylaxis with HBIG is inconvenient and expensive, but is the inconvenient and expensive, but is the mainstay of post-transplant therapy.mainstay of post-transplant therapy.
51
Cost of HBIG in Relation with HBIG Dosing and Strategy of Administration in Patients Receiving HBIG + Lamivudine
Yearly cost of different schedules of HBIg administration in Euros. The “on demand” schedule using 2,000 IU of HBIg allows a savings of over 50% compared with fixed monthly doses of 5,000 IU.
Di Paolo et al. Transplantation 2004; 77: 1203-1208.
52
AimAim
This ongoing randomized study (Study 107) This ongoing randomized study (Study 107) evaluates the safety and evaluates the safety and efficacy of TVD efficacy of TVD with/without HBIG with/without HBIG in preventing recurrence in preventing recurrence of CHB post OLTof CHB post OLT
The aim of this The aim of this interim analysis interim analysis is to is to evaluate the efficacy, safety and tolerability evaluate the efficacy, safety and tolerability of TVD in this populationof TVD in this population
53
Patient Disposition
ScreenedN=51
EnrolledN=40
Randomized at Week 24N=37
Discontinued N=3
TVD+HBIGN=19
TVDN=18
Completed Week 72 N=15 Completed Week 96 N=11
Completed Week 72 N=14Completed Week 96 N=12
Discontinued N=1Death N=1
Discontinued N=1
Virologic OutcomesVirologic Outcomes
No detectable HBV DNA (169 No detectable HBV DNA (169 copies/mL; lower limit of quantitation) copies/mL; lower limit of quantitation) in either groupin either group
No HBsAg positivityNo HBsAg positivity
55
Hepatitis CHepatitis C
Most common indication for Most common indication for transplantation 25 - 45%transplantation 25 - 45% 95% of recipients persist with antibody 95% of recipients persist with antibody
to Cto C At least 50% develop active hepatitis on At least 50% develop active hepatitis on
biopsybiopsy It is unknown how many progress to a It is unknown how many progress to a
chronic statechronic state
56
Treatment for Hepatitis CTreatment for Hepatitis C
InterferonInterferon RibavirinRibavirin Pegylated - InterferonPegylated - Interferon
PegasysPegasys PEG-IntronPEG-Intron
Protease Inhibitors 2011Protease Inhibitors 2011 NYU post tx pilot 7/15 negNYU post tx pilot 7/15 neg
-TIMING--TIMING-57
Baylor Zenapax Trial
Steroid SparingI L 2 Receptor Antagonist Induction
Randomized Controlled Trial
Results: No Difference in Hepatitis C Recurrence,
Diabetes, or Rejection
November 2005
Fasola, C G., Heffron, T. G., Sher, L., Douglas, D. D., Brown, R., Ham, J,. Teperman, L.,…et al. “Multicenter Randomized Hepatitis C (HCV) Three Trial Post Liver Transplantation (OLT): A Preliminary Report.” Transplantation. 78(2) Supplement 1: 146, July 27, 2004.58
A Randomized Multicenter Study Comparing Efficacy and Safety of
Steroid-Free and Standard Immunosuppression for Liver
Transplantation Recipients with Chronic Hepatitis C
(submitted)Goran B. Klintmalm1, Gary L. Davis1, Lewis Teperman2, George J. Netto3, Ken Washburn4, Steven Rudich5, Elizabeth Pomfret6, Hugo E. Vargas7, Robert Brown8, Devin Eckhoff9, Timothy Pruett10, John Roberts11, David C. Mulligan7, Michael Charlton12, Thomas G. Heffron13, John Ham14, David Douglas7, Linda Sher15, Prabhakar Baliga16, Milan Kinkhabwala8, Baburao Koneru17, Michael Abecassis18,
Michael Millis19, Linda W. Jennings1, Carlos G. Fasola13
1 Baylor University Medical Center, Dallas, TX; 2 New York University Medical Center, NY; 3 Johns Hopkins Medical Institutions, Baltimore, MD; 4 University of Texas Health Science Center at San Antonio; 5 University of Cincinnati, Cincinnati, OH; 6 Lahey Clinic, Burlington, MA; 7 Mayo Clinic, Scottsdale, AZ; 8 New York Presbyterian Hospital, New York, NY; 9 University of Alabama – Birmingham, AL; 10 University of Virginia, Charlottesville, VA; 11 University of California, San Francisco, CA; 12 Mayo Clinic, Rochester, MN; 13 Emory University School of Medicine, Atlanta, GA (current address: Scott and White Clinic, Temple, TX); 14 Oregon Health Sciences University, Portland, OR; 15 University of Southern California, Los Angeles, CA; 16 Medical College of South Carolina, Charleston, SC; 17 University of Medicine and Dentistry of New Jersey, Newark NJ; 18 Northwestern Memorial Hospital, Chicago, IL; 19 University of Chicago, Chicago, IL
59
““The challenge of The challenge of transplant surgery is transplant surgery is
NOT the surgeryNOT the surgery””
39
60
40
61
Immunologic Armamentarium Immunologic Armamentarium (Arsenal)(Arsenal)
Vietnam ConflictVietnam Conflict Imuran Imuran - - Ground TroopsGround Troops Steroids Steroids - - Light ArtilleryLight Artillery
Cold WarCold War Cyclosporine Cyclosporine - - F16F16 Okt3Okt3 - - ““TacticalTactical”” warhead / cruise missile warhead / cruise missile
Desert StormDesert Storm PrografPrograf - - Smart BombSmart Bomb Neoral Neoral - - Modified F16Modified F16 Cell CeptCell Cept - - B2 stealth bomberB2 stealth bomber IL2 Receptor AbsIL2 Receptor Abs -- X - PlaneX - Plane RapamycinRapamycin - Osprey Transport - Osprey Transport RapamuneRapamune - Modified Osprey - Modified Osprey
TransportTransport
War on TerrorWar on Terror ThymoglobulinThymoglobulin - - Biologic Weapon Biologic Weapon Campath Campath - Modified Biologic - Modified Biologic
WeaponWeapon
42
62
Risk of Chronic Renal Risk of Chronic Renal FailureFailure
A 15-year experience at Baylor A 15-year experience at Baylor Medical Center found that at 13 Medical Center found that at 13 years after liver transplantationyears after liver transplantation Incidence of severe renal Incidence of severe renal
dysfunction of 18.1%dysfunction of 18.1% Chronic renal failure in 8.6% of Chronic renal failure in 8.6% of
patientspatients ESRD in 9.5% of patientsESRD in 9.5% of patients
Gonwa TA et al. Transplantation 2001;72:1934-1939.
63
Risk of Chronic Renal Risk of Chronic Renal FailureFailure
Number at RiskNumber at RiskHeart-Heart-lunglung 576576 375375 295295 219219 194194 156156 133133 107107 7272 4646 3030
HeartHeart 24,024,01414
19,8819,8855
17,2317,2388
14,6814,6877
12,3412,3411
10,0210,0222
7,9977,997 6,1046,104 4,5264,526 3,0963,096 1,9911,991
IntestiIntestinene 228228 152152 110110 8484 5757 3333 2323 1313 88 55 55
LiverLiver 36,836,84949
28,4928,4955
24,0424,0411
19,5019,5088
15,7215,7244
12,5612,5644
9,8449,844 7,3457,345 5,2925,292 3,6143,614 2,2612,261
LungLung 7,647,6433
5,6335,633 4,3164,316 3,1843,184 2,3272,327 1,6291,629 1,1361,136 745745 468468 258258 133133Ojo AO, et al. N Engl J Med 2003;349:931-40.
Months since Transplantation
Cu
mu
lati
ve
In
cid
en
ce
of
Ch
ron
ic R
en
al
Fa
ilu
re
0.35
0.30
0.25
0.20
0.15
0.10
0.05
0.000 12 24 12010884 967236 48 60
LungIntestine
Heart
Liver
Heart–lung
64
Calcineurin inhibitor-Calcineurin inhibitor-free maintenance with free maintenance with
mycophenolate mycophenolate mofetil/sirolimus in mofetil/sirolimus in
liver transplant liver transplant recipients: Save-the-recipients: Save-the-
Nephron TrialNephron Trial(submitted)(submitted)
L .Teperman,L .Teperman,11 D. Moonka, D. Moonka,22 A.Sebastian, A.Sebastian,33 L. Sher, L. Sher,44 P. Marotta, P. Marotta,55 C. Marsh, C. Marsh,66 B. Koneru, B. Koneru,77 J. Goss, J. Goss,88 D. Preston, D. Preston,99 and J. and J. RobertsRoberts1010
11New York University School of Medicine, New York, New York; New York University School of Medicine, New York, New York; 22Henry Ford Health Systems, Detroit, Michigan; Henry Ford Health Systems, Detroit, Michigan; 33Integris Baptist Medical Center, Oklahoma City, Oklahoma; Integris Baptist Medical Center, Oklahoma City, Oklahoma; 44University of Southern California, Los Angeles, University of Southern California, Los Angeles,
California; California; 55London Health Sciences Hospital, London, Ontario, Canada; London Health Sciences Hospital, London, Ontario, Canada; 66Scripps Green Hospital, La Jolla, Scripps Green Hospital, La Jolla, California; California; 77University of Medicine and Dentistry of New Jersey, Newark, New Jersey; University of Medicine and Dentistry of New Jersey, Newark, New Jersey; 88Saint LukeSaint Luke’’s Episcopal s Episcopal
Hospital, Houston, Texas; Hospital, Houston, Texas; 99Genentech, South San Francisco, California; Genentech, South San Francisco, California; 1010University of California, San Francisco, University of California, San Francisco, CaliforniaCalifornia
Lew, This version contains comments from LS, JR, and DM. PM provided feedback of no comments. Lew, This version contains comments from LS, JR, and DM. PM provided feedback of no comments.
65
STN Trial DesignSTN Trial Design
MMF + MMF + tacrolimustacrolimus corticosteroidscorticosteroids
MMF + cyclosporine corticosteroids
MMF + tacrolimusMMF + tacrolimus
MMF + cyclosporine
MMF + sirolimusMMF + sirolimus
MMF + sirolimusMMF + sirolimus
Post-randomizationPost-randomization
1 year1 year
Pre-randomizationPre-randomization StableStable
4 – 124 – 12
WWEEEEKKSS
PPOOSSTT--TTXX
2 years2 years
ScreeningScreening Enrollment
66
Mean %Mean % Increase in Increase in Calculated GFRCalculated GFR
Baseline to Month 6Baseline to Month 6
N = 8455.81.91.9
N = 8650.61.91.9
0
5
10
15
20
25
30
35
Mea
n P
erce
nt
Incr
ease
(±S
EM
)
MMF/SRL
MMF/CNI
3.2
40
Baseline GFR SEM (mL/min)
29.2
67
ConclusionsConclusions At least At least 62%62% of individuals are able to of individuals are able to
toleratetolerate a maintenance regimen of MMF/SRL a maintenance regimen of MMF/SRL and will benefitand will benefit
In the short term, In the short term, MMF/SRL improvesMMF/SRL improves renal renal functionfunction when compared to CNI-containing when compared to CNI-containing regimens regimens
The addition of The addition of lipid-lowering agentslipid-lowering agents may be may be necessary in patients receiving MMF/SRLnecessary in patients receiving MMF/SRL
Complete follow-up of the 294Complete follow-up of the 294 patients will patients will provide a more provide a more statistically statistically robust conclusion robust conclusion about the long-term effect of this regimenabout the long-term effect of this regimen
68
Donor and NYU Donor and NYU TimelineTimeline
1999 Living Donation (Right Lobe Adult)
1997 Split Livers (peds) (Adult)
1990 Living Donation Lateral Segment (peds)
1988 Reduced Sized Grafts (peds)
52
1963 University Hospital Built
1965 1st Successful Liver Transplant
New Transplant Regulations
69
DONOR RISKSDONOR RISKS
New York Newsday, March 13, 2002
55
70
Transplant Chief at Mt. Sinai Quits Transplant Chief at Mt. Sinai Quits Post in Wake of InquiryPost in Wake of Inquiry
A week after Mount Sinai Medical Center was A week after Mount Sinai Medical Center was cited by the state for dozens of serious cited by the state for dozens of serious violations, the chief of its liver transplant violations, the chief of its liver transplant center has stepped down and the entire center has stepped down and the entire program will be restructured, hospital officials program will be restructured, hospital officials announced yesterday.announced yesterday.
--- --- The New York TimesThe New York Times
56
71
Summer of 2010Summer of 2010
2 Recent U.S. Deaths2 Recent U.S. Deaths ColoradoColorado MassachusettsMassachusetts
72
New York State New York State Report of the Subcommittee on Report of the Subcommittee on Donor Perioperative Care and Donor Perioperative Care and
Facility ReportFacility Report
Lewis Teperman M.D., Chair
73
New Preoperative Care New Preoperative Care RegsRegs
1.1. Psychiatric EvaluationPsychiatric Evaluation2.2. Bank BloodBank Blood3.3. StaffStaff
1.1. 2 donor surgeons*2 donor surgeons*2.2. A third transplant surgeon*A third transplant surgeon*3.3. Anesthesia (2 attendings)Anesthesia (2 attendings)
4.4. Post operative carePost operative care1.1. ICU (days 0 - 1)ICU (days 0 - 1) 1 Nurse / 2 Patients1 Nurse / 2 Patients2.2. Floor Floor 1 Nurse / 4 patients1 Nurse / 4 patients3.3. Residents Residents (pgy2) / NP(pgy2) / NP 24/724/7
5.5. RegistryRegistry1.1. OutcomeOutcome
* Qualified74
Living Donor RecipientsLiving Donor Recipients
InclusionInclusion Listed with UNOS and must have a Listed with UNOS and must have a
significant complication of liver diseasesignificant complication of liver disease Relative ExclusionsRelative Exclusions
MELD > 25MELD > 25 Cholangio CarcinomaCholangio Carcinoma
ExclusionsExclusions AFHFAFHF Retransplant for CRetransplant for C Acute Alcoholic HepatitisAcute Alcoholic Hepatitis
75
HCC: Extra CreditHCC: Extra Credit
Is Living Donation Is Living Donation justified?justified?
Patients meeting criteria receive Patients meeting criteria receive 2222 points. points.
After a three-month reevaluation After a three-month reevaluation patients receive additional points.patients receive additional points.
Thereafter they receive additional Thereafter they receive additional points every three months.points every three months.
76
Hepatoma Predictor Hepatoma Predictor LDLT and Waiting List TimeLDLT and Waiting List Time
20 64 108 1412 1816
2
0
4
8
12
10
Waiting list time (months)
Recip
ien
t li
fe e
xp
ecta
ncy
(years
)
2220 24
6
14
5 yr survival after DLT 70%
DLT drop out 2%/month
DLT drop out 4%/month
Immediate LDLT
Sarasin, F. Hepatology 2001
77
$$
No Selling of OrgansNo Selling of Organs57
78
Donor Candidacy Donor Candidacy Requirements (1)Requirements (1)
Emotionally relatedEmotionally related Age 18 - 60Age 18 - 60 Blood Type CompatibleBlood Type Compatible
A AA A O O, B, A, ABO O, B, A, AB
58
79
MELD Score Comparison of MELD Score Comparison of Cadaveric vs. Living Related Cadaveric vs. Living Related
DonorsDonors
Average Living Donor MELD Score:Average Living Donor MELD Score:
17.417.4
Average Cadaveric MELD Score:Average Cadaveric MELD Score:
3232
66
80
60
81
1% Rule1% Rule
70kg recipient needs a 700cc liver 70kg recipient needs a 700cc liver graft (1% GRWR)graft (1% GRWR)
1% mortality1% mortality(Actually ~0.05% but over (Actually ~0.05% but over emphasize to define risk)emphasize to define risk)
65
82
Living DonorLiving Donor
Right Hepatic resectionRight Hepatic resection 50% - 65% of the hepatic mass50% - 65% of the hepatic mass
Right is RightRight is Right Left hepatic resections will Left hepatic resections will
have more complicationshave more complications
64
83
Living DonorsLiving DonorsWhat the Surgeon Needs to Know:What the Surgeon Needs to Know:
Liver ParenchymaLiver Parenchyma Right lobe volumeRight lobe volume Exclude fatty Exclude fatty
infiltrationinfiltration Characterize Characterize
lesionslesions Hepatic arteriesHepatic arteries
Arterial variantsArterial variants RHA originRHA origin
Portal veinsPortal veins PV variants, RPV PV variants, RPV
originorigin
Hepatic veinsHepatic veins RHV lengthRHV length MHV branches to MHV branches to
right loberight lobe Inferior accessory Inferior accessory
HVHV Biliary ductsBiliary ducts
Biliary variantsBiliary variants Rt lateral duct Rt lateral duct
originorigin84
Volumetric MR Volumetric MR CholangiographyCholangiography
Lee VS, Teperman L, et Al. AJR, 2001.85
CT CholangiographyCT Cholangiography
Higher Spatial Higher Spatial Resolution than Resolution than MRMR
Shorter Exam Shorter Exam TimeTime
Radiation DoseRadiation Dose Contrast AgentContrast Agent
86
Donor Rule #2Donor Rule #2 Know the donorKnow the donor’’s anatomy prior to the s anatomy prior to the
procedureprocedure
Donor Rule #1Donor Rule #1 Do not hurt the Do not hurt the
donordonor See Rule #2See Rule #2
63 SafetySafety
87
Living Donor Biliary Living Donor Biliary TechniqueTechnique
1.1. Demonstrate anatomy prior to ORDemonstrate anatomy prior to OR2.2. Confirm anatomy with an on table Confirm anatomy with an on table
cholangiogramcholangiogram3.3. Exclude right to left cross overExclude right to left cross over4.4. Perform a duct to duct anastomosisPerform a duct to duct anastomosis5.5. Utilize a t-tube for post operative Utilize a t-tube for post operative
studies and drainagestudies and drainage
88
Picture of on table cholangiogram prior Picture of on table cholangiogram prior to splittingto splitting
89
69
90
70
91
71
92
93
NYU Donor NYU Donor ComplicationsComplications
7 Bile leaks requiring intervention7 Bile leaks requiring intervention 1 non-occlusive PV thrombus1 non-occlusive PV thrombus 3 peripheral neuropathies3 peripheral neuropathies 1 pleural effusion drained1 pleural effusion drained 5 Required blood transfusions5 Required blood transfusions 2 late laparotomies for SBO2 late laparotomies for SBO
77
94
NYU Recipient Biliary NYU Recipient Biliary ComplicationsComplications
100 right lobectomies100 right lobectomies 8 patients experienced early biliary 8 patients experienced early biliary
complicationscomplications 4 leaks4 leaks
2 - ERCP and internal stent; 2 - JP drainage2 - ERCP and internal stent; 2 - JP drainage 1 stricture (following a leak treated by ERCP 1 stricture (following a leak treated by ERCP
and internal stent)and internal stent) Endoscopic dilationEndoscopic dilation
13 patients experienced late biliary 13 patients experienced late biliary complicationscomplications All requiring PTC and DilationAll requiring PTC and Dilation
95
Comparative Living Donor Comparative Living Donor Liver Transplant Survival Liver Transplant Survival
RatesRates
Survival Survival CategoriesCategories
NYU NYU Medical Medical CenterCenter
National National AverageAverage
DifferenceDifference
Patient SurvivalPatient Survival 91%91% 86.5%86.5% + 4.5%+ 4.5%
Graft SurvivalGraft Survival 88.4%88.4% 80.6%80.6% + 7.8%+ 7.8%
96
ResultsResults78
97
Extracorporeal Liver Assist Device (ELAD)
98
Extracorporeal Liver Assist Device (ELAD)
99
100