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5Is adult to adult live donor liver transplantation ethical?
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Sixth Congressof the ILTS
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IS ADULT T O ADULT LIVE D O N O R L I V E R T R A N S P L A N T A T I O N E T H I C A L ? D.C. Crooin. J.M. Millis, M. Siegler. Uni',ersitv of Chicago. Section of Transplant and McLean Center for Clinical Etlfic~,. Chicago, IL In 1989, Dr. Francis Moore proposed three criteria to assess whether an innovative transplantation procedure '.*,as ethically justified: I ). Scientific data: 2). "Field strength" 6/the clinical team: ancl 3 ), Tile ethical climate of the team's institution. This paper examines only whether existing scientific data jnstify adult to adult liver transplantation (AALT) in the LI.S, at this time in al/eases requiring transplantation (Tx). After technical feasibility was demonstrated, adult to child living donor liver transplantation (ACLT) was clinically and ethically justified because of the short life span in pediatric patients~with end-stage liver disease, the high mortality rate experienced awaiting Tx, and the absence of recurrent disease in children receiving Tx. Further~ustifieatiou was the predicted and realized low mortality andmorbidl~ty for donors. Recent) ¢, man).' U.S. Txprograms. based on experience gained from ACLT. have initiated AALT. Question: At this time. based on existing scientific data, is extension of ACLT to AALT in the U.S. ethically justified in all cases requiring Tx? Methods: UNOS database (1993-981 was queried for pre-Tx mortalit',', waiting time, and post-Tx patient and graft survival for patients 18 yrs. Data were stratified for blood tspe. recipient age at Tx. primar) diagno[is, and previous Txs. Statistical a~nalysis was confined to events within the bear of listing, hfformation about AALT was obtained from informal survey data and discussions at the 5th Congress, ILTS, Pittsburgh, 8/99. Results: An estimated 100 AAI,T had been performed in the U.S. and anecdotal reports suggest donor mortality of I-3% (a mortality 33-100 x > than in kidnev transplants and 5-15 x > than in ACLT). For potential recipients, pre-Tx wa'itthg list mortality is highest among those patients listed as blood type O, as status 2A. or who have fuiminant hepatic failure. Although post-Tx patient surx,ival was generally good. significant attrition in patient survival was seen in patients Txed ".v~tha primary diagnosis of malignant neoplasm. Additionally. overall patient and graft survival among re-Tx patients was sionificantlv (vorse than in primary Tx. Conclusion: In assessing whether AA[~T is ethiC:ally justified in all Tx patients in the U.S. presently, it is necessary to perform'combined interdependent risk*benefit analysis for both recipient and donor. Curremlv. relatively high donor mortality and morbidiD and increased potential for " recurrent disease in the recipient mandate that this innovati,,e technology not be applied in all cases. Unit/such time that enough scientific data exist to define the collective clinical equipoise of this surgical innovation, we believe that initial application should be Iimited to situations of greatest potential recipient benefit and Iowestpossible donor risk. Therefore, at this time. the procedure should not be ased for re-Tx, or for a primar', diagnosis with the potential for recurrent disease (hepatitis B and Cand n;alienanc'.), or for patients with predictably Io~', t, airing list mortality. To rec]uce donor risks, to an ethicall*, acceptable le,.el strict selection criter[a should be defined and AALT should be done only in institutioos v.ith substantial "field strength" in living donor Tx.
CIRRHOSIS WITH HEPATOCELLULAR CARCINOMA: A GOOD I N D I C A T I O N O F L I V E R T R A N S P L A N T A T I O N (OLT) IN A C E N T E R W I T H S H O R T T I M E IN T H E W A I T I N G - L I S T . M. Berenguer, D. Nicolfis, M. Pastor, V. Aguilera, V. Ortiz, A. Moya, M. Prieto, F. San Juan, D. Carrasco, J. Mir, J. B e r e o g u e r Hospital Universitario La Fe, Valencia, Spain. Cirrhosis with hcpatocellular carcinoma (HCC) is still considered a controversial indication for OLT, mainly due to the bad results obtained in initial studies. Aims: 1) To determine the rate o f tumor recurrence and survival in a cohort of 64 patients undergoing OLT for cirrhosis with FICC: and 2) to conlpare the baseline features, bistologic evolution and survival of these patients with a control group without HCC, in a center with a mean time in the waiting list o f 1.5 months. Methods: Between 1991-1997, 319 patients with cirrhosis of various etiologies underwent OLT. O f these 64 had a HCC (mean age: 56 yr., 74% male). Variables related to the tumor included: alpha-fetoprmein, pre-OLT treatment with quimioonlbolization and/or alcoholization and tumoral staging both clinical and pathological (size and number of nodules, location, presence o f pseudocapsule, lymph node involvement and vascular invasion). The TNM clasification was used for tumoral staging. Patients with and without HCC were compared regarding: baseline features, immunosupression, histologiu evolution and survival. Results: O f the HCC, 77% were known before OLT while the remainder were incidental. Pre-OLT treatment was done in 70% of the cases. Mean follow up of patients with HCC was 60 months. Patients with HCC were characterized by: 1) older age (55.6 _+ 7 vs 50.5 + 9, p<0.0011, 2) more frequent induction with FK506 ((I 1% vs 4%, p=0.06), and 3) higher pereentaje of HCV infection (72% vs 48%, p<0.0001). Based on TNMp clasification. HCC were classified as follows: I (6%), 11 (58%), Ill (20%/ and IVa (14%), After a median of 13 months (4-48), 5 patients developed tumor recurrence. Tbe cumulative probability of tumoral recurrence was 4%, 8% and 13% at I, 3 y 5 years, respectively. Among tumoral variables. only "bilobar involvement" was associated with a higher risk of tumoral recurrence (27% vs 4%, p-0.051. Histologic iojury, mainly rulatud to HCV, was more frequently detected in patients with HCC than in those without; Yet, survival was similar in both groups at land 5 years (78%, 72% vs 83%, 67%, respectively). Conclusions: Liver transplantation is an adequate indication in patients with cirrhosis and hepatocellular carcinoma.
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CLINICAL IMPACT OF INCIDENTAL COMPARED TO KNO'~,q~ HEPATOMAS AFTER ORTOTOPIC LIVER TRANSPLANTATION ? J. F. Buelll. A. Yoshidal. G Kim I, R. Laymanl. J. Hartl. A Swansonl. H Conjeevarum2. A Baker2. D.C Croninl. J M Millisl Department of Surgery and Liver Disease. University of Chicago. School of Medicine. Chicago. IL Controversy continues over the role of liver transplantation in the management of hepatomas due to the widely, vaned survival figures reported betwoen centers Little is mentioned about the impact o f incidental tumors discovered at pathology, thus we reviewed our experience with hepatomas to determine their impact. Methods: We retrospectively reviewed 50 pts transplanted with known (n=291 or tncidental (n=21 ) bepatomas, between '84 and "99. Charts were reviewed for demographics, etiology ofcirrbosis, adjuvant therapy, tumor recurrence and mortality Statistics were performed using student's t-test, actaariul survival and log-rank analysis. Re~uhs: The known minor (KT) group consisted of 22 males and 7 females with a mean age of 55 I + 8 9 yrs The incidental group (IC) consisted of 17 M and 4 F with a mean age of 55 4 ± 7 6 yrs. AFP levels ware higher in the KT group (530.4 vs. 295 ng/ml: p=0.09). Cirrhosis was present in 90% of KT and 100% of IC pts. The majorit) ofpts in KT (14129:48%) and IC (9/20:45%) had hepatitis C as an etiologic factor. In the KT 4 pts recurred after resection, prior to transplant with I pt undergoing systemic chemotherapy and 3 chamoembolization The mean number of lesions between the KT and I C groups were similar (3 5 +_2 3 vs 2.4 + 2 6: peNS), while KT lesions were significantly larger (4.5 + 2.5 vs. 2.1 +_ 1.7 cm; p
EXPERIENCE WITH LIVER TRANSPLANTATION HEPATOCELLLILAR CARCINOMA IN C I R R H O S I S
FOR
J Coppa. E Rcgnlia. A Pulvlrcntl. S. Andreola. R Ronuto, M Schiavo. M Dei Poli. M Ammatuna. V Mazzaferro National Cancer lastitutc. Milan. Ital) Background The role of orthotoplc It~er transplantation (OLT) in the treatmunt of patients ~ith cirri~osis and hcpatoccllular carcinoma (HCC) is controversial, and determining ~.hich patients arc hkcls to have a good outcome after liver transplantatmn is difficult. Methods Our cxperiencc accounts 114 patients ~ith cirrhosis who had small unrescctable hepatocellular carcinomas and u, ho underwent liver transplantation In 92 % of the paucnts, the cirrhosis ~as rclatud to chronic infcction v.ith HBV. 14CV, or both Thc presence of tumour was al'.~a',s confirmed at the spccimun analysis The criteria of eligibilit~ for transplantation were: single nodule
Sixth Congressof the ILTS
5
6
IS ADULT T O ADULT LIVE D O N O R L I V E R T R A N S P L A N T A T I O N E T H I C A L ? D.C. Crooin. J.M. Millis, M. Siegler. Uni',ersitv of Chicago. Section of Transplant and McLean Center for Clinical Etlfic~,. Chicago, IL In 1989, Dr. Francis Moore proposed three criteria to assess whether an innovative transplantation procedure '.*,as ethically justified: I ). Scientific data: 2). "Field strength" 6/the clinical team: ancl 3 ), Tile ethical climate of the team's institution. This paper examines only whether existing scientific data jnstify adult to adult liver transplantation (AALT) in the LI.S, at this time in al/eases requiring transplantation (Tx). After technical feasibility was demonstrated, adult to child living donor liver transplantation (ACLT) was clinically and ethically justified because of the short life span in pediatric patients~with end-stage liver disease, the high mortality rate experienced awaiting Tx, and the absence of recurrent disease in children receiving Tx. Further~ustifieatiou was the predicted and realized low mortality andmorbidl~ty for donors. Recent) ¢, man).' U.S. Txprograms. based on experience gained from ACLT. have initiated AALT. Question: At this time. based on existing scientific data, is extension of ACLT to AALT in the U.S. ethically justified in all cases requiring Tx? Methods: UNOS database (1993-981 was queried for pre-Tx mortalit',', waiting time, and post-Tx patient and graft survival for patients 18 yrs. Data were stratified for blood tspe. recipient age at Tx. primar) diagno[is, and previous Txs. Statistical a~nalysis was confined to events within the bear of listing, hfformation about AALT was obtained from informal survey data and discussions at the 5th Congress, ILTS, Pittsburgh, 8/99. Results: An estimated 100 AAI,T had been performed in the U.S. and anecdotal reports suggest donor mortality of I-3% (a mortality 33-100 x > than in kidnev transplants and 5-15 x > than in ACLT). For potential recipients, pre-Tx wa'itthg list mortality is highest among those patients listed as blood type O, as status 2A. or who have fuiminant hepatic failure. Although post-Tx patient surx,ival was generally good. significant attrition in patient survival was seen in patients Txed ".v~tha primary diagnosis of malignant neoplasm. Additionally. overall patient and graft survival among re-Tx patients was sionificantlv (vorse than in primary Tx. Conclusion: In assessing whether AA[~T is ethiC:ally justified in all Tx patients in the U.S. presently, it is necessary to perform'combined interdependent risk*benefit analysis for both recipient and donor. Curremlv. relatively high donor mortality and morbidiD and increased potential for " recurrent disease in the recipient mandate that this innovati,,e technology not be applied in all cases. Unit/such time that enough scientific data exist to define the collective clinical equipoise of this surgical innovation, we believe that initial application should be Iimited to situations of greatest potential recipient benefit and Iowestpossible donor risk. Therefore, at this time. the procedure should not be ased for re-Tx, or for a primar', diagnosis with the potential for recurrent disease (hepatitis B and Cand n;alienanc'.), or for patients with predictably Io~', t, airing list mortality. To rec]uce donor risks, to an ethicall*, acceptable le,.el strict selection criter[a should be defined and AALT should be done only in institutioos v.ith substantial "field strength" in living donor Tx.
CIRRHOSIS WITH HEPATOCELLULAR CARCINOMA: A GOOD I N D I C A T I O N O F L I V E R T R A N S P L A N T A T I O N (OLT) IN A C E N T E R W I T H S H O R T T I M E IN T H E W A I T I N G - L I S T . M. Berenguer, D. Nicolfis, M. Pastor, V. Aguilera, V. Ortiz, A. Moya, M. Prieto, F. San Juan, D. Carrasco, J. Mir, J. B e r e o g u e r Hospital Universitario La Fe, Valencia, Spain. Cirrhosis with hcpatocellular carcinoma (HCC) is still considered a controversial indication for OLT, mainly due to the bad results obtained in initial studies. Aims: 1) To determine the rate o f tumor recurrence and survival in a cohort of 64 patients undergoing OLT for cirrhosis with FICC: and 2) to conlpare the baseline features, bistologic evolution and survival of these patients with a control group without HCC, in a center with a mean time in the waiting list o f 1.5 months. Methods: Between 1991-1997, 319 patients with cirrhosis of various etiologies underwent OLT. O f these 64 had a HCC (mean age: 56 yr., 74% male). Variables related to the tumor included: alpha-fetoprmein, pre-OLT treatment with quimioonlbolization and/or alcoholization and tumoral staging both clinical and pathological (size and number of nodules, location, presence o f pseudocapsule, lymph node involvement and vascular invasion). The TNM clasification was used for tumoral staging. Patients with and without HCC were compared regarding: baseline features, immunosupression, histologiu evolution and survival. Results: O f the HCC, 77% were known before OLT while the remainder were incidental. Pre-OLT treatment was done in 70% of the cases. Mean follow up of patients with HCC was 60 months. Patients with HCC were characterized by: 1) older age (55.6 _+ 7 vs 50.5 + 9, p<0.0011, 2) more frequent induction with FK506 ((I 1% vs 4%, p=0.06), and 3) higher pereentaje of HCV infection (72% vs 48%, p<0.0001). Based on TNMp clasification. HCC were classified as follows: I (6%), 11 (58%), Ill (20%/ and IVa (14%), After a median of 13 months (4-48), 5 patients developed tumor recurrence. Tbe cumulative probability of tumoral recurrence was 4%, 8% and 13% at I, 3 y 5 years, respectively. Among tumoral variables. only "bilobar involvement" was associated with a higher risk of tumoral recurrence (27% vs 4%, p-0.051. Histologic iojury, mainly rulatud to HCV, was more frequently detected in patients with HCC than in those without; Yet, survival was similar in both groups at land 5 years (78%, 72% vs 83%, 67%, respectively). Conclusions: Liver transplantation is an adequate indication in patients with cirrhosis and hepatocellular carcinoma.
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CLINICAL IMPACT OF INCIDENTAL COMPARED TO KNO'~,q~ HEPATOMAS AFTER ORTOTOPIC LIVER TRANSPLANTATION ? J. F. Buelll. A. Yoshidal. G Kim I, R. Laymanl. J. Hartl. A Swansonl. H Conjeevarum2. A Baker2. D.C Croninl. J M Millisl Department of Surgery and Liver Disease. University of Chicago. School of Medicine. Chicago. IL Controversy continues over the role of liver transplantation in the management of hepatomas due to the widely, vaned survival figures reported betwoen centers Little is mentioned about the impact o f incidental tumors discovered at pathology, thus we reviewed our experience with hepatomas to determine their impact. Methods: We retrospectively reviewed 50 pts transplanted with known (n=291 or tncidental (n=21 ) bepatomas, between '84 and "99. Charts were reviewed for demographics, etiology ofcirrbosis, adjuvant therapy, tumor recurrence and mortality Statistics were performed using student's t-test, actaariul survival and log-rank analysis. Re~uhs: The known minor (KT) group consisted of 22 males and 7 females with a mean age of 55 I + 8 9 yrs The incidental group (IC) consisted of 17 M and 4 F with a mean age of 55 4 ± 7 6 yrs. AFP levels ware higher in the KT group (530.4 vs. 295 ng/ml: p=0.09). Cirrhosis was present in 90% of KT and 100% of IC pts. The majorit) ofpts in KT (14129:48%) and IC (9/20:45%) had hepatitis C as an etiologic factor. In the KT 4 pts recurred after resection, prior to transplant with I pt undergoing systemic chemotherapy and 3 chamoembolization The mean number of lesions between the KT and I C groups were similar (3 5 +_2 3 vs 2.4 + 2 6: peNS), while KT lesions were significantly larger (4.5 + 2.5 vs. 2.1 +_ 1.7 cm; p
EXPERIENCE WITH LIVER TRANSPLANTATION HEPATOCELLLILAR CARCINOMA IN C I R R H O S I S
FOR
J Coppa. E Rcgnlia. A Pulvlrcntl. S. Andreola. R Ronuto, M Schiavo. M Dei Poli. M Ammatuna. V Mazzaferro National Cancer lastitutc. Milan. Ital) Background The role of orthotoplc It~er transplantation (OLT) in the treatmunt of patients ~ith cirri~osis and hcpatoccllular carcinoma (HCC) is controversial, and determining ~.hich patients arc hkcls to have a good outcome after liver transplantatmn is difficult. Methods Our cxperiencc accounts 114 patients ~ith cirrhosis who had small unrescctable hepatocellular carcinomas and u, ho underwent liver transplantation In 92 % of the paucnts, the cirrhosis ~as rclatud to chronic infcction v.ith HBV. 14CV, or both Thc presence of tumour was al'.~a',s confirmed at the spccimun analysis The criteria of eligibilit~ for transplantation were: single nodule