Skip to main content
Top
Published in: Journal of Gastrointestinal Cancer 3/2020

01-09-2020 | Liver Transplantation | Original Research

Liver Transplantation for Hepatocellular Carcinoma: Malatya Experience and Proposals for Expanded Criteria

Authors: Volkan Ince, Sami Akbulut, Emrah Otan, Veysel Ersan, Serdar Karakas, Tolga Tevfik Sahin, Brian I Carr, Adil Baskiran, Emine Samdanci, Harika Gozukara Bag, Cemalettin Koc, Sertac Usta, Fatih Ozdemir, Bora Barut, Fatih Gonultas, Baris Sarici, Koray Kutluturk, Murat Sait Dogan, Dincer Ozgor, Mustafa Dikilitas, Murat Harputluoglu, Murat Aladag, Ramazan Kutlu, Ilknur Varol, Abuzer Dirican, Cemalettin Aydin, Burak Isik, Cengiz Ara, Cuneyt Kayaalp, Sukru Emre, Sezai Yilmaz

Published in: Journal of Gastrointestinal Cancer | Issue 3/2020

Login to get access

Abstract

Survival was examined from a Turkish liver transplant center of patients with HCC, to identify prognostic factors. Data from 215 patients who underwent predominantly live donor liver transplant for HCC at our institute over 12 years were included in the study and prospectively recorded. They were 152 patients within and 63 patients beyond Milan criteria. Patients beyond Milan criteria were divided into two groups according to presence or absence of tumor recurrence. Recurrence-associated factors were analyzed. These factors were then applied to the total cohort for survival analysis. We identified four factors, using multivariate analysis, that were significantly associated with tumor recurrence. These were maximum tumor diameter, degree of tumor differentiation, and serum AFP and GGT levels. A model that included all four of these factors was constructed, the ‘Malatya criteria.’ Using these Malatya criteria, we estimated DFS and cumulative survival, for patients within and beyond these criteria, and found statistically significant differences with improved survival in patients within Malatya criteria of 1, 5, and 10-year overall survival rates of 90.1%, 79.7%, and 72.8% respectively, which compared favorably with other extra-Milan extended criteria. Survival of our patients within the newly defined Malatya criteria compared favorably with other extra-Milan extended criteria and highlight the usefulness of serum AFP and GGT levels in decision-making.
Appendix
Available only for authorised users
Literature
2.
go back to reference Mazzaferro V, Regalia E, Doci R, Andreola S, Pulvirenti A, Bozzetti F, Montalto F, Ammatuna M, Morabito A, Gennari L. Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis. N Engl J Med. 1996;334:693–9.CrossRef Mazzaferro V, Regalia E, Doci R, Andreola S, Pulvirenti A, Bozzetti F, Montalto F, Ammatuna M, Morabito A, Gennari L. Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis. N Engl J Med. 1996;334:693–9.CrossRef
3.
go back to reference Yao FY, Ferrell L, Bass NM, Watson JJ, Bacchetti P, Venook A, Ascher NL, Roberts JP. Liver transplantation for hepatocellular carcinoma: expansion of the tumor size limits does not adversely impact survival. Hepatology. 2001;33(6):1394–403.CrossRef Yao FY, Ferrell L, Bass NM, Watson JJ, Bacchetti P, Venook A, Ascher NL, Roberts JP. Liver transplantation for hepatocellular carcinoma: expansion of the tumor size limits does not adversely impact survival. Hepatology. 2001;33(6):1394–403.CrossRef
4.
go back to reference Llovet JM, Pavel M, Rimola J, Diaz MA, Colmenero J, Saavedra-Perez D, Fondevila C, Ayuso C, Fuster J, Ginès P, Bruix J, Garcia-Valdecasas JC. Pilot study of living donor liver transplantation for patients with hepatocellular carcinoma exceeding Milan criteria (Barcelona clinic liver cancer extended criteria). Liver Transplant. 2018;24:369–79.CrossRef Llovet JM, Pavel M, Rimola J, Diaz MA, Colmenero J, Saavedra-Perez D, Fondevila C, Ayuso C, Fuster J, Ginès P, Bruix J, Garcia-Valdecasas JC. Pilot study of living donor liver transplantation for patients with hepatocellular carcinoma exceeding Milan criteria (Barcelona clinic liver cancer extended criteria). Liver Transplant. 2018;24:369–79.CrossRef
5.
go back to reference Mazzaferro V, Llovet JM, Miceli R, Bhoori S, Schiavo M, Mariani L, Camerini T, Roayaie S, Schwartz ME, Grazi GL, Adam R, Neuhaus P, Salizzoni M, Bruix J, Forner A, de Carlis L, Cillo U, Burroughs AK, Troisi R, Rossi M, Gerunda GE, Lerut J, Belghiti J, Boin I, Gugenheim J, Rochling F, van Hoek B, Majno P, Metroticket Investigator Study Group. Predicting survival after liver transplantation in patients with hepatocellular carcinoma beyond the Milan criteria: a retrospective, exploratory analysis. Lancet Oncol. 2009;10(1):35–43.CrossRef Mazzaferro V, Llovet JM, Miceli R, Bhoori S, Schiavo M, Mariani L, Camerini T, Roayaie S, Schwartz ME, Grazi GL, Adam R, Neuhaus P, Salizzoni M, Bruix J, Forner A, de Carlis L, Cillo U, Burroughs AK, Troisi R, Rossi M, Gerunda GE, Lerut J, Belghiti J, Boin I, Gugenheim J, Rochling F, van Hoek B, Majno P, Metroticket Investigator Study Group. Predicting survival after liver transplantation in patients with hepatocellular carcinoma beyond the Milan criteria: a retrospective, exploratory analysis. Lancet Oncol. 2009;10(1):35–43.CrossRef
6.
go back to reference Sapisochin G, Goldaracena N, Laurence JM, Dib M, Barbas A, Ghanekar A, Cleary SP, Lilly L, Cattral MS, Marquez M, Selzner M, Renner E, Selzner N, McGilvray ID, Greig PD, Grant DR. The extended Toronto criteria for liver transplantation in patients with hepatocellular carcinoma: a prospective validation study. Hepatology. 2016;64(6):2077–88.CrossRef Sapisochin G, Goldaracena N, Laurence JM, Dib M, Barbas A, Ghanekar A, Cleary SP, Lilly L, Cattral MS, Marquez M, Selzner M, Renner E, Selzner N, McGilvray ID, Greig PD, Grant DR. The extended Toronto criteria for liver transplantation in patients with hepatocellular carcinoma: a prospective validation study. Hepatology. 2016;64(6):2077–88.CrossRef
7.
go back to reference Zheng SS, Xu X, Wu J, Chen J, Wang WL, Zhang M, Liang TB, Wu LM. Liver transplantation for hepatocellular carcinoma: Hangzhou experiences. Transplantation. 2008;85(12):1726–32.CrossRef Zheng SS, Xu X, Wu J, Chen J, Wang WL, Zhang M, Liang TB, Wu LM. Liver transplantation for hepatocellular carcinoma: Hangzhou experiences. Transplantation. 2008;85(12):1726–32.CrossRef
8.
go back to reference Isik B, Ince V, Karabulut K, Kayaalp C, Yilmaz S. Living donor liver transplantation for hepatocellular carcinoma. Transplant Proc. 2012;44(6):1713–6.CrossRef Isik B, Ince V, Karabulut K, Kayaalp C, Yilmaz S. Living donor liver transplantation for hepatocellular carcinoma. Transplant Proc. 2012;44(6):1713–6.CrossRef
9.
go back to reference Kayaalp C, Ince V, Ersan V, Karakas S, Kahraman AS, Yilmaz S. Liver transplantation for hepatocellular carcinoma at Inonu University. J Gastrointest Cancer. 2017;48(3):268–71.CrossRef Kayaalp C, Ince V, Ersan V, Karakas S, Kahraman AS, Yilmaz S. Liver transplantation for hepatocellular carcinoma at Inonu University. J Gastrointest Cancer. 2017;48(3):268–71.CrossRef
10.
go back to reference Toso C, Kneteman NM, James Shapiro AM, Bigam DL. The estimated number of patients with hepatocellular carcinoma selected for liver transplantation using expanded selection criteria. Transpl Int. 2009;22(9):869–75.CrossRef Toso C, Kneteman NM, James Shapiro AM, Bigam DL. The estimated number of patients with hepatocellular carcinoma selected for liver transplantation using expanded selection criteria. Transpl Int. 2009;22(9):869–75.CrossRef
11.
go back to reference Mazzaferro V, Battiston C, Sposito C. Pro (with caution): extended oncologic indications in liver transplantation. Liver Transpl. 2018;24(1):98–103.CrossRef Mazzaferro V, Battiston C, Sposito C. Pro (with caution): extended oncologic indications in liver transplantation. Liver Transpl. 2018;24(1):98–103.CrossRef
12.
go back to reference Patel SS, Arrington AK, McKenzie S, et al. Milan criteria and UCSF criteria: a preliminary comparative study of liver transplantation outcomes in the United States. Int J Hepatol. 2012;2012:253517.CrossRef Patel SS, Arrington AK, McKenzie S, et al. Milan criteria and UCSF criteria: a preliminary comparative study of liver transplantation outcomes in the United States. Int J Hepatol. 2012;2012:253517.CrossRef
13.
go back to reference Duffy JP, Vardanian A, Benjamin E, Watson M, Farmer DG, Ghobrial RM, Lipshutz G, Yersiz H, Lu DSK, Lassman C, Tong MJ, Hiatt JR, Busuttil RW. Liver transplantation criteria for hepatocellular carcinoma should be expanded: a 22-year experience with 467 patients at UCLA. Ann Surg. 2007;246(3):502–9.CrossRef Duffy JP, Vardanian A, Benjamin E, Watson M, Farmer DG, Ghobrial RM, Lipshutz G, Yersiz H, Lu DSK, Lassman C, Tong MJ, Hiatt JR, Busuttil RW. Liver transplantation criteria for hepatocellular carcinoma should be expanded: a 22-year experience with 467 patients at UCLA. Ann Surg. 2007;246(3):502–9.CrossRef
14.
go back to reference Toso C, Meeberg G, Hernandez-Alejandro R, Dufour JF, Marotta P, Majno P, Kneteman NM. Total tumor volume and alpha-fetoprotein for selection of transplant candidates with hepatocellular carcinoma: a prospective validation. Hepatology. 2015;62(1):158–65.CrossRef Toso C, Meeberg G, Hernandez-Alejandro R, Dufour JF, Marotta P, Majno P, Kneteman NM. Total tumor volume and alpha-fetoprotein for selection of transplant candidates with hepatocellular carcinoma: a prospective validation. Hepatology. 2015;62(1):158–65.CrossRef
15.
go back to reference Lee SG, Hwang S, Moon DB, Ahn CS, Kim KH, Sung KB, Ko GY, Park KM, Ha TY, Song GW. Expanded indication criteria of living donor liver transplantation for hepatocellular carcinoma at one large-volume center. Liver Transpl. 2008;14(7):935–45.CrossRef Lee SG, Hwang S, Moon DB, Ahn CS, Kim KH, Sung KB, Ko GY, Park KM, Ha TY, Song GW. Expanded indication criteria of living donor liver transplantation for hepatocellular carcinoma at one large-volume center. Liver Transpl. 2008;14(7):935–45.CrossRef
16.
go back to reference Ito T, Takada Y, Ueda M, Haga H, Maetani Y, Oike F, Ogawa K, Sakamoto S, Ogura Y, Egawa H, Tanaka K, Uemoto S. Expansion of selection criteria for patients with hepatocellular carcinoma in living donor liver transplantation. Liver Transpl. 2007;13(12):1637–44.CrossRef Ito T, Takada Y, Ueda M, Haga H, Maetani Y, Oike F, Ogawa K, Sakamoto S, Ogura Y, Egawa H, Tanaka K, Uemoto S. Expansion of selection criteria for patients with hepatocellular carcinoma in living donor liver transplantation. Liver Transpl. 2007;13(12):1637–44.CrossRef
17.
go back to reference Mehta N, Dodge JL, Goel A, Roberts JP, Hirose R, Yao FY. Identification of liver transplant candidates with hepatocellular carcinoma and a very low dropout risk: implications for the current organ allocation policy. Liver Transpl. 2013;19(12):1343–53.CrossRef Mehta N, Dodge JL, Goel A, Roberts JP, Hirose R, Yao FY. Identification of liver transplant candidates with hepatocellular carcinoma and a very low dropout risk: implications for the current organ allocation policy. Liver Transpl. 2013;19(12):1343–53.CrossRef
19.
go back to reference Carr BI, Guerra V, Giannini EG, et al. A liver index and its relationship to indices of HCC aggressiveness. J Integr Oncol. 2016;5(4):178.CrossRef Carr BI, Guerra V, Giannini EG, et al. A liver index and its relationship to indices of HCC aggressiveness. J Integr Oncol. 2016;5(4):178.CrossRef
20.
go back to reference Akkiz H, Carr BI, Yalçın KK, et al. Characteristics of hepatocellular carcinoma aggressiveness factors in Turkish patients. Oncology. 2018;94(2):116–24.CrossRef Akkiz H, Carr BI, Yalçın KK, et al. Characteristics of hepatocellular carcinoma aggressiveness factors in Turkish patients. Oncology. 2018;94(2):116–24.CrossRef
21.
go back to reference Wang NY, Zhang D, Zhao W, Fang GX, Shi YL, Duan MH. Clinical applicaton of an enzyme-linked immunosorbent assay detecting hepatoma-spesific gamma-glutamyltransferase. Hepatol Res. 2009;39:979–87.CrossRef Wang NY, Zhang D, Zhao W, Fang GX, Shi YL, Duan MH. Clinical applicaton of an enzyme-linked immunosorbent assay detecting hepatoma-spesific gamma-glutamyltransferase. Hepatol Res. 2009;39:979–87.CrossRef
22.
go back to reference Yao DF, Dong ZZ, Yao M. Specific molecular markers in hepatocellular carcinoma. Hepatobiliary Pancreat Dis Int. 2007;6(3):241–7.PubMed Yao DF, Dong ZZ, Yao M. Specific molecular markers in hepatocellular carcinoma. Hepatobiliary Pancreat Dis Int. 2007;6(3):241–7.PubMed
23.
go back to reference Xia J, Song P, Sun Z, Sawakami T, Jia M, Wang Z. Advances of diagnostic and mechanistic studies of γ-glutamyl transpeptidase in hepatocellular carcinoma. Drug Discov Ther. 2016;10(4):181–7.CrossRef Xia J, Song P, Sun Z, Sawakami T, Jia M, Wang Z. Advances of diagnostic and mechanistic studies of γ-glutamyl transpeptidase in hepatocellular carcinoma. Drug Discov Ther. 2016;10(4):181–7.CrossRef
24.
go back to reference Lee SD, Kim SH. Role of positron emission tomography/computed tomography in living donor liver transplantation for hepatocellular carcinoma. Hepatobiliary Surg Nutr. 2016;5(5):408–14.CrossRef Lee SD, Kim SH. Role of positron emission tomography/computed tomography in living donor liver transplantation for hepatocellular carcinoma. Hepatobiliary Surg Nutr. 2016;5(5):408–14.CrossRef
25.
go back to reference Lai Q, Avolio AW, Graziadei I, et al. Alpha-fetoprotein and modified response evaluation criteria in solid tumors progression after locoregional therapy as predictors of hepatocellular cancer recurrence and death after transplantation. Liver Transpl. 2013;19(10):1108–18.CrossRef Lai Q, Avolio AW, Graziadei I, et al. Alpha-fetoprotein and modified response evaluation criteria in solid tumors progression after locoregional therapy as predictors of hepatocellular cancer recurrence and death after transplantation. Liver Transpl. 2013;19(10):1108–18.CrossRef
26.
go back to reference Otto G, Herber S, Heise M, Lohse AW, Mönch C, Bittinger F, Hoppe-Lotichius M, Schuchmann M, Victor A, Pitton M. Response to transarterial chemoembolization as a biological selection criterion for liver transplantation in hepatocellular carcinoma. Liver Transpl. 2006;12(8):1260–7.CrossRef Otto G, Herber S, Heise M, Lohse AW, Mönch C, Bittinger F, Hoppe-Lotichius M, Schuchmann M, Victor A, Pitton M. Response to transarterial chemoembolization as a biological selection criterion for liver transplantation in hepatocellular carcinoma. Liver Transpl. 2006;12(8):1260–7.CrossRef
27.
go back to reference Hameed B, Mehta N, Sapisochin G, Roberts JP, Yao FY. Alpha-fetoprotein level > 1000 ng/mL as an exclusion criterion for liver transplantation in patients with hepatocellular carcinoma meeting the Milan criteria. Liver Transpl. 2014;20(8):945–51.CrossRef Hameed B, Mehta N, Sapisochin G, Roberts JP, Yao FY. Alpha-fetoprotein level > 1000 ng/mL as an exclusion criterion for liver transplantation in patients with hepatocellular carcinoma meeting the Milan criteria. Liver Transpl. 2014;20(8):945–51.CrossRef
Metadata
Title
Liver Transplantation for Hepatocellular Carcinoma: Malatya Experience and Proposals for Expanded Criteria
Authors
Volkan Ince
Sami Akbulut
Emrah Otan
Veysel Ersan
Serdar Karakas
Tolga Tevfik Sahin
Brian I Carr
Adil Baskiran
Emine Samdanci
Harika Gozukara Bag
Cemalettin Koc
Sertac Usta
Fatih Ozdemir
Bora Barut
Fatih Gonultas
Baris Sarici
Koray Kutluturk
Murat Sait Dogan
Dincer Ozgor
Mustafa Dikilitas
Murat Harputluoglu
Murat Aladag
Ramazan Kutlu
Ilknur Varol
Abuzer Dirican
Cemalettin Aydin
Burak Isik
Cengiz Ara
Cuneyt Kayaalp
Sukru Emre
Sezai Yilmaz
Publication date
01-09-2020
Publisher
Springer US
Published in
Journal of Gastrointestinal Cancer / Issue 3/2020
Print ISSN: 1941-6628
Electronic ISSN: 1941-6636
DOI
https://doi.org/10.1007/s12029-020-00424-w

Other articles of this Issue 3/2020

Journal of Gastrointestinal Cancer 3/2020 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.