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Published in: BMC Cancer 1/2017

Open Access 01-12-2017 | Research article

Expansion of the Milan criteria without any sacrifice: combination of the Hangzhou criteria with the pre-transplant platelet-to-lymphocyte ratio

Authors: Weiliang Xia, Qinghong Ke, Hua Guo, Weilin Wang, Min Zhang, Yan Shen, Jian Wu, Xiao Xu, Sheng Yan, Jun Yu, Mangli Zhang, Shusen Zheng

Published in: BMC Cancer | Issue 1/2017

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Abstract

Background

The Hangzhou criteria expand the Milan criteria safely and effectively in selecting hepatocellular carcinoma (HCC) candidates for liver transplantation (LT), but some patients exceeding the Milan but fulfilling the Hangzhou criteria still show poor outcomes due to early tumor recurrence. In this study, the platelet-to-lymphocyte ratio (PLR) was employed to differentiate high-risk tumor recurrence recipients, and a new method combining PLR and the Hangzhou criteria was established.

Methods

The clinical data of 343 LT for HCC were retrospectively analyzed. Receiver operating characteristic (ROC) analysis was used to determine the PLR cut-off value to stratify patients exceeding the Milan but fulfilling the Hangzhou criteria. The recurrence-free survival (RFS) of recipients was compared after stratification. The Hangzhou criteria & PLR method was proposed and its feasibility was validated by ROC analysis.

Results

PLR 120 was the most significant cut-off value when comparing RFS of patients exceeding the Milan but fulfilling the Hangzhou criteria. After stratification, the 1-, 3-, and 5-year RFS of patients exceeding the Milan but fulfilling the Hangzhou criteria with PLR < 120 were 84.2%, 73.3%, and 73.3%, respectively, comparable with 85.7%, 73.9%, and 72.8%, respectively, in patients fulfilling the Milan criteria (P = 0.885). Patients exceeding the Milan but fulfilling the Hangzhou criteria with PLR ≥ 120 showed poor outcomes, which were similar in patients exceeding the Hangzhou criteria; 1-, 3-, and 5-year RFS were only 37.5%, 12.5%, and 12.5% vs. 32.3%, 17.6%, and 15.1%, respectively (P = 0.887). ROC analysis demonstrated that the ROC area of the Hangzhou criteria & PLR method was 0.768 for RFS. Multivariate analysis confirmed that PLR ≥ 120 was independently associated with RFS of patients exceeding the Milan but fulfilling the Hangzhou criteria.

Conclusions

The Hangzhou criteria combined with the pre-transplant PLR can accurately exclude high-risk tumor recurrence recipients; this approach expands the Milan criteria effectively without any sacrifice.
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Literature
2.
go back to reference Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65(2):87–108.CrossRefPubMed Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65(2):87–108.CrossRefPubMed
4.
go back to reference O'Grady JG, Polson RJ, Rolles K, Calne RY, Williams R, Liver transplantation for malignant disease. Results in 93 consecutive patients. Ann Surg. 1988;207(4):373–9.CrossRefPubMedPubMedCentral O'Grady JG, Polson RJ, Rolles K, Calne RY, Williams R, Liver transplantation for malignant disease. Results in 93 consecutive patients. Ann Surg. 1988;207(4):373–9.CrossRefPubMedPubMedCentral
5.
go back to reference Mazzaferro V, Regalia E, Doci R, Andreola S, Pulvirenti A, Bozzetti F, et al. Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis. N Engl J Med. 1996;334(11):693–9.CrossRefPubMed Mazzaferro V, Regalia E, Doci R, Andreola S, Pulvirenti A, Bozzetti F, et al. Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis. N Engl J Med. 1996;334(11):693–9.CrossRefPubMed
6.
go back to reference Yao FY, Ferrell L, Bass NM, Watson JJ, Bacchetti P, Venook A, et al. Liver transplantation for hepatocellular carcinoma: expansion of the tumor size limits does not adversely impact survival. Hepatology. 2001;33(6):1394–403.CrossRefPubMed Yao FY, Ferrell L, Bass NM, Watson JJ, Bacchetti P, Venook A, et al. Liver transplantation for hepatocellular carcinoma: expansion of the tumor size limits does not adversely impact survival. Hepatology. 2001;33(6):1394–403.CrossRefPubMed
7.
go back to reference Zheng SS, Xu X, Wu J, Chen J, Wang WL, Zhang M, et al. Liver transplantation for hepatocellular carcinoma: Hangzhou experiences. Transplantation. 2008;85(12):1726–32.CrossRefPubMed Zheng SS, Xu X, Wu J, Chen J, Wang WL, Zhang M, et al. Liver transplantation for hepatocellular carcinoma: Hangzhou experiences. Transplantation. 2008;85(12):1726–32.CrossRefPubMed
8.
go back to reference Mazzaferro V, Llovet JM, Miceli R, Bhoori S, Schiavo M, Mariani L, et al. 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.CrossRefPubMed Mazzaferro V, Llovet JM, Miceli R, Bhoori S, Schiavo M, Mariani L, et al. 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.CrossRefPubMed
9.
go back to reference Xu X, Lu D, Ling Q, Wei X, Wu J, Zhou L, et al. Liver transplantation for hepatocellular carcinoma beyond the Milan criteria. Gut. 2016;65(6):1035–41.CrossRefPubMed Xu X, Lu D, Ling Q, Wei X, Wu J, Zhou L, et al. Liver transplantation for hepatocellular carcinoma beyond the Milan criteria. Gut. 2016;65(6):1035–41.CrossRefPubMed
10.
go back to reference Kilincalp S, Coban S, Akinci H, Hamamci M, Karaahmet F, Coskun Y, et al. Neutrophil/lymphocyte ratio, platelet/lymphocyte ratio, and mean platelet volume as potential biomarkers for early detection and monitoring of colorectal adenocarcinoma. Eur J Cancer Prev. 2015;24(4):328–33.CrossRefPubMed Kilincalp S, Coban S, Akinci H, Hamamci M, Karaahmet F, Coskun Y, et al. Neutrophil/lymphocyte ratio, platelet/lymphocyte ratio, and mean platelet volume as potential biomarkers for early detection and monitoring of colorectal adenocarcinoma. Eur J Cancer Prev. 2015;24(4):328–33.CrossRefPubMed
11.
go back to reference Neofytou K, Smyth EC, Giakoustidis A, Khan AZ, Cunningham D, Mudan S. Elevated platelet to lymphocyte ratio predicts poor prognosis after hepatectomy for liver-only colorectal metastases, and it is superior to neutrophil to lymphocyte ratio as an adverse prognostic factor. Med Oncol. 2014;31(10):239.CrossRefPubMed Neofytou K, Smyth EC, Giakoustidis A, Khan AZ, Cunningham D, Mudan S. Elevated platelet to lymphocyte ratio predicts poor prognosis after hepatectomy for liver-only colorectal metastases, and it is superior to neutrophil to lymphocyte ratio as an adverse prognostic factor. Med Oncol. 2014;31(10):239.CrossRefPubMed
12.
go back to reference Xia W, Ke Q, Wang Y, Wang W, Zhang M, Shen Y, et al. Predictive value of pre-transplant platelet to lymphocyte ratio for hepatocellular carcinoma recurrence after liver transplantation. World J Surg Oncol. 2015;13:60.CrossRefPubMedPubMedCentral Xia W, Ke Q, Wang Y, Wang W, Zhang M, Shen Y, et al. Predictive value of pre-transplant platelet to lymphocyte ratio for hepatocellular carcinoma recurrence after liver transplantation. World J Surg Oncol. 2015;13:60.CrossRefPubMedPubMedCentral
13.
go back to reference Hemming AW, Cattral MS, Reed AI, Van Der Werf WJ, Greig PD, Howard RJ. Liver transplantation for hepatocellular carcinoma. Ann Surg. 2001;233(5):652–9.CrossRefPubMedPubMedCentral Hemming AW, Cattral MS, Reed AI, Van Der Werf WJ, Greig PD, Howard RJ. Liver transplantation for hepatocellular carcinoma. Ann Surg. 2001;233(5):652–9.CrossRefPubMedPubMedCentral
14.
go back to reference Freeman RB, Mithoefer A, Ruthazer R, Nguyen K, Schore A, Harper A, Edwards E. Optimizing staging for hepatocellular carcinoma before liver transplantation: A retrospective analysis of the UNOS/OPTN database. Liver Transpl. 2006;12(10):1504–11.CrossRefPubMed Freeman RB, Mithoefer A, Ruthazer R, Nguyen K, Schore A, Harper A, Edwards E. Optimizing staging for hepatocellular carcinoma before liver transplantation: A retrospective analysis of the UNOS/OPTN database. Liver Transpl. 2006;12(10):1504–11.CrossRefPubMed
15.
go back to reference Vibert E, Azoulay D, Hoti E, Iacopinelli S, Samuel D, Salloum C, et al. Progression of alphafetoprotein before liver transplantation for hepatocellular carcinoma in cirrhotic patients: a critical factor. Am J Transplant. 2010;10(1):129–37.CrossRefPubMed Vibert E, Azoulay D, Hoti E, Iacopinelli S, Samuel D, Salloum C, et al. Progression of alphafetoprotein before liver transplantation for hepatocellular carcinoma in cirrhotic patients: a critical factor. Am J Transplant. 2010;10(1):129–37.CrossRefPubMed
16.
go back to reference Nart D, Yaman B, Yilmaz F, Zeytunlu M, Karasu Z, Kilic M. Expression of matrix metalloproteinase-9 in predicting prognosis of hepatocellular carcinoma after liver transplantation. Liver Transpl. 2010;16(5):621–30.PubMed Nart D, Yaman B, Yilmaz F, Zeytunlu M, Karasu Z, Kilic M. Expression of matrix metalloproteinase-9 in predicting prognosis of hepatocellular carcinoma after liver transplantation. Liver Transpl. 2010;16(5):621–30.PubMed
17.
go back to reference Sieghart W, Wang X, Schmid K, Pinter M, Konig F, Bodingbauer M, et al. Osteopontin expression predicts overall survival after liver transplantation for hepatocellular carcinoma in patients beyond the Milan criteria. J Hepatol. 2011;54(1):89–97.CrossRefPubMed Sieghart W, Wang X, Schmid K, Pinter M, Konig F, Bodingbauer M, et al. Osteopontin expression predicts overall survival after liver transplantation for hepatocellular carcinoma in patients beyond the Milan criteria. J Hepatol. 2011;54(1):89–97.CrossRefPubMed
18.
go back to reference Cheung ST, Fan ST, Lee YT, Chow JP, Ng IO, Fong DY, Lo CM. Albumin mRNA in plasma predicts post-transplant recurrence of patients with hepatocellular carcinoma. Transplantation. 2008;85(1):81–7.CrossRefPubMed Cheung ST, Fan ST, Lee YT, Chow JP, Ng IO, Fong DY, Lo CM. Albumin mRNA in plasma predicts post-transplant recurrence of patients with hepatocellular carcinoma. Transplantation. 2008;85(1):81–7.CrossRefPubMed
19.
21.
go back to reference Mantovani A, Allavena P, Sica A, Balkwill F. Cancer-related inflammation. Nature. 2008;454(7203):436–44.CrossRefPubMed Mantovani A, Allavena P, Sica A, Balkwill F. Cancer-related inflammation. Nature. 2008;454(7203):436–44.CrossRefPubMed
22.
go back to reference Lai Q, Castro Santa E, Rico Juri JM, Pinheiro RS, Lerut J. Neutrophil and platelet-to-lymphocyte ratio as new predictors of dropout and recurrence after liver transplantation for hepatocellular cancer. Transpl Int. 2014;27(1):32–41.CrossRefPubMed Lai Q, Castro Santa E, Rico Juri JM, Pinheiro RS, Lerut J. Neutrophil and platelet-to-lymphocyte ratio as new predictors of dropout and recurrence after liver transplantation for hepatocellular cancer. Transpl Int. 2014;27(1):32–41.CrossRefPubMed
23.
go back to reference Kinoshita A, Onoda H, Imai N, Iwaku A, Oishi M, Tanaka K, et al. The Glasgow Prognostic Score, an inflammation based prognostic score, predicts survival in patients with hepatocellular carcinoma. BMC Cancer. 2013;13:52.CrossRefPubMedPubMedCentral Kinoshita A, Onoda H, Imai N, Iwaku A, Oishi M, Tanaka K, et al. The Glasgow Prognostic Score, an inflammation based prognostic score, predicts survival in patients with hepatocellular carcinoma. BMC Cancer. 2013;13:52.CrossRefPubMedPubMedCentral
24.
go back to reference Xue TC, Jia QA, Ge NL, Zhang BH, Wang YH, Ren ZG, Ye SL. The platelet-to-lymphocyte ratio predicts poor survival in patients with huge hepatocellular carcinoma that received transarterial chemoembolization. Tumour Biol. 2015;36(8):6045–51.CrossRefPubMed Xue TC, Jia QA, Ge NL, Zhang BH, Wang YH, Ren ZG, Ye SL. The platelet-to-lymphocyte ratio predicts poor survival in patients with huge hepatocellular carcinoma that received transarterial chemoembolization. Tumour Biol. 2015;36(8):6045–51.CrossRefPubMed
25.
go back to reference Li X, Han Z, Cheng Z, Yu J, Yu X, Liang P. Clinical significance of preoperative platelet-to-lymphocyte ratio in recurrent hepatocellular carcinoma after thermal ablation: A retrospective analysis. Int J Hyperthermia. 2015;31(7):758–63.CrossRefPubMed Li X, Han Z, Cheng Z, Yu J, Yu X, Liang P. Clinical significance of preoperative platelet-to-lymphocyte ratio in recurrent hepatocellular carcinoma after thermal ablation: A retrospective analysis. Int J Hyperthermia. 2015;31(7):758–63.CrossRefPubMed
26.
go back to reference Li C, Wen TF, Yan LN, Li B, Wang WT, Yang JY, Xu MQ. Postoperative neutrophil-to-lymphocyte ratio plus platelet-to-lymphocyte ratio predicts the outcomes of hepatocellular carcinoma. J Surg Res. 2015;198(1):73–9.CrossRefPubMed Li C, Wen TF, Yan LN, Li B, Wang WT, Yang JY, Xu MQ. Postoperative neutrophil-to-lymphocyte ratio plus platelet-to-lymphocyte ratio predicts the outcomes of hepatocellular carcinoma. J Surg Res. 2015;198(1):73–9.CrossRefPubMed
27.
go back to reference Parisi I, Tsochatzis E, Wijewantha H, Rodriguez-Peralvarez M, De Luca L, Manousou P, et al. Inflammation-based scores do not predict post-transplant recurrence of hepatocellular carcinoma in patients within Milan criteria. Liver Transpl. 2014;20(11):1327–35.CrossRefPubMed Parisi I, Tsochatzis E, Wijewantha H, Rodriguez-Peralvarez M, De Luca L, Manousou P, et al. Inflammation-based scores do not predict post-transplant recurrence of hepatocellular carcinoma in patients within Milan criteria. Liver Transpl. 2014;20(11):1327–35.CrossRefPubMed
Metadata
Title
Expansion of the Milan criteria without any sacrifice: combination of the Hangzhou criteria with the pre-transplant platelet-to-lymphocyte ratio
Authors
Weiliang Xia
Qinghong Ke
Hua Guo
Weilin Wang
Min Zhang
Yan Shen
Jian Wu
Xiao Xu
Sheng Yan
Jun Yu
Mangli Zhang
Shusen Zheng
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2017
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-016-3028-0

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