Skip to main content
Top
Published in: Digestive Diseases and Sciences 2/2018

01-02-2018 | Original Article

Outcomes of Salvage Liver Transplantation and Re-resection/Radiofrequency Ablation for Intrahepatic Recurrent Hepatocellular Carcinoma: A New Surgical Strategy Based on Recurrence Pattern

Authors: Xiaoyun Zhang, Chuan Li, Tianfu Wen, Wei Peng, Lunan Yan, Jiayin Yang

Published in: Digestive Diseases and Sciences | Issue 2/2018

Login to get access

Abstract

Background

The treatment of intrahepatic recurrent hepatocellular carcinoma (HCC) has been poorly investigated, and the optimal treatment strategy remains unclear.

Aims

The aim of this study was to compare outcomes between salvage liver transplantation (SLT) and re-resection (RR)/radiofrequency ablation (RFA) for intrahepatic recurrent HCC according to recurrence pattern.

Methods

Based on postoperative histopathological examination, 122 patients with intrahepatic recurrent HCC were divided into an intrahepatic metastasis (IM, n = 75) group and a multicentric occurrence (MO, n = 47) group. The demographic, clinical, and primary and recurrent tumor characteristics of the IM group and the MO group were collected and compared. Overall survival (OS) and disease-free survival (DFS) were analyzed, and subgroup analysis according to retreatment type (SLT vs. RR/RFA) was conducted. Twenty-nine clinicopathological variables potentially related to prognostic factors affecting survival were analyzed using a Cox proportional hazard model.

Results

The patients that received SLT treatment exhibited favorable DFS compared to patients that received RR/RFA (P = 0.002). OS (P < 0.001) and DFS (P = 0.008) rates were significantly increased in the MO group compared with in the IM group. Subgroup analysis revealed that DFS was significantly improved for patients in the MO group treated with SLT compared to patients treated with RR/RFA (P = 0.017). Recurrence pattern was an independent prognostic factor for both OS [hazard ratio (HR) = 0.093, 95% confidence interval (CI): 0.026–0.337, P < 0.001] and DFS (HR = 0.318, 95% CI: 0.125–0.810, P = 0.016; HR = 3.334, 95% CI: 1.546–7.18, P = 0.002).

Conclusions

For patients with intrahepatic recurrent HCC, an MO recurrence pattern is associated with better long-term outcomes than the IM pattern. SLT is the preferred option for intrahepatic recurrent HCC, especially for MO cases.
Appendix
Available only for authorised users
Literature
1.
go back to reference Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90.CrossRefPubMed Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90.CrossRefPubMed
3.
go back to reference European Association for the Study of the Liver. EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol. 2012;56:908–943.CrossRef European Association for the Study of the Liver. EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol. 2012;56:908–943.CrossRef
4.
go back to reference Fan ST, Mau Lo C, Poon RT, et al. Continuous improvement of survival outcomes of resection of hepatocellular carcinoma: a 20-year experience. Ann Surg. 2011;253:745–758.CrossRefPubMed Fan ST, Mau Lo C, Poon RT, et al. Continuous improvement of survival outcomes of resection of hepatocellular carcinoma: a 20-year experience. Ann Surg. 2011;253:745–758.CrossRefPubMed
5.
go back to reference Regimbeau JM, Abdalla EK, Vauthey JN, et al. Risk factors for early death due to recurrence after liver resection for hepatocellular carcinoma: results of a multicenter study. J Surg Oncol. 2004;85:36–41.CrossRefPubMed Regimbeau JM, Abdalla EK, Vauthey JN, et al. Risk factors for early death due to recurrence after liver resection for hepatocellular carcinoma: results of a multicenter study. J Surg Oncol. 2004;85:36–41.CrossRefPubMed
6.
go back to reference Chen Y-J, Yeh S-H, Chen J-T, et al. Chromosomal changes and clonality relationship between primary and recurrent hepatocellular carcinoma. Gastroenterology. 2000;119:431–440.CrossRefPubMed Chen Y-J, Yeh S-H, Chen J-T, et al. Chromosomal changes and clonality relationship between primary and recurrent hepatocellular carcinoma. Gastroenterology. 2000;119:431–440.CrossRefPubMed
7.
go back to reference Morimoto O, Nagano H, Sakon M, et al. Diagnosis of intrahepatic metastasis and multicentric carcinogenesis by microsatellite loss of heterozygosity in patients with multiple and recurrent hepatocellular carcinomas. J Hepatol. 2003;39:215–221.CrossRefPubMed Morimoto O, Nagano H, Sakon M, et al. Diagnosis of intrahepatic metastasis and multicentric carcinogenesis by microsatellite loss of heterozygosity in patients with multiple and recurrent hepatocellular carcinomas. J Hepatol. 2003;39:215–221.CrossRefPubMed
8.
go back to reference Baffy G. Decoding multifocal hepatocellular carcinoma: an opportune pursuit. Hepatobiliary Surg Nutr. 2015;4:206–210.PubMedPubMedCentral Baffy G. Decoding multifocal hepatocellular carcinoma: an opportune pursuit. Hepatobiliary Surg Nutr. 2015;4:206–210.PubMedPubMedCentral
9.
go back to reference Li Q, Wang J, Juzi JT, et al. Clonality analysis for multicentric origin and intrahepatic metastasis in recurrent and primary hepatocellular carcinoma. J Gastrointest Surg. 2008;12:1540–1547.CrossRefPubMed Li Q, Wang J, Juzi JT, et al. Clonality analysis for multicentric origin and intrahepatic metastasis in recurrent and primary hepatocellular carcinoma. J Gastrointest Surg. 2008;12:1540–1547.CrossRefPubMed
10.
go back to reference Wang B, Xia CY, Lau WY, et al. Determination of clonal origin of recurrent hepatocellular carcinoma for personalized therapy and outcomes evaluation: a new strategy for hepatic surgery. J Am Coll Surg. 2013;217:1054–1062.CrossRefPubMed Wang B, Xia CY, Lau WY, et al. Determination of clonal origin of recurrent hepatocellular carcinoma for personalized therapy and outcomes evaluation: a new strategy for hepatic surgery. J Am Coll Surg. 2013;217:1054–1062.CrossRefPubMed
11.
go back to reference Matsuda M, Fujii H, Kono H, Matsumoto Y. Surgical treatment of recurrent hepatocellular carcinoma based on the mode of recurrence: repeat hepatic resection or ablation are good choices for patients with recurrent multicentric cancer. J Hepato-Biliary-Pancreatic Surg. 2001;8:353–359.CrossRef Matsuda M, Fujii H, Kono H, Matsumoto Y. Surgical treatment of recurrent hepatocellular carcinoma based on the mode of recurrence: repeat hepatic resection or ablation are good choices for patients with recurrent multicentric cancer. J Hepato-Biliary-Pancreatic Surg. 2001;8:353–359.CrossRef
12.
go back to reference Fuks D, Dokmak S, Paradis V, Diouf M, Durand F, Belghiti J. Benefit of initial resection of hepatocellular carcinoma followed by transplantation in case of recurrence: an intention-to-treat analysis. Hepatology. 2012;55:132–140.CrossRefPubMed Fuks D, Dokmak S, Paradis V, Diouf M, Durand F, Belghiti J. Benefit of initial resection of hepatocellular carcinoma followed by transplantation in case of recurrence: an intention-to-treat analysis. Hepatology. 2012;55:132–140.CrossRefPubMed
13.
go back to reference Chan AC, Chan SC, Chok KS, et al. Treatment strategy for recurrent hepatocellular carcinoma: salvage transplantation, repeated resection, or radiofrequency ablation? Liver Transplant. 2013;19:411–419.CrossRef Chan AC, Chan SC, Chok KS, et al. Treatment strategy for recurrent hepatocellular carcinoma: salvage transplantation, repeated resection, or radiofrequency ablation? Liver Transplant. 2013;19:411–419.CrossRef
14.
go back to reference Yamashita Y, Yoshida Y, Kurihara T, et al. Surgical results for recurrent hepatocellular carcinoma after curative hepatectomy: Repeat hepatectomy versus salvage living donor liver transplantation. Liver Transplant. 2015;21:961–968.CrossRef Yamashita Y, Yoshida Y, Kurihara T, et al. Surgical results for recurrent hepatocellular carcinoma after curative hepatectomy: Repeat hepatectomy versus salvage living donor liver transplantation. Liver Transplant. 2015;21:961–968.CrossRef
15.
go back to reference Hao S, Fan P, Chen S, Tu C, Wan C. Distinct recurrence risk factors for intrahepatic metastasis and multicenter occurrence after surgery in patients with hepatocellular Carcinoma. J Gastrointest Surg. 2017;21:312–320.CrossRefPubMed Hao S, Fan P, Chen S, Tu C, Wan C. Distinct recurrence risk factors for intrahepatic metastasis and multicenter occurrence after surgery in patients with hepatocellular Carcinoma. J Gastrointest Surg. 2017;21:312–320.CrossRefPubMed
16.
go back to reference Zhang XY, Li C, Wen TF, et al. Appropriate treatment strategies for intrahepatic recurrence after curative resection of hepatocellular carcinoma initially within the Milan criteria: according to the recurrence pattern. Eur J Gastroenterol Hepatol. 2015;27:933–940.CrossRefPubMed Zhang XY, Li C, Wen TF, et al. Appropriate treatment strategies for intrahepatic recurrence after curative resection of hepatocellular carcinoma initially within the Milan criteria: according to the recurrence pattern. Eur J Gastroenterol Hepatol. 2015;27:933–940.CrossRefPubMed
17.
go back to reference Arii S, Monden K, Niwano M, et al. Results of surgical treatment for recurrent hepatocellular carcinoma; comparison of outcome among patients with multicentric carcinogenesis, intrahepatic metastasis, and extrahepatic recurrence. J Hepato-Biliary-Pancreatic Surg. 1998;5:86–92.CrossRef Arii S, Monden K, Niwano M, et al. Results of surgical treatment for recurrent hepatocellular carcinoma; comparison of outcome among patients with multicentric carcinogenesis, intrahepatic metastasis, and extrahepatic recurrence. J Hepato-Biliary-Pancreatic Surg. 1998;5:86–92.CrossRef
18.
go back to reference Kumada T, Nakano S, Takeda I, et al. Patterns of recurrence after initial treatment in patients with small hepatocellular carcinoma. Hepatology. 1997;25:87–92.CrossRefPubMed Kumada T, Nakano S, Takeda I, et al. Patterns of recurrence after initial treatment in patients with small hepatocellular carcinoma. Hepatology. 1997;25:87–92.CrossRefPubMed
19.
go back to reference Zhang X, Li C, Wen T, et al. Appropriate treatment strategies for intrahepatic recurrence after curative resection of hepatocellular carcinoma initially within the Milan criteria: according to the recurrence pattern. Eur J Gastroenterol Hepatol. 2015;27:933–940.CrossRefPubMed Zhang X, Li C, Wen T, et al. Appropriate treatment strategies for intrahepatic recurrence after curative resection of hepatocellular carcinoma initially within the Milan criteria: according to the recurrence pattern. Eur J Gastroenterol Hepatol. 2015;27:933–940.CrossRefPubMed
20.
go back to reference Huang J, Yan L, Cheng Z, et al. A randomized trial comparing radiofrequency ablation and surgical resection for HCC conforming to the Milan criteria. Ann Surg. 2010;252:903–912.CrossRefPubMed Huang J, Yan L, Cheng Z, et al. A randomized trial comparing radiofrequency ablation and surgical resection for HCC conforming to the Milan criteria. Ann Surg. 2010;252:903–912.CrossRefPubMed
21.
go back to reference Jiang L, Yan L, Li B, et al. Prophylaxis against hepatitis B recurrence posttransplantation using lamivudine and individualized low-dose hepatitis B immunoglobulin. Am J Transplant. 2010;10:1861–1869.CrossRefPubMed Jiang L, Yan L, Li B, et al. Prophylaxis against hepatitis B recurrence posttransplantation using lamivudine and individualized low-dose hepatitis B immunoglobulin. Am J Transplant. 2010;10:1861–1869.CrossRefPubMed
22.
go back to reference Li C, Mi K, Wen T, et al. A learning curve for living donor liver transplantation. Dig Liver Dis. 2012;44:597–602.CrossRefPubMed Li C, Mi K, Wen T, et al. A learning curve for living donor liver transplantation. Dig Liver Dis. 2012;44:597–602.CrossRefPubMed
23.
go back to reference Li C, Zhu WJ, Wen TF, et al. Child-Pugh A hepatitis B-related cirrhotic patients with a single hepatocellular carcinoma up to 5 cm: liver transplantation vs. resection. J Gastrointest Surg. 2014;18:1469–1476.CrossRefPubMed Li C, Zhu WJ, Wen TF, et al. Child-Pugh A hepatitis B-related cirrhotic patients with a single hepatocellular carcinoma up to 5 cm: liver transplantation vs. resection. J Gastrointest Surg. 2014;18:1469–1476.CrossRefPubMed
24.
go back to reference Takenaka K, Adachi E, Nishizaki T, et al. Possible multicentric occurrence of hepatocellular carcinoma: a clinicopathological study. Hepatology. 1994;19:889–894.CrossRefPubMed Takenaka K, Adachi E, Nishizaki T, et al. Possible multicentric occurrence of hepatocellular carcinoma: a clinicopathological study. Hepatology. 1994;19:889–894.CrossRefPubMed
25.
go back to reference Saeki R, Nagai H, Kaneko S, et al. Intratumoral genomic heterogeneity in human hepatocellular carcinoma detected by restriction landmark genomic scanning. J Hepatol. 2000;33:99–105.CrossRefPubMed Saeki R, Nagai H, Kaneko S, et al. Intratumoral genomic heterogeneity in human hepatocellular carcinoma detected by restriction landmark genomic scanning. J Hepatol. 2000;33:99–105.CrossRefPubMed
26.
go back to reference Friemel J, Rechsteiner M, Frick L, et al. Intratumor heterogeneity in hepatocellular carcinoma. Clin Cancer Res. 2015;21:1951–1961.CrossRefPubMed Friemel J, Rechsteiner M, Frick L, et al. Intratumor heterogeneity in hepatocellular carcinoma. Clin Cancer Res. 2015;21:1951–1961.CrossRefPubMed
27.
go back to reference Poon RT, Fan ST, Ng IO, Lo CM, Liu CL, Wong J. Different risk factors and prognosis for early and late intrahepatic recurrence after resection of hepatocellular carcinoma. Cancer. 2000;89:500–507.CrossRefPubMed Poon RT, Fan ST, Ng IO, Lo CM, Liu CL, Wong J. Different risk factors and prognosis for early and late intrahepatic recurrence after resection of hepatocellular carcinoma. Cancer. 2000;89:500–507.CrossRefPubMed
28.
go back to reference Jin YJ, Lee JW, Lee OH, et al. Transarterial chemoembolization versus surgery/radiofrequency ablation for recurrent hepatocellular carcinoma with or without microvascular invasion. J Gastroenterol Hepatol. 2014;29:1056–1064.CrossRefPubMed Jin YJ, Lee JW, Lee OH, et al. Transarterial chemoembolization versus surgery/radiofrequency ablation for recurrent hepatocellular carcinoma with or without microvascular invasion. J Gastroenterol Hepatol. 2014;29:1056–1064.CrossRefPubMed
29.
go back to reference Majno PE, Sarasin FP, Mentha G, Hadengue A. Primary liver resection and salvage transplantation or primary liver transplantation in patients with single, small hepatocellular carcinoma and preserved liver function: an outcome-oriented decision analysis. Hepatology. 2000;31:899–906.CrossRefPubMed Majno PE, Sarasin FP, Mentha G, Hadengue A. Primary liver resection and salvage transplantation or primary liver transplantation in patients with single, small hepatocellular carcinoma and preserved liver function: an outcome-oriented decision analysis. Hepatology. 2000;31:899–906.CrossRefPubMed
30.
go back to reference Ferrer-Fabrega J, Forner A, Liccioni A, et al. Prospective validation of ab initio liver transplantation in hepatocellular carcinoma upon detection of risk factors for recurrence after resection. Hepatology. 2016;63:839–849.CrossRefPubMed Ferrer-Fabrega J, Forner A, Liccioni A, et al. Prospective validation of ab initio liver transplantation in hepatocellular carcinoma upon detection of risk factors for recurrence after resection. Hepatology. 2016;63:839–849.CrossRefPubMed
31.
go back to reference Hu Z, Wang W, Li Z, Ye S, Zheng SS. Recipient outcomes of salvage liver transplantation versus primary liver transplantation: a systematic review and meta-analysis. Liver Transplant. 2012;18:1316–1323.CrossRef Hu Z, Wang W, Li Z, Ye S, Zheng SS. Recipient outcomes of salvage liver transplantation versus primary liver transplantation: a systematic review and meta-analysis. Liver Transplant. 2012;18:1316–1323.CrossRef
32.
go back to reference Imamura H, Matsuyama Y, Tanaka E, et al. Risk factors contributing to early and late phase intrahepatic recurrence of hepatocellular carcinoma after hepatectomy. J Hepatol. 2003;38:200–207.CrossRefPubMed Imamura H, Matsuyama Y, Tanaka E, et al. Risk factors contributing to early and late phase intrahepatic recurrence of hepatocellular carcinoma after hepatectomy. J Hepatol. 2003;38:200–207.CrossRefPubMed
33.
go back to reference Du Z-G, Wei Y-G, Chen K-F, Li B. Risk factors associated with early and late recurrence after curative resection of hepatocellular carcinoma: a single institution’s experience with 398 consecutive patients. Hepatobiliary Pancreatic Dis Int. 2014;13:153–161.CrossRef Du Z-G, Wei Y-G, Chen K-F, Li B. Risk factors associated with early and late recurrence after curative resection of hepatocellular carcinoma: a single institution’s experience with 398 consecutive patients. Hepatobiliary Pancreatic Dis Int. 2014;13:153–161.CrossRef
34.
go back to reference Cheng Z, Yang P, Qu S, et al. Risk factors and management for early and late intrahepatic recurrence of solitary hepatocellular carcinoma after curative resection. HPB. 2015;17:422–427.CrossRefPubMed Cheng Z, Yang P, Qu S, et al. Risk factors and management for early and late intrahepatic recurrence of solitary hepatocellular carcinoma after curative resection. HPB. 2015;17:422–427.CrossRefPubMed
Metadata
Title
Outcomes of Salvage Liver Transplantation and Re-resection/Radiofrequency Ablation for Intrahepatic Recurrent Hepatocellular Carcinoma: A New Surgical Strategy Based on Recurrence Pattern
Authors
Xiaoyun Zhang
Chuan Li
Tianfu Wen
Wei Peng
Lunan Yan
Jiayin Yang
Publication date
01-02-2018
Publisher
Springer US
Published in
Digestive Diseases and Sciences / Issue 2/2018
Print ISSN: 0163-2116
Electronic ISSN: 1573-2568
DOI
https://doi.org/10.1007/s10620-017-4861-y

Other articles of this Issue 2/2018

Digestive Diseases and Sciences 2/2018 Go to the issue