Hepatic| Volume 171, ISSUE 5, P1303-1310, May 2022

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Liver resection is associated with good outcomes for hepatocellular carcinoma patients beyond the Barcelona Clinic Liver Cancer criteria: A multicenter study with the Hiroshima Surgical study group of Clinical Oncology

Published:October 29, 2021DOI:



      Liver resection for hepatocellular carcinoma beyond the Barcelona Clinic Liver Cancer criteria remains controversial. Strict candidate selection is crucial to achieve optimal results in this population. This study explored postoperative outcomes and developed a preoperative predictive formula to identify patients most likely to benefit from liver resection.


      In total, 382 patients who underwent liver resection for hepatocellular carcinoma beyond the Barcelona Clinic Liver Cancer resection criteria between 2000 and 2017 were identified from a multicenter database with the Hiroshima Surgical study group of Clinical Oncology. An overall survival prediction model was developed, and patients were classified by risk status.


      The 5-year overall survival after curative resection was 50.0%. Overall survival multivariate analysis identified that a high a-fetoprotein level, macrovascular invasion, and high total tumor burden were independent prognostic risk factors; these factors were used to formulate risk scores. Patients were divided into low-, moderate-, and high-risk groups; the 5-year overall survival was 65.7%, 49.5%, and 17.0% (P < .001), and the 5-year recurrence-free survival was 31.3%, 26.2%, and 0%, respectively (P < .001). The model performance was good (C-index, 0.76). Both the early and extrahepatic recurrence increased with higher risk score.


      The prognosis of patients with hepatocellular carcinoma beyond the Barcelona Clinic Liver Cancer resection criteria depended on a high a-fetoprotein level, macrovascular invasion, and high total tumor burden, and risk scores based on these factors stratified the prognoses. Liver resection should be considered in patients with hepatocellular carcinoma beyond the Barcelona Clinic Liver Cancer criteria with a low or moderate-risk score.

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        • Villanueva A.
        Hepatocellular carcinoma.
        N Engl J Med. 2019; 380: 1450-1462
        • Yang J.D.
        • Hainaut P.
        • Gores G.J.
        • Amadou A.
        • Plymoth A.
        • Roberts L.R.
        A global view of hepatocellular carcinoma: trends, risk, prevention and management.
        Nat Rev Gastroenterol Hepatol. 2019; 16: 589-604
        • Pinna A.D.
        • Yang T.
        • Mazzaferro V.
        • et al.
        Liver transplantation and hepatic resection can achieve cure for hepatocellular carcinoma.
        Ann Surg. 2018; 268: 868-875
        • Yao F.Y.
        • Bass N.M.
        • Nikolai B.
        • et al.
        Liver transplantation for hepatocellular carcinoma: analysis of survival according to the intention-to-treat principle and dropout from the waiting list.
        Liver Transpl. 2002; 8: 873-883
      1. EASL Clinical Practice Guidelines: management of hepatocellular carcinoma.
        J Hepatol. 2018; 69: 182-236
        • Marrero J.A.
        • Kulik L.M.
        • Sirlin C.B.
        • et al.
        Diagnosis, staging, and management of hepatocellular carcinoma: 2018 practice guidance by the American Association for the Study of Liver Diseases.
        Hepatology. 2018; 68: 723-750
        • Vitale A.
        • Burra P.
        • Frigo A.C.
        • et al.
        Survival benefit of liver resection for patients with hepatocellular carcinoma across different Barcelona Clinic Liver Cancer stages: a multicentre study.
        J Hepatol. 2015; 62: 617-624
        • Roayaie S.
        • Jibara G.
        • Tabrizian P.
        • et al.
        The role of hepatic resection in the treatment of hepatocellular cancer.
        Hepatology. 2015; 62: 440-451
        • Hyun M.H.
        • Lee Y.S.
        • Kim J.H.
        • et al.
        Hepatic resection compared to chemoembolization in intermediate- to advanced-stage hepatocellular carcinoma: a meta-analysis of high-quality studies.
        Hepatology. 2018; 68: 977-993
        • Chen Z.H.
        • Zhang X.P.
        • Lu Y.G.
        • et al.
        Actual long-term survival in HCC patients with portal vein tumor thrombus after liver resection: a nationwide study.
        Hepatol Int. 2020; 14: 754-764
        • Fukami Y.
        • Kaneoka Y.
        • Maeda A.
        • et al.
        Liver resection for multiple hepatocellular carcinomas: a Japanese nationwide survey.
        Ann Surg. 2020; 272: 145-154
        • Takahara T.
        • Furui K.
        • Yata Y.
        • et al.
        Dual expression of matrix metalloproteinase-2 and membrane-type 1-matrix metalloproteinase in fibrotic human livers.
        Hepatology. 1997; 26: 1521-1529
        • Xu X.F.
        • Xing H.
        • Han J.
        • et al.
        Risk factors, patterns, and outcomes of late recurrence after liver resection for hepatocellular carcinoma: a multicenter study from China.
        JAMA Surg. 2019; 154: 209-217
        • Kokudo N.
        • Takemura N.
        • Hasegawa K.
        • et al.
        Clinical practice guidelines for hepatocellular carcinoma: the Japan Society of Hepatology 2017 (4th JSH-HCC guidelines) 2019 update.
        Hepatol Res. 2019; 49: 1109-1113
        • Mallett S.
        • Royston P.
        • Waters R.
        • Dutton S.
        • Altman D.G.
        Reporting performance of prognostic models in cancer: a review.
        BMC Med. 2010; 8: 21
        • Sieghart W.
        • Hucke F.
        • Peck-Radosavljevic M.
        Transarterial chemoembolization: modalities, indication, and patient selection.
        J Hepatol. 2015; 62: 1187-1195
        • Kudo M.
        • Finn R.S.
        • Qin S.
        • et al.
        Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial.
        Lancet. 2018; 391: 1163-1173
        • Zaydfudim V.M.
        • Vachharajani N.
        • Klintmalm G.B.
        • et al.
        Liver resection and transplantation for patients with hepatocellular carcinoma beyond milan criteria.
        Ann Surg. 2016; 264: 650-658
        • Zhong J.H.
        • Rodríguez A.C.
        • Ke Y.
        • Wang Y.Y.
        • Wang L.
        • Li L.Q.
        Hepatic resection as a safe and effective treatment for hepatocellular carcinoma involving a single large tumor, multiple tumors, or macrovascular invasion.
        Medicine (Baltimore). 2015; 94: e396
        • Ho M.C.
        • Huang G.T.
        • Tsang Y.M.
        • et al.
        Liver resection improves the survival of patients with multiple hepatocellular carcinomas.
        Ann Surg Oncol. 2009; 16: 848-855
        • Zhong J.H.
        • Ke Y.
        • Gong W.F.
        • et al.
        Hepatic resection associated with good survival for selected patients with intermediate and advanced-stage hepatocellular carcinoma.
        Ann Surg. 2014; 260: 329-340
        • Tsilimigras D.I.
        • Bagante F.
        • Moris D.
        • et al.
        Defining the chance of cure after resection for hepatocellular carcinoma within and beyond the Barcelona Clinic Liver Cancer guidelines: a multi-institutional analysis of 1,010 patients.
        Surgery. 2019; 166: 967-974
        • Lee S.
        • Kang T.W.
        • Song K.D.
        • Lee M.W.
        • Rhim H.
        • Lim H.K.
        • et al.
        Effect of microvascular invasion risk on early recurrence of hepatocellular carcinoma after surgery and radiofrequency ablation.
        Ann Surg. 2021; 273: 564-571
        • Gelli M.
        • Sebagh M.
        • Porcher R.
        • et al.
        Liver resection for early hepatocellular carcinoma: preoperative predictors of non transplantable recurrence and implications for treatment allocation.
        Ann Surg. 2020; 272: 820-826
        • Shinkawa H.
        • Tanaka S.
        • Takemura S.
        • et al.
        Nomograms predicting extra- and early intrahepatic recurrence after hepatic resection of hepatocellular carcinoma.
        Surgery. 2021; 169: 922-928
        • Vauthey J.N.
        • Lauwers G.Y.
        • Esnaola N.F.
        • et al.
        Simplified staging for hepatocellular carcinoma.
        J Clin Oncol. 2002; 20: 1527-1536
        • Mazzaferro V.
        • Llovet J.M.
        • Miceli R.
        • et al.
        Predicting survival after liver transplantation in patients with hepatocellular carcinoma beyond the Milan criteria: a retrospective, exploratory analysis.
        Lancet Oncol. 2009; 10: 35-43
        • Nault J.C.
        • Sutter O.
        • Nahon P.
        • Ganne-Carrié N.
        • Séror O.
        Percutaneous treatment of hepatocellular carcinoma: state of the art and innovations.
        J Hepatol. 2018; 68: 783-797
        • Lu X.Y.
        • Xi T.
        • Lau W.Y.
        • et al.
        Pathobiological features of small hepatocellular carcinoma: correlation between tumor size and biological behavior.
        J Cancer Res Clin Oncol. 2011; 137: 567-575
        • Schroeder R.A.
        • Marroquin C.E.
        • Bute B.P.
        • Khuri S.
        • Henderson W.G.
        • Kuo P.C.
        Predictive indices of morbidity and mortality after liver resection.
        Ann Surg. 2006; 243: 373-379
        • Bruix J.
        • Fuster J.
        A snapshot of the effective indications and results of surgery for hepatocellular carcinoma in tertiary referral centers: is it adherent to the EASL/AASLD recommendations? An observational study of the HCC East-West Study Group.
        Ann Surg. 2015; 262: e30
        • Llovet J.M.
        • Brú C.
        • Bruix J.
        Prognosis of hepatocellular carcinoma: the BCLC staging classification.
        Semin Liver Dis. 1999; 19: 329-338
        • Hirokawa F.
        • Hayashi M.
        • Miyamoto Y.
        • et al.
        Surgical treatment of extrahepatic recurrence of hepatocellular carcinoma.
        Langenbecks Arch Surg. 2014; 399: 1057-1064
        • Poon R.T.
        • Fan S.T.
        • Ng I.O.
        • Wong J.
        Significance of resection margin in hepatectomy for hepatocellular carcinoma: a critical reappraisal.
        Ann Surg. 2000; 231: 544-551
        • Kokudo T.
        • Hasegawa K.
        • Matsuyama Y.
        • et al.
        Survival benefit of liver resection for hepatocellular carcinoma associated with portal vein invasion.
        J Hepatol. 2016; 65: 938-943