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World J Hepatol. 2018 Jun 27;10(6):433-447. doi: 10.4254/wjh.v10.i6.433.

Systematic review of the outcomes of surgical resection for intermediate and advanced Barcelona Clinic Liver Cancer stage hepatocellular carcinoma: A critical appraisal of the evidence.

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Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore 169608, Singapore.
Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore 169608, Singapore.
Center for Quantitative Medicine, Duke-NUS Graduate Medical School, Singapore 169857, Singapore.
Department of General Surgery, Hepatopancreatobiliary Service, Changi General Hospital, Singapore 529889, Singapore.
Department of Medical Oncology, National Cancer Centre Singapore, Singapore 169610, Singapore.



To perform a systematic review to determine the survival outcomes after curative resection of intermediate and advanced hepatocellular carcinomas (HCC).


A systematic review of the published literature was performed using the PubMed database from 1st January 1999 to 31st Dec 2014 to identify studies that reported outcomes of liver resection as the primary curative treatment for Barcelona Clinic Liver Cancer (BCLC) stage B or C HCC. The primary end point was to determine the overall survival (OS) and disease free survival (DFS) of liver resection of HCC in BCLC stage B or C in patients with adequate liver reserve (i.e., Child's A or B status). The secondary end points were to assess the morbidity and mortality of liver resection in large HCC (defined as lesions larger than 10 cm in diameter) and to compare the OS and DFS after surgical resection of solitary vs multifocal HCC.


We identified 74 articles which met the inclusion criteria and were analyzed in this systematic review. Analysis of the resection outcomes of the included studies were grouped according to (1) BCLC stage B or C HCC, (2) Size of HCC and (3) multifocal tumors. The median 5-year OS of BCLC stage B was 38.7% (range 10.0-57.0); while the median 5-year OS of BCLC stage C was 20.0% (range 0.0-42.0). The collective median 5-year OS of both stages was 27.9% (0.0-57.0). In examining the morbidity and mortality following liver resection in large HCC, the pooled RR for morbidity [RR (95%CI) = 1.00 (0.76-1.31)] and mortality [RR (95%CI) = 1.15 (0.73-1.80)] were not significant. Within the spectrum of BCLC B and C lesions, tumors greater than 10 cm were reported to have median 5-year OS of 33.0% and multifocal lesions 54.0%.


Indication for surgical resection should be extended to BCLC stage B lesions in selected patients. Further studies are needed to stratify stage C lesions for resection.


Barcelona Clinic Liver Cancer; Hepatectomy; Hepatocellular carcinoma; Milan criteria

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