Partial hepatectomy vs. transcatheter arterial chemoembolization for resectable multiple hepatocellular carcinoma beyond the Milan criteria: A randomized controlled trial

Partial hepatectomy vs. transcatheter arterial chemoembolization for resectable multiple hepatocellular carcinoma beyond Milan criteria: A RCTJournal of HepatologyVol. 61Issue 1PreviewThe aim of this randomized comparative trial (RCT) is to compare partial hepatectomy (PH) with transcatheter arterial chemoembolization (TACE) to treat patients with resectable multiple hepatocellular carcinoma (RMHCC) outside of Milan Criteria. Full-Text PDF Target patients for partial hepatectomy and relationship between PLT and prognosis in BCLC B HCCJournal of HepatologyVol. 62Issue 3PreviewThe most common etiology of hepatocellular carcinoma (HCC) in China is hepatitis B virus infection, which is in marked contrast to the United Kingdom with common etiologies like alcoholism, non-alcoholic fatty liver disease, and hepatitis C virus infection. There is no doubt that a randomized comparative trial (RCT), involving a large number of patients with HCC, would provide a clearer answer to the point raised by Metussin et al., in their Letter to the Editor. Unfortunately, such a study would be difficult to carry out. Full-Text PDF Open Access We read with interest the article by Yin et al. [[1]Yin L. Li H. Li A.J. Lau W.Y. Pan Z.Y. Lai E.C. et al.Partial hepatectomy vs. transcatheter arterial chemoembolization for resectable multiple hepatocellular carcinoma beyond Milan Criteria: a RCT.J Hepatol. 2014; 61: 82-88Abstract Full Text Full Text PDF PubMed Scopus (240) Google Scholar], in which they highlighted that partial hepatectomy (PH) was superior to transcatheter arterial chemoembolization (TACE) for patients with resectable multiple hepatocellular carcinoma (HCC) beyond the Milan criteria. However, their findings may need further improvement based on the following two viewpoints. First, the authors excluded patients whose platelet count (PLT) was <80 × 109/L, which might be in view of the influence of thrombocytopenia on therapy. In addition, enrolled patients in the TACE group had a lower preoperative PLT compared to patients who received PH (Yin et al., Table 1, 154.7 × 109/L vs. 172.3 × 109/L, p = 0.087 <0.10). Therefore, we speculated that the PLT might be a potential confounder in the association between the type of treatment and survival in HCC, while the authors might ignore to correct it in the multivariate analysis. Second, the authors did not compare recurrence-free survival (RFS) between the two groups though they considered this as a secondary outcome measure (ClinicalTrials.gov NCT00820157). The discordance between the publication and the registration information might decrease the validity of their findings [[2]Becker J.E. Krumholz H.M. Ben-Josef G. Ross J.S. Reporting of results in ClinicalTrials.gov and high-impact journals.JAMA. 2014; 311: 1063-1065Crossref PubMed Scopus (81) Google Scholar]. Whether or not the high recurrence rate (68.9%) after PH affected RFS was not reported by Yin et al. To estimate the significance of PLT in the prognosis of HCC, we retrospectively analysed in our centre 213 patients (from April 2002 until August 2012) that were beyond the Milan criteria. 91 patients received PH and 122 individuals underwent TACE. The outcomes analysed included overall survival (OS), RFS, and recurrence. The receiver operating characteristic curve showed an optimal cut-off value of 156 × 109/L for PLT with regard to mortality. By Log-rank test, we found that the PLT was significantly associated with OS and recurrence. Variables with a p value <0.10 in the univariate analysis were entered into the Cox proportional hazard model, and the results are presented in Fig. 1. Out of the variables, TACE therapy, older age, and PLT >156 × 109/L were independently associated with poor OS in HCC beyond the Milan criteria. In contrast, age, PLT, and vascular invasion, but not the type of therapy, were independent indicators to predict RFS. The significant risk factors for recurrence included therapeutic method, gamma-glutamyltransferase (GGT), and PLT. Thus, we suggest that patients with a high preoperative PLT had a significantly worse OS and RFS, as well as a higher risk of recurrence compared to patients with a PLT ⩽156 × 109/L, which is consistent with previous studies [3Shen S.L. Fu S.J. Chen B. Kuang M. Li S.Q. Hua Y.P. et al.Preoperative aspartate aminotransferase to platelet ratio is an independent prognostic factor for hepatitis B-induced hepatocellular carcinoma after hepatic resection.Ann Surg Oncol. 2014; 21: 3802-3809Crossref PubMed Scopus (93) Google Scholar, 4Brau N. Fox R.K. Xiao P. Marks K. Naqvi Z. Taylor L.E. et al.Presentation and outcome of hepatocellular carcinoma in HIV-infected patients: a U.S.-Canadian multicenter study.J Hepatol. 2007; 47: 527-537Abstract Full Text Full Text PDF PubMed Scopus (200) Google Scholar]. These findings support the hypothesis that PLT could be a confounder and should be adjusted when estimating the independent significance of the type of treatment or other factors. Not only was PLT a valuable, readily available, and inexpensive parameter to predict survival in HCC, but it was also associated with cirrhosis formation [[5]Udell J.A. Wang C.S. Tinmouth J. FitzGerald J.M. Ayas N.T. Simel D.L. et al.Does this patient with liver disease have cirrhosis?.JAMA. 2012; 307: 832-842Crossref PubMed Scopus (138) Google Scholar] and hepatic carcinogenesis [[6]Kumada T. Toyoda H. Kiriyama S. Sone Y. Tanikawa M. Hisanaga Y. et al.Incidence of hepatocellular carcinoma in hepatitis C carriers with normal alanine aminotransferase levels.J Hepatol. 2009; 50: 729-735Abstract Full Text Full Text PDF PubMed Scopus (40) Google Scholar]. In addition, administration of anti-platelet agents (aspirin and clopidogrel) could prevent hepatocarcinogenesis and greatly improve OS [[7]Sitia G. Iannacone M. Guidotti L.G. Anti-platelet therapy in the prevention of hepatitis B virus-associated hepatocellular carcinoma.J Hepatol. 2013; 59: 1135-1138Abstract Full Text Full Text PDF PubMed Scopus (65) Google Scholar]. However, no statistically significant difference in the RFS between PH and TACE was observed in our study (p = 0.840). Further studies on larger cohorts are needed to validate this finding. The authors declared that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript.