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Ruptured hepatocellular carcinoma (rHCC) generally has a very poor prognosis and is currently classified as T4 in the tumor–node–metastasis (TNM) staging system. In this study, we aimed to demonstrate the actual impact of rHCC, as well as the positive effect of hepatectomy in patients with Barcelona Clinic Liver Cancer (BCLC) stage 0/A rHCC. We enrolled 86 patients with rHCC after surgery and 526 patients with non-rHCC after surgery or transcatheter arterial chemoembolization (TACE). Survival curves were plotted using the Kaplan–Meier method to compare the postoperative prognosis of patients with rHCC with that of patients with non-rHCC. Univariate and multivariate Cox regression analyses were used to identify the risk factors affecting patient survival. BCLC stage 0/A rHCC treated with surgery had a worse prognosis than BCLC stage 0/A non-rHCC treated with surgery (overall survival [OS]: hazard ratio [HR] = 3.12 [2.24–4.34], P < 0.001; recurrence-free survival [RFS]: HR = 2.26 [1.65–3.09], P < 0.001). Rupture was an independent prognostic factor in patients with BCLC stage 0/A rHCC (OS: HR = 1.685 [1.416–2.006], P < 0.001; RFS: HR = 1.484 [1.267–1.737], P < 0.001), and patients with BCLC stage 0/A rHCC who underwent surgery had a comparable prognosis to patients with BCLC stage B HCC who underwent surgery or TACE (OS: P = 0.78). Patients classified as having BCLC stage 0/A rHCC can achieve comparable outcomes to patients with BCLC stage B HCC after hepatectomy. However, not all patients with rHCC should be classified as T4 in the TNM staging system. [ABSTRACT FROM AUTHOR]

Background and Aims. Conflicting results are often observed in the prognosis of patients with ruptured hepatocellular carcinoma (rHCC), and there are currently very few studies on the long-term postoperative outcomes of ruptured hepatocellular carcinoma patients. This study aimed to distinguish between the postoperative prognosis of rHCC patients with cirrhosis (rHCC-C) and those without cirrhosis (rHCC-NC) using some serum markers. Methods. We collected the data of 151 rHCC patients treated at our centers from January 2010 to March 2021. 62 had no cirrhosis, and 89 had cirrhosis. The prognosis of rHCC-C and rHCC-NC groups was compared using the Kaplan-Meier method. We used multivariate Cox regression to analyze prognostic factors in rHCC patients, and subgroup analysis was performed on the two groups of patients. Results. The long-term prognosis of rHCC-NC patients was better than that of rHCC-C patients. Tumor diameter, Barcelona clinic liver cancer (BCLC) stage, HBsAg, positive Hepatitis C virus (HCV) antibodies, elevated creatinine, and elevated T-bilirubin were prognostic factors for overall survival (OS) in rHCC-C patients. However, only alpha-fetoprotein (AFP) > 92 ng/mL was a prognostic factor for OS in rHCC-NC patients. In noncirrhotic patients, HBsAg positivity was only associated with OS. Similarly, the presence or absence of microvascular invasion (MVI) also had different results in the two groups. Conclusions. There are differences in serum alpha-fetoprotein (AFP) levels, the presence of microvascular invasion (MVI), and HBsAg positivity between rHCC-C and rHCC-NC patients, indicating that the analysis of these prognostic factors may help improve the management of rHCC patients and provide a direction for future treatment options. [ABSTRACT FROM AUTHOR]

Background: Cancer stem cells (CSCs) and Circulating tumor cells (CTCs) have been proposed as fundamental causes for the recurrence of hepatocellular carcinoma (HCC). CTCs isolated from patients with HCC illustrate a unique Nanog expression profile analysis. The aim of this study was to enhance the prediction of recurrence and prognosis of the CTC phenotype in patients with HCC by combining Nanog expression into a combined forecasting model. Subjects, Materials, and Methods: We collected 320 blood samples from 160 patients with HCC cancer before surgery and used CanPatrol™ CTC enrichment technology and in situ hybridization (ISH) to enrich and detect CTCs and CSCs. Nanog expression in all CTCs was also determined. In addition, RT-PCR and immunohistochemistry were used to study the expression of Nanog, E-Cadherin, and N-Cadherin in liver cancer tissues and to conduct clinical correlation studies. Results: The numbers of EpCAM mRNA+ CTCs and Nanog mRNA+ CTCs were strongly correlated with postoperative HCC recurrence (CTC number (P = 0.03), the total number of mixed CTCS (P = 0.02), and Nanog> 6.7 (P = 0.001), with Nanog > 6.7 (P = 0.0003, HR = 2.33) being the most crucial marker. There are significant differences in the expression of Nanog on different types of CTC: most Epithelial CTCs do not express Nanog, while most of Mixed CTC and Mesenchymal CTC express Nanog, and their positive rates are 38.7%, 66.7%, and 88.7%, respectively, (P=0.0001). Moreover, both CTC (≤/> 13.3) and Nanog (≤/>6.7) expression were significantly correlated with BCLC stage, vascular invasion, tumor size, and Hbv-DNA (all P < 0.05). In the young group and the old group, patients with higher Nanog expression had a higher recurrence rate. (P < 0.001). Conclusions: The number of Nanog-positive cells showed positive correlation with the poor prognosis of HCC patients. The detection and analysis of CTC markers (EpCAM and CK8, 18, CD45 Vimentin,Twist and 19) and CSCs markers (NANOG) are of great value in the evaluation of tumor progression. [ABSTRACT FROM AUTHOR]

Background and aims: Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) has high morbidity and mortality. In this study, the safety and efficacy of a modification of ALPPS (radiofrequency-assisted ALPPS, RALPPS) were assessed in patients with hepatocellular carcinoma (HCC). Materials and methods: Patients who were diagnosed with HCC and were considered to have an insufficient future liver remnant (FLR) were enrolled. In stage I, a radiofrequency ablation (RFA) device was used to cauterise along the planned transection plane to form a coagulum avascular area. When the FLR reached above 40%, hepatectomy was performed in stage II along the coagulum area established previously. After two stages, operative morbidity, mortality, per cent increase in FLR, operative time and blood loss were evaluated. Results: Between July 2014 and September 2015, 10 patients with HCC (9 with hepatitis-related cirrhosis) were treated with the RALPPS procedure. The incidence of severe complications (Clavien- Dindo≥IIIb) was 20% (2/10). One patient died. No biliary leakage, intraperitoneal infection or post-hepatectomy liver failure (PHLF) occurred after both stages. The median FLR before stage I was 31% (364 ml). This increased to 47% (632 ml) before stage II after a median interval of 28 days. The median percentage increase in FLR was 53% (210 ml). Additionally, the median operative time during the first and second stages was 214 and 281 min, respectively. The corresponding median blood loss was 200 and 550 ml, respectively. Conclusions: RALPPS has a potential advantage in eliminating serious complications of biliary leakage and PHLF associated with classic ALPPS. On the basis of rigorous patient selection criteria, RALPPS may achieve the same effect of promoting significant growth of the FLR in patients with cirrhosis-related HCC and insufficient FLR volume, albeit at the cost of a longer interval time. [ABSTRACT FROM AUTHOR]

Background: There is currently no clear consensus on the relative suitabilities of laparoscopic hepatectomy (LH) and radiofrequency ablation (RFA) as minimally invasive treatment for small hepatocellular carcinoma (HCC).Methods: In this retrospective study, we enrolled 156 patients with a single, small HCC with nodular diameters <4 cm and compared recurrence-free survival (RFS) and overall survival (OS) between patients treated with LH and control patients treated with RFA (n = 78 each). The groups were selected according to predefined criteria and matched in terms of their baseline clinical characteristics.Results: During a median follow-up of 31.2 months, the 1-, 2-, and 3-year OS rates in the LH group were 96.2, 91.3, and 84.1 %, respectively, compared with 96.2, 82.6, and 78.8 % in the RFA group. The corresponding RFS rates were 82.1, 71.5, and 60.0 % in the LH group and 65.4, 47.7, and 37.6 % in the RFA group. Combined RFS rates were significantly higher in the LH groups (P = 0.006), but there was no significant difference in OS rates (P = 0.510). The incidence of postoperative complications was significantly lower in the RFA group (28.2 vs. 10.3 %, P = 0.004), and operation duration, intraoperative blood loss and blood transfusion, use of total parenteral nutrition, and length of stay as indicators of minimal invasiveness were also significantly better in the RFA group.Conclusions: There was no difference between LH and RFA in terms of OS in patients with a single, small HCC. However, RFA was less invasive than the LH, but LH was associated with increased RFS. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma is associated with high mortality, and tumor metastasis is an important reason for poor prognosis. However, metastasis has not been effectively prevented in clinical therapy and the mechanisms underlying metastasis have not been fully characterized. CCAAT/enhancer-binding protein-α (C/EBPα) is a transcriptional regulator with an essential role in tumor metastasis. We used short-activating RNAs (saRNA) to enhance expression of C/EBPα. Intravenous injection of C/EBPα-saRNA in a nude mouse liver orthotopic xenograft tumor model inhibited intrahepatic and distant metastasis. C/EBPα-saRNA-treated mice showed increased serum levels of albumin and decreased alanine aminotransferase (ALT), glutamic-oxalacetic transaminase (AST), indicating a role of C/EBPα in improving liver function. Migration and invasion were inhibited in hepatoma cell lines transfected with C/EBPα-saRNA. We also observed an inhibition of epithelial-mesenchymal transition (EMT) and suppression of epidermal growth factor receptor (EGFR), EGFR phosphorylation, and β-catenin in C/EBPa-saRNA-transfected cells. Our results suggested that C/EBPα-saRNA successfully inhibited HCC metastasis by inhibiting EGFR/β-catenin signaling pathway mediated EMT in vitro and in vivo. [ABSTRACT FROM AUTHOR]

Background and Aims Although a high viral load is an independent risk factor for recurrence of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) after surgery, the prognostic impact of viral load on advanced HCC is unclear. This study investigated the impact of baseline HBV load and antiviral therapy on survival of patients with advanced HCC treated with sorafenib. Methods Of 130 patients with advanced HBV-related HCC received first-line sorafenib therapy were evaluated in a multicenter, retrospective study. Results No patients experienced severe hepatic impairment because of HBV reactivation during sorafenib therapy. The median progression-free survival (PFS) and overall survival (OS) of all patients were 5.7 and 9.6 months respectively. Patients with a baseline HBV DNA ≤104 copies/ml had significantly better OS than those with >104 copies/ml (10.4 vs 6.6 months; P = 0.002), but PFS showed an increasing trend (5.8 vs 4.8 months; P = 0.068). Patients who received antiviral therapy had a better trend in OS than those who did not (12.0 vs 8.3 months; P = 0.058), but there was no difference in PFS (6.4 vs 4.1 months; P = 0.280). In a multivariate analysis, the baseline HBV DNA level >104 copies/ml ( P = 0.001; hazard ration [HR] = 2.294; 95% CI 1.429-3.676) and antiviral therapy ( P = 0.038; HR 0.617; 95% CI 0.390-0.975) were independent predictors of OS. Conclusion In patients with advanced HBV-related HCC treated with sorafenib, a high baseline HBV load was an adverse prognostic factor for survival. However, survival was significantly improved with the use of antiviral therapy. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to evaluate the safety and outcomes of radiofrequency ablation (RFA) in treating elderly patients with hepatocellular carcinoma (HCC). Patients and methods: This was a retrospective analysis of 391 patients with HCC fitting the Milan criteria and treated with RFA for the first time from 1999 to 2012 at the Southwest Hospital, China. The patients were divided into two groups, an elderly group (age ≥70 years, n = 102) and a non-elderly group (age <70 years, n = 289). Long-term outcomes were assessed on all patients and survival rates were calculated. Results: The overall survival rates of the two groups differed significantly. The recurrence-free survival rates of the two groups did not differ significantly. There was no significant difference between the two groups. Excluding comorbid diseases related deaths, the overall survival rates of the two groups did not differ significantly. Conclusions: The safety and outcomes of RFA in treating early HCC were similar among elderly and non-elderly patients. Co-morbid diseases, such as cardiovascular disease and respiratory disease, rather than HCC or liver diseases, contributed to the relatively low overall survival rate found in elderly patients. [ABSTRACT FROM AUTHOR]

Background and aims: Radiofrequency ablation (RFA) is a minimally invasive technique used for the treatment of hepatocellular carcinoma (HCC). It may produce complications. The indocyanine green (ICG) retention rate at 15 min (ICGR15) has been used to predict complications after hepatectomy. In this study, the prediction of the value of ICGR15 for complications of RFA to the patients with HCC was evaluated. Methods: Some 878 cases of HCC treated between June 2009 and June 2013 were evaluated. All patients were treated by percutaneous radiofrequency ablation. Patients were divided into two groups: a complication group (85 cases) and a complication-free group (793 cases). ICGR15 and other baseline characteristics of the two groups were compared. A logistic regression model was used to analyse the merits of assessing liver reserve to predict complications post-RFA. Results: Complications such as intra-abdominal haemorrhage and pleural effusion occurred in 85 (9.68%) patients after RFA. Patients in the two groups did not differ with regard to baseline parameters. Patients in the two groups did differ significantly in ICGR15 and tumour site ( p < 0.05). Tumour site was found to have a significant impact on the rate of complications post-RFA. There was no significant difference in ICGR15 values among patients with the same Child-Pugh scores or in the same tumour site. Conclusions: The present results demonstrated that RFA is minimally invasive and suitable for the treatment of HCC. They also showed that ICGR15 did not independently predict for liklihood of post-RFA complications, after controlling for tumour site. Patients with tumours located subcapsularly or near the porta hepatis were found to have significantly higher rates of post-operative complications after RFA than to patients with tumours in the liver parenchyma. [ABSTRACT FROM AUTHOR]

Background: The prognosis of hepatocellular carcinoma (HCC) patients with extrahepatic metastasis is extremely poor. However, what is the main risk factor for survival remains unclear for these patients. We aimed to find out the relative frequency, incidence and locations of extrahepatic metastases and the risk factors of long-term survival of the patients. Methods: 132 HCC patients with extrahepatic metastasis diagnosed by 18F-FDG PET/CT and conventional workup were enrolled into this study. The incidence and locations of extrahepatic metastases were summarized, and the related risk factors of overall survival were analyzed. Results: The most frequent extrahepatic metastatic sites were lymph nodes in 72 (54.5%), bone in 33 (25.0%) and lung in 28 (21.2%) patients. On univariate analysis, prothrombin time, Child-Pugh grade, portal/hepatic vein invasion and lymph node metastasis were independent risk factors of overall survival. On multivariate analysis, lymph node metastasis was the only independent risk factor of overall survival. The cumulative survival rates at 1- and 3-years after diagnosis of extrahepatic metastasis of HCC were 34.4% and 9.3%, respectively. The median survival time was 7 months (range 1 ∼38 months). The median survival time for patients with or without lymph node metastasis were 5 months (range 1∼38 months) and 12 months (range 1∼30 months), respectively (P = 0.036). Conclusions: This study showed lymph nodes to be the most frequent site of extrahepatic metastases for primary HCC. Lymph node metastasis was the main risk factor of overall survival in patients with HCC with extrahepatic metastasis. [ABSTRACT FROM AUTHOR]

DNA methylation is an important epigenetic modification and is frequently altered in cancer. Convert of 5-methylcytosine (5 mC) to 5-hydroxymethylcytosine (5 hmC) by ten-eleven translocation (TET) family enzymes plays important biological functions in embryonic stem cells, development, aging and disease. Recent reports showed that level of 5 hmC was altered in various types of cancers. However, the change of 5 hmC level in hepatocellular carcinoma (HCC) and association with clinical outcome were not well defined. Here, we reported that level of 5 hmC was decreased in HCC tissues, as compared with non-tumor tissues. Clincopathological analysis showed the decreased level of 5 hmC in HCC was associated with tumor size, AFP level and poor overall survival. We also found that the decreased level of 5 hmC in non-tumor tissues was associated with tumor recurrence in the first year after surgical resection. In an animal model with carcinogen DEN-induced HCC, we found that the level of 5 hmC was gradually decreased in the livers during the period of induction. There was further reduction of 5 hmC in tumor tissues when tumors were developed. In contrast, level of 5 mC was increased in HCC tissues and the increased 5 mC level was associated with capsular invasion, vascular thrombosis, tumor recurrence and overall survival. Furthermore, our data showed that expression of TET1, but not TET2 and TET3, was downregulated in HCC. Taken together, our data indicated 5 hmC may be served as a prognostic marker for HCC and the decreased expression of TET1 is likely one of the mechanisms underlying 5 hmC loss in HCC. [ABSTRACT FROM AUTHOR]

Background: Liver resection offers a chance of cure for patients with hepatocellular carcinoma (HCC). Hepatic pedicle clamping (HPC) is commonly used to reduce blood loss during hepatectomy. Hepatic ischemia-reperfusion (I/R) injury has recently been reported to be a major factor in accelerated tumor growth. We therefore evaluated the effect of intermittent HPC on the prognosis of patients after liver resection. Methods: The clinicopathological features and serum/tissue samples of 386 HCC patients who underwent curative liver resection were prospectively collected. The patients were divided into the HPC group (over 30 min) and the non-HPC group. Disease-free survival and overall survival were analyzed using multivariate analyses, Kaplan-Meier curves, and log-rank tests. Matrix metalloproteinases and E-selectin were measured to study hepatic I/R injury. Results: The preoperative clinicopathological data were comparable between the HPC group ( n = 224) and the non-HPC group ( n = 162). During the study period, 257 of the 386 patients (66.6 %) developed tumor recurrence. The overall tumor recurrence and intrahepatic tumor recurrence rates were not significantly different between the two groups. There were no significant differences between the two groups with respect to the 1-, 3-, and 5-year disease-free and overall survival rates. Similarly, subgroup analyses also showed no marked difference in survival rates for patients with cirrhosis in the two groups. The levels of mRNA in liver tissues and serum concentrations of MMP-2, MMP-9, and E-selectin showed no significant differences between the pre- and post-occlusion periods. Conclusions: Intermittent HPC produced no adverse effect on disease-free and overall survival for patients who underwent liver resection for HCC. [ABSTRACT FROM AUTHOR]

Abstract: Hepatocellular carcinoma (HCC) is a hypervascular cancer characterized by rapid progression as well as resistance to conventional chemotherapy. It has been shown that microRNAs play critical roles in pathogenesis of HCC. MicroRNA-122 (miR-122) is a liver-specific microRNA and is frequently downregulated in HCC. In the present study, we investigated whether restoration of miR-122 in HCC cells could render cells sensitive to chemotherapeutic agents adriamycin (ADM) or vincristine (VCR). Our data showed that overexpression of miR-122 in HCC cells induced by adenovirus expressing miR-122 could render cell sensitive to ADM or VCR. Analysis of cell cycle distribution showed that the anti-proliferative effect of miR-122 is associated with increase of cell number in the G2/M phase. Moreover, treatment with Ad-miR122 and ADM or VCR resulted in high accumulation of HCC cells in G2/M phase. We further demonstrated that overexpression of miR-122 could modulate the sensitivity of the HCC cells to chemotherapeutic drugs through downregulating MDR related genes MDR-1, GST-π, and MRP, antiapoptotic gene Bcl-w and cell cycle related gene cyclin B1. Taken together, our findings demonstrated that combination of Ad-miR122 with chemotherapeutic agents inhibited HCC cell growth by inducing G2/M arrest and that this arrest is associated, at least in part, with reduced expression of MDR related genes and Cyclin B1. [Copyright &y& Elsevier]

The purpose of the study is to evaluate the protective effects of Verapamil on hepatic ischemia–reperfusion injury in cirrhotic patients with HCC. A controlled study was performed on 86 consecutive patients with cirrhosis who underwent liver resection for suffering HCC. Thirty-nine patients were injected with Verapamil through the mesenteric vein before Pringle's maneuver to alleviate hepatic ischemia–reperfusion injury, while 47 patients were not. The serum AST, ALT, and total bilirubin on days 1 and 3 were markedly lower in the Verapamil group than that in the control group postoperatively (AST, P < 0.001 and P < 0.001; ALT, P < 0.001 and P = 0.042; TB, P = 0.037 and 0.049; respectively). The serum hyluronic acid on day 1 was also significantly lower in Verapamil group than that in the control group ( P < 0.01), but no marked difference on days 3 and 7. Meanwhile, the levels of IL6 on days 1 and 3 were markedly lower in the Verapamil group than that in control group ( P < 0.05 and P < 0.01, respectively. The new Clavien's classification of surgical complications showed marked severity in the control group than that in the Verapamil group ( P = 0.021), especially in the grade I level ( P = 0.045). Verapamil may serve as protective agent for hepatic ischemia–reperfusion injury in cirrhotic patients with HCC. Therefore, Verapamil can be used for treatment of patients who are to undergo hepatectomy with occlusion of hepatic blood flow. [ABSTRACT FROM AUTHOR]

: BackgroundResection of a large hepatocellular carcinoma in the right liver or a small tumor located at the superior and posterior part of the right liver requires extensive hepatic mobilization. A thoracoabdominal approach might facilitate hepatic resection in such situations, but the safety and benefits of this approach remain unclear.: Study designA retrospective study based on a prospectively collected database of 488 patients was performed to evaluate the perioperative outcomes of right-sided hepatic resection for hepatocellular carcinoma using the thoracoabdominal approach (n = 92) in comparison with the conventional abdominal approach (n = 396).: ResultsThe two groups were comparable in age, comorbid illnesses, liver function, tumor size, and underlying cirrhosis. There were more extended right hepatectomies in the thoracoabdominal approach group than in the abdominal approach group, but the difference was not significant (33.7% versus 26.0%, p = 0.14). A significantly higher proportion of patients in the thoracoabdominal approach group did not require blood transfusion compared with the abdominal approach group (66.3% versus 54.8%, p = 0.04). The operating time for the former group was longer (median 450 min versus 360 min, p < 0.001). There were no significant differences in hospital stay (median 12.5 days versus 13.0 days, p = 0.82), overall morbidity (41.3% versus 38.6%, p = 0.64), or hospital mortality (4.3% versus 7.3%, p = 0.37) between the two groups.: ConclusionsThe thoracoabdominal approach is a safe operative approach that can facilitate resection of massive tumors in the right liver or tumors involving segments 7 and 8 without increased morbidity. [Copyright &y& Elsevier]

Background The aim of this study was to determine the effect of anatomic resection (AR) versus non-anatomic resection (NAR) on recurrence rates in patients with hepatocellular carcinoma (HCC). Methods Eligible patients were randomized to AR or NAR from January 2006 to July 2007 at a single center. The primary outcome was the 2-year recurrence-free survival (RFS). Secondary outcomes were postoperative complications, time to first recurrence, 1-, 3-, and 5-year RFS, and overall survival (OS). Results Fifty-three (51%) and 52 (50%) patients underwent NAR and AR, respectively. A larger proportion of patients achieved margins ≥20 mm in the AR group (52% vs. 30%; P = 0.023). Complications (blood loss, transfusion requirement, and hospital stay) were similar between the two groups. Median follow-up was 33 (range, 2–77) months. Incidence of local recurrence at 2 years was 30% and 59% in the AR and NAR groups, respectively. Median time to first local recurrence in the AR group was significantly longer than in the NAR group (53 vs. 10 months, P = 0.010). There was no difference in overall RFS between the two groups (P = 0.290). Discussion AR decreased the 2-year local recurrence rate and increased the time to first local recurrence compared to NAR in patients with HCC. [ABSTRACT FROM AUTHOR]

Highlights: [•] HDAC inhibitors suppress cell growth and self-renewal of liver CSCs. [•] HDAC3 is selectively expressed in liver CSCs and participates in self-renewal of liver CSCs. [•] HDAC3 regulates expression of pluripotency factors through histone modification. [•] Overexpression of HDAC3 is associated with poor outcome of liver cancer. [•] HDAC inhibitors render liver CSCs sensitive to sorafenib. [Copyright &y& Elsevier]

Background & Aims: The aim of this study was to compare the efficacy of radiofrequency ablation (RFA) with surgical resection (RES) in the treatment of small hepatocellular carcinoma (HCC). Methods: A total of 168 patients with small HCC with nodular diameters of less than 4cm and up to two nodules were randomly divided into RES (n=84) and RFA groups (n=84). Outcomes were carefully monitored and evaluated during the 3-year follow-up period. Results: The 1-, 2-, and 3-year survival rates for the RES and RFA groups were 96.0%, 87.6%, 74.8% and 93.1%, 83.1%, 67.2%, respectively. The corresponding recurrence-free survival rates for the two groups were 90.6%, 76.7%, 61.1% and 86.2%, 66.6%, 49.6%, respectively. There were no statistically significant differences between the two groups in overall survival rate (p =0.342) or recurrence-free survival rate (p =0.122). Multivariate analysis demonstrated that the independent risk factors associated with survival were multiple occurrences of tumors at different hepatic locations (relative risk of 2.696; 95% CI: 1.189–6.117; p =0.018) and preoperative indocyanine green retention rate at 15min (ICG-15) (relative risk of 3.853; 95% CI: 1.647–9.015; p =0.002). Conclusions: In patients with small hepatocellular carcinomas, percutaneous RFA may provide therapeutic effects similar to those of RES. However, percutaneous RFA is more likely to be incomplete for the treatment of small HCCs located at specific sites of the liver, and open or laparoscopic surgery may be the better choice. [Copyright &y& Elsevier]