• Meta-analysis
• Radiofrequency ablation
• Small liver cancer
• Survival prognosis
• Traditional surgical resection

• hepatocellular carcinoma
• interventional therapy
• oncology

• TACE
• TARE
• TKI
• adjuvant therapy
• clinical trial
• immunotherapy

• Humans
• Carcinoma, Hepatocellular/surgery
• Liver Neoplasms/surgery
• Chemoembolization, Therapeutic/adverse effects
• Antineoplastic Combined Chemotherapy Protocols/therapeutic use

• Cirrhosis
• Hepatocellular carcinoma
• Liver resection
• Radiofrequency ablation
• Tumor size

• Humans
• Carcinoma, Hepatocellular/pathology
• Liver Neoplasms/pathology
• Treatment Outcome
• Catheter Ablation/adverse effects
• Catheter Ablation/methods
• Liver Cirrhosis/complications
• Liver Cirrhosis/diagnosis
• Liver Cirrhosis/surgery
• Radiofrequency Ablation/adverse effects
• Retrospective Studies

• hepatocellular cancer
• adaptive radiation therapy
• stereotactic body radiation therapy

• Humans
• Liver Neoplasms/pathology
• Carcinoma, Hepatocellular/radiotherapy
• Treatment Outcome
• Radiotherapy Dosage
• Radiosurgery/adverse effects
• Radiosurgery/methods

• P01 CA059827 NCI NIH HHS
• P30 CA046592 NCI NIH HHS

• adjuvant therapy
• hepatocellular carcinoma
• immune checkpoint inhibitors
• immunotherapy
• neoadjuvant therapy
• recurrence

• Ablation
• Elderly
• Hepatectomy
• Hepatocellular carcinoma
• Treatment decision-making

Hepatocellular carcinoma (HCC) is the most frequent liver neoplasm, and its incidence rates are constantly increasing. Despite the availability of potentially curative treatments (liver transplantation, surgical resection, thermal ablation), long-term outcomes are affected by a high recurrence rate (up to 70% of cases 5 years after treatment). HCC recurrence within 2 years of treatment is defined as “early” and is generally caused by the occult intrahepatic spread of the primary neoplasm and related to the tumor burden. A recurrence that occurs after 2 years of treatment is defined as “late” and is related to de novo HCC, independent of the primary neoplasm. Early HCC recurrence has a significantly poorer prognosis and outcome than late recurrence. Different pathogenesis corresponds to different predictors of the risk of early or late recurrence. An adequate knowledge of predictive factors and recurrence risk stratification guides the therapeutic strategy and post-treatment surveillance. Patients at high risk of HCC recurrence should be referred to treatments with the lowest recurrence rate and when standardized to combined or adjuvant therapy regimens. This review aimed to expose the recurrence predictors and examine the differences between predictors of early and late recurrence.

• Hepatocellular carcinoma
• Early recurrence
• Late recurrence
• Predictors
• Liver transplant
• Liver resection
• Thermal ablation

• Humans
• Carcinoma, Hepatocellular/epidemiology
• Carcinoma, Hepatocellular/therapy
• Carcinoma, Hepatocellular/etiology
• Liver Neoplasms/epidemiology
• Liver Neoplasms/surgery
• Prognosis
• Neoplasm Recurrence, Local/surgery
• Hepatectomy/adverse effects
• Risk Factors
• Retrospective Studies

• Ablation treatment assessment
• Computed tomography;magnetic resonance imaging
• HCC
• Radiomics
• Ultrasound

To compare the actual 10-year survival outcomes of early single hepatocellular carcinoma (HCC) patients between 3 first-line treatments: radiofrequency ablation (RFA), surgical resection (SR), or transplantation (LT).

A total of 1255 early single HCC patients retrieved from the Surveillance Epidemiology and End Results (SEER) database were included. Patients survived ≥10 years, and patients died <10 years were compared. Significant predictors associated with 10-year survival were identified by multivariate logistic regression analysis. The 10-year survival outcomes of 3 treatments were compared using multivariate model risk adjustment and inverse probability of treatment weighted (IPTW) adjustment.

Of the 1255 patients, 472 patients underwent SR, 259 patients underwent LT, and 524 patients underwent RFA. 149 patients achieved 10-year survival. Multivariate logistic regression analysis showed that age, race, treatment, and fibrosis score were significant predictors for 10-year survival, and LT had the best advantage of 10-year survival, followed by SR. Comparable 10-year survival outcomes were found between SR and RFA after IPTW. Then, a subgroup analysis was performed based on the tumor size, and the results showed that for ≤50 mm tumor, SR showed no significant advantages over RFA for 10-year survival.

Estimates of the observational association of different treatments with 10-year survival are sensitive to the analytic method. LT showed the best outcomes for patients. No significant differences for 10-year survival were found between SR and RFA in the IPTW cohort. Subgroup analysis showed that for >50 mm tumor, SR showed significant advantages over RFA after IPTW.

The first-line therapy for early-stage hepatocellular carcinoma (HCC) is unclear. This study was conducted to assess and compare survival after surgery vs. after radiofrequency ablation (RFA) for early-stage HCC.

Data from HCC patients with a single tumor measuring 31–50 mm were extracted from the Surveillance, Epidemiology, and End Results (SEER) database from 2004 to 2015. Overall survival (OS) and cancer-specific survival (CSS) were assessed and compared between surgery and RFA treatment. Propensity score matching was performed. Multiple imputations were used to create 5 sets of complete data. Fine and Gray competing risk multivariate regression models were used to control biases.

This study included 839 patients: 339 (40.41%) received RFA and 500 (59.59%) underwent surgery. Surgery improved the 5-year OS (63.95% vs. 37.13%, p<0.01) and CSS (64.01% vs. 38.29%, p<0.01) compared with RFA after propensity score matching. The competing risk regression models revealed that, compared with RFA, surgery resulted in better survival in the unmatched cohort with an adjusted sub-distribution hazard ratio of 0.689 (95% confident interval [CI], 0.562–0.868; p=0.001) and in the propensity-matched cohort with an adjusted sub-distribution hazard ratio of 0.642 (95% CI, 0.514–0.801; p<0.001).

Surgery appears to be a better therapy choice than RFA for patients with early-stage HCC with a single tumor measuring 31–50 mm.

Controversies exist for which treatment is optimal for early hepatocellular carcinoma (HCC): radiofrequency ablation (RFA), surgical resection (SR), or transplantation (LT). We compared outcomes between treatments as first-line therapy for HCC patients measuring up to 5 cm or different cancer risk groups.

The Surveillance, Epidemiology, and End Results database was retrieved for HCC patients treated with RFA, SR, or LT between 2004 and 2015. The effects of three treatments were compared using propensity score, inverse probability of treatment weights adjustment, and instrumental variable analysis for overall survival (OS) and competing risks regression models for disease-specific survival (DSS). We also evaluated whether the effect of treatments varied according to baseline clinical characteristics by locally weighted regression method.

Of 7664 patients, RFA and SR yielded worse OS (HR 1.67, CI 1.43–1.70, P<0.001; HR 1.43, CI 1.40–1.67, P<0.001) and DSS (HR 2.00, CI 1.10–3.30, P<0.011; HR 2.50, CI 2.00–3.30, P<0.001) than LT. In patients with small tumors, SR may confer more survival benefits than RFA (HR>1) for different tumor sizes measuring up to 5 cm and may be an appropriate first-line treatment. Additionally, RFA has more survival benefits compared with SR (HR 0.83, CI 0.53–1.25) for those patients with low tumor risk and good general health condition (without any prognostic risk factors). However, those patients with a predicted 5-year overall mortality risk >30% seem to benefit more for SR than RFA.

Due to a shortage of donors, RFA and SR can be applied as either primary management of HCC or as a bridging therapy for LT. Furthermore, SR is an effective option for patients with different HCC tumor size. However, RFA could achieve comparable survival benefits with SR for patients without any risk factors.

• PS
• hepatocellular carcinoma
• outcomes
• propensity score
• radiofrequency ablation
• surgical resection
• transplantation

• Efficacy
• Hepatocellular carcinoma
• Liver metastasis
• Microwave ablation
• Radiofrequency ablation

• Female
• Humans
• Liver Neoplasms/mortality
• Liver Neoplasms/radiotherapy
• Male
• Microwaves/therapeutic use
• Radiofrequency Ablation/methods
• Survival Analysis

Background: Because of the poor health conditions of elderly patients (age >65) with very-early-stage and early-stage hepatocellular carcinoma (HCC), primary treatment via hepatic resection (HR), or radiofrequency ablation (RFA) must be considered. However, few studies have examined this issue.

Methods: A retrospective cohort was obtained from the Surveillance, Epidemiology, and End Results (SEER) database from 2004 to 2015. Patients were grouped by tumor size (0–20, 21–30, 31–35, and 31–50 mm) and age (>65 and ≤65). Overall survival (OS) and disease-specific survival (DSS) were assessed.

Results: In total, 1912 patients aged >65 and 2,784 patients aged ≤65 were analyzed after propensity score matching (PSM). For patients >65 with tumors ≤20 mm, OS and DSS did not differ significantly between the RFA and HR groups (p = 0.47 and p = 0.76, respectively). For patients with tumors measuring 21–30 mm, the HR group had better OS and a trend toward better DSS compared with the RFA group (p = 0.03 and p = 0.09, respectively). For patients with tumors measuring 31–50 mm, the HR group had better OS and DSS compared with the RFA group (p < 0.001 for both). For patients <65, the HR group had better OS and DSS compared with the RFA group for all tumor sizes.

Conclusions: For elderly patients (age >65), RFA is recommended for tumors ≤20 mm. For patients older than 65 with tumors measuring 21–50 mm and for those younger than 65 with tumors of any size, HR is the better choice.

• elderly
• hepatic resection
• radiofrequency ablation
• real-world study
• tumor size

The aim of this study was to predict tumor progression in patients with hepatocellular carcinoma (HCC) treated with radiofrequency ablation (RFA) using histogram analysis of apparent diffusion coefficients (ADC).

Breath-hold diffusion weighted imaging (DWI) was performed in 64 patients (33 progressive and 31 stable) with biopsy-proven HCC prior to RFA. All patients had pre-treatment magnetic resonance imaging (MRI) and follow-up computed tomography (CT) or MRI. The ADC values (ADC₁₀, ADC₃₀, ADC_median and ADC_max) were obtained from the histogram’s 10th, 30th, 50th and 100th percentiles. The ratios of ADC₁₀, ADC₃₀, ADC_median and ADC_max to the mean non-lesion area-ADC (RADC₁₀, RADC₃₀, RADC_median, and RADC_max) were calculated. The two patient groups were compared. Key predictive factors for survival were determined using the univariate and multivariate analysis of the Cox model. The Kaplan-Meier survival analysis was performed, and pairs of survival curves based on the key factors were compared using the log-rank test.

The ADC₃₀, ADC_median, ADC_max, RADC₃₀, RADC_median, and RADC_max were significantly larger in the progressive group than in the stable group (P<0.05). The median progression-free survival (PFS) was 22.9 months for all patients. The mean PFS for the stable and progressive groups were 47.7±1.3 and 9.8±1.3 months, respectively. Univariate analysis indicated that RADC₁₀, RADC₃₀, and RADC_median were significantly correlated with the PFS [hazard ratio (HR)=31.02, 43.84, and 44.29, respectively, P<0.05 for all]. Multivariate analysis showed that RADC_median was the only independent predictor of tumor progression (P=0.04). And the cutoff value of RADC_median was 0.71.

Pre-RFA ADC histogram analysis might serve as a useful biomarker for predicting tumor progression and survival in patients with HCC treated with RFA.

• Diffusion-weighted imaging
• apparent diffusion coefficient
• hepatocellular carcinoma
• histogram analysis
• radiofrequency ablation
• survival time

Vascular invasion, rather than tumor size, was applied into the 7th edition of the AJCC TNM staging system to predict survival of solitary hepatocellular carcinoma (HCC) patients. However, does this mean tumor size is of little value in prognostic prediction? The current study was designed to explore the prognostic ability of tumor sizes in solitary HCC.

A total of 18 591 patients with solitary HCC categorized as T1 and T2 were retrieved from the Surveillance Epidemiology and End Results (SEER) database. The Cox proportional hazards regression model was adopted to evaluate the impact of tumor sizes on overall survival (OS) and disease‐specific survival (DSS) in general and in subgroups stratified by vascular invasion and surgery type.

Large tumor sizes (>39 mm) were associated with unfavorable clinicopathologic characteristics. Compared with tumors ≤30 mm, tumors between 31‐50 mm and tumors >50 mm showed significantly worse OS and DSS in general using multivariate analysis (all P < 0.001). In subgroup analyses, for patients without vascular invasion, tumor size was a notable prognostic indicator for OS in the radiofrequency ablation group (P < 0.001), rather than in the liver resection or transplantation group. Nevertheless, for patients with vascular invasion, tumor sizes exhibited a notable impact on OS in the liver resection and transplantation group.

The AJCC TNM staging system for solitary HCC would be more comprehensive if tumor sizes were integrated into the T2 classification. Additionally, for T1 patients, tumor sizes play no role in the choice between resection and transplantation.

• liver resection
• liver transplantation
• prognosis
• radiofrequency ablation
• solitary hepatocellular carcinoma
• tumor sizes

• Hepatocellular carcinoma (HCC)
• survival calculator

To compare the outcomes of liver resection (LR) with radiofrequency ablation (RFA) for patients with hepatitis B virus (HBV)-related small hepatocellular carcinoma (HCC).

A total of 122 HBV-related small HCC patients who underwent LR (n=64) or RFA (n=58) were involved in this retrospective study. Their basic clinical data, postoperative complications, survival outcomes, and prognostic factors were compared and analyzed.

Patients in the LR group had more serious complications (11 versus 0) and longer postoperative hospital stays (11.3 versus 6.0 days) than those in the RFA group (all P<0.05). LR was associated with better recurrence-free survival (RFS) rates at 1, 3, and 5 years compared with RFA (90.4%, 65.9%, and 49.5% versus 79.3%, 50.3%, and 35.6%, P=0.037), but there was no significant difference in overall survival (OS) (95.2%, 78.1%, 58.6% versus 93.1%, 71.3%, 52.9%, P=0.309). Multivariate Cox analysis showed that the hepatic cirrhosis (hazard ratio [HR]: 2.13), tumor number (HR: 3.73), tumor diameter (HR: 1.92), and postoperative anti-HBV therapy (HR: 0.53) had predictive values for RFS, and the latter three (HR: 4.34, 2.30, and 0.44) were independent predictors of OS (all P<0.05).

LR might be considered the preferred method for patients with HBV-related small HCC, while RFA could apply to selective cases. Anti-HBV therapy after treatment was recommended.

• hepatitis B virus
• hepatocellular carcinoma
• liver resection
• radiofrequency ablation
• survival

Surgical resection remains the initial treatment of choice for the majority of early stage hepatocellular carcinoma (HCC) patients. Although the factors that influence the prognosis of postoperative HCC patients have been well elucidated, there are a limited number of simple, objective, and distinct methods for estimating survival for postoperative patients with solitary HCC within the Milan criteria and Child-Pugh (C-P) A cirrhosis. The Albumin-Bilirubin (ALBI) score is a new evidence-based approach to assess liver function. The ALBI score eliminates subjective variables, such as ascites and encephalopathy which are the requirements for the conventional C-P grading system. This study enrolled 654 patients to determine whether the ALBI score can predict the outcomes of postoperative solitary HCC patients within the Milan criteria and C-P A cirrhosis. Our results showed the ALBI score significantly influenced the overall survival and cumulative recurrence rates. Furthermore, the ALBI score was significantly related to the degree of liver cirrhosis and serum γ-glutamyl transpeptidase (GGT) concentration in solitary HCC cases within the Milan criteria and C-P A cirrhosis. Additionally, the combination of the ALBI score and serum GGT concentration contributed to the prognosis prediction in this cohort. In conclusion, we externally validated the ALBI grade as a novel biomarker to predict prognosis for solitary HCC within the Milan Criteria and C-P A cirrhosis.

• Albumin-Bilirubin Score
• Child-Pugh A
• HCC
• Milan Criteria

This study was designed to investigate the associations between TERT overexpression and the clinicopathologic factors of hepatocellular carcinoma (HCC). A total of 291 patients with HCC were enrolled. The site of first recurrence (anywhere in the liver) was classified as intrahepatic recurrence (IHR). Recurrence was then sub classified as either early or late IHR according to whether it was discovered within 2 years of resection, or after, respectively. TERT overexpression was not significantly correlated with previously recognized prognostic factors. During follow-up, early IHR occurred in 126 (63.6%) patients, while late IHR was detected in 59 patients among 145 patients who remained free of HCC recurrence for ≥ 2 years after surgery. Multivariate analysis showed late IHR was significantly correlated with TERT overexpression (P < 0.001, hazard ratio [HR] 2.67, 95% confidence interval [CI] 1.51–4.72). Intrahepatic metastasis (P < 0.001, HR 4.48, 95% CI 2.62–7.65) and TERT overexpression (P < 0.001, HR 1.77, 95% CI 1.28–2.45) were significant prognostic factors for IHR-free survival in both univariate and multivariate analyses. TERT overexpression was the only significant prognostic factor for late IHR in HCC treated with curative resection. And, the statistical significance of TERT overexpression on late IHR was limited to HBsAg-positive patients.

There is great geographical variation in the distribution of hepatocellular carcinoma (HCC), with the majority of all cases worldwide found in the Asia–Pacific region, where HCC is one of the leading public health problems. Since the “Toward Revision of the Asian Pacific Association for the Study of the Liver (APASL) HCC Guidelines” meeting held at the 25th annual conference of the APASL in Tokyo, the newest guidelines for the treatment of HCC published by the APASL has been discussed. This latest guidelines recommend evidence-based management of HCC and are considered suitable for universal use in the Asia–Pacific region, which has a diversity of medical environments.

• APASL
• Asia–Pacific
• Hepatocellular carcinoma
• Treatment algorithm

• hepatocellular cancer
• outcomes
• radiofrequency ablation (RFA)
• surgical resection
• survival
• transplantation

Each year, hepatocellular carcinoma is diagnosed in more than half a million people worldwide and it is the fifth most common cancer in men and the seventh most common cancer in women. This article reviews the Barcelona-Clínic Liver Cancer protocol for the diagnosis, staging, and treatment of this disease, and four cases are presented for the discussion of the therapeutic approach. Understanding the diagnostic and therapeutic approaches to this disease is essential, especially if we keep in mind the quintessential basics of prevention and early detection.

• hepatocellular carcinoma
• liver cirrhosis
• neoplasm staging

Background. Treatment selection for small hepatocellular carcinoma (sHCC) is controversial. We aimed to compare the outcomes of medical imaging three-dimensional visualization system (MI-3DVS) guided surgical resection (SR) and ultrasonography guided radiofrequency ablation (RFA) for sHCC. Methods. In total, 194 patients who underwent SR or RFA in our hospital between January 2006 and May 2010 were retrospectively enrolled. Overall survival (OS), recurrence-free survival (RFS), and postoperative complications were compared. Cox regression was used to estimate the benefits of MI-3DVS-guided SR on OS and RFS. Results. Ninety-two patients underwent SR and 102 underwent RFA. The SR group experienced more complications (41.3% versus 19.6%) and longer hospital stay (18.04 ± 7.11 versus 13.06 ± 5.59) (both p < 0.05). The 1-, 2-, 3-, 4-, and 5-year OS was 96.7%, 95.7%, 93.5%, 83.5%, and 61.1% in the SR group and 95.0%, 88.1%, 72.7%, 56.9%, and 39.5% in the RFA group. Corresponding RFS was 95.7%, 94.6%, 84.7%, 59.8%, and 40.2% in SR group and 91.2%, 80.3%, 60.5%, 32.3%, and 22.3% in RFA group. The 5-year OS and RFS were higher in SR group (both p < 0.001). Interestingly, there was no significance in OS and RFS among subgroups aged >60 years. Independent predictors of OS and RFS, respectively, were intervention (HR, 2.769 and 1.933), tumor number (HR, 5.128 and 3.903), and serum alpha-fetoprotein (AFP) (HR, 1.871 and 1.474) (all p < 0.05). Conclusions. MI-3DVS based hepatectomy should be considered primary treatment while RFA can be treated as alternative therapy for older patients. Intervention, tumor number, and AFP are independent predictors for both survival and recurrence.

• Ablative therapy
• HCC
• PEI
• RFA
• early stage
• liver transplant
• resection

• Ablation Techniques/methods
• Carcinoma, Hepatocellular/pathology
• Carcinoma, Hepatocellular/surgery
• Hepatectomy/methods
• Humans
• Liver Neoplasms/pathology
• Liver Neoplasms/surgery
• Liver Transplantation/methods

AIM: To investigate the effect of anterior gradient homolog 2 (AGR2) expression on the proliferation of hepatocellular carcinoma cells, and to explore the possible mechanism.

METHODS: The expression of AGR2 and interferon-induced transmembrane protein 3 (IFITM3) in hepatocellular carcinoma and adjacent tissues was detected by fluorescence quantitative PCR and Western blot. The expression of AGR2 mRNA and protein was examined by real-time fluorescence quantitative PCR and Western blot after transfection with pcDNA3.1-AGR2. The cellular growth ability was examined by CCK-8 assay, and the colony formation ability was detected by colony formation assay. Flow cytometry assay was used to determine the apoptosis index. The expression level of IFITM3 protein was examined by Western blot.

RESULTS: AGR2 and IFITM3 mRNA and protein expression in hepatocellular carcinoma tissues was significantly higher than that in the corresponding adjacent tissues. The pcDNA3.1-AGR2 was successfully constructed, and HepG2 cells with stable expression of AGR2 were established. The expression levels of AGR2 mRNA and protein in HepG2 cells after transfection with pcDNA3.1-AGR2 were higher than those in the negative control cells, and the cellular growth ability of HepG2 cells after transfection with pcDNA3.1-AGR2 was significantly increased. IFITM3 protein expression was also increased after transfection with pcDNA3.1-AGR2.

CONCLUSION: Raised AGR2 expression can increase the expression of IFITM3 and promote the proliferation of hepatocellular cells.

• Hepatocellular carcinoma
• Cell proliferation
• AGR2
• IFITM3