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Abstract Purpose To summarize the abdominal computed tomography (CT) imaging and clinicopathological data of patients with SPNs of the pancreas and analyze the accuracy of preoperative CT diagnosis and features. Materials and methods Between June 2006 and June 2023, CT images of 120 histopathologically proven SPNs in the pancreas were retrospectively reviewed. Fifteen features, including age, sex, and CT-determined features, were included in a multiple stepwise regression analysis. The correlations between features and SPNs, including odds ratios (ORs) and 95% confidence intervals (CIs), were evaluated. Results Among the 120 patients, the diagnostic accuracy of CT was 43.3%. The baseline CT results of patients with a correct diagnosis and misdiagnosis revealed significant differences in sex (P = 0.043), age (P = 0.004), boundary (P = 0.037) and encapsulation (P = 0.002) between the two groups. The preoperative imaging diagnostic accuracy was significantly greater in females than in males (47.9% vs. 25.0%, P = 0.043). The immunohistochemical indices did not significantly differ between the two groups. The results of univariate analysis revealed significant differences in sex (P = 0.048), age (P = 0.014), tumor length (P = 0.023), tumor boundaries (P = 0.039) and capsule type (P = 0.003). The results of multivariate analysis revealed that encapsulation was closely related to the diagnostic accuracy of CT (P = 0.04). Conclusions The accuracy of CT in the diagnosis of SPNs is low, but a length‒diameter ratio of the tumor approaching 1.0, encapsulation and clear boundaries are important CT-determined features. The capsule is an independent CT predictor in the diagnosis of SPNs.

Objectives: To summarize current evidence about the influence of body composition on the prognosis of patients with hepatocellular carcinoma (HCC) after transarterial chemoembolization (TACE) treatment. Methods: Public databases were systematically searched to identify relevant studies published from the inception of the database up to May 2023. Studies that evaluated the association between body composition and clinical outcomes in HCC patients who underwent TACE were included. A pre-designed table was applied to summarize relevant information. Meta-analysis was performed to estimate the association of body composition with overall survival. Results: Fourteen studies were included in this review, including 3631 patients (sample size range: 56–908, median 186). All body composition measurements (including skeletal muscle area, visceral and subcutaneous adipose area, and bone mineral density) were based on computer tomography. The commonly used parameter was skeletal muscle index at 3rd lumbar vertebra level (8/14). Three studies evaluated the correlations of body composition changes with the prognosis after TACE. Most studies (12/14) identified body composition parameters as an independent indicator for overall survival, progression-free survival, and treatment response rate. The hazard ratio of different body composition parameters ranged from 1.01 to 2.88, and hazard ratio of body composition changes ranged from 1.88 to 5.93. The pooled hazard ratio of sarcopenia for overall survival was 1.38 (95 %CI: 1.20–1.58). Conclusions: Body composition seems to be an important prognostic factor for a poorer clinical outcome after TACE treatment in patients with hepatocellular carcinoma. Future prospective studies with a larger sample size are required to confirm these findings. Registration study: This study has been prospectively registered at the PROSPERO platform (https://www.crd.york.ac.uk/prospero/) with the registration No. CRD42022345602.

Background: Hepatocellular carcinoma (HCC) often resists traditional treatments, necessitating new therapeutic approaches. With immune checkpoint therapy emerging as a promising alternative, understanding its resistance mechanisms becomes crucial.Methods: Using 22 samples from 11 HCC patients, we conducted a comprehensive transcriptomic and metabolomic analysis of peri-tumoral hepatic tissues from those treated with Atezolizumab.Results: We identified significant metabolic alterations and a correlation between the COMMD3-BMI1 gene and Dephospho-CoA metabolite. Findings suggest these as potential markers for therapeutic resistance, as evidenced by upregulated COMMD3-BMI1 and downregulated Dephospho-CoA in non-responsive patients, with animal models further supporting these observations.Discussion: The study highlights COMMD3-BMI1 and Dephospho-CoA as critical actors in immune checkpoint therapy resistance in HCC, providing insights and potential pathways for more effective therapeutic strategies.

Abstract Objective To evaluate the long‐term efficacy of no‐touch radiofrequency ablation (NT‐RFA) for treating single hepatocellular carcinoma (HCC) less than 3 cm. Methods A total of 331 patients with HCC less than 3 cm undergoing RFA in Southwest Hospital from 2015 to 2020 were analyzed retrospectively. All patients were divided into NT‐RFA group (n = 113) and conventional RFA (C‐RFA) group (n = 218). The survival rate, local tumor progression (LTP) and intrahepatic distant recurrence (IDR) of the two groups were calculated and compared. Results A significant difference was observed in ablation range (p = 0.000) and safety margin (p = 0.000) between the two groups. The 1‐, 2‐, 3‐, 4‐and 5‐year overall survival (OS) rates in NT‐RFA and C‐RFA group were 99.12%, 93.73%, 76.18%, 57.00%, 45.17% and 99.08%, 89.91%, 71.26%, 54.28%, 41.77%, respectively. There was no significant difference between the two groups (p = 0.281). The 1‐, 2‐, 3‐, 4‐and 5‐year recurrence‐free survival (RFS) rates in NT‐RFA and C‐RFA group were 78.51%, 52.59%, 41.02%, 34.36%, 30.92% and 68.81%, 44.95%, 30.88%, 23.73%, 22.88%, respectively. The two groups differed significantly (p = 0.044). The 1‐, 3‐and 5‐year LTP‐free survival rates in NT‐RFA and C‐RFA group were 87.12%, 74.99%, 72.32% and 75.75%, 65.52%, 65.52%, respectively. The two groups also differed significantly (p = 0.024). Furthermore, the RFS rates of D ≤ 2 cm subgroups in NT‐RFA and C‐RFA groups differed significantly (p = 0.037), while the RFS rates of 2 cm

Aim To compare the short- and long-term treatment outcomes of open radiofrequency ablation combined with splenectomy and pericardial devascularization versus liver transplantation for hepatocellular carcinoma patients with portal hypertension and hypersplenism. Methods During the study period, the treatment outcomes of consecutive HCC patients with portal hypertension and hypersplenism who underwent open radiofrequency ablation, splenectomy and pericardial devascularization (the study group) were compared with the treatment outcomes of a case-matched control group of HCC patients who underwent liver transplantation. Results The study group consisted of 32 patients, and the control group comprised 32 patients selected from 155 patients who were case-matched by tumor size, age, gender, MELD sore, tumor location, TNM classification, degree of splenomegaly and Child–Pugh staging. Baseline data on preoperative laboratory tests and tumor characteristics were comparable between the two groups. The mean follow-up was 43.2 ± 5.3 months and 44.9 ± 5.8 months for the study and control groups, respectively. Although the disease-free survival rates of the control group were better than those of the study group (P

Purpose To investigate the long-term efficacy of radiofrequency ablation (RFA) with a multiple-electrode switching system (MESS) in the treatment of early hepatocellular carcinoma (HCC) and evaluate the patterns and risk factors of intrahepatic recurrence of HCC after RFA. Methods In total, 139 patients with early HCC who underwent RFA with MESS as primary treatment at multiple centers were prospectively enrolled according to the inclusion criteria. We evaluated the local tumor progression (LTP), intrahepatic distant recurrence (IDR), the incidence of cumulative disease-free survival (DFS), LTP-free survival, IDR-free survival, and overall survival. We also analyzed the associated risk factors. Results A total of 139 patients were included in the study and the median follow-up time was 64 months, ranging from 11 to 72 months. The complete ablation rate was 98.56%. Sixty-nine (49.64%) were found to have intrahepatic recurrence (LTP, n = 15; IDR, n = 55) during follow-up. The 1-year, 3-year and 5-year cumulative DFS, LTP-free survival, and IDR-free survival rates were 74.82, 94.46 and 78.75%; 54.68, 88.03 and 61.79%; and 51.80, 85.67 and 60.17%, respectively. In the multivariable analysis, tumor size > 4 cm was the only important risk factor for LTP. The alkaline phosphatase (ALP) level and the number of tumors were independent risk factors for IDR; α-fetoprotein (AFP) level > 400 µg/L and recurrence interval were risk factors for the overall survival period. Conclusions The MESS-RFA is an effective method for local control of tumors in early HCC. Early HCC with multiple high-ALP tumors has a higher rate of recurrence, which mainly occurs in an IDR pattern. Early HCC with high AFP levels and a shorter initial recurrence interval resulted in a poorer prognosis. Thus, treatments such as liver transplantation or surgical resection may be a good strategy in those cases. ClinicalTrials.gov ID NCT02046356.

Objective The purpose of this article is to discuss the use, comparative efficacy, and research progress of radiofrequency ablation (RFA), alone or in combination with other therapies, for the treatment of hepatocellular carcinoma (HCC).Method To search and summarize the basic and clinical studies of RFA in recent years.Results RFA is one of the radical treatment methods listed in the guidelines for the diagnosis and treatment of HCC. It has the characteristics of being minimally invasive and safe and can obtain good local tumor control, and it can improve the local immune ability, improve the tumor microenvironment and enhance the efficacy of chemotherapy drugs. It is commonly used for HCC treatment before liver transplantation and combined ALPPS and hepatectomy for HCC. In addition, the technology of RFA is constantly developing. The birth of noninvasive, no-touch RFA technology and equipment and the precise RFA concept have improved the therapeutic effect of RFA.Conclusion RFA has good local tumor control ability, is minimally invasive, is safe and has other beneficial characteristics. It plays an increasingly important role in the comprehensive treatment strategy of HCC. Whether RFA alone or combined with other technologies expands the surgical indications of patients with HCC and provides more benefits for HCC patients needs to be determined.

BackgroundPost-hepatectomy liver failure (PHLF) is a fatal complication after liver resection in patients with hepatocellular carcinoma (HCC). It is of clinical importance to estimate the risk of PHLF preoperatively.AimsThis study aimed to develop and validate a prediction model based on preoperative gadoxetic acid–enhanced magnetic resonance imaging to estimate the risk of PHLF in patients with HCC.MethodsA total of 276 patients were retrospectively included and randomly divided into training and test cohorts (194:82). Clinicopathological variables were assessed to identify significant indicators for PHLF prediction. Radiomics features were extracted from the normal liver parenchyma at the hepatobiliary phase and the reproducible, robust and non-redundant ones were filtered for modeling. Prediction models were developed using clinicopathological variables (Clin-model), radiomics features (Rad-model), and their combination.ResultsThe PHLF incidence rate was 24% in the whole cohort. The combined model, consisting of albumin–bilirubin (ALBI) score, indocyanine green retention test at 15 min (ICG-R15), and Rad-score (derived from 16 radiomics features) outperformed the Clin-model and the Rad-model. It yielded an area under the receiver operating characteristic curve (AUC) of 0.84 (95% confidence interval (CI): 0.77–0.90) in the training cohort and 0.82 (95% CI: 0.72–0.91) in the test cohort. The model demonstrated a good consistency by the Hosmer–Lemeshow test and the calibration curve. The combined model was visualized as a nomogram for estimating individual risk of PHLF.ConclusionA model combining clinicopathological risk factors and radiomics signature can be applied to identify patients with high risk of PHLF and serve as a decision aid when planning surgery treatment in patients with HCC.

Background No-touch combined directed perfusion radiofrequency ablation (NTDP-RFA) is a new technique for the treatment of hepatocellular carcinoma (HCC). The purpose of this study was to evaluate the short-term efficacy of this new technique for the treatment of small HCC with cirrhosis. Methods From January 2017 to March 2018, 56 consecutive patients treated with NTDP-RFA at our center were enrolled in this retrospective study. All NTDP-RFA procedures involved the use of internally cooled wet electrodes with a directional injection function, which can perform both intraelectrode cooling and extraelectrode saline perfusion. Survival curves were analyzed using Kaplan–Meier methods, and Cox proportional hazards regression analyses were used to assess predictors of tumor progression and overall survival. Operative characteristics and complications were also assessed. Results No technical failure occurred, and the complete ablation rate after single NTDP-RFA treatment was 98.2%. The median tumor diameter and ablation time were 26 (18.0 − 28.0) mm and 8 (6 – 8) min, respectively. Mild complications occurred in five patients (8.9%) postoperatively, and the median hospital stay was 4 (4 − 5) days. In the 18 patients (32.1%) with poor liver function reserve (indocyanine green retention rate at 15 min > 15%, their liver function returned to normal on the third day after the postoperation. The 1- and 2-year local and distant progression rates were 1.7%, 7.1%, 3.5% and 10.7%, respectively. Conclusions NTDP-RFA in the treatment of small HCC with cirrhosis has a low incidence of complications and provides a high survival rate without local tumor progression.

Abstract Background The future liver remnant (FLR) faces a risk of poor growth in patients with cirrhosis-related hepatocellular carcinoma (HCC) after stage-1 radiofrequency-assisted ALPPS (RALPPS). The present study presents a strategy to trigger further FLR growth using supplementary radiofrequency ablation (RFA) and percutaneous ethanol injection (PEI). Methods At RALPPS stage-1 the portal vein branch was ligated, followed by intraoperative RFA creating a coagulated avascular area between the FLR and the deportalized lobes. During the interstage period, patients not achieving sufficient liver size (≥ 40%) within 2–3 weeks underwent additional percutaneous RFA/PEI of the deportalized lobes (rescue RFA/PEI) in an attempt to further stimulate FLR growth. Results Seven patients underwent rescue RFA/PEI after RALPPS stage-1. In total five RFAs and eight PEIs were applied in these patients. The kinetic growth rate (KGR) was highest the first week after RALPPS stage-1 (10%, range − 1% to 15%), and then dropped to 1.5% (0–9%) in the second week (p

Background This study aimed to evaluate whether combined therapy with PD-1 blockade (anti-PD-1) and radiofrequency ablation (RFA) is superior to RFA monotherapy for recurrent hepatocellular carcinoma (HCC). Methods A total of 127 patients who underwent anti-PD-1 plus RFA treatment (n = 41) or RFA alone (n = 86) for recurrent HCC were included in this retrospective study. A matched cohort comprising 40 patients from each group was selected after propensity score matching analysis. Clinical data including post-RFA HCC recurrence (primary endpoint), overall survival (OS) (secondary endpoint), adverse events, and toxic effects were retrospectively analyzed. Results The 1-year recurrence-free survival rates for the anti-PD-1 plus RFA and RFA groups were 32.5% and 10.0% after propensity score matching. There were statistically significant differences between the two groups in terms of the recurrence-free survival rate (p = 0.001) and OS rate (p = 0.016). Tumor number, tumor-node metastasis (TNM) stage, antiviral therapy, and anti-PD-1 treatment were demonstrated to be important factors associated with 1-year recurrence-free survival probability by univariate and multivariate analyses. Univariate and multivariate analyses demonstrated that tumor number, TNM stage and anti-PD-1 treatment were significant prognostic factors for OS. RFA treatment-related adverse events included pleural effusions that require drainage and a mild or moderate increase in body temperature. Grade 3 or higher events related to anti-PD-1 treatment occurred in 12.8% (6) of patients and were infrequent. Conclusions Combination therapy with anti-PD-1 plus RFA was superior to RFA alone in improving survival in patients with recurrent HCC.

Abstract Objective To detect the expression level of organic anion-transporting polypeptide 1B3 (OATP1B3) in hepatocellular carcinoma (HCC) and to determine the relationship between OATP1B3 expression, clinicopathological features, and prognosis. Methods Immunohistochemical (IHC) staining was performed to detect the expression of OATP1B3 in 131 HCC specimens and in 89 adjacent nontumorous tissues. Moreover, the expression levels of OATP1B3 in 30 pairs of tumor and matched adjacent nontumorous tissues were detected by quantitative real-time polymerase chain reaction, and 34 pairs of tumor and matched adjacent nontumorous tissues were detected by Western blotting. The χ2 test was applied to analyze the correlation between OATP1B3 expression and the clinical parameters of HCC patients. The prognostic value of OATP1B3 in HCC patients was estimated by Kaplan-Meier survival analysis and the Cox stepwise proportional hazards model. Results Compared with that in adjacent nontumorous tissues (25.8%, 23/89), OATP1B3 expression was significantly downregulated in tumor tissues (59.5%, 78/131) (P < 0.0001). Moreover, OATP1B3 expression was markedly correlated with tumor size, recurrence, tumor differentiation, and tumor node metastasis (TNM) stage (P < 0.05 for each). However, age, sex, tumor capsule status, HBsAg, cirrhosis, tumor number, vascular invasion, and serum alpha fetoprotein were not associated with OATP1B3 expression. The overall survival (OS) and disease-free survival (DFS) of HCC patients who had high expression of OATP1B3 were significantly longer than those of patients with low expression (33.0% vs 12.9%, P = 0.001; 18.8% vs 5.3%, P < 0.0001). Cox multivariate analysis showed that OATP1B3, invasion, and TNM stage (P < 0.05 for each) were independent prognostic factors of OS in HCC patients and that OATP1B3 and TNM stage (both P < 0.05) were independent prognostic factors of DFS in HCC patients. Conclusions The expression of OATP1B3 in HCC patients was significantly lower than that in adjacent nontumorous tissues. OATP1B3 expression may be a potential prognostic marker in HCC patients.

AimThe aim of this study is to establish and validate a radiomics-based model using preoperative Gd-EOB-DTPA-enhanced MRI to predict microvascular invasion (MVI) in patients with hepatocellular carcinoma ≤ 5 cm.MethodsClinicopathologic and MRI data of 178 patients with solitary hepatocellular carcinoma (HCC) (≤5 cm) were retrospectively collected from a single medical center between May 2017 and November 2020. Patients were randomly assigned into training and test subsets by a ratio of 7:3. Imaging features were extracted from the segmented tumor volume of interest with 1-cm expansion on arterial phase (AP) and hepatobiliary phase (HBP) images. Different models based on the significant clinical risk factors and/or selected imaging features were established and the predictive performance of the models was evaluated.ResultsThree radiomics models, the AP_model, the HBP_model, and the AP+HBP_model, were constructed for MVI prediction. Among them, the AP+HBP_model outperformed the other two. When it was combined with a clinical model, consisting of tumor size and alpha-fetoprotein (AFP), the combined model (AP+HBP+Clin_model) showed an area under the curve of 0.90 and 0.70 in the training and test subsets, respectively. Its sensitivity and specificity were 0.91 and 0.76 in the training subset and 0.60 and 0.79 in the test subset, respectively. The calibration curve illustrated that the combined model possessed a good agreement between the predicted and the actual probabilities.ConclusionsThe radiomics-based model combining imaging features from the arterial and hepatobiliary phases of Gd-EOB-DTPA-enhanced MRI and clinical risk factors provides an effective and reliable tool for the preoperative prediction of MVI in patients with HCC ≤ 5 cm.

Histopathologic grade of hepatocellular carcinoma (HCC) is an important predictor of early recurrence and poor prognosis after curative treatments. This study aims to develop a radiomics model based on preoperative gadoxetic acid-enhanced MRI for predicting HCC histopathologic grade and to validate its predictive performance in an independent external cohort. Clinical and imaging data of 403 consecutive HCC patients were retrospectively collected from two hospitals (265 and 138, respectively). Patients were categorized into poorly differentiated HCC and non-poorly differentiated HCC groups. A total of 851 radiomics features were extracted from the segmented tumor at the hepatobiliary phase images. Three classifiers, logistic regression (LR), support vector machine, and Adaboost were adopted for modeling. The areas under the curve of the three models were 0.70, 0.67, and 0.61, respectively, in the external test cohort. Alpha-fetoprotein (AFP) was the only significant clinicopathological variable associated with HCC grading (odds ratio: 2.75). When combining AFP, the LR+AFP model showed the best performance, with an AUC of 0.71 (95%CI: 0.59–0.82) in the external test cohort. A radiomics model based on gadoxetic acid-enhanced MRI was constructed in this study to discriminate HCC with different histopathologic grades. Its good performance indicates a promise in the preoperative prediction of HCC differentiation levels.

Background: To evaluate the feasibility and efficacy of sequential portal vein embolization (PVE) and radiofrequency ablation (RFA) (PVE+RFA) as a minimally invasive variant for associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) stage-1 in treatment of cirrhosis-related hepatocellular carcinoma (HCC).Methods: For HCC patients with insufficient FLR, right-sided PVE was first performed, followed by percutaneous RFA to the tumor as a means to trigger FLR growth. When the FLR reached a safe level (at least 40%) and the blood biochemistry tests were in good condition, the hepatectomy was performed. FLR dynamic changes and serum biochemical tests were evaluated. Postoperative complications, mortality, intraoperative data and long-term oncological outcome were also recorded.Results: Seven patients underwent PVE+RFA for FLR growth between March 2016 and December 2019. The median baseline of FLR was 353 ml (28%), which increased to 539 (44%) ml after 8 (7–18) days of this strategy (p < 0.05). The increase of FLR ranged from 40% to 140% (median 47%). Five patients completed hepatectomy. The median interval between PVE+RFA and hepatectomy was 19 (15–27) days. No major morbidity ≥ III of Clavien-Dindo classification or in-hospital mortality occurred. One patient who did not proceed to surgery died within 90 days after discharge. After a median follow-up of 18 (range 3–50) months, five patients were alive.Conclusion: Sequential PVE+RFA is a feasible and effective strategy for FLR growth prior to extended hepatectomy and may provide a minimally invasive alternative for ALPPS stage-1 for treatment of patients with cirrhosis-related HCC.

Purpose To evaluate the safety and efficacy of percutaneous ultrasound-guided ‘three-step’ radiofrequency ablation (RFA) for the treatment of giant hepatic hemangioma. Materials and methods Patients with giant hepatic hemangioma who underwent percutaneous ultrasound-guided ‘three-step’ RFA (n = 52) and conventional RFA (n = 54) at our center from June 2013 to December 2017 were retrospectively analyzed. The ‘three-step’ RFA proceeds as follows. Step 1: Ablate the feeding artery of the hemangioma. Step 2: Aspirate blood from the tumor. Step 3: Ablation the lesion. Intraoperative information, postoperative recovery, therapeutic effects, and complications were compared between the two groups. Results The duration of RFA was significantly shorter (19.2 ± 0.8 min versus 44.5 ± 2.8 min, p

Abstract Background Radiofrequency ablation (RFA) for the treatment of small hepatocellular carcinoma (HCC) has a drawback of high recurrence rate. No-touch technique was developed to overcome it. However, it has barely been studied in Chinese populations. The aim of this study is to determine the safety and efficacy of no-touch RFA in the treatment of cirrhosis-based small HCC patients. Methods A total of 130 patients of small HCC in Southwest Hospital were enrolled in this study, 46 cases treated by no-touch RFA and 84 cases by conventional RFA. Treatment complications and tumor-free survival rate and overall survival rate were compared and analyzed. Results There were no significant differences in baseline confounding factors between the two groups. The ablation volume of no-touch RFA technique was significantly higher than conventional RFA (P = 0.002) but the remaining liver volume and treatment complications of the two techniques were the same (P = 0.702 and P = 0.269, respectively). Cox regression model revealed that conventional RFA was a predictive factor for short-term HCC recurrence (P = 0.041 for 2-year recurrence rate). Kaplan-Meier survival showed that tumor-free survival in no-touch group was significantly higher than conventional group (P = 0.047). Conclusions Our data showed that no-touch RFA provided a higher short-term tumor-free survival rate than conventional RFA but was as safe as conventional RFA.

Aim: To compare the short- and long-term treatment outcomes of bisegmentectomy 7–8 vs. right hepatectomy for patients with hepatocellular carcinoma and cirrhosis.Methods: Thirty six cirrhotic HCC patients with infiltration of right hepatic vein in segments 7–8 underwent bisegmentectomy 7–8 for small-for-size remanant liver under right hemi-hepatectomy. Its outcome was compared with a case-matched control group of cirrhotic HCC patients who underwent right hemi-hepatectomy during the study period.Results: The study group consisted of 36 patients and the control group 36 patients selected from 1,526 patients matched with age, tumor size, tumor location, and Pugh-Child staging. There were no significant differences between the two groups in operative parameters and in perioperative main complications which included hemorrhage, bile leakage, ascites, pleural effusion, and liver failure. The overall morbidity rate and morbidity rate classified according to Clavien's classification were similar. There was no in-hospital mortality or 90 day post-operative mortality. The mean follow-up was 30 and 32 months for the study group and control group, respectively. The disease free survival rate (DFS) for the study group was just significantly better than the control group. The median DFS was 24 months for the study group and 8 months for the control group (P = 0.049). Meanwhile, the median cumulative overall survival was 35 months for the study group and 27 months for the control group (P = 0.494).Conclusion: Bisegmentectomy 7–8 was safe and feasible for selected cirrhosis patients, and did not increase the perioperative risk and inferior long-term overall survival outcomes. It extended the indications for liver resection in patients with borderline volumes of future liver remnant for HCC cirrhotic liver.

Purpose: Radiofrequency ablation (RFA) is widely accepted as a curative treatment for small hepatocellular carcinoma (HCC). However, insufficient RFA (IRFA) can lead to rapid local recurrence. The underlying mechanisms remain poorly understood. This study aimed to elucidate the role and regulatory mechanisms of autophagy in the recurrence of HCC after IRFA. Materials and methods: SMMC7721 and Huh7 cells were exposed to sublethal heat stress to stimulate the transition zone of IRFA treatment. The levels of autophagy were measured by western blot, immunofluorescence and transmission electron microscopy. Functional assays, such as CCK-8, EdU incorporation and flow cytometry, were performed to determine the role of heat-induced autophagy. The involved signaling pathways were explored by western blot. Finally, the antitumor effects of chloroquine (CQ) on heat-treated HCC cells were evaluated via an in vivo xenograft tumor model. Results: Sublethal heat stress induced autophagy in a temperature- and time-dependent manner in HCC cells. Furthermore, the inhibition of autophagy by CQ or siRNA targeting the autophagy-related genes Beclin-1 and Atg5 enhanced heat-induced apoptosis. The combination of CQ and heat treatment significantly suppressed tumor growth both in vitro and in vivo. Mechanistically, we reported for the first time that the ATP-AMPK-mTOR signaling pathway was involved in heat-induced autophagy. Conclusions: Heat stress induced protective autophagy against heat-induced apoptosis in HCC via the ATP-AMPK-mTOR axis, suggesting that targeting autophagy may be a promising strategy for improving the efficacy of RFA treatment for HCC.

Abstract Background Sub-lethal heat treatment characterizes a transition zone of radiofrequency ablation (RFA) which explains hepatocellular carcinoma (HCC) residual cancer occurrence in this area after RFA treatment. The biochemistry of residual cancer cell recurrence is poorly understood, but long noncoding RNAs (lncRNAs) may have aberrant expression that is associated with diverse cancers. Thus, we measured lncRNA gene expression in sub-lethally heat-treated HCC cells using microarray. Method Differentially expressed lncRNA and mRNA were measured with an Agilent Human lncRNA + mRNA Array V4.0 (4 × 180 K format) containing 41,000 lncRNAs and 34,000 mRNAs. Bioinformatics analysis was used to assess differentially expressed lncRNA and mRNA. Seven lncRNA and seven mRNA were validated by qRT-PCR analysis in HCC cells. Results Genome-wide lncRNA and mRNA expression data in sub-lethal heat-treated SMMC-7721 HCC cells 558 lncRNA and 250 mRNA were significantly up-regulated and 224 lncRNA and 1031 mRNA down-regulated compared to normal cultured SMMC-7721 cells. We demonstrated for the first time that ENST00000570843.1, ENST00000567668.1, ENST00000582249.1, ENST00000450304.1, TCONS_00015544, ENST00000602478.1, TCONS_00001266 and ARC, IL12RB1, HSPA6 were upregulated, whereas STAT3, PRPSAP1, MCU, URB2 were down-regulated in sub-lethally heat-treated HCC cells. Conclusions lncRNA expression data in sub-lethally heat-treated HCC cells will provide important insights about lncRNAs’ contribution to HCC recurrence after RFA treatment.

Limited data exists in China on the comparative cost of gadolinium ethoxybenzyl diethylenetriamine magnetic resonance imaging (Gd-EOB-DTPA-MRI) with other imaging techniques. This study compared the total cost of Gd-EOB-DTPA-MRI with multidetector computed tomography (MDCT) and extracellular contrast media-enhanced MRI (ECCM-MRI) as initial imaging procedures in patients with suspected hepatocellular carcinoma (HCC). We developed a decision-tree model on the basis of the Chinese clinical guidelines for HCC, which was validated by clinical experts from China. The model compared the diagnostic accuracy and costs of alternative initial imaging procedures. Compared with MDCT and ECCM-MRI, Gd-EOB-DTPA-MRI imaging was associated with higher rates of diagnostic accuracy, i.e. higher proportions of true positives (TP) and true negatives (TN) with lower false positives (FP). Total diagnosis and treatment cost per patient after the initial Gd-EOB-DTPA-MRI evaluation was similar to MDCT (¥30,360 vs. ¥30,803) and lower than that reported with ECCM-MRI (¥30,360 vs. ¥31,465). Lower treatment cost after initial Gd-EOB-DTPA-MRI was driven by reduced utilization of confirmatory diagnostic procedures and unnecessary treatments. The findings reported that Gd-EOB-DTPA-MRI offered higher diagnostic accuracy compared with MDCT and ECCM-MRI at a comparable cost, which indicates Gd-EOB-DTPA-MRI could be the preferred initial imaging procedure for the diagnosis of HCC in China.

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.

BACKGROUND AND AIM: Researchers have demonstrated dead cells in radiofrequency ablation (RFA) lesions that have morphological similarities to viable tumor cells and are thus referred to as ghost cells. However, studies on how long ghost cells persist have not been systematically performed. METHODS: A tumor model was established by implanting VX2 tumor tissue into the livers of 48 New Zealand rabbits. Two weeks later, these tumors were eliminated with RFA. The lesions were resected at 0 weeks, 1 week, 2 weeks, 4 weeks, 8 weeks, or 12 weeks after treatment, and samples were stained either with hematoxylin and eosin (HE) or nicotinamide adenine dinucleotide (NADH). The presence of the cells and the morphological changes that they underwent were examined by light microscopy. RESULTS: Four weeks after RFA, there were no obvious morphological changes observed in HE-stained ghost cells, and NADH staining revealed no viable cells. Eight weeks after RFA, the cell structure became indistinct. Twelve weeks after RFA, ghost cells were no longer present. CONCLUSIONS: The morphological characteristics of ghost cells are maintained for at least 4 weeks, during which time HE staining cannot be used to differentiate ghost cells from residual tumor cells. NADH staining for cell viability is necessary to differentiate residual tumor cells from ghost cells. This evidence adds to our understanding of the mechanisms of RFA when used on solid tumors.

Abstract Background Hepatic resection is currently still the best choice of therapeutic strategies for liver cancer, but the long-term survival rate after surgery is unsatisfactory. Most patients develop intra- and/or extrahepatic recurrence. The reasons for this high recurrence rate are not entirely clear. Recent studies have indicated that ischemia-reperfusion injury to the liver may be a significant factor promoting tumor recurrence and metastasis in animal models. If this is also true in humans, the effects of the Pringle maneuver, which has been widely used in hepatectomy for the past century, should be examined. To date, there are no reported data or randomized controlled studies examining the relationship between use of the Pringle maneuver and local tumor recurrence. We hypothesize that the long-term prognosis of patients with liver cancer could be worsened by use of the Pringle maneuver due to an increase in the rate of tumor recurrence in the liver remnant. We designed a multicenter, prospective, randomized surgical trial to test this hypothesis. Methods At least 498 eligible patients from five participating centers will be enrolled and randomized into either the Pringle group or the non-Pringle group in a ratio of 1:1 using a permuted-blocks randomization protocol. After the completion of surgical intervention, patients will be included in a 3-year follow-up program. Discussion This multicenter surgical trial will examine whether the Pringle maneuver has a negative effect on the long-term outcome of hepatocellular carcinoma patients. The trial will also provide information about prognostic differences, safety, advantages and disadvantages between Pringle and non-Pringle surgical procedures. Ultimately, the results will increase the available information about the effects of ischemia-reperfusion injury on tumor recurrence, which will be of immense benefit to general surgery. Trial registration http://www.clinicaltrials.gov NCT00725335

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumor of the gastrointestinal tract, and typically metastasize to the liver. In patients with recurrent metastatic GISTs, no single treatment is effective. The current study reports a case of GIST with 27 metastases in the liver, which was successfully treated using radiofrequency ablation (RFA) combined with surgical resection and imatinib therapy. The patient remains tumor-free 36 months after the first RFA treatment. This case suggests that comprehensive therapy including surgical resection, RFA and imatinib, may be an effective strategy for the treatment of GIST with multiple liver metastases. [ABSTRACT FROM AUTHOR]

Background: Neoplastic and bland portal vein thrombi (PVT) are both common in patients with hepatocellular carcinoma (HCC). The correct discrimination of them is essential for therapeutic strategies planning and survival predicting. The current study aims to investigate the value of susceptibility-weighted imaging (SWI) in differentiating bland from neoplastic PVT in HCC patients. Methods: 20 HCC patients with bland PVT and 22 HCC patients with neoplastic PVT were imaged with non-contrast SWI at 3.0 Tesla MRI. The signal intensity (SI) of the PVT and HCC lesions in the same patients was compared on SW images. The phase values of the PVT were compared between neoplastic and bland thrombi cohorts. Receiver operator characteristics (ROC) analysis was conducted to evaluate the diagnostic ability of the phase values for neoplastic and bland thrombi discrimination. Results: 20 of 22 neoplastic PVT were judged similar SI and 2 were judged lower SI than their HCC. For 20 bland PVT, 19 were judged lower SI and 1 was judged similar SI as their HCC (P<0.001). The average phase values (0.361 ± 0.224) of the bland PVT were significantly higher than those of the neoplastic PVT (-0.328 ± 0.127, P<0.001). The AUC for phase values in differentiating bland from neoplastic PVT was 0.989. The best cut-off value was -0.195, which gave a sensitivity of 95% and a specificity of 95.5%. Conclusions: SW imaging appears to be a promising new method for distinguishing neoplastic from bland PVT. The high sensitivity and specificity suggest its high value in clinical practice. [ABSTRACT FROM AUTHOR]

Radiofrequency ablation (RFA) is a minimally invasive technique used to treat liver tumors. The current study presents the case of a patient with hepatocellular carcinoma who suffered from post-operative pericardial effusion following RFA treatment. We hypothesize that RFA thermal conduction may damage the diaphragm and pericardium, leading to local edema in the pericardium. RFA is a minimally invasive technique, however, adequate preparatory work must be performed prior to surgery, including a comprehensive assessment of the patient. During surgery, the location and extent of the region to receive RFA must be determined precisely in order to reduce the range of damage and to avoid post-operative complications. This study describes a case of pericardial effusion caused by RFA of liver cancer. We analyzed the causes and preventive measures for pericardial effusion in order to contribute to the prevention pericardial effusion that is complicated by RFA of liver cancer. [ABSTRACT FROM AUTHOR]

Current options for the treatment of the early-stage HCC conforming to the Milan criteria consist of liver transplantation, hepatic resection (HR), transcatheter arterial chemoembolization (TACE) and radiofrequency ablation (RFA) .Whether HR or RFA is the better treatment for early HCC has long been debated. The aim of our paper is to compare the therapeutic effects of radiofrequency ablation (RFA) and hepatic resection (HR) in the treatment of early-stage hepatocellular carcinoma (HCC). Controlled trials evaluating the efficacy between RFA and HR for the treatment of early-stage HCC published before June 2013 were searched electronically using MEDLINE, PubMed, Cochrane Library, and EMBASE databases. Using inclusion and exclusion criteria, two randomized controlled trials and 10 nonrandomized controlled trials were included in the meta- analysis. The results showed that the 3,5-year overall survival rates and 1,3,5 disease-free survival rates were significantly lower after RFA than after HR. However, complications after treatment were less common and the length of hospital stay was significantly shorter after RFA. Additionally, there was no significant difference in the 1-year overall survival rate between RFA and HR. The conclusions of the results show that the difference in the short-term effectiveness of RFA and HR in the treatment of small HCC is not notable, but the long-term efficacy of HR is better than that of RFA. However, HR is associated with more complications and a longer hospital stay. [ABSTRACT FROM AUTHOR]

The present study was designed to investigate the efficacy and safety of continuous occlusion of the hepatic artery proper combined with intermittent use of the Pringle maneuver for reduction of blood loss during enucleation of giant liver hemangiomas. A retrospective study was performed on 115 patients who underwent enucleation of giant liver hemangiomas with or without continuous occlusion of the hepatic artery proper at a tertiary care university hospital. The characteristics of patients and perioperative parameters including intraoperative blood loss, the degree of ischemia–reperfusion injury, the incidence and severity of postoperative complications, and the length of hospital stay were summarized and compared in the two groups. Seventy-three and 42 patients underwent enucleation of hepatic hemangiomas with and without continuous occlusion of the hepatic artery proper, respectively. The Pringle maneuver was routinely used in all patients in cycles of 15/5 min of clamp/unclamp times. Patient characteristics were comparable between the two groups. Intraoperative blood loss and blood transfusion in the continuous occlusion group were significantly lower than in the non-occlusion group ( P < 0.001 and P = 0.012, respectively). In a comparison of the two groups, there were no significant differences in the changes of the perioperative serum aspartate transaminase and total bilirubin levels ( P = 0.086, P = 0.829, respectively), and in the postoperative hospital stay and surgical complications according to Clavien’s classification ( P = 0.378, P = 0.227, respectively). Continuous occlusion of the hepatic artery proper when added to intermittent use of the Pringle maneuver significantly reduced intraoperative blood loss when compared with intermittent Pringle maneuver alone. Enucleation of giant hepatic hemangiomas using continuous occlusion of the hepatic artery proper in addition to intermittent application of the Pringle maneuver for up to 1 h was safe. [ABSTRACT FROM AUTHOR]

The objective of this study was to compare the short- and long-term outcomes of radiofrequency-assisted liver resection (RFLR) and conventional clamp-crushing liver resection (CCLR) and to evaluate the safety and efficiency of RFLR. Between January 2008 and December 2012, a total of 597 patients with hepatocellular carcinoma (HCC) who underwent curative hepatectomy were identified. A total of 272 patients underwent RFLR, and 325 patients received CCLR. The short- and long-term outcomes were compared. The patients in the RFLR and CCLR groups showed similar baseline characteristics. The RFLR group showed less intraoperative blood loss (485.5 vs. 763.2 mL, p = 0.003), a lower transfusion requirement rate (19.1 vs. 31.7%, p ⩽ 0.01), shorter surgery duration (211 vs. 296 min, p ⩽ 0.01) and a lower vascular inflow occlusion rate (25.7 vs. 33.8%, p = 0.032). No significant postoperative changes in bilirubin or liver enzymes were observed in the two groups. The degree of postoperative complications and morbidity did not significantly differ between the two groups. There were no significant differences in the 1-, 2- and 3-year overall survival rates (73.8%, 58.5%, and 55.7% vs. 80.8%, 65.8%, and 56.2%, respectively) or disease-free rates (51.9%, 47.2%, and 46.0% vs. 54.5%, 44.9%, and 38.5%, respectively) between the RFLR and CCLR groups. These results suggested RFLR was a safe and efficient method for patients with HCC. RFLR was associated with decreased blood loss, fewer blood transfusions, shorter surgery times and less vascular inflow occlusion application. The RFLR group did not show increased liver injury or postoperative morbidity or mortality. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the clinical utility of simultaneous measurement of alphafetoprotein (AFP) and des-γ-carboxy prothrombin (DCP) for hepatocellular carcinoma (HCC) diagnosis in Chinese patients predominantly caused by hepatitis B virus infection by a multi-center case-controlled study. Subjects were 1,153 individuals from three major hospitals in China, including 550 cases in HCC group, 164 in Malignant disease group, 182 in Benign disease group, 85 in Chronic liver disease group, and 173 in Normal group. Serum levels of AFP and DCP were measured and clinicopathological features were determined for all subjects. Results showed that the levels of DCP and AFP were significantly higher in HCC group (550 patients, 74.18% with HBV infection) than that in other four groups (P < 0.001). Receiver operating curves (ROC) indicated the optimal cut-off value was 86 mAU/ mL for DCP with a sensitivity of 71.50% and specificity of 86.30%, and 21 ng/mL for AFP with a sensitivity of 68.00% and specificity of 93.20%. The area under ROC curve was 0.846 for DCP, 0.832 for AFP, and 0.890 for the combination of DCP and AFP. The combination of DCP and AFP resulted in a higher Youden index and a sensitivity of approximately 90%, even for small tumors. The simultaneous measurement of AFP and DCP could achieve a better sensitivity in diagnosing Chinese HCC patients, even for small tumors. [ABSTRACT FROM AUTHOR]

In China, hepatocellular carcinoma (HCC) is the second most common cancer in urban areas and first most common in rural areas. It ranks as the second leading cause of cancer-related deaths in males and the third leading cause of cancer-related deaths in females, with the total mortality rate of 26.26 per 100,000. Currently, people with hepatitis B virus (HBV) infection are a major population at risk of developing HCC in China. In fact, there are 93 million Chinese who are HBV carriers, and about 20 million of them have chronic HBV infection. Several cohort studies have shown that screening high-risk patients with HBV or HCV-related chronic liver disease may improve the rate of early HCC detection and the rate of curative treatment. However, a government-funded national program to screen for high-risk patients with HBV-related chronic liver disease has yet to be established in China. Although several remarkable advances in HCC management have been made during the past few decades, most patients with HCC still present with advanced-stage disease, thus reducing the chance of curative treatment. Based on firsthand experience in Japan and other countries or areas, this work examined the current status, challenges, and prospects for the future of early detection of HCC in China. Findings suggested the need for a systematic guideline for the standardized management of HCC, a government-funded nationwide screening and surveillance program for high-risk patients with HBV-related chronic liver disease, and extensive use of des-γ-carboxyprothrombin (DCP) as a screening tool in China in order to facilitate the early detection of HCC in China. [ABSTRACT FROM AUTHOR]