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Background: The aim of this study was to compare the efficacy of laparoscopic liver resection versus radiofrequency ablation for treatment of small hepatocellular carcinoma. Methods: This single-centre RCT was conducted at a tertiary referral centre in China. Patients with small hepatocellular carcinoma who had a single nodule no larger than 5 cm, or up to three nodules of 3 cm or smaller, were eligible. Patients were assigned randomly in a 1 : 1 ratio to either laparoscopic liver resection or radiofrequency ablation. Blinding was not attempted. Sample size calculations led to 75 patients per group. The primary outcome was overall survival, and the secondary outcome was recurrence-free survival. Results: Seventy-five patients were included in each group. Overall survival (HR 1.26, 95% c.i. 0.69 to 2.30; P = 0.451) and recurrence-free survival (HR 1.34, 0.86 to 2.08; P = 0.189) did not differ between the resection and ablation groups. The 1-, 3- and 5-year overall survival rates were 94.7, 80.0, and 74.7% respectively after laparoscopic liver resection versus 93.3, 78.7, and 67.9% after radiofrequency ablation. Corresponding recurrence-free survival rates were 78.7, 61.3, and 51.6%, and 69.3, 53.3, and 41.0%, respectively. Conclusion: For small hepatocellular carcinoma, percutaneous radiofrequency ablation provides therapeutic effects similar to those of laparoscopic liver resection. Registration number: NCT02243384 (http://www.clinicaltrials.gov). Percutaneous radiofrequency ablation may provide therapeutic effects similar to those of laparoscopic liver resection for patients with hepatocellular carcinoma. The choice of treatment should be based on the regional economic conditions, the patient's quality of life, and the skill level of the medical team, and additional research results and guidelines should be considered comprehensively to achieve precise treatment and better benefit the patient. Lay Summary: Percutaneous radiofrequency ablation may provide similar therapeutic effects to laparoscopic liver resection for patients with small hepatocellular carcinoma. This study compared the two treatments. Survival was similar after the two treatments. The choice of treatment may depend on the patient's preference and local availability. [ABSTRACT FROM AUTHOR]

Simple Summary: The liver function reserve of patients with hepatocellular carcinoma (HCC) is heterogeneous. The preoperative accurate evaluation of liver function has a vital role in the prevention of unfavorable postoperative complications such as post-hepatectomy liver failure. In this study, unsupervised clustering analysis of radiomics features extracted from preoperative gadoxetic-acid-enhanced MRIs was performed for liver function stratification on 276 HCC patients. Two distinct subgroups were identified (i.e., subgroups 1 and 2). Subgroup 2 had impaired liver function as presented by older age, more albumin–bilirubin grades 2 and 3, and a higher indocyanine green retention rate than that of subgroup 1 (all p < 0.05). Compared with subgroup 1, subgroup 2 was associated with a higher risk of postoperative liver failure, postoperative complications, and longer hospital stays (all p < 0.05). Our findings indicate the potential for the use of radiomics features based on preoperative gadoxetic-acid-enhanced MRI for noninvasive liver function assessment in HCC patients. Objective: To identify subgroups of patients with hepatocellular carcinoma (HCC) with different liver function reserves using an unsupervised machine-learning approach on the radiomics features from preoperative gadoxetic-acid-enhanced MRIs and to evaluate their association with the risk of post-hepatectomy liver failure (PHLF). Methods: Clinical data from 276 consecutive HCC patients who underwent liver resections between January 2017 and March 2019 were retrospectively collected. Radiomics features were extracted from the non-tumorous liver tissue at the gadoxetic-acid-enhanced hepatobiliary phase MRI. The reproducible and non-redundant features were selected for consensus clustering analysis to detect distinct subgroups. After that, clinical variables were compared between the identified subgroups to evaluate the clustering efficacy. The liver function reserve of the subgroups was compared and the correlations between the subgroups and PHLF, postoperative complications, and length of hospital stay were evaluated. Results: A total of 107 radiomics features were extracted and 37 were selected for unsupervised clustering analysis, which identified two distinct subgroups (138 patients in each subgroup). Compared with subgroup 1, subgroup 2 had significantly more patients with older age, albumin–bilirubin grades 2 and 3, a higher indocyanine green retention rate, and a lower indocyanine green plasma disappearance rate (all p < 0.05). Subgroup 2 was also associated with a higher risk of PHLF, postoperative complications, and longer hospital stays (>18 days) than that of subgroup 1, with an odds ratio of 2.83 (95% CI: 1.58–5.23), 2.41(95% CI: 1.15–5.35), and 2.14 (95% CI: 1.32–3.47), respectively. The odds ratio of our method was similar to the albumin–bilirubin grade for postoperative complications and length of hospital stay (2.41 vs. 2.29 and 2.14 vs. 2.16, respectively), but was inferior for PHLF (2.83 vs. 4.55). Conclusions: Based on the radiomics features of gadoxetic-acid-enhanced MRI, unsupervised clustering analysis identified two distinct subgroups with different liver function reserves and risks of PHLF in HCC patients. Future studies are required to validate our findings. [ABSTRACT FROM AUTHOR]

Background: The optimal occlusion and reperfusion time to balance blood loss and ischemia–reperfusion injury to the remnant liver remains unclear. The aim was to explore the clinical impact of prolonging the hepatic hilum occlusion time from 15 to 20 min using the intermittent Pringle maneuver (IPM) combined with controlled low central venous pressure (CLCVP). Methods: A total of 151 patients were included and divided into an experimental group (Group 20,75 cases) and a control group (Group 15,76 cases). In both groups, the hepatic hilum was blocked by the IPM combined with CLCVP to control intraoperative hepatic cross-sectional bleeding. The preoperative, intraoperative and postoperative parameters and safety were compared between the two groups. Results: There were no significant differences between the two groups in the postoperative aminotransferase serum levels (p > 0.05). However, the operation time in Group 20 was significantly lower than that in Group 15 (222.4 ± 87.8 vs. 250.7 ± 94.5 min, p < 0.05). The procalcitonin at 1 day after operation in Group 20 was lower than that at 1 day after operation in Group 15 (0.78 ± 0.66 vs. 1.45 ± 1.33 ng/mL, p < 0.05). There was no significant difference in the incidence of postoperative bleeding, postoperative bile leakage and postoperative infection between the two groups (p > 0.05). Conclusions: For patients with hepatocellular carcinoma after hepatitis B cirrhosis, it is feasible and safe to prolong the hepatic hilum occlusion time from 15 to 20 min using the IPM combined with CLCVP. [ABSTRACT FROM AUTHOR]

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 < D ≤ 3 cm subgroups in two groups showed no significant difference (p = 0.578). Conclusions: The RFS rates of single HCC less than 3 cm treated by NT‐RFA was significantly higher than that of C‐RFA. Due to a larger ablation range and safety margin, NT‐RFA could significantly reduce LTP and improve RFS. Dual‐electrode NT‐RFA can significantly improve the RFS rate of patients with HCC less than 2 cm, but there is no obvious advantage compared with C‐RFA in the treatment of HCC over 2 cm. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. 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. 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 < 0.001), there was no significant difference in the cumulative overall survival time or the incidence of portal vein thrombosis between the two groups (P = 0.670, 0.083). Compared with the control group, the study group had significantly less intraoperative blood loss, and lower incidences of postoperative pleural effusion and pneumonia (all P < 0.05). Open radiofrequency ablation, splenectomy and pericardial devascularization for small HCCs with portal hypertension and hypersplenism can be an alternative therapy for a subset of carefully selected patients under the shortage of liver donors. [ABSTRACT FROM AUTHOR]

Aim: The 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. Methods: Clinicopathologic 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. Results: Three 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. Conclusions: The 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. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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 FROM AUTHOR]

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 < 0.05). With rescue RFA/PEI applied, KGR increased significantly to 4% (2-5%) compared with that before the rescue procedures (p < 0.05). Five patients proceeded to RALPPS stage-2. Two patients failed: In one patient the FLR remained at a constant level even after four rescue PEIs. The other patient developed metastasis. Except one patient died after RALPPS stage-2, no severe complications (Clavien-Dindo ≥ IIIb) occurred among remaining six patients.Conclusions: Rescue RFA/PEI may provide an alternative to trigger further growth of the FLR in patients with cirrhosis-related HCC showing insufficient FLR after RALPPS stage-1. Trial registration Retrospectively registered. [ABSTRACT FROM AUTHOR]

Abstract Background To understand the molecular mechanisms of caveolin-1 downregulation by hepatitis B virus X protein (HBx). Methods The DNA methylation status of the caveolin-1 promoter was examined by nested methylation-specific PCR of 33 hepatitis B virus (HBV)-infected hepatocellular carcinoma (HCC) samples. The SMMC-7721 hepatoma cell line was transfected with a recombinant HBx adenoviral vector, and the effects of HBx protein on caveolin-1 expression and promoter methylation were examined and confirmed by sequencing. A reporter gene containing the caveolin-1 promoter region was constructed, and the effects of HBx on the transcriptional activity of the promoter were also studied. Results Methylation of the caveolin-1 promoter was detected in 84.8% (28/33) of HBV-infected HCC samples. Expression of caveolin-1 was significantly downregulated (P = 0.022), and multiple CpG sites in the promoter region of caveolin-1 were methylated in SMMC-7721 cells after HBx transfection. Transfected HBx significantly suppressed caveolin-1 promoter activity (P = 0.001). Conclusions HBx protein induces methylation of the caveolin-1 promoter region and suppresses its expression.

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. [ABSTRACT FROM AUTHOR]

Purpose: To assess the long-term outcome of 516 consecutive patients treated with multiple-electrode switching system (MESS) radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) that met the Milan criteria. Materials and methods: We performed 522 MESS RFAs on 516 patients from December 2006 to June 2011. A total of 956 tumours that met the Milan criteria with an average diameter of 2.64 cm (range, 0.9-4.6 cm) were treated with MESS RFA. Ultrasonic contrast and serum α-fetoprotein (AFP) were measured every 2 months during the first postoperative year and every 4 months thereafter. Enhanced computed tomography was performed every 6 months. Survival was estimated using the Kaplan-Meier method. Follow-up was censored at 60 months. Multivariate analysis was performed using the Cox proportional hazards model. Results: For the 956 HCC tumours, the complete ablation rate with MESS was 98.83% (510/516). During a median of 34 months (IQR, 23-52 months) of follow-up, 171 patients died and 4 were lost to follow-up (15, 30, 38 and 42 months). The cumulative incidence of local tumour progression at 1, 3 and 5 years was 0.39%, 4.96% and 6.66%, respectively, and the 1-, 3- and 5-year overall survival was 99.42%, 83.97% and 68.42%, respectively. Tumour size >30 mm was the only parameter that was predictive of local tumour progression (p < .0001). Risk factors associated with overall survival included prothrombin time >14 s, serum AFP levels >200 ng/mL and tumour abutting vessel diameter <5 mm. The complication rate was 1.74%. Conclusion: MESS RFA is a safe and effective method for HCC treatment. This approach results in a high local progression-free survival for HCC tumours that meet the Milan criteria. [ABSTRACT FROM AUTHOR]

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. [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]

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: 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]

Simple Summary: Microvascular invasion (MVI) is regarded as a sign of early metastasis in liver cancer and can be only diagnosed by a histopathology exam in the resected specimen. Preoperative prediction of MVI status may exert an effect on patient treatment management, for instance, to expand the resection margin. Radiomics can identify delicate imaging features from routinely used radiological images that are invisible to the naked eye and has been increasingly adopted to predict MVI. We reviewed the available radiomics models to evaluate their role in the prediction of MVI. The discriminative capacity of the models ranged from 0.69 to 0.94. Even though the studies were preliminary and the methodologic quality was suboptimal, radiomics models hold promise for the accurate and non-invasive prediction of MVI. In accordance with a standardized radiomics workflow, future prospective studies with external validation are expected to provide a reliable and robust prediction tool for clinical implementation. Preoperative prediction of microvascular invasion (MVI) is of importance in hepatocellular carcinoma (HCC) patient treatment management. Plenty of radiomics models for MVI prediction have been proposed. This study aimed to elucidate the role of radiomics models in the prediction of MVI and to evaluate their methodological quality. The methodological quality was assessed by the Radiomics Quality Score (RQS), and the risk of bias was evaluated by the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2). Twenty-two studies using CT, MRI, or PET/CT for MVI prediction were included. All were retrospective studies, and only two had an external validation cohort. The AUC values of the prediction models ranged from 0.69 to 0.94 in the test cohort. Substantial methodological heterogeneity existed, and the methodological quality was low, with an average RQS score of 10 (28% of the total). Most studies demonstrated a low or unclear risk of bias in the domains of QUADAS-2. In conclusion, a radiomics model could be an accurate and effective tool for MVI prediction in HCC patients, although the methodological quality has so far been insufficient. Future prospective studies with an external validation cohort in accordance with a standardized radiomics workflow are expected to supply a reliable model that translates into clinical utilization. [ABSTRACT FROM AUTHOR]

Background: In patients with cirrhosis excessive hemorrhage and the need for blood transfusion are associated with increased postoperative morbidity and mortality as well as a poor long-term outcome. Saline-linked radiofrequency dissecting sealer (TissueLink) is a recent advance in technology that improves hemostasis during difficult liver resections. Preliminary studies have shown that this technique reduces blood loss without inflow occlusion. Patients and methods: A controlled study was performed on 122 consecutive patients with cirrhosis who underwent liver resection for hepatocytotic carcinoma. The outcomes of liver transection with clamp crushing and TissueLink were compared to evaluate which strategy is most beneficial to the patients. Results: Both intraoperative blood loss and blood transfusion requirements were significantly higher in the crushing clamp group than in the TissueLink group (P = 0.047 and P = 0.031, respectively). In addition, a significantly higher number of patients required a blood transfusion in the crushing clamp group (P < 0.001). However, the transection time was significantly faster in the crushing clamp group than in the TissueLink group (P < 0.001). The number of patients that required Pringle''s maneuver was markedly higher in the crushing clamp group (P < 0.001). In addition, the hemostasis time was significantly longer in the crushing clamp group (P < 0.001). The serum aspartate aminotransferase levels 3 and 7 days after surgery were significantly higher in the crushing clamp group than in the TissueLink group (P = 0.035 and P = 0.003, respectively). Serum total bilirubin levels were markedly increased 3 days after surgery in the crushing clamp group than in the TissueLink group (P = 0.011). Biliary leakage occurred in a higher number of crushing clamp patients (six) than TissueLink patients (three), although this difference was not significant. The operative morbidity not including biliary leakage was higher in the crushing clamp group than the TissueLink group (nine patients versus five patients, respectively). Conclusion: This study reveals that the TissueLink procedure has beneficial effects during liver transection under cirrhotic conditions in terms of blood loss and reperfusion-related liver injury. However, this procedure requires a significantly longer transection time of the parenchyma. [Copyright &y& Elsevier]

The therapeutic efficacy of radiofrequency ablation (RFA) against liver cancer is often limited by proliferation and metastasis of residual tumor cells. These phenomena are closely associated with the Warburg effect, wherein ErbB2 is activated. While RFA inhibits the Warburg effect of residual tumor cells at the early stage, the specific mechanisms remain unclear. We explored the regulatory relationship between the long noncoding RNA ENST00000570843.1 (lncENST) and ErbB2 using lentiviral transfection of lncENST and ErbB2 overexpression/interference vectors in in vitro and in vivo models of hepatocellular carcinoma in the presence of sublethal heat at 50°C. ErbB2-mediated Warburg effect was suppressed by lncENST, as manifested by reduced glucose uptake and lactic acid production in SMMC-7721 cells. lncENST also increased tumor apoptosis and inhibited tumor progression in nude Balb/c mice for up to 28 days after RFA. Additionally, we predicted through bioinformatic analysis that the promoter of ErbB2 binds to the transcription factor Nkx2-5, resulting in a negative regulatory effect. This speculation was confirmed by chromatin immunoprecipitation of the Nkx2-5 protein and ErbB2, indicating that ErbB2 transcription was curbed by Nkx2-5. We propose that lncENST downplays the Warburg effect in residual tumor cells by downregulating ErbB2 via Nkx2-5 activation. This study is aimed at providing molecular targets that can prevent residual tumor cell proliferation after RFA, with clinical significance in hepatocellular carcinoma treatment. [ABSTRACT FROM AUTHOR]

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]