Laparoscopic liver resection versus radiofrequency ablation for small hepatocellular carcinoma: randomized clinical trial.

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 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.

Regorafenib combined with a PD-1 inhibitor in the second-line setting for unresectable hepatocellular carcinoma in real-world practice.

Background: Most advanced hepatocellular carcinoma (HCC) cases administered molecular targeted agents and/or anti-programmed cell death-1 (PD-1) inhibitors have no response or develop resistance. Moreover, second-line therapies still cannot provide beneficial clinical outcomes. A pilot study assessing combined regorafenib and PD-1 inhibitor as second-line treatment of advanced HCC reported promising effectiveness. Methods: The current single-center, retrospective, real-world study was carried out between January 2019 and July 2021. Advanced HCC cases were administered second-line regorafenib combined with a PD-1 inhibitor or regorafenib alone were assessed. Progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR) were determined. Results: Totally 46 HCC cases were analyzed, most of whom underwent previous systemic treatment comprising targeted therapy and immunotherapy. Tumor response was evaluated in 25 and 21 individuals in the regorafenib + PD-1 inhibitor and regorafenib monotherapy groups, respectively: ORRs were 21.7% and 8.7%, and DCRs were 47.8% and 32.6%, respectively. Median PFS was markedly longer in the regorafenib plus PD-1 inhibitor group (11.5 months) compared with the regorafenib monotherapy group (5.1 months, P=0.049). Conclusions: This study suggested regorafenib and a PD-1 inhibitor in combination may provide significant clinical benefits in HCC cases showing progression following first-line treatment. Further analysis in real-world studies with large cohorts is warranted to confirm these findings.

Impact of body composition on the prognosis of hepatocellular carcinoma patients treated with transarterial chemoembolization: A systematic review and meta-analysis.

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.

A radiomics model based on preoperative gadoxetic acid-enhanced magnetic resonance imaging for predicting post-hepatectomy liver failure in patients with hepatocellular carcinoma.

Background: Post-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. Aims: This 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. Methods: A 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. Results: The 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. Conclusion: A 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.

Unsupervised Machine Learning of MRI Radiomics Features Identifies Two Distinct Subgroups with Different Liver Function Reserve and Risks of Post-Hepatectomy Liver Failure in Patients with Hepatocellular Carcinoma.

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.

Development and External Validation of a Radiomics Model Derived from Preoperative Gadoxetic Acid-Enhanced MRI for Predicting Histopathologic Grade of Hepatocellular Carcinoma.

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.

Long-term efficacy of no-touch radiofrequency ablation in the treatment of single small hepatocellular carcinoma: A single center long-term follow-up study.

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.

Intermittent Pringle maneuver combined with controlled low Central venous pressure prolongs hepatic hilum occlusion time in patients with hepatocellular carcinoma complicated by post hepatitis B cirrhosis: a randomized controlled trial.

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.

Open Radiofrequency Ablation Combined with Splenectomy and Pericardial Devascularization vs. Liver Transplantation for Hepatocellular Carcinoma Patients with Portal Hypertension and Hypersplenism: A Case-Matched Comparative Study.

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 < 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). CONCLUSION: 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.

Transcriptomic and metabolomic analysis of peri-tumoral hepatic tissue in hepatocellular carcinoma: unveiling the molecular landscape of immune checkpoint therapy resistance.

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.

Radiofrequency ablation in the treatment of hepatocellular carcinoma.

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.

A Radiomics Model Based on Gd-EOB-DTPA-Enhanced MRI for the Prediction of Microvascular Invasion in Solitary Hepatocellular Carcinoma ≤ 5 cm.

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.

Preoperative Assessment of Abdominal Adipose Tissue to Predict Microvascular Invasion in Small Hepatocellular Carcinoma.

Background and Aims: Microvascular invasion (MVI) affects recurrence after treatment of small hepatocellular carcinoma (sHCC) of ≤3 cm in size. The present study aimed to investigate whether abdominal subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), and intermuscular adipose tissue (IMAT) are associated with MVI in patients with sHCC. Methods: A total of 124 patients with pathologically-confirmed sHCC diagnosed on surgical resection at the First Hospital Affiliated to Army Military University were recruited and divided into two groups according to MVI classification criteria (i.e., MVI-positive or MVI-negative). The SAT, VAT, and IMAT areas at the lumbar 3 vertebral level were imaged with abdominal computed tomography and measured using ImageJ software. Their association with MVI in sHCC was analyzed. Results: Of the 124 patients with sHCC, 67 were MVI-positive and 57 were MVI-negative. Univariate analysis revealed a significant difference in the abdominal VAT and SAT between the MVI-positive and MVI-negative groups (p<0.05), with an area under the receiver operating characteristic curve of 0.76 and 0.65, respectively. Conclusions: The results of this study suggest that the areas of abdominal SAT and VAT are of significant clinical value because they can effectively predict the MVI status in patients with sHCC.

Risk factors for the recurrence of early hepatocellular carcinoma treated by percutaneous radiofrequency ablation with a multiple-electrode switching system: a multicenter prospective study.

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.

Predictive value of gadoxetic acid-enhanced MRI for posthepatectomy liver failure: a systematic review.

OBJECTIVES: Effective and non-invasive biomarkers to predict and avoid posthepatectomy liver failure (PHLF) are urgently needed. This systematic review aims to evaluate the efficacy of gadoxetic acid-enhanced MRI-derived parameters as an imaging biomarker in preoperative prediction of PHLF. METHODS: A systematic literature search was performed in the databases of PubMed/Medline, Web of Science, Embase, and Cochrane Library up to 11 December 2020. Studies evaluating the incidence of PHLF on patients who underwent hepatectomy with preoperative liver function assessment using gadoxetic acid-enhanced MRI were included. Data was extracted using pre-designed tables. The Quality In Prognostic Studies (QUIPS) tool was adopted to evaluate the risk of bias. RESULTS: A total of 15 studies were identified for qualitative synthesis and most studies were marked as low to moderate risk of bias in each domain of QUIPS. The most commonly used parameter was relative liver enhancement or its related parameters. The reported incidence of PHLF ranged from 3.9 to 40%. The predictive sensitivity and specificity of gadoxetic acid-enhanced MRI parameters varied from 75 to 100% and from 54 to 93% in ten reported studies. A majority of the studies revealed that the gadoxetic acid-enhanced MRI parameter was a predictor for PHLF. CONCLUSIONS: Gadoxetic acid-enhanced MRI showed a high predictive capacity for PHLF and represents a promising imaging biomarker in prediction of PHLF. Multicenter, prospective trials with large sample size and reliable, unified liver function parameters are required to validate the efficacy of individual liver function parameters. KEY POINTS: • There is an obvious heterogeneity of the published studies, not only in variance of MRI liver function parameters but also in indication and extent of the liver resection. • Signal intensity (SI)-based parameters derived from gadoxetic acid-enhanced MRI are the commonly used method for PHLF prediction. • Gadoxetic acid-enhanced MRI-derived parameters showed high predictive efficacy for PHLF and can potentially serve as a predictor for the incidence of PHLF.

The Short-Term Efficacy of Novel No-Touch Combined Directional Perfusion Radiofrequency Ablation in the Treatment of Small Hepatocellular Carcinoma with Cirrhosis.

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.

The diagnostic value of contrast-enhanced ultrasound LI-RADS for hepatocellular carcinoma in patients with cirrhosis and chronic hepatitis B.

PURPOSE: To explore the diagnostic value of American College of Radiology Contrast-Enhanced Ultrasound-Liver Imaging Reporting and Data System (ACR-CEUS-LI-RADS) for hepatocellular carcinoma (HCC) in patients with cirrhosis and chronic hepatitis B. METHODS: A total of 205 patients at high risk of HCC with solitary hepatic nodule were enrolled and retrospectively analyzed. All patients were over 18 years old and had a single lesion with a diameter < 50 mm. Lesions were categorized according to size and contrast enhancement patterns in the arterial, portal venous and late phases. Diagnostic efficacy of CEUS LI-RADS for HCC, and the rate of non-HCC malignancies in the LR-M class were compared between patients with cirrhosis and chronic hepatitis B. RESULTS: Of all 205 nodules (median nodule size was 34 mm), 142 (69.3%) were HCC. Of the 127 (61.9%) LR-5 category nodules, 95.8% (92/96) nodules were corresponded to HCC in cirrhosis, while 61.3% (19/31) nodules were corresponded to HCC in chronic hepatitis B (P = 0.000). Positive predictive value (PPV) of LR-5 category for HCC was 95.8% in cirrhosis and 61.3% in chronic hepatitis B (P = 0.000). More category of LR-4 nodules were proved to be HCC in patients with cirrhosis than chronic hepatitis B (80.0% vs 8.3%, P = 0.000). Of 41 LR-M category nodules, more non-HCC malignancies were found in chronic hepatitis B (76.0%) than that in cirrhosis (25.0%, P = 0.001). CONCLUSIONS: The LR-5 category is highly specific for the diagnosis of HCC in patients with cirrhosis. However, LR-5 category nodules require further CT or MRI examination or histological confirmation in patients with chronic hepatitis B for its unsatisfactory PPV for HCC.

lncENST Suppress the Warburg Effect Regulating the Tumor Progress by the Nkx2-5/ErbB2 Axis in Hepatocellular Carcinoma.

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.

Radiomics Models for Predicting Microvascular Invasion in Hepatocellular Carcinoma: A Systematic Review and Radiomics Quality Score Assessment.

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.

Sequential Portal Vein Embolization and Percutaneous Radiofrequency Ablation for Future Liver Remnant Growth: A Minimally Invasive Alternative to ALPPS Stage-1 in Treatment of Hepatocellular Carcinoma.

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.