Radiofrequency Ablation For Hepatocellular Carcinoma Research Articles

Percutaneous radiofrequency ablation of hepatocellular carcinomas abutting the right posterior diaphragm: factors associated with tumor recurrence and overall survival.

Radiofrequency ablation (RFA) of subphrenic hepatocellular carcinomas (HCCs) using ultrasound (US) guidance presents a challenge. To evaluate local tumor progression (LTP) and overall survival (OS) after RFA of right posterior subphrenic HCCs, and to identify the risk factors for LTP and OS after RFA. We screened patients who underwent US-guided RFA for a single HCC <3 cm in the right posterior subphrenic area. Cumulative rates of LTP and OS were compared between multiple- and single-electrode treatments and artificial pleural effusion versus no-effusion groups using Kaplan-Meier curves and the log-rank test. The risk factors for LTP and OS were assessed. A total of 36 patients were included. The cumulative 5-year and 10-year LTP rates were 32.9% and 39.6%, respectively, and the corresponding OS rates were 72.2% and 48.7%, respectively. The multiple-electrode group had significantly lower cumulative LTP rates compared to the single-electrode group (P < 0.001). The group receiving artificial pleural effusion showed a trend towards lower LTP rates than the no-effusion group (P = 0.076). The albumin-bilirubin (ALBI) grade was the only risk factor for LTP (hazard ratio [HR] = 4.17, 95% confidence interval [CI] = 1.26-14.55; P = 0.020). A lower albumin level was a risk factor for mortality (HR = 0.24, 95% CI = 0.07-0.79; P = 0.020). US-guided RFA with multiple electrodes and artificial pleural effusion tends to be linked with lower LTP rates. The ALBI grade and serum albumin level are risk factors for LTP and OS, respectively.

Laparoscopic liver resection versus radiofrequency ablation for hepatocellular carcinoma within Milan criteria: a meta-analysis and systematic review.

Minimally invasive techniques have significantly gained popularity for hepatocellular carcinoma (HCC) based on the Milan criteria. However, whether or not laparoscopic liver resection (LLR) or radiofrequency ablation (RFA) is a better treatment option remains debatable. We conducted a meta-analysis to review the published data comparing LLR and RFA for HCC through Milan criteria depending on tumor recurrence risk and survival. PubMed, OvidSP, Web of Science, and Cochrane Library databases were searched from inception to December 31, 2023. The studies comparing the outcomes and methods between LLR and RFA for HCC within the Milan criteria were included. We recruited 19 cohort studies with 2532 patients. The postoperative complication rate was low, and hospital stays were shorter in the RFA group than in the LLR group. The total tumor recurrence, the local tumor recurrence rate, and the intrahepatic tumor recurrence rate were lower within the LLR group than in the RFA group. There was no significant difference in the extrahepatic recurrence rate between the two groups. Moreover, no significant differences were observed between the groups concerning 1-, 3-, and 5-year overall survival (OS) and 1-year recurrence-free survival (RFS). However, 3-year and 5-year RFS were better within the LLR group than among the RFA group. The treatment of HCC within the Milan criteria is moving toward multidisciplinary and minimally invasive approaches. Our meta-analysis identified a lower postoperative complication rate and higher recurrence rate for RFA than LLR. RFA could be an alternative treatment due to its comparable long-term efficacy with LLR.

Enhancing Radiofrequency Ablation for Hepatocellular Carcinoma: Nano-Epidrug Effects on Immune Modulation and Antigenicity Restoration.

Radiofrequency ablation (RFA), a critical therapy for hepatocellular carcinoma (HCC), carries a significant risk of recurrence and metastasis, particularly owing to mechanisms involving immune evasion and antigen downregulation via epigenetic modifications. This study introduces a "nano-epidrug" named MFMP. MFMP, which is composed of hollow mesoporous manganese dioxide (MnO2) nanoparticles, FIDAS-5 as an MAT2A inhibitor, macrophage membrane, and anti-PD-L1 (aPD-L1), targets HCC cells. By selectively binding to these cells, MFMP initially reverses immune suppression via PD-L1 inhibition. After endocytosis, MFMP disassembles in the tumor microenvironment, releasing FIDAS-5 and Mn2+. FIDAS-5 prevents cGAS methylation, whereas Mn2+ aids STING pathway restoration. In addition, FIDAS-5 reduces m6A RNA modification, suppressing EGFR expression. These changes enhance HCC antigenicity to promote cytotoxic T cell recognition and cytotoxic killing. Furthermore, MFMP mediates immunogenic cell death in HCC by synergizing with RFA through cGAS DNA demethylation, EGFR mRNA demethylation, and TBK1 protein phosphorylation, thereby inhibiting recurrence and metastasis and enhancing immune memory. Thus, MFMP is a potential adjunctive therapy requiring clinical validation.

Exosomal circPTPRK promotes angiogenesis after radiofrequency ablation in hepatocellular carcinoma.

Radiofrequency ablation (RFA) is an effective treatment for hepatocellular carcinoma (HCC), but the recurrence rate remains high due to angiogenesis in residual cancer cells. We used thermal stimulation to simulate the post-RFA microenvironment. The expression profile of circRNAs between normal control HCC cell-derived exosomes and exosomes after heat stimulation were analyzed by RNA sequencing. Quantitative real-time PCR was applied to evaluate the expression of circPTPRK in exosomes and human umbilical vein endothelial cells (HUVECs). Then, the functions of heat-stimulated HCC cell-derived exosomes and exosomal circPTPRK on HUVECs were unveiled. Transcriptome sequencing was utilized to determine targeted genes of circPTPRK. Heat-stimulated HCC cell-derived exosomes augmented cell proliferation, migration, and angiogenesis of HUVECs. In total, 229 differentially expressed circRNAs were obtained, including 211 upregulated circRNAs and 18 downregulated circRNAs in heat-stimulated HCC cell-derived exosomes. The expression of circPTPRK was remarkably increased in heat-stimulated HCC cell-derived exosomes and the HUVECs incubated with them. Heat-stimulated HCC cell-derived exosomes with circPTPRK knockdown significantly inhibited cell proliferation, migration, and angiogenesis of HUVECs. Mechanistic studies indicated that PLA2G4E is a downstream target of circPTPRK, and PLA2G4E overexpression reversed the inhibitory effect of circPTPRK knockdown on HUVEC angiogenesis. Our results indicated that exosomal circPTPRK activated HUVEC angiogenesis by upregulating PLA2G4E expression.

Upregulation of EFCAB7 after radiofrequency ablation promoting hepatocellular carcinoma metastasis and survival by regulating PARK7.

Radiofrequency ablation (RFA) is an established treatment for unresectable and early-stage hepatocellular carcinoma (HCC). However, in some cases, residual tumor cells undergo malignant transformation following RFA. The molecular mechanisms underlying this phenomenon remain poorly understood. EFCAB7, a member of the EF-hand structure family, is of particular interest due to its association with oncogenesis. Nevertheless, the role of EFCAB7 in oncogenesis remains unclear. Gene expression level of EFCAB7 in HCC tissues before and after RFA was measured, while in vitro and in vivo experiments were proposed for exploring the roles of EFCAB7 in tumor cell proliferation and metastasis. Mass spectrometry and CO-IP were adopted to validate the interaction between PARK7 and EFCAB7. Finally, PARK7 in EFCAB7 silencing cells was overexpressed and different functions were measured in vitro to determine regulation between two genes. EFCAB7 showed increased expression after RFA in patient samples and EFCAB7 expression correlated with poor prognosis in HCC patients from the TCGA database. Then, EFCAB7 promoted HCC tumor cell proliferation and metastasis while inhibiting apoptosis. Furthermore, Mass spectrometry and Co-IP experiments revealed a direct interaction between EFCAB7 and PARK7. Finally, when we overexpressed PARK7 in EFCAB7 knockdown tumor cells, it rescued proliferation and metastasis, indicating a functional relationship between these two genes. EFCAB7 might be a core contributor to HCC cells' malignant transformation after RFA and could be a potential novel target to provide a therapeutic strategy for the prevention of recurrence after RFA in HCC.

Temporal trends and long-term outcomes of radiofrequency ablation for hepatocellular carcinoma within the Milan criteria

No study has analysed the temporal trends of the long-term results and clinical characteristics of patients with hepatocellular carcinoma (HCC) treated using radiofrequency ablation (RFA). Therefore, we examined temporal trends of characteristics of patients and treatment-naïve HCCs within the Milan criteria treated by RFA over 20 years. We retrospectively analysed 1099 patients with HCC within the Milan criteria treated with percutaneous RFA from January 2000 to December 2019. The overall survival (OS), recurrence-free survival (RFS), and factors affecting survival and local tumor progression were analysed using the Kaplan‒Meier method and Cox proportional hazards model. A trend test was performed to analyse the changing trends in participants and treatment outcomes. The overall and RFS of patients improved during the later period. In addition, viral hepatitis-related HCC incidence decreased, whereas that of alcohol- or non-alcoholic fatty liver disease-related HCC increased from the earlier to the later period (P for trend < 0.001). HBV antiviral therapy was increased and improved OS and RFS in patients treated using RFA. The outcomes after RFA over a 20-year period improved due to changes over time in target tumors and patients. The results could be useful for selecting patients who will benefit from RFA.

A novel role of AIM2 inflammasome-mediated pyroptosis in radiofrequency ablation of hepatocellular carcinoma

Introduction and ObjectivesThe absence of melanoma 2 (AIM2) protein triggers the activation of the inflammasome cascade. It is unclear whether AIM2 plays a role in hepatocellular carcinoma (HCC) and radiofrequency ablation (RFA), which uses radiofrequency waves to treat tumors. In this study, we investigated if RFA could induce pyroptosis, also called cell inflammatory necrosis, in HCC through AIM2-inflammasome signaling in vivo and in vitro. Materials and MethodsBALB/c nude mice were used to generate HepG2 or SMMC-7721 cell-derived tumor xenografts. HCC cells with knockdown or overexpression of AIM2 were created using short hairpin RNA (shRNA) and expression vector transfection, respectively, for functional and mechanistic studies. Downstream effects were examined using flow cytometry, qRT-PCR, ELISAs, and other molecular assays. ResultsRFA significantly suppressed tumor growth in HCC cell xenografts. Flow cytometry analysis revealed that RFA could induce pyroptosis. Furthermore, AIM2, NLRP3, caspase-1, γ-H2AX, and DNA-PKc had significantly greater expression levels in liver tissues from mice treated with RFA compared with those of the controls. Additionally, interleukin (IL)-1β and IL-18 expression levels were significantly higher in the HCC cell-derived xenograft mice treated with RFA compared with those without RFA. Notably, a significantly greater effect was achieved in the RFA complete ablation group versus the partial ablation group. Knockdown or overexpression of AIM2 in HCC cells demonstrated that AIM2 exerted a role in RFA-induced pyroptosis. ConclusionsRFA can suppress HCC tumor growth by inducing pyroptosis via AIM2. Therefore, therapeutically intervening with AIM2-mediated inflammasome signaling may help improve RFA treatment outcomes for HCC patients.

Liver resection had better disease-free survival rates compared with radiofrequency ablation in hepatocellular carcinoma: A meta-analysis based on randomized clinical trials.

Liver resection (LR) and radiofrequency ablation (RFA) are the most commonly used treatment modalities for early-stage hepatocellular carcinoma (ES-HCC). The comparative efficacy of LR and RFA in ES-HCC remains debated. We conducted a meta-analysis based on randomized trials to compare the outcomes of LR and RFA. We searched PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov for randomized controlled trials (RCTs) comparing RFA and LR interventions for the treatment of ES-HCC. The primary outcomes were overall survival (OS) and disease-free survival (DFS). We used meta-regression to determine the source of heterogeneity and conducted a trial sequential analysis to examine whether the outcome was statistically reliable. Our meta-analysis included nine RCTs with a total of 1,516 HCC patients. Compared with patients receiving RFA, those receiving LR did not have significantly different 2-year OS (HR=1.28, 95% CI: 0.73-2.23) and 5-year OS (HR=1.49, 95% CI: 0.99-2.24). However, patients receiving LR showed a favorable trend in 2-year DFS (HR=1.40, 95% CI: 1.16-1.69) and 5-year DFS (HR=1.37; 95% CI: 1.05-1.77), although these results are not conclusive due to underpowered significance. The heterogeneity was low, and the outcomes were statistically reliable. Meta-analysis suggests that while LR shows a favorable trend in DFS compared to RFA for ES-HCC, the present evidence does not thoroughly support recommending LR over RFA. The inconclusive nature of these findings highlights the need for further large-scale RCTs to establish definitive comparative efficacy.

Evolution of Systemic Treatment for Hepatocellular Carcinoma: Changing Treatment Strategies and Concepts.

Systemic therapy for hepatocellular carcinoma (HCC) has undergone substantial advancements. With the advent of atezolizumab plus bevacizumab (ATZ/BEV) combination therapy, followed by durvalumab plus tremelimumab, the era of immunotherapy for HCC has commenced. The emergence of systemic treatment with high response rates has led to improvements in overall survival while enabling conversion to radical surgical resection in some patients with HCC. In patients with intermediate-stage HCC, new treatment strategies combining systemic treatment and transcatheter arterial chemoembolization (TACE) are under development in clinical trials. Moreover, the addition of local therapies, such as TACE, to systemic treatment according to the treatment effect could achieve a certain percentage of complete response. In the IMbrave050 trial, the efficacy of ATZ/BEV combination therapy was validated in patients predicted to have a high risk of recurrence, especially in those who had undergone radical surgery or radiofrequency ablation for HCC. Therefore, systemic treatment for HCC is entering a new phase for all disease stages. The objective of this review is to organize the current position of systemic therapy for each HCC stage and discuss the development of new treatment methods and strategies, with a focus on regimens incorporating immune checkpoint inhibitors, along with future prospects.

The application of dynamic contrast-enhanced ultrasonography in immediate distinguishing residual tumour from benign periablational enhancement after hepatocellular carcinoma radiofrequency ablation.

This study set out to access the performance of quantitative analysis of contrast-enhanced ultrasound (CEUS) indistinguishing between benign periablational enhancement (BPE) and residual tumor (RT) following radiofrequency ablation(RFA). 165 tumors from 124 patients with hepatocellular carcinoma between 2021 and 2023underwent RFA, contrast-enhanced computed tomography (CECT), and CEUS in less than 24 hours. Analysis was done onthe quantitative parameters from RT and BPE found by CEUS. Complete ablation was obtained in 89.1% of lesions.When compared to BPE, RT had significantly greater peak intensity (PI), time to peak (TTP), area under the curve (AUC),ratio of PI and base intensity (PI/BI), and enhanced intensity (EI) values (all p<0.05). PI, TTP, AUC, PI/BI, and EI had largeareas under the receiver operating (ROC) curves. A binary logistic regression analysis, respectively, demonstrated that PI andPI/BI were independent favorable prognostic variables. Multiple parameters of quantitative analysis of CEUScan aid in distinguishing immediately between RT and BPE lesions. PI and PI/BI may be a more promising parameter. ImmediateCEUS evaluation following RFA may allow immediate retreatment of RT during the same operation time, which reducespatients' hospital stays and financial costs.

Safety of propofol sedation administered by interventional radiologists for radiofrequency ablation in patients with hepatocellular carcinoma

PurposeTo evaluate the safety of propofol sedation administered by interventional radiologists during radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC).Materials and methodsPropofol sedation was administered by interventional radiologists in 72 patients (85 procedures, 93 tumors) during RFA for HCC between August 2018 and December 2020. Interventional radiologists equipped with adequate knowledge and skills in sedation and respiratory management were responsible for sedation. Sedation was carefully assessed based on vital signs, including end-tidal carbon dioxide, consciousness status, and bispectral index. The primary endpoint was the incidence of sedation-related complications, which were evaluated separately as respiratory and cardiovascular complications. Secondary endpoints were technical success rate, ablation-related complications, and local tumor control rate. Technical success was defined as completion of ablation in the planned area. Complications were evaluated using the Clavien–Dindo classification. Sedation-related complications, technical success rate, and ablation-related complications were evaluated on a procedure basis, and local tumor control was evaluated on a tumor basis.ResultsRespiratory and cardiovascular complications were observed in eight (8/85, 9.4%) and two (2/85, 2.4%) patients, respectively. Four patients required the jaw thrust maneuver due to glossoptosis, whereas a decrease in oxygen saturation to < 90% was recorded in the other four patients. However, these were temporary, and none required manual ventilation or endotracheal intubation. Bradycardia (< 50 bpm) was detected in two patients; one recovered immediately without treatment, whereas the other rapidly improved after atropine sulfate administration. No severe hypotension (< 80 mmHg) was observed. The technical success rate was 100% (85/85). Grade 3 ablation-related complications were identified in three patients (3/85, 3.5%). The local tumor control rate was 95.7% (89/93).ConclusionPropofol sedation can be safely administered by interventional radiologists during RFA for HCC. Although it requires special safety considerations, it may be a sedation option during hepatic RFA.

Comparative Efficacy of Microwave versus Radiofrequency Ablation in Hepatocellular Carcinoma: Systematic Review and Meta-Analysis of Randomized-Controlled Trials.

Introduction: Hepatocellular carcinoma (HCC) is a leading global cause of cancer-related deaths. Thermal ablation techniques, especially radiofrequency ablation (RFA) and microwave ablation (MWA), have become pivotal treatments for HCC. This systematic review and meta-analysis aim to compare these modalities, highlighting their efficacy, strengths, and limitations in treating HCC. Methods: A comprehensive literature search was conducted across major databases (PubMed, MEDLINE, Springer, ProQuest, EBSCOhost, Cochrane, and EMBASE) targeting studies on hepatocellular carcinoma with RFA and MWA. Heterogeneity analyses and pooled outcomes using random-effect models with were evaluated to compare both thermal ablation methods. Results: Nine studies, which consists of 368 patients underwent RFA and 387 patients underwent MWA, were included in review. The findings showed no significant differences in pooled analysis of volume of ablation, complete ablation rate, local tumor progression, survival rates, major complications, and adverse events. Subgroup analysis showed significantly higher risk of local tumor progression in RFA in African populations. Conclusion: No statistically significant difference was seen between outcomes across studies. MWA may offer a potential for longer therapeutic response with comparable risk of complications and adverse outcomes.

Lusutrombopag Reduces the Risk of Hemoperitoneum Caused by Percutaneous Radiofrequency Ablation for Hepatocellular Carcinoma Compared with Platelet Transfusion

Introduction: Patients with liver cirrhosis develop thrombocytopenia and an increased risk of bleeding events after invasive procedures. Lusutrombopag, a thrombopoietin receptor agonist, can increase the platelet count. This study assessed whether lusutrombopag reduces the risk of hemoperitoneum following percutaneous radiofrequency ablation for hepatocellular carcinoma, compared with platelet transfusion. Methods: Participants in the present study comprised patients with severe thrombocytopenia (platelet count <50,000/μL) enrolled between November 2012 and March 2020, excluding patients with idiopathic thrombocytopenia or anticoagulant use. Hemoperitoneum rate, hemostasis rate, hemoglobin reduction rate, rate of achieving a platelet count ≥50,000/μL, and increases in platelet count and factors contributing to hemoperitoneum were retrospectively analyzed. Results: This study enrolled 41 patients, comprising 18 patients administered lusutrombopag and 23 patients who received platelet transfusion. The major hemoperitoneum rate after RFA was tend to be lower in the lusutrombopag group (0%) than in the platelet transfusion group (21.7%). All of the major hemoperitoneum was observed in the platelet transfusion group. Hemoglobin reduction rate was lower in the lusutrombopag group (−0.17%) than in the platelet transfusion group (6.79%, p = 0.013). Hemostasis rate was lower in the lusutrombopag group (0%) than in the platelet transfusion group (21.7%, p = 0.045). The rate of achievement of platelet counts ≥50,000/μL the day after RFA was higher in the lusutrombopag group (100%) than in the platelet transfusion group (60.9%, p = 0.005). Conclusion: Lusutrombopag may be able to perform RFA more safely with respect to the hemoperitoneum caused by percutaneous radiofrequency ablation compared with platelet transfusion.

Radiofrequency ablation of hepatocellular carcinoma guided by real-time physics-based ablation simulation: a prospective study

Objectives To assess the safety and efficacy of radiofrequency ablation (RFA) guidance software that incorporated patient-specific physics-based simulation of each ablation volume. Materials and methods Patients referred for curative ablation of hepatocellular carcinoma (HCC) of 2–5 cm diameter were prospectively enrolled. RFA was performed under general anesthesia. Procedure planning and intraprocedural modifications were guided by computer simulation of each ablation. The segmented target (tumor with 5 mm margin) was registered to and superimposed on subsequent 3D multiplanar images. The applied RF energy was used to calculate a simulated ablation volume which was displayed relative to the electrode and segmented target, to depict any untreated target tissue. After each additional ablation, the software updated the accumulated simulated ablation volume in relation to the target. The primary endpoints were technical efficacy and rate of local tumor progression (LTP). Results Sixty-eight tumors were ablated during 57 procedures in 52 patients (68.3 ± 9.2 years old, 78.8% male); 15 (26.3%) had multiple lesions and 23 (39.1%) had prior HCC treatment. The mean tumor diameter was 2.73 (±0.64) cm. The intraprocedural simulation directed additional overlapping ablations in 75.9% of tumors. Technical success and efficacy were 100% at 3-month contrast enhanced CT or MRI follow-up after the single treatment session. Cumulative incidence function estimates for 1- and 2-year LTP were 3.9% and 20.2%, respectively. Conclusion This prospective study found computer-assisted guidance that simulated each ablation was both safe and efficacious. The low rate of LTP was similar to studies that employed stereotactic guidance and ablation confirmation, without requiring a second contrast enhanced study.

Radiofrequency hyperthermia enhances the effect of OK-432 for Hepatocellular carcinoma by activating of TLR4-cGAS-STING pathway

Radiofrequency ablation (RFA) has been used as an alternative to surgical management of early-stage hepatocellular carcinoma (HCC). However, when large and irregular HCCs are subjected to RFA, a safety margin is usually difficult to obtain, thus causing a sublethal radiofrequency hyperthermia (RFH) at the ablated tumor margin. This study investigated the feasibility of using RFH to enhance the effect of OK-432 on HCC, with the aim to generate a tumor-free margin during RFA of HCC. Our results showed OK-432 could activate the cGAS-STING pathway, and RFH could further enhance the activation. Meanwhile, RFH could induce a high expression of TLR4, and TLR4 might be an upstream molecular of the cGAS-STING pathway. The combined therapy of RFH with OK-432 resulted in a better tumor response, and a prolonged survival compared to the other three treatments. In conclusion, RFH in combination with OK-432 might reduce the residual and recurrent tumor after RFA of large and irregular HCCs, and serve as a new option for other solid malignancies treated by RFA.

Can Machine Learning Predict Favorable Outcome After Radiofrequency Ablation of Hepatocellular Carcinoma?

The standard practice for limited-stage hepatocellular carcinoma (HCC) is the resection or the use of local ablative techniques, such as radiofrequency ablation (RFA). The outcome after RFA depends on a complex interaction between the patient's general condition, hepatic function, and disease stage. In this study, we aimed to explore using a machine learning model to predict the response. A retrospective study was conducted for patients with RFA for a localized HCC between 2018 and 2022. The collected clinical, radiologic, and laboratory data were explored using Python and XGBoost. They were split into a training set (70%) and a validation set (30%). The primary end point of this study was to predict the probability of achieving favorable outcomes 12 months after RFA. Favorable outcomes were defined as the patient was alive and HCC was controlled. One hundred and eleven patients were eligible for the study. Males were 78 (70.3%) with a median age of 57 (range of 43-81) years. Favorable outcome was seen in 62 (55.9%) of the patients. The 1-year survival rate and control rate were 94.6%, and 61.3%, respectively. The final model harbored an accuracy and an AUC of 90.6% and 0.95, respectively, for the training set, while they were 78.9% and 0.80, respectively, for the validation set. Machine learning can be a predictive tool for the outcome after RFA in patients with HCC. Further validation by a larger study is necessary.

Incidence and clinical impact of bile ducts changes after multibipolar radiofrequency ablation for hepatocellular carcinoma.

This study aimed to evaluate the incidence and clinical implications of bile duct changes following multibipolar radiofrequency ablation (mbpRFA) for hepatocellular carcinoma (HCC). Radiological, clinical, and biological data from consecutive cirrhotic patients who underwent first-line mbpRFA between 2007 and 2014 for uninodular HCC ≤ 5 cm were retrospectively collected. Follow-up imaging was reviewed to identify bile duct changes and factors associated with biliary changes were assessed using multivariable analysis. Baseline and 6-month liver function tests were compared in patients with and without bile duct changes. Complications, cirrhosis decompensation, and survival rates were compared in both groups. A total of 231 patients (mean age 68 years [39-85], 187 men) underwent 266 mbpRFA sessions for uninodular HCC (mean size 26 mm). Of these, 76 (33%) developed bile duct changes (upstream bile duct dilatations and/or bilomas) with a mean onset time of 3 months. Identified risk factors for these changes were the infiltrative aspect of the tumor (p = 0.035) and its location in segment VIII (p < 0.01). The average increase in bilirubin at 6 months was higher in the group with biliary changes (+2.9 vs. +0.4 µg/mL; p = 0.03). There were no significant differences in terms of complications, cirrhosis decompensation at 1 year (p = 0.95), local and distant tumor progression (p = 0.91 and 0.14 respectively), and overall survival (p = 0.4) between the two groups. Bile duct changes are common after mbpRFA for HCC, especially in tumors with an infiltrative aspect or those located in segment VIII. These changes do not appear to negatively impact the course of cirrhosis at 1 year or overall survival. Bile duct changes following mbpRFA for HCC are relatively common. Nevertheless, they do not raise clinical concerns in terms of complications, deterioration in liver function, or survival rates. Consequently, specific monitoring or interventions for these bile duct changes are not warranted. • Bile duct changes are frequently observed after multibipolar radiofrequency ablation for hepatocellular carcinoma, occurring in 33% of cases in our study. • Patients with bile duct changes exhibited a higher increase in bilirubin levels at 6 months but no more cirrhosis decompensation or liver abscesses. • Biliary changes following multibipolar radiofrequency ablation for hepatocellular carcinoma are not alarming and do not necessitate any specific monitoring or intervention.

Simultaneous inhibition of heat shock proteins and autophagy enhances radiofrequency ablation of hepatocellular carcinoma.

Radiofrequency ablation (RFA) is a commonly used minimally invasive treatment for hepatocellular carcinoma (HCC). However, incomplete radiofrequency ablation (iRFA) promotes tumor progression and metastasis. There is an urgent need to develop innovative strategies to enhance the efficacy of iRFA. The upregulation of heat shock proteins (HSPs) and activation of protective autophagy in tumor cells upon exposure to sublethal heat enhance the thermotolerance, thereby promoting tumor cell survival. Here, 3-methyladenine (3-MA) and lonidamine (LND) co-encapsulated liposomes (Lip@LND/3-MA) are designed to enhance the efficacy of iRFA by simultaneous inhibition of glycolysis and autophagy. On one hand, LND inhibits hexokinase, a key enzyme in glycolysis, and thus reduces ATP production and consequently suppresses the expression of HSPs. On the other hand, 3-MA, as an autophagy inhibitor, can inhibit protective autophagy after iRFA. Lip@LND/3-MA is confirmed to suppress the expression of HSPs and reduce the autophagy level during RFA. Therefore, the thermotolerance of tumor cells is significantly weakened, leading to remarkably enhanced therapeutic efficacy of iRFA. It is believed that simultaneous inhibition of HSPs and autophagy is a promising therapeutic strategy in clinical practice of RFA.

Combined Ultrasound and Computed Tomography Guidance in Radiofrequency Ablation for Hepatocellular Carcinoma Reduces Local Recurrence Rate

Background/Aim: In radiofrequency ablation (RFA) treatment of hepatocellular carcinoma (HCC), the therapeutic effect depends on the appropriate position of the electrode. To improve the accuracy of the electrode needle position, we currently perform RFA with combined ultrasound sonography (US) and computed tomography (CT) guidance. The purpose of this study was to evaluate the effectiveness of this US/CT-guided RFA method. Patients and Methods: This retrospective study recruited 97 patients with single tumors treated with transcatheter arterial chemoembolization and monopolar RFA between January 2013 and December 2017. Among these, 50 patients were treated with RFA under US/CT guidance (US/CT-guided group) and 47 were treated with RFA under US guidance alone (US-guided group). We analyzed the efficacy of US/CT guidance compared with US guidance alone. Results: The 1-, 2-, and 3-year local recurrence rates for the US/CT-guided and US-guided groups were 4.1%, 6.3%, and 8.6%, and 19.6%, 31.6%, and 41.9%, respectively. The local recurrence rate was lower in the US/CT-guided group (p=0.0030). Cox proportional hazards model for multivariate analysis demonstrated that the independent risk factors associated with local recurrence were tumor size (p=0.0028) and US/CT guidance (p=0.0037). Conclusion: US/CT-guided RFA for HCC reduced the local recurrence rate compared with US-guided RFA alone.

Combined Transarterial Chemoembolization and Radiofrequency Ablation for Hepatocellular Carcinoma Infeasible for Ultrasound-Guided Percutaneous Radiofrequency Ablation: A Comparative Study with General Ultrasound-Guided Radiofrequency Ablation Outcomes.

This study aimed to evaluate the therapeutic outcomes of transarterial chemoembolization combined with radiofrequency ablation (TACE + RFA) for hepatocellular carcinomas (HCC) measuring ≤3 cm infeasible for ultrasound (US)-guided percutaneous RFA. Twenty-four patients who underwent fluoroscopy-guided TACE + RFA for single HCC between January 2012 and December 2016 were screened. To evaluate the TACE + RFA outcomes compared with those of US-guided RFA, 371 patients who underwent US-guided RFA during the same period were screened. We compared local tumor progression (LTP) and intrahepatic distant recurrence (IDR) between the two groups before and after propensity score (PS) matching, and performed univariable and multivariable Cox proportional hazard regression analyses for all patients. PS matching yielded 21 and 42 patients in the TACE + RFA and US-guided RFA groups, respectively. Cumulative LTP rates after PS matching were not significantly different between the two groups at 1 (0.0% vs. 7.4%, p = 0.072), 2 (10.5% vs. 7.4%, p = 0.701), and 5 years (16.9% vs. 10.5%, p = 0.531). IDR rates did not differ significantly between the two groups at 1 (20.6% vs. 10%, p = 0.307), 2 (25.9% vs. 25.9%, p = 0.999), or 5 years (49.9% vs. 53%, p = 0.838). Multivariable analysis showed that treatment type was not a significant factor for LTP or IDR. The outcomes of TACE + RFA for HCC were similar to those of general US-guided RFA. Fluoroscopy-guided TACE + RFA may be an effective treatment when US-guided RFA is not feasible.