Local Ablation Therapy for Hepatocellular Carcinoma: Clinical Significance of Tumor Size, Location, and Biology.

ABSTRACT: Local ablation therapy, encompassing radiofrequency ablation (RFA), microwave ablation, and cryoablation, has emerged as a crucial strategy for managing small hepatocellular carcinomas (HCCs), complementing liver resection and transplantation. This review delves into the clinical significance of tumor size, location, and biology in guiding treatment decisions for HCCs undergoing local ablation therapy, with a focus on tumors smaller than 3 cm. Tumor size significantly influences treatment outcomes, with larger tumors associated with poorer local tumor control due to challenges in creating sufficient ablative margins and the likelihood of microvascular invasion and peritumoral satellite nodules. Advanced ablation techniques such as centripetal or no-touch RFA using multiple electrodes, cryoablation using multiple cryoprobes, and microwave ablation offer diverse options for HCC treatment. Notably, no-touch RFA demonstrates superior local tumor control compared with conventional RFA by achieving sufficient ablative margins, making it particularly promising for hepatic dome lesions or tumors with aggressive biology. Laparoscopic RFA proves beneficial for treating anterior subphrenic HCCs, whereas artificial pleural effusion-assisted RFA is effective for controlling posterior subphrenic HCCs. However, surgical resection generally offers better survival outcomes for periportal HCCs compared with RFA. Cryoablation exhibits a lower incidence of vascular or biliary complications than RFA for HCCs adjacent to perivascular or periductal regions. Additionally, aggressive tumor biology, such as microvascular invasion, can be predicted using magnetic resonance imaging findings and serum tumor markers. Aggressive HCC subtypes frequently exhibit Liver Imaging Reporting and Data System M features on magnetic resonance imaging, aiding in prognosis. A comprehensive understanding of tumor size, location, and biology is imperative for optimizing the benefits of local ablation therapy in managing HCCs.

Gastrointestinal tract perforation after radiofrequency ablation for hepatic tumor: Incidence and risk factors.

OBJECTIVE: We analyzed the incidence and mortality rate of gastrointestinal (GI) tract perforation after radiofrequency ablation (RFA) for hepatic tumors and assess its risk factors. METHODS: This retrospective cohort study included 4799 patients with malignant tumors who underwent RFA (n = 7206). Sixty-nine cases of thermal injury to the GI tract were identified via a search of the electronic medical record system using index terms and divided into two groups according to the thermal injury with (n = 8) or without (n = 61) GI tract perforation based on follow-up CT reports. The risk factors for GI tract perforation were identified via multivariable logistic regression analysis using clinical, technical, and follow-up CT findings. RESULTS: The incidence of thermal injury to the GI tract and GI tract perforation was 0.96 % (69/7206) and 0.11 % (8/7206), respectively. The type of adjacent GI tract and history of diabetes mellitus differed significantly between the two groups (p < 0.05). The index tumor being located around the small intestine was the only significant risk factor for GI tract perforation after ablation (Odds ratio, 22.69; 95 % confidence interval, 2.59-198.34; p = 0.005 [reference standard, stomach]). All perforations were not identified on CT images immediately after RFA. The median time to detection was 20 days (range, 3-41 days). Two patients (25 %, 2/8) died due to perforation-related complications. CONCLUSION: GI tract perforation after RFA for hepatic tumors is rare; however, it is associated with high mortality. Thus, careful follow-up is required after RFA if the index tumor is located around the small intestine.

Proton Beam Radiotherapy as a Curative Alternative to Radiofrequency Ablation for Newly Diagnosed Hepatocellular Carcinoma.

BACKGROUND/AIM: This study aimed to compare the oncological outcomes of proton beam radiotherapy (PBT) with those of radiofrequency ablation (RFA) for newly diagnosed hepatocellular carcinoma (HCC). PATIENTS AND METHODS: This study included 323 patients who underwent PBT (n=40) or RFA (n=283) as a curative treatment for previously untreated HCC between October 2016 and June 2021. The primary endpoints were local progression and toxicity. RESULTS: The median follow-up was 3.4 years (range=1.1-5.7 years). In terms of portal vein tumor thrombosis, tumor size, alpha-fetoprotein, and prothrombin-induced by vitamin K absence-II, the PBT group had significantly more severe tumor burdens than those of the RFA group (p<0.0001, p<0.0001, p=0.0004, and p<0.0001, respectively). No significant difference was observed in cumulative local progression rate (10.4% in PBT vs. 7.8% in RFA at 3-years, p=0.895). Grade 3 or higher toxicity was reported in only one patient (0.4%) after RFA. Multivariable analysis demonstrated that treatment modality was not a significant prognostic factor for local progression (hazard ratio=1.05; 95% confidence interval=0.32-3.48; p=0.934). CONCLUSION: PBT demonstrated comparable local control with acceptable toxicity to RFA in newly diagnosed HCC. Therefore, PBT may be a valid alternative.

LI-RADS category is associated with treatment outcomes of small single HCC: surgical resection vs. radiofrequency ablation.

OBJECTIVES: To assess whether the Liver Imaging Reporting and Data System (LI-RADS) category is associated with the treatment outcomes of small single hepatocellular carcinoma (HCC) after surgical resection (SR) and radiofrequency ablation (RFA). METHODS: This retrospective study included 357 patients who underwent SR (n = 209) or RFA (n = 148) for a single HCC of ≤ 3 cm between 2014 and 2016. LI-RADS categories were assigned. Overall survival (OS), recurrence-free survival (RFS), and local tumor progression (LTP) rates after treatment were compared according to the LI-RADS category (LR-4/5 vs. LR-M) before and after propensity score matching (PSM). Prognostic factors for treatment outcomes were assessed. RESULTS: In total, 357 patients (mean age, 59 years; men, 272) with 357 HCCs (294 LR-4/5 and 63 LR-M) were included. After PSM (n = 78 in each treatment group), there were 10 and 11 LR-M HCCs in the SR and RFA group, respectively. There were no significant differences in OS or RFS. However, SR provided a lower 5-year LTP rate than RFA (1.4% vs. 14.9%, p = 0.001). SR provided a lower 5-year LTP rate than RFA for LR-M HCCs (0% vs. 34.4%, p = 0.062) and LR-4/5 HCCs (1.5% vs. 12.0%, p = 0.008). The LI-RADS category was the sole risk factor associated with poor OS (hazard ratio [HR] 3.79, p = 0.004), RFS (HR 2.12; p = 0.001), and LTP (HR 2.89; p = 0.032). CONCLUSION: LI-RADS classification is associated with the treatment outcome of HCC, supporting favorable outcomes of SR over RFA for LTP, especially for HCCs categorized as LR-M. CLINICAL RELEVANCE STATEMENT: Liver Imaging Reporting and Data System category has a potential prognostic role, supporting favorable outcomes of surgical resection over radiofrequency ablation for local tumor progression, especially for hepatocellular carcinoma categorized as LR-M. KEY POINTS: • SR provided a lower 5-year LTP rate than RFA for HCCs categorized as LR-M (0% vs. 34.4%, p = 0.062) and HCCs categorized as LR-4/5 (1.5% vs. 12.0%, p = 0.008). • There is a steeply increased risk of LTP within 1 year after RFA for LR-M HCCs, compared to SR. • The LI-RADS category was the sole risk factor associated with poor OS (HR 3.79, p = 0.004), RFS (HR 2.12; p = 0.001), and LTP (HR 2.89; p = 0.032) in patients with HCC of ≤ 3 cm treated with SR or RFA.

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.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

The efficacy of treatment for hepatocellular carcinoma in elderly patients.

BACKGROUND/AIM: Despite the increasing proportion of elderly patients with hepatocellular carcinoma (HCC) over time, treatment efficacy in this population is not well established. METHODS: Data collected from the Korean Primary Liver Cancer Registry, a representative cohort of patients newly diagnosed with HCC in Korea between 2008 and 2017, were analyzed. Overall survival (OS) according to tumor stage and treatment modality was compared between elderly and non-elderly patients with HCC. RESULTS: Among 15,186 study patients, 5,829 (38.4%) were elderly. A larger proportion of elderly patients did not receive any treatment for HCC than non-elderly patients (25.2% vs. 16.7%). However, OS was significantly better in elderly patients who received treatment compared to those who did not (median, 38.6 vs. 22.3 months; P<0.001). In early-stage HCC, surgery yielded significantly lower OS in elderly patients compared to non-elderly patients (median, 97.4 vs. 138.0 months; P<0.001), however, local ablation (median, 82.2 vs. 105.5 months) and transarterial therapy (median, 42.6 vs. 56.9 months) each provided comparable OS between the two groups after inverse probability of treatment weighting (IPTW) analysis (all P>0.05). After IPTW, in intermediate-stage HCC, surgery (median, 66.0 vs. 90.3 months) and transarterial therapy (median, 36.5 vs. 37.2 months), and in advanced-stage HCC, transarterial (median, 25.3 vs. 26.3 months) and systemic therapy (median, 25.3 vs. 26.3 months) yielded comparable OS between the elderly and non-elderly HCC patients (all P>0.05). CONCLUSIONS: Personalized treatments tailored to individual patients can improve the prognosis of elderly patients with HCC to a level comparable to that of non-elderly patients.

Transarterial chemoembolization for hepatocellular carcinoma: 2023 Expert consensus-based practical recommendations of the Korean Liver Cancer Association.

Transarterial chemoembolization (TACE) was introduced in 1977 with the administration of chemotherapeutic agent to gelatin sponge particles through the hepatic artery in patients with hepatocellular carcinoma (HCC) and was established as conventional TACE using Lipiodol in the 1980s. In the 2000s, drug-eluting beads were developed and applied clinically. Currently, TACE is a commonly used non-surgical treatment modality for patients with HCC who are unsuitable for curative treatment. Considering the vital role of TACE in the management of HCC, it is crucial to organize current knowledge and expert opinions regarding patient preparation, procedural techniques, and post-treatment care in TACE, which can enhance therapeutic efficacy and safety. A group of 12 experts in the fields of interventional radiology and hepatology, convened by the Research Committee of the Korean Liver Cancer Association (KLCA), has developed expert consensus-based practical recommendations in TACE. These recommendations have been endorsed by the Korean Society of Interventional Radiology and provide useful information and direction in performing TACE procedure as well as pre- and post- procedural patient care.

Transarterial chemoembolization for hepatocellular carcinoma: 2023 expert consensus-based practical recommendations of the Korean Liver Cancer Association.

Transarterial chemoembolization (TACE) was introduced in 1977 with the administration of chemotherapeutic agent to gelatin sponge particles through the hepatic artery in patients with hepatocellular carcinoma (HCC) and was established as conventional TACE using Lipiodol in the 1980s. In the 2000s, drug-eluting beads were developed and applied clinically. Currently, TACE is a commonly used non-surgical treatment modality for patients with HCC who are unsuitable for curative treatment. Considering the vital role of TACE in the management of HCC, it is crucial to organize current knowledge and expert opinions regarding patient preparation, procedural techniques, and post-treatment care in TACE, which can enhance therapeutic efficacy and safety. A group of 12 experts in the fields of interventional radiology and hepatology, convened by the Research Committee of the Korean Liver Cancer Association (KLCA), has developed expert consensus-based practical recommendations in TACE. These recommendations have been endorsed by the Korean Society of Interventional Radiology and provide useful information and direction in performing TACE procedure as well as pre- and post- procedural patient care.

Treatment Outcomes of Percutaneous Radiofrequency Ablation for Hepatocellular Carcinomas: Effects of the Electrode Type and Placement Method.

OBJECTIVE: To investigate the association among the electrode placement method, electrode type, and local tumor progression (LTP) following percutaneous radiofrequency ablation (RFA) for small hepatocellular carcinomas (HCCs) and to assess the risk factors for LTP. MATERIALS AND METHODS: In this retrospective study, we enrolled 211 patients, including 150 males and 61 females, who had undergone ultrasound-guided RFA for a single HCC < 3 cm. Patients were divided into four combination groups of the electrode type and placement method: 1) tumor-puncturing with an internally cooled tip (ICT), 2) tumor-puncturing with an internally cooled wet tip (ICWT), 3) no-touch with ICT, and 4) no-touch with ICWT. Univariable and multivariable Cox proportional-hazards regression analyses were performed to evaluate the risk factors for LTP. The major RFA-related complications were assessed. RESULTS: Overall, 83, 34, 80, and 14 patients were included in the ICT, ICWT, no-touch with ICT, and no-touch with ICWT groups, respectively. The cumulative LTP rates differed significantly among the four groups. Compared to tumor puncturing with ICT, tumor puncturing with ICWT was associated with a lower LTP risk (adjusted hazard ratio [aHR] = 0.11, 95% confidence interval [CI] = 0-0.88, P = 0.034). However, the cumulative LTP rate did not differ significantly between tumor-puncturing with ICT and no-touch RFA with ICT (aHR = 0.34, 95% CI = 0.03-1.62, P = 0.188) or ICWT (aHR = 0.28, 95% CI = 0-2.28, P = 0.294). An insufficient ablative margin was a risk factor for LTP (aHR = 6.13, 95% CI = 1.41-22.49, P = 0.019). The major complication rates were 1.2%, 0%, 2.5%, and 21.4% in the ICT, ICWT, no-touch with ICT, and no-touch with ICWT groups, respectively. CONCLUSION: ICWT was associated with a lower LTP rate compared to ICT when performing tumor-puncturing RFA. An insufficient ablation margin was a risk factor for LTP.

Transarterial Chemoembolization for Hepatocellular Carcinoma: 2023 Expert Consensus-Based Practical Recommendations of the Korean Liver Cancer Association.

Transarterial chemoembolization (TACE) was introduced in 1977 with the administration of chemotherapeutic agent to gelatin sponge particles through the hepatic artery in patients with hepatocellular carcinoma (HCC) and was established as conventional TACE using Lipiodol in the 1980s. In the 2000s, drug-eluting beads were developed and applied clinically. Currently, TACE is a commonly used non-surgical treatment modality for patients with HCC who are unsuitable for curative treatment. Considering the vital role of TACE in the management of HCC, it is crucial to organize current knowledge and expert opinions regarding patient preparation, procedural techniques, and post-treatment care in TACE, which can enhance therapeutic efficacy and safety. A group of 12 experts in the fields of interventional radiology and hepatology, convened by the Research Committee of the Korean Liver Cancer Association (KLCA), has developed expert consensus-based practical recommendations in TACE. These recommendations have been endorsed by the Korean Society of Interventional Radiology and provide useful information and direction in performing TACE procedure as well as pre- and post-procedural patient care.

Rescue therapy for local tumor progression after radiofrequency ablation of small hepatocellular carcinoma: a comparison between repeated ablation and transcatheter arterial chemoembolization.

OBJECTIVE: To compare the therapeutic outcomes of repeated radiofrequency ablation (RFA) and transcatheter arterial chemoembolization (TACE) as rescue therapy for the treatment of local tumor progression (LTP) after initial RFA for hepatocellular carcinoma (HCC). METHODS: This retrospective study evaluated 44 patients who had LTP as initial tumor recurrence after RFA and underwent repeated RFA (n = 23) or TACE (n = 21) for local disease control. Local disease control and overall survival rates were evaluated using the Kaplan-Meier method. A Cox proportional-hazards regression model was used to identify the independent prognostic factors. The local disease control rate after the first rescue therapy and the number of rescue therapies applied until the last follow-up were also evaluated. RESULTS: Local disease control after rescue therapy for LTP was significantly higher with repeated RFA than with TACE (p < 0.001). Treatment type was a significant factor for local disease control (p < 0.001). The overall survival rates after rescue therapy were not significantly different between the two treatments (p = 0.900). The local disease control rate after the first rescue therapy was significantly higher with RFA than with TACE (78.3% vs 23.8%, p < 0.001). The total number of rescue therapies applied was significantly higher in the TACE group than that in the repeated RFA group (median 3 vs 1, p < 0.001). CONCLUSION: Repeated RFA as rescue therapy for LTP after initial RFA for HCC was more efficient and had significantly better local disease control than TACE. ADVANCES IN KNOWLEDGE: Even if LTP occurs after initial RFA, it should not be considered a failure of RFA, and repeated RFA should be performed over TACE if possible for more effective local disease control.

Risk Group Stratification for Recurrence-Free Survival and Early Tumor Recurrence after Radiofrequency Ablation for Hepatocellular Carcinoma.

PURPOSE: Although the prognosis after radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) may vary according to different risk levels, there is no standardized follow-up protocol according to each patient's risk. This study aimed to stratify patients according to their risk of recurrence-free survival (RFS) and early (≤2 years) tumor recurrence (ETR) after RFA for HCC based on predictive models and nomograms and to compare the survival times of the risk groups derived from the models. METHODS: Patients who underwent RFA for a single HCC (≤3 cm) between January 2012 and March 2014 (n = 152) were retrospectively reviewed. Patients were classified into low-, intermediate-, and high-risk groups based on the total nomogram points for RFS and ETR, respectively, and compared for each outcome. Restricted mean survival times (RMSTs) in the three risk groups were evaluated for both RFS and ETR to quantitatively evaluate the difference in survival times. RESULTS: Predictive models for RFS and ETR were constructed with c-indices of 0.704 and 0.730, respectively. The high- and intermediate-risk groups for RFS had an 8.5-fold and 2.9-fold higher risk of events than the low-risk group (both p < 0.001), respectively. The high- and intermediate-risk groups for ETR had a 17.7-fold and 7.0-fold higher risk than the low-risk group (both p < 0.001), respectively. The RMST in the high-risk group was significantly lower than that in the other two groups 9 months after RFA, and that in the intermediate-risk group became lower than that in the low-risk group after 21 months with RFS and 24 months with ETR. CONCLUSION: Our predictive models were able to stratify patients into three groups according to their risk of RFS and ETR after RFA for HCC. Differences in RMSTs may be used to establish different follow-up protocols for the three risk groups.

Percutaneous radiofrequency ablation of hepatocellular carcinoma in a recent cohort at a tertiary cancer center: incidence and factors associated with major complications and unexpected hospitalization events.

PURPOSE: This study aimed to assess the incidence of and factors associated with major complications, delayed discharge, and emergency room (ER) visits or readmission after percutaneous radiofrequency ablation (RFA) for single hepatocellular carcinoma (HCC) <3 cm in a recent cohort at a tertiary cancer center. METHODS: A total of 188 patients with treatment-naïve single HCCs <3 cm who underwent RFA between January 2018 and April 2021 were included in the analysis. Univariable and multivariable logistic regression analyses were performed to identify the factors associated with major complications, delayed discharge, and ER visits or readmission. Local tumor progression (LTP) and overall survival were estimated using the Kaplan-Meier method and Cox proportional-hazards regression analysis. RESULTS: Major complications occurred in 3.2% (6/188) of the patients. The longest diameter of the ablation zone was significantly larger in patients with major complications (P=0.023). Delayed discharge occurred in 5.8% (9/188) of the patients, for which albumin-bilirubin grade 3 was identified as an important determinant. No variables other than major complications were significantly associated with ER visits or readmission, which occurred in 7.0% (13/188) of the patients. Major complications, delayed discharge, and ER visits or readmission were not substantially related to the post-treatment outcomes of LTP and overall survival. CONCLUSION: This study confirmed RFA as a highly safe procedure for single HCCs <3 cm, despite the rapidly changing RFA techniques in the most recent cohort. A large ablation zone and poor liver function were predictors of major complications and delayed discharge, respectively.

Percutaneous radiofrequency ablation of solitary hepatic metastases from colorectal cancer: risk factors of local tumor progression-free survival and overall survival.

PURPOSE: This study aimed to evaluate local tumor progression-free survival (LTPFS) and overall survival (OS) after percutaneous radiofrequency ablation (RFA) for solitary colorectal liver metastases (CLM) <3 cm and to identify the risk factors associated with poor LTPFS and OS after percutaneous RFA. METHODS: This study screened 219 patients who underwent percutaneous RFA for CLM between January 2013 and November 2020. Of these, 92 patients with a single CLM <3 cm were included. LTPFS and OS were calculated using the Kaplan-Meier method, and the differences between curves were compared using the log-rank test. Risk factors for LTPFS and OS were assessed using Cox proportional-hazard regression models. RESULTS: Technical efficacy was achieved in the first (n=91) or second (n=1) RFA sessions. During the follow-up (median, 20.0 months), cumulative LTPFS rates at 1, 3, and 5 years were 92.4%, 83.4%, and 76.5%, respectively. During the follow-up (median, 27.8 months), the corresponding OS rates were 97.5%, 81.3%, and 74.8%, respectively. In multivariable Cox regression analyses, the group with both tumor-puncturing RFA and a T4 stage primary tumor (hazard ratio, 3.3; 95% confidence interval, 1.1 to 10.2; P=0.037) had poor LTPFS. In the univariable analysis, no factors were significantly associated with poor OS. CONCLUSION: Both LTPFS and OS were promising after percutaneous RFA for a single CLM <3 cm. The group with both tumor-puncturing RFA and a T4 stage primary tumor showed poor LTPFS. No risk factors were identified for poor OS.

Laparoscopic radiofrequency ablation versus percutaneous radiofrequency ablation for subphrenic hepatocellular carcinoma.

PURPOSE: Radiofrequency ablation is a curative treatment option for very early-stage or earlystage hepatocellular carcinoma (HCC). However, percutaneous radiofrequency ablation (PRFA) for subphrenic tumors is technically challenging. Laparoscopic radiofrequency ablation (LRFA) has been used to overcome this disadvantage. This study compared the treatment outcomes between LRFA and PRFA for subphrenic HCC. METHODS: This retrospective study screened patients who underwent PRFA or LRFA for subphrenic HCC between 2013 and 2018. Therapeutic outcomes, including local tumor progression (LTP), intrahepatic distant recurrence (IDR), extrahepatic metastasis (EM), disease-free survival (DFS), and overall survival (OS), were compared between the two groups. RESULTS: Thirty patients in the PRFA group and 23 patients in the LRFA group were included. LTP was observed in six patients in the PRFA group (20%), but in no patients in the LRFA group. The cumulative LTP rates at 1, 3, and 5 years were 3.7%, 23.4%, and 23.4%, respectively, in the PRFA group and 0.0% in the LRFA group (P=0.015). The IDR, EM, and DFS rates were not significantly different between the two groups (P=0.304, P=0.175, and P=0.075, respectively). The OS rates at 1, 3, and 5 years were 96.6%, 85.7%, and 71.6%, respectively, in the PRFA group and 100%, 95.7%, and 95.7%, respectively, in the LRFA group (P=0.049). CONCLUSION: LRFA demonstrated better therapeutic outcomes than did PRFA for subphrenic tumors in terms of LTP and OS. Therefore, LRFA can be considered as the first-line treatment option for subphrenic HCC.

Laparoscopic Hepatic Resection Versus Laparoscopic Radiofrequency Ablation for Subcapsular Hepatocellular Carcinomas Smaller Than 3 cm: Analysis of Treatment Outcomes Using Propensity Score Matching.

OBJECTIVE: To compare the therapeutic outcomes of laparoscopic hepatic resection (LHR) and laparoscopic radiofrequency ablation (LRFA) for single subcapsular hepatocellular carcinoma (HCC). MATERIALS AND METHODS: We screened 244 consecutive patients who had received either LHR or LRFA between January 2014 and December 2016. The feasibility of LRFA in patients who underwent LHR was retrospectively assessed by two interventional radiologists. Finally, 60 LRFA-feasible patients who had received LHR and 29 patients who had received LRFA as the first treatment for a solitary subcapsular HCC between 1 cm and 3 cm were finally included. We compared the therapeutic outcomes, including local tumor progression (LTP), recurrence-free survival (RFS), and overall survival (OS) between the two groups before and after propensity score (PS) matching. Multivariable Cox proportional hazard regression was also used to evaluate the difference in OS and RFS between the two groups for all 89 patients. RESULTS: PS matching yielded 23 patients in each group. The cumulative LTP and OS rates were not significantly different between the LHR and LRFA groups after PS matching (p = 0.900 and 0.003, respectively). The 5-year LTP rates were 4.6% and 4.4%, respectively, and OS rates were 100% and 90.7%, respectively. The RFS rate was higher in LHR group without statistical significance (p = 0.070), with 5-year rates of 78.3% and 45.3%, respectively. OS was not significantly different between the LHR (reference) and LRFA groups in multivariable analyses, with a hazard ratio (HR) of 1.33 (95% confidence interval, 0.12-1.54) (p = 0.818). RFS was higher in LHR (reference) than in LRFA without statistical significance in multivariable analysis, with an HR of 2.01 (0.87-4.66) (p = 0.102). CONCLUSION: There was no significant difference in therapeutic outcomes between LHR and LRFA for single subcapsular HCCs measuring 1-3 cm. The difference in RFS should be further evaluated in a larger study.

Ablative Outcomes of Various Energy Modes for No-Touch and Peripheral Tumor-Puncturing Radiofrequency Ablation: An Ex Vivo Simulation Study.

OBJECTIVE: To compare the outcomes of radiofrequency ablation (RFA) using dual switching monopolar (DSM), switching bipolar (SB), and combined DSM + SB modes at two different interelectrode distances (25 and 20 mm) in an ex vivo study, which simulated ablation of a 2.5-cm virtual hepatic tumor. MATERIALS AND METHODS: A total of 132 ablation zones were created (22 ablation zones for each protocol) using three separable clustered electrodes. The performances of the DSM, SB, and combined DSM + SB ablation modes were compared by evaluating the following parameters of the RFA zones at two interelectrode distances: shape (circularity), size (diameter and volume), peritumoral ablative margins, and percentages of the white zone at the midpoint of the two electrodes (ablative margin at midpoint, AMm) and in the electrode path (ablative margin at electrode path, AMe). RESULTS: At both distances, circularity was the highest in the SB mode, followed by the DSM + SB mode, and was the lowest in the DSM mode. The circularity of the ablation zone showed a significant difference among the three energy groups (p < 0.001 and p = 0.002 for 25-mm and 20-mm, respectively). All size measurements, AMm, and AMe were the greatest in the DSM mode, followed by the DSM + SB mode, and the lowest were with the SB mode (all statistically significant). The white zone proportion in AMm and AMe were the greatest in the SB mode, followed by the DSM + SB mode and DSM in general. CONCLUSION: DSM and SB appear to be complementary in creating an ideal ablation zone. RFA with the SB mode can efficiently eradicate tumors and create a circular ablation zone, while DSM is required to create a sufficient ablative margin and a large ablation zone.

Hepatocellular carcinoma patients with high circulating cytotoxic T cells and intra-tumoral immune signature benefit from pembrolizumab: results from a single-arm phase 2 trial.

BACKGROUND: A limited number of studies have characterized genomic properties of hepatocellular carcinoma (HCC) patients in response to anti-PD-1 immunotherapy. METHODS: Herein, we performed comprehensive molecular characterization of immediate (D-42 to D-1) pre-treatment tumor biopsy specimens from 60 patients with sorafenib-failed HCC in a single-arm prospective phase II trial of pembrolizumab. Objective response rate was the primary efficacy endpoint. We used whole-exome sequencing, RNA sequencing, and correlative analysis. In addition, we performed single-cell RNA sequencing using peripheral blood mononuclear cells. RESULTS: The overall response rate of pembrolizumab in sorafenib-failed HCC patients was 10% ([6/60] 95% CI, 2.4-17.6). In a univariate analysis using clinicopathological features, female gender, PD-L1 positivity, and low neutrophil-to-lymphocyte ratio (NLR) were identified as contributing factors to pembrolizumab response. Somatic mutations in CTNNB1 and genomic amplifications in MET were found only in non-responders. Transcriptional profiles through RNA sequencing identified that pembrolizumab responders demonstrated T cell receptor (TCR) signaling activation with expressions of MHC genes, indicating increased levels of T cell cytotoxicity. In single-cell sequencing from 10 pre- and post-treatment peripheral blood mononuclear cells (PBMCs), patients who achieved a partial response or stable disease exhibited immunological shifts toward cytotoxic CD8+ T cells. Conversely, patients with progressive disease showed an increased number of both CD14+ and CD16+ monocytes and activation of neutrophil-associated pathways. CONCLUSIONS: Taken together, HCC patients with infiltration of cytotoxic T cells, along with increased active circulating CD8+ T cells during pembrolizumab treatment and down-regulation of neutrophil-associated markers, significantly benefited from pembrolizumab treatment. TRIAL REGISTRATION: NCT#03163992 (first posted: May 23, 2017).

Direction of Tissue Contraction after Microwave Ablation: A Comparative Experimental Study in Ex Vivo Bovine Liver.

OBJECTIVE: This study aimed to investigate the direction of tissue contraction after microwave ablation in ex vivo bovine liver models. MATERIALS AND METHODS: Ablation procedures were conducted in a total of 90 sites in ex vivo bovine liver models, including the surface (n = 60) and parenchyma (n = 30), to examine the direction of contraction of the tissue in the peripheral and central regions from the microwave antenna. Three commercially available 2.45-GHz microwave systems (Emprint, Neuwave, and Surblate) were used. For surface ablation, the lengths of two overlapped square markers were measured after 2.5- and 5-minutes ablations (n = 10 ablations for each system for each ablation time). For parenchyma ablation, seven predetermined distances between the markers were measured on the cutting plane after 5- and 10-minutes ablations (n = 5 ablations for each system for each ablation time). The contraction in the radial and longitudinal directions and the sphericity index (SI) of the ablation zones were compared between the three systems using analysis of variance. RESULTS: In the surface ablation experiment, the mean longitudinal contraction ratio and SI from a 5-minutes ablation using the Emprint, Neuwave, and Surblate systems were 28.92% and 1.04, 20.10% and 0.53, and 24.90% and 0.45, respectively (p < 0.001). A positive correlation between longitudinal contraction and SI was noted, and a similar radial contraction was observed. In the parenchyma ablation experiment, the mean longitudinal contraction ratio and SI from a 10-minutes ablation using the three pieces of equipment were 38.60% and 1.06, 32.45% and 0.61, and 28.50% and 0.50, respectively (p < 0.001). There was a significant difference in the longitudinal contraction properties, whereas there was no significant difference in the radial contraction properties. CONCLUSION: The degree of longitudinal contraction showed significant differences depending on the microwave ablation equipment, which may affect the SI of the ablation zone.