Liver resection for single large hepatocellular carcinoma: a prognostic factors study.

INTRODUCTION AND OBJECTIVES: Liver resection is the only curative therapeutic option for large hepatocellular carcinoma (> 5 cm), but survival is worse than in smaller tumours, mostly due to the high recurrence rate. There is currently no proper tool for stratifying relapse risk. Herein, we investigated prognostic factors before hepatectomy in patients with a single large hepatocellular carcinoma (HCC). MATERIAL AND METHODS: We retrospectively identified 119 patients who underwent liver resection for a single large HCC in 2 tertiary academic French centres and collected pre- and post-operative clinical, biological and radiological features. The primary outcome was overall survival at five years. Secondary outcomes were recurrence-free survival at five years and prognostic factors for recurrence. RESULTS: A total of 84% of the patients were male, and the median age was 66 years old (IQR 58-74). Thirty-nine (33%) had Child-Pugh A cirrhosis, and the mean Model for End-Stage Liver Disease (MELD) score was 6 (6-6). The aetiology of liver disease was predominantly alcohol-related (48%), followed by nonalcoholic steatohepatitis (22%), hepatitis B (18%) and hepatitis C (10%). The mean tumour size was 70 mm (55-110). The median overall survival was 72.5 months (IC 95%: 56.2-88.7), and the five-year overall survival was 55.1 ± 5.5%. The median recurrence-free survival was 26.6 months (95% CI: 16.0-37.1), and the five-year recurrence-free survival rate was 37.8 ± 5%. In multivariate analysis, preoperative prognostic factors for recurrence were baseline alpha-fetoprotein (AFP) > 7 ng/mL (p<0.001), portal veinous invasion (p=0.003) and cirrhosis (p=0.020). Using these factors, we created a simple recurrence-risk scoring system that classified three groups with distinct disease-free survival medians (p<0.001): no risk factors (65 months), 1 risk factor (36 months), and ≥2 risk factors (8.9 months). CONCLUSION: Liver resection is the only curative option for large HCC, and we confirmed that survival could be acceptable in experienced centres. Recurrence is the primary issue of surgery, and we proposed a simple preoperative score to help identify patients with the most worrisome prognosis and possible candidates for combined therapy.

NAD(P)HX epimerase downregulation promotes tumor progression through ROS/HIF-1α signaling in hepatocellular carcinoma.

Reactive oxygen species (ROS) derived from aberrant tumor metabolism could contribute to tumor invasion and metastasis. NAD(P)HX Epimerase (NAXE), an epimerase that allows the repair of damaged forms of antioxidant NADPH, is a potential cellular ROS scavenger and its role in tumor development is still elusive. Here, we found that NAXE is significantly downregulated in hepatocellular carcinoma (HCC) tissues and cell lines. NAXE downregulation is associated with poor clinicopathological characteristics and is an independent risk factor for overall and disease-free survival of HCC patients after liver resection. In addition, low NAXE expression could identify worse prognosis of HCC patients before vascular invasion or in early stages of disease. In particularly, low NAXE expression in HCC is markedly associated with microvascular invasion (MVI) and its combination with MVI predicts poorer prognosis of HCC patients after liver resection. Furthermore, in vitro and in vivo experiments both showed that knockdown of NAXE expression in HCC cells promoted migration, invasion, and metastasis by inducing epithelial-mesenchymal transition (EMT), whereas NAXE overexpression causes the opposite effects. Mechanistically, low NAXE expression reduced NADPH levels and further caused ROS level increase and hypoxia-inducible factor-1α (HIF-1α) activation, thereby promoting invasion and metastasis of HCC by facilitating EMT. What is more, the tumor-promoting effect of NAXE knockdown in HCC xenograft can be abolished by giving mice N-acetyl-l-cysteine (NAC) in drinking water. Taken together, our findings uncovered a tumor suppressor role for NAXE in HCC by scavenging excessive ROS and inhibiting tumor-promoting signaling pathways, suggesting a new strategy for HCC therapy by targeting redox signaling.

[The progresses of liver resection for solitary large hepatocellular carcinoma].

Large hepatocellular carcinoma (HCC) is one of the most common malignancies and was mistaked as "advanced and unresectable" . Liver resection is still the best curable treatment for HCC.The resection of large HCC is very difficult, which seriously restrict the progress of liver surgery.Our study proved that solitary large HCC (SLHCC) has unique clinicopathological and molecular biological characteristics.No matter how big the tumor size is, it belongs to early stage if there is no vascular invasion.Liver resection should be aggressively recommended for the patients with SLHCC, in which they can obtain good outcome, with 40% 5-year survival rate.We has also defined the borderline resectable hepatocellular carcinoma, and suggested that strictly master and correctly judge the surgical indications, syntheticly evaluate the surgical safety and patient's tolerability for liver resection.After that, with hands of experienced surgeons, liver resection for SLHCC can be safely and reliablely performed.

MicroRNA-130b promotes proliferation and EMT-induced metastasis via PTEN/p-AKT/HIF-1α signaling.

Hepatocellular carcinoma (HCC) is a major cause of cancer-related deaths owing to its high rate of postoperative recurrence and metastasis. New research is continuously identifying novel metastasis-associated oncogenes and tumor suppressor genes. miRNAs are noncoding RNAs that regulate protein synthesis post-translationally. miR-130b is one of several miRNAs involved in tumor metastasis. However, the role of miR-130b in HCC remains controversial. Here, we demonstrate that miR-130b is highly expressed in HCC and that it correlates with tumor number, vascular invasion, and TNM stage-important predictors of postoperative recurrence and metastases. Moreover, high levels of miR-130b predicted poor overall and disease-free survival of HCC patients, and in vitro and in vivo research revealed that knockdown or overexpression of miR-130b inhibited and promoted proliferation and metastasis of HCC cells, respectively. We identified PTEN as a direct functional target of miR-130b using miRNA databases and a dual luciferase report assay. Next, using a gain and loss assay and epithelial-mesenchymal transition (EMT) relative assays, we show that miR-130b may promote proliferation and EMT-induced metastasis via PTEN/p-AKT/HIF-1α signaling. Collectively, our data suggests that miR-130b may have prognostic value in HCC. Additionally, the miR-130b/PTEN/p-AKT/HIF-1α axis identified in this study provides novel insight into the mechanisms of HCC metastasis, which may facilitate the development of new therapeutics against HCC.

BCLC stage B is a better designation for single large hepatocellular carcinoma than BCLC stage A.

BACKGROUND AND AIM: Although the Barcelona Clinic Liver Cancer (BCLC) staging system is widely used for hepatocellular carcinoma (HCC) staging, the most appropriate BCLC stage designation for single large HCC (SLHCC, single nodule > 5 cm) remains controversial. This study investigated the prognosis of patients with SLHCC. METHODS: Patients with newly diagnosed HCCs (BCLC stages A or B) were classified according to tumor burden: group 1, a single nodule > 2 and ≤ 5 cm or two or three nodules ≤ 3 cm; group 2, a single nodule > 5 cm; and group 3, two or three nodules > 3 cm or > 3 nodules. Survival analysis was performed according to tumor stage, treatment type, and Child-Pugh grade. RESULTS: A total of 1005 patients were enrolled. Age was 59.3 ± 10.6 years, and 788 patients (78.4%) were men. Groups 1, 2, and 3 consisted of 613 (61.0%), 124 (12.3%), and 268 (26.7%) patients, respectively. HCC treatment included resection in 202 patients (20.1%), radiofrequency ablation ± transarterial chemoembolization in 311 patients (30.9%), and transarterial chemoembolization in 492 patients (49.0%). The median survival time differed significantly according to tumor stage (75.2, 44.9, and 30.3 months in groups 1, 2, and 3, respectively; P < 0.001). Multivariate analysis showed that group 2 had significantly worse survival compared with group 1 and similar survival to group 3. CONCLUSIONS: Patients in group 2 had a worse prognosis than those in group 1 and a similar prognosis to those in group 3. Our results suggest that BCLC stage B is the best stage designation for SLHCC.

MicroRNA-188-5p suppresses tumor cell proliferation and metastasis by directly targeting FGF5 in hepatocellular carcinoma.

BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. However, the detailed molecular mechanisms underlying HCC progression are still not completely clear. Given the crucial role of microRNAs (miRNAs) in cancer metastasis, we aimed to analyze the expression and function of a metastasis-associated miRNA named miR-188-5p in HCC. METHODS: miRNA array analysis was performed to search for metastasis-associated miRNAs in HCC. miR-188-5p expressions in tumor tissues and adjacent non-tumorous liver tissues of HCC patients and cell lines were evaluated by real-time PCR. The protein expression levels were analyzed by Western blot and immunohistochemistry. Luciferase reporter assays was used to validate the target of miR-188-5p. The effect of miR-188-5p on HCC progression was studied in vitro and in vivo. RESULTS: miR-188-5p was significantly decreased in HCC and its expression levels were highly correlated with multiple nodules, microvascular invasion, overall and disease-free survival of HCC. Ectopic expression of miR-188-5p suppressed HCC cell proliferation and metastasis in vitro and in vivo. Fibroblast growth factor 5 (FGF5) was identified as a major target of miR-188-5p. Enforced expression of miR-188-5p inhibited the expression of FGF5 significantly and the restoration of FGF5 expression reversed the inhibitory effects of miR-188-5p on HCC cell proliferation and metastasis. CONCLUSIONS: These findings collectively demonstrate a tumor suppressor role of miR-188-5p in HCC progression via targeting FGF5, suggesting that miR-188-5p could serve as a potential prognostic biomarker and therapeutic target for HCC.

The successful posterior sectionectomy accompanied with caudate lobectomy for hepatocellular carcinoma located in segment 1 after LEN-TACE: a case report.

Nowadays, the novel molecular targeting chemotherapy provides possibility of safe hepatectomy for progressive hepatocellular carcinoma (HCC). Further, combination of the conventional transarterial chemoembolization (TACE) may add an effect of tumor shrink. We present a successful radical hepatectomy for a large HCC located in segment 1 accompanied with the preoperative Lenvatinib (LEN)-TACE sequential treatment. We present a woman patient without any complaints who had a 7 cm-in-size of solitary HCC compressing vena cava and right portal pedicle. To achieve radical hepatectomy by tumor shrinking, LEN-TACE for 2 months. After confirming downsizing or devascularization of the HCC, we scheduled radical posterior sectionectomy combined with caudate lobectomy according to tumor location and expected future remnant liver volume from three-dimensional computed tomography simulation before surgery. Under the thoraco-abdominal incision laparotomy, we safely achieved scheduled radical hepatectomy without any vascular injuries. The postoperative course was uneventful and no tumor recurrence were observed for 1 year. Histological findings showed the Japan TNM stage III HCC with 70% necrosis. The multi-modal strategy of LEN-TACE followed by radical hepatectomy by confirming downsizing or devascularization in tumor is supposed to be useful and would be a preoperative chemotherapy option, and promising for curative treatment in HCC patients with progressive or large HCC, which may lead to safety by prevention surrounding major vascular injury.

Clinical prognosis of surgical resection versus transarterial chemoembolization for single large hepatocellular carcinoma (≥5 cm): A propensity score matching analysis.

Favorable prognostic factors and therapeutic strategies are important for patients with single large hepatocellular carcinoma (HCC). This retrospective study aimed to investigate the prognostic factors in patients with single large (≥5 cm) HCC with Child-Pugh (CP) class A patients and to recommend therapeutic strategies. Overall, 298 HCC patients with single and large (≥5 cm) tumors with CP class A, but without distant metastasis and macrovascular invasion were included, and their clinicopathological data, overall survival (OS), and progression-free survival (PFS) were recorded. OS and PFS was analyzed by the Kaplan-Meier method and Cox regression analysis. Propensity score matching (PSM) analysis was performed. The 298 HCC patients were 79.2% male and median age of 64 years. For the initial treatment, surgical resection (SR) and transarterial chemoembolization (TACE) was 50.8% and 49.2%, respectively. The OS and PFS were significantly higher in patients receiving SR than those receiving TACE before and after PSM. Furthermore, in multivariate analysis, cirrhosis (Hazard ratio [HR]: 2.04; 95% confidence interval [CI]: 1.35-3.03, p < 0.001, CP class A5/6 [HR: 4.01; 95% CI: 2.43-6.66, p < 0.001], and initial treatment [SR vs. TACE HR = 3.23; 95% CI: 2.13-5.01, p < 0.001]) remained significantly associated with mortality. Moreover, in multivariate analysis, CP class A5/6 (HR: 3.23; 95% CI: 1.89-5.88, p < 0.001), and initial treatment (Resection vs. TACE; HR = 4.17; 95% CI: 1.64-8.33, p = 0.039) remained significantly associated with recurrence. In conclusion, SR was associated with significantly higher OS and PFS rates than TACE before and after PSM for single large HCC patients.

Perioperative and long-term survival outcomes of laparoscopic versus open hepatectomy for BCLC stage A large hepatocellular carcinoma patients in difficult segments: A two-centre, propensity score matching analysis.

Background: The differences in short- and long-term outcome between laparoscopic liver resection (LLR) and open liver resection (OLR) for BCLC stage A large hepatocellular carcinoma (HCC) in difficult segments (I, IVa, VII, VIII) remain unclear. This PSM two-centre study aimed to compare perioperative and long-term survival outcomes of LLR with OLR for this HCC. Methods: HCC patients with BCLC stage A who underwent OLR or LLR in two medical centres were enrolled in the study. PSM analysis was performed to match patients between the LLR cohort and OLR cohort. Survival was analysed based on the Kaplan-Meier method. Independent risk factors were identified by Cox regression. Results: After PSM, 35 patients remained in the LLR cohort, and 84 remained in the OLR cohort. Patients in the LLR cohort had more intraoperative blood loss (p=0.036) and shorter hospital stays after surgery (p<0.001). The LLR cohort and OLR cohort had no difference in intraoperative blood transfusion, surgical margin or postoperative short-term outcomes. The OS and RFS were not significantly different between the two cohorts. The OS and RFS of these two cohorts were not different in the subgroup analysis. Surgical margin was identified as an independent risk factor for tumour recurrence. Conclusion: For BCLC stage A large HCC patients with lesions in difficult segments, LLR was feasible and had shorter hospital stay than OLR. In addition, a surgical margin ≥1 cm could significantly decrease the recurrence probability for large HCC located in different segments without compromising short-term outcomes.

Hepatic Resection Versus Stereotactic Body Radiation Therapy Plus Transhepatic Arterial Chemoembolization for Large Hepatocellular Carcinoma: A Propensity Score Analysis.

BACKGROUND AND AIMS: There are no comparative studies on the efficacy of hepatic resection (HR) and CyberKnife stereotactic body radiation therapy (CK-SBRT) plus transhepatic arterial chemotherapy embolization (TACE) in the treatment of large hepatocellular carcinoma (HCC). Therefore, this study aimed to compare the efficacy of HR and CK-SBRT+TACE in large HCC. METHODS: A total of one hundred and sixteen patients were selected from November 2011 to December 2016. Among them, 50 were allocated to the CK-SBRT+TACE group and 66 were allocated to the HR group. The Kaplan-Meier method was applied to calculate overall survival (OS) and progression-free survival (PFS) rates. Propensity score matching was performed to control for baseline differences between the groups. RESULTS: Thirty-six paired patients were selected from the CK-SBRT+TACE and HR groups. After propensity score matching, the 1-, 2- and 3-year OS rates were 83.3%, 77.8% and 66.7% in the HR group and 80.6%, 72.2% and 52.8% in the CK-SBRT+TACE group, respectively. The 1-, 2- and 3-year PFS rates were 71.6%, 57.3% and 42.3% in the HR group and 66.1%, 45.8% and 39.3% in the CK-SBRT+TACE group, respectively (OS: p=0.143; PFS: p=0.445). Both a high platelet count and low alpha-fetoprotein value were revealed as influencing factors in improving OS and PFS. CONCLUSIONS: CK-SBRT+TACE brought local effects that were similar to those of HR in HCC patients with a large and single lesion. Moreover, the liver injury occurrence rate was acceptable in both groups.

Preoperative Versus Postoperative Transarterial Chemoembolization on Prognosis of Large Hepatocellular Carcinoma.

Background: Transarterial chemoembolization (TACE) has proven to be an effective adjuvant therapy with liver resection (LR) to treat patients with hepatocellular carcinoma (HCC). The aim of this study was to evaluate outcomes in patients with HCC larger than 5 cm, comparing those who had TACE before LR to those who had TACE after LR. Materials and methods: A total of 320 consecutive patients who underwent LR in combination with TACE for HCC larger than 5 cm from January 2009 to December 2014 were enrolled in study. Patients were divided into two groups: preoperative TACE group (n=199) and postoperative TACE group (n=121). Overall survival (OS) and recurrence-free survival (RFS) of patients were compared between preoperative TACE and postoperative TACE groups by propensity score-matching (PSM). We determined prognostic factors for recurrence and death using multivariate cox regression analysis. Results: Among the 320 patients, the median age was 48 (range, 18 to 75) years, and 285 (89.1%) patients were male. During the follow- up period, 88 (44.2%) patients in the preoperative TACE group and 69 (57.0%) patients in the postoperative TACE group died. Before PSM, both OS and RFS were significantly longer in the preoperative TACE group than those in the postoperative TACE group (P=0.001 and P<0.001, respectively). After PSM, compared to those received postoperative TACE, patients with preoperative TACE had significantly better OS (Hazard ratio [HR]=1.92; 95% confidence interval [CI], 1.22-3.02; P=0.005) and RFS (HR=1.64; 95% CI, 1.16-2.32; P=0.005). Conclusions: Patients with large HCC undergoing LR appear to derive greater disease control and survival benefit from a single preoperative TACE treatment than from postoperative TACE.

Assessment of efficacy and safety by CalliSpheres versus HepaSpheres for drug-eluting bead transarterial chemoembolization in unresectable large hepatocellular carcinoma patients.

This study aimed to compare efficacy and safety of HepaSpheres and CalliSpheres in unresectable large hepatocellular carcinoma (HCC) patients. One hundred and twenty-seven unresectable large HCC patients receiving drug-eluting bead transarterial chemoembolization (DEB-TACE) treatment with CalliSpheres or HepaSpheres microspheres were analyzed. Treatment response, Karnofsky performance status (KPS) score, adverse events, main liver function indexes, time to progression (TTP), and overall survival (OS) were analyzed. Objective response rate (82.7% vs. 63.8%, p=.030) and disease control rate (100.0% vs. 91.5%, p=.030) were increased in CalliSpheres group compared to HepaSpheres group at 1 month after treatment, while no difference was found between the two groups regarding treatment response at 3 or 6 months post treatment (all p>.05). The KPS score at 1, 3, and 6 months was similar between the two groups (all p>.05). As for the liver function, the ALT, AST, ALB, and TBIL levels at 7 and 30 days were of no difference between the two groups (all p>.05). In addition, the adverse events including nausea/vomiting, pain, fever, myelosuppression, biloma, and abscess were of no difference between the two groups, either (all p>.05). In terms of survival profile, there was no difference regarding TTP (6.3 months (95%CI: 5.9-6.6 months) vs. 6.0 months (95%CI: 5.6-6.4 months), p=.082) or OS (23.0 months (95%CI: 20.1-25.9 months) vs. 22.0 months (95%CI: 20.2-23.8 months), p=.571) between the two groups. In conclusion, CalliSpheres seems to be superior in short-term efficacy and equal in long-term efficacy as well as safety compared to HepaSpheres for DEB-TACE treatment in unresectable large HCC patients.

Pretreatment Apparent Diffusion Coefficient as a Predictor of Response to Transcatheter Arterial Chemoembolization Immediately Combined with Radiofrequency Ablation for Treatment of Solitary Large Hepatocellular Carcinoma.

PURPOSE: To evaluate whether the pretreatment apparent diffusion coefficient (ADC) measured with diffusion weighted imaging (DWI) of tumor can be used as an imaging biomarker for predicting prognosis in solitary large hepatocellular carcinomas (HCCs) treated with transcatheter arterial chemoembolization (TACE) immediately combined with radiofrequency ablation (RFA). PATIENTS AND METHODS: In this single institution retrospective study, 40 solitary large HCCs that underwent treatment with TACE immediately combined with RFA were analyzed. All patients underwent abdominal dynamic contrast-enhanced magnetic resonance imaging within one month before treatment with DWI, and ADC values in the lesions were measured by two independent radiologists. Associations among patients' preoperative ADC values and objective response (OR), progression-free survival (PFS) and overall survival (OS) were examined. Survival curves were drawn with the Kaplan-Meier method, and differences were determined with the Log rank test. The Cox proportional-hazards model was used for univariate and multivariate analyses of PFS and OS. RESULTS: Forty solitary large HCCs (mean 9.54 cm, range 5.04-16.06 cm) were successfully treated with TACE in immediate combination with RFA (OR 75%). The ADC values were significantly higher in the response group than the non-response group (1.51±0.32×10-3 mm2/s vs 1.09±0.17×10-3 mm2/s; P<0.001). As predicted on the basis of the ADC values, the optimal cutoff value for the efficacy of TACE combined with RFA was 1.32×10-3 mm2/s, with a predictive sensitivity of 0.63 and a specificity of 1.00. Patients with high ADC had longer PFS than those with low ADC (14.9 months vs 5.3 months; P<0.001) and had significantly longer survival rates (22.6 months vs 12.1 months; P=0.004). CONCLUSION: Preoperative ADC values <1.32×10-3 mm2/s are an independent predictor of poorer prognosis in patients with solitary large HCCs who have undergone TACE immediately combined with RFA.

Assessment of efficacy and safety of the transcatheter arterial chemoembolization with or without apatinib in the treatment of large hepatocellular carcinoma.

PURPOSE: The goal of this study was to assess the clinical efficacy and safety of the transcatheter arterial chemoembolization (TACE) in combination with apatinib or TACE treatment alone in patients with large hepatocellular carcinoma (HCC). METHODS: A total of 82 patients with large HCC were consecutively enrolled between January 2016 and December 2017. Of the 82 patients, 34 underwent the combined treatment, while 48 underwent TACE alone. The treatment response was assessed at first month and third month after TACE therapy, and the survival rate at median follow-up time was also compared between the two treatment groups. Furthermore, progression-free survival (PFS), overall survival (OS) and treatment-related complications were assessed and compared. RESULTS: Patients treated with TACE + apatinib presented with better objective response rate and disease control rate compared to those who only underwent TACE. Median OS as well as median PFS was longer in the TACE plus apatinib group compared to the TACE alone group. Multivariate Cox's regression analysis further illustrated that TACE plus apatinib compared to TACE alone was an independent protective factor for PFS and OS. CONCLUSION: TACE combined with apatinib is a safe and promising treatment approach for patients with large HCC.

A comprehensive intervention on feasibility, efficacy, and safety between TAE combined with multi-applicator ablation therapy and TACE in the treatment of large hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common tumors in recent days with high mortality and low early diagnosis rate, resulting in the fourth leading cause of deaths globally. This study aimed to evaluate the feasibility, efficacy, and safety between transcatheter arterial embolization (TAE) therapy followed by multi-applicator ablation and transarterial chemoembolization (TACE) for the treatment of large HCC. METHODS: An intervention study conducted at the Cancer Center of Sun Yat-sen University, Guangzhou, China, with whom had large HCC. A comparison between the two groups (intervention and control group) was evaluated at different time dimensions by repeated-measures analysis of variance, Mann-Whitney U rank-sum test, where Kaplan-Meier and log-rank test calculated for the overall survival (OS), tumor response (TR), and progression-free survival (PFS). RESULTS: This study found the improved survival rate (SR) and PFS after 1-year treatment in the observation group (Group-I) by 56.4% and 12.8%, compared to 38.3% and 8.5% in the control group (Group-II). Likewise, 1- and 2-year OS rates (OSRs) in Group-I were 66.7% and 51.4%, wherein Group-II were 48.9% and 30.0%, respectively. The short-term efficacy of Group-I, such as complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD) were 28.21%, 56.41%, 0, 15.38%, while in Group-II was 2.13%, 68.79%, 6.38% 22.70% respectively, which were significant. The short-term efficacy was more excellent in the Group-I than Group-II. The quality of life (QOL) was better in Group-I than that of Group-II. CONCLUSIONS: TAE combined with multi-applicator ablation therapy is safer, effective with prolonged survival, and less severe adverse reactions compared to TACE therapy for the treatment of large HCC.

Comparison of Angio-CT and cone-beam CT-guided immediate radiofrequency ablation after transcatheter arterial chemoembolization for large hepatocellular carcinoma.

PURPOSE: To evaluate the rapeutic effectiveness of Angio-CT or cone-beam CT (CBCT)-guided immediate radiofrequency ablation (RFA) after transcatheter arterial chemoembolization (TACE) for large hepatocellular carcinoma (HCC). METHODS: 117 large HCC patients (mean maximum diameter: 9.3 cm; range 5.3-17.7 cm) were retrospective studied and divided into Angio-CT group (n = 66 cases), CBCT group (n = 21 cases), and single TACE group (n = 30 cases) according to treatment (Angio-CT/CBCT-guided immediate RFA after TACE, single TACE, respectively). The operative time, effective radiation dose, local-regional tumor responses, overall survival (OS), and progression­free survival (PFS) time and complications were recorded. RESULTS: The operative time and effective radiation dose of Angio-CT group and CBCT group were higher than those of TACE group (P < 0.01). The local-regional tumor responses on 1-month follow-up MRI (complete response + partial response) of Angio-CT group and CBCT group were 100%, which were significantly higher than that of single TACE group (76.7%, P < 0.05). There was no significant difference in local-regional tumor responses of 1-month follow-up between Angio-CT group and CBCT group (P = 0.831). The median PFS and OS time of Angio-CT group were 14.7 ± 1.43 months and 18.21 ± 0.88 months, CBCT group were 13.9 ± 1.53 months and 17.87 ± 1.78 months, TACE group were 10.4 ± 1.21 months and 12.87 ± 0.91 months, respectively. No procedure-related major complications occurred. CONCLUSIONS: MIYABI Angio-CT or CBCT-guided immediate RFA after TACE for large HCC both have more effective than single TACE. The former is worth popularizing, due to its advantages of convenience, shorter operative time, and less radiation dose for doctors.

Angio-CT-Guided Transarterial Chemoembolization Immediately in Combination with Radiofrequency Ablation for Large Hepatocellular Carcinoma.

RATIONALE AND OBJECTIVES: To evaluate the method and effectiveness of Angio-CT-guided transcatheter arterial chemoembolization (TACE) immediately in combination with radiofrequency ablation (RFA) in the treatment of large hepatocellular carcinomas (HCCs; maximum enhancing diameter >5 cm). MATERIALS AND METHODS: A retrospective analysis was conducted on 48 patients with solitary large HCCs who were admitted from October 2012 to June 2016 and treated by immediate combination therapy, and 48 patients with solitary large HCCs who were treated by a sequential combination (RFA at 2-4 weeks after TACE) therapy in the same period were randomly selected as controls. After treatment, the success rates of the immediately combined technique, the short-term outcomes of the immediately combined treatment (using the modified response evaluation criteria in solid tumor standard), and the survival rates were evaluated. RESULTS: The success rate of the immediately combined technique was 100%. The complete remission rates 1, 3, and 6 months after treatment in the study group were 58.3%༌56.2%, and 47.9%, respectively, while the corresponding complete remission rates of control group were 37.5%, 33.3%, and 27.1%, respectively. The 1-, 2-, and 3-year survival rates of the study group were 95.8%, 85.4%, and 58.3%, respectively, while the corresponding survival rates of the control group were 83.3%, 68.7%, and 43.8%, respectively. None of the patients had any serious complications. CONCLUSION: Angio-CT-guided TACE immediately in combination with RFA is a feasible, safe method for the treatment of large HCCs with excellent short-term outcomes and improved long-term prognoses.

Hydrochloric acid enhanced radiofrequency ablation for treatment of large hepatocellular carcinoma in the caudate lobe: Report of three cases.

BACKGROUND: To report on the use of percutaneous hydrochloric acid (HCl) enhanced radiofrequency ablation (HRFA) for the treatment of large (maximum diameter ≥ 5 cm) hepatocellular carcinoma (HCC) in the caudate lobe. CASE SUMMARY: Between August 2013 and June 2016, three patients with a large HCC (maximum diameter: 5.0, 5.7, and 8.1 cm) in the caudate lobe were treated by transarterial chemoembolization followed by computer tomography (CT) guided RFA using a monopolar perfusion RF electrode, which was enhanced by local infusion of 10% HCl at 0.2 mL/min (total volume, 3 to 12 mL). The output power of HRFA reached 100 W, and the average ablation time was 39 min (range, 15 to 60 min). Two patients each underwent one session of HRFA and one patient two sessions. After treatment, CT/magnetic resonance imaging showed that all the three lesions were completely ablated. There was no major complication. Two patients had asymptomatic bile duct dilatation. One patient died of tongue cancer 24 mo after ablation. The remaining two patients were alive and no area of enhancement is detected in the caudate lobe at 28 and 60 mo after ablation, respectively. CONCLUSION: Percutaneous CT-guided HRFA is safe and efficacious in treating large HCC in the caudate lobe.

Combination of Permanent Interstitial 125I-Seed Brachytherapy and Surgery for the Treatment of Large Hepatocellular Carcinoma.

The treatment methods available for large primary hepatocellular carcinomas (diameter >5 cm) are inadequate. Here, we report the successful management of 80 cases of large hepatocellular carcinoma, using a combination of custom-designed permanent interstitial iodine-125 seed brachytherapy and palliative surgery. Patients were enrolled in the study between 2011 and 2014. All patients underwent surgical treatment along with permanent interstitial iodine-125 seed brachytherapy; for the latter, patients received minimum doses covering 90% of the target (D90 s) of iodine-125 seeds ranging from 100 to 160 Gy (median: 110 Gy). All patients received 6 cycles of chemotherapy and were followed up at 6, 12, 24, and 36 months postoperatively. The clinical symptom remission rate was 95.3% (61 of 64). Alanine aminotransferase and aspartate aminotransferase levels decreased to normal in 80% (50 of 60) and 75% of the patients (45 of 60), respectively. The posttreatment alpha-fetoprotein levels decreased by 50% in 80% of the patients (40 of 50). The effective therapy rates were 80% (76 of 95) for 95 tumor nodules (diameters 5-10 cm) and 78.6% (33 of 42) for 42 tumor nodules (diameters >10 cm). The 3-year disease-free survival rate was 66.6%. Palliative surgery plus permanent interstitial iodine-125 seed brachytherapy appears to be a reasonable therapeutic alternative for large hepatocellular carcinoma.

The effect of radiotherapy in liver-confined but non-resectable Barcelona Clinic Liver Cancer stage C large hepatocellular carcinoma.

BACKGROUND AND AIMS: Clinical trials to determine the efficacy of radiotherapy (RT) in liver-confined but non-resectable Barcelona Clinic Liver Cancer (BCLC) stage C hepatocellular carcinoma (HCC) are scarce. We aimed to determine the benefit of RT in such tumors and investigated large HCC tumors. METHODS: HCC data from the Korea Central Cancer Registry recorded from 2008 to 2010 were used. A total of 593 patients met our inclusion criteria; 67 were treated with RT while the remainder made up the non-RT group. Fifty-two RT recipients underwent combination treatments within 4 weeks after the first RT treatment, and were defined as the combination RT group. We performed propensity score matching (PSM) to compare the RT or combination RT groups with the non-RT group. The endpoint was overall survival (OS). RESULTS: Median follow-up time for surviving patients was 48 months. After PSM, there was no difference in OS between the RT and non-RT groups or between the combination RT and non-RT groups. However, the combination RT group had a longer median survival time (MST) (10.7 vs. 6.9 months, respectively). Next, we conducted PSM between the combination RT and non-RT groups in patients with tumor sizes ≥10 cm; MST was significantly longer in the former group (10.1 vs. 5.4 months, respectively; bootstrap 95% confidence interval of the difference in MST: 0.2-11.8). CONCLUSIONS: As a combined modality, RT is a plausible therapeutic option for liver-confined but non-resectable BCLC stage C large HCC patients.