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

Background The future liver remnant (FLR) faces a risk of poor growth in patients with cirrhosis-related hepatocellular carcinoma (HCC) after stage-1 radiofrequency-assisted ALPPS (RALPPS). The present study presents a strategy to trigger further FLR growth using supplementary radiofrequency ablation (RFA) and percutaneous ethanol injection (PEI). Methods At RALPPS stage-1 the portal vein branch was ligated, followed by intraoperative RFA creating a coagulated avascular area between the FLR and the deportalized lobes. During the interstage period, patients not achieving sufficient liver size (≥ 40%) within 2–3 weeks underwent additional percutaneous RFA/PEI of the deportalized lobes (rescue RFA/PEI) in an attempt to further stimulate FLR growth. Results Seven patients underwent rescue RFA/PEI after RALPPS stage-1. In total five RFAs and eight PEIs were applied in these patients. The kinetic growth rate (KGR) was highest the first week after RALPPS stage-1 (10%, range − 1% to 15%), and then dropped to 1.5% (0–9%) in the second week (p Conclusions Rescue RFA/PEI may provide an alternative to trigger further growth of the FLR in patients with cirrhosis-related HCC showing insufficient FLR after RALPPS stage-1. Trial registration Retrospectively registered.

Purpose: We assessed the efficacy and safety of camrelizumab [an anti-programmed death (PD-1) mAb] plus apatinib (a VEGFR-2 tyrosine kinase inhibitor) in patients with advanced hepatocellular carcinoma (HCC). Patients and Methods: This nonrandomized, open-label, multicenter, phase II study enrolled patients with advanced HCC who were treatment-naïve or refractory/intolerant to first-line targeted therapy. Patients received intravenous camrelizumab 200 mg (for bodyweight ≥50 kg) or 3 mg/kg (for bodyweight Results: Seventy patients in the first-line setting and 120 patients in the second-line setting were enrolled. As of January 10, 2020, the ORR was 34.3% [24/70; 95% confidence interval (CI), 23.3–46.6] in the first-line and 22.5% (27/120; 95% CI, 15.4–31.0) in the second-line cohort per IRC. Median progression-free survival in both cohorts was 5.7 months (95% CI, 5.4–7.4) and 5.5 months (95% CI, 3.7–5.6), respectively. The 12-month survival rate was 74.7% (95% CI, 62.5–83.5) and 68.2% (95% CI, 59.0–75.7), respectively. Grade ≥3 treatment-related adverse events (TRAE) were reported in 147 (77.4%) of 190 patients, with the most common being hypertension (34.2%). Serious TRAEs occurred in 55 (28.9%) patients. Two (1.1%) treatment-related deaths occurred. Conclusions: Camrelizumab combined with apatinib showed promising efficacy and manageable safety in patients with advanced HCC in both the first-line and second-line setting. It might represent a novel treatment option for these patients. See related commentary by Pinato et al., p. 908

BACKGROUND This study aimed to evaluate whether combined therapy with PD-1 blockade (anti-PD-1) and radiofrequency ablation (RFA) is superior to RFA monotherapy for recurrent hepatocellular carcinoma (HCC). METHODS A total of 127 patients who underwent anti-PD-1 plus RFA treatment (n = 41) or RFA alone (n = 86) for recurrent HCC were included in this retrospective study. A matched cohort comprising 40 patients from each group was selected after propensity score matching analysis. Clinical data including post-RFA HCC recurrence (primary endpoint), overall survival (OS) (secondary endpoint), adverse events, and toxic effects were retrospectively analyzed. RESULTS The 1-year recurrence-free survival rates for the anti-PD-1 plus RFA and RFA groups were 32.5% and 10.0% after propensity score matching. There were statistically significant differences between the two groups in terms of the recurrence-free survival rate (p = 0.001) and OS rate (p = 0.016). Tumor number, tumor-node metastasis (TNM) stage, antiviral therapy, and anti-PD-1 treatment were demonstrated to be important factors associated with 1-year recurrence-free survival probability by univariate and multivariate analyses. Univariate and multivariate analyses demonstrated that tumor number, TNM stage and anti-PD-1 treatment were significant prognostic factors for OS. RFA treatment-related adverse events included pleural effusions that require drainage and a mild or moderate increase in body temperature. Grade 3 or higher events related to anti-PD-1 treatment occurred in 12.8% (6) of patients and were infrequent. CONCLUSIONS Combination therapy with anti-PD-1 plus RFA was superior to RFA alone in improving survival in patients with recurrent HCC.

Background: To evaluate the feasibility and efficacy of sequential portal vein embolization (PVE) and radiofrequency ablation (RFA) (PVE+RFA) as a minimally invasive variant for associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) stage-1 in treatment of cirrhosis-related hepatocellular carcinoma (HCC).Methods: For HCC patients with insufficient FLR, right-sided PVE was first performed, followed by percutaneous RFA to the tumor as a means to trigger FLR growth. When the FLR reached a safe level (at least 40%) and the blood biochemistry tests were in good condition, the hepatectomy was performed. FLR dynamic changes and serum biochemical tests were evaluated. Postoperative complications, mortality, intraoperative data and long-term oncological outcome were also recorded.Results: Seven patients underwent PVE+RFA for FLR growth between March 2016 and December 2019. The median baseline of FLR was 353 ml (28%), which increased to 539 (44%) ml after 8 (7–18) days of this strategy (p < 0.05). The increase of FLR ranged from 40% to 140% (median 47%). Five patients completed hepatectomy. The median interval between PVE+RFA and hepatectomy was 19 (15–27) days. No major morbidity ≥ III of Clavien-Dindo classification or in-hospital mortality occurred. One patient who did not proceed to surgery died within 90 days after discharge. After a median follow-up of 18 (range 3–50) months, five patients were alive.Conclusion: Sequential PVE+RFA is a feasible and effective strategy for FLR growth prior to extended hepatectomy and may provide a minimally invasive alternative for ALPPS stage-1 for treatment of patients with cirrhosis-related HCC.

Aim: To compare the short- and long-term treatment outcomes of bisegmentectomy 7–8 vs. right hepatectomy for patients with hepatocellular carcinoma and cirrhosis.Methods: Thirty six cirrhotic HCC patients with infiltration of right hepatic vein in segments 7–8 underwent bisegmentectomy 7–8 for small-for-size remanant liver under right hemi-hepatectomy. Its outcome was compared with a case-matched control group of cirrhotic HCC patients who underwent right hemi-hepatectomy during the study period.Results: The study group consisted of 36 patients and the control group 36 patients selected from 1,526 patients matched with age, tumor size, tumor location, and Pugh-Child staging. There were no significant differences between the two groups in operative parameters and in perioperative main complications which included hemorrhage, bile leakage, ascites, pleural effusion, and liver failure. The overall morbidity rate and morbidity rate classified according to Clavien's classification were similar. There was no in-hospital mortality or 90 day post-operative mortality. The mean follow-up was 30 and 32 months for the study group and control group, respectively. The disease free survival rate (DFS) for the study group was just significantly better than the control group. The median DFS was 24 months for the study group and 8 months for the control group (P = 0.049). Meanwhile, the median cumulative overall survival was 35 months for the study group and 27 months for the control group (P = 0.494).Conclusion: Bisegmentectomy 7–8 was safe and feasible for selected cirrhosis patients, and did not increase the perioperative risk and inferior long-term overall survival outcomes. It extended the indications for liver resection in patients with borderline volumes of future liver remnant for HCC cirrhotic liver.

Purpose: Radiofrequency ablation (RFA) is widely accepted as a curative treatment for small hepatocellular carcinoma (HCC). However, insufficient RFA (IRFA) can lead to rapid local recurrence. The underlying mechanisms remain poorly understood. This study aimed to elucidate the role and regulatory mechanisms of autophagy in the recurrence of HCC after IRFA. Materials and methods: SMMC7721 and Huh7 cells were exposed to sublethal heat stress to stimulate the transition zone of IRFA treatment. The levels of autophagy were measured by western blot, immunofluorescence and transmission electron microscopy. Functional assays, such as CCK-8, EdU incorporation and flow cytometry, were performed to determine the role of heat-induced autophagy. The involved signaling pathways were explored by western blot. Finally, the antitumor effects of chloroquine (CQ) on heat-treated HCC cells were evaluated via an in vivo xenograft tumor model. Results: Sublethal heat stress induced autophagy in a temperature- and time-dependent manner in HCC cells. Furthermore, the inhibition of autophagy by CQ or siRNA targeting the autophagy-related genes Beclin-1 and Atg5 enhanced heat-induced apoptosis. The combination of CQ and heat treatment significantly suppressed tumor growth both in vitro and in vivo. Mechanistically, we reported for the first time that the ATP-AMPK-mTOR signaling pathway was involved in heat-induced autophagy. Conclusions: Heat stress induced protective autophagy against heat-induced apoptosis in HCC via the ATP-AMPK-mTOR axis, suggesting that targeting autophagy may be a promising strategy for improving the efficacy of RFA treatment for HCC.

Jun Yan,1– 3,* Zhongsong Man,3,* Qian Lu,1 Kuansheng Ma2 1Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Institute for Precision Medicine, Tsinghua University, Beijing, People’s Republic of China; 2The Institute of Hepatobiliary Surgery, The First Hospital Affiliated of Army Medical University, Chongqing, People’s Republic of China; 3Center of Hepatobiliary Pancreatic Disease, Xuzhou Central Hospital, Jiangsu, People’s Republic of China*These authors contributed equally to this workCorrespondence: Kuansheng MaThe Institute of Hepatobiliary Surgery, The First Hospital Affiliated of Army Medical University, Chongqing, People’s Republic of ChinaEmail makuansheng@vip.sina.comQian LuBeijing Tsinghua Changgung Hospital, School of Clinical Medicine, Institute for Precision Medicine, Tsinghua University, Beijing, People’s Republic of ChinaEmail luqian01971@tsinghua.edu.cnObjective: To evaluate the survival outcomes of combined liver resection (LR) and radiofrequency ablation (RFA) on multi-focal hepatocellular carcinoma (HCC) in patients with Barcelona clinic liver cancer (BCLC) stage B.Methods: A total of 210 cases of HCC were included in this study. In 42 cases, patients were treated with combination therapy using LR and RFA (LRCRFA). In 84 cases, patients underwent transarterial chemoembolization (TACE), and in another 84 cases, patients underwent LR; both the TACE and LR groups served as controls. It both categorized as BCLC stage B for LRCRFA and TACE groups but as BCLC stage A for LR group.Results: The overall survival (OS) rate of the LRCRFA group was significantly higher than that of the TACE group (P< 0.001) but was not significantly different when compared with the LR group (P=0.544). The disease-free survival (DFS) rate of the LRCRFA group was significantly lower than that of the LR group (P=0.029). Patients with ≤ 4 tumors or those with ≤ 5 tumors no larger than 6 cm in diameter experienced better long-term outcomes than other patients in the same LRCRFA group. The OS rates and DFS rates were not significantly different from those of patients in the LR group (P> 0.05). Having more than 2 existing tumors was an independent risk factor for OS rate.Conclusion: Combination therapy using LR and RFA can more effectively improve the prognosis of these patients than TACE. Patients with BCLC stage B HCC with ≤ 4 tumors or ≤ 5 tumors smaller than 6 cm in diameter are the ideal candidates for the application of LRCRFA.Keywords: hepatocellular carcinoma, surgical resection, radiofrequency ablation, transarterial chemoembolization, survival, Barcelona clinic liver cancer stage

This study aimed to analyze the influence of the cellular differentiation, the tumor size and the underlying hepatic condition on the enhancement pattern of hepatocellular carcinoma (HCC) on contrast-enhanced ultrasound (CEUS). 276 patients with single lesion ≤ 5 cm who underwent CEUS exam and were pathologically confirmed as HCC were retrospectively enrolled. Enhancement patterns, washout patterns, wash-in time and washout time were observed and recorded. During the arterial phase, more poorly differentiated HCCs (42.5%) and lesions > 3 cm (35.2%) performed inhomogeneous enhancement (p 3 cm (97.2 ± 51.3 s) washed out more rapidly than lesions ≤ 3 cm (113.9 ± 53.5 s) (p

Background The aim of this study was to determine the effect of anatomic resection (AR) versus non-anatomic resection (NAR) on recurrence rates in patients with hepatocellular carcinoma (HCC). Methods Eligible patients were randomized to AR or NAR from January 2006 to July 2007 at a single center. The primary outcome was the 2-year recurrence-free survival (RFS). Secondary outcomes were postoperative complications, time to first recurrence, 1-, 3-, and 5-year RFS, and overall survival (OS). Results Fifty-three (51%) and 52 (50%) patients underwent NAR and AR, respectively. A larger proportion of patients achieved margins ≥20 mm in the AR group (52% vs. 30%; P = 0.023). Complications (blood loss, transfusion requirement, and hospital stay) were similar between the two groups. Median follow-up was 33 (range, 2–77) months. Incidence of local recurrence at 2 years was 30% and 59% in the AR and NAR groups, respectively. Median time to first local recurrence in the AR group was significantly longer than in the NAR group (53 vs. 10 months, P = 0.010). There was no difference in overall RFS between the two groups (P = 0.290). Discussion AR decreased the 2-year local recurrence rate and increased the time to first local recurrence compared to NAR in patients with HCC.

Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) has high morbidity and mortality. In this study, the safety and efficacy of a modification of ALPPS (radiofrequency-assisted ALPPS, RALPPS) were assessed in patients with hepatocellular carcinoma (HCC).Patients who were diagnosed with HCC and were considered to have an insufficient future liver remnant (FLR) were enrolled. In stage I, a radiofrequency ablation (RFA) device was used to cauterise along the planned transection plane to form a coagulum avascular area. When the FLR reached above 40%, hepatectomy was performed in stage II along the coagulum area established previously. After two stages, operative morbidity, mortality, per cent increase in FLR, operative time and blood loss were evaluated.Between July 2014 and September 2015, 10 patients with HCC (9 with hepatitis-related cirrhosis) were treated with the RALPPS procedure. The incidence of severe complications (Clavien-Dindo ≥ IIIb) was 20% (2/10). One patient died. No biliary leakage, intraperitoneal infection or post-hepatectomy liver failure (PHLF) occurred after both stages. The median FLR before stage I was 31% (364 ml). This increased to 47% (632 ml) before stage II after a median interval of 28 days. The median percentage increase in FLR was 53% (210 ml). Additionally, the median operative time during the first and second stages was 214 and 281 min, respectively. The corresponding median blood loss was 200 and 550 ml, respectively.RALPPS has a potential advantage in eliminating serious complications of biliary leakage and PHLF associated with classic ALPPS. On the basis of rigorous patient selection criteria, RALPPS may achieve the same effect of promoting significant growth of the FLR in patients with cirrhosis-related HCC and insufficient FLR volume, albeit at the cost of a longer interval time.

Background Radiofrequency ablation (RFA) for the treatment of small hepatocellular carcinoma (HCC) has a drawback of high recurrence rate. No-touch technique was developed to overcome it. However, it has barely been studied in Chinese populations. The aim of this study is to determine the safety and efficacy of no-touch RFA in the treatment of cirrhosis-based small HCC patients. Methods A total of 130 patients of small HCC in Southwest Hospital were enrolled in this study, 46 cases treated by no-touch RFA and 84 cases by conventional RFA. Treatment complications and tumor-free survival rate and overall survival rate were compared and analyzed. Results There were no significant differences in baseline confounding factors between the two groups. The ablation volume of no-touch RFA technique was significantly higher than conventional RFA (P = 0.002) but the remaining liver volume and treatment complications of the two techniques were the same (P = 0.702 and P = 0.269, respectively). Cox regression model revealed that conventional RFA was a predictive factor for short-term HCC recurrence (P = 0.041 for 2-year recurrence rate). Kaplan-Meier survival showed that tumor-free survival in no-touch group was significantly higher than conventional group (P = 0.047). Conclusions Our data showed that no-touch RFA provided a higher short-term tumor-free survival rate than conventional RFA but was as safe as conventional RFA.

BACKGROUND The usefulness of Des-g-carboxyprothrombin (DCP) has been indicated in areas where hepatitis C virus is prevalent. DCP has yet to be used in China. The aim of this study was to evaluate the usefulness of DCP in Chinese patients with hepatocellular carcinoma (HCC) predominantly caused by hepatitis B. MATERIAL AND METHODS 329 subjects with HCC and 371 subjects without HCC that all underwent surgery were consecutively enrolled. Serum AFP and plasma DCP levels in all subjects and 153 healthy volunteers were measured and analyzed. RESULTS Of 329 subjects with HCC, 258 (78.4%) were HBsAg positive. The median level of plasma DCP was 853.72 mAU/mL in subjects with HCC, 26.43 mAU/mL in subjects without HCC, and 29.91 m AU/mL in healthy volunteers. A cut-off DCP value of 87 mAU/mL yielded the optimal sensitivity of 74.80% and a specificity of 83.33% for differentiating subjects with HCC from subjects without HCC. The combination of AFP of 21.33 ng/mL and DCP of 87 mAU/mL had a sensitivity of 82.60% for tumors no larger than 2 cm, as well as a sensitivity of 90% for tumors larger than 5 cm. CONCLUSIONS The combination of DCP and AFP yielded great improvement in sensitivity in differentiating subjects with HCC from subjects without HCC. These two markers may be incorporated in the protocol for surveillance and diagnosis of HCC in the high-risk Chinese population.

Primary hepatic neuroendocrine tumor (PHNET) is an extremely rare liver neoplasm, and its clinical characteristics and imaging features are not well understood. The aim of this study was to analyze the clinical profiles and imaging features of PHNETs on contrast-enhanced ultrasound (CEUS) and computed tomography (CT) METHODS: Patients with PHNET between January 2008 and December 2015 were retrospectively identified, and their demographics, laboratory data, and imaging characteristics on CEUS and CT analyzed.Ten consecutive patients with PHNETs were included (including one G1, seven G2, and two G3 of tumor grades).The median age of patient was 45 years (range: 27-72 years), and 60.0% of patients were male. The most common symptom was abdominal pain (60.0%), and cirrhosis was found in 40.0% of patients. Tumors were confined within the liver in 60.0% of patients, while the remaining patients had extra-hepatic metastasis. The tumors revealed hyperechoic in 60% of patients and mixed echoic in 30% of patients on conventional US, displaying intense arterial enhancement followed by washout in the portal and/or the late phases in 80.0% of patients on CEUS and 60% at CT.Although PHNET is a very rare liver tumor, it should be considered as a possible differential diagnosis in the management of hepatic tumors. Most PHNETs were hyperechoic or mixed echoic on conventional US, showing similar enhancement patterns to that of hepatocellular carcinoma on CEUS.

Insufficient radiofrequency ablation (iRFA) often leads to residual hepatocellular carcinoma (HCC) progression. However, the mechanism is still poorly understood. In the present study, we demonstrated that LC3B protein expression levels were significantly increased in the residual hepatocellular carcinoma cells after radiofrequency ablation (RFA) treatment in vivo. Moreover, iRFA promoted autophagy, autophagosome formation and autophagic flux in Huh-7 and SMMC7721 cell lines in vitro. In addition, iRFA induced HCC cell viability and invasion. However, blockade of autophagy by the autophagosome inhibitor 3-methyladenine (3-MA) suppressed iRFA-induced cell viability and invasion. Furthermore, we revealed that the expression of liver cancer stem cell marker CD133 was also significantly increased in the residual hepatocellular carcinoma cells after RFA treatment in vivo, and was positively correlated with LC3B protein expression. iRFA also promoted CD133 protein expression in Huh-7 and SMMC7721 cell lines in vitro. CD133 was localized to autophagosomes, and was suppressed by 3-MA or chloroquine (CQ) after iRFA treatment. CD133 downregulation also suppressed iRFA-induced cell viability, invasion and autophagy. Collectively, our results indicated that RFA may promote residual HCC cell progression by autophagy and CD133 feedback loop.

The objective of this study was to compare the short- and long-term outcomes of radiofrequency-assisted liver resection (RFLR) and conventional clamp-crushing liver resection (CCLR) and to evaluate the safety and efficiency of RFLR. Between January 2008 and December 2012, a total of 597 patients with hepatocellular carcinoma (HCC) who underwent curative hepatectomy were identified. A total of 272 patients underwent RFLR, and 325 patients received CCLR. The short- and long-term outcomes were compared. The patients in the RFLR and CCLR groups showed similar baseline characteristics. The RFLR group showed less intraoperative blood loss (485.5 vs. 763.2 mL, p = 0.003), a lower transfusion requirement rate (19.1 vs. 31.7%, p ≤ 0.01), shorter surgery duration (211 vs. 296 min, p ≤ 0.01) and a lower vascular inflow occlusion rate (25.7 vs. 33.8%, p = 0.032). No significant postoperative changes in bilirubin or liver enzymes were observed in the two groups. The degree of postoperative complications and morbidity did not significantly differ between the two groups. There were no significant differences in the 1-, 2- and 3-year overall survival rates (73.8%, 58.5%, and 55.7% vs. 80.8%, 65.8%, and 56.2%, respectively) or disease-free rates (51.9%, 47.2%, and 46.0% vs. 54.5%, 44.9%, and 38.5%, respectively) between the RFLR and CCLR groups. These results suggested RFLR was a safe and efficient method for patients with HCC. RFLR was associated with decreased blood loss, fewer blood transfusions, shorter surgery times and less vascular inflow occlusion application. The RFLR group did not show increased liver injury or postoperative morbidity or mortality.

To assess the long-term outcome of 516 consecutive patients treated with multiple-electrode switching system (MESS) radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) that met the Milan criteria.We performed 522 MESS RFAs on 516 patients from December 2006 to June 2011. A total of 956 tumours that met the Milan criteria with an average diameter of 2.64 cm (range, 0.9-4.6 cm) were treated with MESS RFA. Ultrasonic contrast and serum α-fetoprotein (AFP) were measured every 2 months during the first postoperative year and every 4 months thereafter. Enhanced computed tomography was performed every 6 months. Survival was estimated using the Kaplan-Meier method. Follow-up was censored at 60 months. Multivariate analysis was performed using the Cox proportional hazards model.For the 956 HCC tumours, the complete ablation rate with MESS was 98.83% (510/516). During a median of 34 months (IQR, 23-52 months) of follow-up, 171 patients died and 4 were lost to follow-up (15, 30, 38 and 42 months). The cumulative incidence of local tumour progression at 1, 3 and 5 years was 0.39%, 4.96% and 6.66%, respectively, and the 1-, 3- and 5-year overall survival was 99.42%, 83.97% and 68.42%, respectively. Tumour size30 mm was the only parameter that was predictive of local tumour progression (p .0001). Risk factors associated with overall survival included prothrombin time14 s, serum AFP levels200 ng/mL and tumour abutting vessel diameter5 mm. The complication rate was 1.74%.MESS RFA is a safe and effective method for HCC treatment. This approach results in a high local progression-free survival for HCC tumours that meet the Milan criteria.

Combination Therapy With Sorafenib and Radiofrequency Ablation for BCLC Stage 0–B1 Hepatocellular Carcinoma: A Multicenter Retrospective Cohort Study

To the Editor: We thank you very much for your kind comments, Combination Therapy with Sorafenib and Radiofrequency Ablation for Hepatocellular Carcinoma: a Glimmer of Light after the STORM Trial? (1). We appreciate the professional and precise point of view on this study, which will undoubtedly help us improve our understanding.

AIM: To investigate the efficacy and safety of adjuvant sorafenib after curative resection for patients with Barcelona Clinic Liver Cancer (BCLC)-stage C hepatocellular carcinoma (HCC). METHODS: Thirty-four HCC patients, classified as BCLC-stage C, received adjuvant sorafenib for high-risk of tumor recurrence after curative hepatectomy at a tertiary care university hospital. The study group was compared with a case-matched control group of 68 patients who received curative hepatectomy for HCC during the study period in a 1:2 ratio. RESULTS: The tumor recurrence rate was markedly lower in the sorafenib group (15/34, 44.1%) than in the control group (51/68, 75%, P = 0.002). The median disease-free survival was 12 mo in the study group and 10 mo in the control group. Tumor number more than 3, macrovascular invasion, hilar lymph nodes metastasis, and treatment with sorafenib were significant factors of disease-free survival by univariate analysis. Tumor number more than 3 and treatment with sorafenib were significant risk factors of disease-free survival by multivariate analysis in the Cox proportional hazards model. The disease-free survival and cumulative overall survival in the study group were significantly better than in the control group (P = 0.034 and 0.016, respectively). CONCLUSION: Our study verifies the potential benefit and safety of adjuvant sorafenib for both decreasing HCC recurrence and extending disease-free and overall survival rates for patients with BCLC-stage C HCC after curative resection.

Significant intraoperative bleeding and injuries to vital structures in the liver remnant can occur during liver parenchymal transection using the conventional clamp-crushing technique. We performed liver resection on 242 patients using a mosquito clamp-crushing technique combined with a self-assembled saline-linked diathermy for liver parenchymal transection. The mean blood loss was 215 mL (range 20-1100). There was no damage to the vital structures in the liver remnant. The mean liver transection time was 53 minutes (range 15-125). Our technique has the advantages of reducing blood loss, exposing vessles clearly and being simple, cheap and efficacious.

There is currently no clear consensus on the relative suitabilities of laparoscopic hepatectomy (LH) and radiofrequency ablation (RFA) as minimally invasive treatment for small hepatocellular carcinoma (HCC). In this retrospective study, we enrolled 156 patients with a single, small HCC with nodular diameters

Limited data exists in China on the comparative cost of gadolinium ethoxybenzyl diethylenetriamine magnetic resonance imaging (Gd-EOB-DTPA-MRI) with other imaging techniques. This study compared the total cost of Gd-EOB-DTPA-MRI with multidetector computed tomography (MDCT) and extracellular contrast media-enhanced MRI (ECCM-MRI) as initial imaging procedures in patients with suspected hepatocellular carcinoma (HCC). We developed a decision-tree model on the basis of the Chinese clinical guidelines for HCC, which was validated by clinical experts from China. The model compared the diagnostic accuracy and costs of alternative initial imaging procedures. Compared with MDCT and ECCM-MRI, Gd-EOB-DTPA-MRI imaging was associated with higher rates of diagnostic accuracy, i.e. higher proportions of true positives (TP) and true negatives (TN) with lower false positives (FP). Total diagnosis and treatment cost per patient after the initial Gd-EOB-DTPA-MRI evaluation was similar to MDCT (¥30,360 vs. ¥30,803) and lower than that reported with ECCM-MRI (¥30,360 vs. ¥31,465). Lower treatment cost after initial Gd-EOB-DTPA-MRI was driven by reduced utilization of confirmatory diagnostic procedures and unnecessary treatments. The findings reported that Gd-EOB-DTPA-MRI offered higher diagnostic accuracy compared with MDCT and ECCM-MRI at a comparable cost, which indicates Gd-EOB-DTPA-MRI could be the preferred initial imaging procedure for the diagnosis of HCC in China.

AIM: To assess the efficiency and safety of radiofrequency-assisted hepatectomy in patients with hepatocellular carcinoma (HCC) and cirrhosis. METHODS: From January 2010 to December 2013, 179 patients with HCC and cirrhosis were recruited for this retrospective study. Of these, 100 patients who received radiofrequency-assisted hepatectomy (RF+ group) were compared to 79 patients who had hepatectomy without ablation (RF- group). The primary endpoint was intraoperative blood loss. The secondary endpoints included liver function, postoperative complications, mortality, and duration of hospital stay. RESULTS: The characteristics of the two groups were closely matched. The Pringle maneuver was not used in the RF+ group. There was significantly less median intraoperative blood loss in the RF+ group (300 vs 400 mL, P = 0.01). On postoperative days (POD) 1 and 5, median alanine aminotransferase was significantly higher in the RF+ group than in the RF- group (POD 1: 348.5 vs 245.5, P = 0.01; POD 5: 112 vs 82.5, P = 0.00), but there was no significant difference between the two groups on POD 3 (260 vs 220, P = 0.24). The median AST was significantly higher in the RF+ group on POD 1 (446 vs 268, P = 0.00), but there was no significant difference between the two groups on POD 3 and 5 (POD 3: 129.5 vs 125, P = 0.65; POD 5: 52.5 vs 50, P = 0.10). Overall, the rate of postoperative complications was roughly the same in these two groups (28.0% vs 17.7%, P = 0.11) except that post hepatectomy liver failure was far more common in the RF+ group than in the RF- group (6% vs 0%, P = 0.04). CONCLUSION: Radiofrequency-assisted hepatectomy can reduce intraoperative blood loss during liver resection effectively. However, this method should be used with caution in patients with concomitant cirrhosis because it may cause severe liver damage and liver failure.

This study aimed to investigate the clinical utility of simultaneous measurement of alphafetoprotein (AFP) and des-γ-carboxy prothrombin (DCP) for hepatocellular carcinoma (HCC) diagnosis in Chinese patients predominantly caused by hepatitis B virus infection by a multi-center case-controlled study. Subjects were 1,153 individuals from three major hospitals in China, including 550 cases in HCC group, 164 in Malignant disease group, 182 in Benign disease group, 85 in Chronic liver disease group, and 173 in Normal group. Serum levels of AFP and DCP were measured and clinicopathological features were determined for all subjects. Results showed that the levels of DCP and AFP were significantly higher in HCC group (550 patients, 74.18% with HBV infection) than that in other four groups (P < 0.001). Receiver operating curves (ROC) indicated the optimal cut-off value was 86 mAU/mL for DCP with a sensitivity of 71.50% and specificity of 86.30%, and 21 ng/mL for AFP with a sensitivity of 68.00% and specificity of 93.20%. The area under ROC curve was 0.846 for DCP, 0.832 for AFP, and 0.890 for the combination of DCP and AFP. The combination of DCP and AFP resulted in a higher Youden index and a sensitivity of approximately 90%, even for small tumors. The simultaneous measurement of AFP and DCP could achieve a better sensitivity in diagnosing Chinese HCC patients, even for small tumors.

The aim of this study was to evaluate the safety and outcomes of radiofrequency ablation (RFA) in treating elderly patients with hepatocellular carcinoma (HCC).This was a retrospective analysis of 391 patients with HCC fitting the Milan criteria and treated with RFA for the first time from 1999 to 2012 at the Southwest Hospital, China. The patients were divided into two groups, an elderly group (age ≥70 years, n = 102) and a non-elderly group (age70 years, n = 289). Long-term outcomes were assessed on all patients and survival rates were calculated.The overall survival rates of the two groups differed significantly. The recurrence-free survival rates of the two groups did not differ significantly. There was no significant difference between the two groups. Excluding comorbid diseases related deaths, the overall survival rates of the two groups did not differ significantly.The safety and outcomes of RFA in treating early HCC were similar among elderly and non-elderly patients. Co-morbid diseases, such as cardiovascular disease and respiratory disease, rather than HCC or liver diseases, contributed to the relatively low overall survival rate found in elderly patients.

Radiofrequency ablation (RFA) is a minimally invasive technique used for the treatment of hepatocellular carcinoma (HCC). It may produce complications. The indocyanine green (ICG) retention rate at 15 min (ICGR15) has been used to predict complications after hepatectomy. In this study, the prediction of the value of ICGR15 for complications of RFA to the patients with HCC was evaluated.Some 878 cases of HCC treated between June 2009 and June 2013 were evaluated. All patients were treated by percutaneous radiofrequency ablation. Patients were divided into two groups: a complication group (85 cases) and a complication-free group (793 cases). ICGR15 and other baseline characteristics of the two groups were compared. A logistic regression model was used to analyse the merits of assessing liver reserve to predict complications post-RFA.Complications such as intra-abdominal haemorrhage and pleural effusion occurred in 85 (9.68%) patients after RFA. Patients in the two groups did not differ with regard to baseline parameters. Patients in the two groups did differ significantly in ICGR15 and tumour site (p 0.05). Tumour site was found to have a significant impact on the rate of complications post-RFA. There was no significant difference in ICGR15 values among patients with the same Child-Pugh scores or in the same tumour site.The present results demonstrated that RFA is minimally invasive and suitable for the treatment of HCC. They also showed that ICGR15 did not independently predict for liklihood of post-RFA complications, after controlling for tumour site. Patients with tumours located subcapsularly or near the porta hepatis were found to have significantly higher rates of post-operative complications after RFA than to patients with tumours in the liver parenchyma.

Background Neoplastic and bland portal vein thrombi (PVT) are both common in patients with hepatocellular carcinoma (HCC). The correct discrimination of them is essential for therapeutic strategies planning and survival predicting. The current study aims to investigate the value of susceptibility-weighted imaging (SWI) in differentiating bland from neoplastic PVT in HCC patients. Methods 20 HCC patients with bland PVT and 22 HCC patients with neoplastic PVT were imaged with non-contrast SWI at 3.0 Tesla MRI. The signal intensity (SI) of the PVT and HCC lesions in the same patients was compared on SW images. The phase values of the PVT were compared between neoplastic and bland thrombi cohorts. Receiver operator characteristics (ROC) analysis was conducted to evaluate the diagnostic ability of the phase values for neoplastic and bland thrombi discrimination. Results 20 of 22 neoplastic PVT were judged similar SI and 2 were judged lower SI than their HCC. For 20 bland PVT, 19 were judged lower SI and 1 was judged similar SI as their HCC (P

BACKGROUND: The prognosis of hepatocellular carcinoma (HCC) patients with extrahepatic metastasis is extremely poor. However, what is the main risk factor for survival remains unclear for these patients. We aimed to find out the relative frequency, incidence and locations of extrahepatic metastases and the risk factors of long-term survival of the patients. METHODS: 132 HCC patients with extrahepatic metastasis diagnosed by 18F-FDG PET/CT and conventional workup were enrolled into this study. The incidence and locations of extrahepatic metastases were summarized, and the related risk factors of overall survival were analyzed. RESULTS: The most frequent extrahepatic metastatic sites were lymph nodes in 72 (54.5%), bone in 33 (25.0%) and lung in 28 (21.2%) patients. On univariate analysis, prothrombin time, Child-Pugh grade, portal/hepatic vein invasion and lymph node metastasis were independent risk factors of overall survival. On multivariate analysis, lymph node metastasis was the only independent risk factor of overall survival. The cumulative survival rates at 1- and 3-years after diagnosis of extrahepatic metastasis of HCC were 34.4% and 9.3%, respectively. The median survival time was 7 months (range 1 ∼38 months). The median survival time for patients with or without lymph node metastasis were 5 months (range 1∼38 months) and 12 months (range 1∼30 months), respectively (P = 0.036). CONCLUSIONS: This study showed lymph nodes to be the most frequent site of extrahepatic metastases for primary HCC. Lymph node metastasis was the main risk factor of overall survival in patients with HCC with extrahepatic metastasis.

Hepatocellular carcinoma (HCC) is a malignant disease that substantially affects public health worldwide. It is especially prevalent in east Asia and sub-Saharan Africa, where the main etiology is the endemic status of chronic hepatitis B. Effective treatments with curative intent for early HCC include liver transplantation, liver resection (LR), and radiofrequency ablation (RFA). RFA has become the most widely used local thermal ablation method in recent years because of its technical ease, safety, satisfactory local tumor control, and minimally invasive nature. This technique has also emerged as an important treatment strategy for HCC in recent years. RFA, liver transplantation, and hepatectomy can be complementary to one another in the treatment of HCC, and the outcome benefits have been demonstrated by numerous clinical studies. As a pretransplantation bridge therapy, RFA extends the average waiting time without increasing the risk of dropout or death. In contrast to LR, RFA causes almost no intra-abdominal adhesion, thus producing favorable conditions for subsequent liver transplantation. Many studies have demonstrated mutual interactions between RFA and hepatectomy, effectively expanding the operative indications for patients with HCC and enhancing the efficacy of these approaches. However, treated tumor tissue remains within the body after RFA, and residual tumors or satellite nodules can limit the effectiveness of this treatment. Therefore, future research should focus on this issue.

Liver cancer is one of the top six leading causes of cancer-related death. Radiofrequency ablation (RFA) is an important means of treating liver cancer. Residual cancer after RFA is the most frequent cause of recurrence in cases of liver cancer. The main difference between residual cancer cells and ordinary liver cancer cells is that residual cancer cells experience heat shock. The secretable form of trimeric human tumor necrosis factor-related apoptosis-inducing ligand (stTRAIL) induces apoptosis in a variety of human cancers but not in normal tissues. It has shown potent cancer-selective killing activity and has drawn considerable attention as a possible cancer therapy. In the present work, the therapeutic potential of this stTRAIL-based gene therapy was evaluated in hepatocellular carcinoma subjected to RFA. Rat bone marrow mesenchymal stem cells (BM-MSCs) were isolated and transduced with a lentiviral vector encoding stTRAIL (stTRAIL-MSCs, T-MSCs). Cells treated with heat treatment at 43 °C for 45 min served as simulated residual cancer cells. After treatment with T-MSCs, apoptosis in heat-shock-treated liver cancer cells increased significantly, and caspase-3 was upregulated. When T-MSCs were subcutaneously injected into nude mice, they localized to the tumors and inhibited tumor growth, significantly increasing survival. Collectively, the results of the present study indicate that BM-MSC can provide a steady source of stTRAIL and may be suitable for use in the prevention of the recurrence of hepatocellular carcinoma after RFA with secretable trimeric TRAIL.

In China, hepatocellular carcinoma (HCC) is the second most common cancer in urban areas and first most common in rural areas. It ranks as the second leading cause of cancer-related deaths in males and the third leading cause of cancer-related deaths in females, with the total mortality rate of 26.26 per 100,000. Currently, people with hepatitis B virus (HBV) infection are a major population at risk of developing HCC in China. In fact, there are 93 million Chinese who are HBV carriers, and about 20 million of them have chronic HBV infection. Several cohort studies have shown that screening high-risk patients with HBV-or HCV-related chronic liver disease may improve the rate of early HCC detection and the rate of curative treatment. However, a government-funded national program to screen for high-risk patients with HBV-related chronic liver disease has yet to be established in China. Although several remarkable advances in HCC management have been made during the past few decades, most patients with HCC still present with advanced-stage disease, thus reducing the chance of curative treatment. Based on firsthand experience in Japan and other countries or areas, this work examined the current status, challenges, and prospects for the future of early detection of HCC in China. Findings suggested the need for a systematic guideline for the standardized management of HCC, a government-funded nationwide screening and surveillance program for high-risk patients with HBV-related chronic liver disease, and extensive use of des-γ-carboxyprothrombin (DCP) as a screening tool in China in order to facilitate the early detection of HCC in China.

Radiofrequency ablation (RFA) is a minimally invasive technique used to treat liver tumors. The current study presents the case of a patient with hepatocellular carcinoma who suffered from post-operative pericardial effusion following RFA treatment. We hypothesize that RFA thermal conduction may damage the diaphragm and pericardium, leading to local edema in the pericardium. RFA is a minimally invasive technique, however, adequate preparatory work must be performed prior to surgery, including a comprehensive assessment of the patient. During surgery, the location and extent of the region to receive RFA must be determined precisely in order to reduce the range of damage and to avoid post-operative complications. This study describes a case of pericardial effusion caused by RFA of liver cancer. We analyzed the causes and preventive measures for pericardial effusion in order to contribute to the prevention pericardial effusion that is complicated by RFA of liver cancer.

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