Search

Simple Summary: The liver function reserve of patients with hepatocellular carcinoma (HCC) is heterogeneous. The preoperative accurate evaluation of liver function has a vital role in the prevention of unfavorable postoperative complications such as post-hepatectomy liver failure. In this study, unsupervised clustering analysis of radiomics features extracted from preoperative gadoxetic-acid-enhanced MRIs was performed for liver function stratification on 276 HCC patients. Two distinct subgroups were identified (i.e., subgroups 1 and 2). Subgroup 2 had impaired liver function as presented by older age, more albumin–bilirubin grades 2 and 3, and a higher indocyanine green retention rate than that of subgroup 1 (all p < 0.05). Compared with subgroup 1, subgroup 2 was associated with a higher risk of postoperative liver failure, postoperative complications, and longer hospital stays (all p < 0.05). Our findings indicate the potential for the use of radiomics features based on preoperative gadoxetic-acid-enhanced MRI for noninvasive liver function assessment in HCC patients. Objective: To identify subgroups of patients with hepatocellular carcinoma (HCC) with different liver function reserves using an unsupervised machine-learning approach on the radiomics features from preoperative gadoxetic-acid-enhanced MRIs and to evaluate their association with the risk of post-hepatectomy liver failure (PHLF). Methods: Clinical data from 276 consecutive HCC patients who underwent liver resections between January 2017 and March 2019 were retrospectively collected. Radiomics features were extracted from the non-tumorous liver tissue at the gadoxetic-acid-enhanced hepatobiliary phase MRI. The reproducible and non-redundant features were selected for consensus clustering analysis to detect distinct subgroups. After that, clinical variables were compared between the identified subgroups to evaluate the clustering efficacy. The liver function reserve of the subgroups was compared and the correlations between the subgroups and PHLF, postoperative complications, and length of hospital stay were evaluated. Results: A total of 107 radiomics features were extracted and 37 were selected for unsupervised clustering analysis, which identified two distinct subgroups (138 patients in each subgroup). Compared with subgroup 1, subgroup 2 had significantly more patients with older age, albumin–bilirubin grades 2 and 3, a higher indocyanine green retention rate, and a lower indocyanine green plasma disappearance rate (all p < 0.05). Subgroup 2 was also associated with a higher risk of PHLF, postoperative complications, and longer hospital stays (>18 days) than that of subgroup 1, with an odds ratio of 2.83 (95% CI: 1.58–5.23), 2.41(95% CI: 1.15–5.35), and 2.14 (95% CI: 1.32–3.47), respectively. The odds ratio of our method was similar to the albumin–bilirubin grade for postoperative complications and length of hospital stay (2.41 vs. 2.29 and 2.14 vs. 2.16, respectively), but was inferior for PHLF (2.83 vs. 4.55). Conclusions: Based on the radiomics features of gadoxetic-acid-enhanced MRI, unsupervised clustering analysis identified two distinct subgroups with different liver function reserves and risks of PHLF in HCC patients. Future studies are required to validate our findings. [ABSTRACT FROM AUTHOR]

Objectives: Large hepatocellular carcinoma (LHCC) is prone to short‐term recurrence and poor long‐term survival after hepatectomy, and there is still a lack of effective neoadjuvant treatments to improve recurrence‐free survival (RFS) and overall survival (OS). We retrospectively analyzed the efficacy of preoperative transcatheter arterial chemoembolization (TACE) in solitary LHCC (≥5 cm). Materials and Methods: A multicenter medical database was used to analyze preoperative TACE's effects on RFS, OS, and perioperative complications in patients with solitary LHCC who received surgical treatment from January 2005 to December 2015. The patients were divided into Group A (5.0–9.9 cm) and Group B (≥10 cm), with 10 cm as the critical value, and the effect of preoperative TACE on RFS, OS and perioperative complications was assessed in each subgroup. Results: In the overall population, patients with preoperative TACE had better RFS and OS than those without preoperative TACE. However, after stratifying the patients into the two HCC groups, preoperative TACE only improved the survival outcomes of patients with Group B (≥10 cm). Multivariate Cox‐regression analysis showed that lack of preoperative TACE was an independent risk factor for RFS and OS in the overall population and in Group B but not in Group A. Conclusions: Preoperative TACE is beneficial for patients with solitary HCC (≥10 cm). [ABSTRACT FROM AUTHOR]

The impact of currently clinically significant portal hypertension (CSPH) for patients with early-stage HCC after surgery remains controversial. The purpose of this study is to understand the specific effect of CSPH on patients with early-stage (BCLC A stage) HCC after surgery. We collected data from 386 HCC patients treated at two centers from December 2009 to January 2017.224 patients (all treated by hepatectomy) were in BCLC stage A, of which, 122 had no CSPH, and 102 had CSPH. There were 162 patients in BCLC stage B (who underwent surgery, TACE, and conservative treatment). The prognosis of the CSPH and non-CSPH groups in BCLC stage A was compared using the Kaplan-Meier method. We used multivariate Cox regression to analyze prognostic factors in patients in BCLC stage A and compared the prognosis of the two groups with the BCLC stage B group. Among the 224 BCLC stage A patients after surgery, the overall survival (OS) and recurrence-free survival (RFS) of the CSPH group were worse than those of the non-CSPH group (P < 0.001, HR = 2.340[1.554–3.523]; P < 0.001, HR = 2.577[1.676–3.812]) The multivariate Cox proportional hazards model indicated that CSPH was an independent prognostic factor for OS and RFS in BCLC stage A patients. BCLC stage A patients with CSPH treated by hepatectomy had a comparable prognosis to BCLC B stage patients (P = 0.378), and the OS and RFS (P = 0.229; P = 0.077) in the CSPH (BCLC A) group were also comparable to BCLC stage B patients treated with surgery alone. CSPH can affect the surgical prognosis of early-stage (BCLC stage A) HCC. BCLC stage A patients with CSPH have a prognosis comparable to patients with BCLC stage B. An additional stage, such as the BCLC stage A-B, can be considered. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the long‐term efficacy of no‐touch radiofrequency ablation (NT‐RFA) for treating single hepatocellular carcinoma (HCC) less than 3 cm. Methods: A total of 331 patients with HCC less than 3 cm undergoing RFA in Southwest Hospital from 2015 to 2020 were analyzed retrospectively. All patients were divided into NT‐RFA group (n = 113) and conventional RFA (C‐RFA) group (n = 218). The survival rate, local tumor progression (LTP) and intrahepatic distant recurrence (IDR) of the two groups were calculated and compared. Results: A significant difference was observed in ablation range (p = 0.000) and safety margin (p = 0.000) between the two groups. The 1‐, 2‐, 3‐, 4‐and 5‐year overall survival (OS) rates in NT‐RFA and C‐RFA group were 99.12%, 93.73%, 76.18%, 57.00%, 45.17% and 99.08%, 89.91%, 71.26%, 54.28%, 41.77%, respectively. There was no significant difference between the two groups (p = 0.281). The 1‐, 2‐, 3‐, 4‐and 5‐year recurrence‐free survival (RFS) rates in NT‐RFA and C‐RFA group were 78.51%, 52.59%, 41.02%, 34.36%, 30.92% and 68.81%, 44.95%, 30.88%, 23.73%, 22.88%, respectively. The two groups differed significantly (p = 0.044). The 1‐, 3‐and 5‐year LTP‐free survival rates in NT‐RFA and C‐RFA group were 87.12%, 74.99%, 72.32% and 75.75%, 65.52%, 65.52%, respectively. The two groups also differed significantly (p = 0.024). Furthermore, the RFS rates of D ≤ 2 cm subgroups in NT‐RFA and C‐RFA groups differed significantly (p = 0.037), while the RFS rates of 2 cm < D ≤ 3 cm subgroups in two groups showed no significant difference (p = 0.578). Conclusions: The RFS rates of single HCC less than 3 cm treated by NT‐RFA was significantly higher than that of C‐RFA. Due to a larger ablation range and safety margin, NT‐RFA could significantly reduce LTP and improve RFS. Dual‐electrode NT‐RFA can significantly improve the RFS rate of patients with HCC less than 2 cm, but there is no obvious advantage compared with C‐RFA in the treatment of HCC over 2 cm. [ABSTRACT FROM AUTHOR]

Histopathologic grade of hepatocellular carcinoma (HCC) is an important predictor of early recurrence and poor prognosis after curative treatments. This study aims to develop a radiomics model based on preoperative gadoxetic acid-enhanced MRI for predicting HCC histopathologic grade and to validate its predictive performance in an independent external cohort. Clinical and imaging data of 403 consecutive HCC patients were retrospectively collected from two hospitals (265 and 138, respectively). Patients were categorized into poorly differentiated HCC and non-poorly differentiated HCC groups. A total of 851 radiomics features were extracted from the segmented tumor at the hepatobiliary phase images. Three classifiers, logistic regression (LR), support vector machine, and Adaboost were adopted for modeling. The areas under the curve of the three models were 0.70, 0.67, and 0.61, respectively, in the external test cohort. Alpha-fetoprotein (AFP) was the only significant clinicopathological variable associated with HCC grading (odds ratio: 2.75). When combining AFP, the LR+AFP model showed the best performance, with an AUC of 0.71 (95%CI: 0.59–0.82) in the external test cohort. A radiomics model based on gadoxetic acid-enhanced MRI was constructed in this study to discriminate HCC with different histopathologic grades. Its good performance indicates a promise in the preoperative prediction of HCC differentiation levels. [ABSTRACT FROM AUTHOR]

To compare the short- and long-term treatment outcomes of open radiofrequency ablation combined with splenectomy and pericardial devascularization versus liver transplantation for hepatocellular carcinoma patients with portal hypertension and hypersplenism. During the study period, the treatment outcomes of consecutive HCC patients with portal hypertension and hypersplenism who underwent open radiofrequency ablation, splenectomy and pericardial devascularization (the study group) were compared with the treatment outcomes of a case-matched control group of HCC patients who underwent liver transplantation. The study group consisted of 32 patients, and the control group comprised 32 patients selected from 155 patients who were case-matched by tumor size, age, gender, MELD sore, tumor location, TNM classification, degree of splenomegaly and Child–Pugh staging. Baseline data on preoperative laboratory tests and tumor characteristics were comparable between the two groups. The mean follow-up was 43.2 ± 5.3 months and 44.9 ± 5.8 months for the study and control groups, respectively. Although the disease-free survival rates of the control group were better than those of the study group (P < 0.001), there was no significant difference in the cumulative overall survival time or the incidence of portal vein thrombosis between the two groups (P = 0.670, 0.083). Compared with the control group, the study group had significantly less intraoperative blood loss, and lower incidences of postoperative pleural effusion and pneumonia (all P < 0.05). Open radiofrequency ablation, splenectomy and pericardial devascularization for small HCCs with portal hypertension and hypersplenism can be an alternative therapy for a subset of carefully selected patients under the shortage of liver donors. [ABSTRACT FROM AUTHOR]

Ruptured hepatocellular carcinoma (rHCC) generally has a very poor prognosis and is currently classified as T4 in the tumor–node–metastasis (TNM) staging system. In this study, we aimed to demonstrate the actual impact of rHCC, as well as the positive effect of hepatectomy in patients with Barcelona Clinic Liver Cancer (BCLC) stage 0/A rHCC. We enrolled 86 patients with rHCC after surgery and 526 patients with non-rHCC after surgery or transcatheter arterial chemoembolization (TACE). Survival curves were plotted using the Kaplan–Meier method to compare the postoperative prognosis of patients with rHCC with that of patients with non-rHCC. Univariate and multivariate Cox regression analyses were used to identify the risk factors affecting patient survival. BCLC stage 0/A rHCC treated with surgery had a worse prognosis than BCLC stage 0/A non-rHCC treated with surgery (overall survival [OS]: hazard ratio [HR] = 3.12 [2.24–4.34], P < 0.001; recurrence-free survival [RFS]: HR = 2.26 [1.65–3.09], P < 0.001). Rupture was an independent prognostic factor in patients with BCLC stage 0/A rHCC (OS: HR = 1.685 [1.416–2.006], P < 0.001; RFS: HR = 1.484 [1.267–1.737], P < 0.001), and patients with BCLC stage 0/A rHCC who underwent surgery had a comparable prognosis to patients with BCLC stage B HCC who underwent surgery or TACE (OS: P = 0.78). Patients classified as having BCLC stage 0/A rHCC can achieve comparable outcomes to patients with BCLC stage B HCC after hepatectomy. However, not all patients with rHCC should be classified as T4 in the TNM staging system. [ABSTRACT FROM AUTHOR]

Background: Large hepatocellular carcinoma (LHCC) is highly malignant and prone to recurrence, leading to a poor long-term prognosis for patients. There is an urgent need for measures to intervene in postoperative recurrence. Preoperative Transcatheter Arterial Embolization (TACE) is an effective treatment. However, there is a lack of reliable preoperative indicators to guide the application of preoperative TACE. We, therefore, investigated whether the preoperative status of circulating tumor cells (CTCs) could be used to guide preoperative TACE for HCC treatment. Methods: This study recruited 361 HCC patients and compared recurrence-free survival (RFS) and overall survival (OS) in patients treated with TACE prior to surgery and those not treated with TACE. Patients were divided into CTC-positive group and CTC-negative group according to CTC status, and the effect of preoperative TACE on RFS and OS was compared in each subgroup. Results: In CTC-positive patients, preoperative TACE reduces early recurrence and improves long-term survival. However, HCC patients did not benefit from preoperative TACE for the overall population and CTC-negative patients. Conclusions: Preoperative CTC testing is a reliable indicator of whether HCC patients received TACE preoperatively. CTC positivity was associated with early tumor recurrence, and preoperative TACE could reduce early recurrence and long-term prognosis in CTC-positive patients. [ABSTRACT FROM AUTHOR]

Background and Aim: Ruptured hepatocellular carcinoma (rHCC) is classified as T4 according to the TNM staging system with a very poor (does not achieve expected) prognosis, which has always been controversial. This study aimed at assessing the specific impact of different tumor diameters on the posttreatment prognosis of BCLC stage 0/A rHCC patients. Methods: Data from 258 patients with BCLC stage 0/A HCC treated in our center from January 2008 to December 2017 were collected, including 143 rHCC patients and 115 patients with non-ruptured HCC (nrHCC). With the help of X-tile software, we determined the cutoff value of the tumor diameter in patients with rHCC. Using 8 cm as the cutoff, we divided rHCC patients into Small-rHCC (n = 96) and Large-rHCC (n = 47) groups, compared the prognoses of the S-rHCC and L-rHCC groups, as well as the prognoses of the two groups with the nrHCC group using the Kaplan–Meier method, and screened the prognostic factors of rHCC patients using the multivariate Cox risk model. Results: The OS of the S-rHCC group was significantly higher than that of the L-rHCC group [HR = 2.41 (1.60–3.63)], and the OS of the nrHCC group was comparable to that of the S-rHCC group (P = 0.204). In patients treated with surgery only, OS and RFS were also comparable in the S-rHCC nrHCC group. Meanwhile, multivariate Cox regression analysis revealed that alpha-fetoprotein (AFP), alkaline phosphatase (ALP), and the main method of treatment were also prognostic factors for OS in patients with rHCC. Conclusions: Ruptured HCC with a relatively small diameter (≤8 cm) can also achieve the same prognosis as nrHCC patients after aggressive treatment. It is also not recommended to include all patients with rHCC in stage T4. [ABSTRACT FROM AUTHOR]

Background. This research is aimed at establishing a scoring system alpha-fetoprotein+alkaline phosphatase (A-A score) based on preoperative serum alpha-fetoprotein (AFP) and alkaline phosphatase (ALP) levels and to investigate its clinical significance in patients with ruptured hepatocellular carcinoma (rHCC) after hepatectomy. Methods. 175 ruptured hepatocellular carcinoma (HCC) patients treated with hepatectomy were included. Survival analysis was assessed by the Kaplan-Meier method. Prognostic factors were analyzed in a multivariate model. Preoperative serum AFP and ALP values are assigned a score of 1 if they exceed the threshold value and 0 if they are below the threshold value, A-A score is obtained by summing the scores of two variables (AFP, ALP), and the predictive values of AFP, ALP, and A-A score were compared by receiver operating characteristic curve (ROC) analysis, and subgroup analyses were performed to further evaluate the power of A-A scores. Results. Of the 175 patients, 67 (38.3%) had an A-A score of 0, 72 (41.1%) had an A-A score of 1, and 36 (20.6%) had an A-A score of 2. In multivariate analysis, the A-A score, the BCLC stage, and the extent of resection were independent predictors of OS in patients with rHCC. The 1-, 3-, and 5-year OS and RFS in patients with an A-A score of 1 were better than those with an A-A score of 0 and worse than those with an A-A score of 1 (all p < 0.05). Based on the results of ROC analysis, the A-A score is superior to AFP or ALP alone in predicting the prognosis of patients with ruptured HCC. In subgroup analysis, A-A score could accurately predict the prognosis of patients with or without microvascular invasion (MVI) and with different Child-Pugh grades or gender. Conclusions. The A-A score can effectively predict the prognosis of patients after hepatectomy of ruptured hepatocellular carcinoma. At the same time, it also has good evaluation ability in different subgroups. [ABSTRACT FROM AUTHOR]

No-touch combined directed perfusion radiofrequency ablation (NTDP-RFA) is a new technique for the treatment of hepatocellular carcinoma (HCC). The purpose of this study was to evaluate the short-term efficacy of this new technique for the treatment of small HCC with cirrhosis. From January 2017 to March 2018, 56 consecutive patients treated with NTDP-RFA at our center were enrolled in this retrospective study. All NTDP-RFA procedures involved the use of internally cooled wet electrodes with a directional injection function, which can perform both intraelectrode cooling and extraelectrode saline perfusion. Survival curves were analyzed using Kaplan–Meier methods, and Cox proportional hazards regression analyses were used to assess predictors of tumor progression and overall survival. Operative characteristics and complications were also assessed. No technical failure occurred, and the complete ablation rate after single NTDP-RFA treatment was 98.2%. The median tumor diameter and ablation time were 26 (18.0 − 28.0) mm and 8 (6 – 8) min, respectively. Mild complications occurred in five patients (8.9%) postoperatively, and the median hospital stay was 4 (4 − 5) days. In the 18 patients (32.1%) with poor liver function reserve (indocyanine green retention rate at 15 min > 15%, their liver function returned to normal on the third day after the postoperation. The 1- and 2-year local and distant progression rates were 1.7%, 7.1%, 3.5% and 10.7%, respectively. NTDP-RFA in the treatment of small HCC with cirrhosis has a low incidence of complications and provides a high survival rate without local tumor progression. [ABSTRACT FROM AUTHOR]

Background and Aims. Conflicting results are often observed in the prognosis of patients with ruptured hepatocellular carcinoma (rHCC), and there are currently very few studies on the long-term postoperative outcomes of ruptured hepatocellular carcinoma patients. This study aimed to distinguish between the postoperative prognosis of rHCC patients with cirrhosis (rHCC-C) and those without cirrhosis (rHCC-NC) using some serum markers. Methods. We collected the data of 151 rHCC patients treated at our centers from January 2010 to March 2021. 62 had no cirrhosis, and 89 had cirrhosis. The prognosis of rHCC-C and rHCC-NC groups was compared using the Kaplan-Meier method. We used multivariate Cox regression to analyze prognostic factors in rHCC patients, and subgroup analysis was performed on the two groups of patients. Results. The long-term prognosis of rHCC-NC patients was better than that of rHCC-C patients. Tumor diameter, Barcelona clinic liver cancer (BCLC) stage, HBsAg, positive Hepatitis C virus (HCV) antibodies, elevated creatinine, and elevated T-bilirubin were prognostic factors for overall survival (OS) in rHCC-C patients. However, only alpha-fetoprotein (AFP) > 92 ng/mL was a prognostic factor for OS in rHCC-NC patients. In noncirrhotic patients, HBsAg positivity was only associated with OS. Similarly, the presence or absence of microvascular invasion (MVI) also had different results in the two groups. Conclusions. There are differences in serum alpha-fetoprotein (AFP) levels, the presence of microvascular invasion (MVI), and HBsAg positivity between rHCC-C and rHCC-NC patients, indicating that the analysis of these prognostic factors may help improve the management of rHCC patients and provide a direction for future treatment options. [ABSTRACT FROM AUTHOR]

Background and Aim: It has been previously reported that inflow occlusion does not affect postoperative outcomes in hepatocellular carcinoma patients. However, for patients with ruptured hepatocellular carcinoma(rHCC), the effect of hepatic inflow occlusion and the number of occlusion times on the prognosis is unknown.Methods: 203 patients with ruptured hepatocellular carcinoma were enrolled in this study. They were first divided into the non-hepatic inflow occlusion (non-HIO) group and the hepatic inflow occlusion (HIO) group. The Kaplan-Meier method was used to compare the recurrence-free survival and overall survival between the two groups. Patients in the HIO group were further divided into one-time HIO and two times HIO groups. KM method was also used to compare the two groups. Finally, independent risk factors affecting RFS and OS were determined by multivariate Cox regression analysis.Result: In the non-HIO group, 1-,3- and 5-year OS rates were 67.0%, 41.0%, and 22.0%respectively, and RFS rates were 45.0%, 31.0%, and 20.0% respectively; In the one-HIO group, the 1-,3-, and 5-year OS rates were 55.1%, 32.1%, and 19.2% respectively, and RFS rates were 33.3%, 16.7%, and 7.7% respectively; In the two-HIO group, 1-,3-, and 5-year OS rates were 24.0%, 0.0%, and 0.0% respectively, and RFS rates were 8.0%, 0.0%, and 0.0% respectively. By Cox regression analysis, HIO was an independent risk factor for a poor prognosis in rHCC patients.Conclusion: One time hepatic inflow occlusion did not affect postoperative OS, but negatively affected the RFS of rHCC patients; two times hepatic inflow occlusion negatively affected the postoperative OS and RFS in patients with rHCC. [ABSTRACT FROM AUTHOR]

Background: Ruptured hepatocellular carcinoma (rHCC) is considered a rare and life-threatening manifestation; when it happens, it often requires acute and positive intervention. At present, the mechanism of rHCC development is gradually being understood while there are many kinds of rHCC treatment. From our clinical observation, the prognosis of rHCC patients is not as poor as it is currently believed. It may not be appropriate to include all patients with rHCC in T4. Main Body: The incidence of ruptured hepatocellular carcinoma is now rising. Especially in the Asian region, it can even reach 10% – 15%. The most common symptom of HCC rupture is abdominal pain, and there are now a variety of treatments for hepatocellular carcinoma rupture. With aggressive treatment, rHCC patients can also achieve a better prognosis. The patient's condition varies on admission, so the treatment methods will also be different. It is critical to identify prognostic factors simultaneously, and rHCC can be effectively managed by focusing on important prognostic factors. Conclusion: A review was carried out to analyze diagnosis, mechanism, treatment, and prognostic risk factors on this disease condition during the current situation; it is hoped that it will provide better guidance for clinicians. Moreover, patients with rHCC were managed hierarchically to prolong their prognosis. [ABSTRACT FROM AUTHOR]

Background: Cancer stem cells (CSCs) and Circulating tumor cells (CTCs) have been proposed as fundamental causes for the recurrence of hepatocellular carcinoma (HCC). CTCs isolated from patients with HCC illustrate a unique Nanog expression profile analysis. The aim of this study was to enhance the prediction of recurrence and prognosis of the CTC phenotype in patients with HCC by combining Nanog expression into a combined forecasting model. Subjects, Materials, and Methods: We collected 320 blood samples from 160 patients with HCC cancer before surgery and used CanPatrol™ CTC enrichment technology and in situ hybridization (ISH) to enrich and detect CTCs and CSCs. Nanog expression in all CTCs was also determined. In addition, RT-PCR and immunohistochemistry were used to study the expression of Nanog, E-Cadherin, and N-Cadherin in liver cancer tissues and to conduct clinical correlation studies. Results: The numbers of EpCAM mRNA+ CTCs and Nanog mRNA+ CTCs were strongly correlated with postoperative HCC recurrence (CTC number (P = 0.03), the total number of mixed CTCS (P = 0.02), and Nanog> 6.7 (P = 0.001), with Nanog > 6.7 (P = 0.0003, HR = 2.33) being the most crucial marker. There are significant differences in the expression of Nanog on different types of CTC: most Epithelial CTCs do not express Nanog, while most of Mixed CTC and Mesenchymal CTC express Nanog, and their positive rates are 38.7%, 66.7%, and 88.7%, respectively, (P=0.0001). Moreover, both CTC (≤/> 13.3) and Nanog (≤/>6.7) expression were significantly correlated with BCLC stage, vascular invasion, tumor size, and Hbv-DNA (all P < 0.05). In the young group and the old group, patients with higher Nanog expression had a higher recurrence rate. (P < 0.001). Conclusions: The number of Nanog-positive cells showed positive correlation with the poor prognosis of HCC patients. The detection and analysis of CTC markers (EpCAM and CK8, 18, CD45 Vimentin,Twist and 19) and CSCs markers (NANOG) are of great value in the evaluation of tumor progression. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is reported to associate with abnormal expression of SCF E3 ubiquitin ligases. FBXW10, an F-box protein of the E3 ubiquitin ligases, was abnormally regulated in HCC patients. However, whether FBXW10 is associated with HCC has not yet been evaluated. Here, we analyzed the associations between overall survival and various risk factors in 191 HCC tissues. Univariate and multivariate analyses demonstrated that FBXW10 was an independent risk factor related to HCC prognosis. The results showed that FBXW10, gender and tumor state were strongly associated with overall survival in HCC patients. Furthermore, high expression of FBXW10 was associated with poor survival among male HCC patients but not female HCC patients. FBXW10 was more highly expressed in male HCC tissues and more strongly related to vascular invasion in male HCC patients. Consistent with these findings, the male FBXW10-Tg(+) mice were more susceptible to tumorigenesis, changes in regenerative capacity, and liver injury and inflammation but not changes in liver function than FBXW10-Tg(–) mice. FBXW10 promoted cell proliferation and migration in HCC cell lines. Our findings reveal that FBXW10, an independent risk factor for HCC, promotes hepatocarcinogenesis in male patients, and is also a potential prognostic marker in male patients with HCC. [ABSTRACT FROM AUTHOR]

Background: There is no guideline recommendation for preventing hepatocellular carcinoma (HCC) recurrence after hepatic resection. Moreover, an unmet need exists on the effectiveness of sorafenib therapy in recurrent HCC. Purpose: We therefore assessed the efficacy and safety of sorafenib in Chinese HCC patients with high risk of recurrence. Patients and methods: Data were collected retrospectively from 15 Chinese research centers from January 1, 2012 to November 15, 2013, by chart reviews of patients with moderate-advanced HCC who received hepatic carcinectomy. The primary end point was recurrence-free survival rate at 1 year in patients with a high recurrence risk. Secondary end points included 1-year survival rate, time to recurrence and safety assessment. Results: A total of 209 high-risk patients (sorafenib, n=98; control, n=111) who underwent carcinectomy were analyzed. There was no significant difference in the proportion of patients with recurrence-free survival at 1 year between the sorafenib and control (70.43% vs 68.90%: χ2=0.007, P=0.934). One-year survival rate was significantly higher with sorafenib than observed with control (95.5% vs 83.35%; χ2=7.441, P=0.006). Time to recurrence between sorafenib and control groups was similar. Incidences of all the adverse events (AEs) were similar in both the groups and transaminase elevation was most common in both groups (20.37% vs 24.79%). Thrombocytopenia incidence was significantly lower with the sorafenib group than with control (1.85% vs 9.40%; P=0.015). Conclusion: Sorafenib may be considered as a feasible option in the treatment of HCC recurrence. [ABSTRACT FROM AUTHOR]

Background and aims: 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). Materials and methods: 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. Results: 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. Conclusions: 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. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma is associated with high mortality, and tumor metastasis is an important reason for poor prognosis. However, metastasis has not been effectively prevented in clinical therapy and the mechanisms underlying metastasis have not been fully characterized. CCAAT/enhancer-binding protein-α (C/EBPα) is a transcriptional regulator with an essential role in tumor metastasis. We used short-activating RNAs (saRNA) to enhance expression of C/EBPα. Intravenous injection of C/EBPα-saRNA in a nude mouse liver orthotopic xenograft tumor model inhibited intrahepatic and distant metastasis. C/EBPα-saRNA-treated mice showed increased serum levels of albumin and decreased alanine aminotransferase (ALT), glutamic-oxalacetic transaminase (AST), indicating a role of C/EBPα in improving liver function. Migration and invasion were inhibited in hepatoma cell lines transfected with C/EBPα-saRNA. We also observed an inhibition of epithelial-mesenchymal transition (EMT) and suppression of epidermal growth factor receptor (EGFR), EGFR phosphorylation, and β-catenin in C/EBPa-saRNA-transfected cells. Our results suggested that C/EBPα-saRNA successfully inhibited HCC metastasis by inhibiting EGFR/β-catenin signaling pathway mediated EMT in vitro and in vivo. [ABSTRACT FROM AUTHOR]

Background and Aims Although a high viral load is an independent risk factor for recurrence of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) after surgery, the prognostic impact of viral load on advanced HCC is unclear. This study investigated the impact of baseline HBV load and antiviral therapy on survival of patients with advanced HCC treated with sorafenib. Methods Of 130 patients with advanced HBV-related HCC received first-line sorafenib therapy were evaluated in a multicenter, retrospective study. Results No patients experienced severe hepatic impairment because of HBV reactivation during sorafenib therapy. The median progression-free survival (PFS) and overall survival (OS) of all patients were 5.7 and 9.6 months respectively. Patients with a baseline HBV DNA ≤104 copies/ml had significantly better OS than those with >104 copies/ml (10.4 vs 6.6 months; P = 0.002), but PFS showed an increasing trend (5.8 vs 4.8 months; P = 0.068). Patients who received antiviral therapy had a better trend in OS than those who did not (12.0 vs 8.3 months; P = 0.058), but there was no difference in PFS (6.4 vs 4.1 months; P = 0.280). In a multivariate analysis, the baseline HBV DNA level >104 copies/ml ( P = 0.001; hazard ration [HR] = 2.294; 95% CI 1.429-3.676) and antiviral therapy ( P = 0.038; HR 0.617; 95% CI 0.390-0.975) were independent predictors of OS. Conclusion In patients with advanced HBV-related HCC treated with sorafenib, a high baseline HBV load was an adverse prognostic factor for survival. However, survival was significantly improved with the use of antiviral therapy. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to evaluate the safety and outcomes of radiofrequency ablation (RFA) in treating elderly patients with hepatocellular carcinoma (HCC). Patients and methods: 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 (age <70 years, n = 289). Long-term outcomes were assessed on all patients and survival rates were calculated. Results: 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. Conclusions: 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

DNA methylation is an important epigenetic modification and is frequently altered in cancer. Convert of 5-methylcytosine (5 mC) to 5-hydroxymethylcytosine (5 hmC) by ten-eleven translocation (TET) family enzymes plays important biological functions in embryonic stem cells, development, aging and disease. Recent reports showed that level of 5 hmC was altered in various types of cancers. However, the change of 5 hmC level in hepatocellular carcinoma (HCC) and association with clinical outcome were not well defined. Here, we reported that level of 5 hmC was decreased in HCC tissues, as compared with non-tumor tissues. Clincopathological analysis showed the decreased level of 5 hmC in HCC was associated with tumor size, AFP level and poor overall survival. We also found that the decreased level of 5 hmC in non-tumor tissues was associated with tumor recurrence in the first year after surgical resection. In an animal model with carcinogen DEN-induced HCC, we found that the level of 5 hmC was gradually decreased in the livers during the period of induction. There was further reduction of 5 hmC in tumor tissues when tumors were developed. In contrast, level of 5 mC was increased in HCC tissues and the increased 5 mC level was associated with capsular invasion, vascular thrombosis, tumor recurrence and overall survival. Furthermore, our data showed that expression of TET1, but not TET2 and TET3, was downregulated in HCC. Taken together, our data indicated 5 hmC may be served as a prognostic marker for HCC and the decreased expression of TET1 is likely one of the mechanisms underlying 5 hmC loss in HCC. [ABSTRACT FROM AUTHOR]

Abstract: Hepatocellular carcinoma (HCC) is a hypervascular cancer characterized by rapid progression as well as resistance to conventional chemotherapy. It has been shown that microRNAs play critical roles in pathogenesis of HCC. MicroRNA-122 (miR-122) is a liver-specific microRNA and is frequently downregulated in HCC. In the present study, we investigated whether restoration of miR-122 in HCC cells could render cells sensitive to chemotherapeutic agents adriamycin (ADM) or vincristine (VCR). Our data showed that overexpression of miR-122 in HCC cells induced by adenovirus expressing miR-122 could render cell sensitive to ADM or VCR. Analysis of cell cycle distribution showed that the anti-proliferative effect of miR-122 is associated with increase of cell number in the G2/M phase. Moreover, treatment with Ad-miR122 and ADM or VCR resulted in high accumulation of HCC cells in G2/M phase. We further demonstrated that overexpression of miR-122 could modulate the sensitivity of the HCC cells to chemotherapeutic drugs through downregulating MDR related genes MDR-1, GST-π, and MRP, antiapoptotic gene Bcl-w and cell cycle related gene cyclin B1. Taken together, our findings demonstrated that combination of Ad-miR122 with chemotherapeutic agents inhibited HCC cell growth by inducing G2/M arrest and that this arrest is associated, at least in part, with reduced expression of MDR related genes and Cyclin B1. [Copyright &y& Elsevier]

Background: In patients with cirrhosis excessive hemorrhage and the need for blood transfusion are associated with increased postoperative morbidity and mortality as well as a poor long-term outcome. Saline-linked radiofrequency dissecting sealer (TissueLink) is a recent advance in technology that improves hemostasis during difficult liver resections. Preliminary studies have shown that this technique reduces blood loss without inflow occlusion. Patients and methods: A controlled study was performed on 122 consecutive patients with cirrhosis who underwent liver resection for hepatocytotic carcinoma. The outcomes of liver transection with clamp crushing and TissueLink were compared to evaluate which strategy is most beneficial to the patients. Results: Both intraoperative blood loss and blood transfusion requirements were significantly higher in the crushing clamp group than in the TissueLink group (P = 0.047 and P = 0.031, respectively). In addition, a significantly higher number of patients required a blood transfusion in the crushing clamp group (P < 0.001). However, the transection time was significantly faster in the crushing clamp group than in the TissueLink group (P < 0.001). The number of patients that required Pringle''s maneuver was markedly higher in the crushing clamp group (P < 0.001). In addition, the hemostasis time was significantly longer in the crushing clamp group (P < 0.001). The serum aspartate aminotransferase levels 3 and 7 days after surgery were significantly higher in the crushing clamp group than in the TissueLink group (P = 0.035 and P = 0.003, respectively). Serum total bilirubin levels were markedly increased 3 days after surgery in the crushing clamp group than in the TissueLink group (P = 0.011). Biliary leakage occurred in a higher number of crushing clamp patients (six) than TissueLink patients (three), although this difference was not significant. The operative morbidity not including biliary leakage was higher in the crushing clamp group than the TissueLink group (nine patients versus five patients, respectively). Conclusion: This study reveals that the TissueLink procedure has beneficial effects during liver transection under cirrhotic conditions in terms of blood loss and reperfusion-related liver injury. However, this procedure requires a significantly longer transection time of the parenchyma. [Copyright &y& Elsevier]

The sympathetic nervous system (SNS) is known to play a significant role in tumor initiation and metastasis. Hepatocellular carcinoma (HCC) frequently occurs in cirrhotic livers after chronic inflammation, and the SNS is hyperactive in advanced liver cirrhosis. However, it remains unclear whether the SNS promotes hepatocarcinogenesis by modulating chronic liver inflammation. In this study, a retrospective pathological analysis and quantification of sympathetic nerve fiber densities (tyrosine hydroxylase, TH + ) in HCC patients, and diethylnitrosamine (DEN)-induced hepatocarcinogenesis in rats were performed. Our data showed that high density of sympathetic nerve fibers and α1-adrenergic receptors (ARs) of Kupffer cells (KCs) were associated with a poor prognosis of HCC. Sympathetic denervation or blocking of α1-ARs decreased DEN-induced HCC incidence and tumor development. In addition, synergistic effects of interleukin-6 (IL-6) and transforming growth factor-beta (TGF-β) in hepatocarcinogenesis were observed. The suppression of the SNS reduced IL-6 and TGF-β expression, which suppressed hepatocarcinogenesis, and KCs play a key role in this process. After the ablation of KCs, IL-6 and TGF-β expression and the development of HCC were inhibited. This study demonstrates that sympathetic innervation is crucial for hepatocarcinogenesis and that the SNS promotes hepatocarcinogenesis by activating α1-ARs of KCs to boost the activation of KCs and to maintain the inflammatory microenvironment. These results indicate that sympathetic denervation or α1-ARs blockage may represent novel treatment approaches for HCC. [ABSTRACT FROM AUTHOR]

Background & Aims: The aim of this study was to compare the efficacy of radiofrequency ablation (RFA) with surgical resection (RES) in the treatment of small hepatocellular carcinoma (HCC). Methods: A total of 168 patients with small HCC with nodular diameters of less than 4cm and up to two nodules were randomly divided into RES (n=84) and RFA groups (n=84). Outcomes were carefully monitored and evaluated during the 3-year follow-up period. Results: The 1-, 2-, and 3-year survival rates for the RES and RFA groups were 96.0%, 87.6%, 74.8% and 93.1%, 83.1%, 67.2%, respectively. The corresponding recurrence-free survival rates for the two groups were 90.6%, 76.7%, 61.1% and 86.2%, 66.6%, 49.6%, respectively. There were no statistically significant differences between the two groups in overall survival rate (p =0.342) or recurrence-free survival rate (p =0.122). Multivariate analysis demonstrated that the independent risk factors associated with survival were multiple occurrences of tumors at different hepatic locations (relative risk of 2.696; 95% CI: 1.189–6.117; p =0.018) and preoperative indocyanine green retention rate at 15min (ICG-15) (relative risk of 3.853; 95% CI: 1.647–9.015; p =0.002). Conclusions: In patients with small hepatocellular carcinomas, percutaneous RFA may provide therapeutic effects similar to those of RES. However, percutaneous RFA is more likely to be incomplete for the treatment of small HCCs located at specific sites of the liver, and open or laparoscopic surgery may be the better choice. [Copyright &y& Elsevier]