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Transarterial embolization, the first-line treatment for hepatocellular carcinoma, does not always lead to promising outcomes in all patients. A better understanding of how the immune lymphocyte changes after transarterial embolization might be the key to improve the efficacy of transarterial embolization. However, there are few studies evaluating immune lymphocytes in transarterial embolization patients. Therefore, we aimed to evaluate the short- and long-term effects of transarterial embolization on lymphocyte subsets in patients with hepatocellular carcinoma to identify those that predict transarterial embolization prognosis. Peripheral blood samples were collected from 44 patients with hepatocellular carcinoma at the following time points: 1 d before the initial transarterial embolization, 3 d after the initial transarterial embolization, and 1 mo after the initial transarterial embolization and subjected to peripheral blood mononuclear cell isolation and flow cytometry. Dynamic changes in 75 lymphocyte subsets were recorded, and their absolute counts were calculated. Tumor assessments were made every 4 to 6 wk via computed tomography or magnetic resonance imaging. Our results revealed that almost all lymphocyte subsets fluctuated 3 d after transarterial embolization, but only Tfh and B cells decreased 1 mo after transarterial embolization. Univariate and multivariate Cox regression showed that high levels of Th2 and conventional killer Vδ2 cells were associated with longer progressive-free survival after transarterial embolization. Longer overall survival after transarterial embolization was associated with high levels of Th17 and viral infection-specific Vδ1 cells and low levels of immature natural killer cells. In conclusion, transarterial embolization has a dynamic influence on the status of lymphocytes. Accordingly, several lymphocyte subsets can be used as prognostic markers for transarterial embolization., Competing Interests: Conflict of interest statement. None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of Society for Leukocyte Biology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Objective: To investigate the safety and feasibility of laparoscopic resection of focal nodular hyperplasia (FNH) in the hepatic caudate lobe., Methods: The clinical data of eight patients who underwent laparoscopic hepatic caudate lobe FNH resection at the Department of Hepatobiliary Surgery, Southwest Hospital, First Affiliated Hospital of Army Medical University, were retrospectively analyzed., Results: The laparoscopic procedures were successful in all eight patients, and no patients required conversion to open surgery. Five patients underwent partial caudate lobe resection, one patient underwent caudate lobe resection, and two patients underwent combined left hemihepatectomy with caudate lobe resection. Tumor resection was performed using the left approach in five cases, the right approach in one case, the middle hepatic fissure approach in one case, and the left and right combined approach in one case. The operation time ranged from 120 to 360 min, with a mean of 225 min. The intraoperative blood loss ranged from 50 to 600 ml, with a mean of 235 ml. No postoperative bleeding, bile leakage or abdominal infection occurred., Conclusions: Laparoscopic resection of hepatic caudate lobe FNH was safe and feasible in appropriate patients. Skilled laparoscopic hepatectomy techniques, adequate preoperative evaluation, appropriate choice of surgical approach and the control of intraoperative bleeding are critical to perform this surgery., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Asian Surgical Association and Taiwan Robotic Surgery Association. Published by Elsevier B.V. All rights reserved.)

Objective: To identify specific Chinese medicines (CM) that may benefit patients with primary liver cancer (PLC), and to explore the mechanism of action of these medicines., Methods: In this retrospective, singlecenter study, prescription information from PLC patients was used in combination with Traditional Chinese Medicine Inheritance Supports System to identify the specific core drugs. A system pharmacology approach was employed to explore the mechanism of action of these medicines., Results: Taking CM more than 6 months was significantly associated with improved survival outcomes. In total, 77 putative targets and 116 bioactive ingredients of the core drugs were identified and included in the analysis (P<0.05). A total of 1,036 gene ontology terms were found to be enriched in PLC. A total of 75 pathways identified from Kyoto Encyclopedia of Genes and Genomes were also enriched in this disease, including fluid shear stress, interleukin-17 signaling, signaling between advanced glycan end products and their receptors, cellular senescence, tumor necrosis factor signaling, p53 signaling, cell cycle signaling, steroid hormone biosynthesis, T-helper 17 cell differentiation, and metabolism of xenobiotics by cytochrome. Docking studies suggested that the ingredients in the core drugs exert therapeutic effects in PLC by modulating c-Jun and interleukin-6., Conclusions: Receiving CM for 6 months or more improves survival for the patients with PLC. The core drugs that really benefit for PLC patients likely regulates the tumor microenvironment and tumor itself., (© 2021. The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Contrast-enhanced ultrasound (CEUS) can be used to diagnose focal liver lesions (FLLs) in children. The America College of Radiology developed the CEUS liver imaging reporting and data system (LI-RADS) for standardizing CEUS diagnosis of FLLs in adult patients. Until now, no similar consensus or guidelines have existed for pediatric patients to improve imaging interpretation as adults., Aim: To evaluate the performance of CEUS LI-RADS combined with alpha-fetoprotein (AFP) in differentiating benign and malignant FLLs in pediatric patients., Methods: Between January 2011 and January 2021, patients ≤ 18 years old who underwent CEUS for FLLs were retrospectively evaluated. The following criteria for diagnosing malignancy were proposed: Criterion I considered LR-4, LR-5, or LR-M lesions as malignancies; criterion II regarded LR-4, LR-5 or LR-M lesions with simultaneously elevated AFP (≥ 20 ng/mL) as malignancies; criterion III took LR-4 Lesions with elevated AFP or LR-5 or LR-M lesions as malignancies. The sensitivity, specificity, accuracy and area under the receiver operating characteristic curve (AUC) were calculated to determine the diagnostic value of the aforementioned criteria., Results: The study included 63 nodules in 60 patients (mean age, 11.0 ± 5.2 years; 26 male). There were no statistically significant differences between the specificity, accuracy, or AUC of criterion II and criterion III (95.1% vs 80.5%, 84.1% vs 87.3%, and 0.794 vs 0.902; all P > 0.017). Notably, criterion III showed a higher diagnostic sensitivity than criterion II (100% vs 63.6%; P < 0.017). However, both the specificity and accuracy of criterion I was inferior to those of criterion II and criterion III (all P < 0.017). For pediatric patients more than 5 years old, the performance of the three criteria was overall similar when patients were subcategorized by age when compared to all patients in aggregate., Conclusion: CEUS LI-RADS combined with AFP may be a powerful diagnostic tool in pediatric patients. LR-4 with elevated AFP, LR-5 or LR-M lesions is highly suggestive of malignant tumors., Competing Interests: Conflict-of-interest statement: There are no conflicts of interest to report., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background/purpose: This over 7-year case study is the first to compare the results of laparoscopic Glissonian pedicle approach hemihepatectomy (LGAH) and laparoscopic hilar dissection approach hemihepatectomy (LHAH) in a randomized controlled trial (RCT)., Methods: Patients who had undergone laparoscopic hemihepatectomy, either LGAH or LHAH, between March 2012 and December 2019 at our center were prospectively enrolled and assigned to the LGAH or LHAH group. Both groups were stratified and compared, and the preoperative and follow-up outcomes were analyzed. The primary endpoint was total operative time., Results: The groups were equally matched for age, sex, HBsAg, Child-Pugh class, benign disease, malignancy, liver cirrhosis, tumor diameter and type of resection. Ninety-six patients had undergone LGAH and 94 had undergone LHAH. No preoperative death occurred in the two groups. LGAH did not enhance the postoperative overall complication rates (P = .465) or intraoperative blood loss (P = .535) compared with LHAH. However, the overall operative time (P = .014) and hilar dissection time (P = .000) were significantly shorter in the LGAH group than in the LHAH group. No significant differences were found between the groups regarding the 1-year (P = .384), 3-year (P = .332), and 5-year overall survival rates (P = .662) or 1-year (P = .856), 3-year (P = .348), and 5-year disease-free survival rates (P = .573)., Conclusions: LGAH and LHAH are both effective procedures for treating the hilar structures in selected patients. LGAH has advantages over LHAH in reducing total operation time under the condition where both procedures can be used. LGAH for selected patients is worthy of promotion owing to its simplicity and convenience., Registration Number: NCT01567631 (http://www., Clinicaltrials: gov)., (© 2022 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

The crosstalk between tumor and stroma plays a critical role in cancer metastasis. However, the function of miR-10a-5p on liver fibroblasts in the metastatic microenvironment of colon cancer (CC) and the effect of activated fibroblasts on CC cells are still unclear. In our study, miR-10a-5p overexpression inhibited the proliferation, migration, and IL-6/IL-8 level of LX-2 cells and human liver cancer fibroblasts (HLCFs). Moreover, miR-10a-5p had lower expression in HLCFs than in human liver normal fibroblasts (HLNFs). The conditioned medium (CM) from LX-2 cells with miR-10a-5p overexpression or HLNFs could inhibit the invasion, migration, and stemness of CC SW480 cells, whereas HLCFs CM could promote these malignant phenotypes of SW480 cells. The present study illustrates the effect of miR-10a-5p on the liver fibroblasts and the altered liver fibroblasts in the microenvironment on CC cells induced by miR-10a-5p, which may aid the understanding of the mechanisms underlying CC liver metastasis.

Background: The paracaval portion of the caudate lobe is located in the core of the liver. Lesions originating in the paracaval portion often cling to or even invade major hepatic vascular structures. The traditional open anterior hepatic transection approach has been adopted to treat paracaval-originating lesions. With the development of laparoscopic surgery, paracaval-originating lesions are no longer an absolute contraindication for laparoscopic liver resection. This study aimed to evaluate the safety and feasibility of laparoscopic anterior hepatic transection for resecting paracaval-originating lesions., Methods: This study included 15 patients who underwent laparoscopic anterior hepatic transection for paracaval-originating lesion resection between August 2017 and April 2020. The perioperative indicators, follow-up results, operative techniques and surgical indications were retrospectively evaluated., Results: All patients underwent laparoscopic anterior hepatic transection for paracaval-originating lesion resection. The median operation time was 305 min (220-740 min), the median intraoperative blood loss was 400 ml (250-3600 ml), and the median length of postoperative hospital stay was 9 days (5-20 days). No conversion to laparotomy or perioperative deaths occurred. Six patients had Clavien grade III-IV complications (III/IV, 5/1). Two patients developed tumor recurrence after 13 months and 8 months., Conclusion: Although technically challenging, laparoscopic anterior hepatic transection is still a safe and feasible procedure for resecting paracaval-originating lesions in select patients., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The exposure and protection of middle hepatic vein (MHV) is crucial and difficult for anatomic laparoscopic left hemihepatectomy in the treatment of left hepatic tumor. 1, 2 The traditional caudal approach, which the liver is transected from the branch to the main trunk of MHV, is prone to damage the vessels. 3, 4 The ventral approach is easy to expose the main trunk of MHV; however, the risk of vascular laceration caused by the caudal approach cannot be completely avoided, since the direction of endoscopic view and liver dissection are from the foot to the head side. We herein present a cranial-dorsal approach along the middle hepatic vein during laparoscopic left hemihepatectomy.The key point of the cranial-dorsal approach was the hepatic parenchyma transection from the root of MHV toward its distal branches. Briefly, left hepatic blood inflow was blocked, followed by the dissociation and transection from the left hepatic duct and vein. Along the direction of the main trunk of the MHV, the liver resection plane could be clearly exposed from the cranial and dorsal sides, and then the branches of the MHV were managed separately. Owing to the full exposure along the MHV trunk, the remaining liver parenchyma could be quickly transected to complete the anatomic left hepatectomy finally. This technique was performed in 10 patients who underwent laparoscopic left hemihepatectomy from March 2017 to December 2019. The median operative time was 188 min (range 150-265 min), and the intraoperative blood loss was 191 mL (range 100-300 mL). The median postoperative hospital stay was 6 days (range 4-8 days). No major postoperative complications or mortality was reported (Table 1). Cranial-dorsal approach along the MHV may be a feasible and effective technique during laparoscopic left hemihepatectomy, contributing to the process of anatomic left liver resection by full exposure and protection of hepatic veins.

Background: Combined hepatocellular-cholangiocarcinoma (CHC) is a rare type of primary liver cancer. Due to its complex histopathological characteristics, the imaging features of CHC can overlap with those of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC)., Aim: To investigate the possibility and efficacy of differentiating CHC from HCC and ICC by using contrast-enhanced ultrasound (CEUS) Liver Imaging Reporting and Data System (LI-RADS) and tumor biomarkers., Methods: Between January 2016 and December 2019, patients with histologically confirmed CHC, ICC and HCC with chronic liver disease were enrolled. The diagnostic formula for CHC was as follows: (1) LR-5 or LR-M with elevated alpha-fetoprotein (AFP) and carbohydrate antigen 19-9 (CA19-9); (2) LR-M with elevated AFP and normal CA19-9; or (3) LR-5 with elevated CA19-9 and normal AFP. The sensitivity, specificity, accuracy and area under the receiver operating characteristic curve were calculated to determine the diagnostic value of the criteria., Results: After propensity score matching, 134 patients (mean age of 51.4 ± 9.4 years, 108 men) were enrolled, including 35 CHC, 29 ICC and 70 HCC patients. Based on CEUS LI-RADS classification, 74.3% (26/35) and 25.7% (9/35) of CHC lesions were assessed as LR-M and LR-5, respectively. The rates of elevated AFP and CA19-9 in CHC patients were 51.4% and 11.4%, respectively, and simultaneous elevations of AFP and CA19-9 were found in 8.6% (3/35) of CHC patients. The sensitivity, specificity, positive predictive value, negative predictive value, accuracy and area under the receiver operating characteristic curve of the aforementioned diagnostic criteria for discriminating CHC from HCC and ICC were 40.0%, 89.9%, 58.3%, 80.9%, 76.9% and 0.649, respectively. When considering the reported prevalence of CHC (0.4%-14.2%), the positive predictive value and NPV were revised to 1.6%-39.6% and 90.1%-99.7%, respectively., Conclusion: CHCs are more likely to be classified as LR-M than LR-5 by CEUS LI-RADS. The combination of the CEUS LI-RADS classification with serum tumor markers shows high specificity but low sensitivity for the diagnosis of CHC. Moreover, CHC could be confidently excluded with high NPV., Competing Interests: Conflict-of-interest statement: All authors have no financial relationships to disclose., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) differ in treatment and prognosis, warranting an effective differential diagnosis between them. The LR-M category in the contrast-enhanced ultrasound (CEUS) liver imaging reporting and data system (LI-RADS) was set up for lesions that are malignant but not specific to HCC. However, a substantial number of HCC cases in this category elevated the diagnostic challenge., Aim: To investigate the possibility and efficacy of differentiating ICC from HCC classified in the LR-M category according to the CEUS LI-RADS., Methods: Patients with complete CEUS records together with pathologically confirmed ICC and LR-M HCC (HCC classified in the CEUS LI-RADS LR-M category) between January 2015 and October 2018 were included in this retrospective study. Each ICC was assigned a category as per the CEUS LI-RADS. The enhancement pattern, washout timing, and washout degree between the ICC and LR-M HCC were compared using the χ 2 test. Logistic regression analysis was used for prediction of ICC. Receiver operating characteristic (ROC) curve analysis was used to investigate the possibility of LR-M criteria and serum tumor markers in differentiating ICC from LR-M HCC., Results: A total of 228 nodules (99 ICCs and 129 LR-M HCCs) in 228 patients were included. The mean sizes of ICC and LR-M HCC were 6.3 ± 2.8 cm and 5.5 ± 3.5 cm, respectively ( P = 0.03). Peripheral rim-like arterial phase hyperenhancement (APHE) was detected in 50.5% (50/99) of ICCs vs 16.3% (21/129) of LR-M HCCs ( P < 0.001). Early washout was found in 93.4% (93/99) of ICCs vs 96.1% (124/129) of LR-M HCCs ( P > 0.05). Marked washout was observed in 23.2% (23/99) of ICCs and 7.8% (10/129) of LR-M HCCs (P = 0.002), while this feature did not show up alone either in ICC or LR-M HCC. Homogeneous hyperenhancement was detected in 15.2% (15/99) of ICCs and 37.2% (48/129) of LR-M HCCs ( P < 0.001). The logistic regression showed that rim APHE, carbohydrate antigen 19-9 (CA 19-9), and alpha fetoprotein (AFP) had significant correlations with ICC ( r = 1.251, 3.074, and -2.767, respectively; P < 0.01). Rim APHE presented the best enhancement pattern for diagnosing ICC, with an area under the ROC curve (AUC) of 0.70, sensitivity of 70.4%, and specificity of 68.8%. When rim hyperenhancement was coupled with elevated CA 19-9 and normal AFP, the AUC and sensitivity improved to 0.82 and 100%, respectively, with specificity decreasing to 63.9%., Conclusion: Rim APHE is a key predictor for differentiating ICC from LR-M HCC. Rim APHE plus elevated CA 19-9 and normal AFP is a strong predictor of ICC rather than LR-M HCC. Early washout and marked washout have limited value for the differentiation between the two entities., Competing Interests: Conflict-of-interest statement: The authors have no financial relationships to disclose., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

The prognostic role of programmed death ligand-1 (PD-L1) expression in hepatocellular carcinoma (HCC) has been widely studied but the results are controversial. In this comprehensive meta-analysis, we elucidated the clinical value of PD-L1 in HCC. Relevant studies were systematically searched in the Cochrane Library, EMBASE, and PubMed until June 27, 2019. Eligible studies were validated for the prognostic effect of PD-L1 on the overall survival (OS), disease-free survival (DFS), and relapse-free survival (RFS) in HCC using a hazard ratio (HR) and its 95% confidence interval (95% CI). Twenty-three studies with 3529 patients were involved in this meta-analysis. The pooled results revealed that high membrane-bound PD-L1 (mPD-L1) expression was associated with poor OS (HR: 1.42; 95% CI: 1.12-1.80; P = 0.004) and had no significant correlation with RFS (HR: 1.14; 95% CI: 0.85-1.54; P = 0.39), and DFS (HR: 1.36; 95% CI: 0.81-2.28; P = 0.25). The results also indicated that high soluble PD-L1 (sPD-L1) levels were associated with worse OS (HR: 2.93; 95% CI: 2.20-3.91; P < 0.00001). In addition, high mPD-L1 expression was associated with high alpha-fetoprotein levels (AFP; OR = 1.46; 95% CI: 1.16-1.84; P = 0.001), hepatitis (OR = 0.72; 95% CI: 0.54-0.98; P = 0.03), poor tumor differentiation (OR = 0.68; 95% CI: 0.55-0.84; P = 0.03), and tumor-infiltrating lymphocytes (OR = 3.39; 95% CI: 1.06-10.91; P = 0.04). The mPD-L1 expression had no significant correlation with age, number of tumors, gender, tumor size, liver cirrhosis, vascular invasion, tumor encapsulation, or TNM stage. The study revealed that high mPD-L1 expression in the tumor tissue and high sPD-L1 levels were associated with shorter OS in HCC. Moreover, overexpression of mPD-L1 was significantly associated with poor tumor differentiation, hepatitis, AFP elevation, and tumor-infiltrating lymphocytes., (© 2020 The Author(s).)

Background American College of Radiology contrast agent-enhanced US Liver Imaging Reporting and Data System (CEUS LI-RADS) was developed to improve the accuracy of hepatocellular carcinoma (HCC) diagnosis at contrast agent-enhanced US. However, to the knowledge of the authors, the diagnostic accuracy of the system in characterization of liver nodules 20 mm or smaller has not been fully evaluated. Purpose To evaluate the diagnostic accuracy of CEUS LI-RADS in diagnosing HCC in liver nodules 20 mm or smaller in patients at risk for HCC. Materials and Methods Between January 2015 and February 2018, consecutive patients at risk for HCC presenting with untreated liver nodules 20 mm or less were enrolled in this retrospective double-reader study. Each nodule was categorized according to the CEUS LI-RADS and World Federation for Ultrasound in Medicine and Biology (WFUMB)-European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) criteria. Diagnostic performance of CEUS LI-RADS and WFUMB-EFSUMB characterization was evaluated by using tissue histologic analysis, multiphase contrast-enhanced CT and MRI, and imaging follow-up as reference standard and compared by using McNemar test. Results The study included 175 nodules (mean diameter, 16.1 mm ± 3.4) in 172 patients (mean age, 51.8 years ± 10.6; 136 men). The sensitivity of CEUS LR-5 versus WFUMB-EFSUMB criteria in diagnosing HCC was 73.3% (95% confidence interval [CI]: 63.8%, 81.5%) versus 88.6% (95% CI: 80.9%, 94%), respectively ( P < .001). The specificity of CEUS LR-5 versus WFUMB-EFSUMB criteria was 97.1% (95% CI: 90.1%, 99.7%) versus 87.1% (95% CI: 77%, 94%), respectively ( P = .02). No malignant lesions were found in CEUS LR-1 and LR-2 categories. Only two nodules (of 41; 5%, both HCC) were malignant in CEUS LR-3 category. The incidences of HCC in CEUS LR-4, LR-5, and LR-M were 48% (11 of 23), 98% (77 of 79), and 75% (15 of 20), respectively. Two of 175 (1.1%) histologic analysis-confirmed intrahepatic cholangiocarcinomas were categorized as CEUS LR-M by CEUS LI-RADS and misdiagnosed as HCC by WFUMB-EFSUMB criteria. Conclusion The contrast-enhanced US Liver Imaging Reporting and Data System (CEUS LI-RADS) algorithm was an effective tool for characterization of small (≤20 mm) liver nodules in patients at risk for hepatocellular carcinoma (HCC). Compared with World Federation for Ultrasound in Medicine and Biology-European Federation of Societies for Ultrasound in Medicine and Biology criteria, CEUS LR-5 demonstrated higher specificity for diagnosing small HCCs with lower sensitivity. Published under a CC BY 4.0 license. See also the editorial by Crocetti in this issue.

Posthepatectomy liver failure (PHLF) is the most leading cause of mortality following hepatectomy in patients with hepatocellular carcinoma (HCC). Platelet count was reported to be a simple but useful indicator of liver cirrhosis and function of spleen. Spleen stiffness (SS) was used to evaluate the morphological change of spleen and was reported to be related to liver cirrhosis and portal hypertension. However, the predictive value of platelet to spleen stiffness ratio (PSR) on PHLF remains unknown. A retrospective study was performed to analyze 158 patients with HCC following hepatectomy from August 2015 to February 2016. Univariate and multivariate analyses were performed to evaluate the value of each risk factor for predicting PHLF. The predictive efficiency of the risk factors was evaluated by receiver operating characteristic (ROC) curve. PHLF occured in 23 (14.6%) patients. PSR (P<0.001, odds ratio (OR) = 0.622, 95% confidence interval (CI) 0.493~0.784), hepatic inflow occlusion (HIO) (P = 0.003, OR = 1.044, 95% CI 1.015~1.075) and major hepatectomy (P = 0.019, OR = 5.967, 95% CI 1.346~26.443) were demonstrated to be the independent predictive factors for development of PHLF in a multivariate analysis. Results of the present study suggested PSR is a novel and non-invasive model for predicting PHLF in patients with HCC., Competing Interests: The authors have declared that no competing interests exist.

This work aims to study the roles and related mechanisms of six2 in 5-FU sensitivity of hepatocellular carcinoma (HCC) cells. KM-Plotter analysis showed that HCC patients with higher six2 expression levels had shorter overall survival. Six2 expression was higher in clinical HCC tissues than in normal tissues, and was negatively correlated with E-cadherin expression. Additionally, six2 overexpression decreased the sensitivity of HCC cells to 5-Fu, characterized as attenuating 5-FU-induced cell apoptosis and downregulation of cell viability, and promoted HCC cells stemness. Mechanistically, six2 overexpression repressed E-cadherin expression via stimulating promoter methylation of the E-cadherin. And E-cadherin overexpression rescued six2-induced decrease of 5-FU sensitivity and promotion on HCC cells stemness. Therefore, our results suggest that Six2 is negatively correlated with good prognosis and decreases 5-FU sensitivity via suppressing E-cadherin expression in HCC cells., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Aim: To compare the Barcelona Clinic Liver Cancer (BCLC) and Hong Kong Liver Cancer (HKLC) classification systems when applied to HCC patients from the largest tertiary-level centre in Singapore., Methods: One thousand two hundred and seventy hepatocellular carcinoma (HCC) patients prospectively enrolled in a tertiary-level centre registry in Singapore since 1988 were studied. Patients were grouped into their respective BCLC and HKLC stages. Data such as demography, aetiology of HCC and type of treatment were collected. Survival data was based on census with the National Registry of Births and Deaths on 31 st October 2015. Statistical analyses were done using SPSS version 21 (Chicago, IL, United States). Survival analyses were done by the Kaplan-Meier method. Differences in survival rates were compared using the log-rank test., Results: The median age at presentation was 63 years (range 13-94); male 82.4%; Chinese 89.4%, Malay 7.1%, Indian, 2.8%. Hepatitis B was the predominant aetiology (75.0%; Hepatitis C 7.2%, Hepatitis B and C co-infection 3.8%, non-viral 14.0%). Both BCLC and HKLC staging systems showed good separation with overall log rank test confirming significant survival differences between stages in our cohort ( P < 0.001). 206 out of the 240 patients (85.8%) assigned for curative treatment by the BCLC treatment algorithm received curative therapy for HCC [Stage 0 93.2% (68/73); Stage A 82.6% (138/167)]. In contrast, only 341/558 (61.1%) patients received curative treatment despite being assigned for curative treatment by the HKLC treatment algorithm [Stage I 72.7% (264/363); Stage II 40.2% (66/164); Stage Va 35.5% (11/31)]. Patients who were assigned to curative treatment by HKLC but did not receive curative treatment had significantly poorer ECOG ( P < 0.001), higher Child-Pugh status ( P < 0.001) and were older (median age 66 vs 61, P < 0.001) than those who received curative therapy. Median overall survival in patients assigned to curative treatment groups by BCLC and HKLC were 6.1 and 2.6 years respectively ( P < 0.001). When only patients receiving curative treatment were analyzed, BCLC still predicted overall median survival better than HKLC (7.1 years vs 5.5 years, P = 0.037)., Conclusion: BCLC performs better than HKLC in our multiethnic Asian population in allocating patients to curative treatment in a real-life situation as well as in predicting survival., Competing Interests: Conflict-of-interest statement: We have no financial relationships to disclose.

Aim: This study aimed to investigate the clinical significance of liver stiffness and serum alpha-fetoprotein (AFP) in differentiating small hepatocellular carcinoma (HCC) from cirrhotic nodule., Methods: A total of 95 chronic hepatitis B patients who were diagnosed with small HCC (n = 53) or cirrhotic nodule (n = 42) underwent ultrasound elastography point quantification (ElastPQ) examinations on lesion and background liver. Three stiffness parameters, lesion stiffness value (SV), absolute stiffness difference (ASD) of lesion and background liver, stiffness ratio (lesion/background liver) (SR), and serum AFP were retrospectively analyzed. Then, the capabilities of lesion SV, ASD, SR, AFP, and the combination of each individual stiffness parameter with AFP were evaluated in differentiating small HCC from cirrhotic nodule., Results: Significantly higher lesion SV, ASD, SR, and serum AFP were observed in small HCC compared with cirrhotic nodule patients (all P ≤ 0.0001). By comparing the stiffness parameters on the patients with AFP greater than 20 ng/mL and AFP of 20 ng/mL or smaller, a higher lesion SV and comparable ASD and SR were found in the small HCC patients. The diagnostic accuracy of lesion SV, ASD, SR, and AFP in the discrimination of small HCC and cirrhotic nodule was 0.731, 0.825, 0.820, and 0.789, respectively. Moreover, the improved sensitivity was observed in the combination of liver stiffness with AFP (83%, 100%, and 92% for lesion SV/AFP, ASD/AFP, and SR/AFP, respectively)., Conclusions: This study illustrated that the combination of liver stiffness and serum AFP has considerable clinical value in detecting suspicious small HCC from cirrhotic nodule.

Background: The reported protocol was difficult to expose the hepatic veins for laparoscopic anatomical hepatectomy of segments VII and VIII. We introduce a new, convenient, applicable approach with the hepatic vein exposed from the head side., Methods: This study included 10 patients who underwent laparoscopic liver resection for HCC in the segments VII and VIII between October, 2014 and November, 2015. Their perioperative course and operative techniques were retrospectively evaluated., Results: All patients underwent laparoscopic anatomical segmentectomy of segments VII and/or VIII of the liver with the hepatic vein exposed from the head side. None of the cases was converted to open surgery. The average procedure duration was 326.20 ± 51.13 min, and the average blood loss volume was 375.0 ± 166.42 ml. No postoperative complications were observed. The average postoperative hospital stay was 6.7 ± 0.82 days. No recurrence or metastasis was observed., Conclusions: Laparoscopic anatomical segmentectomy of liver segments VII and VIII, with the hepatic vein exposed from the head side, may be safe, convenient, and applicable to perform. J. Surg. Oncol. 2016;114:752-756. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Objective: To investigate the relationship between the changes of the copy numbers of mtDNA in peripheral blood mono-nucle- ar cell(PBMC) and the disordered of antioxidant capacity of hepatocellular carcinoma (HCC) patients., Methods: The Ficoll Hypaque method was used to isolate the PBMC from blood specimens. The ND1 gene of the mitochondrial was amplified by real-time PCR; meantime β-actin was served as a quantitative standard marker; the difference of mtDNA copy number in PBMC was compared between HCC and healthy control group. The level of reactive oxygen species (ROS) in PBMC was determined by flow cytometry. The change of total antioxidant capacity (T- AOC) of plasma was detected by the biochemistry examination., Results: The copy numbers of ND1 gene in PBMC of HCC was 73% that of the healthy control group,which suggested a decrease of the copy numbers of mtDNA in HCC. The levels of ROS of PBMC in HCC was (417. 82 ± 110.62) and (301.82 ± 75.54) in control group, which showed that the levels of ROS of PBMC in HCC were significant higher than that in control group (P < 0.01).Plasma T-AOC in HCC was (1.30 ± 0.85), and (3.20 ± 1.62) in control. The T-AOC of plasma of HCC was significantly lower than in control group (P < 0.01)., Conclusion: There was a certain relationship between the decrease of the copy numbers of mtDNA and the disordered antioxidant capacity in hepatocellular carcinoma, which may be associated with the development of hepatocellular carcinoma.

Background: Traditional open liver resection remains the classic procedure for hepatocellular carcinoma (HCC) located in the posterosuperior segments of the liver (segments I, IVa, VII, and VIII). This study compared the perioperative and oncologic results for laparoscopic versus open liver resection of HCC located in the posterosuperior segments, especially in patients with cirrhosis., Methods: This study included 41 patients who underwent laparoscopic liver resection (LLR) and 86 who underwent open liver resection (OLR) for HCC in the posterosuperior segments between January 1, 2010, and December 31, 2012. There perioperative course and oncologic outcomes were retrospectively evaluated., Results: There were no significant differences between the LLR and OLR groups in length of operation (242.41 ± 73.69 vs. 235.38 ± 65.80 min), transfusion rate (7.3 vs. 14.0 %), R0 resection rate (100 vs. 97.7 %), or tumor size (4.22 ± 2.05 vs. 4.30 ± 1.49 cm). In contrast, postoperative hospital stay (9.44 ± 2.72 vs. 14.53 ± 6.03 days) was significantly shorter, and postoperative complication rates (17.1 vs. 37.2 %) and intraoperative blood loss (272.20 ± 170.86 vs. 450.12 ± 344.70 mL) significantly lower in the LLR than in the OLR group. In addition, there was no significant difference between the two groups (LLR vs. OLR) regarding 1-year overall survival rate (95.1 vs. 89.5 %), 3-year overall survival rate (78 vs. 76.7 %,), 1-year disease-free survival rate (87.8 vs. 82.6 %,), and 3-year disease-free survival rate (70.7 vs. 68.6 %)., Conclusions: LLR for selected patients with HCC in the posterosuperior segments may offer the same oncologic outcomes as conventional procedures, while being associated with such advantages as lower blood loss, fewer postoperative complications, and shorter hospital stay.

Background: Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) is a breakthrough in the field of hepatobiliary surgery [1], resulting in the growth of remnant liver volume by 74-87.2% in 9-13 days [2, 3]. However, patients required to undergo two open operations in a short period of time [2-5]. To our knowledge, this video is the first description of the technical aspects of totally laparoscopic ALPPS for the treatment of cirrhotic hepatocellular carcinoma (HCC)., Methods: A patient with 6-cm cirrhotic HCC in the right liver was referred for surgical treatment. Preoperative examination confirmed that the remnant liver volume to standard liver volume ratio was 27%. Therefore, a totally laparoscopic ALPPS was planned. In the first stage of the operation, the right portal vein was ligated after laparoscopic cholecystectomy. A tape was passed along the retrohepatic avascular space and the liver was suspended during parenchymal transection, resulting in the successful completion of liver partition using the anterior approach, which conformed to the "No Touch" principle. Thirteen days after the first stage, the ratio had reached 40.6%. The second stage involved the transections of the right hepatic pedicle and the right hepatic vein., Results: The operative times were 255 min for the first stage and 210 min for the second stage. Pathology confirmed the diagnosis of HCC. A complication, pleural effusion, occurred after the second stage. Following pleural puncture drainage, the patient was discharged 9 days postoperatively. Follow-up 4 months after surgery was uneventful. Comparing with our open ALPPS results in two patients, the laparoscopic approach reduced the rate of postoperative complications and peritoneal adhesions, which often complicate the second stage of the operation, thus contributing to more rapid recovery., Conclusion: Totally laparoscopic ALPPS is feasible, with satisfactory short-term efficacy, conforming to the "No Touch" principle. ALPPS may be safe for the treatment of HCC in cirrhotic patients, but the interval between the two stages may be extended.

The mutagenic effect of hepatitis B (HBV) integration in predisposing risk to hepatocellular carcinoma (HCC) remains elusive. In this study, we performed transcriptome sequencing of HBV-positive HCC cell lines and showed transcription of viral-human gene fusions from the site of genome integrations. We discovered tumor-promoting properties of a chimeric HBx-LINE1 that, intriguingly, functions as a hybrid RNA. HBx-LINE1 can be detected in 23.3% of HBV-associated HCC tumors and correlates with poorer patient survival. HBx-LINE1 transgenic mice showed heightened susceptibility to diethylnitrosamine-induced tumor formation. We further show that HBx-LINE1 expression affects β-catenin transactivity, which underlines a role in activating Wnt signaling. Thus, this study identifies a viral-human chimeric fusion transcript that functions like a long noncoding RNA to promote HCC., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Post-hepatectomy hemorrhage (PHH) requiring re-laparotomy is a life-threatening situation and is associated with a considerably high hospital mortality rate. However, risk factors of hospital mortality in patients with this condition have not yet been investigated., Methods: The perioperative data of 258 patients with hepatocellular carcinoma who underwent re-laparotomy for PHH from 1997 to 2011 were retrospectively reviewed and evaluated by univariate and multivariate analyses to identify risk factors of hospital mortality., Result: Hospital death occurred in 43 patients between 16 h and 40 days after re-laparotomy, and the overall mortality rate was 16.7 %. The median time lag between first recognition of active bleeding and re-laparotomy was 6 h (range 0.5-34 h). The mortality of patients undergoing late re-laparotomy (≥6 h) was much higher than those undergoing early re-laparotomy (<6 h) (25 vs 8.6 %; P = 0.001). Multivariate analysis showed early time period (1997-2004) (P = 0.040), liver cirrhosis (P = 0.025), ineffective hemostasis during re-laparotomy due to coagulopathy (P = 0.038), late re-laparotomy (≥6 h) (P = 0.032), postoperative liver failure (P = 0.001), and postoperative acute renal failure requiring hemodialysis (P = 0.024) were independent risk factors of hospital mortality., Conclusion: Immediate re-laparotomy is a key factor to reduce hospital mortality for patients with active bleeding after partial hepatectomy. More care should be taken in those patients who develop acute liver failure and/or serious acute renal failure after re-laparotomy.

Background: Although laparoscopic liver resection has developed rapidly and gained widespread acceptance for the treatment of benign liver diseases and hepatocellular carcinoma with a small tumor size, its usefulness for the treatment of large tumors is less clear, due to concerns about compromising oncological principles and patient safety. The purpose of this study was to explore the safety and feasibility of laparoscopic liver resection for the treatment of hepatocellular carcinoma with a tumor size of 5-10 cm., Methods: From March 2007 to December 2011, we performed liver resection in 275 patients with hepatocellular carcinoma with a tumor size of 5-10 cm. Laparoscopic liver resection was performed in 97 patients (Lap-Hx group) and open liver resection was performed in 178 patients (Open-Hx group). Operative time, estimated intraoperative blood loss, blood transfusion rate, and length of postoperative hospital stay were compared between the two groups. Early and intermediate-term postoperative outcomes were also compared., Results: Only one liver resection was performed for every patient with HCC in the present study.No operative deaths occurred in either group. Nine of the laparoscopic procedures were converted to open resection (conversion rate 9.28%). There were no significant differences in mean operative time (245±105 min vs 225±112 min; P = .469), mean estimated intraoperative blood loss (460±426 mL vs 454±365 mL; P = .913), or blood transfusion rate (4.6%, 4/88) vs (2.8%, 5/178)(P = .480) between the Lap-Hx and Open-Hx groups. However, postoperative hospital stay was shorter in the Lap-Hx group than the Open-Hx group (8.2±3.6 days vs 13.5±3.8 days; P = .028). There was a lower rate of postoperative complications in the Lap-Hx group than the Open-Hx group (9% vs 30%; P = .001), but there were no severe complications in either group. The median overall follow-up time was 21 months (range 2-50 months) and the median follow-up of time of survivors was 23 months. The median follow-up time was 25 months in the Lap-Hx group and 20 months in the Open-Hx group. The follow-up rate was 95% (84 patients) in the Lap-Hx group and 95% (169 patients) in the Open-Hx group, which was not a significant difference between the two groups (P = .20). Tumor recurrence occurred in 17 patients (20%) in the Lap-Hx group and 35 patients (21%) in the Open-Hx group, which was not a significant difference between the two groups (P = .876). A total of 33 patients (13%) died during the study period, including 12 patients (14%) in the Lap-Hx group and 21 patients (12%) in the Open-Hx group, which was not a significant difference between the two groups (P = .695). There were also no significant differences in the 1-year rates of overall survival (94% vs 95%; P = .942) or disease-free survival (93% vs 92%; P = .941), or the 3-year rates of overall survival (86% vs 88%; P = .879) or disease-free survival (66% vs 67%; P = .931), between the Lap-Hx and Open-Hx groups., Conclusions: Laparoscopic liver resection is safe and feasible in patients with hepatocellular carcinoma with a tumor size of 5-10 cm. Laparoscopic liver resection can avoid some of the disadvantages of open resection, and is beneficial in selected patients based on preoperative liver function, tumor size and location.