Abstract:Objective: To compare the clinical efficacy of laparoscopic right hemihepatectomy (LRH) and open right hemihepatectomy (ORH) in treatment of liver tumor.
Methods: The controlled studies comparing LRH and ORH in treatment of liver tumor published in English and Chinese were searched through online databases. The retrieval time was up to April 2018. After the quality evaluation and data extraction of the included studies, Meta-analysis was conducted by using RevMan5.3 software.
Results: Seven studies were finally included involving 472 patients, with 207 cases in LRH group and 265 in ORH group. The results of Meta-analysis showed that in LRH group compared with ORH group, the intraoperative blood loss was reduced (WMD=–166.14, 95% CI=–254.59––77.68, P<0.000 2), incidence of complications was decreased (OR=0.35, 95% CI=0.21–0.57, P<0.000 1) and length of postoperative hospital stay was shortened (WMD=–4.97, 95% CI=-6.13––3.81, P<0.000 01), while the operative time was prolonged (WMD=51.39, 95% CI=14.88–87.90, P=0.006); no significant differences were noted with regard to the transfusion rate, mortality, surgical margin and tumor size (all P>0.05).
Conclusion: LRH shows no difference in efficacy for the treatment of liver tumor compared with ORH, and also has better safety. However, this conclusion still needs to be verified by more high-quality studies.

Abstract:Objective: To investigate the influence of hepatitis B virus (HBV) infection and antiviral treatment on the formation of microvascular invasion (MVI) in hepatocellular carcinoma.
Methods: The clinical and pathological data of 660 patients with hepatocellular carcinoma who underwent radical hepatectomy from January 2015 to December 2017 in Affiliated Hospital of Qingdao University were retrospectively analyzed. 
Results: In the 660 patients, the incidence of MVI was 46.8% (309/660). Results of univariate analysis showed that MVI formation was significantly related to positive HBsAg, detectable HBV DNA load, and whether or not underwent antiviral treatment, and was also associated with the age, sex, preoperative levels of AFP, tumor markers and liver function parameters, histological grade, the size and number of lesions, capsule integrity and presence or absence of satellite nodules (all P<0.05). In the HBV-related patients, the results of multivariate Logistic regression analysis showed that detectable HBV DNA load was an independent risk factor for MVI (OR=5.33, P<0.001), while antiviral therapy for more than half a year was an independent protective factor against MVI (OR=0.37, P=0.002), and other independent influential factors for MVI were included sex, AFP level, tumor diameter, histological grade, incomplete capsule and presence of satellite nodules (all P<0.05). In patients with severe MVI, the proportions of HBV infection, high detectable HBV DNA load (>100 IU/mL) and cases without antiviral treatment were significantly increased compared with those with mild or without MVI (all P<0.05), moreover, the proportion of cases with liver cirrhosis was increased in patients with mild MVI (80.0%).
Conclusion: HBV infection and HBV DNA level are independent factors for MVI formation in hepatocellular carcinoma and antiviral therapy may have a preventive effect against the formation of MVI.

Abstract:Objective: To investigate the factors for early recurrence of patients with hepatocellular carcinoma (HCC) after surgical resection.
Methods: The clinical and follow-up data of 450 HCC patients undergoing surgical resection from January 2014 to January 2016 in the First Affiliated Hospital of Zhengzhou University were retrospectively analyzed. The factors for early postoperative recurrence of HCC were determined by statistical analysis.
Results: Of the 450 patients, recurrence within 2 years after surgery occurred in 182 cases (40.4%). Results of univariate analysis showed that portal vein tumor thrombus and preoperative serum AFP level as well as the number, maximum diameter and differentiation of the tumor were significantly associated with the postoperative recurrence of HCC (all P<0.05). Results of Cox proportional risk regression analysis showed that lesion number (RR=2.148, 95% CI=1.175–3.924, P=0.013), maximum diameter of tumor (RR=1.591, 95% CI=1.006–2.518, P=0.047), presence and absence of the portal vein tumor thrombus (RR=1.835, 95% CI=1.242–2.709, P=0.001), serum AFP level (RR=1.722, 95% CI=1.141–2.601, P=0.010), and degree of differentiation (RR=1.463, 95% CI=1.071–1.998, P=0.017) were all independent factors for postoperative recurrence of HCC. The functional prediction equation established by incorporating these factors had certain value in estimating the early postoperative recurrence of HCC (likelihood-ratio test: χ2=45.727, P<0.001).
Conclusion: There are multiple factors that affect the early recurrence of HCC patients after surgical resection, among which portal vein tumor thrombus, lesion number, and maximum diameter and differentiation degree of the tumor and serum AFP level may be independent risk factors for recurrence. Integrated evaluation of these factors before operation has certain directive significance in preventing postoperative recurrence.

Abstract:Objective: To compare the efficacy and prognosis of percutaneous radiofrequency ablation and laparoscopic hepatectomy in treatment of small hepatocellular carcinoma (HCC).
Methods: The clinical data of 140 patients with small HCC treated from January 2012 to December 2014 were retrospectively analyzed. Of the patients, 80 cases underwent percutaneous radiofrequency ablation (ablation group) and 60 cases underwent laparoscopic hepatectomy (laparoscopic group). The changes in postoperative serum liver function parameters and tumor markers and incidence of postoperative complications, as well as the radical cure rate, and the recurrence and survival rates were compared between the two groups of patients.
Results: There were no significant differences in baseline data and levels of liver function parameters and tumor markers between the two groups of patients before operation (all P>0.05). After operation, the liver function parameters in ablation group first rose and then fell, and declined continuously in laparoscopic group, and in the ablation group, the levels of alanine aminotransferase and aspartate aminotransferase were significantly higher than those in laparoscopic group for a short period of time after the operation (all P<0.05); the levels of tumor markers were gradually reduced in both groups, which showed no significant differences between the two groups (all P>0.05). The incidence of postoperative complications in ablation group was significantly lower than that in laparoscopic group (3.75% vs. 20.00%, P=0.002). There were no significant differences concerning the radical cure rate and the recurrence rate, and the 1-, 2- and 3-year survival rates between the two groups (all P>0.05).
Conclusion: There is no evident difference in efficacy and prognosis between the two treatment methods in treatment of small HCC. Radiofrequency ablation is associated with fewer complications, but with short-term injury to liver function.

Abstract:Objective: To investigate the change in serum exosomeal miR-1290 level in patients with hepatitis B virus (HBV) related hepatocellular carcinoma (HCC) and its diagnostic value.
Methods:  The blood samples from 31 patients with HBV-related HCC, 20 HBV carriers, 20 patients with hepatitis B induced liver cirrhosis, and 19 subjects undergoing health maintenance examination were collected. The serum exosomes were isolated and purified and then identified. The expression levels of exosomal miR-1290 were determined by RT-PCR. The diagnostic efficacy of exosomal miR-1290 for HBV-related HCC was evaluated using the ROC curve.
Results: The purified samples contained a large number of exosomal particles with the typical characteristics of the exosomes. Compared with healthy individuals, the exosomal miR-1290 level showed no significant difference in HBV carriers (P>0.05), and was significantly elevated in patients with HBV-related HCC (P<0.001), in advanced stage HCC patients was significantly higher than in early stage HCC patients (P=0.036), but was significantly decreased in patients with hepatitis B induced liver cirrhosis (P=0.006). The area under the curve (AUC) of the ROC of exosomel miR-1290 for diagnosis of HBV-related HCC was 0.82 (95% CI=0.73 0.91), with good specificity (88.1%), and its diagnostic efficiency was higher than that of AFP (AUC=0.792).
Conclusion: Serum level of exosomal miR-1290 is increased in patients with HBV-related HCC, and it has better diagnostic efficacy for HBV-related HCC. It is hopeful to become a serological marker for the diagnosis of HBV-related HCC.

Abstract:Objective: To investigate the mechanism for the selective killing effect of oncolyic adenovirus SG600-IL24 bearing human mda-7/IL-24 on l hepatocullular carcinoma (HCC) cells. 
Methods: The oncolytic adenovirus SG600-IL24 carrying human MDA-7/IL-24 (SG600-IL24) was constructed, and then was infected into the HCC cell lines HepG2 and HCCLM3 and normal liver cell line L02, respectively. In each cell line after infection, the changes in gene and protein expressions of STAT3 and its downstream signaling molecules as well as the protein expression of phosphorylated STAT3 were determined by RT-PCR and Western blot, respectively.
Results: The oncolytic adenovirus SG600-IL24 carrying human mda-7/IL-24 was constructed successfully. After SG600-IL24 infection, the expressions of human mda-7/IL-24 gene and protein were significantly increased in all the cell lines (all P<0.05). In the two types of HCC cells, the STAT3 expression level was significantly downregulated, and its downstream signaling molecule c-myc, Bcl-xl, Bcl-2, cyclin D2, survivin, MMP-2, MMP-9, XIAP, OPN, and VEGF were downregulated while Bax were upregulated significantly, and all presented with a time-dependent trend (all P<0.05); the protein expression of p-STAT3 was increased after infection and reached to a peak in 2 hours, and then decreased. No significant changes were noted in expressions of STAT3 and its downstream molecules in L02 cells after infection (all P>0.05).
Conclusion: The mechanism for the selective killing effect of oncolyic adenovirus SG600-IL24 bearing human mda-7/IL-24 on HCC cells may probably be associated with its selectively inhibiting STAT3 signaling pathway in HCC cells, with no influence on normal liver cells.

Abstract:Objective: To investigate the expression of splicing factor proline- and glutamine-rich (SFPQ) in hepatocellular carcinoma (HCC) and its actions.
Methods: The expression levels of SFPQ mRNA and protein in tumor tissues and their adjacent tissues were determined by real-time quantitative PCR and Western blot. The difference in SFPQ mRNA abundance between normal liver tissue and HCC tissue were analyzed by using TCGA and GEO database. The relations of SFPQ mRNA level with the clinical stage, histopathological grade and survival time of HCC patients as well as the correlation of the SFPQ mRNA with the proliferation gene PCNA and Ki-67, and cell cycle protein CCNE1 and CDK2 were analyzed by using TCGA database. The changes in proliferation and cell cycle in HCC HepG2 and Hep3B cells after SFPQ knock down were observed.
Results: The results of tissue sample analysis showed that the expression levels of both SFPQ mRNA and protein were significantly higher in HCC tissue than those in the adjacent tissue (both P<0.05). The results of database analysis showed that the SFPQ mRNA abundance in HCC tissue was significantly higher than that in normal liver tissue, SFPQ mRNA level was increased with the increase of histopathological grade and the progression of clinical stage, the survival rate was significantly reduced in patients with high SFPQ mRNA expression, and SFPQ mRNA expression was positively correlated with the expressions of PCNA, Ki-67, CCNE1 and CDK2 (P<0.05). In both HepG2 and Hep3B cells after SFPQ knockdown, the proliferative abilities were significantly decreased with significant G1 phase arrest (all P<0.05).
Conclusion: SFPQ expression is increased in HCC, and the increased SFPQ may accelerate HCC progression via regulating cell cycle and promoting proliferation of the HCC cells.

Abstract:Objective: To investigate the expression of kinesin family member 15 (KIF15) in liver cancer and its relation with the biological behaviors of liver cancer cells. 
Methods: Using TCGA database, the KIF15 expressions in liver cancer patients with different clinical conditions and its association with the survival rates of liver cancer patients were analyzed. In liver cancer SMMC-7721 cells after down-regulating KIF15 expression, the changes in proliferative ability, cell cycle characteristics and invasion capacity were observed. 
Results: The results of database analysis showed that the more advanced TNM or T stages corresponded to higher KIF15 expression (both P<0.05); The survival rate in liver cancer patients with higher KIF15 expression was significantly lower than that in liver cancer patients with low KIF15 expression (P<0.05). In SMMC-7721 cells after transfection with siKIF15, the proliferative ability was significantly reduced, G0/G1 phase arrest was significantly increased, and the invasion capability was significantly weakened (all P<0.05).
Conclusion: KIF15 expression is closely related to the progression of liver cancer, and the mechanism may probably be associated with its promoting the proliferation and invasion of the liver cancer cells.

Abstract:Objective: To investigate the expression of exportin 5 (XPO5) in hepatocellular carcinoma (HCC) tissue and its relations with clinicopathologic characteristics and prognosis of the patients. 
Methods: The protein expressions of XPO5 in 92 specimens of HCC and paired adjacent liver tissue were determined by Western blot and immunohistochemical staining, respectively. The relations of XP05 expression level with the clinicopathologic features and prognosis of HCC patients were determined by statistical analyses.
Results: The expression levels of XPO5 protein in HCC tissue was markedly higher than that in adjacent liver tissue. The XPO5 expression was significantly associated with the tumor size, degree of differentiation, clinical stage, distant metastasis and liver cirrhosis of the patients (all P<0.05). The 1- and 5-year disease-free survival rates and 1- and 5-year overall survival rates in patients with high XPO5 expression were significantly lower than those with low XPO5 expression (46.8% vs.78.5%, 20.3% vs. 37.4%; 75.9% vs. 91.2%, 36.1% vs. 58.8%, all P<0.05). High XPO5 expression was an independent risk factor for either disease-free survival and overall survival in HCC patients (P=0.036; P=0.013).
Conclusion: XPO5 expression is increased in HCC tissue, and is associated with the malignant profiles of HCC and unfavorable outcomes of the patients.

Abstract:Objective: To investigate the immune tolerance in liver transplantation in rats induced by dendritic cells (DCs) transfected with B and T lymphocyte attenuator (BTLA) gene mediated by lentivirus and the mechanism.
Methods: The animal models of orthotopic liver transplantation were established by using DA rats as donors and Lewis rats as recipient respectively. DCs were isolated from SD rats, and then were infected with recombinant lentivirus carrying or without BTLA gene, respectively. Thirty-six rats after liver transplantation were equally randomized into model group (without any treatment after liver transplantation), DC group (transfused with DCs without BTLA gene after liver transplantation) and BTLA-DC group (transfused with DCs bearing BTLA gene after liver transplantation). In each group of rats, after completion of serum biochemical tests and liver pathological examination on postoperative 7 d, the remaining rats were used for determining the survival time.
Results: After transplantation, the liver function injury parameters, immune-stimulating cytokine IFN-γ level and rejection pathological score of the liver transplant were decreased and the immune-inhibiting cytokine IL-10 was increased in BTLA-DC group, but all above variables presented an opposite trend in DC group compared with model group, and the differences in all quantitative variables had a statistical significance (all P<0.05). The mean survival times for model group, DC group and BTLA-DC group were 15, 13, and 79 d respectively, and difference in survival time had statistical significance among the three groups (χ2=16.14, P=0.000 3).
Conclusion: DCs with high BTLA expression can alleviate rejection reactions of the liver transplant and prolong the survival time of the recipient rats, and the mechanism may possibly be associated with its inducing T cell immune tolerance.

Abstract:Objective: To investigate the application effects of the goal-directed fluid therapy (GDFT) guided by stroke volume variation (SVV) on elderly patients undergoing open hepatectomy.
Methods: Sixty-four elderly patients (≥65 years) undergoing elective open hepatectomy were randomly and equally assigned to two groups, to receive the controlled low central venous pressure (CLCVP) technique (CLCVP group) and SVV-guided GDFT (GDFT group) respectively during operation. Hemodynamic and blood gas indexes were compared between the two groups at 5 time points: 5 min before anesthesia induction (T0), immediately entering the abdominal cavity (T1), the second hepatic blood flow occlusion (T2), starting closure of abdomen (T3), and operation completion (T4). Other variables such as intraoperative blood loss, amount of fluid infusion, urine volume and time of hepatic blood flow occlusion were also compared.
Results:  The general data of the two groups of patients were comparable. Compared with the hemodynamic variables at T0 time point within group, the mean arterial pressure (MAP) and central venous pressure (CVP) values were significantly decreased at T1, T2, T3 and T4 time points, the heart rates (HR) were significantly reduced at T1 time point in both groups, and the cardiac index (CI) was significantly increased at T2, T3 and T4 time points in CLCVP group and significantly increased at all T1, T2, T3 and T4 time points in GDFT group (all P<0.05). The MAP and HR showed no significant differences between the two groups at any time point (all P>0.05), but the CVP at T3 time point, CI at T2, T3 and T4 time points in GDFT group were significantly higher than those in CLCVP group (all P<0.05). Compared with the blood gas variables at T0 time point within group, the blood pH values were significantly decreased in both groups at T2, T3 and T4 time points (all P<0.05), the central venous oxygen saturation (SCVO2) showed no significant differences in CLCVP group at each time point (all P>0.05), but was significantly increased at T2, T3 and T4 points in GDFT group (all P<0.05), and the blood lactic acid (Lac) levels were significantly increased at all T1, T2, T3 and T4 time points in both group (all P<0.05). The pH values showed no significant differences between the two groups at any time point (all P>0.05), but the SCVO2 values were significantly higher at T2, T3 and T4 time points and the Lac levels were significantly lower at T3 and T4 time points in GDFT group than those in CLCVP group (all P<0.05). There were no statistically significant differences between the two groups in the amounts of crystal fluid, colloidal fluid and total fluid and urine volume (all P>0.05), but the intraoperative blood loss and time of hepatic blood flow occlusion were reduced in GDFT group compared with CLCVP group (both P<0.05).
Conclusion: In elderly patients undergoing open hepatectomy, using SVV-guided GDFT can stabilize the hemodynamic status, improve the blood gas indexes and reduce intraoperative hemorrhage and the time of liver blood flow occlusion.

Abstract:Objective: To investigate the relations of carotid plaque characteristics of MRI and clinical factors with ischemic stroke in patients with carotid artery stenosis≤50%.
Methods: From September 2014 to February 2016, a total of 43 patients with carotid artery stenosis ≤50% were selected by ultrasound screening. All patients underwent the black-blood MRI examination. The relations of the plaque MRI characteristics and other risk factors with ischemic stroke were analyzed.
Results: In the 43 patients, the degree of carotid artery stenosis ranged from 5% to 50%, and the follow-up time ranged from 1.9 to 19.4 months. During the follow-up period, ipsilateral ischemic stroke occurred in 4 patients. The results of univariate and multivariate Logistic regression analysis showed that only the intra-plaque hemorrhage (IPH) was significantly associated with ischemic stroke (OR=297.797, 95% CI=2.638–33620, P=0.018), while other MRI features and clinical factors were irrelevant to ischemic stroke (all P>0.05). Kaplan-Meier survival analysis showed that the mean ischemic stroke-free time in patients with IPH was significantly shorter than that in patients without IPH (14.3 months vs. 18.6 months, P=0.001), and in patients with coronary heart disease (CHD) was significantly shorter than that in patients without CHD (12.1 months vs. 18.7 months, P=0.029); Cox regression analysis showed that IPH (HR=18.2, 95% CI=2.7–123.3, P=0.003) and CHD (HR=27.4; 95% CI=1.6–464.3; P=0.022) were independent risk factors for ischemic stroke.
Conclusion: In patients with carotid artery stenosis ≤50%, IPH and CHD are closely associated with the occurrence of ischemic stroke.

Abstract:Hepatocellular carcinoma (HCC) is one of the common malignant tumors in China. Chronic hepatitis B virus (HBV) infection has been considered as a risk factor for HCC. Hepatitis B virus X protein (HBx) is a multifunctional regulator that regulates signal transduction and epigenetic gene expressions, and also is involved in cell proliferation and apoptotic pathways. HBx can promote the self-renewal ability, differentiation, and resistance to chemotherapy and other biological behaviors of the liver cancer stem cells (LCSCs), and thereby promote tumor metastasis, infiltration and recurrence. The authors address HBx regulating LCSCs to maintain the biological behaviors of HCC.

Abstract:Postoperative liver failure has always been a difficult issue for liver surgeons, which is often directly related to the small volume of future liver remnant (FLR). The associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) is an innovative technique for rapid growth of FLR in a short period of time, which brings hope to those who cannot withstand a radical surgery because of insufficient volume of FLR. However, after the high postoperative mortality rates of ALPPS reported by many large medical centers, how to correctly grasp the indications of ALPPS and improve the traditional ALPPS becomes particularly important. Here, the authors address the mechanism of ALPPS promoting FLR hyperplasia, the case selection for ALPPS, the controversies regarding ALPPS and the latest progress of the derivative procedures based on the classical ALPPS.

Abstract:Esophogastric variceal bleeding is one of the severe and lethal complications of liver cirrhosis, and portal hypertension and esophogastric variceal vein damage are essential and main risk factors for its occurrence. Its clinical treatment includes medications, endoscopic or interventional therapy, surgery and liver transplantation, each with specific advantages. From the perspectives of control of the risk factors such as portal vein pressure, varicose vein damage and liver function injury, the authors analyzed and evaluated the clinical effect and mechanism of various clinical treatment methods. The clinical effect of single risk factor control is often limited, while the combined treatment for multiple control of the risk factors has better clinical efficacy. Furthermore, endoscopy combined with splenic arterial trunk embolization has theoretical advantages over other treatment options.

Abstract:Idiopathic portal hypertension (IPH) is a very rare disease, characterized by portal hypertension with obstruction or stenosis of the intrahepatic peripheral portal branches, in the absence of liver cirrhosis or obstruction of hepatic vein and main portal vein. This condition also has other denominations such as idiopathic non-cirrhotic portal hypertension and non-cirrhotic portal fibrosis. The etiology and pathogenesis of IPH remain unclear, and may be related to heredity, immunity, infection and other factors. The main manifestations of this disease are hypersplenism and gastroesophageal varices, with less occurrence of hepatic insufficiency and hepatic encephalopathy. There are still many controversies in the diagnosis and treatment of IPH. Its diagnosis is only made by exclusion, and treatment chiefly refers to the guidelines for cirrhotic portal hypertension. There are few data on prognosis of IPH, and IPH is considered to have a better prognosis than that of cirrhotic portal hypertension, and in only a few patients may progress to liver failure.