Abstract:Tumor recurrence after liver transplantation for hepatocellular carcinoma (HCC) is the major cause affecting the prognosis of the recipients. Investigating the factors for post-transplant HCC recurrence and reducing the recurrence rate are crucial for improving survival of the recipients. In recent years, numerous studies have been conducted from the aspects of pre-, intra- and post-transplantation by scholars at home and abroad. They found that recipient selection criteria, down-staging treatment, biomarkers, intra-operative blood loss, allograft ischemic time, immunosuppressive agents and systemic adjuvant therapy are factors for the post-transplant HCC recurrence. These achievements have great importance in prevention and treatment of HCC recurrence after liver transplantation.

Abstract:With the popularization of the minimally invasive laparoscopic techniques, laparoscopic hepatectomy has increasingly become the mainstay for the treatment of both benign and malignant liver diseases. Living donor hepatectomy is one of its most attention-drawing and controversial practical uses. From the first pure laparoscopic donor hepatectomy reported in 2002, pure laparoscopic living donor hepatectomy has been frequently used in some experienced transplant centers. Evolving from the early left/left lateral segment grafts to the more complex right liver graft, and from the hand-assisted to pure laparoscopic approach, laparoscopic living donor hepatectomy is now much more mature. Here, the authors review the development history of laparoscopic living donor hepatectomy, and also analyze its technical details based on personal experiences.

Abstract:Primary liver cancer is the most common malignant tumor of the liver. In China, it is still the fourth most common malignant tumor and the second cause of cancer-related death. According to the basic principles of evidence-based medicine, the National Health and Family Planning Commission of the People’s Republic of China updated the relevant recommendations and released the guidelines for diagnosis and treatment of primary liver cancer (2017 edition), on basis of 2011 edition combined with the progress of diagnosis and treatment of hepatocellular carcinoma in recent years. The authors interpret the main points and updates of the guidelines in terms of screening, diagnosis, staging and treatment of hepatocellular carcinoma.

Abstract:Objective: To attempt to establish a new clinical staging system for hepatocellular carcinoma (HCC) based on analysis of the critical prognostic factors for HCC. 
Methods: A total of 338 HCC specimens were collected from Xiangya Hospital of Central South University and the Affiliated Tumor Hospital of Guangxi Medical University, and then, the presence of tumor necrosis and incidence of microvascular invasion were detected. The incidence of lymph node metastasis in HCC was analyzed through review of the relevant literature. Based on the follow-up survival data of 236 HCC patients in Xiangya Hospital, the recurrence and survival rates of the patients were determined using tumor necrosis and vascular invasion as variables. The T (tumor) “N” (necrosis plus vascular invasion) M (metastasis) staging system was established by integrating the tumor necrosis with or without concomitant vascular invasion as a component into the AJCC 8th edition TNM staging system, and then, the efficacy of prognosis judgment of the T“N”M staging system and 8th edition TNM staging system was compared through survival analysis.
Results: In the two HCC cohorts, the incidence of tumor necrosis was 75.4% (177/236) and 59.8% (61/102), and the detection rate of microvascular invasion was 71.6% (169/236) and 86.2% (88/102), respectively. The incidence of HCC with lymph node metastasis was only 0.8%–8.33% reported in the literature. The area under the ROC curve for the recurrence and 1-, 3- and 5-year overall survival of HCC patients was 0.940, 0.834, 0.748 and 0.721, respectively. The prognosis differences among patients with Ia, Ib, IIIa and IIIc HCC were clearly distinguished by the T“N”M staging system. The C index of 5-year survival rate (0.672) and the linear trend χ2 test value (0.732) were higher while the AIC value (1 798.142) was lower than the corresponding values of the 8th edition TNM staging system (0.537, 0.626, 1 806.256).
Conclusion: The established T“N”M staging system based on the clinical pathological features of HCC is a simple and effective staging system, which can overcome the limitations in predictive efficiency of the N category of the TNM staging system, with more relevance to the actual clinical situation.

Abstract:Objective: To evaluate the efficacy and safety of apatinib combined with transcatheter arterial chemoembolization (TACE) in treatment of intermediate and advanced liver cancer.    
Methods: The publicly published randomized controlled studies comparing apatinib plus TACE (study group) and TACE alone (control group) for intermediate and advanced liver cancer were searched on computer in several national and international databases. The search was restricted from inception of each respective database to March 2019. The quality assessment was carried out using the Cochrane risk of bias tool after data extraction, and Meta-analysis was performed by using RevMan 5.3 software. 
Results: Eight randomized controlled studies were finally included, involving a total of 486 patients, with 243 cases each in study group and control group. In study group compared with control group, both short-term efficacy (objective remission rate: OR=2.88, 95% CI=1.80–4.62, P<0.000 1; disease control rate: OR=3.29, 95% CI=1.96–5.53, P<0.000 01) and long-term results (6-month survival rate: OR=2.89, 95% CI=1.74–4.80, P<0.000 1; 12-month survival rate: OR=2.37, 95% CI=1.46–3.83, P=0.000 5; 24-month survival rate: OR=2.67, 95% CI=1.41–5.04, P=0.002) were significantly improved. The incidence of hand-foot syndrome and albuminuria were significantly higher in study group compared to control group (both P<0.05), while other adverse reactions such as fever, nausea/vomiting, diarrhea, myelosuppression and hypertension showed no significant differences between the two groups (all P>0.05).
Conclusion: Both short-term efficacy and long-term results of apatinib combined with TACE are superior to those of TACE alone in treatment of intermediate and advanced liver cancer. The overall survival time of apatinib group is longer, and can improve the short-term efficacy and long-term survival rate of patients, but the related side effects are common. However, the associated adverse effects may probably affect its application range and the patients’ quality of life.

Abstract:Objective: To compare the safety and efficacy of laparoscopic and open liver resection for BCLC-A hepatocellular carcinoma (HCC) between well-matched patient groups.  
Methods: The clinical data of 313 patients with BCLC-A HCC undergoing primary hepatectomy from January 2012 to December 2016 in the Department of Hepatobiliary Surgery of Hunan Provincial People's Hospital were retrospectively analyzed. Among them, 102 cases underwent laparoscopic hepatectomy (laparoscopic group) and 211 cases underwent open hepatectomy (laparotomy group). The 1:1 propensity score matching (PSM) was performed using the baseline variables that included tumor characteristics, general conditions and resection types of the patients. Then, the relevant clinical variables were compared between the two groups.
Results: The baseline variables were well balanced between the two groups after PSM (the area under ROC curve was 0.584), with 86 matched patients in each group. In laparoscopic group compared with laparotomy group, no significant differences were noted regarding the histological grade, microvascular invasion and positive margin (all P>0.05), but the intraoperative blood loss (100 mL vs. 200 mL), proportion of cases requiring intraoperative blood transfusion (4.7% vs.16.3%), operative time (160 min vs. 200 min), postoperative hospital stay (9 d vs. 12 d) and incidence of complications (5.8% vs. 16.3%) were significantly reduced (all P<0.05); the overall survival rate and tumor-free survival rate had no significant differences between them (P=0.863, P=0.789).
Conclusion: For BCLC-A HCC, laparoscopic hepatectomy has efficacy similar to that of open hepatectomy, but the former has better perioperative safety.

Abstract:Objective: To compare the clinical effects of total hepatic inflow occlusion (Pringle’s maneuver) and hemihepatic inflow occlusion (HHO) in hepatectomy for hepatocellular carcinoma (HCC).  
Methods: The clinical data of 141 patients with HCC undergoing liver resection from January 2012 to December 2016 were analyzed retrospectively. Of the patients, 71 cases underwent hepatic inflow occlusion with Pringle’s maneuver (Pringle group) and 70 cases underwent hepatic inflow occlusion with HHO method (HHO group). The main clinical variables between the two groups of patients were compared. 
Results: There were no significant differences in the baseline data between the two groups of patients (all P>0.05). The operative time in HHO group was significantly longer than that in Pringle group (P=0.001), but no significant differences were noted in other clinical variables that included intraoperative blood loss, amount of blood transfusion, proportion needing blood transfusion, liver resection scope, length of postoperative hospital stay and incidence of postoperative complications between the two groups (all P>0.05). In terms of postoperative pathology, all variables except the presence of vessel tumor emboli (P=0.022) showed no significant differences between the two groups (all P>0.05). In the stratification analyses of patients with hepatitis B, liver cirrhosis or major liver resection, the operative times in HHO group were all significantly longer than those in Pringle group (all P<0.05); the majority of postoperative liver function parameters in HHO group were superior to those in Pringle group, but only the differences of albumin levels on postoperative day (POD) 7 in patients with hepatitis B and the ALB levels on POD 7 and aspartate aminotransferase levels on POD 5 in patients with major liver resection had statistical significance (all P<0.05), all differences in the remaining liver function parameters and other clinical variables did not reach a statistical significance (all P>0.05).
Conclusion: In hepatectomy for HCC, both methods for hepatic inflow occlusion are safe and effective. However, in those with hepatitis, cirrhosis or major hepatectomy, HHO method is recommended for hepatic inflow occlusion.

Abstract:Objective: To investigate the association between the Ki-67 expression and the prognosis of patients with primary liver cancer receiving prophylactic transarterial chemoembolization (TACE) after radical resection.  
Methods: Using a retrospective cohort method, a total of 150 patients with primary liver cancer udergoing prophylactic TACE within 2 months after radical resection in Mengchao Hepatobiliary Hospital of Fujian Medical University from December 2014 to January 2016 were enrolled. According to postoperative pathological score of Ki-67 in the tumor tissue, the patients were divided into low Ki-67 expression group (Ki-67 score ≤20%, 44 cases) and high Ki-67 expression group (Ki-67 score >20%, 106 cases). The relations of Ki-67 expression level with the clinicopathologic factors as well as recurrence and survival of the patients were analyzed.
Results: The proportions of patients with multiple lesions, incomplete capsule and concomitant microvascular tumor thrombus were significantly higher in high Ki-67 expression group than those in low Ki-67 expression group (all P<0.05). High Ki-67 expression along with multiple lesions and large tumor size were independent risk factors for disease-free survival of the patients (all P<0.05); high Ki-67 expression together with multiple lesions, large tumor size, incomplete tumor capsule and presence of microvascular tumor thrombus were independent risk factors for overall survival of the patients (all P<0.05). The recurrence rate was significantly higher (57.9% vs. 37.7%, χ2=6.777, P<0.05) and the overall survival rate was significantly lower (45.6% vs. 75.9%, χ2=8.447, P<0.05) in patients in high Ki-67 expression group than those in patients in low Ki-67 expression group.
Conclusion: The Ki-67 expression level exerts significant impact on the prognosis of patients with primary liver cancer undergoing prophylactic TACE after radical resection. Those with high Ki-67 expression may have an unfavorable prognosis.

Abstract:Objective: To investigate the clinical effect of using interposition of the hepatic round ligament in surgical treatment of tumor in the hepatic hilar region. 
Methods: Ninety-seven patients with tumor in the hepatic hilar region admitted in Department of Hepatobiliary Surgery of the Second Affiliated Hospital of Shandong First Medical University were enrolled, and were randomly assigned into the study group (49 cases) and the control group (48 cases) by using random number table. Both groups of patients underwent hilar tumor resection, and patients in study group underwent enterohepatic anastomosis with interposition of the hepatic round ligament, while those in control group underwent conventional anastomosis during operation. The main surgical variables, liver function parameters and survival rates were compared between the two groups of patients.
Results: The preoperative data showed no significant differences between the two groups (all P>0.05). No statistical differences were noted in operative time, intraoperative blood loss, and length of hospitalization between groups (all P>0.05). The main parameters of liver function, the hemoglobin levels and the white blood cell counts were all significantly increased in both groups on 48 h after operation compared with their preoperative values (all P<0.05), but all showed no significant differences between the two groups (all P>0.05). The overall incidence of postoperative complications was significantly lower in study group than that in control group (26.53% vs. 54.17%, P<0.05). There were no significant differences in 1-, 2- and 3-year survival rates between the two groups (all P>0.05).
Conclusion: In surgical treatment of tumor in the hepatic hilar region, enterohepatic anastomosis with interposition of the hepatic round ligament can achieve the similar short- and long-term efficacy as the conventional enterohepatic anastomosis, with reduced complications. So, it is recommended to be used in clinical practice.

Abstract:Objective: To investigate the expression of microRNA-942-5p (miR-942-5p) in hepatocellular carcinoma (HCC) tissue and its functions. 
Methods: The expressions of miR-942-5p in 73 specimens of HCC tissue and paired tumor-adjacent tissue stored in the specimen bank of the First Affiliated Hospital, Xian Jiaotong University were determined by real-time quantitative PCR, and the relations of miR-942-5p expression with clinicopathologic parameters of HCC patients were analyzed. Meanwhile, the relationship between miR-942-5p expression and overall survival of HCC patients was identified by analyzing TCGA database. The changes in migration and invasion abilities of HCC cells after miR-942-5p expression interference were observed by Transwell assay. The downstream target of miR-942-5p was predicted and identified by using StarBase V3.0 database and Luciferase reporter assay, and then validated by Western blot.  
Results: The miR-942-5p expression in HCC tissues was significantly higher than that in tumor-adjacent tissue (2.390 vs. 1.764, P<0.05). The expression level of miR-942-5p was significantly associated with the number of lesions, vascular invasion and tumor stage of HCC patients (all P<0.05). The overall survival rate of HCC patients with high miR-942-5p expression was significantly lower than HCC patients with low miR-942-5p expression (19.535% vs. 53.873%, P<0.05). After silencing the miR-942-5p expression, the migration and invasion abilities of liver cancer HCCLM3 and MHCC97H cells were significantly weakened (both P<0.05). The results of prediction and analysis showed that fiblulin 5 (FBLN5) was a direct downstream target of miR-942-5p (P<0.05). Knockdown of the miR-942-5p expression led to increased expression of FBLN5 in HCCLM3 and MHCC97H cells.
Conclusion: The miR-942-5p expression is aberrantly up-regulated in HCC tissue and its overexpression is closely related to the malignant clinical features and poor prognosis. The mechanism may probably be responsible for miR-942-5p inhibiting FBLN5 expression and then promoting migration and invasion of HCC cells.

Abstract:Objective: To investigate the expression of long non-coding RNA MIF-AS1 (lncRNA MIF-AS1) in hepatocellular carcinoma (HCC) and its significance.   
Methods: The expressions of lncRNA MIF-AS1 in 94 paired specimens of HCC and adjacent tissue, and in different types of HCC cell lines and normal hepatic cells were detected by qRT-PCR. The relations of lncRNA MIF-AS1 expression with the clinicopathologic variables and prognosis of the patients were analyzed. The HCC cells were transfected with lncRNA MIF-AS1 interference sequences (silence group), lncRNA MIF-AS1 mimics (overexpression group) or negative control sequences (control group) respectively, and then, the changes in proliferative and invasion abilities as well as the protein expressions of epithelial–mesenchymal transition (EMT)-related molecules were examined.
Results: The lncRNA MIF-AS1 expression in HCC tissue was significantly higher than that in adjacent tissue, and in each studied HCC cell lines was significantly higher than that in normal hepatic cells (all P<0.05). The lncRNA MIF-AS1 expression was significantly associated with the serum AFP level, tumor size, portal vein microthrombus and TNM stage (all P<0.05). The tumor-free survival and overall survival rates in patients with high lncRNA MIF-AS1 expression were significantly lower than those with low lncRNA MIF-AS1 expression (both P<0.05). The lncRNA MIF-AS1 expression was an independent risk factor for both tumor-free survival and overall survival rates of the patients (both P<0.05). Results of cell experiment showed that compared with control group, the proliferative and invasion abilities were significantly reduced, and the protein expression of the epithelial phenotype molecule E-cadherin expression was increased, while the expressions of the mesenchymal phenotype molecules N-cadherin and vimentin were decreased in silence group (all P<0.05); the proliferative and invasion abilities were significantly enhanced, and the protein expression of E-cadherin expression was decreased, while the expressions of N-cadherin and vimentin were increased in overexpression group (all P<0.05).
Conclusion: The expression of lncRNAMIF-AS1 is up-regulated in HCC, and its expression level is closely related to malignant clinicopathologic features and poor prognosis of the HCC patients. The action mechanism of lncRNAMIF-AS1 may probably be related to its promoting EMT process.

Abstract:Objective: To investigate the value of using liver parenchyma transection-first approach in laparoscopic right hemihepatectomy. 
Methods: The clinical data of 20 patients undergoing laparoscopic right hemihepatectomy from October 2016 to October 2017 in the Second Affiliated Hospital of Army Medical University were retrospectively analyzed. Of the patients, 10 cases underwent laparoscopic right hemihepatectomy using liver parenchyma transection-first approach (observation group), namely, liver parenchyma transection was prioritized rather than dissection of the first hepatic hilum, and the other 10 cases underwent laparoscopic right hemihepatectomy with the conventional process, namely liver parenchyma transection after dissection of the first hepatic hilum (control group). The main clinical variables were compared between the two groups. 
Results: There were on significant differences in the general data between the two groups (all P>0.05). Operations were successfully completed in all patients of the two groups. In observation group compared with control group, the operative time was significantly shortened [(273.0±70.4) min vs. (203.0±61.3) min, P<0.05], and the intraoperative blood loss was significantly decreased [(470.0±427.0) mL vs. (270.0±149.4) mL, P<0.05], while the amount of intraoperative blood transfusion showed no significant difference (P>0.05). There were no significant differences in postoperative liver function parameters, length of postoperative hospital stay and incidence of complications as well as the incidence of tumor recurrence and metastasis (all P>0.05).
Conclusion: Liver parenchyma transection-first approach is a safe and effective procedure for laparoscopic right hemihepatectomy.

Abstract:Objective: To investigate the safety, feasibility and effectiveness of using enhanced recovery after surgery (ERAS) concept in precise laparoscopic hepatectomy for hepatic hemangioma.   
Methods: The clinical data of 96 patients undergoing precise laparoscopic hepatectomy for hepatic hemangioma from January 2014 to January 2019 were retrospectively analyzed. Of the patients, 40 cases received perioperative management directed by ERAS concept (ERAS group), and 56 cases underwent perioperative management with a conventional protocol (control group). The preoperative general characteristics, intraoperative variables, length of postoperative hospital stay, hospitalization costs, incidence of postoperative complications, liver function recovery patterns, and C-reactive protein (CRP) as well as other laboratory indicators were compared between the two groups.
Results: There were no statistical differences in any preoperative or intraoperative variables between the two groups (all P>0.05). In ERAS group, the length of postoperative stay was significantly shortened and the hospitalization cost was significantly reduced compared with control group (both P<0.05). As for the laboratory parameters, the CRP level on postoperative day 7 was significantly lower in ERAS group than that in control group (P<0.05), but all other parameters showed no significant differences between the two groups (all P>0.05). There were no statistical differences in incidence of each postoperative complication and readmission rates between the two groups (all P>0.05).  
Conclusion: In patients undergoing precise laparoscopic hepatectomy for hepatic hemangioma, using perioperative ERAS is safe and feasible, and it can reduce the length of hospital stay, the hospitalization cost and the surgical stress response, and accelerate the postoperative recovery of the patients.

Abstract:Objective: To compare the consistency between contrast-enhanced CT and contrast-enhanced magnetic resonance imaging (CE-MRI) for determining the volume of tumor in the same patient with hepatocellular carcinoma (HCC) by 3D segmentation technique. 
Methods: The data of 60 HCC patients with initial diagnosis in the Second Xiangya Hospital of Central South University without any previous treatment from November 2014 to December 2018 were retrospectively collected. All patients underwent both contrast-enhanced CT scan and CE-MRI examination. The tumor volume corresponding to each imaging examination was calculated by the 3D lesion segmentation technique using region-based active and contour model, and then their consistency was analyzed.
Results: Fifteen cases were excluded for atypical imaging manifestations, so a total of 60 target lesions in 60 patients were analyzed (the largest lesion was selected in cases with multiple lesions). The mean volume of tumor in the 60 patients measured by enhanced CT was (22.72±7.49) cm3, by CE-MRI image was (23.53±7.64) cm3. There was no statistical difference between the two imaging methods in measuring tumor volume (t=0.59, P=0.55). The results of linear regression model showed that there was a strong correlation between the lesion volumes measured by the two imaging methods (r=0.99, 95% CI=0.97–0.99).
Conclusion: In determination of the lesion volume of HCC with 3D segmentation technique, the results obtained by contrast-enhanced CT and CE-MRI are highly consistent.

Abstract:New onset diabetes mellitus after transplantation (NODAT) is a common complication after liver transplantation and has attracted the attention of many scholars, for its high incidence and great harm, and severe influence on the function of the graft and the quality of life of the recipient. There are many risk factors for NODAT, which can be divided into non-regulable and regulable risk factors. The non-regulable risk factors include age, gender, donor liver steatosis, cirrhosis, and family history of diabetes. The regulable risk factors comprise obesity, calcineurin inhibitors, glucocorticoids, hepatitis virus infection, cytomegalovirus infection, and pre-transplant blood glucose. Here, the authors address the pathogenetic mechanism and risk factors for NODAT based on recent research reports.

Abstract:Hepatocellular carcinoma (HCC) is the second most common primary liver tumor in children. It has complex clinical features, high malignancy and poor prognosis. There are many treatment modalities for pediatric HCC, such as surgical resection, liver transplantation, chemotherapy, transarterial chemoembolization, and targeted therapy. Here, the authors address the current status of various treatments for HCC in children under 14 years of age.