Abstract:Liver needle biopsy has been used for a long time as a diagnostic measure for liver disease in several clinical departments such as liver surgery, liver transplantation, infectious disease, and digestive disease. Because it is usually performed by selecting a safe puncture route under the guidance of B-ultrasound or CT, it is safe and its incidence of postoperative massive hemorrhage or bile leakage is not high in most cases. However, there have been clinical reports of death due to liver needle biopsy, and this raised a great concern by clinicians. At present, there are no standards, guidelines or expert consensus on liver needle biopsy in China. Therefore, this expert consensus statement was developed through the organization by the Department of Medical Affairs and Department of Liver Surgery of Xiangya Hospital, Central South University in collaboration with the experts in own hospital from the Department of Hepatopathy, Ultrasound, Interventional Radiology and Pathology, so as to provide a reference for  performing liver needle biopsy in clinical practice.

Abstract:Anatomic laparoscopic hepatectomy (ALH) is one of the most difficult operations in general surgery. Being restricted by the limited operation space of laparoscopic surgery, the liver, as the largest solid organ in the human body, is difficult to manipulate and expose. In addition, uncontrollable bleeding is likely to occur during the process of liver parenchyma dissection because of the abundant blood supply of the liver and the complex structure of the intrahepatic vessels, which may lead to a forced conversion to open surgery, and therefore cause a long learning curve to achieve the skill for ALH. Although after nearly 30 years of development as well as this operation has been carried out in most large medical institutions in our country, there are few systematic explanations for the selection of individualized surgical approach, which is the premise and basis for successful implementation of ALH. Here, the authors discuss the issues about this topic.

Abstract:Background and Aims: Existing studies have shown that hepatic vascular involvement and tumor compression are closely related to the decline of regional liver function. Dynamic SPECT/CT 99mTc-galactosyl-human serum albumin (GSA) imaging has been proved to be a more accurate technique for regional assessment of liver function. Previous studies have used this technique to elucidate the changes of regional liver function after vascular involvement, but there is still a lack of quantitative research on the effect of tumor mechanical compression on regional liver function. The purpose of this study was to investigate the effect of mechanical compression of tumor on the function of its adjacent liver tissue.
Methods: The SPECT/CT imaging and clinical data of 45 patients with primary liver cancer were retrospectively analyzed. Of the patients, 14 patients had vascular or biliary invasion or received liver radiotherapy (affected group), and 31 patients had no such situations (non-affected group). After the corresponding areas at 2, 4 and 6 cm from the edge of the tumor (D1, D2, D3) and hemihepatic lobe regions on the CT images were drawn, the morphological liver volume (MLV) of above areas were calculated. Functional liver volume (FLV), functional liver density (FLD) and hepatocyte uptake rate constant (GSA-K) of bilateral lobes and D1-D3 regions were calculated after further fusion of SPECT image and CT image. The relevant variables of liver lobes in affected group and of D1-D3 regions within the two groups were compared. Correlation analysis and multiple linear regression analysis were used to analyze the influencing factors of the function of liver tissue adjacent to primary liver cancer.
Results: In the affected group, the FLV and FLD of tumor-bearing lobe were significantly lower than those of the other side (both P<0.01); the FLD of D1 region in non-affected group was significantly lower than that in the D2 and D3 regions (both P<0.01). The results of correlation analysis showed that tumor diameter and tumor volume were related factors affecting the FLD of D1 region in the non-affected group (both P<0.05); Child-Pugh grade was related factor influencing FLD of D2 region in the non-affected group (P<0.05). The result of multiple linear regression analysis showed that tumor diameter was the main factor affecting FLD of D1 region in non-affected group (P<0.05).
Conclusion: The mechanical compression of tumor may be an important factor affecting the function of liver tissue adjacent to primary liver cancer and thereby leading to the decline of regional liver function. When the tumor diameter is large, the risk of hepatectomy may be overestimated in patients with marginal reserved liver volume, which affects the choice of treatment for such patients.

Abstract:Background and Aims: The incidence of complications after hepatectomy is relatively high, and early screening of high-risk population for severe complications after hepatectomy is of great significance to reduce the incidence of severe complications after surgery. This study was conducted to analyze the risk factors for severe postoperative complications in patients undergoing surgery for hepatocellular carcinoma (HCC) and establish an individualized nomogram risk prediction model for severe postoperative complications, so as to provide a reference for the optimization of the perioperative management of HCC patients.  
Methods: The data of HCC 854 patients who underwent hepatectomy from January 2018 to June 2020 in the Department of Hepatobiliary Surgery of the First Affiliated Hospital of Guangxi Medical University were retrospectively analyzed. The risk factors for severe postoperative complications were screened by univariate analysis and Logistic regression analysis, and then a nomogram risk prediction model was established. The internal validation of the model was assessed using the Bootstrap method, and the discrimination and calibration aspects of the model were assessed by ROC curves and calibration plots. 
Results: Among the 854 patients, serious postoperative complications (≥ grade III) occurred in 86 cases (10.1%). The results of univariate analysis and Logistic regression analysis revealed that liver cirrhosis (OR=1.905, 95% CI=1.153–3.147, P=0.012), surgical procedure (OR=3.412, 95% CI=1.618–7.192, P=0.001), intraoperative plasma transfusion (OR=2.518, 95% CI=1.51–4.199, P<0.001), operative time (OR=1.003, 95% CI=1.002–1.005, P<0.001), postoperative albumin level (OR=0.922, 95% CI=0.873–0.973, P=0.003) and postoperative aspartate transaminase level (OR=1.001, 95% CI=1.000–1.002, P=0.006) were independent influencing factors for severe complications in HCC patients after hepatectomy. The C-index of the nomogram model to predict the risk of severe postoperative complications was 0.774, and the area under the ROC curve for the nomogram model was 0.788 (95% CI=0.74–0.836). 
Conclusion: The established individualized nomogram risk prediction model for severe complications after hepatectomy based on 6 clinical factors has good predictive performance. This model can be used for early identification of high-risk patients and provide a basis for medical staff to take preventive measures.

Abstract:Background and Aims: Hepatocellular carcinoma (HCC) is a common primary liver cancer with a poor prognosis. The activation and inactivation of genes can promote the occurrence and development of HCC. This study was conducted to investigate the key genes and their functions in the occurrence and development of HCC based on bioinformatics and verify their expressions in clinical samples. 
Methods: The HCC and paracancerous tissue gene chips were downloaded from the public gene GEO database, the differentially expressed genes (DEGs) were screened through GEO2R online tools and Venn diagrams, and the GO function analysis and KEGG pathway enrichment analysis were performed on the selected DEGs using the DAVID website, and then the core DEGs were picked up from the DEGs by protein-protein interaction (PPI) network analysis using STRING website and Cytscape software. The prognosis-related DEGs were determined by survival analysis using Kaplan-Meier Plotter website, and the expression levels of the prognosis-related DEGs were analyzed using the GEPIA website to obtain the differential expressions betwen HCC and paracancerous tissue, and then the key genes associated with the occurrence and development of HCC were screened from the highly expressed prognosis-related DEGs in HCC by function and enrichment pathway analysis using Metascape website. Finally, the expression verification of select key genes was performed in the specimens of HCC and paracancerous tissue.
Results: A total of 78 DEGs were screened from the three eligible gene chips (GSE14520, GSE41804, GSE45267) downloaded from GEO. Then, 17 core DEGs (CDK1, ASPM,CENPF, RRM2, CCNB1, TOP2A, PTTG1, ECT2, CDKN3, CYP2B6,SLCO1B3, CYP1A2, CYP4A11, CYP26A1,CYP2E1,NAT2, CYP3A4) were screened out after using DAVID website GO function analysis and KEGG pathway enrichment analysis as well as STRING website and Cytscape software analysis. After the survival analysis of the 17 core DEGs on Kaplan-Meier Plotter website, 9 genes (CDK1, ASPM, CENPF, RRM2, CCNB1, TOP2A, PTTG1, ECT2, CDKN3) were detected to be associated with the prognosis of HCC (all P<0.05). The expression level analysis by GEPIA website showed that all the 9 genes were highly expressed in HCC tissue (all P<0.05). Metascape website analysis showed that the 9 highly expressed genes were mainly enriched in the processes of negative regulation of mitotic cell cycle, nuclear chromosome segregation and female gamete generation. The CDK1 was selected to verify in HCC and paracancerous tissues, and the result showed that the CDK1 expression level was significantly higher than that in paracancerous tissue (P<0.05).
Conclusion: The 9 genes obtained in this study may be the key genes in the occurrence and development of HCC, which provide a reference for the study of the pathogenetic mechanism as well as the diagnosis and treatment of HCC.

Abstract:Background and Aims: As one of the most common malignant tumors, liver cancer has long been a human health concern. Hepatectomy is the preferred treatment of liver cancer, but the high postoperative recurrence rate and short survival time seriously influence the surgical efficacy. With the deepening of studies in tumor-associated inflammation, a series of systemic inflammatory indicators, including platelet to lymphocyte ratio (PLR), have been gradually proposed, and are considered to be markers that can be used to predict the prognosis of patients with malignant tumors. In recent years, studies have found that preoperative PLR can be used as an evaluation index to predict the prognosis of patients after hepatectomy, but the results of various studies are controversial. This study was designated to evaluate the relationship between preoperative PLR and prognosis of patients after hepatectomy by Meta-analysis, so as to provide reference for clinical treatment of liver cancer. 
Methods: The relevant studies concerning PLR and hepatocellular carcinoma published as of March 11, 2020 were searched in PubMed, Embase, Cochrane Library, Web of Science, CNKI, Wanfang Database and SinoMed databases. After literature screening and data extraction, Meta-analysis was performed by Stata 12.0 software, using hazard ratio (HR) and its 95% confidence interval (CI) as effect indicators.
Results: A total of 26 studies with 12 288 patients were finally included. The results of Meta-analysis showed that the shortened overall survival time (OS) after hepatectomy was related to high preoperative PLR (HR=1.03, 95% CI=1.01–1.04, P<0.001), and the increased preoperative PLR could predict poor disease-free survival (DFS) or recurrence free survival time (RFS) after operation (HR=1.05, 95% CI=1.02–1.07, P<0.001). Subgroup analysis showed that preoperative PLR could predict OS shortening in patients with BCLC-0/A disease (HR=1.47, 95% CI=1.17–1.80, P<0.05), but was irrelevant to DFS/RFS (HR=1.16, 95%CI=0.91–1.48, P=0.227); in patients receiving postoperative transarterial chemoembolization, local ablation therapy and other anti-cancer therapy, the poor OS was also related to the preoperative PLR (HR=1.07, 95% CI=1.030–1.109, P<0.001). Further exploring the range of effective cut-off value of PLR found that preoperative PLR was irrelevant to the shortened OS or DFS/RFS (HR=1.12, 95% CI=0.88–1.41, P=0.365; HR=1.26, 95% CI=0.93–1.72, P=0.135) when the cut-off value was less than 100. Heterogeneity analysis and publication bias test found that the heterogeneity was due to different tumor stages, different cut-off values of PLR and there was a significant publication bias among the included studies (Egger's test: P>|t|=0.000). After 11 studies were added, the results still steadily showed that high preoperative PLR was associated with poor OS.
Conclusion: Preoperative PLR is a biological index to predict the poor prognosis of patients undergoing hepatectomy, and the cut-off value for effective prediction should be more than 100. The above conclusions need to be further verified by high-quality multicenter prospective studies in the future, so that PLR can be better used in clinical practice.

Abstract:Background and Aims: The dysregulation of oncogenes and tumor suppressors is a critical factor for the initiation and progression of hepatocellular carcinoma (HCC). Previous studies demonstrated that G-protein-signaling modulator 2 (GPSM2) functions as a tumor suppressor in lung cancer, while acts as an oncogene in breast cancer and pancreatic cancer. However, the expression of GPSM2 in HCC and its biological functions have not been reported yet. This study aimed to investigate the expression GPSM2 in HCC tissues and its effects on cell proliferation and glycolysis. 
Methods: The GPSM2 mRNA and protein expressions in HCC tissues and adjacent non-tumor tissues qRT-PCR and Western blot. The relations of GPSM2 expression in HCC tissues with the clinicopathologic features and prognosis of the patients were analyzed. In HCC Huh7 cells after GPSM2 knockdown by a specific small interfering RNA (siRNA), the changes in cell proliferation as well as the glucose consumption and lactate production were determined by CCK-8 assay and corresponding kits, and the changes in protein levels of the key rate-limiting enzymes of glycolysis hexokinase 2 (HK2), phosphofructokinase, liver type (PFKL) and pyruvate kinase M2 (PKM2) were examined by Western blot. The difference in GPSM2 expression in Huh7 cells between normoxic and hypoxic conditions was compared. 
Results: Both GPSM2 mRNA and protein levels in HCC tissue were significantly higher than those in adjacent nontumor tissue (both P<0.000 1). Results of clinical data analysis indicated that GPSM2 mRNA expression was significantly associated with tumor sized, Edmondson-Steiner grading and TNM stage (all P<0.05). TCGA data analysis based on the GEPIA platform showed that HCC patients with high GPSM2 mRNA level had a significantly lower overall survival and disease-free survival than those with low GPSM2 mRNA level (both P<0.000 1). In Huh7 cells after GPSM2 knockdown, the proliferation was significantly inhibited, and glucose consumption and lactate production were significantly reduced, furthermore, the protein level of HK2 was significantly decreased (all P<0.05). In addition, protein level of GPSM2 was significantly upregulated in hypoxic condition compared with those in normoxic condition (P<0.05). 
Conclusion: The GPSM2 expression is increased in HCC tissue, and is closely related to the unfavorable prognosis of the patients. GPSM2 is a hypoxia response gene, which promotes the proliferation and glycolysis of HCC cells probably by enhancing HK2 expression. These results indicate that GPSM2 is a potential prognostic biomarker and therapeutic target for HCC.

Abstract:Background and Aims: Long non-coding RNA HULC (lncRNA HULC) is specifically highly expressed in hepatocellular carcinoma (HCC), and is an important tumor marker of HCC. This study was conducted to investigate the relations of serum lncRNA HULC level with the clinical features and prognosis of patients with hepatitis B virus-related HCC (HBV-related HCC). 
Methods: The samples of serum and surgical specimens of 30 patients with HBV-related HCC undergoing surgical treatment from June 2012 to September 2017 were collected. The relative levels of lncRNA HULC in the serum of the patients were determined by qRT-PCR, and the expressions of tumor invasion/metastasis-associated markers VEGF, MMP-2 and E-cadherin in the cancer tissues of the patients were detected by immunohistochemical staining. The relations of serum lncRNA HULC level with the clinicopathologic factors and expressions of tumor invasion/metastasis-associated markers as well as the prognosis of the patients were analyzed.
Results: The relative level of serum lncRNA HULC of the patients ranged from 2.6 to 9.5. Using the median value of 5.0 as the threshold, the patients were divided into high lncRNA HULC group (12 cases) and low lncRNA HULC group (18 cases). Results of statistical analysis showed that the proportion of cases with high pathological differentiation in low lncRNA HULC group was significantly higher than that in high lncRNA HULC group; the proportion of stage III-IV cases in high lncRNA HULC group was significantly higher than that in low lncRNA HULC group; the proportion of cases with intrahepatic and distant metastasis in low lncRNA HULC group was significantly lower than that in high lncRNA HULC group; the proportion of cases with recurrence in high lncRNA HULC group was significantly higher than that in low lncRNA HULC group, and all the differences had statistical significance (all P<0.05). Results of immunohistochemical staining showed that the positive expressions of tumor invasion/metastasis-promoting proteins VEGF and MMP-2 were increased while the tumor invasion/metastasis-suppressing protein E-cadherin was decreased in HCC tissues from patients in high lncRNA HULC group compared with those in low lncRNA HULC group. Results of Kaplan-Meier analysis showed that the survival rate of patients in high lncRNA HULC group was lower than that of patients in low lncRNA HULC group, and the recurrence rate of patients in high lncRNA HULC group was higher than that of patients in low lncRNA HULC group (both P<0.05). Results of Cox proportional hazard regression analysis showed that preoperative serum lncRNA HULC level was an independent influencing factor for the prognosis of patients with HBV-related HCC (OR=1.769, P=0.045).
Conclusion: The serum lncRNA HULC level is closely related to the malignant clinical features of patients with HBV-related HCC, and those with high serum lncRNA HULC level may face a poor prognosis.

Abstract:Background and Aims: Complications and hepatic insufficiency are likely to occur in patients with liver tumor and concomitant liver cirrhosis after hepatectomy due to the always presence of poor liver functional reserve. So, accurate preoperative clinical assessment and precise intraoperative resection scope are of great importance for the outcomes of patients with liver tumor and concomitant liver cirrhosis undergoing hepatectomy. This study was conducted to investigate the efficacy of using three-dimensional visualization technology (3DVT) combined with indocyanine green (ICG) clearance test in operation for patients with liver tumor and cirrhosis. 
Methods: The clinical data of 57 patients with liver tumor and cirrhosis undergoing hepatectomy with 3DVT plus ICG clearance assessment from May 2019 to March 2020 (observation group), as well as 62 patients with the same conditions undergoing hepatectomy with 3DVT plus traditional Child-Pugh assessment from January 2018 to April 2019 (control group) were retrospectively analyzed. The main clinical variables and the incidence rates of postoperative liver dysfunction and other complications were compared between the two groups of patients. 
Results: There were no significant differences in the basic data and each inflammatory factor and liver function parameter between the two groups before operation (all P>0.05). The operative time showed no significant difference between the two groups (P>0.05), but the intraoperative blood loss and length of hospital stay were reduced in observation group compared with control group (both P<0.05). In either group, all inflammatory factors and liver function parameters were significantly improved compared to preoperative values, but the improving degrees of them in observation group were significantly superior to those in control group (all P<0.05). The overall incidence rates of postoperative liver dysfunction and complications in observation group were significantly lower than those in control group (both P<0.05). 
Conclusion: Using 3DVT plus ICG clearance test in operation for patients with liver tumor and concomitant liver cirrhosis is helpful for accurate preoperative judgment of the space structure relations between liver tumor and surrounding tissues, determination of the liver resection volume and residual liver volume, and estimation of the liver functional reserve, and also can reduce the intraoperative blood loss and postoperative traumatic stress reactions of the patients, shorten hospitalization time, and decrease the incidence rates of postoperative complications and hepatic insufficiency. So, it has good application value and is recommended to be used.

Abstract:Background and Aims: Enhanced recovery after surgery (ERAS) is an interdisciplinary collaboration model that has been proven to be safe and effective in multidisciplinary applications, but the theory of ERAS is still in the exploratory stage in the field of liver transplantation. This study aimed to systematically evaluate the application effectiveness of ERAS protocol in the perioperative management of patients undergoing liver transplantation. 
Methods: The relevant studies were searched in the PubMed, Cochrane Library, Embase, CNKI, VIP, WanFang Data databases as well as in the clinical trial registration platform and gray literature databases. The retrieval time was from the inception date of the databases to July 8, 2020. The literature was selected independently by two reviewers. After data extraction and evaluation of the risk of bias, Meta-analysis was performed using Stata 16.0 software.
Results: A total of 21 articles were finally selected involving 2 136 patients, of whom, 1 008 cases received ERAS intervention (ERAS group) and 1 128 cases underwent traditional perioperative management (traditional group), and including 13 randomized controlled trial studies and 8 clinical controlled trial studies. The results of Meta-analysis showed that in ERAS group compared with traditional group, the incidence rate of overall postoperative complications (OR=0.31, 95% CI=0.22–0.43, P<0.001) as well as the incidence rates of rejection reaction (OR=0.26, 95% CI=0.13–0.53, P<0.001), pleural effusion (OR=0.31, 95% CI=0.17–0.57, P<0.001), bile leakage (OR=0.19, 95% CI=0.05–0.65, P=0.008), infections (OR=0.28, 95% CI=0.16–0.50, P<0.001) and pulmonary infection (OR=0.53, 95% CI=0.33–0.86, P=0.010) were significantly reduced, the lengths of hospital stay (WMD=–5.76, 95% CI=–6.89––4.63, P<0.001), ICU stay (WMD=–2.26, 95% CI=–3.21––1.31, P<0.001), operative time (WMD=–41.07, 95% CI=–67.82––14.32, P=0.003) and anhepatic phase (WMD=–5.78, 95% CI=–11.50––0.07, P=0.047) were all significantly shortened, the intraoperative blood loss (WMD=–794.67, 95% CI=–1302.96––286.39, P=0.002) was significantly decreased, and the patient satisfaction was improved (P<0.05).
Conclusion: The use of ERAS in liver transplantation is safe and effective, and it can promote postoperative recovery of the patients.

Abstract:Hepatocellular carcinoma (HCC) is a common malignant tumor disease in China. In recent years, more and more attention has been paid to the influence of microenvironment on cancer tissue. Extracellular matrix (ECM), as an important microenvironment component of HCC tissue, plays an important role in tumor occurrence and development, involving tumor growth, apoptosis, drug resistance, invasion, metastasis and so on. The fibronectin (FN), laminin (LN), hyaluronic acid (HA), collagen (COL) and matrix stiffness play special roles in the tumorigenesis and progression of HCC. It is precisely because of the special role of each protein component of ECM in HCC, blindly degrading or knocking out any protein component in ECM may probably not be able to achieve the desired therapeutic effect, but accelerate the progress of HCC. Therefore, it is necessary to explore some specific drugs or methods for targeted regulation of ECM components, and purposeful control of ECM remodeling, thus affecting the occurrence and development of HCC. Considering that the microenvironment of HCC is a dynamically changing environment, it is a feasible research direction for exploring the co-action of ECM multi-components on HCC cells by co-culture of HCC cells with multiple ECM protein components instead of a single component to simulate the microenvironment of HCC cells as much as possible.

Abstract:
The insufficient remnant liver volume (RLV) is the main reason for postoperative hepatic failure and death of patients. The lesions of hepatic alveolar echinococcosis (HAE) often involve the intra- and extra-hepatic vessels, which causes difficult situations for preservation of the functional hepatic segment (s) and low radical resection rates. Although the ex-vivo liver resection combined with autologous liver transplantation (ERAT) has greatly extended the surgical indications for end-stage HAE, the insufficient RLV remains the restrictions on HAE radical resection. In recent years, some novel techniques such as the staged hepatectomy, percutaneous stenting of hepatic vein followed by ERAT, and auxiliary ERAT as well as the associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) have been applied in the surgical treatment for HAE patients with insufficient RLV, which improve the radical resection rate for end-stage HAE. Herein, the authors present a brief overview on the latest surgical progress for end-stage HAE with insufficient RLV.