Volume 29,Issue 1,2020 Table of Contents

1 Clinical efficacy of salvage liver transplantation versus repeat hepatectomy for recurrent hepatocellular carcinoma after hepatectomy: a Meta-analysis

GAO Benjian , LUO Jia , LIU Ying , ZHONG Furui , YANG Xiaoli , SU Song , LI Bo

2020, 29(1):1-10. DOI: 10.7659/j.issn.1005-6947.2020.01.001

[Abstract](367) [HTML](1025) [PDF 1.19 M](1117)

Abstract:
Background and Aims: Salvage liver transplantation (SLT) versus repeat hepatectomy (RH), which one is more beneficial to patients with recurrent hepatocellular carcinoma after primary resection is still inconclusive, and has no verification from the large multicenter clinical trials as well at present time. This study was aimed to evaluate the clinical efficacy of LT and RH for recurrent hepatocellular carcinoma after hepatectomy through a Meta-analysis, so as to provide reference for treatment selection of this condition.
Methods: The clinical studies comparing efficacy of SLT versus RH in treatment of recurrent hepatocellular carcinoma after hepatectomy were collected by searching several national and international databases in the time period from the inception of the databases to August 2019. After literature screening, data extraction and quality assessment conducted by two independent reviewer, Meta-analysis was performed using the overall survival rate and disease-free survival rate as the main outcome variables.
Results: Six retrospective cohort studies meeting the inclusion criteria were finally included, involving 650 patients with 134 case in SLT group and 516 case in RH group. Results of Meta-analysis showed that the 1- and 3-year overall survival rates had no statistically significant difference between SLT group and RH group (OR=1.70, 95% CI=0.82–3.53, P=0.15; OR=1.10, 95% CI=0.70–1.72, P=0.67), but the 5-year overall survival rate in SLT group was significantly superior to that in RH group (OR=1.56, 95% CI=1.03–2.37, P=0.04); the 1-, 3- and 5- year disease-free survival rates in SLT group were all significantly to those in RH group (OR=5.91, 95% CI=3.16–11.05, P<0.000 01; OR=3.98, 95% CI=2.57–6.16, P<0.000 01; OR=4.37, 95% CI=2.03–9.44, P=0.000 2). The incidence of postoperative complications in SLT group was significantly higher than that in the RH group (OR=4.67, 95% CI=2.72–8.01, P<0.000 01). There was no significant difference in perioperative mortality between the two groups (OR=3.92, 95% CI=0.41–37.80, P=0.24). The intraoperative blood loss was significantly higher and the length of hospital stay were significantly longer SLT group than those in the RH group (both P<0.05).
Conclusion: SLT is a safe and effective approach for postoperative recurrent hepatocellular carcinoma. Compared to RH, SLT can significantly improve postoperative disease-free survival rate and obtain a better long-term prognosis. However, considering the shortage of liver donor, RH is still an important treatment for postoperative recurrent hepatocellular carcinoma.

2 Prognostic analysis of transcatheter hepatic artery chemoembolization combined with percutaneous microwave ablation in treatment of recurrent hepatocellular carcinoma

舒强 , 刘小玲 , 杨小李 , 苏松 , 罗斌 , 李波

2020, 29(1):11-18. DOI: 10.7659/j.issn.1005-6947.2020.01.002

[Abstract](435) [HTML](1052) [PDF 1.33 M](1064)

Abstract:
Background and Aims: For recurrent hepatocellular carcinoma (HCC), liver transplantation and repeat hepatectomy are the major treatment methods, but they all have their limitations and are not applicable to all patients. Moreover, transarterial chemoembolization (TACE) and percutaneous microwave ablation (PMCT) are also effective methods for recurrent HCC. However, whether the combined treatment of TACE and PMCT can further improve the treatment efficacy has not been reported. Therefore, this study was aimed to compare the clinical efficacy of TACE plus PMCT and TACE alone in treatment of recurrent HCC.
Methods: According to the inclusion criteria, the clinical data of 530 patients treated in the Department of Hepatobiliary Surgery of the Affiliated Hospital of Southwest Medical University from January 2007 to January 2019 were collected. Of the patients, 161 cases underwent TACE plus PMCT treatment (observation group), and 369 cases underwent PMCT alone (control group). Patients in both groups underwent repeated performance of the procedures until complete tumor ablation shown by CT examination. The overall survival rate (OS) and relapse-free survival (RFS) of the two groups after treatment were compared, and the prognostic factors were also analyzed.
Results: There were differences in some baseline data between the two groups of patients, so the two groups of patients were 1:1 matched by propensity score matching (PSM) method, and then resulted in 150 pairs of patients with balanced baseline data from the two groups. In the 300 patients, the median follow-up time was 24.5 months. the median OS and RFS in observation group were significantly longer than those in control group (43.1 months vs. 19.0 months, P=0.001; 36.0 months vs. 16.7 months, P=0.002). The 1- and 2-year OS and RFS between the two groups showed no significant differences (all P>0.05), but the 3-, 4- and 5-year OS and RFS in observation group were significantly superior to those in control group (all P<0.05). Cox multivariate regression analysis showed that TACE plus PMCT treatment (HR=1.473, 95% CI=1.094–1.983, P=0.011) and liver cirrhosis (HR=1.101, 95% CI=1.041–1.165, P=0.001) were independent factors affecting the OS of patients with recurrent HCC; TACE plus PMCT treatment (HR=1.093, 95% CI=1.037–1.151, P=0.001) and degree of differentiation (HR=1.445, 95% CI= 1.135–1.840, P=0.003) were independent factors affecting the RFS of patients with recurrent HCC.
Conclusion: TACE combined with PMCT is a safe and effective method for recurrent HCC, its clinical efficacy in superior to that of TACE alone, and it can significantly improve the prognosis of patients with recurrent HCC.

3 Meta-analysis of application value of three-dimensional visualization technique in liver cancer surgery

WANG Cheng , HUANG Qiang , YANG Ji

2020, 29(1):19-26. DOI: 10.7659/j.issn.1005-6947.2020.01.003

[Abstract](549) [HTML](1033) [PDF 1.32 M](959)

Abstract:
Background and Aims: Three-dimensional visualization helps the surgeons further directly observe the vascular network inside the liver and categorize the variations as well as calculate the resection volume of the liver and future liver remnant. The aim of this study was to evaluate the application value of three-dimensional visualization technique in liver cancer surgery.
Methods: The clinical trials and observational studies concerning the application of three-dimensional visualization technique in the surgical operation of liver cancer were collected by systematically searching the databases at home and abroad in the time period from the inception of the databases to October 2019. The literature screening, data extraction and quality assessment were conducted by two independent reviewers. Meta-analysis was performed by using Revman5.3 software.
Results: Fifteen studies were finally included, involving 1 283 patients, of whom 647 cases underwent preoperative evaluation with three-dimensional imaging (three-dimensional group) and 636 cases underwent preoperative evaluation with two-dimensional images (two-dimensional group). The results of Meta-analysis showed that in three-dimensional group compared with two-dimensional group, the radical resection rate (R0 resection rate) was increased (OR=3.05, 95% CI=1.42–6.55, P=0.004), the intraoperative blood loss was reduced (MD=–83.87, 95% CI=–104.68––63.05, P<0.05), the incidence of postoperative complications was decreased (OR=0.52, 95% CI=0.36–0.76, P<0.05), and the difference between the predicted resected liver volume and the actual resected liver weight was lessened (MD=–103.25, 95% CI=–173.24––33.26, P<0.05); there were no significant differences in operative time (MD=–2.03, 95% CI=–10.23–6.17, P>0.05) and length of hospital stay (MD=–1.10, 95% CI=–2.52–0.32, P>0.05) between the two groups.
Conclusion: The application of three-dimensional visualization technique in liver tumor surgery can improve the R0 resection rate, reduce the surgical injury and decrease the occurrence of postoperative complications, which may be related to its clear, accurate and direct display and measurement of the liver and targets. Therefore, compared to the traditional imaging technology, the application of three-dimensional visualization technique can improve the safety of liver surgery, and has important application value in surgical practice.

4 Application of controlled low central venous pressure in laparoscopic hepatectomy for patients with primary liver cancer and post-hepatitis cirrhosis

SHI Huizhong , XIONG Qiru , XIA Jun , ZHANG Chao , JIA Ran , YU Guangjin , DAI Wei

2020, 29(1):27-34. DOI: 10.7659/j.issn.1005-6947.2020.01.004

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Background and Aims: Application of controlled low central venous pressure (CLCVP) in hepatectomy can effectively reduce the liver cut surface bleeding. However, the relative low blood pressure and potential hypoperfusion resulted from low central venous pressure (CVP) may probably cause harmful effects, which impose certain restrictions on its promotion. The aim of this study was to investigate the effectiveness and safety of using CLCVP technique in laparoscopic hepatectomy for patients with primary liver cancer and concomitant post-hepatitis cirrhosis.
Methods: The clinical data of 44 patients with primary liver cancer associated post-hepatitis cirrhosis undergoing laparoscopic anatomical hepatectomy in the Department of Hepatobiliary and Pancreatic Surgery of the First Affiliated Hospital of Anhui Medical University from April 2017 to March 2019 were retrospectively analyzed. All patients were operated by the same surgical team, of whom, 24 cases received CLCVP (observation group) and 20 cases did not receive CLCVP (control group) during surgery. The main pre- intra- and postoperative clinical variables of the two groups of patients were analyzed and compared.
Results: There were no significant differences in preoperative data that included the sex, age, BMI, Child classification, degree of cirrhosis between and parameters for liver and renal functions between the two groups of patients (all P>0.05). The operations were uneventfully performed in both groups of patients without perioperative death. No complications associated with low CVP such as gas embolism or liver and renal function injuries occurred in observation group during and after the operation. In observation group compared with control group, the intraoperative arterial systolic blood pressure and CVP were significantly decreased, the operative time and time for hepatic portal occlusion were significantly shortened, and the intraoperative blood loss and blood transfusion rate were significantly reduced, but the intraoperative lactic acid concentration was significantly increased (all P<0.05). There were no significant differences in the incidence rates of postoperative bleeding, infection, pleural effusion and bile leakage as well as the parameters for liver and renal functions, time to tube removal and length of hospital stay between the two groups (all P>0.05), while the postoperative drainage volume in observation group was significantly higher than that in control group (P<0.05). The postoperative tumor recurrence rates showed no significant difference between the two groups (P>0.05).
Conclusion: Based on the premise of accurate evaluation of preoperative liver function and carefully observation of intraoperative perfusion index, CLCVP technique is safe and reliable for laparoscopic hepatectomy in patients with post-hepatitis cirrhosis. Although low CVP can reduce the perfusion, enhance the anaerobic metabolism, and increase the lactic acid content of the body, it has no effect on liver and renal functions as well as the recurrence of the liver cancer. Moreover, the low CVP can effectively reduce intraoperative blood loss and transfusion volume, shorten the operative time and portal occlusion time, and thereby reduce the impact of long-term ischemia and hypoxia on the liver. So, LCVP is a recommended technique for controlling the liver cut surface bleeding in liver cancer patients with post-hepatitis cirrhosis without underlying cardiopulmonary, cerebral and renal diseases.

5 Efficacy analysis of transcatheter arterial chemoembolization combined with radiofrequency ablation for intermediate and advanced hepatocellular carcinoma

张浩 , 仲富瑞 , 程宦立 , 张婷 , 夏先明

2020, 29(1):35-42. DOI: 10.7659/j.issn.1005-6947.2020.01.005

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Abstract:
Background and Aims: Transcatheter arterial chemoembolization (TACE) is an important treatment modality for intermediate and advanced hepatocellular carcinoma (HCC). For further improving the therapeutic efficacy of intermediate and advanced HCC, the combined treatment of TACE and radiofrequency ablation (RFA) has also been applied in clinical practice. However, there is still no high quality randomized controlled studies to verify the efficacy of the combined treatment. Therefore, this study was designed to investigate the clinical efficacy of TACE combined with RFA in treatment of intermediate and advanced HCC after reducing the confounding bias by propensity score matching (PSM).
Methods: The clinical data of patients with intermediate or advanced HCC undergoing TACE alone (TACE) or TACE combined with RFA (combined group) and meeting the inclusion criteria from January 2012 to January 2018 in the Department of Hepatobiliary Surgery of the Affiliated Hospital of Southwest Medical University were collected. After the clinical data of the two groups of patients matched 1:1 using PSM, the differences in overall survival rates and the survival rates among stratified subgrouping with different clinical factors between the two groups of patients were compared by Kaplan-Meier method.
Results: A total of 211 eligible patients were enrolled, with 127 case in TACE group and 94 cases in combined group, and then 160 patients were successfully matched after PSM. The median survival time of patients in TACE group and combined group were 18 and 22 months, respectively, and the 1, 2 and 3-year survival rates were 91.3% 57.9, and 16.1%, and 94.4%, 66.2% and 29.2%, respectively. The survival rate of patients in combined group was significantly superior to that of patients in TACE group (P=0.024). The results of further subgroup analysis showed that the survival rate in combined group was significantly superior to that in TACE group among patients with AFP≤400 ng/mL or patients with solitary lesion (P=0.044, P=0.037), while the survival rate had no significant difference between TACE group and combined group among patients with AFP>400 ng/mL, or patients multiple lesions as well as with Child A or B disease (all P>0.05).
Conclusion: Compared with TACE alone, the combined treatment of TACE and RFA has obvious advantage in improving the survival time of patients with intermediate or advanced HCC. TACE combined with RFA can significantly prolong the survival time of patients with AFP≤400 ng/mL and single tumor, but has no evident superiority for those with multiple tumors and AFP>400 ng/mL. Moreover, the Child classification may not be the reference index for the selection of TACE plus RFA treatment.

6 Expression of microRNA-671-5p in hepatocellular carcinoma and the relationship between its negative regulating cofilin 2 and epithelial-mesenchymal transition

LI Yazhao , YAO Bowen , SHI Lei

2020, 29(1):43-52. DOI: 10.7659/j.issn.1005-6947.2020.01.006

[Abstract](300) [HTML](947) [PDF 2.99 M](925)

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Background and Aims: Recent investigations demonstrated that microRNA-671-5p (miR-671-5p) participates in the occurrence and development of several types of cancer, and is associated with the liver injury induced by various types of virus. However, the role of miR-671-5p in hepatocellular carcinoma (HCC) has not yet been reported to date. This study was conducted to observe the miR-671-5p expression in HCC, analyze its function and its association with the biological behaviors and clinicopathologic features of HCC, and preliminarily investigate the possible mechanism.
Methods: The miR-671-5p expressions in 80 paired specimens of HCC and tumor adjacent tissue as well as different HCC cell lines (Hep3B, MHCC-97H, HepG2 and SMMC-7721) and normal human hepatic cell line (L02) were determined by qRT-PCR method, and meanwhile, the expression difference in miR-671-5p between HCC tissue and tumor adjacent tissue were analyzed in TCGA database. The relations of miR-671-5p expression level with the clinicopathologic factors were analyzed. In MHCC-97H cells after knockdown of miR-671-5p expression by transfection with miR-671-5p inhibitors, the changes in proliferative and invasion/migration abilities were examined by CCK-8 assay and Transwell assay, respectively. The target genes of miR-671-5p were predicted by using the TargetScan and Starbase online websites, and then verified by Western blot, dual luciferase assay and TCGA database analysis, respectively. The influences of miR-671-5p knockdown on the expressions of target gene of miR-671-5p and the proteins (E-cadherin, N-cadherin and vimentin) associated with epithelial-mesenchymal transition (EMT) in MHCC-97H cells, as well as the changes in expressions of above proteins upon the same condition with the synchronous knockdown of the target gene were detected by Western blot.
Results: The miR-671-5p expressions in HCC tissue and all studied HCC cell lines were significantly higher than that in tumor adjacent tissue or the normal hepatic cell line, and was increased with the elevation of the tumor stage of the sample and invasion ability of the HCC cells (all P<0.05); the TCGA database analysis also showed that the miR-671-5p expression level in HCC tissue was significantly higher than that in tumor adjacent tissue (P<0.05). The miR-671-5p expression level was significantly related to AFP level, tumor number, venous invasion, Edmondson-Steiner grade and TNM stage (all P<0.05). In MHCC-97H cells after transfected with miR-671-5p inhibitors, the proliferative, invasion and migration abilities were all significantly reduced (all P<0.05). Bio-informatics analysis and dual luciferase assay suggested that cofilin 2 (CFL2) was the potential target gene of miR-671-5p, and the TCGA database analysis also showed that there was a negative correlation between miR-671-5p expression and CFL2 expression (P<0.05). In MHCC-97H cells with down-regulated miR-671-5p expression, the CFL2 expression was significantly increased and the expressions of EMT-associated proteins were significantly decreased (all P<0.05), but all these changes were reversed to significant extents by synchronous interference of the CFL2 expression (all P<0.05).
Conclusion: The miR-671-5p expression is up-regulated in HCC, which is closely associated with the unfavorable clinicopathologic features of HCC. MiR-671-5p can promote the proliferation, invasion and migration of HCC cells, and the mechanism may be probably related to its down-regulating CFL2 expression and thereby promote EMT process.

7 Analysis of expression profile of serum exosomal mRNAs in patients with hepatocellular carcinoma and the clinical significance

YANG Jiaxing , XU Hongwei , WANG Ying , WANG Liang , WANG Jianguo , LI Shipeng

2020, 29(1):53-60. DOI: 10.7659/j.issn.1005-6947.2020.01.007

[Abstract](486) [HTML](981) [PDF 2.43 M](926)

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Background and Aims: Exosomes are small vesicles containing diverse RNAs and proteins, and those secreted from tumor cells carry considerable genetic information of the tumor cells. So, investigations of the specific mRNAs in the exosomes may provide chances for finding new molecular markers and therapeutic targets of tumors. This study was undertaken to investigate the expression profiles of the exosomal RNAs in hepatocellular carcinoma (HCC) patients and their potential functions by high-throughput screening and bioinformatics method.
Methods: The venous blood samples were collected from 3 HCC patients and 3 healthy subjects, the serum exosomes were extracted by using exosome isolation kit, and exosomal RNAs were extracted by Magen kit. Then, the serum exosomal mRNAs were purified, reverse-transcribed into cDNAs, amplified by PCR, and identified by sequencing. Finally, the obtained data were compared with the reference data after quality assessment (BAM files) and the differentially expressed exosomal mRNAs were identified and evaluated, and the GO and KEGG Pathway enrichment analysis were used to annotate the function and pathway of the differentially expressed genes.
Results: In HCC patients compared with healthy subjects, there were 397 up-regulated exosomal mRNAs and 192 down-regulated was up-regulated exosomal mRNAs, in which 17 genes such as NRGN, PF4 and RGS18 were significantly up-regulated, and 14 genes such as CXCL8, MORF4L2 and SYCP1 were significantly down-regulated. GO enrichment analysis showed that the target genes of the up-regulated exosomal mRNAs were related to the protein binding, protein heterodimerization activity, regulation of the immune system process of adjusting and second extracellular vesicles, outside the cell organelles, stress reaction and so on, while the target genes of down-regulated exosomal mRNAs were related to olfactory receptor activity, cytokine activity, CXCR chemokine receptor binding, intermediate filaments, intermediate filamentous cytoskeleton. KEGG pathway analysis showed that and 30 pathways were significantly enriched in the up-regulated exosomal mRNAs and 9 pathways were significantly enriched in the down-regulated exosomal mRNAs, in which, the platelet activation, Rap 1 signaling pathway, phagocytosis, viral carcinogenesis, regulation of actin cytoskeleton and antigen processing and presentation were the most abundant and significant pathways in the upregulated exosome mRNA, while, the basal transcription factor and cytokine-cytokine receptor interaction were the most abundant and significant pathways in the down-regulated exosomal mRNAs.
Conclusion: There is a significant difference in expression profile in serum exosomal mRNAs between HCC patients and healthy individuals, which may be closely related to the occurrence, development and metastasis of HCC, and also provide a basis for finding new diagnostic markers and therapeutic targets.

8 Effect of chloroquine on growth of liver cancer cells and its relationship with autophagy

HU Ruobing , YANG Yuxiu , LI Xiuling , DING Hui , HAN Shuangyin , DING Songze , SUN Suofeng

2020, 29(1):61-68. DOI: 10.7659/j.issn.1005-6947.2020.01.008

[Abstract](960) [HTML](1260) [PDF 1.44 M](1159)

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Background and Aims: Chloroquine is a widely used agent for the treatment of malaria and rheumatoid disorders, and it is also an autophagy inhibitor. Moreover, several studies have demonstrated that chloroquine exerts inhibitory effect on a variety of cancer cells, including the liver cancer cells. This study was designed to further observe the inhibitory effect of chloroquine on liver cancer cells in vitro and in tumor-bearing mice, and the connection with autophagy.
Methods: Liver cancer Huh7 cells were exposed to different concentrations of chloroquine (0, 25 and 50 μmol/L) in vitro, and then the cell proliferation was determined by MTT assay. Tumor xenograft models were established in 75 nude mice by subcutaneous inoculation of Huh7 cells, and then the mice were equally randomized into 3 groups, and at 7 d after inoculation (tumor formation established), were intraperitoneally administrated with saline (control group), 25 mg/kg chloroquine (low-dose chloroquine group) and 50 mg/kg chloroquine (high-dose chloroquine group) respectively, once per day for 30 d. The tumor growth in each group was recorded. The xenografts were harvested at end of the experiment, and the expressions of autophagy-related proteins (LC3, p62) were determined by immunochemical staining and Western blot, respectively.
Results: The results of MTT assay showed that the proliferation of Huh7 cells was significantly inhibited by either concentration of chloroquine compared with control (0 μmol/L), with a time- and concentration-dependent manner (all P<0.05). In the tumor-bearing mice, the xenograft growths in both chloroquine treated groups were significantly suppressed compared with control group, and the tumor growth suppression in high-dose chloroquine group was more evident than that in low-dose chloroquine group (all P<0.05); the results of immunohistochemical staining and Western blot showed that the expression levels of LC3 and p62 in the tumor tissues in both chloroquine treated groups were significantly increased compared with control group, and the increasing amplitudes in high-dose chloroquine group were greater than those in low-dose chloroquine group (all P<0.05).
Conclusion: Chloroquine can inhibit the growth of liver cancer cells both in vitro and in vivo, and the mechanism may be related to its regulating the expressions of autophagy-related proteins and then inhibiting the autophagy of the liver cancer cells.

9 Expression of glia maturation factor β in hepatocellular carcinoma and its clinical significance

CHEN Xin , LU Hui , GE Yongsheng , JIA Weidong

2020, 29(1):69-77. DOI: 10.7659/j.issn.1005-6947.2020.01.009

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Background and Aims: Glia maturation factor β (GMFB) is a 17 kDa and highly conserved brain-specific protein. Recent investigations demonstrated that GMFB expression is up-regulated in variety of cancers and closely associated with the unfavorable outcomes of the patients. However, the knowledge about the expression and function of GMFB in hepatocellular carcinoma (HCC) is still insufficient. This study was designed to investigate the clinical significance of GMFB in HCC by examining the expression of GMFB in HCC tissue and analyzing its relations with the clinicopathologic features and prognosis as well as Ki-67 expression of the patients.
Methods: The mRNA and protein expressions of GMFB in 36 paired fresh-froze HCC and adjacent tissue were determined by qRT-PCR and Western blot respectively. The protein expressions of GMFB and Ki-67 in 91 paired paraffin specimens of HCC and adjacent tissue were determined by immunohistochemical staining. The relations of GMFB expression with the clinicopathologic factors and postoperative survival time of the patients as well as Ki-67 expression were analyzed by statistical methods.
Results: The results of qRT-PCR and Western blot showed that the relative expression levels of both GMFB mRNA and protein in HCC tissue were significantly higher than those in tumor adjacent tissue (both P<0.001). The results of immunohistochemical staining showed that the positive expression rates of both GMFB and Ki-67 in HCC tissue were significantly higher than those in tumor adjacent tissue (both P<0.001); GMFB expression was significantly related to the microvascular invasion (P=0.045), Edmondson grade (P=0.032) and BCLC stage (P=0.012); there was a positive correlation between GMFB expression and Ki-67 expression in HCC tissue (rs=0.265, P=0.011). Kaplan-Meier survival analysis showed that disease-free survival (DFS) and overall survival (OS) in patients with positive GMFB were significantly shorter than those in patients with negative GMFB expression (DFS: 4.52 months vs. 10.48 months, P=0.001; OS: 27.67 months vs. 39.75 months, P=0.007). Cox multivariate regression analysis showed that the upregulations of GMFB and Ki-67 were independent risk factors for both DFS (HR=0.441, 95% CI=0.242–0.801, P=0.007; HR=1.818, 95% CI=1.012–3.269, P=0.046) and OS (HR=0.504, 95% CI=0.287–0.886, P=0.017; HR=1.787, 95% CI=1.083–2.935, P=0.023) of HCC patients.
Conclusion: GMFB presents a high expression in HCC, and is closely associated with tumor progression and poor prognosis of the patients. GMFB expression is positively correlated with Ki-67 expression, suggesting that GMFB exerts its actions by regulating the proliferative ability of the cancer cells.

10 Clinical value of nanonife ablation in treatment of unresectable hilar cholangiocarcinoma

GUO Kai , LI Xiaoyong , ZHOU Baizhong , CHEN Yanjun , CHEN Shengyang , CHENG Bingbing , HU Shuiquan , SU Dongchao

2020, 29(1):78-84. DOI: 10.7659/j.issn.1005-6947.2020.01.010

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Background and Aims: For unresectable hilar cholangiocarcinoma, effective treatments should be performed to relieve the biliary obstruction, and thereby to improve the quality of life and survival rates of the patients. This study was aimed to investigate the application value of nanoknife ablation in treatment of unresectable hilar cholangiocarcinoma through comparison of the efficacy and safety between nanoknife ablation combined with percutaneous transhepatic cholangial drainage (PTCD) and PTCD alone for unresectable hilar cholangiocarcinoma, so as to provide the basis and reference for the treatment selection of the condition.
Methods: Thirty-five patients with unresectable hilar cholangiocarcinoma admitted in the Fifth Affiliated Hospital of Zhengzhou University from July 2016 to July 2017 were designated to observation group (15 cases) and control group (20 cases). Patients in observation group underwent nanoknife ablation 1 to 2 weeks after PTCD treatment, and patients in control group underwent PTCD alone. The changes in the levels of transaminases and total bilirubin (TBIL), scores for quality of life and postoperative survival rates were compared between the two groups of patients before and after treatment, and the recanalization of the bile duct as well as the adverse reactions and complications in the patients after nanoknife ablation treatment, and the incidence of rehospitalization due to internal PTCD tube obstruction and infection in patients undergoing PTCD alone were observed.
Results: There were no significant differences in the general data and liver function parameters between the two groups of patients (all P>0.05). The levels of transaminases and TBIL, and scores for quality of life at 1 and 3 months after operation were significantly improved compared with those before operation in observation group (all P<0.05), which were significantly improved at 1 month after operation (all P<0.05), but showed no significant difference at 3 months after operation compared those before operation in control group (all P>0.05). All above variables in observation group were significantly superior to those in control group at both 1 month and 3 months after operation (all P<0.05). The median survival time in observation group was significantly longer than that in control group (15 months vs. 5 months, P<0.05.), and the 1-year survival rate in observation group was significantly higher than that in control group (80.0% vs. 15.0%, P<0.05), but the 2-year survival rates showed no significant difference between the two groups (6.7% vs. 0, P>0.05). In observation group, the removal rates of PTCD tube were 82.6% and 98.0% at 1 and 3 months after operation, and the patency time of the bile duct was (185.1±95.8) d; the discomfortable symptoms such as abdominal distention and fever occurred in some patients, biliary infection occurred in 2 cases and upper gastrointestinal hemorrhage occurred in 1 case. In control group, the rates of rehospitalization due to PTCD tube obstruction or infection was 50%.
Conclusion: Nanoknife ablation has demonstrable efficacy in treatment of unresectable hilar cholangiocarcinoma, which can effectively improve the liver function, prolong the survival time of the patients, and also can recanalize the bile duct, then provide the patients an opportunity for drainage tube removal, thereby improve the patients’ quality of life, with a high safety. It offers a new treatment modality for patients with unresectable hilar cholangiocarcinoma.

11 Advances in preoperative assessment of liver functional reserve in patients with primary liver cancer

LU Huaze , WANG Xiaobo , LI Lequn

2020, 29(1):85-96. DOI: 10.7659/j.issn.1005-6947.2020.01.011

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Primary liver cancer is the fourth most common malignancy and third most frequent cancer-related cause of death in China. Hepatectomy is a radical treatment for primary liver cancer. Advancement in surgical techniques and perioperative managements have apparently improved the safety of hepatectomy. However, the posthepatectomy liver failure caused by the insufficient residual liver function is still the main reason of perioperative death. Therefore, it is essential to assess hepatic functional reserve before hepatectomy. There are several examinations to assess hepatic function, including traditional blood tests, the Child‐Pugh score, model for end-stage liver disease (MELD) score, indocyanine green (ICG), ultrasound, computed tomography volumetry, Gd-EOB-DTPA MRI and nuclear medicine. Although the Child-Pugh score is the most widely used model in evaluating hepatic function, its predictive value is limited. According to the Child‐Pugh classification, the majority of patients are classified as grade A, but their liver functions may vary significantly. MELD was originally used to predict survival in patients after transjugular intrahepatic portosystemic shunt and has been used as a tool for ranking candidates for transplantation, but cannot determine the scope of liver resection. The indocyanine green and other metabolic quantitative liver function tests can evaluate functional hepatocytes, making them more accurate in predicting liver function. Ultrasound is a non-invasive method that has been proposed for the assessment of the degree of hepatic fibrosis in patients with chronic liver diseases by measuring liver stiffness and indirectly predict liver function. CT volumetry can provide anatomic information on the remnant liver volume but not on functional volume. In addition, its use is limited by radiation, especially when repetitive examinations are required. Arterial enhancement fraction can detect the presence of mild, moderate, and advanced liver fibrosis. Gd-EOB-DTPA is a paramagnetic hepatobiliary magnetic resonance contrast agent having the same transport mechanisms like ICG. Therefore, similar to ICG clearance, Gd-EOB-DTPA MRI should provide information for quantitative evaluation of liver function and allow for anatomic delineation of hepatic function. 99mTC-GSA, combined with single photon emission computed tomography, CT and three-dimensional reconstruction, may be a better quantitative measure of liver function, especially for damaged livers with functional heterogeneity among the hepatic segments. 99mTc mebrofenin hepatobiliary scintigraphy in combination with single-photon emission computed tomography/computed tomography is increasingly applied for the quantitative assessment of liver function before liver surgery. This dynamic quantitative liver function test allows assessment of both total and regional liver function, represented by the hepatic mebrofenin uptake rate, thereby assisting in adequate patient selection. Assessing hepatic functional reserve before hepatectomy is beneficial to reduce the incidence of post hepatectomy liver failure. However, it is difficult to accurately evaluate liver function before surgery because of the limitations of the liver function tests available. Here, the authors analyze above methods and their advantages.

12 Research progress of mechanism for hypoxia promoting the occurrence and development of hepatocellular carcinoma

MENG Yongbin , CHENG Binbin , DU Juan , CHEN Hongyun , LING Changquan

2020, 29(1):97-103. DOI: 10.7659/j.issn.1005-6947.2020.01.012

[Abstract](730) [HTML](1160) [PDF 1.11 M](999)

Abstract:
Hepatocellular carcinoma (HCC) is one of the deadliest cancers in the world. Hypoxia is closely related to the occurrence and development of HCC. The researches on hypoxia, hypoxia markers and hypoxia-induced tumor neovascularization in HCC have great significance for clinical diagnosis and treatment. Here, the authors address the action mechanisms of hypoxia inducible factors, matrix metalloproteinases, high mobility group protein 1, autophagy gene Beclin-1, neuroglobin, cytoglobin and microRNAs (miRNAs) in HCC.

13 Progresses of treatment and diagnosis of polycystic liver disease

ZHANG Zeyu , HUANG Yun , WANG Zhiming

2020, 29(1):104-114. DOI: 10.7659/j.issn.1005-6947.2020.01.013

[Abstract](1186) [HTML](1589) [PDF 1.20 M](1296)

Abstract:
Polycystic liver disease (PLD) is a rare inherited disorder that can exist independently, or as an accompanying symptom of autosomal dominant polycystic kidney disease and autosomal recessive polycystic kidney disease. The pathogenic genes and associated mechanisms of PLD are complex and diverse, which are still not completely clear, and are now considered to be associated with the developmental abnormalities of the bile ducts caused by various factors. PLD is characterized by multiple scattered liver cysts, which cause no symptoms in majority of cases, but will cause symptoms in some cases such as abdominal distention, tachypnea, esophageal reflux, abdominal pain and back pain as cysts grow in size and number, and thereby affect the quality of life. The use of ultrasound, CT or magnetic MRI can help to diagnose PLD. Among patients with no family history, the diagnosis of PLD can be made when the number of hepatic cysts exceeds 20. Furthermore, if genetic analysis is available, PLD can be diagnosed at the genetic level and classified. For symptomatic PLD patients, different treatment schemes can be selected according to the different general conditions and the ranges affected by the lesions. The treatments of PLD mainly include the pharmacotherapy and surgical intervention. For pharmacotherapy, studies have shown that somatostatin analogues, mammalian target of rapamycin, ursodeoxycholic acid, vasopressin 2 receptor antagonists have potentially therapeutic capacity, however currently only the somatostatin analogues are widely accepted and used in clinical practice, while the others need further researches to validate the safety and effectiveness. The commonly used surgical intervention includes cyst aspiration and sclerosis, fenestration, transcatheter arterial embolization, hepatic resection, and liver transplantation, in which liver transplantation is the only method of radical treatment. However, it should be noted that there is no breakthrough in diagnosis and treatment of PLD at percent. In this article, the authors address the progress of clinical diagnosis and treatment of PLD and comprehensive information of clinical application of the treatments in order to deepen the understanding of the current clinical diagnosis and treatment of PLD and guide the future direction. In addition, the diagnosis and treatment process according to the experience of our medical center are provided for reference.

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Volume 29,Issue 1,2020 Table of Contents

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