Research progress on the formation mechanism of hepatocellular carcinoma with portal vein tumor thrombus / 中华肝胆外科杂志

Hepatocellular carcinoma is a common malignant disease in clinical practice, and portal vein tumor thrombosis (PVTT) is one of the important factors affecting the prognosis of hepatocellular carcinoma. PVTT has strong oncologic characteristics and is highly susceptible to extrahepatic metastasis, complicating portal hypertension, leading to gastrointestinal bleeding or liver failure and causing death. In this paper, we review the formation mechanism of hepatocellular carcinoma combined with PVTT in terms of local anatomy, hemodynamics, molecular biology and tumor microenvironment to provide effective reference for clinical treatment.

Effect of Echinococcus multilocularis secreted antigen on the phenotype and function of mouse bone marrow - derived dendritic cells induced by lipopolysaccharide / 临床肝胆病杂志

Objective To investigate the effect of different concentrations of Echinococcus multilocularis secretion antigen (Em-sAg) on the phenotype and function of mouse bone marrow-derived dendritic cells (BMDCs) induced by lipopolysaccharide (LPS). Methods The bone marrow precursor cells isolated from the mouse bone marrow cavity were stimulated by mouse recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) to form BMDCs, and then cell morphology was observed under an inverted microscope. After the purity of BMDCs was identified by flow cytometry, BMDCs were divided into control group, positive control group (LPS 1 μg/ml), LPS+3 mg/ml Em-sAg group, LPS+1.5 mg/ml Em-sAg group, LPS+0.75 mg/ml Em-sAg group, and LPS+0.375 mg/ml Em-sAg group. Flow cytometry was used to measure the expression of BMDC surface molecules (CD80, CD86, and MHC-Ⅱ molecules) in each group, and ELISA was used to measure the expression level of the cytokine IL-12p70. A one-way analysis of variance was used for comparison of normally distributed continuous data between multiple groups, and the least significant difference t -test was used for further comparison between two groups. Results Observation under an inverted microscope showed that after 8-10 days of culture, the cells had burr-like protrusions and were in a state of complete suspension. Flow cytometry showed that the positive rate of CD11c was above 70% and most of the cultured cells were identified as BMDCs based on this. Flow cytometry further showed that compared with the control group, the LPS group had significant increases in the cell molecules CD80, CD86, and MHC-Ⅱ on surface (all P 0.05). ELISA showed that there was a significant difference in the level of IL-12 p70 between groups ( F =73.140, P < 0.05); compared with the control group, the LPS group had a significant increase in the expression level of IL-12p70 after stimulation ( P < 0.05); compared with the positive control group, the LPS+3 mg/ml Em-sAg group, the LPS+1.5 mg/ml Em-sAg group, the LPS+0.75 mg/ml Em-sAg group, and the LPS+0.375 mg/ml Em-sAg group had a significant reduction in the expression level of IL-12p70 ( P < 0.05), and the degree of reduction in the pro-inflammatory factor IL-12p70 increased with the increase in the concentration of Em-sAg. Conclusion Different concentrations of Em-sAg can inhibit LPS-induced maturity of BMDCs and the expression of the pro-inflammatory cytokine IL-12p70.

Establishment and evaluation of a nomogram for predicting post-hepatectomy complications in two types of hepatic echinococcosis / 临床肝胆病杂志

Objective To establish a nomogram for predicting the risk of post-hepatectomy complications (PHC) in hepatic echinococcosis by analyzing the risk factors for PHC in two types of hepatic echinococcosis, and to investigate its value in clinical practice. Methods A retrospective analysis was performed for the clinical data of 263 patients with two types of hepatic echinococcosis who underwent hepatectomy in Qinghai University Affiliated Hospital from January 2015 to August 2020, and among these patients, 93 were enrolled as PHC group and 170 were enrolled as control group. The Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups, and the independent samples t -test was used for comparison of normally distributed continuous data between two groups; the chi-square test and the Fisher's exact test were used for comparison of categorical data between two groups. Univariate and multivariate logistic regression analyses were used to screen out independent risk factors for PHC, and a nomogram risk prediction model was established based on the weight of each independent risk factor. The Bootstrap resampling method was used for internal verification of the model; the receiver operating characteristic (ROC) curve was plotted to evaluate the discriminatory ability of the model; calibration curve and the Hosmer-Lemeshow test were used to evaluate the consistency of the model; decision curve analysis (DCA) was performed to verify the clinical effectiveness of the model. Results Albumin-bilirubin (ALBI) score (odds ratio [ OR ]=3.694, 95% confidence interval [ CI ]: 1.860-7.336, P < 0.05), time of operation ( OR =2.848, 95%CI: 1.384-5.859, P < 0.05), intraoperative blood loss ( OR =4.832, 95%CI: 2.384-9.793, P < 0.05), and hydatid diameter ( OR =3.073, 95%CI: 1.528-6.177, P < 0.05) were independent risk factors for PHC in two types of hepatic echinococcosis. A nomogram risk prediction model was established based on the weight of the above four independent risk factors, and the model had an area under the ROC curve of 0.877 (95% CI : 0.831-0.923). The model had a consistency index of 0.871 after internal verification using the Bootstrap resampling method, suggesting that the model had good discriminatory ability. The fitting of the observed value and the actual value of the calibration curve and the Hosmer-Lemeshow test ( P =0.905) showed that the predicted value of the nomogram risk prediction model had good consistency with the actual observed value. When the threshold probability was 35.6%, DCA showed a net clinical benefit of 22%, and the model had good clinical applicability within the threshold probability ranging from 8% to 89%. Conclusion ALBI score, time of operation, intraoperative blood loss, and hydatid diameter are independent risk factors for PHC in patients with two types of hepatic echinococcosis, and the nomogram risk prediction model established based on these factors has good accuracy, consistency, and clinical practicability.

Association between serum macrophage polarization-related factors and liver fibrosis in echinococcosis multilocularis / 临床肝胆病杂志

Objective To investigate the association between serum macrophage polarization-related factors and liver fibrosis in patients with alveolar echinococcosis (AE). Methods A total of 120 patients with AE who attended Department of Hepatobiliary and Pancreatic Surgery in The Affiliated Hospital of Qinghai University from September 2018 to October 2020 were enrolled as AE group, and 33 healthy controls were enrolled as normal control group. The two groups and the patients with varying degrees of liver fibrosis were compared in terms of the levels of interleukin-6 (IL-6), interleukin-10 (IL-10), tumor necrosis factor-α (TNF-α), and transforming growth factor-β1 (TGF-β1). Comparison of normally distributed continuous data between two groups was made by the independent samples t -test, while comparison of non-normally distributed continuous data was made by the Mann-Whitney U test or Kruskal-Wallis H test. Comparison of categorical data between groups was made by the chi-square test. Univariate and multivariate logistic regression analyses were used to investigate the association between serum macrophage polarization-related factors and liver fibrosis in patients with AE, and the receiver operating characteristic (ROC) curve was used to analyze the value of serological examination in the diagnosis of liver fibrosis in patients with AE. A Spearman correlation analysis was used to analyze the correlation of each index with HAI score and Metavir score. Results Compared with the normal control group, the AE group had significant increases in the serum levels of IL-6 [13.97 (9.64-23.62) pg/mL vs 1.30 (0.35-2.71) pg/mL, Z =-5.980, P < 0.001], TNF-α [2.26 (1.65-4.13) pg/mL vs 1.40 (1.04-2.10) pg/mL, Z =-3.114, P < 0.01], and TGF-β1 [3.64(2.71-5.72) pg/mL vs 2.91(2.20-3.35) pg/mL, Z =-2.594, P < 0.05], and increases in the serum levels of IL-6 (hazard ratio [ HR ]=2.721, 95% confidence interval [ CI ]: 1.730-4.280, P < 0.05) and TNF-α( HR =3.527, 95% CI : 1.158-10.747, P < 0.05) were independent risk factors for the onset of liver fibrosis in AE patients. The ROC curve analysis showed that hydatid IgG combined with the serum levels of IL-6 and TNF-α had a sensitivity of 88.4%, a specificity of 95.8%, and an area under the ROC curve of 0.951(95% CI : 0.937-0.964) in the diagnosis of liver fibrosis, which were significantly higher than those of IL-6, TNF-α, or hydatid IgG alone ( Z =-3.458, -4.011, and 2.379, all P < 0.05). The Spearman analysis showed that the serum levels of IL-6, TNF-α, and TGF-β1 were positively correlated with HAI score ( r =0.560, 0.644, and 0.465, all P < 0.001) and Metavir fibrosis score ( r =0.530, 0.758, and 0.567, all P < 0.001), and the serum level of IL-10 was negatively correlated with HAI score ( r =-0.232, P =0.011) and Metavir fibrosis score ( r =-0.288, P =0.001). Conclusion Macrophage polarization is often observed in patients with hepatic AE, and the levels of the macrophage polarization-related factors IL-6, TNF-α, and TGF-β1 are associated with the development and progression of liver fibrosis, which can provide certain reference information for predicting the onset of liver fibrosis.

Effect of hepatitis B virus infection on patients with hepatic alveolar echinococcoisis after surgical resection / 中华肝胆外科杂志

Objective:To investigate the effect of hepatitis B virus (HBV) infection in patients with hepatic alveolar echinococcoisis after surgical resection and determine the differences of liver function between patients with different HBV-DNA levels.Methods:Patients were selected from January 2014 to July 2018 in the Affiliated Hospital of Qinghai University. Twenty-eight patients with hepatitis B and hepatic alveolar echinococcoisis were included in the experimental group, and 20 patients with hepatic alveolar echinococcoisis but without hepatitis B virus were included in the control group. Based on HBV-DNA level, the experimental group was divided into low-level group (HBV-DNA level<200 IU/ml, n=6), intermediate-level group (HBV-DNA level 200-20 000 IU/ml, n=15) and high level group (HBV-DNA level>20 000 IU/ml, n=7). Comparison of complications and liver function after liver resection in two groups.Univariate and multivariate logistic regression were used to analyze the influential factors of postoperative complications in patients.Comparison of postoperative liver function indexes in patients with different HBV-DNA levels. Results:In the control group, postoperative total bilirubin 10.6(8.3, 16.9) μmol/L, direct bilirubin 5.3(3.4, 10.0) μmol/L, prothrombin time 13.6(13.0, 15.8)s, and the incidence of complications 25.0%(5/20), were better than the experimental group 12.6(8.4, 46.9) μmol/L, 6.7(3.1, 26.4) μmol/L, 15.4(13.5, 18.1)s, 78.6% (22/28), the differences were statistically significant significance (all P<0.05). Multivariate logistic analysis showed that patients with HBV infection ( OR=4.593, 95% CI: 1.128-18.708) and intraoperative blood loss ≥1 000 ml ( OR=2.200, 95% CI: 1.106-4.378) were the hepatic alveolar echinococcoisis independent risk factors for postoperative complications. There were no significant differences in total bilirubin and albumin between the three groups of patients with different HBV-DNA levels ( P>0.05). Conclusion:Patients with HBV and hepatic alveolar echinococcoisis have worse liver function and are more prone to complications after surgical resection, but there is no significant difference in liver function among patients with different HBV-DNA levels.

Experimental study on the effect of radioactive 125I particles on alveolar echinococcosis / 中华肝胆外科杂志

Objective:To investigate the effect of 125I particles in alveolar echinococcosis with the animal model (nude mice and Sprague Dawley rats). Methods:Twenty 10 weeks nude mice with body weight ranged from 20 to 24 g were divided into three groups. Sixteen nude mice were divided into experimental group ( n=8), puncture group ( n=4) and model group ( n=4). There was no intervention in the model group and only particle puncture needle was used in the puncture group. 125I particles were implanted in the experimental group. 14 male Sprague Dawley rats without specific pathogen, with body weight 280-320 g, 12 weeks old, were used to construct the model of hepatic alveolar echinococcosis. Then the rats were divided into intervention group ( n=10) and control group ( n=4). In the intervention group, 125I particles were pushed into the lesions. The abdomen was only open and closed in the control group. All the mice were sacrificed 45 days after intervention. The tumor size was measured. The activity of protoscolex and pathological changes of Echinococcus multilocularis in each group were observed. Results:At the timepoint of 22nd, 30th and 40th day of intervention, the largest diameter of tumor in nude mice experimental group was (10.7±5.2) mm, (10.9±5.0) mm, (8.5±4.3) mm, smaller than that in puncture group (24.5±4.4) mm, (25.4±4.1) mm, (31.4±2.8) mm and model group (22.5±7.3) mm, (25.0±5.4) mm, (26.7±6.3) mm, with statistically significant difference ( P<0.05). The number and activity of protoscoleces in experimental group were lower than those in puncture group and model group. Under the light microscope, the structure of echinococcus vesiculae and its body in the experimental group was obviously destroyed, and the cuticle and germinal layer of echinococcus vesiculae in the puncture group and the model group were normal, with multiple intact protoscoleces. The pathological changes of Sprague Dawley rats in the intervention group and the control group were basically the same as those in the nude mice model. Conclusion:The 125I particle radiation effect can kill Echinococcus multilocularis protoscoleces and inhibit the growth of alveolar echinococcosis.