Objective To summarize the research progress of magnetic resonance imaging (MRI) in evaluating microvascular invasion (MVI) of hepatocellular carcinoma (HCC) in order to provide information and evidence for therapy of HCC. Methods Papers published from May 1950 to May 2017, were retrieved in PubMed, OVID, CNKI database using the keywords on hepatocellular carcinoma, microvascular invasion, and magnetic resonance imaging. Sixty-seven papers were retrieved in English literatures and 13 in Chinese literatures. Criteria of paper adoption: ① the imaging method was MRI; ② the assessment content was MVI of HCC; ③ the golden standard was postoperative pathologic diagnosis. fifty-four papers were finally analyzed and reviewed. Results Currently there were various ways to evaluating the MVI of HCC using MRI, including morphology, texture analysis, diffusion-weighted imaging, dynamic-enhanced MRI, fat assessment, hepatocellular function and comprehensive evaluation. Conclusions Various methods perform differently in evaluating MVI. The use of multiparametric MRI techniques offers the potential for comprehensive assessment of MVI of HCC.
ObjectiveTo detect the expression of FXYD domain-containing ion transport regulator 6 (FXYD6) protein in hepatocellular carcinoma tissues and the corresponding paracancerous liver tissues, and to explore the clinical significance of FXYD6 protein expression in hepatocellular carcinoma.MethodsEighty hepatocellular carcinoma tissues and the corresponding 40 paracancerous tissues were retrospectively collected in Cangzhou Central Hospital from March 2012 to January 2018, and the expression of FXYD6 protein was examined in these tissues by strept avidin-biotin complex (SABC) immunohistochemistry. We analyzed the relationship between the expression of FXYD6 protein and clinicopathological characteristics of the patients with hepatocellular carcinoma, and the relationship between the expression of the protein and early recurrence or overall survival.ResultsThe positive expression rate of FXYD6 protein was statistically higher in hepatocellular carcinoma tissues than that in the corresponding paracancerous tissues [77.5% (62/80) vs. 40.0% (16/40), P<0.001]. Its expression in hepatocellular carcinoma was not related with gender, age, histological differentiation, tumor maximum diameter, tumor number, AFP concentration in serum, and HBV or HCV infection (P>0.05), but with integrity of tumor capsule, microvascular invasion, and tumor stage (P<0.05). The positive FXYD6 protein expression group had a significantly higher recurrence rate than that of the negative FXYD6 protein expression group [53.2% (33/62) vs. 16.7% (3/18), P=0.006]. However, multivariate analysis results showed that high FXYD6 protein expression was not a risk factor for early relapse (P=0.422). The positive FXYD6 protein expression group had a significantly shorter postoperative survival than the negative FXYD6 expression group ( P=0.043). However, multivariate analysis results showed high FXYD6 protein expression was not a risk factor for overall survival (P=0.754).ConclusionsFXYD6 protein was expressed abnormally in hepatocellular carcinoma tissues, which might be involved in the carcinogenesis and the progression of hepatocellular carcinoma. It might be a poor prognostic factor for patient with hepatocellular carcinoma.
ObjectiveTo assess value of preoperative clinical data and enhanced CT imaging features in predic-tion of microvascular invasion (MVI) and early recurrence (recurrence in one year) after curative resection for hepatoce-llular carcinoma (HCC). MethodsA retrospective analysis was conducted for 150 patients with HCC who underwent curative tumor resection in West China Hospital of Sichuan University from April 2014 to May 2015. The roles of preoperative CT characteristics and clinical data on MVI and early recurrence after curative tumor resection were evaluated by univariate and multivariate analyses. Resultscompared with HCC with no MVI and no early recurrence after curative resection, univariate analysis results showed that HCC with MVI and early recurrence had larger tumor size (P=0.002, P=0.005), a higher proportion of non-smooth tumor margin (P<0.001, P<0.001), and tumor multifocality (P=0.005, P=0.038), HCC with MVI had a higher proportion of incomplete tumor capsule (P=0.032), HCC with early recurrence had a higher proportion of incomplete and absence tumor capsules (P=0.038) and a faster washout on portal venous phase-the percentage attenuation ratio on the portal venous phase (P=0.049) and relative washout ratio on the portal venous phase (P=0.020) were higher. A multivariate logistic regression analysis results showed that non-smooth tumor margin (OR=7.075, P<0.001; OR=4.125, P<0.001) and tumor multifocality (OR=3.290, P=0.008; OR=2.354, P=0.047) were the independent predictors for MVI and early recurrence after curative tumor resection, HCC with early recurrence also had a faster washout on the portal venous phase (OR=1.023, P=0.017). ConclusionNon-smooth tumor margin and tumor multifocality are independent risk factors for MVI and early recurrence after curative tumor resection, and HCC with early recurrence has a faster washout on portal venous phase. Preoperative enhanced CT imaging could predict MVI and early recurrence after curative tumor resection and CT imaging findings are helpful to choose reasonable treatment and predict prognosis.
Objective To explore the impact of microvascular invasion (MVI) on the survival prognosis of patients after radical hepatectomy for hepatocellular carcinoma, to analyze its related risk factors and preoperative prediction methods, and to provide reference and support for the treatment of early postoperative recurrence. MethodsBy searching domestic and international medical literature databases, we screened studies related to MVI in hepatocellular carcinoma, focusing on the definition, grading, risk factors, preoperative prediction methods, and postoperative treatment strategies of MVI, and summarized the results of the existing studies. ResultsMVI was a well-established risk factor for the intrahepatic metastasis and early postoperative recurrence of hepatocellular carcinoma. Currently, various methods were employed to predict MVI, including laboratory indicators, imaging genomics, and genomics. The laboratory indicators used for prediction included alpha-fetoprotein, protein induced by vitamin K absence or antagonist-Ⅱ, hepatitis B virus, tumor diameter, vascular endothelial growth factor A, and circulating tumor cells. Imaging genomics involved preoperative MRI with irregular tumor shape and intra-voxel incoherent motion diffusion-weighted imaging D value < 1.16 × 10-3 mm2/S, CT enhancement imaging features with irregular tumor margins, multiple foci, and contrast-enhanced ultrasound portal venous and delayed phase scores. Genomics included the maximum variant allele frequency of circulating tumor DNA. In cases where MVI was detected after surgery, adjuvant therapy options had gained attention, such as transcatheter arterial chemoembolization, hepatic arterial infusion chemotherapy, targeted therapy, immunotherapy, radiation therapy, antiviral therapy, and local treatment combined with systemic treatment. ConclusionsThe study of MVI and its targeted treatment strategies are important for reducing the postoperative recurrence rate of hepatocellular carcinoma and improving patient survival. The preoperative prediction model and postoperative treatment plan should be optimized in the future to provide more effective treatment reference for patients.
ObjectiveTo evaluate therapeutical effects of Huaier granule combined with transcatheter arterial chemoembolization (TACE) following radical resection of primary hepatocellular carcinoma with microvascular invasion. MethodsThe clinical data of 45 cases of primary hepatocellular carcinoma with microvascular invasion underwent Huaier granule combined with transcatheter arterial chemoembolization (TACE) following radical resection from June 2010 to June 2013 in Liaoning Cancer Hospital were retrospectively analyzed. These patients were divided into Huaier granule plus TACE treatment group (20 cases) and simple TACE treatment group (25 cases) according to the postoperative treatment of the patients. The immune function (CD4+/CD8+ ratio and IL-2 level), 1and 3-year tumor recurrence rates and 3-year cumulative survival rate were compared between two groups after operation. Result① The CD4+/CD8+ ratio and IL-2 level had no significant differences between the 2 groups before operation (P > 0.05), which in the Huaier granule plus TACE treatment group were significantly higher than those in the simple TACE treatment group (P < 0.05) on month 3, 6, and 12 after operation.② 1and 3-year tumor recurrence rates in the Huaier granule plus TACE treatment group were significantly lower than those in the simple TACE treatment group[15% (3/20) versus 48% (12/25), P < 0.05; 45% (9/20) versus 80% (20/25), P < 0.05]. ③ The 3-year cumulative survival rate was 75% and 68% in the Huaier granule plus TACE treatment group and the simple TACE treatment group, respectively. The survival curve analysis showed that the 3-year survival rate had a decreased trend, which in the Huaier granule plus TACE treatment group was slightly higher than that in the simple TACE treatment group, but the difference had no statistical significance between the 2 groups (P > 0.05). ConclusionsAlthough the results of this study fails to confirm that Huaier granule plus TACE treatment for primary hepatocellular carcinoma with microvascular invasion following radical resection could significantly improve the 3-year cumulative survival rate, it could effectively decrease the recurrence rate. It is needed larger sample size to further explore in future research.
ObjectiveTo find out the risk factors affecting the prognoses and microvascular invasion (MVI) of patients with China Liver Cancer Staging-stageⅠ a (CNLC Ⅰ a) hepatocellular carcinoma (HCC). MethodsBased on the established inclusion and exclusion criteria, the clinicopathologic information and follow-up data of patients with CNLC Ⅰ a HCC were retrospectively collected, who underwent radical resection in the West China Hospital of Sichuan University from Jan. 2012 to Dec. 2016. The Cox proportional hazards regression was utilized to analyze the risk factors affecting the prognosis of patients with CNLC Ⅰ a HCC, and the non-conditional logistic regression was utilized to analyze the preoperative clinical indicators associating with MVI. ResultsA total of 300 patients with CNLC Ⅰ a HCC were included in this study, among which 51 (17.0%) cases accompanied with MVI. The follow-up period ranged from 2 to 104 months (median 39 months), with a recurrence time ranging from 2 to 104 months (median 52 months), and an overall survival time ranging from 3 to 104 months (median 98 months). During the follow-up period, postoperative recurrence occurred in 145 (48.3%) cases. The Cox proportional hazards regression analysis revealed that: tumor diameter >3 cm, presences of MVI and satellite nodules increased the risk of shortened recurrence time for the patients with CNLC Ⅰ a HCC (P<0.05); Factors including gamma-glutamyltranspeptidase level >60 U/L, tumor low differentiation, presences of MVI and satellite nodules were associated with shortened overall survival time for the patients with CNLC Ⅰ a HCC (P<0.05). The preoperative alpha-fetoprotein level ≥400 μg/L and tumor diameter >3 cm increased the risk of presence of MVI for the patients with CNLC Ⅰ a HCC [χ2=3.059, OR(95%CI)=2.357(1.047, 5.306), P=0.038; χ2=3.002, OR(95%CI)=2.301(1.026, 5.162), P=0.043]. ConclusionThe results of this study suggest that adopting corresponding strategies to address the risk factors affecting prognosis of patients with CNLC Ⅰ a HCC and the risk factors associated with MVI can have a significant clinical impact on improving surgical treatment outcomes for these patients.
ObjectiveTo explore the risk factors that affect the long-term prognosis of liver cancer after liver transplantation, and to evaluate the clinical value of the Chinese Medical Association’s new microvascular invasion pathological classification.MethodsThe clinical pathology and follow-up data of 112 patients with liver cancer who underwent liver transplantation from January 2015 to December 2018 were retrospectively analyzed. Prognostic risk factors were analyzed by Cox proportional hazard regression model.ResultsAll of the 112 patients were followed up. The postoperative follow-up period was 12 to 60 months [(28.3±13.5) months], and the median overall survival time was 38-month. The results of the Cox proportional hazard regression model suggested that the preoperative Child classification and microvascular invasion pathological classification were independent factors affecting the prognosis of patients (P<0.05), the higher microvascular invasion pathological classification and Child grade, the worse the prognosis.ConclusionThe Chinese Medical Association’s new microvascular invasion pathological classification can predict the prognosis of patients with liver cancer after liver transplantation and has a good predictive value.
ObjectiveTo assess the feasibility of intravoxel incoherent motion diffusion-weighted imaging (IVIM) in evaluating microvessel density (MVD) and microvascular invasion (MVI) of hepatocellular carcinoma (HCC).MethodsRat models were established to be scanned by IVIM. HCC lesions corresponding to IVIM image were examined pathologically to get data of MVD and MVI. Spearman correlation analysis was used to compare the apparent diffusion coefficient (ADC), D, D*, and f with MVD, independent samples t test was used to compare ADC, D, D*, and f between MVI (+) and MVI (–) groups.ResultsFifty HCC lesions were included finally. ADC and D values both showed a negative correlation with MVD (r=–0.406, P=0.003; r=–0.468, P=0.001), D* and f showed no statistical correlation with MVD (P=0.172, 0.074, respectively). The differences in ADC and all the IVIM parameters (D, D*, and f) between MVI (+) and MVI (–) HCCs were not statistically significant (P=0.393, 0.395, 0.221, 0.550).ConclusionADC and D can be used to evaluate MVD of HCC, but ADC and IVIM parameters were limited in evaluating MVI.
ObjectiveTo explore the predictive value of serum prothrombin induced by vitamin K absence-Ⅱ (PIVKA-Ⅱ) detection for the biological characteristics of hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC).MethodsThis retrospective study included 394 patients with HBV-related HCC who were newly diagnosed and treated with surgical resection in West China Hospital of Sichuan University between June 2017 and December 2018. Their clinical information such as tumor size, tumor number, tumor cell differentiation, presence of microvascular invasion (MVI), distant metastasis, and portal vein tumor thrombus was collected from the medical record. The laboratory test results of patients during diagnosis and before surgery were collected, including alpha-fetoprotein (AFP), PIVKA-Ⅱ, alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (γ-GGT), etc., and the relationships between PIVKA-Ⅱ levels and tumor biological characteristics were analyzed. Non-normal continuous variables were presented as medium (lower quartile, upper quartile).ResultsCompared with the patients with low HCC serum PIVKA-Ⅱ levels (≤40 mAU/mL), patients with high serum PIVKA-Ⅱ levels (>40 mAU/mL) had larger tumor diameters [5.00 (3.00, 9.00) vs. 2.50 (1.63, 4.95) cm, P<0.001], more severe Barcelona Clinic Liver Cancer (BCLC) stage (P<0.001), and higher AFP [186.05 (6.86, 1 210.00) vs. 17.83 (4.33, 231.95) ng/mL, P<0.001], ALT [38.00 (26.00, 66.25) vs. 32.00 (22.00, 51.00) U/L, P=0.018], AST [42.00 (30.00, 76.00) vs. 34.00 (25.50, 48.25) U/L, P<0.001], and γ-GGT [71.00 (39.00, 165.50) vs. 55.50 (25.00, 93.00) U/L, P=0.005], and were more likely to form portal vein tumor thrombi (16.61% vs. 3.75%, P=0.003) and MVI (43.67% vs. 11.11%, P<0.001). In BCLC stage 0 HCC patients, the positive rate of PIVKA-Ⅱ was only 51.35%. Multivariate logistic regression analysis showed that PIVKA-Ⅱ>40 mAU/mL was an independent predictor of MVI [odds ratio=6.588, 95% confidence interval (CI) (1.645, 26.383), P=0.008]. The area under receiver operating characteristic curve of PIVKA-Ⅱ level predicting MVI was 0.761 [95%CI (0.693, 0.830)], with a sensitivity of 66.22% and a specificity of 79.06%.ConclusionIn HBV-related HCC patients, high PIVKA-Ⅱ is associated with the poor biological characteristics of tumor, and is an independent risk factor for tumor MVI.
ObjectiveTo establish a model for predicting microvascular invasion (MVI) of hepatocellular carcinoma based on magnetic resonance imaging (MRI) radiomics features.MethodsThe clinical and pathological datas of 190 patients with hepatocellular carcinoma who received surgical treatment in our hospital from September 2017 to May 2020 were prospectively collected. The patients were randomly divided into training group (n=158) and test group (n=32) with a ratio of 5∶1. Gadoxetate disodium (Gd-EOB-DTPA) -enhanced MR images of arterial phase and hepatobiliary phase were used to select radiomics features through the region of interest (ROI). The ROI included the tumor lesions and the area dilating to 2 cm from the margin of the tumor. Based on a machine learning algorithm logistic, a radiomics model for predicting MVI of hepatocellular carcinoma was established in the training group, and the model was evaluated in the test group.ResultsSeven radiomics features were obtained. The area under the receiver operating characteristic curve (AUC) of the training group and the test group were 0.830 [95%CI (0.669, 0.811)] and 0.734 [95%CI (0.600, 0.936)], respectively.ConclusionThe model based on MRI radiomics features seems to be a promising approach for predicting the microvascular invasion of hepatocellular carcinoma, which is of clinical significance for the management of hepatocellular carcinoma treatment.