Microvascular Invasion In Hepatocellular Carcinoma Research Articles

A study of effect of lncRNA MVIH on sensitivity of gastric cancer cells to gemcitabine.

To study the effect of expression of long non-coding ribonucleic acid (lncRNA) associated with microvascular invasion in hepatocellular carcinoma (MVIH) on the sensitivity of gastric cancer cells to gemcitabine. BGC-823 cell lines were divided into control group (no treatment), low expression group (lentiviral transfection with sh-lncRNA MVIH), and high expression group (lentiviral transfection with lncRNA MVIH). The expression of lncRNA MVIH, the protein expressions of E-cadherin and Vimentin, and the differences in proliferation, migration, invasion, and apoptosis of gastric cancer cells were detected via Reverse Transcription-Polymerase Chain Reaction (RT-PCR), Western blotting, Cell counting kit-8 (CCK-8) assay, transwell assay, wound healing assay, methyl thiazolyl tetrazolium (MTT) assay, and flow cytometry. The results of RT-PCR revealed that compared with that in control group, the mRNA expression of lncRNA MVIH was significantly decreased in low expression group and markedly increased in high expression group. Also, there were statistically significant differences (p<0.05). The results of Western blotting showed that compared with those in control group and low expression group, the protein expression of E-cadherin was significantly decreased, while the protein expression of Vimentin was markedly increased in high expression group (p<0.05). The results of transwell assay manifested that the number of invading gastric cancer cells was the largest in high expression group at 48 h (p<0.05), significantly larger than that in control group and low expression group (p<0.05), while it was the smaller in low expression group. It was found through the wound healing assay that the migration ability of gastric cancer cells was enhanced in high expression group, markedly stronger than in control group and low expression group, while it significantly declined in low expression group compared to control group. Besides, the results of CCK-8 assay showed that compared with that in control group, the sensitivity of gastric cancer cells to gemcitabine was remarkably increased in low expression group (p<0.05), while it significantly declined in high expression group (p<0.05). Finally, according to the flow cytometry, the apoptosis rate of gastric cancer cells was markedly higher in low expression group than that in control group and high expression group (p<0.05), indicating that the low expression of lncRNA MVIH can promote the apoptosis of gastric cancer cells. Reducing the expression of lncRNA MVIH can significantly lower the migration and invasion ability of gastric cancer cells and raise the sensitivity of gastric cancer cells to gemcitabine.

LncRNA MVIH knockdown inhibits the malignancy progression through downregulating miR-505 mediated HMGB1 and CCNE2 in acute myeloid leukemia.

BackgroundThis study aimed to investigate the regulatory role of long non-coding RNA associated with microvascular invasion in hepatocellular carcinoma (lnc-MVIH) in the progression of acute myeloid leukemia (AML) and the underlying mechanism.MethodsLnc-MVIH expression was detected in AML cell lines AML-193, KG-1, HL-60, OCI-AML2 and primary normal bone marrow mononuclear cells (BMMC). The effect of lnc-MVIH knockdown on cell proliferation, apoptosis and miR-505 expression were detected by transfection of lnc-MVIH shRNA and control shRNA into KG-1 cells. And the effect of miR-505 knockdown on lnc-MVIH, cell proliferation, cell apoptosis as well as potential miR-505 target genes [high mobility group box 1 (HMGB1) and cyclin E2 (CCNE2)] in lnc-MVIH knockdown treated KG-1 cells was assessed by transfection of lnc-MVIH shRNA and lnc-MVIH shRNA & miR-505 shRNA into KG-1 cells.ResultsLnc-MVIH expression was elevated in AML-193, KG-1, OCI-AML2 cell lines, but similar in HL-60 cell line compared with primary normal BMMC. Lnc-MVIH knockdown inhibited cell proliferation but promoted cell apoptosis in KG-1 cells, meanwhile miR-505 expression was increased by lnc-MVIH knockdown in KG-1 cells. And in rescue experiments, miR-505 knockdown had no effect on expression of lnc-MVIH, while it increased the expressions of HMGB1 and CCNE2, promoted cell proliferation, inhibited cell apoptosis in lnc-MVIH knockdown treated KG-1 cells.ConclusionsLnc-MVIH knockdown inhibits cell proliferation but promotes cell apoptosis via regulating miR-505 mediated HMGB1 and CCNE2 in AML.

MicroRNAs associated with microvascular invasion in hepatocellular carcinoma and their prognostic impacts in patients undergoing hepatic resection.

Although microvascular invasion (McVI) has prognostic value for patients with hepatocellular carcinoma (HCC) who have undergone hepatic resection, few studies have investigated the relationship between McVI and the aberrant expression of microRNAs (miRNAs). The present study identified the miRNAs that were selectively expressed in HCC with McVI and investigated their prognostic value. Clinical data and the miRNA expression profiles of 372 patients with HCC were extracted from The Cancer Genome Atlas database. miRNAs that were differentially expressed between patients with McVI and those without vascular invasion (VI) were identified and investigated as potential prognostic factors for HCC. The results demonstrated that McVI was a significant predictor of shortened recurrence-free survival (RFS). The 3 year RFS rate in patients with HCC accompanied by McVI was 28.2 and 49.3% in HCC without VI (P<0.001). miRNA-141/-582/-9 were upregulated, while miRNA-675 was downregulated in patients with McVI when compared with HCC patients without VI. Log2 fold-changes of miRNA-141/-582/-675/-9 were 0.80 [false discovery rate (FDR), 0.005], 0.55 (FDR, 0.045), -0.99 (FDR, 0.005) and 1.22 (FDR, <0.001), respectively. Kaplan-Meier analysis indicated that the overexpression of miR-141/-582/-9 was significantly associated with poor RFS and a poor overall survival. A text mining analysis revealed that these miRNAs were significantly associated with multifaceted hallmarks of cancer, including 'invasion and metastasis'. In conclusion, the overexpression of miRNA-141/-582/-9 was associated with McVI and a poor survival in patients undergoing hepatic resection for HCC.

Preoperative neutrophil-lymphocyte ratio predicts the risk of microvascular invasion in hepatocellular carcinoma: A meta-analysis.

Preoperative estimation of microvascular invasion is of great significance for the clinical decision making in hepatocellular carcinoma. Neutrophil-lymphocyte ratio (NLR) has been reported to be correlated with the poor prognosis of hepatocellular carcinoma. However, the conclusions are conflicting on whether high preoperative NLR level is associated with the presence of microvascular invasion. To evaluate the association between preoperative NLR level and the risk of microvascular invasion in hepatocellular carcinoma. Relevant studies were identified by searching PubMed and Embase through February 2019. Fixed or random models were applied to analyze the data based on the heterogeneity. Subgroup, sensitivity, and publication bias analyses were performed. Review Manager 5.3 and STATA software were used for the meta-analysis. A total of 15 studies were eventually included in this meta-analysis. Pooled data based on retrospective cohort studies showed there are more hepatocellular carcinoma patients with vascular invasion (OR 1.74; 95% Cl 1.42, 2.12; P < 0.001) and microvascular invasion (OR 1.62 95% Cl 1.39, 1.89; P < 0.001) in the high NLR group than in the low NLR group. Of case-control studies, a higher preoperative NLR level was found in the microvascular invasion positive group than in the microvascular invasion negative group (OR 0.62; 95% Cl 0.35, 0.90; P < 0.001). The subgroup, sensitivity, and publication bias analyses did not change the results. A higher preoperative NLR level is positively correlated with the risk of microvascular invasion in hepatocellular carcinoma.

A nomogram based on bi-regional radiomics features from multimodal magnetic resonance imaging for preoperative prediction of microvascular invasion in hepatocellular carcinoma.

We aimed to develop and validate a nomogram combining bi-regional radiomics features from multimodal magnetic resonance imaging (MRI) and clinicoradiological characteristics to preoperatively predict microvascular invasion (MVI) of hepatocellular carcinoma (HCC). A total of 267 HCC patients were divided into training (n=194) and validation (n=73) cohorts according to MRI data. Bi-regional features were extracted from whole tumors and peritumoral regions in multimodal MRI. The minimum redundancy maximum relevance (mRMR) algorithm was applied to select features and build signatures. The predictive performance of the optimal radiomics signature was further evaluated within subgroups defined by tumor size and alpha fetoprotein (AFP) level. Then, a radiomics nomogram including the optimal radiomics signature, radiographic descriptors, and clinical variables was developed using multivariable regression. The nomogram performance was evaluated based on its discrimination, calibration, and clinical utility. The fusion radiomics signature derived from triphasic dynamic contrast-enhanced (DCE) MR images can effectively classify MVI and non-MVI HCC patients, with an AUC of 0.784 (95% CI: 0.719-0.840) in the training cohort and 0.820 (95% CI: 0.713-0.900) in the validation cohort. The fusion radiomics signature also performed well in the subgroups defined by the two risk factors, respectively. The nomogram, consisting of the fusion radiomics signature, arterial peritumoral enhancement, and AFP level, outperformed the clinicoradiological prediction model in the validation cohort (AUCs: 0.858 vs. 0.729; P=0.022), fitting well in the calibration curves (P>0.05). Decision curves confirmed the clinical utility of the nomogram. The radiomics nomogram can serve as a visual predictive tool for MVI in HCCs, and thus assist clinicians in selecting optimal treatment strategies to improve clinical outcomes.

Radiomics models for diagnosing microvascular invasion in hepatocellular carcinoma: which model is the best model?

ObjectivesTo explore the feasibility of diagnosing microvascular invasion (MVI) with radiomics, to compare the diagnostic performance of different models established by each method, and to determine the best diagnostic model based on radiomics.MethodsA retrospective analysis was conducted with 206 cases of hepatocellular carcinoma (HCC) confirmed through surgery and pathology in our hospital from June 2015 to September 2018. Among the samples, 88 were MVI-positive, and 118 were MVI-negative. The radiomics analysis process included tumor segmentation, feature extraction, data preprocessing, dimensionality reduction, modeling and model evaluation.ResultsA total of 1044 sets of texture feature parameters were extracted, and 21 methods were used for the radiomics analysis. All research methods could be used to diagnose MVI. Of all the methods, the LASSO+GBDT method had the highest accuracy, the LASSO+RF method had the highest sensitivity, the LASSO+BPNet method had the highest specificity, and the LASSO+GBDT method had the highest AUC. Through Z-tests of the AUCs, LASSO+GBDT, LASSO+K-NN, LASSO+RF, PCA + DT, and PCA + RF had Z-values greater than 1.96 (p<0.05). The DCA results showed that the LASSO + GBDT method was better than the other methods when the threshold probability was greater than 0.22.ConclusionsRadiomics can be used for the preoperative, noninvasive diagnosis of MVI, but different dimensionality reduction and modeling methods will affect the diagnostic performance of the final model. The model established with the LASSO+GBDT method had the optimal diagnostic performance and the greatest diagnostic value for MVI.

Value of Imaging Findings in the Prediction of Microvascular Invasion in Hepatocellular Carcinoma

BackgroundThe purpose of this study was to determine the utility of some imaging findings in predicting microvascular invasion (MVI) and hepatocellular carcinoma (HCC) recurrence risk after liver transplantation. MethodThis retrospective study included 123 patients with histopathologically proven HCC at explant. All HCCs were classified as MVI positive (group I) or negative (group II) based on histopathological findings. In each group, multifocality, largest tumor size, bulging (tumor causing liver capsule expansion), beak sign (the acute angle between the tumor and liver parenchyma), and diffusion restriction on diffusion weighted images (DWI) were evaluated. These findings were compared between the groups by Student’s t test. The relation between the parameters and MVI was analyzed by using the Spearman’s correlation test. ResultsOf the total patients, 30.1% had MVI (group I) and 69.9% (group II) did not have MVI. Presence of beak sign (P ≤ .005), bulging sign (P = .002), and diffusion restriction (P = .045) were significantly more frequent in group I than group II. The beak sign, bulging sign, and diffusion restriction were correlated with presence of MVI. Largest tumor size and multifocality were higher in group I than group II, but the differences were not statistically significant. ConclusionRadiologists and transplant surgeons should be aware of some clue imaging findings, especially beak and bulging signs because these findings may predict the presence of MVI in HCC. These patients might benefit from histologic confirmation of the tumor characteristics through biopsy and subsequent bridging treatment options before liver transplantation to reduce the risk of recurrence.

Incomplete tumor capsule on preoperative imaging reveals microvascular invasion in hepatocellular carcinoma: a systematic review and meta-analysis.

Microvascular invasion (MVI), which is difficult to diagnose before surgery, is a major factor affecting postoperative recurrence in patients with hepatocellular carcinoma (HCC). The relationship between the radiological tumor capsule and MVI is controversial. This study aimed to evaluate the association between the tumor capsule and MVI. We searched Medline (by PubMed) and Embase (by OvidSP). Two review authors independently screened titles and abstracts, selected studies about MVI prediction with radiologic tumor capsule and studies with enough data for extracted, assessed the methodological quality and collected data. Summary results were presented as the diagnostic odds ratio (DOR), sensitivity, specificity, and 95% confidence interval. Fifteen studies with 2038 patients were included; fourteen studies, including 1331 patients, with no significant heterogeneity indicated no relationship between absent tumor capsule and MVI [DOR = 0.90 (0.64, 1.26)]. Six studies, including 541 patients, with no significant heterogeneity showed incomplete capsule could be used to predict MVI of HCC preoperatively [DOR = 1.85 (1.13, 3.04)]. The overall sensitivity and specificity estimate were 0.50 (0.37, 0.64) and 0.64 (0.53, 0.74), respectively. Eight studies, including 1349 patients, with highly significant heterogeneity revealed that complete capsule could be a protective factor for MVI [DOR = 1.97 (1.01, 3.86)]. For MVI of HCC, incomplete tumor capsule is a risk factor, while a complete tumor capsule might be a protective factor. However, absent capsule doesn't show significant relationship with MVI. This might be due to combination of the risk and protective effects of present capsule in MVI.

Model-based three-dimensional texture analysis of contrast-enhanced magnetic resonance imaging as a potential tool for preoperative prediction of microvascular invasion in hepatocellular carcinoma.

The purpose of the present study was to investigate the value of contrast-enhanced magnetic resonance imaging (CE-MRI) texture analysis for preoperatively predicting microvascular invasion (MVI) in hepatocellular carcinoma (HCC). Accordingly, a retrospective study of 142 patients with pathologically confirmed HCC was performed. The patients were divided into two cohorts: The training cohort (n=99) and the validation cohort (n=43), including the MVI-positive group (n=53) and MVI-negative group (n=89). On the basis of three-dimensional texture analysis, 58 features were extracted from the preoperative CE-MR images of arterial-phase (AP) and portal-venous-phase (PP). The t-test or Kruskal-Wallis test, univariate logistic regression analysis and Pearson correlation were applied for feature reduction. Clinical-radiological features were also analyzed. Multivariate logistic regression analysis was used to build the texture model and combined model with clinical-radiological features. The MVI-predictive performance of the models was evaluated using receiver operating characteristic (ROC) analysis and presented using nomogram. Among the clinical features, a significant difference was found in maximum tumor diameter (P=0.002), tumor differentiation (P=0.026) and α-fetoprotein level (P=0.025) between the two groups in the training cohort. Four MR texture features in AP and five in PP images were identified through feature reduction. On ROC analysis, the AP texture model showed better diagnostic performance than did the PP model in the validation cohort, with an area under the curve (AUC) of 0.773 vs. 0.623, sensitivity of 0.750 vs. 0.500, and specificity of 0.815 vs. 0.926. Together with the clinical features, the combined model of AP improved the AUC, sensitivity and specificity to 0.810, 0.811 and 0.790, respectively, which was demonstrated in nomogram. To conclude, model-based texture analysis of CE-MRI could predict MVI in HCC preoperatively and noninvasively, and the AP image shows better predictive efficiency than PP image. The combined model of AP with clinical-radiological features could improve MVI prediction ability.

Postsurgical multiple-sites sampling procedure for the precise detection of microvascular invasion of hepatocellular carcinoma.

e15657 Background: Microvascular invasion (MVI) is an important risk factor of recurrence for hepatocellular carcinoma (HCC). We aimed to explore the relationship of the number of sampling sites (NuSS) and sampling location with positive rate of MVI, and investigate cut-off values for NuSS. Methods: From May 2010 to Feb 2017, 910 HCC patients undergone hepatectomy with well-preserved tissue blocks were retrospectively enrolled. Associations between NuSS and positive rates of MVI were investigated. The thresholds of NuSS according to different factors were determined by Chow test and Breakpoints function, and validated prospectively in 118 patients. In validation cohort, MVI positive rates in different sampling locations were estimated. Results: The positive rates of MVI increased as NuSS increased ( P &lt; 0.001). Tumor size and number were two factors influencing NuSS. A minimum of four, six, eight and eight sampling sites were required for detecting MVI in solitary tumors measuring 1.0-3.0 cm, 3.1-4.9 cm and ≥ 5.0 cm and multiple tumors. The positive rates of MVI as per developed thresholds were significantly higher in all the tumor subgroups of validation cohort than those in routine clinical practice in training cohort (46.7% vs. 20.6%, P= 0.048; 44.4% vs. 24.4%, P= 0.025; 73.3% vs. 50.3%, P= 0.004; 67.7% vs. 45.4%, P= 0.026). The positive rates of MVI in tumor interface were higher than those in proximal and distal paracancerous and normal liver parenchyma. Conclusions: The different thresholds of NuSS according to tumor size and number, and sampling distribution according to location provided evidences of standardized sample collection of liver cancer specimen for accurate MVI diagnosis.

Circulating cell-free tumor DNA chromosomal instability and circulating tumor cells as tools to predict microvascular invasion of hepatocellular carcinoma.

e14524 Background: Extended hepatic surgical margins, especially anatomical resections, were suggested for hepatocellular carcinoma (HCC) patients with pathological microvascular invasion (MVI) to improve patient survival. Here we investigated plasma cell-free tumor DNA (ctDNA) and circulating tumor cells as a tool to evaluate MVI before surgery. Methods: 47 treatment-naïve patients with liver lesions were recruited since June 2018, Peripheral blood samples were collected before surgery for all the individuals. Plasma cfDNA was sent to low-coverage genome-wide sequencing, followed by chromosomal instability analyses by a customized workflow UCAD. Circulating tumor cells (CTC) were analyzed by CELLSEARCH@ System. MVI was reported by pathological examination after surgery. Results: Of the 47 patients recruited, there are 32 hepatocellular carcinoma (HCC), 8 intrahepatic cholangiocarcinoma (ICC), 4 benign lesions, 1 solitary fibrous tumor, 1 neuroendocrine tumor and 1 hepatic epithelioid cell tumor by pathological examinations. MVI was also reported for HCCs. Nineteen of 32 HCC patients (59.4%) was found with elevated chromosomal instability (CIN). The most frequent changed chromosomes include 1q, 6p and 8q. Nine of 19 (47.4%) elevated CIN patients were MVI positive by pathological examinations. Among them, 4 was confirmed as MVI = 2. The other 5 was MVI = 1. 11 of 13 (84.6%) patients with low CIN were MVI negative (MVI = 0) as reported by pathological examinations. The rest 2 were reported as MVI = 1. Two of 32 HCC patients (6.25%) was found with positive CTC (tumor cell count &gt; 0). The patient with CTC = 2 was reported as MVI = 1. The other one with CTC = 1 was MVI = 0. Taking together, 20 patients (62.5%) were found either elevated ctDNA or positive CTC. 9 were confirmed as MVI negative. The overall positive predictive value is 45.0%. 12 patients (38.7%) were both ctDNA CIN low and CTC negative. 10 were confirmed as MVI negative. The negative predictive value (NPV) is 83.3%. Conclusions: Elevated circulating tumor DNA chromosomal instability has good PPV and NPV in the predicting of MVI. In such patients, anatomical hepatic resections might be recommended to improve survival.

The value of preoperative ultrasound in predicting microvascular invasion of hepatocellular carcinoma

Objective To analyze the ultrasound imaging features and clinical characteristics in patients with hepatocellular carcinoma (HCC), and assess the value of ultrasound in preoperatively predicting microvascular invasion(MVI) of HCC. Methods One hundred and seventy-one patients with HCC were retrospectively collected from January 2016 to July 2018. The ultrasound imaging features and clinical data that may be associated with MVI were analyzed by univariate and multivariate analyses, and the diagnostic efficacy of independent risk factors was further evaluated. ROC curves were plotted to compare the diagnostic efficacy of combined diagnostic mode 1, mode 2, peritumoral enhancement, and tumor margin. Results Univariate analysis showed that the serum AFP level, tumor size, peritumoral hypoechoic halo, peritumoral enhancement, and tumor margin were significantly correlated with MVI (P<0.05). Multivariate logistic regression analysis further indicated that peritumoral enhancement and non-smooth tumor margin were the independent risk factors for predicting MVI. The sensitivity, specificity, positive predictive value and negative predictive value of peritumoral enhancement and non-smooth tumor margin were 51.4% vs 83.8%, 81.4% vs 48.5%, 67.9% vs 55.4%, and 68.7% vs 79.7%, respectively. The AUC of mode 1, mode 2, peritumoral enhancement and tumor margin were 0.741, 0.716, 0.664, and 0.661, respectively. Conclusions Preoperative ultrasound is valuable in predicting MVI of HCC. Peritumoral enhancement and non-smooth tumor margins are independent risk factors for predicting MVI of HCC. Tumor size, hypoechoic halo around the tumor, and serum AFP levels must be taken into account when predicting MVI of HCC by using preoperative ultrasound. Key words: Ultrasonography; Carcinoma, hepatocellular; Contrast-enhanced ultrasound; Microvascular invasion; Risk factors

Radiomic features to predict microvascular invasion in hepatocellular carcinoma based on conventional MRI: preliminary findings

Objective To identify the preoperative MRI findings for predicting microvascular invasion (MVI) using texture analysis (TA) on multiple MRI sequences. Methods Two hundred and fifty patients with HCC pathologically confirmed by surgery in Zhongshan Hospital from October 2015 to October 2016 were analyzed retrospectively. All patients underwent conventional MRI plain scan and dynamic contrast-enhanced examination within 2 weeks before operation. According to the ratio of 1∶1, the patients were divided into a training set (125 cases) and a test set (125 cases).The training set was used to establish a classifier to predict MVI of HCCs via the TA, and the test set was used to evaluate the performance of the classifier. An image analysis was performed using an in-house software contained a set of 2 415 features which were generated from all conventional axial sequences, including the T2WI, DWI, ADC map, and dynamic enhancement images.. A four-fold cross validation (FFCV) and sequential forward floating feature selection strategy (SFFS) were employed to select an optimal subset of features and a linear discriminant analysis (LDA) was employed to establish a classifier. The clinical laboratory examination, morphologic characteristics and quantitative analysis of conventional MR were used to compare the performance of predicting MVI with the classifier. A Chi-squared test or Fisher exact probablities test were used for categorical variables, and independent t test or Mann-Whitney U test were used for used for continuous variables. Factors with a P value less than 0.05 at univariate analyses were entered into the multivariate model to identify independent predictors. The Hosmer-Lemeshow test was performed to explain the goodness of fit of the multivariate logistic model. A receiver operating characteristic curve analysis was performed to evaluate the diagnostic performance. Results The classifier set up by the training set consists of 13 texture features. When conventional MRI texture features of test set were used to judge whether there was MVI or not, the AUC of all texture features of arterial phase (AP) was the highest (0.506 3). Univariate regression analysis showed that there were significant differences in pathological grade (P=0.026), AFP level (P=0.033), lesion edge shape (P=0.038), AP enhancement (P=0.038), and AP peritumoral enhancement (P=0.008). Multivariate binary logistic regression analysis showed that peritumoral enhancement and texture classifier assessed MVI with P values of 0.005 and 0.001,which were independent risk factors for MVI. The significance level of Hosmer Lemeshow test was 0.796, indicating the goodness of fit of acceptable models. The AUCs of single variable, combined variable (including of AFP level, irregular tumor margin, enhancement intensity in AP and peritumoral enhancement in AP) and texture classifier for MVI were 0.588 to 0.627, 0.798 and 0.733, respectively. When compared the AUC of the combination features (including of AFP level, irregular tumor margin, enhancement intensity in AP and peritumoral enhancement in AP) with the classifier to identify MVI of HCC in the test set, no significant difference was found(P=0.108 6). However, although the sensitivity of them were same as 70.73%, the specificity of the combination features was mildly higher than that of classifier (82.14% vs. 78.57%). Conclusions Combination features of AFP level, tumor margin, enhancement intensity in AP and peritumoral enhancement in AP can be used to predict MVI of HCCs. It is a new method of noninvasive evaluation of MVI before operation. The performance of the classifier made by TA was not superior to that of combination features based on clinic and conventional MR sequences. Key words: Liver neoplasms; Magnetic resonance imaging; Radiomics; Microvascular invasion

Diagnosis and treatment of microvascular invasion in hepatocellular carcinoma

Microvascular invasion (MVI) is currently only confirmed by histopathological studies of surgical specimens. Preoperative diagnosis of MVI combined with clinical treatment is still a research problem and direction in hepatocellular carcinoma (HCC). How to assess the presence of MVI early and give appropriate treatment has become a research hotspot. This review focuses on recent advances in MVI-related research, including the use of serum markers, tumor tissue markers, and new imaging techniques to predict MVI, as well as the molecular biology mechanisms and therapeutic advances in MVI. The emergence of MVI may be caused by the interaction of many complex biological processes and various pathogenic factors. We need to try to select several risk factors and establish a systematic evaluation method to solve their respective deficiencies, so as to provide more practical applications for the preoperative prediction of MVI program. Simultaneously, the preoperative, intraoperative, and postoperative comprehensive treatment strategies for MVI are particularly important. The presence of MVI is thought to reflect increased capacity for local infiltration and distant metastases and affects the prognosis of HCC patients. To accurately assess MVI early based on some biomarkers prior to surgery, we need to work hard to explore and integrate various treatments to create a personalized treatment plan for MVI.

Predictive model for microvascular invasion of hepatocellular carcinoma among candidates for either hepatic resection or liver transplantation

BackgroundMicrovascular invasion is the strongest prognostic factor of survival in patients with hepatocellular carcinoma. We therefore developed a predictive model for microvascular invasion of hepatocellular carcinoma to help guide treatment strategies in patients scheduled for either hepatic resection or liver transplantation. MethodsPatients with hepatocellular carcinoma who underwent hepatic resection or liver transplantation from 1994 to 2016 were divided into training and validation cohorts. A predictive model for microvascular invasion was developed based on microvascular invasion risk factors in the training cohort and validated in the validation cohort. ResultsA total of 910 patients (425 having received hepatic resection, 485 having received liver transplantation) were included in the training (n = 637) and validation (n = 273) cohorts. Multivariate analysis identified α-fetoprotein ≥100 ng/mL (relative risk 3.05, P < .0001), tumor size ≥40 mm (relative risk 1.98, P = .0002), nonboundary hepatocellular carcinoma type (relative risk 1.91, P = .001), neutrophil-to-lymphocyte ratio (relative risk 1.86, P = .002), and aspartate aminotransferase (relative risk 1.53, P = .02) as associated with microvascular invasion. The estimated probability of microvascular invasion ranged from 17.0% in patients with none of these factors to 86.9% in the presence of all factors. This model achieved a C-index of 0.732 in the validation cohort. The 5-year overall survival of patients with ≥50% probability of microvascular invasion was poorer than that of patients with <50% probability (hepatic resection; 39.1% vs 61.2%, P < .0001, liver transplantation; 5-year overall survival, 54.8% vs 79.0%, P = .05). ConclusionThis model developed from preoperative data allows reliable prediction of microvascular invasion in candidates for either hepatic resection or liver transplantation.

Influencing factors analysis of microvascular invasion in patients with hepatocellular carcinoma

Objective To evaluate the correlation between microvascular invasion(MVI ) and prognosis in patients with hepatocellular carcinoma (HCC), and to analyse the influencing factors of MVI in patients with HCC. Methods Total of 81 patients with hepatocellular carcinoma treated in Beijing Hospital from January 2014 to December 2016 were retrospectively studied. There were 65 males and 16 females. The mean age was 59.6±12.7 years, and the age ranged from 21 to 87 years old. Pathological examination showed presence of MVI in 35 patients. Results Total of seventy-six patients with hepatocellular carcinoma were followed-up. The 1-, 2-, 3- and 4-year overall survival rates in the 35 patients with microvascular invasion of hepatocellular carcinoma were 78.6%, 55.4%, 38.3%, and 32.2%, respectively. The 1-, 2-, 3-, and 4-year overall survival rates of the 41 patients without microvascular invasion were 93.4%, 76.5%, 68.2% and 68.2%, respectively. The difference was significant (P 0.05). Multivariate logistic regression analysis showed the maximum diameter of tumor >5 cm (OR=6.340, 95%CI: 2.000~20.096), preoperative total bilirubin (TBil)>17 μmol/L (OR=5.067, 95%CI: 1.386~18.525), and preoperative alpha-fetoprotein (AFP)>400 μg/L (OR=6.042, 95%CI: 1.435~25.444) were independent risk factors of microvascular invasion (P<0.05). Conclusion Hepatocellular carcinoma patients with microvascular invasion had poor prognosis. Preoperative AFP, preoperative TBil, and diameter of tumor were independent risk factors of microvascular invasion in patients with hepatocellular carcinoma. Key words: Carcinoma, hepatocellular; Prognosis; Microvascular invasion; Influencing factors

Effect of hepatitis B virus DNA replication level and anti-HBV therapy on microvascular invasion of hepatocellular carcinoma

BackgroundChronic hepatitis B virus (HBV) infection is a major risk factor for the occurrence and development of cirrhosis and hepatocellular carcinoma (HCC). Microvascular invasion (MVI) of HCC is closely related to postoperative recurrence. We aimed to investigate the effect of HBV DNA replication levels and anti-HBV treatment on the occurrence of MVI in HCC.MethodsA retrospective analysis of the clinical and pathological data of 660 patients undergoing hepatectomy for hepatocellular carcinoma at the Affiliated Hospital of Qingdao University from January 2015 to December 2017 is included in this study.ResultsThis study involved a total of 660 patients with an MVI incidence rate of 46.8% (309/660). Univariate analysis revealed that positive HBV surface antigen (HBsAg), detectable HBV DNA load, and administration of antiviral treatment were significantly associated with the formation of MVI. Multivariable logistic regression analysis in patients with positive seral HBsAg showed that detectable HBV DNA load (OR = 5.33, P < 0.001) was an independent risk factor for MVI. Antiviral treatment for more than six months (OR = 0.37, P = 0.002) was an independent protective factor against MVI. Patient groups with severe MVI had significantly higher rates of HBV infection (P = 0.017), a detectable HBV DNA load (> 100 IU/ml) rate (P < 0.001), and obvious low antiviral treatment rate (P = 0.021).ConclusionsHBV DNA replication level is an independent risk factors for the formation of HCC MVI, and anti-hepatitis B virus treatment has an inhibitory effect on MVI formation.

Microvascular invasion in hepatocellular carcinoma: is it predictable with quantitative computed tomography parameters?

Objective To investigate whether quantitative computed tomography (CT) measurements can predict microvascular invasion (MVI) in hepatocellular carcinoma (HCC).Materials and Methods This was a retrospective analysis of 200 cases of surgically proven HCCs in 125 consecutive patients evaluated between March 2010 and November 2017. We quantitatively measured regions of interest in lesions and adjacent areas of the liver on unenhanced CT scans, as well as in the arterial, portal venous, and equilibrium phases on contrast-enhanced CT scans. Enhancement profiles were analyzed and compared with histopathological references of MVI. Univariate and multivariate logistic regression analyses were used in order to evaluate CT parameters as potential predictors of MVI.Results Of the 200 HCCs, 77 (38.5%) showed evidence of MVI on histopathological analysis. There was no statistical difference between HCCs with MVI and those without, in terms of the percentage attenuation ratio in the portal venous phase (114.7 vs. 115.8) and equilibrium phase (126.7 vs. 128.2), as well as in terms of the relative washout ratio, also in the portal venous and equilibrium phases (15.0 vs. 8.2 and 31.4 vs. 26.3, respectively).Conclusion Quantitative dynamic CT parameters measured in the preoperative period do not appear to correlate with MVI in HCC.

Long noncoding RNA microvascular invasion in hepatocellular carcinoma is an indicator of poor prognosis and a potential therapeutic target in gastric cancer.

Long noncoding RNAs (lncRNAs) have been shown to have a fundamental role in cancer initiation and development. LncRNA microvascular invasion in hepatocellular carcinoma (MVIH) has been identified as a potential prognostic marker in several cancers; however, its role in gastric cancer (GC) has not been elucidated. A total of 152 tissue samples from patients underwent GC surgical resection in Linyi People's Hospital between 2007 and 2010 were collected. Quantitative real-time polymerase chain reaction was conducted to examine the expression level of lncRNA MVIH. The selection of clinically important cut-off scores for MVIH expression was based on receiver operating characteristic curve analysis. Then, the association between MVIH and GC clinicopathological parameters was analyzed. Moreover, univariate and multivariate Cox regression analysis were performed to reveal the relationship between MVIH and GC prognosis. GC tissues exhibited a higher lncRNA MVIH expression level than paired nontumoros tissues. High MVIH level was revealed to be associated with the T stage, tumor-node-metastasis (TNM) stage and lymphatic metastasis of GC. Specially, patients with high MVIH expression level showed significantly shorter overall survival rate and progression-free survival rate. Moreover, invasion depth, distant metastasis, TNM stage, and MVIH expression were identified as risk factors of GC poor prognosis on univariate Cox regression analyses. By further analyzing these factors with multivariate logistic regression, high MVIH, and distant metastasis were discovered to be independent risk factors of GC prognosis. High MVIH is an independent risk factor of GC prognosis. LncRNA MVIH may serve as a potential therapeutic target and a prognostic marker of GC patients.

Total tumor volume based prediction model for microvascular invasion in hepatocellular carcinoma

Total tumor volume based prediction model for microvascular invasion in hepatocellular carcinoma