Safety and efficacy of catheter ablation of para-Hisian accessory pathway via a direct superior vena cava approach: A multicenter study.

BACKGROUND: Radiofrequency (RF) catheter ablation of para-Hisian accessory pathways (APs) can be challenging due to proximity to the conduction system. METHODS: A total of 30 consecutive patients with para-Hisian AP were enrolled for ablation in three centers, 12 (40%) of whom had previously failed attempted ablation from the inferior vena cava (IVC) approach. Ablation was preferentially performed using a superior approach from the superior vena cava (SVC) in all patients. RESULTS: The para-Hisian AP was eliminated from the SVC approach in 28 of 30 (93.3%) patients. In the remaining two patients, additional ablation from IVC was required to successfully eliminate the AP. There were two patients experienced reversible complete atrial-ventricular block and PR prolongation during the first RF application. Long-term freedom from recurrent arrhythmia was achieved in 29 (96.7%) patients over a mean follow-up duration of 15.6 ± 4.6 months. CONCLUSION: Catheter ablation of para-Hisian AP from above using a direct SVC approach is both safe and effective, and should be considered especially in patients who have failed conventional ablation attempts from IVC approach.

Exosome is involved in liver graft protection after remote ischemia reperfusion conditioning.

BACKGROUND: Remote ischemic perconditioning (RIPerC) has been demonstrated to protect grafts from hepatic ischemia-reperfusion injury (IRI). This study investigated the role of exosomes in RIPerC of liver grafts in rats. METHODS: Twenty-five rats (including 10 donors) were randomly divided into five groups (n = 5 each group): five rats were used as sham-operated controls (Sham), ten rats were for orthotopic liver transplantation (OLT, 5 donors and 5 recipients) and ten rats were for OLT + RIPerC (5 donors and 5 recipients). Liver architecture and function were evaluated. RESULTS: Compared to the OLT group, the OLT + RIPerC group exhibited significantly improved liver graft histopathology and liver function (P < 0.05). Furthermore, the number of exosomes and the level of P-Akt were increased in the OLT + RIPerC group. CONCLUSIONS: RIPerC effectively improves graft architecture and function, and this protective effect may be related to the increased number of exosomes. The upregulation of P-Akt may be involved in underlying mechanisms.

Cryoballoon ablation of persistent atrial fibrillation for de novo pulmonary vein isolation: a single-center follow-up study.

BACKGROUND: Pulmonary vein isolation (PVI) alone for persistent atrial fibrillation (PersAF) remains controversial. The characteristics of cryoballoon ablation (CBA) to treat PersAF and the blanking period recurrence are underreported. METHODS: This study retrospectively analyzed patients with PersAF undergoing second-generation CBA for de novo PVI. The post-procedural efficacy and survival analysis were compared between patients with different PersAF durations. The multivariate Cox regression analysis was used to detect the risk factors for recurrence. Early and long-term recurrence were analyzed relative to each other. RESULTS: A total of 329 patients were enrolled, with a median PersAF duration of 4.0 months (interquartile range: 2.0-12.0 months); 257 patients (78.1%) were male. Kaplan-Meier analysis of freedom from atrial fibrillation recurrence at 12, 24, and 30 months showed 71.0%, 58.5%, and 54.9%, respectively. Early PersAF had a relatively favorable survival rate and a narrow P-wave duration of restoring sinus rhythm compared with that of PersAF lasting more than three months (P < 0.05). The multivariate Cox regression analysis revealed that PersAF duration and left atrial anteroposterior diameter ≥ 42 mm were the risk factors for atrial fibrillation recurrence after CBA [hazard ratio (HR) = 1.89, 95% CI: 1.01-1.4, P = 0.042; HR = 3.6, 95% CI: 2.4-5.4, P < 0.001, respectively]. The blanking period recurrence predicted the long-term recurrence (P < 0.0001). CONCLUSIONS: CBA of PersAF had safety and efficacy to reach de novo PVI. The PersAF duration and left atrial size were risk factors for atrial fibrillation recurrence after CBA. Blanking period recurrence was associated with long-term recurrence.

Risk of New-Onset Atrial Fibrillation Post-cavotricuspid Isthmus Ablation in Typical Atrial Flutter Without History of Atrial Fibrillation.

Aims: The aim was to describe the incidence of atrial fibrillation (AF) after cavotricuspid isthmus (CTI) ablation in patients with typical atrial flutter (AFL) without history of AF and to identify risk factors for new-onset AF after the procedure. Methods: A total of 191 patients with typical AFL undergoing successful CTI ablation were enrolled. Patients who had history of AF, structural heart disease, cardiac surgery, or ablation or who received antiarrhythmic drug after procedure were excluded. Clinical and electrophysiological data were collected. Results: There were 47 patients (24.6%) developing new AF during a follow-up of 3.3 ± 1.9 years after CTI ablation. Receiver operating characteristic (ROC) curves indicated that the cut-off values of left atrial diameter (LAD) and CHA2DS2-VASc score were 42 mm and 2, with area under the curve of 0.781 and 0.550, respectively. The multivariable Cox regression analysis revealed that obstructive sleep apnea (OSA) [hazard ratio (HR) 3.734, 95% confidence interval (CI) 1.470-9.484, P = 0.006], advanced interatrial block (aIAB) (HR 2.034, 95% CI 1.017-4.067, P = 0.045), LAD > 42 mm (HR 2.710, 95% CI 1.478-4.969, P = 0.001), and CHA2DS2-VASc score > 2 (HR 2.123, 95% CI 1.118-4.034, P = 0.021) were independent risk factors of new-onset AF. Conclusion: A combination of OSA, aIAB, LAD > 42 mm, and CHA2DS2-VASc > 2 was a strongly high risk for new-onset AF after ablation for typical AFL, and it had significance in postablation management in clinical practice.

Predictors and Long-Term Outcome of Ablation of Discrete Pre-potentials in Patients With Idiopathic Ventricular Arrhythmias Originating From the Aortic Sinuses of Valsalva.

Background: The predictability and long-term outcome of the discrete pre-potential (DPP) of idiopathic ventricular arrhythmias (VAs) arising from the aortic sinuses of Valsalva (ASV) have not been fully identified. Methods: Of 687 consecutive patients undergoing ablation of outflow tract VAs, there were 105 (15.3%) patients with VAs originating from the ASV region who were included. Detailed mapping was performed within the ASV in all patients. Electrocardiographic, electrophysiological parameters, and long-term success rate were compared between patients with and without the DPPs. Results: A DPP was recorded in 67 of 105 (63.8%) patients, including 38 left sinus of Valsalva (LSV)-VAs (38/105, 36.2%) and 29 right sinus of Valsalva (RSV)-VAs (29/105, 27.6%). The patients with DPPs had wider QRS duration (152 ± 17 vs. 145 ± 14 ms, p < 0.001). The average of earliest activation time was significantly earlier in patients with DPPs (-38.6 ± 8.5 vs. -27.7 ± 5.7 ms, p < 0.001). Mean time from the first lesion to elimination of VAs was shorter in patients with DPPs (2.3 ± 2.1 s vs. 4.9 ± 1.0 s, p < 0.001). A stepwise logistic multivariable analysis identified only younger age as a significant predictor of DPP (age ≤ 35.5 years predicted DPP with 92.9% positive predictive value). During a follow-up duration of 42.5 ± 22.3 months, 63 (94.0%) patients with DPPs and 30 (78.9%) patients without DPPs remained free of recurrent VAs (p = 0.027). Conclusion: Discrete pre-potentials were observed in 63.8% of patients with VAs arising from the ASV. Ablation in patients with DPPs was associated with higher long-term success. DPPs were seen more commonly in younger (age ≤ 35.5 years) patients.

Safety and Efficacy Using the Second-Generation Cryoballoon in Patients With Atrial Fibrillation and a Common Ostium of Inferior Pulmonary Veins.

Background: Common ostium of inferior pulmonary veins (COIPV) is a kind of pulmonary vein variation. The safety and efficacy of COIPV isolation using the second-generation cryoballoon (CB) ablation remain unknown. Methods: A total of 10 patients with COIPV from a consecutive series of 1,751 patients with atrial fibrillation (AF) were included. Pulmonary vein isolation (PVI) was performed using the second-generation CB. Results: The prevalence of a COIPV was 0.57% in this study. PVI was achieved in all pulmonary veins (PVs) without the need for a touch-up. A segmental freeze strategy was applied for each inferior PV, respectively. The mean number of freeze cycles of inferior PVs was 1.4 ± 0.5 for the left inferior pulmonary vein (LIPV), and 2.0 ± 0.9 for the right inferior pulmonary vein (RIPV). Pulmonary vein potential (PVP) of RIPV could not be monitored in real-time in three cases. Eight of 10 patients (80%) were free from atrial arrhythmias without the use of antiarrhythmic drugs during a follow-up period of 23.6 ± 12.9 months. No procedure-related complications occurred in any of the 10 patients. Conclusions: Common ostium of inferior pulmonary veins is a rare but challenging PV variant. PVI with this unusual anatomic variation using the second-generation 28-mm CB is effective and safe.

Novel Clue to Locate Conduction Gaps in the Pulmonary Vein Isolation Ablation Line.

Background: Several methods have been reported for locating the conduction gap (CG) in the pulmonary vein isolation (PVI) ablation line. However, the value of the interval between far-field atrial potential (FFP) and pulmonary vein potential (PVP) remains unknown. Methods: Consecutive patients with a CG during observation on the table after PVI were included. The PVP, FFP, and the CG location were evaluated to develop a novel algorithm to identify the CG location in the left superior pulmonary vein. The performance of this novel algorithm was prospectively tested in a validation cohort of consecutive patients undergoing repeat PVI ablation. Results: A total of 116 patients with atrial fibrillation (AF) were recruited, 56 of whom formed the validation cohort. The interval between FFP and PVP of the left superior pulmonary vein was associated with the CG location, and an interval <5 ms predicted the presence of CG in the upper portion of the ostium with a sensitivity of 92.9% and a specificity of 96.9%. In the prospective evaluation, the interval was able to correctly predict the site of CG in 89.6% of cases. Conclusions: The interval between FFP and PVP is a novel and accurate index that can be used to predict the CG location in the left superior pulmonary vein. An far-field atrial potential and pulmonary vein potential (FFP-PVP) interval value of ≥5 ms could be used to exclude a CG in the upper portion of the ostium in the majority of patients undergoing AF ablation.

Key factors and potential drug combinations of nonalcoholic steatohepatitis: Bioinformatic analysis and experimental validation-based study.

BACKGROUND: Nonalcoholic fatty liver disease and its advanced stage, nonalcoholic steatohepatitis (NASH), are the major cause of hepatocellular carcinoma (HCC) and other end-stage liver disease. However, the potential mechanism and therapeutic strategies have not been clarified. This study aimed to identify potential roles of miRNA/mRNA axis in the pathogenesis and drug combinations in the treatment of NASH. METHODS: Microarray GSE59045 and GSE48452 were downloaded from the Gene Expression Omnibus and analyzed using R. Then we obtained differentially expressed genes (DE-genes). DAVID database was used for Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment pathway analysis. Protein-protein interaction (PPI) networks were used for the identification of hub genes. We found upstream regulators of hub genes using miRTarBase. The expression and correlation of key miRNA and its targets were detected by qPCR. Drug Pair Seeker was employed to predict drug combinations against NASH. The expression of miRNA and hub genes in HCC was identified in the Cancer Genome Atlas database and Human Protein Atlas database. RESULTS: Ninety-four DE-genes were accessed. GO and KEGG analysis showed that these predicted genes were linked to lipid metabolism. Eleven genes were identified as hub genes in PPI networks, and they were highly expressed in cells with vigorous lipid metabolism. hsa-miR-335-5p was the upstream regulator of 9 genes in the 11 hub genes, and it was identified as a key miRNA. The hub genes were highly expressed in NASH models, while hsa-miR-335-5p was lowly expressed. The correlation of miRNA-mRNA was established by qPCR. Functional verification indicated that hsa-miR-335-5p had inhibitory effect on the development of NASH. Finally, drug combinations were predicted and the expression of miRNA and hub genes in HCC was identified. CONCLUSIONS: In the study, potential miRNA-mRNA pathways related to NASH were identified. Targeting these pathways may be novel strategies against NASH.

Outcomes of Different Ablation Approaches for Para-Hisian Accessory Pathway and Ablation Safety at Each Site.

BACKGROUND: This study describes the electrophysiologic characteristics of the para-hisian accessory pathway (AP), the outcome of different ablation approaches, and ablation safety at different sites. METHOD: A total of 120 patients diagnosed as para-hisian AP were included in this study. The electrophysiologic characteristics and outcomes at different ablation sites were analyzed. RESULTS: In total, 107 APs and 13 APs were diagnosed as right anteroseptal (RAS) and right midseptal (RMS), respectively. The significant ECG difference between RAS and RMS was lead III, which mainly manifested as positive and negative delta waves, respectively. Catheter trauma to AP was recorded in 21 of 120 (17.5%) patients. The recurrence rate of direct ablation at the "bumped" sites was higher than the conventional ablation method (37.5 vs. 14.1 %, p = 0.036). For RAS APs, there was no significant difference in the success rate between the inferior vena cava (IVC) and superior vena cava (SVC) approaches (76.6 vs. 73.3%, p = 0.63). The RAS was separated into three regions: (1) Site 1: superior part above the real "His" recorded site with far-field "His" potential; (2) Site 2 (true para-hisian): the site with near-field "His" potential; and (3) Site 3: inferior part below the biggest real "His" with far-field "His" potential. Mid-septal was defined as an area that is bounded anteriorly by His recording location and posteriorly by the roof of coronary sinus (CS) ostium. The incidence of atrioventricular (AV) conduction injury at different sites was as follows: 3 of 6 (50%) at Site 2, 4 of 13 (30.8%) at RMS, 7 of 34 (20.6%) at Site 3, and 3 of 46 (6.5%) at Site 1. Even if ablation was performed at the atrial side of the para-hisian region, the right bundle branch block (RBBB) was caused in 6 patients (5%). CONCLUSION: Ablation via IVC or SVC was comparative for para-hisian APs, but not for the noncoronary cusp (NCC) approach. The AV conduction injury risk ranks as follows: Site 2 > RMS > Site 3 > Site 1. RBBB could be caused while ablating at the atrial side, which could further demonstrate the His bundle longitudinal dissociation theory.

Comparison of Using Second-Generation Cryoballoon and Radiofrequency Catheter for Atrial Fibrillation Ablation in Patients With the Common Ostium of Inferior Pulmonary Veins.

Aims: To compare the procedural outcomes of cryoballoon ablation (CBA) and radiofrequency ablation (RFA) in atrial fibrillation (AF) patients with the common ostium of inferior pulmonary veins (COIPV) and to explore the effect of COIPV on CBA performance through the assessment of anatomical factors. Methods: A total of 18 AF patients with COIPV were included. Pulmonary vein isolation (PVI) was performed with second-generation CBA or RFA. The anatomical characteristics of COIPV and procedural outcomes were collected. Results: The prevalence of COIPV was 0.82% in the enrolled population. PVI was achieved in all pulmonary veins (PVs) without any complications. The "tricircle" strategy was applied for RFA, and the segmental freeze strategy was performed for CBA. Compared with RFA, CBA had shorter procedural time (median: 53.0 vs. 78.0 min, p < 0.001) and longer fluoroscopy time (median: 13.5 vs. 6.0 min, p < 0.001). Higher ovality index of the ostium was seen in patients with ≥4 freezes in inferior PVs [IPVs; 0.95 (0.78-1.05) vs. 0.49 (0.21-0.83), p = 0.047]. During a median of 23.5 months of follow-up, the atrial arrhythmias-free survival after the procedure was comparable between CBA and RFA (p = 0.729). Conclusion: The second-generation CBA is an efficient and safe alternative for RFA in AF patients with COIPV. Anatomical characteristics of COIPV bring the challenge to the procedure performance of RFA and CBA.

Endoplasmic reticulum stress triggers delanzomib-induced apoptosis in HCC cells through the PERK/eIF2α/ATF4/CHOP pathway.

For limited clinical benefits and acquired resistance by sorafenib, new therapeutic strategies and molecular targets for the treatment of advanced hepatocellular carcinoma (HCC) are urgently needed. This study aimed to evaluate the potential antitumor effects of the second-generation proteasome inhibitor delanzomib on HCC. The results demonstrated that delanzomib displayed excellent antitumor activity on HCC cells with sensitivity or resistance to sorafenib in a time- and dose-response manner, by inducing G2/M cell cycle arrest and apoptosis in vitro. Cell cycle arrest was associated with the activation of p21/Cdc2/cyclin B1 pathway, and cell apoptosis was confirmed by PARP and caspase-3 cleavage. In addition, delanzomib induced endoplasmic reticulum stress (ERS) in HCC cells by activating the PERK and ERS-associated proteins including p-eIF2α, ATF4 and CHOP. Selective inhibition of eIF2α dephosphorylation by salubrinal could significantly reduce delanzomib-induced apoptosis in HCC cells. In vivo, delanzomib could also exhibit effective antitumor properties on patient-derived xenograft mouse model of HCC with relative low drug-associated cytotoxicity. Compared to control group, 3 and 10 mg/kg of delanzomib significantly reduced the tumor volume by 33.1% and 87.2% respectively after 3 weeks treatment, with no significant change on the body weight and the level of serum biochemical indexes including ALT, AST and BUN. In conclusion, delanzomib could exhibit good pre-clinical antitumor effects against HCC cells by inducing ERS and activating the PERK/eIF2α/ATF4/CHOP pathway, as potential drug candidate on treatment of advanced HCC patients.

Cancer-Testis Gene Expression in Hepatocellular Carcinoma: Identification of Prognostic Markers and Potential Targets for Immunotherapy.

BACKGROUND: Cancer-testis genes can serve as prognostic biomarkers and valuable targets for immunotherapy in multiple tumors because of their restricted expression in testis and cancer. However, their expression pattern in hepatocellular carcinoma is still not well understood. The purpose is to comprehensively characterize the cancer-testis gene expression in hepatocellular carcinoma as well as identify prognostic markers and potential targets for immunotherapy. METHODS: Cancer-testis database and publicly available data sets reporting new cancer-testis genes were integrated, and then restricted them in a testis and hepatocellular carcinoma expression pattern. Pathway enrichment analysis and survival analysis were conducted to evaluate the biological function and prognostic effect of cancer-testis genes. Clustering analysis and coexpression analysis were performed to illustrate cancer-testis gene expression patterns in hepatocellular carcinoma. The association of gene expression of each cancer-testis gene to the corresponding methylation status was detected. Finally, we explored the associations between cancer-testis genes and CD8+ T-cell infiltration in hepatocellular carcinoma by TISIDB, and then validated it in an independent hepatocellular carcinoma cohort with 72 patients. RESULTS: A total of 59 testis-specific genes were identified highly expressed in hepatocellular carcinoma. Pathway enrichment analysis revealed that cancer-testis genes in hepatocellular carcinoma significantly involves in the process of cell cycle regulation. Most of the cancer-testis genes were coexpressed, and cluster analysis suggested that cancer-testis gene expressed in hepatocellular carcinoma is independent of sex, hepatitis status, and histology type. We also found that demethylation might be a regulatory mechanism of cancer-testis gene expression in hepatocellular carcinoma. Survival analysis indicated that cancer-testis genes could predict the prognosis of patients with hepatocellular carcinoma. Furthermore, BUB1B was identified contributing to the resistance of CD8+ T-cell infiltration in hepatocellular carcinoma and was an independent prognostic factor both for overall survival and disease-free survival. CONCLUSIONS: Our analysis enables better understanding of cancer-testis genes in hepatocellular carcinoma and provides potential targets for hepatocellular carcinoma treatment. Experimental and clinical studies are needed for further validations.

Hangzhou criteria as downstaging criteria in hepatocellular carcinoma before liver transplantation: A multicenter study from China.

BACKGROUND: The downstaging of hepatocellular carcinoma (HCC) has been confirmed to benefit liver transplantation (LT) patients whose tumors are beyond the transplantation criteria. Milan criteria (MC), a tumor size and number-based assessment, is currently used as the endpoint in these patients. However, many studies believe that tumor biological behavior should be added to the evaluation criteria for downstaging efficacy. Hence, this study aimed to explore the feasibility of Hangzhou criteria (HC), which introduced tumor grading and alpha-fetoprotein in addition to tumor size and number, as an endpoint of downstaging. METHODS: We performed a multicenter and retrospective study of 206 patients accepted locoregional therapy (LRT) as downstaging/bridge treatment prior to LT in three centers of China. RESULTS: Recipients were divided into four groups: failed downstaging to the HC (group A, n = 46), successful downstaging to the HC (group B, n = 30), remained within the HC all the time (group C, n = 113), and tumor progressed (group D, n = 17). The 3-year HCC recurrence probabilities of groups B and C were not significantly different (10.3% vs. 11.6%, P = 0.87). The HCC recurrent rate was significantly higher in group A (52.3%) compared with that in group B/C (P < 0.05). Seven patients (7/76, 9.2%) whose tumor exceeded the the HC were successfully downstaged to the MC, and 39.5% (30/76) to the the HC. In group B, 23 patients remained beyond the MC and their survivals were as well as those of patients within the MC. CONCLUSIONS: Compared to the MC, HC downstaging criteria can give more HCC patients access to LT and furthermore, the outcome of these patients is the same as those matching MC downstaging criteria. Hangzhou downstaging criteria therefore is applicable in clinical practice.

Electrical isolation of the superior vena cava using second-generation cryoballoon in patients with atrial fibrillation.

BACKGROUND: The safety and efficacy of superior vena cava (SVC) isolation using second-generation cryoballoon (CB) ablation remain unknown. METHODS: A total of 26 (3.2%) patients with SVC-related paroxysmal atrial fibrillation (AF) from a consecutive series of 806 patients who underwent second-generation CB were included. Pulmonary vein isolation was initially achieved by CB ablation. If the SVC trigger was determined, the electrical isolation of SVC isolation was performed using the second-generation CB. RESULTS: Real-time SVC potential was observed in all patients. Isolation of the SVC was successfully accomplished in 21 (80.8%) patients. The mean number of freeze cycles in each patient was 2.1 ± 1.1. The mean time to isolation and ablation duration were 22.5 ± 14.2 seconds and 94.5 ± 22.3 seconds, respectively. A transient phrenic nerve (PN) injury was observed in five patients (19.2%). There were two patients (7.7%) experienced reversible sinus node injury during the first application. During a mean follow-up period of 13.2 ± 5.8 months, four patients (15.4%) had atrial arrhythmia recurrences. CONCLUSION: Isolation of SVC using the second-generation 28-mm CB is feasible when SVC driver during AF is identified. Vigilant monitoring of PN function during CB ablation of SVC is needed to avoid PN injury.

Erratum to: Exosome-derived galectin-9 may be a novel predictor of rejection and prognosis after liver transplantation.

Erratum to: J Zhejiang Univ-Sci B (Biomed & Biotechnol) 2019 20(7):605-612. https://doi.org/10.1631/jzus.B1900051. The original version of this article unfortunately contained a mistake. In p.605, the number of the Zhejiang Provincial Natural Science Foundation of China (No. Y17H160118) in Funding is incorrect. The correct number should be LY17H160026, which is the approval number of the project, whereas Y17H160118 is the application number of the project.

Macrovascular Endothelial Cells Enhance the Motility of Liver Cancer Cells by Up-regulation of MMP-3, Activation of Integrin/FAK Signaling Pathway and Induction of Non-classical Epithelial-mesenchymal Transition.

Background: Liver cancer with portal vein tumor thrombus (PVTT) indicates a serious prognosis. The molecular mechanism of PVTT formation is not totally clarified, the invasion of blood vessels by liver cancer cells is the key step and portal vein endothelial cells plays critical role. Methods: Conditioned medium (CM) of human umbilical vein endothelial cells (HUVEC) were used to culture liver cancer cells and prostate cancer cells for cell motility and viability analysis for the purpose of simulating the role of macrovascular endothelial cells in the development of liver cancer. Results: HUVEC-CM caused long spindle-shaped changes in liver cancer cells; the invasion and migration ability of Bel-7402 and MHCC-LM3 (cultured in HUVEC-CM) increased significantly. Integrins/FAK (focal adhesion kinase) signaling pathway was activated and MMP-3 was up-regulated. However, classical epithelial-mesenchymal transition (EMT) did not involve. HUVEC-CM caused a decrease of cell population in G1- and S-phase of Bel-7402, it also caused an accumulation of cell population in G1 phase and a decrease of cell population in S-phase of MHCC-LM3, MHCC-97L and DU-145. HUVEC-CM promotes apoptosis of Bel-7402 and MHCC-97L and the nude mouse tumorigenic experiment did not find that the HUVEC-CM increase the tumorigenic ability of liver cancer cells. Conclusion: HUVEC may provide an easy-to-adhere roadbed for liver cancer cells invasion of blood vessels by altering extracellular matrix (ECM), activating integrins/FAK pathway and inducing non-classical EMT. The effect of HUVEC-CM on cell viability was cancer cell type dependent. It is a meaningful glance at the mechsanism of PVTT.