Portal vein tumor thrombus is a frequent, challenging complication in hepatocellular carcinoma. Hepatocellular carcinoma patients with portal vein tumor thrombus may show worse liver function, less treatment tolerance and worse prognosis than patients without portal vein tumor thrombus, and they may be at higher risk of comorbidity related to portal hypertension. Western and some Asian guidelines stratify hepatocellular carcinoma with portal vein tumor thrombus together with metastatic hepatocellular carcinoma and therefore recommend only palliative treatment with sorafenib or other systemic agents. In recent years, more treatment options have become available for hepatocellular carcinoma patients with portal vein tumor thrombus, and an evidence-based approach to optimizing disease management and treatment has become more widespread. Nevertheless, consensus policies for managing hepatocellular carcinoma with portal vein tumor thrombus have not been established. This comprehensive literature review, drawing primarily on studies published after 2010, examines currently available management options for patients with hepatocellular carcinoma and portal vein tumor thrombus.
For patients with advanced hepatocellular carcinoma (HCC), official guidelines recommend palliative treatments such as transarterial chemoembolization (TACE) but not hepatic resection (HR). This study compared short- and long-term outcomes in patients with advanced HCC treated by either HR or TACE. A retrospective analysis was performed for a consecutive series of 444 patients with advanced HCC who underwent HR (n = 339) or TACE (n = 205). Analyses were performed over all participants as well as for propensity score-matched patients to adjust for any baseline differences. When all patients were included in the analysis, the HR and TACE groups showed similar postoperative complication rate and mortality at 30 and 90 days (all P > 0.05). However, median survival time was significantly higher in the HR group (16.4 months) than in the TACE group (11.8 months; P = 0.012). Overall survival at 1, 3, 5, and 7 years was 58, 26, 18, and 18 % in the HR group, higher than the corresponding rates of 49, 14, 12, and 7 % in the TACE group. Similar results were obtained in the analysis of propensity score-matched patients. Therefore, HR can be safe and effective for patients with advanced HCC. Randomized controlled trials are warranted to confirm this finding.
The safety and efficacy of perioperative antiviral therapy for patients with hepatitis B virus related hepatocellular carcinoma and low serum levels of hepatitis B virus DNA are unknown. This retrospective study compared serum levels of hepatitis B virus DNA, liver function, morbidity, and length of hospital stay between patients who underwent hepatic resection alone and patients who received entecavir therapy before and after resection (n = 44 in each group). Propensity score matching was used to reduce confounding due to baseline differences between the groups. Hepatitis B virus reactivation during follow-up, which lasted a median of 6.1 months, occurred in one patient in the entecavir group (2.3%) and 11 patients in the resection-only group (25%; P = 0.02). Liver function, especially alanine aminotransferase levels, recovered much faster in the entecavir group. This group also showed a slightly lower rate of morbidity (P = 0.081) as well as significantly shorter overall hospital stay (20.1 ± 4.9 vs 24.9 ± 13.2 days; P = 0.028) and postoperative hospital stay (11.4 ± 1.9 vs 16.8 ± 13.1 days; P = 0.008). These results from this pilot study suggest that patients with hepatitis B virus related hepatocellular carcinoma and low levels of hepatitis B virus DNA are at risk of hepatitis B virus reactivation following resection, and that perioperative entecavir therapy can safely and effectively reduce this risk. Such therapy also appears to improve liver function and shorten hospitalization.
Background and Aim Previous smaller meta‐analyses comparing the incidence of hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) patients treated with tenofovir disoproxil fumarate (TDF) versus entecavir (ETV) provided controversial results. This updated meta‐analysis aimed to reliably identify any difference in the HCC incidence between TDF‐treated or ETV‐treated CHB patients in general or in specific subgroups. Methods PubMed, EMBASE, Web of Science, and Cochrane Library were systematically searched for relevant studies with hazard ratios (HRs) for HCC between TDF‐treated and ETV‐treated CHB patients. Retrieved dates ranged from January 2009 to October 2021. HRs with or without adjustment were pooled with random‐effects model. Results Twenty‐four comparative studies involving 37 771 CHB patients treated with TDF and 72 094 treated with ETV were included. TDF was associated with lower risk of HCC compared with ETV, with pooled unadjusted HR of 0.76 (95% confidence interval [CI]: 0.67–0.86) (24 studies) and adjusted HR of 0.81 (95% CI: 0.72–0.91) (21 studies). In propensity score matching cohorts, the TDF superiority was confirmed for unadjusted HR 0.83 (95% CI: 0.71–0.97) (14 studies) and was close to significance for adjusted HR (0.78, 95% CI: 0.58–1.04) (8 studies). Subgroup analyses showed that TDF was associated with lower HCC risk than ETV treatment in CHB patients who were from Asia (adjusted HR: 0.76, 95% CI: 0.66–0.87; 15 studies) or nucleos(t)ide naïve (adjusted HR:0.74, 95% CI: 0.65–0.84; 18 studies). Conclusion Current evidence from a sizable population suggests that TDF is associated with significantly lower HCC risk compared with ETV treatment in patients who are from Asia and/or nucleos(t)ide naïve.
Accumulating evidence suggested that calcium release-activated calcium modulator 1(ORAI1), a key calcium channel pore-forming protein-mediated store-operated Ca2+ entry (SOCE), is associated with human cancer. However, its role in colorectal cancer (CRC) progression has not been well studied. Epithelial-mesenchymal transition (EMT) is a multistep process that occurs during the progression of cancers and is necessary for metastasis of epithelial cancer. Transforming growth factor-β (TGF-β) is a pleiotropic cytokine that has been shown to induce EMT. In this study, we are aimed at exploring the effects of ORAI1 on TGF-β1-induced EMT process in CRC cells. Herein, we confirmed ORAI1 expression was higher in CRC tissues than in adjacent non-cancerous tissues by using immunohistochemical staining and Western blot analysis. Higher ORAI1 expression was associated with more advanced clinical stage, higher incidence of metastasis and shorter overall survival. We compared ORAI1 expression in SW480 and SW620 cells, two CRC cell lines with the same genetic background, but different metastatic potential. We found ORAI1 expression was significantly higher in SW620 cells which exhibited higher EMT characteristics. Furthermore, knockdown of ORAI1 suppressed the EMT of SW620 Cells. After induced the EMT process in SW480 cells with TGF-β1, we found treatment of TGF-β1 showed a significant increase in cell migration along with the loss of E-cadherin and an increase in N-cadherin and Vimentin protein levels. Also, TGF-β1 treatment increased ORAI1 expression and was closely associated with the increase of SOCE. Silencing ORAI1 significantly suppressed Ca2+ entry, reversed the changes of EMT-relevant marks expression induced by TGF-β1, and inhibited TGF-β1-mediated calpain activation and cell migration. Finally, we blocked SOCE with 2-APB (2-Aminoethyl diphenylborinate), a pharmacological inhibitor. Interestingly, 2-APB and sh-ORAI1 both exhibited similar inhibition effects to the SW480 cells. In conclusion, our results demonstrated that ORAI1 could mediate TGF-β-Induced EMT by promoting Ca2+ entry and calpain activity in Colorectal Cancer Cells.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.