Timing of endoscopy for acute variceal bleeding in patients with cirrhosis (CHESS1905): A nationwide cohort study.

BACKGROUND: Endoscopy plays an important role in the management of acute variceal bleeding (AVB) in patients with cirrhosis. This study aimed at determining the optimal endoscopy timing for cirrhotic AVB. METHODS: Patients with cirrhosis with AVB across 34 university hospitals in 30 cities from February 2013 to May 2020 who underwent endoscopy within 24 hours were included in this study. Patients were divided into an urgent endoscopy group (endoscopy <6 h after admission) and an early endoscopy group (endoscopy 6-24 h after admission). Multivariable analysis was performed to identify risk factors for treatment failure. Primary outcome was the incidence of 5-day treatment failure. Secondary outcomes included in-hospital mortality, need for intensive care unit, and length of hospital stay. A propensity score matching analysis was performed. In addition, we performed an analysis, in which we compared the 5-day treatment failure incidence and the in-hospital mortality among patients with endoscopy performed at <12 hours and 12-24 hours. RESULTS: A total of 3319 patients were enrolled: 2383 in the urgent endoscopy group and 936 in the early endoscopy group. After propensity score matching, on multivariable analysis, Child-Pugh class was identified as an independent risk factor for 5-day treatment failure (HR, 1.61; 95% CI: 1.09-2.37). The incidence of 5-day treatment failure was 3.0% in the urgent endoscopy group and 2.9% in the early group ( p = 0.90). The in-hospital mortality was 1.9% in the urgent endoscopy group and 1.2% in the early endoscopy group ( p = 0.26). The incidence of need for intensive care unit was 18.2% in the urgent endoscopy group and 21.4% in the early endoscopy group ( p = 0.11). The mean length of hospital stay was 17.9 days in the urgent endoscopy group and 12.9 days in the early endoscopy group ( p < 0.05). The incidence of 5-day treatment failure in the <12-hour group was 2.3% and 2.2% in the 12-24 hours group ( p = 0.85). The in-hospital mortality was 2.2% in the <12-hour group and 0.5% in the 12-24 hours group ( p < 0.05). CONCLUSIONS: The data suggest that performance of endoscopy within 6-12 or within 24 hours of presentation among patients with cirrhosis with AVB led to similar treatment failure outcomes.

The Novel LncRNA WASH5P Inhibits Colorectal Cancer Carcinogenesis via Targeting AKT Signaling Pathway.

Emerging evidence has shown that long non-coding RNAs (lncRNAs) play an important role in colorectal cancer (CRC) carcinogenesis, so more specific mechanisms of key lncRNAs in CRC initiation and development are needed. Here, we evaluated the expression profiles of lncRNAs in CRC tissues and identified a novel lncRNA generated from the pseudogene Wiskott-Aldrich syndrome protein (WASP) family homolog 5, termed lncRNA WASH5P. However, the role and potential molecular mechanism of this novel lncRNA in diseases, including CRC carcinogenesis, is unknown. Our present study found that WASH5P was significantly downregulated in CRC cell lines and tissues compared with normal controls. The ectopic expression of WASH5P in CRC cells could significantly inhibit CRC cell proliferation, invasion, and migration. In addition, WASH5P could increase the expression of E-cadherin and decrease Vimentin expression. WASH5P-overexpressing CRC cells developed tumors more slowly in different mouse models. Meanwhile, the overexpression of WASH5P could significantly inhibit AKT activation via suppressing AKT phosphorylation. The treatment of PI3K/AKT (phosphatidlinositol 3-kinase /protein kinase B) signaling agonist 740Y-P rescued WASH5P-reduced AKT phosphorylation and abolished the inhibitory effects of WASH5P on cell viability, migration, and invasion. Moreover, 740Y-P restored the WASH5P-induced downregulation of p-AKT and vimentin and the upregulation of E-cadherin via Western blot. In summary, our findings suggested that the novel lncRNA WASH5P might be a potential candidate biomarker and therapeutic target that could inhibit CRC by repressing the AKT signaling pathway.

Risk of Lymph Node Metastasis and Feasibility of Endoscopic Treatment in Ulcerative Early Gastric Cancer.

BACKGROUND: When the risk of lymph node metastasis (LNM) is considered minimal in patients with early gastric cancer (EGC), endoscopic submucosal dissection (ESD) is an effective alternative to radical resection. This study aims to estimate the feasibility of ESD for EGC with ulceration. PATIENTS AND METHODS: We retrospectively reviewed data from 691 patients who underwent gastrectomy for EGC with ulceration. Subsequently, a stratification system for lesions was created based on the expanded ESD criteria, and the associations between the subgroups and the rate of LNM were analyzed. RESULTS: LNM was confirmed in 16.5% (114/691) of patients. Univariate analysis demonstrated that age, sex, tumor size, macroscopic features, depth of invasion, tumor differentiation, Lauren type, lymphovascular invasion (LVI), and perineural invasion were associated with LNM. Multivariate analysis showed that LVI [odds ratio (OR) = 16.761, P < 0.001], SM1 invasion (OR = 2.159, P = 0.028), and SM2 invasion (OR = 3.230, P < 0.001) were independent risk factors for LNM. LNM occurred in undifferentiated mucosal tumors, with ulceration being 1.7% (2/116) when the lesion was smaller than 20 mm. Further stratification revealed that among lesions < 30 mm in size, undifferentiated tumors with SM1 invasion had a higher rate of LNM and a lower disease-free survival rate than differentiated tumors with SM1 invasion and tumors limited to the mucosal layer. CONCLUSIONS: Depth of invasion and LVI were strongly associated with LNM in ulcerative EGC. Endoscopic resection may be applicable for undifferentiated mucosal ulcerative EGC < 30 mm in size, and additional investigation is needed to evaluate its safety.

The anti-cancer effects of fucoidan: a review of both in vivo and in vitro investigations.

Fucoidan is a kind of the polysaccharide, which comes from brown algae and comprises of sulfated fucose residues. It has shown a large range of biological activities in basic researches, including many elements like anti-inflammatory, anti-cancer, anti-viral, anti-oxidation, anticoagulant, antithrombotic, anti-angiogenic and anti-Helicobacter pylori, etc. Cancer is a multifactorial disease of multiple causes. Most of the current chemotherapy drugs for cancer therapy are projected to eliminate the ordinary deregulation mechanisms in cancer cells. Plenty of wholesome tissues, however, are also influenced by these chemical cytotoxic effects. Existing researches have demonstrated that fucoidan can directly exert the anti-cancer actions through cell cycle arrest, induction of apoptosis, etc., and can also indirectly kill cancer cells by activating natural killer cells, macrophages, etc. Fucoidan is used as a new anti-tumor drug or as an adjuvant in combination with an anti-tumor drug because of its high biological activity, wide source, low resistance to drug resistance and low side effects. This paper reviews the mechanism by which fucoidan can eliminate tumor cells, delay tumor growth and synergize with anticancer chemotherapy drugs in vitro, in vivo and in clinical trials.

Analyzing large-scale samples confirms the association between rs16892766 polymorphism and colorectal cancer susceptibility.

Colorectal cancer (CRC) is a common complex disease caused by the combination of genetic variants and environmental factors. Genome-wide association studies (GWAS) have been performed and reported some novel CRC susceptibility variants. The rs16892766 (8q23.3) polymorphism was first identified to be significantly associated with CRC in European ancestry. The following studies investigated this association in Chinese, Japanese, Romanian, Swedish, African American, European American, and Croatian populations. These studies reported consistent and inconsistent results. Here, we reevaluated this association using the relatively large-scale samples from 13 studies (N = 59737, 26237 cases and 33500 controls) using a meta-analysis by searching the PubMed, Google Scholar and CRCgene databases. We observed no significant heterogeneity among the included studies. Our results showed significant association between rs16892766 polymorphism and CRC (P = 1.33E-35, OR = 1.23, 95% CI 1.20-1.27). Collectively, our analysis further supports previous findings that the rs16892766 polymorphism is significantly associated with CRC susceptibility. We believe that our findings will be very useful for future genetic studies on CRC.

Pathway analysis of genome-wide association study and transcriptome data highlights new biological pathways in colorectal cancer.

Colorectal cancer (CRC) is a common malignancy that meets the definition of a complex disease. Genome-wide association study (GWAS) has identified several loci of weak predictive value in CRC, however, these do not fully explain the occurrence risk. Recently, gene set analysis has allowed enhanced interpretation of GWAS data in CRC, identifying a number of metabolic pathways as important for disease pathogenesis. Whether there are other important pathways involved in CRC, however, remains unclear. We present a systems analysis of KEGG pathways in CRC using (1) a human CRC GWAS dataset and (2) a human whole transcriptome CRC case-control expression dataset. Analysis of the GWAS dataset revealed significantly enriched KEGG pathways related to metabolism, immune system and diseases, cellular processes, environmental information processing, genetic information processing, and neurodegenerative diseases. Altered gene expression was confirmed in these pathways using the transcriptome dataset. Taken together, these findings not only confirm previous work in this area, but also highlight new biological pathways whose deregulation is critical for CRC. These results contribute to our understanding of disease-causing mechanisms and will prove useful for future genetic and functional studies in CRC.