Comparison of Over-the-Scope Clips to Standard Endoscopic Treatment as the Initial Treatment in Patients With Bleeding From a Nonvariceal Upper Gastrointestinal Cause : A Randomized Controlled Trial.

BACKGROUND: Current endoscopic methods in the control of acute nonvariceal bleeding have a small but clinically significant failure rate. The role of over-the-scope clips (OTSCs) as the first treatment has not been defined. OBJECTIVE: To compare OTSCs with standard endoscopic hemostatic treatments in the control of bleeding from nonvariceal upper gastrointestinal causes. DESIGN: A multicenter, randomized controlled trial. (ClinicalTrials.gov: NCT03216395). SETTING: University teaching hospitals in Hong Kong, China, and Australia. PATIENTS: 190 adult patients with active bleeding or a nonbleeding visible vessel from a nonvariceal cause on upper gastrointestinal endoscopy. INTERVENTION: Standard hemostatic treatment (n = 97) or OTSC (n = 93). MEASUREMENTS: The primary outcome was 30-day probability of further bleeds. Other outcomes included failure to control bleeding after assigned endoscopic treatment, recurrent bleeding after initial hemostasis, further intervention, blood transfusion, and hospitalization. RESULTS: The 30-day probability of further bleeding in the standard treatment and OTSC groups was 14.6% (14 of 97) and 3.2% (3 of 93), respectively (risk difference, 11.4 percentage points [95% CI, 3.3 to 20.0 percentage points]; P = 0.006). Failure to control bleeding after assigned endoscopic treatment in the standard treatment and OTSC groups was 6 versus 1 (risk difference, 5.1 percentage points [CI, 0.7 to 11.8 percentage points]), respectively, and 30-day recurrent bleeding was 8 versus 2 (risk difference, 6.6 percentage points [CI, -0.3 to 14.4 percentage points]), respectively. The need for further interventions was 8 versus 2, respectively. Thirty-day mortality was 4 versus 2, respectively. In a post hoc analysis with a composite end point of failure to successfully apply assigned treatment and further bleeds, the event rate was 15 of 97 (15.6%) and 6 of 93 (6.5%) in the standard and OTSC groups, respectively (risk difference, 9.1 percentage points [CI, 0.004 to 18.3 percentage points]). LIMITATION: Clinicians were not blinded to treatment and the option of crossover treatment. CONCLUSION: Over-the-scope clips, as an initial treatment, may be better than standard treatment in reducing the risk for further bleeding from nonvariceal upper gastrointestinal causes that are amenable to OTSC placement. PRIMARY FUNDING SOURCE: General Research Fund to the University Grant Committee, Hong Kong SAR Government.

Efficacy and safety of a novel submucosal injection solution for endoscopic resection in porcine models.

OBJECTIVE: A submucosal injection is usually required to improve the efficacy and safety of endoscopic submucosal dissection (ESD) and endoscopic mucosal resection (EMR). This study aimed to evaluate the performance of 3.3% sodium carboxymethyl starch (Na-CMS) solution, a novel submucosal injection solution, for ESD and EMR. METHODS: Na-CMS, normal saline (NS) and two commercially available agents (sigMAVisc and Eleview) were injected into the esophageal submucosa of randomly grouped pigs. The level of submucosal elevation was examined. Subsequently, ESD or EMR procedures using 3.3% Na-CMS or NS as submucosal injections were performed in the gastrointestinal tract of the pigs. RESULTS: Submucosal elevation was significantly higher and more sustained in the 3.3% Na-CMS group than in the controls (P < 0.05). The volume required for ESD or EMR was significantly lower in the 3.3% Na-CMS group than in the NS group (ESD: 12.21 ± 4.09 mL vs 28.25 ± 8.02 mL, P < 0.001; EMR: 3.99 ± 1.98 mL vs 7.15 ± 3.67 mL, P = 0.001). The ESD resection time was significantly shorter in the 3.3% Na-CMS group than in the NS group (16.58 ± 7.30 min vs 25.29 ± 11.89 min, P = 0.004). Hemorrhage after ESD in the 3.3% Na-CMS group was less severe than that in the NS group (P = 0.006). CONCLUSION: 3.3% Na-CMS is an effective, safe and low-cost submucosal injection solution and holds promise as preferable agent for submucosal injection in ESD and EMR procedures.

Inactivation of BLU is associated with methylation of Sp1-binding site of BLU promoter in gastric cancer.

BLU is a candidate tumor suppressor gene, which is epigenetically inactivated in many human malignancies. However, the expression and biological functions of BLU in gastric cancer has not yet been reported. In the present study, we identified a functional BLU promoter which was regulated by the transcription activator Sp1. Bisulfite sequencing and qRT-PCR assays indicated that the silence of BLU expression in gastric cancer was significantly associated with DNA hypermethylation of BLU promoter including -39 CpG site located in the Sp1 transcription element. The expression of BLU was notably restored in AGS and SGC7901 cells following the demethylation-treatment with 5'-Aza-2'-deoxycytidine. Moreover, the results from ChIP, EMSA and luciferase reporter gene showed that -39 CpG methylation could prevent Sp1 from binding to the promoter of BLU and decreased transcription activity of the BLU gene by ~70%. In addition, knockdown of BLU significantly promoted cellular proliferation and colony formation in gastric cancer cells. In conclusion, we identified a novel functional BLU promoter and proved that BLU promoter activity was regulated by Sp1. Furthermore, we found that hypermethylated -39 CpG in BLU proximal promoter directly reduced its binding with Sp1, which may be one of the mechanisms accounting for the inactivation of BLU in gastric cancer.

Association of RASSF1A promoter methylation with gastric cancer risk: a meta-analysis.

Ras-association domain family 1A (RASSF1A), a candidate tumor suppressor gene, is frequently silenced and inactivated by hypermethylation of its promoter region in several human tumors. However, the association between RASSF1A promoter methylation and gastric cancer risk remains conflicting. The aim of this study was to assess the association of RASSF1A promoter methylation with gastric cancer risk by a comprehensive meta-analysis. Relevant studies were identified by searches of PubMed and Web of Science databases with no restrictions. Combined odds ratio (OR) and 95 % confidence interval (CI) were used to assess the strength of the association between RASSF1A promoter methylation and gastric cancer risk. A chi-square-based Q test and sensitivity analyses were performed to test the between-study heterogeneity and the contributions of single studies to the final results, respectively. Funnel plots were carried out to evaluate publication bias. Overall, a significant association was observed between RASSF1A promoter methylation and gastric cancer risk (OR, 12.67; 95 % CI, 8.12-19.78; p < 0.001) with no between-study heterogeneity. Subgroup analyses further revealed that gastric cancer risk was increased for individuals carrying the methylated RASSF1A compared with those with unmethylated RASSF1A. In addition, no publication bias was detected in the overall and subgroup analyses. This study identified a strong association between RASSF1A promoter methylation and risk of gastric cancer and highlighted a promising potential for RASSF1A promoter methylation in gastric cancer risk prediction.