Background and Objectives:Endoscopic therapy is an option for the treatment of refractory gastroesophageal reflux disease (GERD). We aimed to evaluate the efficacy and safety of transoral incisionless fundoplication with the Medigus ultrasonic surgical endostapler (MUSE™) for refractory GERD. Materials and Methods:Patients with 2 years of documented GERD symptoms and at least 6 months of proton-pump inhibitors (PPIs) therapy were enrolled in four medical centers from March 2017 to March 2019. The GERD health-related quality of life (HRQL) score, GERD questionnaire score, total acid exposure on esophageal pH probe monitoring, the gastroesophageal flap valve (GEFV), esophageal manometry, and PPIs dosage were compared between the pre- and post-MUSE procedure. All of the side effects were recorded. Results:A reduction of at least 50% in the GERD-HRQL score was observed in 77.8% (42/54) patients. Most patients 74.1% (40/54) discontinued PPIs and 11.1% (6/54) reported a ≥50% dose reduction. The percentage of patients who had normalized acid exposure time after the procedure was 46.9% (23/49). The existence of hiatal hernia at baseline was negatively correlated with the curative effect. Mild pain was common and resolved within 48 h postprocedure. Serious complications were pneumoperitoneum (one case), mediastinal emphysema combined with pleural effusion (two cases). Conclusions:Endoscopic anterior fundoplication with MUSE was an effective treatment for refractory GERD, but still needs refinement and improvement in safety aspect. Esophageal hiatal hernia may affect the efficacy of MUSE. (www.chictr.org.cn, ChiCTR2000034350).
Background:Gut microbiota has been identified as an imbalance in patients with irritable bowel syndrome (IBS). Fecal microbiota transplantation (FMT) is a novel method to restore microbiota and treat IBS patients.ObjectiveTo conduct a meta-analysis and estimate the efficacy and safety of FMT for the treatment of IBS patients with subgroup analyses to explore the most effective way of FMT for IBS.MethodsAll eligible studies were searched from PubMed, Embase, Web of Science, and the Cochrane Library through multiple search strategies. Data were extracted from studies comprising the following criteria: double-blind, randomized controlled trials (RCTs) that compared the efficacy of FMT with placebo for adult patients (≥18 years old) with IBS. A meta-analysis was performed to evaluate the summary relative risk (RR) and 95% confidence intervals (CIs).ResultsA total of seven RCTs comprising 489 subjects were eligible for this meta-analysis. Pooled data showed no significant improvement of global IBS symptoms in patients with FMT compared with placebo (RR = 1.34; 95% CI 0.75–2.41, p = 0.32). A significant heterogeneity was observed among the studies (I2 = 83%, p < 0.00001). There was no significant evidence of funnel plot asymmetry (Egger's test, p = 0.719; Begg's test, p = 1.000), indicating no existence of publication bias. Subgroup analyses revealed that FMT operated by invasive routes, including gastroscope, colonoscope, and nasojejunal tube, significantly improved global IBS symptoms (RR = 1.96; 95% CI 1.23–3.11, p = 0.004) with heterogeneity (I2 = 57%, p = 0.06) and an NNT of 3 (95% CI 2–14). However, FMT delivered via oral capsules showed a negative impact on patients with IBS (RR = 0.56; 95% CI 0.33–0.96, p = 0.03) with a low heterogeneity (I2 = 39%, p = 0.2) and an NNH of 3 (95% CI 2–37).ConclusionThe current evidence from RCTs with all routes of FMT does not show significant global improvement in patients with IBS. However, FMT operated by invasive routes significantly improved global IBS symptoms.
Objective Aberrant activation of Wnt/β-catenin signaling contributes to the maintenance of cancer stem cells and chemoresistance in colorectal cancer (CRC). Retinoic acid-induced 2 (RAI2) was proved to be a tumor suppressor in CRC in our previous report. In this study, the role of RAI2 in Wnt/β-catenin signaling was further investigated. Methods As a transcriptional co-regulator, C-terminal Binding Protein 2 (CtBP2) was reported to be involved in Wnt signaling in multiple and complex ways. The correlation of RAI2 and CtBP2 in CRC was analyzed by TCGA dataset, and the interaction between RAI2 and CtBP2 was explored by co-immunoprecipitation (Co-IP) in CRC cells. The effect of RAI2 on the activity of Wnt signaling and the location of β-catenin was detected by Dual-Luciferase reporter assay and Immunofluorescence respectively. Western blotting analysis was performed to detect the expression of target genes involved in Wnt signaling. Sphere formation assay was employed to detect the effect of RAI2 on stem cell like properties. Cell viability assay was used to detect the chemosensitivity of cells before and after transfection of RAI2. Results The interaction between RAI2 and CtBP2 was confirmed by Co-IP in CRC cells. Besides, the negative correlation of RAI2 and CtBP2 in CRC was found by analyzing the TCGA dataset. Re-expression of RAI2 in human colon cancer cells (HCT116 and LoVo) suppressed the fluorescent activity of Wnt signaling, increased the phosphorylation and inhibited nuclear translocation of β-catenin, with down-regulation of target genes like c-Myc, CyclinD1, ASCL2, and LGR5. In contrast, the mutated RAI2, which can’t interact with CtBP2, has no above effects. We observed low expression of RAI2 in 33.89% (101/298) of CRC patients, which was significantly associated with reduced phosphorylation of β-catenin (r=0.8866, P<0.0001), poor 5-year relapse-free survival (RFS) (P = 0.0029) and overall survival (OS) (P = 0.0102). Restoration of RAI2 in HCT116 and LoVo cells inhibited stem cell-like properties of CRC cells and increased chemosensitivity of these cells to oxaliplatin and fluorouracil. Conclusion Low expression of RAI2 can serve as an independent poor prognostic marker. RAI2 inhibits Wnt signaling by interacting with or down-regulating CtBP2, resulting in repression of stem cell-like properties and increased chemosensitivity of CRC cells.
Objective: The present study aimed to analyze the risk factors and clinical outcomes of the incomplete endoscopic resection of rectal neuroendocrine tumors (rNETs). Methods: This study retrospectively analyzed the cases of 428 patients with rNETs who had undergone endoscopic treatment in the Department of Gastroenterology at the PLA General Hospital, China, between January 2010 and September 2019. Results: Of the 428 patients with rNETs, 266 were men (62.1%) and 162 were women (37.9%). Of these, 54 had been pathologically diagnosed with positive incisal margins without lymphatic vessel invasion, and the incomplete resection (R1) rate was 12.6%. Among the R1 patients, 28 had received endoscopic submucosal dissection, 22 had received endoscopic mucosal resection, two had received snare resection, and two had undergone removal with forceps. In addition, there were 31 cases of grade G1 R1 resection (11.2%; 31/277), 13 cases of grade G2 R1 resection (23.2%; 13/56), and 10 cases whose grading was not described. The univariate analysis showed the pathological grade was statistically correlated with R1 resection (P < 0.05), and the grade G2 R1 resection rate was higher than that of grade G1. The multivariate logistic regression analysis showed that grade G2 was an independent risk factor leading to R1 resection (P = 0.02). All patients with R1 resection were followed up for 10-110 months, with an average of 38 months. No salvage treatment was performed. The endoscopic monitoring showed there were no recurrences during the follow-up period. Conclusion: Endoscopic resection is a good option for rNETs, with a high complete resection rate and good prognosis, with rare recurrence even if endoscopic resection is not complete.
Background and Aims: The use of endoscopic submucosal dissection (ESD) for management of widespread superficial esophageal squamous carcinoma is closely associated with esophageal stenosis. We investigated the efficacy and feasibility of endoscopic injection of botulinum toxin type A (BTX-A) for preventing esophageal strictures after ESD for superficial esophageal squamous carcinoma.Methods: Sixty-seven patients with superficial esophageal squamous cell carcinomas with mucosal defects that exceeded one half of the circumference of the esophagus after ESD treatment were enrolled and randomly divided into 2 groups (group A, n = 33; group B, n = 34). Patients in group A (BTX-A group) were immediately injected with BTX-A after ESD, whereas patients in group B (control group) received ESD only. Endoscopy was performed when patients reported dysphagia symptoms and at 12 weeks post-ESD in patients without symptoms. Patients who experienced post-ESD esophageal strictures in both groups received bougie dilation.Results: The number of patients who experienced esophageal strictures in group A (per protocol analysis, 6.1%, 2/33; intention to treat analysis, 11.4%, 4/35) was significantly less than that seen in group B (per protocol analysis, 32.4%, 11/34; intention to treat analysis, 37.8%, 14/37) (P <.05). Moreover, the number of bougie dilation procedures was significantly lower in group A (mean, 1.5; range, 0-2) than in group B (mean, 2.8; range, 0-5) (P <.05).Conclusions: Endoscopic injection of BTX-A was effective in preventing post-ESD esophageal strictures and decreasing the times of bougie dilation procedures.
Hemosuccus pancreaticus is defined as intermittent bleeding from the pancreatic duct into the GI tract, usually caused by the rupture of an pseudoaneurysm, which is usually associated with pancreatitis, abdominal surgery, and can result in life-threatening hemorrhage. Hyperparathyroidism is a rare cause of pancreatitis, it should be suspected in all patients with a history of primary hyperpara¬t hyroidism, When these diseases coexist, the course of pancreatitis can be rather severe and often complicated. This report detail a case of Hemosuccus pancreaticus due to hyperparathyroidism associated pancreatitis and its successful emergency conservative management by Embolization Techniques.