Background: Inflammatory bowel disease (IBD) is an autoimmune bowel disease with poor clinical outcome. Proinflammatory cytokines are the main targets of biological therapies. Interleukin-23 (IL-23) is a key factor in IBD pathogenesis. Monoclonal antibodies against subunit of IL-23 have been reported to have therapeutic effects. Aims: To investigate the therapeutic effect of IL-23 RNA interference in mice with experimental colitis and the underlying mechanism. Methods: 2,4,6-trinitrobenzenesulfonic acid (TNBS) enema was used to induce experimental colitis in mice, which were then injected with IL-23 p19 shRNA lentivirus or control shRNA lentivirus through caudal vein. Mice without lentivirus injection were served as model controls. After 2 weeks, disease activity index and histopathological inflammatory score, serum and colon tissue IL-23, IL-17 and tumor necrosis factor-α (TNF-α) expressions, as well as colon tissue Th17 cells were detected and compared. Results: IL-23 p19 shRNA therapy significantly reduced disease activity index and histopathological inflammatory score in mice with experimental colitis (P<0.05). By inhibiting IL-23 expression, IL-23 p19 shRNA suppressed further the colon tissue Th17 cells and subsequently reduced systemic and colon tissue IL-17 and TNF-α expressions significantly (P<0.05). Conclusions: IL-23 RNA interference has therapeutic effect in mice with experimental colitis. The mechanism lies in suppression of Th17 cells and its effector cytokine IL-17.

BACKGROUND/AIMS: The motility change after peroral endoscopic myotomy (POEM) in achalasia is currently focused on lower esophageal sphincter (LES). This study aims to investigate the correlation of motility response between distal and proximal esophagus after POEM. METHODS: A total of 32 achalasia patients who received POEM and high-resolution manometry (HRM) were included for analysis. Eckardt score was used to assess symptom improvement. HRM was applied for studying motility. Main parameters analyzed were (1) LES: resting pressure (restP), 4-second integrated relaxation pressure; (2) esophageal body (EB): contractile integral of distal segment with myotomy (CI-DM) and proximal segment without myotomy (CI-PNM); and (3) upper esophageal sphincter (UES): relaxation pressure (UES-RP). RESULTS: There were 6 type I, 17 type II, and 9 type III achalasia patients included for analysis. (1) Eckardt score, LES tone, CI-DM, CI-PNM and UES-RP were reduced remarkably after POEM (P < 0.001). (2) no significant correlation was noted between LES tone and contractile intergral of EB. (3) a positive linear correlation of CI-DM and CI-PNM changes was detected (P < 0.001). (4) the change of UES-RP was positively correlated with the change of contractile integral of EB (P < 0.001). CONCLUSIONS: Myotomy of the distal esophagus would attenuate proximal EB contraction and assist UES relaxation in achalasia patients after POEM.
Esophageal Achalasia* ; Esophageal Sphincter, Lower ; Esophageal Sphincter, Upper* ; Esophagus* ; Humans ; Manometry ; Relaxation*

BACKGROUND/AIMS: In recent years, endoscopic submucosal tunnel dissection (ESTD) has gained popularity worldwide. The aim of this study was to evaluate the safety and efficacy of ESTD in treating upper gastrointestinal submucosal tumors (SMTs) in a large-volume endoscopic center. METHODS: Patients with SMTs were enrolled in this study between January 2012 and January 2015. Demographic data, clinical data, and treatment outcome were collected and analyzed. RESULTS: Seventy SMTs originating from the muscularis propria (MP) layer were identified in 69 patients. All patients successfully underwent the ESTD procedure. The mean procedure time was 49.0±29.5 minutes, and the mean tumor size was 18.7±7.2 mm. Among all lesions, the majority (70.0%) were located in the esophagus, 12.9% in the cardia, and 17.1% in the stomach. Complete resection was achieved in 67 lesions (95.7%). Perforation occurred in three patients (4.3%), who were treated by endoclips. Pneumothorax occurred in two patients (2.9%) and was successfully managed by thoracic drainage. During a median follow-up of 18.1 months, patients were free of local recurrence or distant metastasis. CONCLUSIONS: Our results demonstrated the feasibility and safety of ESTD in treating upper gastrointestinal SMTs originating from the MP layer. Large-scale comparative studies with other treatment methods should be conducted in the future.
Cardia ; Drainage ; Esophagus ; Follow-Up Studies ; Humans ; Neoplasm Metastasis ; Pneumothorax ; Recurrence ; Stomach ; Treatment Outcome

Objective: To analyze the risk factors of positive vertical resection margin of the postoperative specimens after endoscopic treatment of rectal neuroendocrine tumors (NET). Methods: A case-control study was performed. Clinical data of patients with rectal NET (G1) undergoing endoscopic treatment between January 2015 and June 2018 at the Department of Gastroenterology, Beijing Tsinghua Changgung Hospital were retrospectively collected. Inclusion criteria: cases underwent endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD), whose mucosal specimens were pathologically confirmed as NET, and NET was confined to the rectum by nuclide imaging examination before endoscopic treatment. Those with incomplete clinical data or follow-up data were excluded. Resected specimen was fixed and sliced every 2 mm, and when tumor cells were found to infiltrate the vertical cutting edge, the positive vertical margin was defined. Associations of gender, age, resection method, tumor diameter, lesion morphology (nodular lesions, biopsy or post-treatment scar-like changes), mitotic figure, Ki-67 index, etc. and positive vertical margin were analyzed. Univariate analysis was performed using binary logistic analysis and multivariate analysis was performed using logistic regression model. Results: A total of 133 patients with rectal NET were enrolled, including 93 males and 40 females, with an average age of (50.0±10.7) years. Sixty-four patients received EMR treatment and 3 patients (4.7%) had positive vertical margins. While 69 patients received ESD treatment and 13 (18.8%) had positive vertical margins. After endoscopic treatment, 16 cases (12.0%) were vertical positive margin, including 11 males and 5 females with an average age of (52.4±10.4) years. The lesion diameter was (9.0±4.7) mm. Univariate analysis showed that lesion diameter ≥10 mm (χ²=5.575, P=0.018) and scar-like changes (χ²=3.894, P=0.048) were significantly associated with positive vertical margin. Multivariate analysis showed that the lesion diameter ≥10 mm (OR=10.136, 95%CI: 2.114 to 48.591, P=0.004) was an independent risk factor for positive vertical margin of the specimen after endoscopic treatment of rectal NET. Conclusion The diameter of rectal NET ≥10 mm indicates a high risk for positive vertical margin after endoscopic treatment.

Peroral endoscopic myotomy (POEM) has emerged as a rescue treatment for recurrent or persistent achalasia after failed initial management. Therefore, we aimed to investigate the efficacy and safety of POEM in achalasia patients with failed previous intervention. We searched the MEDLINE, Embase, Cochrane, and PubMed databases using the queries “achalasia,” “peroral endoscopic myotomy,” and related terms in March 2019. Data on technical and clinical success, adverse events, Eckardt score and lower esophageal sphincter (LES) pressure were collected.The pooled event rates, mean differences (MDs) and risk ratios (RR) were calculated. A total of 15 studies with 2,276 achalasia patients were included. Overall, the pooled technical success, clinical success and adverse events rate of rescue POEM were 98.0% (95% confidence interval [CI], 96.6% to 98.8%), 90.8% (95% CI, 88.8% to 92.4%) and 10.3% (95% CI, 6.6% to 15.8%), respectively. Seven studies compared the clinical outcomes of POEM between previous failed treatment and the treatment naïve patients. The RR for technical success, clinical success, and adverse events were 1.00 (95% CI, 0.98 to 1.01), 0.98 (95% CI, 0.92 to 1.04), and 1.17 (95% CI, 0.78 to 1.76), respectively. Overall, there was significant reduction in the pre- and post-Eckardt score (MD, 5.77; p<0.001) and LES pressure (MD, 18.3 mm Hg; p<0.001) for achalasia patients with failed previous intervention after POEM. POEM appears to be a safe, effective and feasible treatment for individuals who have undergone previous failed intervention. It has similar outcomes in previously treated and treatment-naïve achalasia patients.

BACKGROUND/AIMS: Achalasia patients would feel exacerbated dysphagia, chest pain and regurgitation when they drink cold beverages or eat cold food. But these symptoms would relieve when they drink hot water. Reasons are unknown. METHODS: Twelve achalasia patients (mean age, 34 +/- 10 years; F:M, 3:9) who never had any invasive therapies were chosen from Peking Union Medical College Hospital. They were asked to fill in the questionnaire on eating habits including food temperature and related symptoms and to receive high-resolution manometry examination. The exam was done in 2 separated days, at swallowing room temperature (25degrees C) then hot (50degrees C) water, and at room temperature (25degrees C) then cold (2degrees C) water, respectively. Parameters associated with esophageal motility were analyzed. RESULTS: Most patients (9/12) reported discomfort when they ate cold food. All patients reported no additional discomfort when they ate hot food. Drinking hot water was effective in 5/8 patients who ever tried to relieve chest pain attacks. On manometry, cold water increased lower esophageal sphincter (LES) resting pressure (P = 0.003), and prolonged the duration of esophageal body contraction (P = 0.002). Hot water decreased LES resting pressure and residue pressure during swallow (P = 0.008 and P = 0.002), increased LES relaxation rate (P = 0.029) and shortened the duration of esophageal body contraction (P = 0.003). CONCLUSIONS: Cold water could increase LES resting pressure, prolong the contraction duration of esophageal body, and exacerbate achalasia symptoms. Hot water could reduce LES resting pressure, assist LES relaxation, shorten the contraction duration of esophageal body and relieve symptoms. Thus achalasia patients are recommended to eat hot and warm food and avoid cold food.
Beverages ; Chest Pain ; Cold Temperature ; Contracts ; Deglutition ; Deglutition Disorders ; Drinking ; Eating ; Esophageal Achalasia ; Esophageal Motility Disorders ; Esophageal Sphincter, Lower ; Esophagus ; Humans ; Manometry ; Surveys and Questionnaires ; Relaxation ; Water

Irritable bowel syndrome (IBS) is characterized by abdominal pain associated with changes in defecation frequency and blood folate level. FODMAP stands for fermentable oligosaccharides, disaccharides, monosaccharides and polyols. High-FODMAP diet could elicit or exacerbate IBS-associated bowel symptoms, which is inadequately recognized among gastroenterologists in China. Here we report an IBS case, focusing on the association between high-FODMAP diet and bowel symptoms and the intervention of low-FODMAP diet.

OBJECTIVE: To assess the value of Improved Mayo Endoscopic Score (IMES) for evaluation of treatment efficacy for active ulcerative colitis (UC). METHODS: We retrospectively analyzed the clinical and endoscopic data of 103 patients diagnosed with active UC in Beijing Tsinghua Changgung Hospital from January, 2015 to December, 2020. The severity of endoscopic lesions was determined by Mayo Endoscopic Score and the Ulcerative Colitis Endoscopic Index of Severity (UCEIS), and the area of the endoscopic lesions was evaluated based on the Montreal classification system. The IMES was established by combining the MES with the Montreal classification. RESULTS: Univariate analysis suggested that young patients (<40 years old), patients with extensive disease type (E3), patients with high endoscopic scores (MES=3, UCEIS>4, and IMES>4), and patients receiving advanced drug therapy (with systemic hormones, immunosuppressants, immunomodulators, and biological agents, etc.) had lower clinical and endoscopic remission rates. COX survival analysis showed that IMES≤4 was an independent risk factor for clinical and endoscopic remission. ROC curve indicated that the predictive value of IMSE≤4 for clinical and endoscopic remission (AUC=0.7793 and 0.7095, respectively; P<0.01) was better than that of Montreal (AUC=0.7357 and 0.6847, respectively; P<0.01), MES=2 (AUC=0.6671 and 0.5929, respectively; P<0.01), and UCEIS≤4 (AUC=0.6823 and 0.6459, respectively; P<0.01); IMES=5 had a better predictive value for patients with active UC undergoing colectomy tham E3 and MES=3. CONCLUSION IMES has good value in evaluating treatment efficacy for active UC.
Humans ; Adult ; Colitis, Ulcerative ; Retrospective Studies ; Endoscopy ; Immunosuppressive Agents ; Treatment Outcome