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Objective: Esophageal white lesions (EWL) are commonly observed under upper endoscopy, while their clinical significance remains undetermined. The aim of this study was to identify the endoscopic characteristics of EWL and distinguish between different types of EWL. Methods: Consecutive patients with upper gastrointestinal complaints and participants admitted for health check‐up who underwent esophagogastroduodenoscopy from October 2018 to August 2019 in a tertiary hospital were prospectively screened. EWL were detected under endoscopy and biopsy was performed for histological analysis. Participants' characteristics, lifestyle, esophageal motility and reflux monitoring variables were analyzed. Results: Of the 3641 consecutive participants screened, 303 of them aged 56.12 ± 10.95 years were found to have EWL (detection rate of 8.3%). More than one‐third of them preferred hot drinks, eating pickled or spicy food, smoking and alcohol consumption and 5.3% had current or former upper gastrointestinal or head and neck cancers. The common endoscopic appearance of the EWL (2.9 mm ± 1.2 mm in diameter) included slightly elevated plaque, translucent white in color, with a clear border, round or oval in shape, and a scaly, rough or smooth surface. Histology showed low‐grade intraepithelial dysplasia in 13 cases, leukoplakia in 10 and intestinal metaplasia in one. No significant differences were found between the histological findings and endoscopic manifestations of EWL. Conclusions: EWL are not uncommon in daily endoscopic examination, with some of them being precancerous lesions. Conventional white‐light endoscopy is insufficient to identify EWL, while histological assessment is important. Further studies using advanced endoscopic techniques with long‐term follow‐up are needed. [ABSTRACT FROM AUTHOR]

Abstract Background Gastroenteropancreatic neuroendocrine neoplasm (GEP-NEN) is the most common type of neuroendocrine tumors accounting for 65–75% of neuroendocrine neoplasms (NENs). Given the fact that there are few studies on GEP-NENs among Chinese patients, we performed a retrospective study in South China. Methods Totally 178 patients with GEP-NENs treated at the First Affiliated Hospital of Sun Yat-sen University between January 1995 and May 2012 were analyzed retrospectively. Results Pancreas was found the most common site of involvement (34.8%). 149 patients (83.7%) presented as non-functional tumors with non-specific symptoms such as abdominal pain (33.7%); carcinoid syndrome was not found in this study. Several methods are useful for localization of GEP-NENs, yielding varied detection rates from 77.8% to 98.7%. Positive rates of chromogranin A (CgA) and synaptophysin (Syn) immunhistochemically were 69.1% and 90.2%, respectively. 87 patients (51.5%) had G1 tumors, 31(18.3%) G2 tumors and 51 (30.2%) G3 tumors. Neuroendocrine tumor (NET), neuroendocrine carcinoma (NEC) and mixed adenoendocrine carcinoma (MANEC) were 69.8%, 27.2% and 3.0%, respectively. 28.1% of patients presented with distant disease. Surgery was performed in 152 (85.4%) patients, and overall 5-year survival rate was 54.5%. Functionality, G1 grading and NET classification were associated with favorable prognosis in univariate analysis. Distant metastasis contributed to unfavorable prognosis of these tumors. Conclusions Nonfunctional tumors with non-specific symptoms account for the majority of GEP-NENs. Diagnosis depends on pathological classification. Multidisciplinary treatments could help improve the outcome.

Abstract Background Gastrokine-1 (GKN1), a secreted protein, is specifically expressed in gastric mucosa to protect and maintain the integrity of gastric epithelium. The present study investigated differential expression of GKN1 in normal, precancerous, and cancerous gastric tissues, and explored the biological functions of GKN1 protein in gastric cancer cells. Methods RT-PCR, Western blot, and immunohistochemistry were performed to detect GKN1 expression in normal, precancerous, cancerous gastric tissues and seven gastric cancer cell lines. Gene transfection was used to restore GKN1 expression in gastric cancer AGS cells. Phenotypic changes (i.e., cell viability, apoptosis, cell cycle modulation, and sensitivity of gastric cancer cells to fluorouracil (5-FU)) were assayed in the transfected cells. DNA microarrays were used to analyze expression changes of apoptosis-related genes. Results Significant downregulation or absence of GKN1 expression in seven gastric cancer cell lines were detected and progressive decrease of GKN1 expression from normal mucosa, precancerous tissue, to cancer tissues was observed. Moreover, restoration of GKN1 expression suppressed gastric cancer cell viability and induced the cells to undergo apoptosis. GKN1 expression also enhanced tumor cell sensitivity to 5-FU treatment. Moreover, it was found that GKN1 expression in AGS cells modulated expression of 19 apoptosis-related genes. Conclusions Expression of GKN1 is progressively lost from normal mucosa, precancerous to cancerous gastric tissues, while restoration of GKN1 expression induces gastric cancer cells to undergo apoptosis, and enhances sensitivity of gastric cancer cells to 5-FU-induced apoptosis.

Abstract Background Aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor associated with gastric carcinogenesis. 3,3'-Diindolylmethane (DIM) is a relatively non-toxic selective AhR modulator. This study was to detect the effects of DIM on gastric cancer cell growth. Methods Gastric cancer cell SGC7901 was treated with DIM at different concentrations (0,10,20,30,40,50 μmol/L) with or without an AhR antagonist, resveratrol. The expression of AhR and Cytochrome P4501A1 (CYP1A1), a classic target gene of AhR pathway, were detected by RT-PCR and Western blot; cell viability was measured by MTT assay, and the changes in cell cycle and apoptosis were analyzed by flow cytometry. Results RT-PCR and western-blot showed that with the increase of the concentration of DIM, AhR protein gradually decreased and CYP1A1 expression increased, suggesting that DIM activated the AhR pathway and caused the translocation of AhR from cytoplasm to nucleus. MTT assay indicated that the viability of SGC7901 cells was significantly decreased in a concentration- and time-dependent manner after DIM treatment and this could be partially reversed by resveratrol. Flow cytometry analysis showed that DIM arrested cell cycle in G1 phase and induced cell apoptosis. Conclusion Selective aryl hydrocarbon receptor modulator 3,3'-Diindolylmethane inhibits SGC7901 cell proliferation by inducing apoptosis and delaying cell cycle progression. AhR may be a potential therapeutic target for gastric cancer treatment.

Abstract Background Abberant aryl hydrocarbon receptor (AhR) expression and AhR pathway activation are involved in gastric carcinogenesis. However, the relationship between AhR pathway activation and gastric cancer progression is still unclear. In present study, we used 2,3,7,8-tetrachlorodibenzo-para-dioxin (TCDD), a classic and most potent ligand of AhR, to activate AhR pathway and investigated the effect of AhR pathway activation on human gastric cancer AGS cell invasion and explored the corresponding mechanism. Results To determine whether AhR pathway can be activated in AGS cells, we examined the expression of CYP1A1, a classic target gene of AhR pathway, following TCDD exposure. RT-PCR and western blot analysis showed that both CYP1A1 mRNA and protein expression were increased in a dose-dependent manner following TCDD treatment and AhR antagonist resveratrol (RSV) could reverse this TCDD-induced CYP1A1 expression. To determine whether TCDD treatment of AGS cells results in an induction of MMP-9 expression, we detected MMP-9 mRNA using RT-PCR and detected MMP-9 enzymatic activity using gelatin zymography. The results showed that both MMP-9 mRNA expression and enzymatic activity were gradually increased with the concentration increase of TCDD in media and these changes could be reversed by RSV treatment in a dose-dependent manner. To examine whether AhR activation-induced MMP-9 expression and activity in AGS cells results in increased migration and invasion, we performed wound healing migration assay and transwell migration and invasion assay. After TCDD treatment, the migration distance and the migration and invasion abilities of AGS cells were increased with a dose-dependent manner. To demonstrate AhR activation-induced MMP-9 expression is mediated by c-Jun, siRNA transfection was performed to silence c-Jun mRNA in AGS cells. The results showed that MMP-9 mRNA expression and activity in untreated control AGS cells were very weak; After TCDD (10 nmol/L) treatment, MMP-9 mRNA expression and activity were significant increased; This TCDD-induced MMP-9 expression and activity increase could be abolished by c-Jun siRNA transfection. Conclusion AhR pathway activation enhances gastric cancer cell invasiveness likely through a c-Jun-dependent induction of MMP-9. Our results provide insight into the mechanism and function of the AhR pathway and its impact on gastric cancer progression.

Background Infliximab (IFX) is effective at inducing and maintaining clinical remission and mucosal healing in patients with Crohn's disease (CD); however, 9%–40% of patients do not respond to primary IFX treatment. This study aimed to construct and validate nomograms to predict IFX response in CD patients. Methods A total of 343 patients diagnosed with CD who had received IFX induction from four tertiary centers between September 2008 and September 2019 were enrolled in this study and randomly classified into a training cohort (n  = 240) and a validation cohort (n  = 103). The primary outcome was primary non-response (PNR) and the secondary outcome was mucosal healing (MH). Nomograms were constructed from the training cohort using multivariate logistic regression. Performance of nomograms was evaluated by area under the receiver-operating characteristic curve (AUC) and calibration curve. The clinical usefulness of nomograms was evaluated by decision-curve analysis. Results The nomogram for PNR was developed based on four independent predictors: age, C-reactive protein (CRP) at week 2, body mass index, and non-stricturing, non-penetrating behavior (B1). AUC was 0.77 in the training cohort and 0.76 in the validation cohort. The nomogram for MH included four independent factors: baseline Crohn's Disease Endoscopic Index of Severity, CRP at week 2, B1, and disease duration. AUC was 0.79 and 0.72 in the training and validation cohorts, respectively. The two nomograms showed good calibration in both cohorts and were superior to single factors and an existing matrix model. The decision curve indicated the clinical usefulness of the PNR nomogram. Conclusions We established and validated nomograms for the prediction of PNR to IFX and MH in CD patients. This graphical tool is easy to use and will assist physicians in therapeutic decision-making. [ABSTRACT FROM AUTHOR]

Background: The clinical significance of the endoscopic appearance of rectal neuroendocrine tumors (NETs) is poorly understood. We aimed to develop a novel scoring system based on endoscopic appearances to predict endoscopically advanced disease in patients with rectal NETs when initially diagnosed.Methods: Patients diagnosed with well-differentiated rectal NETs between January 2005 and December 2019 were retrospectively included. Logistic regression analyses were applied to study the relationship between endoscopic appearance and advanced disease. The whole dataset was randomly divided into training and validation sets, which were used to develop and validate a novel scoring system, respectively.Results: 309 patients were included. The endoscopic appearance of rectal NETs was significantly associated with advanced disease (P < 0.001). A novel scoring system was developed based on endoscopic appearance, including tumor size, tumor shape, and mucosal surface, using the training set. The area under curve (AUC) of the scoring system to predict advanced disease was 0.953 (95 % confidence interval [CI] 0.915 - 0.991; P < 0.001) and 0.960 (95 %CI 0.905 - 1.000; P < 0.001) in the training and validation sets, respectively. Furthermore, the scoring system was significantly associated with tumor grade. Patients with high scores had significantly worse disease-free and overall survival than patients with low scores (P < 0.001).Conclusion: This novel scoring system based on the endoscopic appearance of the primary tumor can help to accurately identify patients with endoscopically advanced disease who are not suitable for endoscopic resection. In addition, it is of great value in monitoring tumor recurrence and overall survival in patients with rectal NETs. [ABSTRACT FROM AUTHOR]

A meta-analysis of 1437 patients from 14 RCTs in China showed that prokinetics combined with PPI were more effective in alleviating symptoms than PPI monotherapy; however, no significant intergroup differences were observed in the mucosal healing rate.104 B Statement 16: Endoscopic radiofrequency ablation (RFA) can improve the GERD symptoms b B Overall agreement: A+, 30.0%; A, 60.0% b B Level of evidence: Moderate b Endoscopic treatments for GERD include endoscopic RFA, transoral incisionless fundoplication (TIF) and anti-reflux mucosectomy (ARMS). Gastroesophageal reflux disease (GERD) is common in clinical practice and its prevalence differs significantly in different countries and regions. The results showed that MSA was superior to PPI in reducing reflux symptoms and had fewer complications.122 A meta-analysis of 19 studies in which MSA was used to treat GERD has revealed that MSA and fundoplication are both effective, and there are no significant differences between them with respect to the reduction of PPI use and improvement of patients' QoL, and only 13.2% of patients require PPI after MSA.123 At present, RCTs and long-term follow-up studies of MSA are scarce; therefore, more clinical evidence is required. It was observed that in 308 patients with upper gastrointestinal symptoms the sensitivity and specificity of the reflux disease questionnaire (RDQ) in diagnosing GERD were 62% and 67%, respectively; while those of the gastroesophageal reflux disease questionnaire (GerdQ) were 65% and 71%, respectively.24,25 The diagnostic value of both questionnaires is higher in patients with typical reflux symptoms than in those with atypical symptoms. [Extracted from the article]

Background and Aims: Epidemics pose a great challenge to health care of patients. However, the impact of unprecedented situation of COVID‐19 outbreak on health care of inflammatory bowel disease (IBD) patients in real‐world setting has seldom been investigated. Methods: We performed an observational study in a tertiary referral IBD center in China. The mode of health care and medication use was compared before and after COVID‐19 outbreak. Electronic questionnaire surveys were performed among gastroenterologists and IBD patients to investigate the impact of COVID‐19 outbreak on their attitudes towards telemedicine. Results: COVID‐19 outbreak resulted in substantial decrease of patients participating in standard face‐to‐face visit during 1 month post‐outbreak (n = 51) than pre‐outbreak (n = 249), whereas the participation in telemedicine was significantly higher than comparable period in 2019 (414 vs 93). During the 1 month after COVID‐19 outbreak, 39 (39/56, 69.6%) patients had their infliximab infusion postponed with the mean delay of 3 weeks. The immunomodulator use was similar between pre‐outbreak and post‐outbreak. Six elective surgeries were postponed for a median of 43 days. In post‐outbreak period, 193 (193/297, 64.98%) of the surveyed physicians have used telemedicine with an increase of 18.9% compared with 46.13% (137/292) in the pre‐outbreak period (P < 0.001); 331 (331/505, 65.54%) of the surveyed IBD patients supported that the use of telemedicine should be increased in future health care. Conclusion: COVID‐19 outbreak resulted in a great change in health‐care access among IBD patients including decrease in standard face‐to‐face visit and delay of biologics use. There was an increased use and need of telemedicine after COVID‐19 outbreak. [ABSTRACT FROM AUTHOR]

Background: Contemporary treatments for functional dyspepsia have limitations. Herbal medicine has been suggested as adjunctive treatment. With growing scientific recognition and public interests, an in‐depth review of this is timely. Aims/Purpose: To evaluate the therapeutic potential and problems that may be associated with the adoption of herbal medicines in functional dyspepsia. Methods: We reviewed the treatment landscape of functional dyspepsia and assessed the scientific community's interest in herbal medicine. Preclinical pharmacological and clinical trial data were reviewed for several herbal medicines available in the market. Challenges associated with adoption of herbal medicine in mainstream medicine were critically evaluated. Results: We found that herbal medicines frequently comprise a combination of herbs with multiple reported pharmacological effects on gastrointestinal motility and secretory functions, as well as cytoprotective and psychotropic properties. We identified a number of commercially available herbal products that have undergone rigorous clinical trials, involving large numbers of well‐defined subjects, reporting both efficacy and safety for functional dyspepsia. Persisting concerns include lack of rigorous assessments for majority of products, toxicity, consistency of ingredients, dose standardizations, and quality control. We provide a quality framework for its evaluation. Conclusions: We commend herbal medicine as a viable future option in managing functional dyspepsia. An attractive appeal of herbal medicine is the prospect to simultaneously target multiple pathophysiological mechanisms. Wider adoption and acceptance of herbal medicines in treatment algorithms of functional dyspepsia will require the application of the scientific rigor expected of chemical therapies, to all stages of their development and evaluation. [ABSTRACT FROM AUTHOR]

Background and Aims: Efficacy of adalimumab in Crohn's disease (CD) has not been shown in China. The aim of this study was to evaluate the efficacy and safety of adalimumab in Chinese patients with CD. Methods: This 26-week, multicenter, phase III study evaluated patients with moderately to severely active CD and elevated high-sensitivity C-reactive protein (⩾3 mg/l) who were naïve to anti–tumor necrosis factor therapy. Patients were randomized to double-blind adalimumab 160/80 mg at weeks 0/2 and 40 mg at weeks 4/6 or placebo at weeks 0/2 followed by blinded adalimumab 160/80 mg at weeks 4/6. At week 8, all patients received open-label 40 mg adalimumab every other week through week 26. The primary endpoint was clinical remission [CD activity index (CDAI) <150] at week 4. Clinical remission at week 26 was assessed in week-8 responders (decrease in CDAI ⩾70 points at week 8 from baseline) and compared with a clinically meaningful threshold of 30%. Adverse events (AEs) were recorded throughout the study. Results: At baseline, 205 patients were enrolled, with mean [standard deviation (SD)] age of 32.9 (9.9) years and CD duration of 2.7 (3.0) years. At week 4, 38/102 patients (37%) receiving adalimumab and 7/103 (7%) receiving placebo (p < 0.001) achieved clinical remission. Among week-8 responders, 93/144 (65%) achieved clinical remission at week 26 (p < 0.001). No unexpected AEs and no malignancies, active tuberculosis, or deaths were reported. Conclusions: Adalimumab induced and maintained remission in Chinese patients with CD. Safety results were consistent with the known safety profile of adalimumab. ClinicalTrials.gov identifier: NCT02499783 [ABSTRACT FROM AUTHOR]

The Asia–Pacific Working Group on Inflammatory Bowel Disease was established in Cebu, Philippines, under the auspices of the Asia–Pacific Association of Gastroenterology with the goal of improving inflammatory bowel disease care in Asia. This consensus is carried out in collaboration with Asian Organization for Crohn's and Colitis. With biologic agents and biosimilars becoming more established, it is necessary to conduct a review on existing literature and establish a consensus on when and how to introduce biologic agents and biosimilars in conjunction with conventional treatments for ulcerative colitis and Crohn's disease in Asia. These statements also address how pharmacogenetics influences the treatments of ulcerative colitis and Crohn's disease and provides guidance on response monitoring and strategies to restore loss of response. Finally, the review includes statements on how to manage treatment alongside possible hepatitis B and tuberculosis infections, both common in Asia. These statements have been prepared and voted upon by members of inflammatory bowel disease workgroup employing the modified Delphi process. These statements do not intend to be all‐encompassing, and future revisions are likely as new data continue to emerge. [ABSTRACT FROM AUTHOR]

Background and Aim Penetrating disease is a common condition complicating Crohn's disease [CD]. Establishing the presence of a fistula and the anatomical definition of the fistulous tracts are essential for deciding on appropriate treatment strategies. We aimed to assess the diagnostic accuracy of intra-cavitary contrast-enhanced ultrasound [IC-CEUS] for the detection of a fistulous tract associated with abscesses in CD patients. Methods In this prospective cohort study, consecutive CD patients suspected of having an intra-abdominal abscess, who were referred for US-guided aspiration were recruited. IC-CEUS was performed by injecting diluted contrast agent [SonoVue] into the abscess cavity immediately following the ultrasound-guided needle abscess aspiration and drainage. The diagnostic accuracy of IC-CEUS in demonstrating the presence of fistulous tracts was compared with that of computed tomography enterography/magnetic resonance enterography [CTE/MRE], using surgical and gross pathological findings as the reference standard. Results Thirty-one patients who underwent IC-CEUS and subsequent surgery were included in the final analysis. IC-CEUS demonstrated fistulous/sinus tracts in 26 of 31 participants with a sensitivity and specificity of 86.7 % (95% confidence interval [CI], 68.4–95.6%) and 100% [95% CI, 5.5–100.0%], respectively. Moreover, IC-CEUS correctly demonstrated fistulous/sinus tracts in 13 participants without delineation of fistulous/sinus tracts on CTE/MRE. Combining IC-CEUS and CTE/MRE, the fistula/sinus tract was clearly demonstrated in 29 patients [93.5%, 29/31]. The mean duration of the IC-CEUS procedure was 8.6 min [range 5.0–12.0]. No severe adverse events occurred during the IC-CEUS procedure. Conclusion In this pilot study, IC-CEUS accurately delineated the anatomical definition of fistulous/sinus tracts associated with intra-abdominal abscesses in CD patients. As a radiation-free and safe technique, IC-CEUS may be used as an alternative/adjunctive method to CTE/MRE for detecting penetrating disease in patients with CD. [ABSTRACT FROM AUTHOR]