Effectiveness and safety of Moluodan in the treatment of precancerous lesions of gastric cancer: A randomized clinical trial.

OBJECTIVE: To investigate the clinical potential and safety of Moluodan to reverse gastric precancerous lesions. METHODS: Patients aged 18-70 years diagnosed with moderate-to-severe atrophy and/or moderate-to-severe intestinal metaplasia, with or without low-grade dysplasia, and negative for Helicobacter pylori were recruited in this randomized, double-blind, parallel-controlled trial. The primary outcome was the improvement of global histological diagnosis at 1-year follow-up endoscopy using the operative link for gastritis assessment, the operative link for gastric intestinal metaplasia assessment, and the disappearance rate of dysplasia. RESULTS: Between November 3, 2017 and January 27, 2021, 166 subjects were randomly assigned to the Moluodan group, 168 to the folic acid group, 84 to the combination group, and 84 to the high-dose Moluodan group. The improvement in global histological diagnosis was achieved in 60 (39.5%) subjects receiving Moluodan, 59 (37.8%) receiving folic acid, 26 (32.1%) receiving the combined drugs, and 36 (47.4%) receiving high-dose Moluodan. Moluodan was non-inferior to folic acid (95% confidence interval: -9.2 to 12.5; P = 0.02). High-dose Moluodan had a trend for better protective efficacy, though there was no statistical significance. The disappearance rate of dysplasia was 82.8% in the Moluodan group, which was superior to folic acid (53.9%; P = 0.006). No drug-related serious adverse events were observed. CONCLUSIONS: One pack of Moluodan three times daily for 1 year was safe and effective in reversing gastric precancerous lesions, especially dysplasia. Doubling its dose showed a better efficacy trend.

Progression of Gastrointestinal Injury During Antiplatelet Therapy After Percutaneous Coronary Intervention: A Secondary Analysis of the OPT-PEACE Randomized Clinical Trial.

Importance: Gastrointestinal injury progression induced by antiplatelet therapy in patients after percutaneous coronary intervention (PCI) has not been well studied. Objective: To assess the association of aspirin, clopidogrel, and their combination with gastrointestinal injury progression among patients without high bleeding risk after PCI. Design, Setting, and Participants: This secondary analysis assessed data from the Optimal Antiplatelet Therapy for Prevention of Gastrointestinal Injury Evaluated by ANKON Magnetically Controlled Capsule Endoscopy (OPT-PEACE) double-masked, placebo-controlled, multicenter randomized clinical trial. The OPT-PEACE trial was conducted at 28 centers in China, and recruitment took place from July 13, 2017, to July 13, 2019. The trial included patients with stable coronary artery disease or acute coronary syndromes without ST-segment elevation after PCI. Statistical analysis was conducted from September 13, 2022, to January 23, 2023. Interventions: Patients underwent magnetically controlled capsule endoscopy (MCE) at baseline and after 6 months of dual antiplatelet therapy (DAPT) with aspirin (100 mg/d) plus clopidogrel (75 mg/d). Those with no evidence of gastrointestinal ulcers or bleeding (ie, the intention-to-treat [ITT] cohort) were randomized (1:1:1) to aspirin (100 mg/d) plus matching placebo (aspirin alone), clopidogrel (75 mg/d) plus matching placebo (clopidogrel alone), or DAPT for an additional 6 months. A third MCE was performed 12 months after PCI. Main Outcomes and Measures: The primary outcome was the rate of gastric injury progression as assessed with the results of the 3 MCEs (at baseline, 6 months, and 12 months) in the modified intention-to-treat (mITT) population. The key secondary outcome was the rate of small-intestinal injury progression. Gastric or small-intestinal injury progression was defined as a quantitative increase in erosions or ulcers between the second and third MCEs (at 6 and 12 months, respectively). Results: This study included the 394 patients in the mITT cohort. Their mean (SD) age was 56.9 (8.7) years, and most were men (296 [75.1%]). A total of 132 patients were randomized to aspirin alone, 132 to clopidogrel alone, and 130 to DAPT. Gastric injury progression occurred in 49 aspirin users (37.1%), 64 clopidogrel users (48.5%), and 69 DAPT users (53.1%) (P = .02), reflecting a lower rate of gastric injury progression among aspirin users vs DAPT users (risk ratio [RR], 0.70 [95% CI, 0.49-0.99]; P = .009). No significant difference was observed between clopidogrel alone and DAPT (48.5% vs 53.1%; P = .46) or between aspirin alone and clopidogrel alone (37.1% vs 48.5%; P = .06). A total of 51 aspirin users (38.6%), 65 clopidogrel users (49.2%), and 71 DAPT users (54.6%) (P = .03) developed progressive small-intestinal injury, reflecting a lower rate of small-intestinal injury among aspirin users vs DAPT users (RR, 0.71 [95% CI, 0.50-0.99]; P = .01). No difference was observed between patients treated with clopidogrel vs DAPT (49.2% vs 54.6%; P = .38) or with aspirin vs clopidogrel (38.6% vs 49.2%; P = .08). Conclusions and Relevance: In this secondary analysis of a randomized clinical trial, ongoing use of aspirin, clopidogrel, or their combination between 6 and 12 months after PCI was associated with progressive gastric and small-intestinal injury in a substantial proportion of patients, more so with DAPT than with monotherapy. Clopidogrel was at least as likely as aspirin to induce gastrointestinal injury progression. Future research is warranted to determine what impact the findings from MCEs would have on decision-making of antiplatelet therapy. Trial Registration: ClinicalTrials.gov Identifier: NCT03198741.

Establishment and validation of symptomatic patients colorectal screening score for predicting colorectal neoplasia risk.

OBJECTIVES: Currently, most colorectal neoplasia (CRN) screening strategies target asymptomatic individuals. However, studies on patients with non-specific gastrointestinal symptoms (NSGS) are limited. We aimed to develop a CRN risk score specifically for patients with NSGS. METHODS: We prospectively enrolled patients who underwent initial colonoscopy between June 2020 and June 2021. A new risk scoring system was constructed and its applicability was evaluated. RESULTS: A total of 1522 consecutive patients were enrolled, among whom 1016 symptomatic patients were randomly divided into a training cohort and a validation cohort at a ratio of 7:3. The constructed Symptomatic Patients Colorectal Screening (SPCS) score showed higher diagnostic efficacy and sensitivity than several previous scoring systems. Using the SPCS score, the patients were divided into a low-risk group (-2 to 3 points) and a high-risk group (4-10 points) for CRN. Additionally, the detection rate of CRN in the training and validation cohorts of the high-risk group were 41.7% and 37.0%, respectively. The SPCS score detected 79.3% (188/237) of CRN and 87.5% (42/48) of advanced CRN in the high-risk group, which reduced the workload of colonoscopy to 45.9% (466/1016). CONCLUSION: An effective CRN risk scoring system was established and validated for symptomatic patients, which accurately classified individuals into low-risk and high-risk groups for CRN and might be used to optimize colonoscopic resource allocation.

Microbiota regulation in constipation and colorectal cancer.

The relevance of constipation to the development and progression of colorectal cancer (CRC) is currently a controversial issue. Studies have shown that changes in the composition of the gut microbiota, a condition known as ecological imbalance, are correlated with an increasing number of common human diseases, including CRC and constipation. CRC is the second leading cause of cancer-related deaths worldwide, and constipation has been receiving widespread attention as a risk factor for CRC. Early colonoscopy screening of constipated patients, with regular follow-ups and timely intervention, can help detect early intestinal lesions and reduce the risks of developing colorectal polyps and CRC. As an important regulator of the intestinal microenvironment, the gut microbiota plays a critical role in the onset and progression of CRC. An increasing amount of evidence supports the thought that gut microbial composition and function are key determinants of CRC development and progression, with alterations inducing changes in the expression of host genes, metabolic regulation, and local and systemic immunological responses. Furthermore, constipation greatly affects the composition of the gut microbiota, which in turn influences the susceptibility to intestinal diseases such as CRC. However, the crosstalk between the gut microbiota, constipation, and CRC is still unclear.

Blue rubber bleb nevus syndrome complicated with disseminated intravascular coagulation and intestinal obstruction: A case report.

BACKGROUND: Blue rubber bleb nevus syndrome is a rare vascular malformation syndrome with unclear etiopathogenesis and noncurative treatments. It is characterized by multiple vascular malformations of the skin, gastrointestinal tract, and other visceral organs. The most common symptoms are intermittent gastrointestinal bleeding and secondary iron deficiency anemia, thus requiring repeated blood transfusions and hospitalizations. It is easily missed and misdiagnosed, and there is no specific treatment. CASE SUMMARY: We report a case of blue rubber bleb nevus syndrome combined with disseminated intravascular coagulation and efficacy of treatment with argon plasma coagulation under enteroscopy and sirolimus. A 56-year-old female patient was admitted to the hospital with 3-year history of fatigue and dizziness that had aggravated over the past 10 d with melena. The patient had a history of repeated melena and multiple venous hemangiomas from childhood. After treatment with argon plasma coagulation combined with sirolimus for nearly 8 wk, the patient's serum hemoglobin increased to 100 g/L. At the 12-mo follow-up, the patient was well with stable hemoglobin (102 g/L) and no recurrent intestinal bleeding. CONCLUSION: Argon plasma coagulation and sirolimus may be an efficacious and safe treatment for blue rubber bleb nevus syndrome, which currently has no recommended treatments.

Efficacy of keverprazan for duodenal ulcer: A phase II randomized, double-blind, parallel-controlled trial.

BACKGROUND AND AIM: Considering the limitation of varying acid suppression of proton pump inhibitors, this study was aimed to assess the efficacy, safety, and dose-effect relationship of keverprazan, a novel potassium-competitive acid blocker, in the treatment of duodenal ulcer (DU) compared with lansoprazole. METHODS: A randomized, double-blind, double-dummy, multicenter, low-dose, high-dose, and positive-drug parallel-controlled study was conducted to verify the non-inferiority of keverprazan (20 or 30 mg) to lansoprazole of 30 mg once daily for 4 to 6 weeks and dose-effect relationship of keverprazan in the treatment of patients with active DU confirmed by endoscopy. RESULTS: Of the 180 subjects randomized, including 55 cases in the keverprazan_20 mg group, 61 cases in the keverprazan_30 mg group, and 64 cases in the lansoprazole_30 mg group, 168 subjects (93.33%) completed the study. The proportions of healed DU subjects in the keverprazan_20 mg, keverprazan_30 mg, and lansoprazole_30 mg groups were respectively 87.27%, 90.16%, and 79.69% at week 4 (P = 0.4595) and were respectively 96.36%, 98.36%, and 92.19% at week 6 (P = 0.2577). The incidence of adverse events in the keverprazan_20 mg group was lower than that in the lansoprazole_30 mg (P = 0.0285) and keverprazan_30 mg groups (P = 0.0398). CONCLUSIONS: Keverprazan was effective and non-inferior to lansoprazole in healing DU. Based on the comparable efficacy and safety data, keverprazan of 20 mg once daily is recommended for the follow-up study of acid-related disorders. (Trial registration number: ChiCTR2100043455.).

Efficacy and safety of vibrating capsule for functional constipation (VICONS): A randomised, double-blind, placebo-controlled, multicenter trial.

Background: Functional constipation (FC) is an intractable disease that carries large financial burden as well as emotional and physical stress. We aimed to assess the efficacy and safety of the newly developed smartphone-controlled vibrating capsule (VC) in patients with FC. Methods: From December 2018 to February 2020, we did a multicenter, blinded, placebo-controlled randomised trial in six top general hospitals in China focusing on patients aged 18 to 80 with FC. Patients were randomly assigned in a 1:1 ratio to receive VCs or placebo treatment for six weeks (two capsules per week) after a two-week baseline period. The primary outcome was the responder rate, defined as the proportion of patients with an increase of at least one complete spontaneous bowel movement (CSBM) per week during treatment compared to baseline in the full analysis set. This trial is registered with ClinicalTrials.gov, number NCT04671264, and is completed. Findings: 107 patients aged from 18 to 74 were randomly assigned to receive VC (n = 53) or placebo treatment (n = 54). The responder rate in the VC group was significantly higher than that in the placebo group (64·2% vs. 35·8%; difference, 27·7% [95% CI, 10·4-45·1]; P = 0·005). More patients in the VC group reported weekly CSBMs ≥ 1 for at least four weeks during treatment (difference, 22·7% [95% CI, 8-46]; P = 0·022) and follow-up period (difference, 17.3% [95% CI, 0-35]; P = 0·048). The mean Patient Assessment of Constipation-Symptoms score and Patient Assessment of Constipation-Quality of Life score differed significantly from the baseline in both groups (all P < 0·0001). The most common adverse event associated with VC was abdominal discomfort (3·7%). Interpretation: VCs can promote defecation, as well as ameliorating symptoms and improving the quality of life in patients with FC with sustained efficacy. VC appears to be a potential alternative physical treatment for FC with the exact mechanism and parameters warranting further investigation. Funding: The study was supported by "One hundred leading scientists for 21st century" of Health Department of Shanghai Municipal Government (to ZL, No.2017BR005).

Effect of Bacillus subtilis, Enterococcus faecium, and Enterococcus faecalis supernatants on serotonin transporter expression in cells and tissues.

BACKGROUND: Bacillus subtilis (B. subtilis), Enterococcus faecium (E. faecium), and Enterococcus faecalis (E. faecalis) are probiotics that are widely used in the clinical treatment of irritable bowel syndrome (IBS). Whether the supernatants of these three probiotics can improve gastrointestinal sensation and movement by regulating the serotonin transporter (SERT) expression needs to be clarified. AIM: To investigate whether B. subtilis, E. faecium, and E. faecalis supernatants can upregulate SERT expression in vitro and in vivo. METHODS: Caco-2 and HT-29 cells were stimulated with probiotic culture supernatants for 12 and 24 h, respectively. A male Sprague-Dawley rat model of post-infectious irritable bowel syndrome (PI-IBS) was established and the rats were treated with phosphate-buffered saline (group A) and three probiotics culture supernatants (groups B, C, and D) for 4 wk. The levels of SERT were detected by quantitative PCR and western blotting. RESULTS: The levels of SERT at post-treatment 12 and 24 h were significantly elevated in Caco-2 cells treated with B. subtilis supernatant compared with those in the control group (a P < 0.05). Those levels were markedly upregulated in Caco-2 cells stimulated with E. faecium and E. faecalis supernatants at 24 h (a P < 0.05). In addition, SERT expression in groups B, C, and D was significantly higher than that in group A in the 2nd wk (a P < 0.05). Increased SERT expression was only found in group D in the 3rd wk (a P < 0.05). However, there was no significant difference in SERT expression between the groups in the last week (P > 0.05). CONCLUSION: The supernatants of B. subtilis, E. faecium, and E. faecalis can upregulate SERT expression in intestinal epithelial cells and the intestinal tissues in the rat model of PI-IBS.

Fecal Signatures of Streptococcus anginosus and Streptococcus constellatus for Noninvasive Screening and Early Warning of Gastric Cancer.

BACKGROUND & AIMS: Most patients with gastric cancer (GCa) are diagnosed at an advanced stage. We aimed to investigate novel fecal signatures for clinical application in early diagnosis of GCa. METHODS: This was an observational study that included 1043 patients from 10 hospitals in China. In the discovery cohort, 16S ribosomal RNA gene analysis was performed in paired samples (tissues and feces) from patients with GCa and chronic gastritis (ChG) to determine differential abundant microbes. Their relative abundances were detected using quantitative real-time polymerase chain reaction to test them as bacterial candidates in the training cohort. Their diagnostic efficacy was validated in the validation cohort. RESULTS: Significant enrichments of Streptococcus anginosus (Sa) and Streptococcus constellatus (Sc) in GCa tumor tissues (P < .05) and feces (P < .0001) were observed in patients with intraepithelial neoplasia, early and advanced GCa. Either the signature parallel test Sa∪Sc or single signature Sa/Sc demonstrated superior sensitivity (Sa: 75.6% vs 72.1%, P < .05; Sc: 84.4% vs 64.0%, P < .001; and Sa∪Sc: 91.1% vs 81.4%, P < .01) in detecting early GCa compared with advanced GCa (specificity: Sa: 84.0% vs 83.9%, Sc: 70.4% vs 82.3%, and Sa∪Sc: 64.0% vs 73.4%). Fecal signature Sa∪Sc outperformed Sa∪CEA/Sc∪CEA in the discrimination of advanced GCa (sensitivity: 81.4% vs 74.2% and 81.4% vs 72.3%, P < .01; specificity: 73.4% vs 81.0 % and 73.4% vs 81.0%). The performance of Sa∪Sc in the diagnosis of both early and advanced GCa was verified in the validation cohort. CONCLUSION: Fecal Sa and Sc are noninvasive, accurate, and sensitive signatures for early warning in GCa. (ClinicalTrials.gov, Number: NCT04638959).

Alterations in the composition of the gut microbiota affect absorption of cholecalciferol in severe osteoporosis.

INTRODUCTION: To evaluate the relationship between the gut microbial composition and intestinal cholecalciferol absorption in patients with severe osteoporosis (SOP). MATERIALS AND METHODS: Eighteen patients with primary osteoporosis (OP) and 18 with SOP were included. Their clinical data were collected and their circulating concentrations of cholecalciferol and 25(OH)D3 were measured. Fecal samples were collected and their microbial contents were analyzed using 16S rDNA sequencing. RESULTS: The age, sex, body mass index, and body mass of the participants did not differ between the groups. The prevalence of gastrointestinal symptoms in the participants with SOP was significantly higher than that in the participants with OP. There were significant differences in the 25(OH)D3 and cholecalciferol concentrations between participants with SOP or OP and there was a significant positive correlation between the concentrations of these substance. The diversity of the gut microbiota in participants with SOP was significantly higher than that in participants with OP. Firmicutes was more abundant in the SOP group and the ratio of Firmicutes/Bacteroidetes in participants with SOP was higher. Conversely, Bifidobacterium was significantly less abundant, as were the order and family it belongs to. At the species level, Bifidobacterium was the most significant difference between the two groups. CONCLUSION: Differences in the intestinal microecology, especially Bifidobacterium, are associated with differences in the absorption of cholecalciferol and in the circulating 25(OH)D3 concentration, which may influence the progression of OP to SOP.

Interplay between gut microbiota and bile acids in diarrhoea-predominant irritable bowel syndrome: a review.

Irritable bowel syndrome (IBS) is a common functional gastrointestinal disease that disturbs the physiology and psychology of patients and increases the burden on families, the healthcare system, society, and economic development, affecting more and more people around the world. Despite the multiple factors that account for IBS remaining incompletely studied, emerging evidence demonstrated the abnormal changes in gut microbiota and bile acids (BAs) metabolism closely associated with IBS. Moreover, microbiota drives significant modifications for BAs, consisting of deconjugation, 7α-dehydroxylation, oxidation, epimerization, desulfation, esterification, and so on, while BAs, in turn, affect the microbiota directly or indirectly. In light of the complex connection among gut microbiota, BAs, and IBS, it is urgent to review the latest research progress in this field. In this review, we described the disorders of intestinal microecology and BAs profiles in IBS-D and also highlighted the cross-talk between gut microbiota and BAs in the context of IBS-D. Integrating these, we suggest that new therapeutic strategies targeting the microbiota-BAs axis for IBS-D, even for other related diseases caused by bacteria-bile acid dysbiosis should be expected.

Cronkhite-Canada syndrome: An investigation in clinical features and pathogenesis.

OBJECTIVE: This study aimed to investigate the clinical features and potential pathogenesis of a rare nonhereditary polyposis syndrome, Cronkhite-Canada syndrome (CCS). METHODS: Medical records of eight patients with CCS who were admitted to our hospital from January 2005 to November 2019 were reviewed. Transcriptome profiling was performed in one patient to investigate its difference between gastric polyp tissue and normal mucosa. Differentially expressed genes (DEGs) were determined for functional analysis. The expression of inhibin beta A (INHBA) was further assessed by using immunohistochemistry. RESULTS: All patients presented with gastrointestinal polyposis, accompanied by diarrhea, skin hyperpigmentation, hair loss and nail dystrophy. Hyperplastic polyps were observed in seven patients, tubular adenoma in two, inflammatory polyps in one and hamartomatous polyps in one, respectively. All patients underwent comprehensive treatment and five achieved clinical remission. A total of 2107 DEGs, including 1265 upregulated and 842 downregulated, were found in the gastric polyp. Gene ontology analysis showed that upregulated genes were significantly enriched in the positive regulation of cell proliferation, epithelium development and angiogenesis. A protein-protein interaction analysis suggested that INHBA was at the center of the interaction network and might play an important role in CCS. Immunohistochemistry confirmed that INHBA expression was upregulated in CCS gastric polyps. CONCLUSIONS: CCS is a rare disease and its diagnosis mainly depends on typical clinical manifestations, endoscopic findings and histological features. INHBA upregulation may contribute to its pathogenesis.

Identification of Key Genes and Immune Infiltrate in Nonalcoholic Steatohepatitis: A Bioinformatic Analysis.

BACKGROUND: Nonalcoholic steatohepatitis (NASH) can progress to cirrhosis and hepatic carcinoma and is closely associated with changes in the neurological environment. The discovery of new biomarkers would aid in the treatment of NASH. METHODS: Data GSE89632 were downloaded from the Gene Expression Omnibus (GEO) database, and R package "limma" was used to identify differentially expressed genes (DEGs) for NASH vs. normal tissues. The STRING database was used to construct a protein-protein interaction (PPI) network, and the Cytoscape software program (Version 3.80) was used to visualize the PPI network and identify key genes. The immune infiltration of NASH was determined using the R package "CIBERSORT". RESULTS: We screened 41 DEGs. GO and KEGG enrichment analyses of the DEGs revealed the enrichment of pathways related to NAFLD steatosis and inflammation. A PPI network analysis was also performed on the DEGs, and seven genes (MYC, CXCL8, FOS, SOCS1, SOCS3, IL6, and PTGS2) were identified as hub genes. An immune infiltration assessment revealed that macrophages M2, memory resting CD4+ T cells, and Î³Δ T cells play important roles in the immune microenvironment of NASH, which may be mediated by the seven identified hub genes.

The relationship between gut microbiota and proteolytic activity in irritable bowel syndrome.

Irritable bowel syndrome (IBS) is a common functional gastrointestinal disease that affects 3.8-9.2% of the world population. It affects the physiology and psychology of patients and increases the burden on families, the healthcare system, society, and economic development. Presently, a large number of studies have shown that compared to healthy individuals, the composition and diversity of gut microbiota in IBS patients have changed, and the proteolytic activity (PA) in fecal supernatant and colonic mucosa of IBS patients has also increased. These findings indicate that the imbalance of intestinal microecology and intestinal protein hydrolysis is closely related to IBS. Furthermore, the intestinal flora is a key substance that regulates the PA and is associated with IBS. The current review described the intestinal microecology and intestinal proteolytic activity of patients with IBS and also discussed the effect of intestinal flora on PA. In summary, this study proposed a pivotal role of gut microbiota and PA in IBS, respectively, and provided an in-depth insight into the diagnosis and treatment targets of IBS as well as the formulation of new treatment strategies for other digestive diseases and protease-related diseases.

Peroral endoscopic myotomy for the treatment of achalasia after failed pneumatic dilation.

BACKGROUND AND AIMS: POEM is a rescue endoscopic therapy for patients who had previously failed surgical or endoscopic treatment. However, data regarding its effectiveness after failed pneumatic dilation (PD) and its long-term effects are limited. We aimed to retrospectively investigate the long-term outcomes in patients who had undergone POEM after failed PD. METHODS: Data from 66 achalasia patients with a 2-year follow-up period were analyzed. Intraprocedural events were compared between the first POEM group (patients without prior-endoscopic intervention) and prior PD group (patients who had pre-POEM PD). Symptom evaluation, HRM and 24 h-pH DeMeester scores between the two groups were performed at 2 years after the POEM procedure. Muscularis externa samples were obtained from the lower esophagus using POEM to assess the muscle fibrosis with Azan-Mallory staining. RESULTS: POEM was successfully performed for all achalasia patients. During the 2-year follow-up period, the success rate of POEM was 96.15% (25/26) for patients with prior PD and 95% (38/40) with primary POEM. For patients with type II achalasia and who underwent prior PD, the post-procedure DeMeester score was higher compared to patients who underwent POEM only (P < 0.05). A larger number of patients who underwent primary POEM (27.50%, 11/40) complained of mild heartburn compared to patients who underwent POEM after PD (7.69%, 2/26) (P < 0.05). With regards to fibrosis, the majority of patients who underwent POEM only were classified as F-1 (45.00%, 18/40), while the majority of patients who underwent prior PD were classified as F-2 (42.3%, 11/26). The degree of fibrosis was significantly different between the two groups (P < 0.05). Both surgical time and prior PD were correlated with the degree of fibrosis (P < 0.05). CONCLUSIONS: Despite the technical challenges, pre-POEM endoscopic treatment does not impact the safety and efficacy of POEM in achalasia patients. Longer follow-up studies using larger cohorts are needed to determine long-term outcomes and complications of POEM.

An Update on Eosinophilic Esophagitis: Etiological Factors, Coexisting Diseases, and Complications.

BACKGROUND: Eosinophilic esophagitis (EoE) is an immune-mediated clinicopathological condition characterized by esophageal infiltration with eosinophils resulting in chronic inflammation and stricture. SUMMARY: The recent increase in the incidence of EoE and the characteristic presentation of symptoms with difficulty swallowing and food bolus impaction has raised key concerns of clinicians as well as researchers. EoE often presents with dysphagia, food impaction, nausea, regurgitation or vomiting, and decreased appetite. It is more common in males, affecting both adults and children. The causative manner of this condition is complex and multifactorial. Throughout recent years, researchers have made a significant contribution to understanding the pathogenesis of EoE, genetic background, natural history, work on allergy, and standardization in the evaluation of disease activity. There is relatively high prevalence of EoE among the population, emphasizing the importance of this disease. Key messages: Esophageal involvement with eosinophils may be manifested as isolated or with coexisting conditions and should be taken into consideration in the differential diagnosis. This study aimed to provide gastroenterologists with novel insights into the evaluation of esophageal involvement with eosinophils and to pay special attention to the etiological factors, coexisting clinical diseases, and complications.

miR­31 promotes tumorigenesis in ulcerative colitis­associated neoplasia via downregulation of SATB2.

Ulcerative colitis (UC) features chronic, non-infectious inflammation of the colon. The risk of ulcerative colitis­associated neoplasia (UCAN) increases in direct association with the duration of this disease. Whether miRNAs exert a regulatory effect on the pathogenesis of UCAN has remained to be elucidated. In the present study, differentially expressed genes (DEGs) and microRNAs (miRNAs/miRs) were identified using bioinformatics analysis of Gene Expression Omnibus datasets. Enrichment analyses were performed to determine the function of the DEGs. The target genes of key miRNAs were predicted using miRWalk. Validation of DEGs and miRNAs in patients with UC, UC with low­grade dysplasia and UC with high­grade dysplasia (UC­HGD) was performed using reverse transcription­quantitative PCR analysis. A total of 38 differentially expressed miRNAs and 307 mRNAs were identified from the profiles and miR­31 was validated as being overexpressed in UCAN tissues, particularly in the UC­HGD samples. Furthermore, special AT­rich DNA­binding protein 2 (SATB2) was validated as a target gene of miR­31 and SATB2 expression was negatively correlated with miR­31 expression. Therefore, miR­31 is upregulated in UCAN and it may promote tumorigenesis through downregulation of SATB2.

Trastuzumab plus docetaxel and capecitabine as a first-line treatment for HER2-positive advanced gastric or gastroesophageal junction cancer: a phase II, multicenter, open-label, single-arm study.

Gastric cancer (GC) is the second most common cancer in China. The ToGA study showed that trastuzumab in combination with fluoropyrimidine plus cisplatin prolonged overall survival (OS) in patients with human epidermal growth factor receptor 2 (HER2)-positive advanced GC (AGC). However, some patients may not be able to receive this regimen. We conducted a clinical study to evaluate the efficacy and safety of trastuzumab in combination with docetaxel+capecitabine (DX) in patients with HER2-positive AGC. This phase II, multi-center, open-label, single arm study enrolled patients with HER2-positive AGC who had not received prior treatment for metastatic disease. Patients were treated with a regimen of trastuzumab (8 mg/kg loading dose followed by 6 mg/kg, day 1), capecitabine (1000 mg/m2 twice daily, days 1-14) and docetaxel (60 mg/m2, day 1 for 6 cycles) every 3 weeks. The primary endpoint was progression-free survival (PFS) and the secondary endpoints were objective response rate (ORR), OS and safety profiles. Sixty-seven patients with AGC were enrolled from 14 centers. 64 were included in the full analysis set (FAS). The median PFS was 8.1 months (95% confidence interval [CI]: 5.6-12.8) and the median OS was 20.9 months (95% CI: 15.1-33.0). Response was evaluated in 59 patients. The ORR was 67.8%. The most common adverse events of Grade ≥3 were neutropenia, leukopenia, hand-foot syndrome, febrile neutropenia and anemia. We concluded that combination treatment with trastuzumab and DX was well-tolerated and highly effective in patients with HER2-positive AGC, and may offer an alternative to current treatments.

Gastrointestinal bleeding caused by jejunal angiosarcoma: A case report.

BACKGROUND: Angiosarcoma is a rare disease with a poor prognosis. Its occurrence in the small intestine is low, and gastrointestinal bleeding caused by small intestinal angiosarcoma is unusual. CASE SUMMARY: Here, we report the case of a 57-year-old man who presented with hematochezia for 1 mo. The patient had a medical history of chronic viral hepatitis B for 15 years. The causes of gastrointestinal bleeding were initially diagnosed as esophagogastric variceal bleeding or portal hypertensive gastropathy before endoscopy. However, after a complicated diagnostic and therapeutic process, including gastroendoscopy, colonoscopy, contrast-enhanced computed tomographic (CT), positron emission computed tomography/CT, capsule endoscopy, and pathological and immunohistochemical examinations, small intestinal angiosarcoma was diagnosed. Arrest of bleeding was achieved after surgical treatment. Furthermore, the patient had lung cancer with bone and adrenal metastases. At the follow-up 10 mo after the operation, the patient was alive. CONCLUSION: Gastroenterologists should maintain strong vigilance to small intestinal angiosarcoma, which is necessary for the early identification of this infrequent but fatal disease.