World Journal of Gastroenterology最新文献

Glucagon-like peptide-1 receptor (GLP-1R) agonist, a subgroup of incretin-based anti-diabetic therapies, is an emerging medication with benefits in reducing blood glucose and weight and increasing cardiovascular protection. Contrarily, concerns have been raised about GLP-1R agonists increasing the risk of particular cancers. Recently, several epidemiological studies reported contradictory findings of incretin-based therapy on the risk modification for cholangiocarcinoma (CCA). The first cohort study demonstrated that incretin-based therapy was associated with an increased risk of CCA. Later studies, however, showed a null effect of incretin-based therapy on CCA risk for dipeptidyl peptidase-4 inhibitor nor GLP-1R agonist. Mechanistically, glucagon-like peptide 1 receptor is multifunctional, including promoting cell growth. High GLP-1R expressions were associated with progressive phenotypes of CCA cells in vitro. Unexpectedly, the GLP-1R agonist showed anti-tumor effects on CCA cells in vitro and in vivo with unclear mechanisms. Our recent report also showed that GLP-1R agonists suppressed the expression of GLP-1R in CCA cells in vitro and in vivo, leading to the inhibition of CCA tumor growth. This editorial reviews recent evidence, discusses the potential effects of GLP-1R agonists in CCA patients, and proposes underlying mechanisms that would benefit from further basic and clinical investigation.

In this editorial, we comment on the article by Zhou et al published in a recent issue. We specifically focus on the crucial roles of ferroptosis and pyroptosis in acute liver failure (ALF), a disease with high mortality rates. Ferroptosis is the result of increased intracellular reactive oxygen species due to iron accumulation, glutathione (GSH) depletion, and decreased GSH peroxidase 4 activity, while pyroptosis is a procedural cell death mediated by gasdermin D which initiates a sustained inflammatory process. In this review, we describe the characteristics of ferroptosis and pyroptosis, and discuss the involvement of the two cell death modes in the onset and development of ALF. Furthermore, we summarize several interfering methods from the perspective of ferroptosis and pyroptosis for the alleviation of ALF. These observations might provide new targets and a theoretical basis for the treatment of ALF, which are also crucial for improving the prognosis of patients with ALF.

Per-oral endoscopic myotomy (POEM) is an innovative minimally invasive technique and has emerged as the preferred modality for treating achalasia and spastic esophageal disorders in numerous specialized centers worldwide. Gastroesophageal reflux (GER) is a common complication following POEM procedures. Recently, an article in the World Journal of Gastroenterology, providing a comprehensive update on post-POEM GER. In this article, the authors present novel insights and strategies that offer valuable implications for endoscopy.

As the Editor-in-Chief of the World Journal of Gastroenterology, I carefully review all articles every week before a new issue's online publication, including the title, clinical and research importance, originality, novelty, and ratings by the peer reviewers. Based on this review, I select the papers of choice and suggest pertinent changes (e.g., in the title or text) to the company editors responsible for publication. This process, while time-consuming, is essential for assuring the quality of publications and highlighting important articles that readers may revisit.

Background: Gastroesophageal reflux disease (GERD) is a common disease worldwide with varying clinical presentations and risk factors. Prevalence data for Africa is lacking, but an increasing trend is expected due to demographic and epidemiological transitions. Although endoscopic studies for general gastrointestinal disorders have shown some patients with erosive esophagitis (EE), no studies in Ethiopia have investigated the clinical characteristics, risk factors, and severity of GERD using esophagogastroduodenoscopy (EGD).

Aim: To assess the clinical features of GERD in Ethiopian patients who underwent EGD and determine the severity and risk factors of EE.

Methods: We conducted a multicenter, retrospective cross-sectional study of 221 patients diagnosed with GERD and endoscopic findings of EE at Trauma Associated Severe Hemorrhage and Amniotic Membrane Stem Cell between January 2019 and August 2022. Data were collected from electronic medical records and phone call interviews. We used descriptive statistics and binary logistic regression analysis with SPSS version 26 to identify the association between variables with a statistical significance set at P value < 0.05.

Results: The mean ± SD age of the patients was 44.8 (± 15.9) years, with a male-to-female ratio of 1.6:1. The most commonly reported symptom was epigastric pain (80.5%), followed by heartburn (43%). Los Angeles (LA)-A EE was diagnosed in 71.1% of patients, followed by LA-B (14.9%), LA-C (7.7%), and LA-D (5.9%). Multivariate analysis showed that age 50 or above, presence of bleeding, and endoscopic findings of duodenitis/duodenopathy were significantly associated with severe EE (P < 0.05). Stricture and Barrett's esophagus were observed in 4.5% and 1.36% of patients with EE, respectively.

Conclusion: Most of the patients had milder EE with fewer complications. However, severe EE was more prevalent in older patients and those with duodenitis/duodenopathy.

Tofacitinib is an oral small-molecule Janus kinase (JAK) inhibitor that preferentially inhibits JAK1 and JAK3. Its efficacy in inducing and maintaining remission in ulcerative colitis (UC) as well as its safety profile has been demonstrated in multicenter, randomized, double-blind, placebo-controlled trials. Additionally, real-world studies evaluating the effectiveness and adverse effects of tofacitinib have been conducted, affirming its clinical efficacy in moderate-to-severe UC.

This editorial builds on the article by Shakhshir et al. We conducted an overview of evidence-based dietary interventions in adults with inflammatory bowel disease (IBD). In the IBD population, there may be a role for the Mediterranean diet due to its anti-inflammatory effects, long-term sustainability, and role in improving cardiovascular health. In active Crohn's disease, the use of exclusive enteral nutrition, the Crohn's disease exclusion diet, or the specific carbohydrate diet may be used as a short-term adjunct to medical therapy and may improve mucosal healing. The low-FODMAP diet can assist in reducing symptoms for patients without evidence of active bowel inflammation. As interest in nutritional therapy increases amongst clinicians and patients alike, it is integral that dietary therapies are understood and discussed in routine management of patients with IBD as part of holistic care, ideally through a multidisciplinary setting with involvement of experienced dietitians. This serves to improve clinician-patient engagement and reduce complications of IBD including micro and micronutrient deficiencies.

In this editorial, we comment on the article published in the recent issue of the World Journal of Gastroenterology. Acute liver failure (ALF) is a fatal disease that causes uncontrolled massive hepatocyte death and rapid loss of liver function. Ferroptosis and pyroptosis, cell death forms that can be initiated or blocked concurrently, can play significant roles in developing inflammation and various malignancies. However, their roles in ALF remain unclear. The article discovered the positive feedback between ferroptosis and pyroptosis in the progression of ALF, and revealed that the silent information regulator sirtuin 1 (SIRT1) inhibits both pathways through p53, dramatically reducing inflammation and protecting hepatocytes. This suggests the potential use of SIRT1 and its downstream molecules as therapeutics for ALF. Thus, we will discuss the role of ferroptosis and pyroptosis in ALF and the crosstalk between these cell death mechanisms. Additionally, we address potential treatments that could alleviate ALF by simultaneously inhibiting both cell death pathways, as well as examples of SIRT1 activators being used as disease treatment strategies, providing new insights into the therapy of ALF.

Cancer cell dormancy (CCD) in colorectal cancer (CRC) poses a significant challenge to effective treatment. In CRC, CCD contributes to tumour recurrence, drug resistance, and amplifying the disease's burden. The molecular mechanisms governing CCD and strategies for eliminating dormant cancer cells remain largely unexplored. Therefore, understanding the molecular mechanisms governing dormancy is crucial for improving patient outcomes and developing targeted therapies. This editorial highlights the complex interplay of signalling pathways and factors involved in colorectal CCD, emphasizing the roles of Hippo/YAP, pluripotent transcription factors such as NANOG, HIF-1α signalling, and Notch signalling pathways. Additionally, ERK/p38α/β/MAPK pathways, AKT signalling pathway, and Extracellular Matrix Metalloproteinase Inducer, along with some potential less explored pathways such as STAT/p53 switch and canonical and non-canonical Wnt and SMAD signalling, are also involved in promoting colorectal CCD. Highlighting their clinical significance, these findings may offer the potential for identifying key dormancy regulator pathways, improving treatment strategies, surmounting drug resistance, and advancing personalized medicine approaches. Moreover, insights into dormancy mechanisms could lead to the development of predictive biomarkers for identifying patients at risk of recurrence and the tailoring of targeted therapies based on individual dormancy profiles. It is essential to conduct further research into these pathways and their modulation to fully comprehend CRC dormancy mechanisms and enhance patient outcomes.

Background: Antibody-mediated rejection following liver transplantation (LT) has been increasingly recognized, particularly with respect to the emergence of de novo donor-specific antibodies (DSAs) and their impact on graft longevity. While substantial evidence for adult populations exists, research focusing on pediatric LT outcomes remains limited.

Aim: To investigate the prevalence of human leukocyte antigen (HLA) mismatches and DSA and evaluate their association with rejection episodes after pediatric LT.

Methods: A cohort of pediatric LT recipients underwent HLA testing at Santa Casa de Porto Alegre, Brazil, between December 2013 and December 2023. Only patients who survived for > 30 days after LT with at least one DSA analysis were included. DSA classes I and II and cross-matches were analyzed. The presence of de novo DSA (dnDSA) was evaluated at least 3 months after LT using the Luminex^® single antigen bead method, with a positive reaction threshold set at 1000 MFI. Rejection episodes were confirmed by liver biopsy.

Results: Overall, 67 transplanted children were analyzed; 61 received grafts from living donors, 85% of whom were related to recipients. Pre-transplant DSA (class I or II) was detected in 28.3% of patients, and dnDSA was detected in 48.4%. The median time to DSA detection after LT was 19.7 [interquartile range (IQR): 4.3-35.6] months. Biopsy-proven rejection occurred in 13 patients at follow-up, with C4d positivity observed in 5/13 Liver biopsies. The median time to rejection was 7.8 (IQR: 5.7-12.8) months. The presence of dnDSA was significantly associated with rejection (36% vs 3%, P < 0.001). The rejection-free survival rates at 12 and 24 months were 76% vs 100% and 58% vs 95% for patients with dnDSA anti-DQ vs those without, respectively.

Conclusion: Our findings highlight the importance of incorporating DSA assessment into pre- and post-transplantation protocols for pediatric LT recipients. Future implications may include immunosuppression minimization strategies based on this analysis in pediatric LT recipients.