Current Opinion in Gastroenterology最新文献

Purpose of review: Multiple endoscopic ultrasound (EUS) guided therapeutic interventions have been developed for the management of benign and malignant pancreaticobiliary and gastrointestinal luminal pathology. Recent high-quality evidence is increasingly validating these interventions and positioning them within evidence-based therapeutic algorithms.

Recent findings: Here we review therapeutic EUS-guided interventions including pancreatic fluid collection drainage, gastroenterostomy, biliary drainage, pancreatic duct drainage and gallbladder drainage. The most up-to-date high-quality evidence supporting these interventions is presented including comparative data with other conventional treatment options. Newer emerging interventions such as tumor ablation are also reviewed. Current controversies and future avenues for research are discussed. The key role of EUS-guided interventions in managing pancreaticobiliary pathology in patients with a surgically altered anatomy is highlighted.

Summary: Multiple EUS therapeutic interventions have evolved from experimental or rescue options to now well established first- and second-line interventions over other endoscopic, percutaneous and surgical alternatives with the support of high-quality data. Further research is needed to better optimize patient selection and guide long term postintervention follow-up.

Purpose of review: The contributions of intestinal barrier loss, that is, increased permeability, to multiple disorders, including inflammatory bowel disease (IBD), have been a topic of speculation for many years, and the literature is replete with conclusions based on correlation and speculation. The goal of this article is to critically review recent advances in mechanistic understanding of barrier regulation and the evidence for and against contributions of intestinal barrier loss to disease pathogenesis.

Recent findings: It is now recognized that intestinal permeability reflects the combined effects of two distinct routes across tight junctions, which form selectively permeable seals between adjacent epithelial cells, and mucosal damage that leads to nonselective barrier loss. These are referred to as pore and leak pathways across the tight junction and an unrestricted pathway at sites of damage. Despite advances in phenotypic and mechanistic characterization of three distinct permeability pathways, development of experimental agents that specifically target these pathways, and remarkable efficacy in preclinical models, pathway-targeted therapies have not been tested in human subjects.

Summary: After decades of speculation, therapeutic interventions that target the intestinal barrier are nearly within reach. More widespread use of available tools and development of new tools that discriminate between pore, leak, and unrestricted pathway permeabilities and underlying regulatory mechanisms will be essential to understanding the local and systemic consequences of intestinal barrier loss.

Purpose of review: The aim of this review is to present the current state of the field, highlight recent developments, and describe the clinical outcomes of endoscopic therapies for bariatric surgery complications.

Recent findings: The field of interventional endoscopy now presents a range of minimally invasive procedures for addressing postbariatric complications. Lumen-opposing metal stents have emerged as a reliable solution for managing gastrojejunal strictures following Roux-en-Y gastric bypass, whether with or without associated leaks. Additionally, they serve as a conduit for performing endoscopic retrograde cholangiopancreatography (ERCP) post-RYGB via EUS-directed ERCP (EDGE). Gastric peroral endoscopic myotomy, originally designed for gastroparesis, has demonstrated effectiveness in treating postgastric sleeve stenosis, particularly the challenging helical stenosis cases. Furthermore, innovative endoscopic antireflux techniques are showing encouraging outcomes in addressing gastroesophageal reflux disease (GERD) following sleeve gastrectomy. Additionally, several modifications have been proposed to enhance the efficacy of transoral outlet reduction (TORe), originally developed to treat weight regain due to gastrojejunal anastomotic issues post-RYGB.

Summary: Endoscopic management of bariatric surgery complications is continuously evolving. The development of new techniques and devices allows endoscopists to provide novel, minimally invasive alternatives that were not possible in the near past. Many techniques, however, are limited to expert centers because they are technically demanding, and specialized training in bariatric endoscopy is still required.

Purpose of review: Although the mucosal barrier serves as a primary interface between the environment and host, little is known about the repair of acute, superficial lesions or deeper, persistent lesions that if not healed, can be the site of increased permeability to luminal antigens, inflammation, and/or neoplasia development.

Recent findings: Studies on acute superficial lesions have been sparse in the past year, with more focus given to novel mechanisms of mucosal protection, and the way in which mature epithelial cells or committed stem cells dedifferentiate, reprogram, proliferate, and then regenerate the gastroduodenal mucosa after injury. For this, adenoviral therapy showed organ specific targeting with mRNA and protein expression of effectors to protect against mucosal injury and ulceration. A large database of plant-based agents known to protect against injury and ulceration was published, along with studies using plant-based compounds delivered with alginates, polysaccharide/gel floating rafts, or incorporated into nanoparticles or green carbon dots to improve targeting and retention at the ulcerated lesion. With RNA technology developing rapidly, particularly single-cell RNA sequencing, important and novel data was forthcoming on mucosal regeneration. In particular, the role of interleukin-17 hub proteins in mucosal healing was highlighted. The presence and role of injury reserve cells was determined, as was the composition of ligand gradients for cell differentiation in both stomach and duodenum. The role of amphiregulin in parietal cell differentiation from lineage-restricted stem cells and the Yap1 gene signature in metaplasia vs. healing ulcers were of particular importance. Additionally, studies unveiled the important role of mesenchymal stromal cells in differentiation and repair mechanisms, in Muse cells as an exciting new therapy for mucosal repair after injury, and the role of sympathetic neurons in activating the immune system to regulate mucosal repair mechanisms.

Summary: Recent studies highlight novel mechanisms that promote mucosal regeneration after injury of the gastroduodenal mucosa.

Purpose of review: This review highlights recent research in the field of celiac disease.

Recent findings: Epidemiological studies continue to identify celiac disease-associated diseases such as inflammatory arthritis, irritable bowel syndrome, and cardiovascular disease. Recently published consensus guidelines provide recommendations for the long-term management and monitoring of patients with celiac disease. There are multiple pharmaceutical therapies for celiac disease under investigation, and recent phase I and phase II trials are reviewed here. Finally, a recent trial of patients with nonceliac gluten sensitivity demonstrates a significant nocebo effect in this condition.

Summary: Recent advances in celiac disease include the development of new clinical guidelines as well as promising new therapeutics. Continued high-quality research is needed to improve the outcomes of patients with celiac disease and nonceliac enteropathies.

Purpose of review: Functional dyspepsia is a common gastrointestinal disease that is under-recognized and under-diagnosed. It is a complex disorder of gut-brain interaction with no FDA-approved treatment options. The purpose of this review is to highlight updates in the proposed pathophysiology and present new data regarding potential therapies for functional dyspepsia.

Recent findings: Alterations in the intestinal microbiome and integrity of the intestinal membrane may play a crucial role in the pathogenesis of functional dyspepsia. The low FODMAP diet, in addition to modulating the microbiome with antibiotics and probiotics, are targets for large future studies. Novel methods of delivery of gut-brain therapies have shown promising results, especially virtual reality.

Summary: The pathophysiology and management of functional dyspepsia is complex and there is still much unknown; however, continued research is identifying new targets for treatment. New and more targeted treatment options provide clinicians a variety of tools to offer patients with functional dyspepsia.

Purpose of review: This review describes pathologic conditions of retrograde flow into the esophagus along with recent therapeutic advances and treatment options.

Recent findings: The esophagus facilitates anterograde and retrograde movement of contents, the latter of which is mediated by transient lower esophageal sphincter relaxations (TLESRs). Gastroesophageal reflux disease (GERD) often includes esophageal-specific symptoms such as heartburn or regurgitation. Volume regurgitation responds less frequently to acid suppression with proton pump inhibitors (PPIs) than heartburn, given its relationship with incompetence of the esophagogastric junction (EGJ) and increased frequency of TLESRs. Therefore, although the refluxate pH can be altered with PPIs, the frequency of reflux episodes is generally not reduced and surgical and endoscopic treatments may be favored. Other instances of abnormal retrograde esophageal flow respond better to medical therapy, or lifestyle interventions. Compared to gastric belching because of increased stomach distension, supragastric belching is caused by intake of air from pharynx into the esophagus followed by rapid expulsion of air. These conditions can be distinguished on esophageal tests such as high-resolution manometry and are likely to respond to behavioral modifications.

Summary: Retrograde flow into the esophagus can be a normal occurrence, but diagnostic testing to distinguish causes can guide appropriate intervention.

Purpose of review: The purpose of this review was to highlight most recent updates on nutritional aspects in gastroparesis (GP) focusing on dietary recommendations, utilization of enteral and parenteral nutrition, endoscopic and surgical interventions.

Recent findings: Recent data addressed eating patterns, nutritional interventions, and clarifications on the role of endoscopic and surgical interventions underlying an impact on nutritional management of GP patients. They support the importance of gastroparesis-specific diet in addition to drug therapy, and confirm the benefits of a modified low-fat, low-fiber diet. Current guidelines suggest a new approach to GP management based on predominant symptoms. Gastric peroral endoscopic pyloromyotomy (G-POEM) and surgical gastric electrical stimulator (GES) placement may be considered in individuals with nausea and vomiting before the need for jejunostomy tube placement for enteral feeding or parenteral nutrition.

Summary: Current literature supports the importance of dietary interventions, focusing on low-fat and low-fiber diets, in addition to drug therapies. Severely fiber-restrictive diets may not be necessary. There is enhanced understanding when jejunal feeding should be incorporated for refractory cases with consideration of G-POEM or/and GES even before jejunal tube placement. This approach will require patient evaluation in specialized motility centers.