Trending Topics in Gastroenterology | GastroAGI

MEK Inhibitors and Gastric Precancerous Lesions: Gastroenterology | March 2026

What Are MEK Inhibitors? MEK inhibitors are targeted drugs that block the MAPK/ERK signalling pathway, specifically the MEK (mitogen-activated protein kinase kinase) enzyme. This pathway regulates cell proliferation, survival, and differentiation, and its abnormal activation contributes to several cancers. Drugs such as trametinib are already used in oncology (e.g., melanoma and BRAF-mutant cancers) and are now being explored for reversing early precancerous changes in tissues before cancer develops. What Are Gastric Precancerous Lesions? Gastric precancerous lesions are pathological changes in the stomach lining that increase the risk of gastric cancer. The most important include: 1. Chronic atrophic gastritis 2. Intestinal metaplasia (IM) 3. Dysplasia These lesions often arise after long-term Helicobacter pylori infection and may progress to gastric cancer over many years. Summary In a phase 1 clinical trial evaluating trametinib, a MEK inhibitor, for reversing gastric precancerous lesions such as intestinal metaplasia and parietal cell atrophy. The trial suggested that short-term, low-dose MEK inhibition may improve gastric mucosal histology, indicating a potential preventive strategy against gastric cancer. However, the authors highlight important limitations. The study included only 15 patients, lacked a randomised placebo-controlled group, and focused exclusively on patients with previously resected stage I gastric cancer and prior H. pylori eradication, limiting generalizability. Additionally, histologic improvements are intermediate markers and do not prove reduced cancer risk, particularly with only 1 year of follow-up. Statistical concerns, such as a lack of adjustment for multiple comparisons, were also noted. Despite these limitations, the study represents the first human investigation of MEK inhibitors for gastric cancer prevention, providing early proof-of-concept and laying the groundwork for larger, long-term trials assessing cancer incidence as the ultimate outcome.

Eosinophilic Gastrointestinal Diseases in 2026: Gastroenterology | March 26

Introduction Eosinophilic gastrointestinal diseases (EGIDs) are chronic, immune-mediated disorders defined by eosinophil-predominant inflammation in the GI tract. Over the past 30 years, EGIDs—especially eosinophilic esophagitis (EoE)—have risen sharply without a clear plateau. This review summarises what has changed most in epidemiology, natural history, diagnosis, and treatment, and where the biggest gaps remain. 20 Key Takeaways (Clinician-focused) Two big buckets: EGIDs are now classified as EoE (oesophagus only) and non-EoE EGIDs (stomach, small bowel, colon ± overlap). New nomenclature matters: “Eosinophilic gastroenteritis” is being de-emphasised in favour of site-specific labels (EoG, EoN, EoC), improving clarity for care and research. EoE is no longer rare: Incidence and prevalence have continued to climb globally, often faster than endoscopy/biopsy rates. “Tip of the iceberg” problem: Many patients likely remain undiagnosed due to under-biopsying, missed follow-up after food bolus impaction, and diagnostic delay (often years). High-yield clinical settings for EoE: EoE is common in dysphagia, extremely common in food impaction, and should be excluded before antireflux surgery or when strictures are present. Atopy linkage is strong: Food allergy, asthma, eczema, and allergic rhinitis markedly increase EoE probability; risk rises with more atopic comorbidities. Diagnosis of EoE is straightforward: Symptoms of oesophageal dysfunction + ≥15 eos/hpf on oesophageal biopsy + exclusion of competing causes. Severity tracking is evolving: Tools like I-SEE help frame symptoms/complications, inflammatory activity, and fibrostenotic features over time. Non-EoE EGIDs remain uncommon—but likely underrecognized: Prevalence is low in many datasets, but symptom nonspecificity and biopsy/reading variability may miss cases. Non-EoE diagnosis is harder because eosinophils are “normal” distally: Unlike the oesophagus, eosinophils are normal residents in stomach/small bowel/colon—so thresholds and context matter. Proposed histologic thresholds vary by segment: Practical cutoffs (approximate) increase from stomach/duodenum toward ileum/right colon and then decline leftward. Non-EoE EGIDs can be mucosal, muscular, or serosal: Symptoms and complications reflect depth—muscular disease can obstruct; serosal disease can present with eosinophilic ascites. Natural history of EoE is chronic and often progressive: Untreated inflammation can move toward fibrosis/stricture (fibrostenosis); risk increases with time and gaps in care. EoE relapse is the rule when therapy stops: Multiple RCTs show high recurrence rates after withdrawing effective treatment. EoE treatment pillars are now established: PPI, swallowed topical corticosteroids (STCs), food elimination diets (FEDs), and dupilumab are central options. PPI is a legitimate anti-inflammatory strategy in EoE: About half achieve histologic remission; twice-daily dosing tends to perform better than once daily; maintenance can work for many responders. STCs are highly effective and now disease-specific: Budesonide formulations (e.g., oral suspension/orodispersible tablet) have strong induction and maintenance data; candidiasis is the most common AE. Dupilumab is the first approved biologic for EoE: It targets IL-4/IL-13 signaling and achieves meaningful histologic and symptom benefits, with a generally favourable safety profile. Diet therapy is effective but should start simply: Empiric elimination is recommended, often beginning with the least restrictive (commonly milk elimination) and escalating stepwise if needed; allergy tests do not reliably identify triggers. Non-EoE EGIDs: steroids still dominate; biologics are emerging: Evidence is mostly observational; systemic/topical steroids and elemental/elimination diets are used, while newer agents (e.g., IL-13 pathway drugs, dupilumab in EoG/EoN trials) are promising, but the field still lacks approved therapies and robust endpoints.

Falling Prevalence of GI Malignancy in Adults With Iron Deficiency Anaemia – IDIOM V: Endoscopy | 2026

Introduction Iron deficiency anaemia (IDA) has long been considered an important red flag for underlying gastrointestinal (GI) malignancy. However, with evolving referral patterns, widespread endoscopic access, and prior imaging, the true contemporary cancer yield in IDA requires reassessment. Summary In this audit of 1253 consecutive adults referred to a hospital IDA service (2022–2023), 934 underwent full GI investigation. The prevalence of GI cancer was 5.6%, confirming a continued decline compared with historical figures. Two variables showed strong negative associations with malignancy: prior colonic imaging within 5 years and long-term proton pump inhibitor (PPI) exposure. Incorporating PPI status into the existing IDIOM risk score improved predictive discrimination (c-statistic 0.84 vs 0.77). These findings support a shift toward refined risk stratification rather than universal invasive investigation, with prospective validation needed before practice change.

Wedge Pillow vs Evening PPI for Nocturnal Reflux: Neurogastro & Motility | Feb. 2026

Many patients continue to experience nocturnal heartburn or regurgitation despite taking a standard morning proton pump inhibitor (PPI). Current practice often escalates to a second (evening) PPI dose, while wedge pillows are recommended as a non-pharmacologic option—yet direct comparative evidence has been limited. This randomized noninferiority trial enrolled patients with frequent nocturnal reflux symptoms despite at least four weeks of morning PPI therapy. Participants were randomized for four weeks to either (1) add a wedge pillow while continuing morning PPI, or (2) intensify to twice-daily PPI. Outcomes included nocturnal symptom burden (NGSSIQ), quality of life, sleep quality, daytime sleepiness, and objective reflux metrics using 24-hour pH-impedance monitoring. Pillow adherence was objectively tracked using a pressure-sensing timekeeper. At four weeks, the wedge pillow strategy was non-inferior to twice-daily PPI for improving nocturnal reflux symptoms. Notably, sleep quality improved more with the wedge pillow. Objective reflux testing showed only limited differences between groups, suggesting that the symptomatic benefit may not be solely explained by measurable reductions in reflux episodes, and may involve improved sleep mechanics or arousal thresholds. Compliance and satisfaction with the pillow were high. Clinical takeaway: For patients with persistent nocturnal reflux symptoms on morning PPI, adding a wedge pillow is a credible, low-risk alternative to escalating acid suppression—particularly when sleep disruption is a dominant complaint.

Capsule Sponge Triage for Reflux

This large, single-center, prospective cohort study evaluated a non-endoscopic capsule sponge (CS) triage pathway for patients routinely referred with reflux symptoms over 4 years. The goal was to assess its impact on endoscopy utilisation, diagnostic yield, and long-term safety. Among 871 patients who underwent capsule sponge testing, nearly 88% provided adequate samples. Importantly, 62% avoided endoscopy, and most of these low-risk patients were safely discharged. Abnormal CS results were seen in approximately 10% of patients and were strongly associated with significant pathology. One case of esophageal cancer, two cases of Barrett’s dysplasia, and 34 cases of Barrett’s esophagus were detected. The positive predictive value for Barrett’s esophagus in patients with abnormal CS was 43.5%, while the negative predictive value was high at 98.2%. Long-term follow-up (over 2,000 patient-years) confirmed safety. Only a small proportion of patients with a negative CS who later underwent endoscopy for persistent symptoms were found to have Barrett’s or atrophic gastritis. Patient acceptability was excellent, with over 97% finding the test acceptable. Overall, the capsule sponge pathway safely stratifies reflux patients, increases the yield of significant endoscopic diagnoses, reduces unnecessary procedures, and supports more efficient endoscopy resource utilization.

Metopimazine in Gastroparesis: Safe, Mixed Efficacy Signals- AJG Feb.2026

Gastroparesis is a chronic, debilitating disorder characterised by nausea, vomiting, early satiety, postprandial fullness, and abdominal pain. Current pharmacologic options are limited by modest efficacy and safety concerns, particularly central nervous system and cardiac adverse effects. There is therefore a strong need for new, well-tolerated therapies that effectively target core symptoms—especially nausea. Metopimazine is a dopamine D2 receptor antagonist that is peripherally restricted, reducing the risk of central neurologic side effects. It has been used in Europe for decades to treat nausea and vomiting. This phase 2 study evaluated NG101, an oral mesylate formulation of metopimazine, for the treatment of gastroparesis. In this multicenter, double-blind trial, patients with diabetic or idiopathic gastroparesis received NG101 at varying doses or placebo for 12 weeks. Symptom severity was tracked using daily patient-reported outcome diaries, with a primary focus on nausea severity and multiple secondary assessments of global symptom improvement. Although NG101 did not significantly reduce nausea severity compared with placebo on the primary symptom score, patients receiving NG101 consistently reported greater overall improvement in nausea when asked to rate their global change in symptoms. This suggests that patients perceived meaningful benefit, even if the magnitude of symptom change on numeric scales was modest. Importantly, NG101 was well tolerated, with a favorable safety profile across all doses. Notably, treatment effects appeared more favorable in idiopathic gastroparesis than in diabetic gastroparesis, raising the possibility of phenotype-specific benefit. This finding aligns with emerging evidence that gastroparesis subtypes respond differently to pharmacologic therapies. In summary, while NG101 did not meet its primary efficacy endpoint, it demonstrated good tolerability and encouraging patient-reported improvements, particularly in idiopathic gastroparesis. These results support further targeted studies to clarify its role in symptom-directed management of gastroparesis.

LPS vs LPRD: The San Diego Consensus Redefines LPR- AJG Feb.26

Introduction “Laryngopharyngeal reflux (LPR)” has become a catch-all label for chronic throat and upper airway complaints—cough, throat clearing, hoarseness, phlegm, throat pain—often without objective evidence of reflux. This has led to overdiagnosis, prolonged proton-pump inhibitor (PPI) trials, unnecessary testing, and frequent frustration for both patients and clinicians. The San Diego Consensus is a multidisciplinary effort (GI + ENT + speech-language pathology + psychology) that proposes a modern, objective, and practical care pathway. The central paradigm shift 1) Rename the symptom state Laryngopharyngeal Symptoms (LPS) = the symptom cluster (throat/upper airway symptoms) that may be reflux-related. Laryngopharyngeal Reflux Disease (LPRD) = LPS plus objective evidence of reflux. ✅ Key message: LPS ≠ LPRD. Most patients with LPS do not have proven reflux-driven disease. What changes in daily practice? 2) Laryngoscopy is necessary, but it cannot diagnose LPRD Laryngoscopy is valuable to: evaluate nonreflux laryngeal pathology (including malignancy), identify benign lesions and alternative ENT diagnoses. But laryngoscopic signs are nonspecific and should not be used alone to diagnose “LPR.” 3) Split patients early: LPS with GERD symptoms vs isolated LPS This is a major practical step because the algorithm diverges: A) LPS + typical oesophageal reflux symptoms (heartburn/regurgitation) Reasonable to start lifestyle measures + empiric acid suppression (often PPI twice daily for ~3 months) ± alginate. If symptoms persist or management will escalate (long-term therapy or invasive reflux procedures): objective testing is required. B) Isolated LPS (no typical GERD symptoms) Do not default to empiric PPI-first management. Prioritize: ENT evaluation (laryngoscopy), early consideration of behavioural/laryngeal hypersensitivity mechanisms, and objective reflux testing if reflux is being considered as the driver. 4) Reflux monitoring is the reference standard for LPRD For diagnosing reflux-driven disease, the consensus emphasises: 24-hour pH-impedance (best to characterise reflux episodes, nonacid/proximal events; helpful in isolated LPS when mechanism matters) 96-hour wireless pH (best for day-to-day variability and confirming/ excluding abnormal acid burden; particularly useful when considering escalation of reflux management) These modalities are not mutually exclusive; they answer different questions. Also: Testing in “unproven GERD” should typically be done off acid suppression. Oropharyngeal pH monitoring alone is not supported as a stand-alone diagnostic test due to poor specificity. The “forgotten driver”: laryngeal hyperresponsiveness and hypervigilance The consensus brings a clinician-friendly framing: many patients have symptoms driven or amplified by: laryngeal hypersensitivity, hyperresponsive behaviors (cough/throat clearing cycles), symptom-specific anxiety and hypervigilance. These respond to: laryngeal recalibration therapy (voice-specialized SLP approaches), neuromodulators (selected cases), targeted behavioral therapies (e.g., CBT aimed at symptom-specific processes). ✅ Key message: Even when reflux exists, brain–larynx behavioral drivers can coexist and perpetuate symptoms. Bottom-line takeaway: The San Diego Consensus replaces “LPR as a diagnosis” with a more accurate framework: define LPS, confirm LPRD only with objective reflux evidence, avoid reflexive long-term PPI use in isolated throat symptoms, and explicitly treat laryngeal hyperresponsiveness/hypervigilance when present. One-line GastroAGI takeaway Most “LPR” isn’t reflux disease—diagnose LPRD with objective testing and treat the brain–larynx axis when needed.

Psychological Factors Shape Outcomes After Achalasia Treatment- Gastroenterology Feb.26

Introduction Achalasia is traditionally managed as a pure motility disorder, and treatment success is usually judged by technical outcomes—lower oesophageal sphincter (LES) disruption, improved emptying on timed barium esophagram (TBE), and manometric changes. Yet, many clinicians recognise a frustrating reality: Some patients continue to report dysphagia, chest pain, and poor quality of life despite objectively successful treatment. This study addresses an often-overlooked question: Do psychological factors—specifically oesophageal hypervigilance and anxiety—predict how patients feel after achalasia treatment? The clinical problem Persistent symptoms after pneumatic dilation, POEM, or Heller myotomy are commonly attributed to: incomplete myotomy, reflux, or residual obstruction. However, these explanations do not fully account for patients who have: good oesophageal emptying, acceptable manometry, and no major structural issues—yet remain highly symptomatic. This raises the possibility that central symptom processing, not oesophageal mechanics alone, influences outcomes. What the authors studied: The investigators evaluated achalasia patients after definitive therapy and assessed: Oesophageal Hypervigilance and Anxiety using the EHAS (a validated scale), Oesophageal-specific quality of life (E-QOL / NEQOL), Objective measures such as TBE. They then examined whether psychological measures predicted post-treatment symptoms and quality of life independent of objective oesophageal findings. Key findings clinicians should understand 1) Hypervigilance and anxiety strongly predict patient-reported outcomes Higher scores on oesophageal hypervigilance and anxiety were associated with: worse post-treatment symptoms, and poorer oesophageal-specific quality of life. This relationship persisted even when objective measures were acceptable. 2) Objective success does not guarantee symptomatic success Patients with good TBE results and technically successful interventions still reported poor outcomes if hypervigilance and anxiety were high. 3) Achalasia outcomes are not purely mechanical These findings support a brain–esophagus interaction, where heightened symptom monitoring, fear of symptoms, and anxiety amplify symptom perception after treatment. Why this matters in clinical practice Explains “unexplained failure” This study helps explain why some patients remain dissatisfied after technically successful achalasia therapy. Pre-treatment counseling Identifying high hypervigilance/anxiety before intervention may: set realistic expectations, reduce post-treatment dissatisfaction. Post-treatment management Persistent symptoms should not automatically trigger: repeat dilation, redo POEM, or escalation to surgery. In selected patients, psychological or behavioural interventions may be more appropriate. Practical take-home messages If post-treatment symptoms do not match objective findings, consider hypervigilance and anxiety. Use validated tools (like EHAS) to identify at-risk patients. A multidisciplinary approach—including behavioural therapy, reassurance, and symptom education—may improve outcomes more than additional procedures. Bottom-line takeaway: In achalasia, patient outcomes are driven not only by oesophagal emptying, but also by how symptoms are perceived and processed. Addressing oesophagal hypervigilance and anxiety is essential to improving real-world treatment success. One-line GastroAGI takeaway Successful achalasia treatment requires treating both the esophagus and the brain.

Beyond Gastric Cancer: The True Burden of H. pylori- Gastroenterology Feb.26

Introduction Helicobacter pylori is universally recognised as a major cause of gastric cancer, and screen-and-treat strategies are often evaluated almost exclusively through this lens. However, H. pylori also drives a broad spectrum of other gastrointestinal diseases—many far more common than cancer—that substantially affect patients, healthcare systems, and quality of life. This study asks an important but often ignored question: How much disease burden attributable to H. pylori are we overlooking when we focus only on gastric cancer? The problem with current policy thinking Most cost-effectiveness models and guideline discussions around H. pylori eradication prioritise: gastric cancer incidence and mortality. What they frequently exclude or underweight: peptic ulcer disease (PUD), functional dyspepsia, and gastric lymphomas (eg, MALT lymphoma). As a result, the true public-health benefit of eradication is likely underestimated, especially in countries with moderate H. pylori prevalence. What the authors did: Performed a systematic review of studies linking H. pylori to PUD, dyspepsia, and gastric lymphoma. Calculated population attributable fractions (PAF)—the proportion of disease directly caused by H. pylori. Estimated how many cases of each condition could be prevented through eradication, both globally and in individual countries with different H. pylori prevalence. Key findings clinicians and policymakers should grasp 1) H. pylori drives a large share of ulcer disease worldwide More than half of peptic ulcer disease globally is attributable to H. pylori. This translates into millions of preventable ulcer cases—far exceeding the absolute number of gastric cancers prevented. 2) Dyspepsia matters—even with lower attributable fractions Although only a smaller proportion of dyspepsia is attributable to H. pylori, the sheer prevalence of dyspepsia means that tens of millions of cases worldwide could potentially be prevented or improved with eradication. 3) Gastric lymphoma prevention is real, though less frequent A meaningful fraction of gastric lymphomas—rare but serious—are also attributable to H. pylori, reinforcing eradication as a cancer-prevention strategy beyond adenocarcinoma. 4) Benefits persist even in low-prevalence countries Even in countries like the United States, where H. pylori prevalence is relatively low, preventable numbers of ulcers and dyspepsia cases remain substantial. This challenges the notion that eradication only “makes sense” in high-prevalence Asian settings. This paper reframes H. pylori eradication as: not just a cancer-prevention tool, but a multidisease prevention strategy with broad population-level benefits. When PUD and dyspepsia are included: The health gains increase dramatically, Cost-effectiveness improves, and screen-and-treat strategies may be justified in a wider range of healthcare systems. Key nuance: timing matters The authors rightly caution that the true benefit depends on biology: If H. pylori triggers irreversible disease pathways early in life, later eradication may not fully prevent disease. This highlights the importance of early-life or young-adult eradication strategies in future models. Bottom-line takeaway: By focusing only on gastric cancer, we are substantially underestimating the public-health value of H. pylori eradication. Including peptic ulcer disease and dyspepsia fundamentally changes the balance in favour of broader screen-and-treat strategies. One-line GastroAGI takeaway H. pylori eradication prevents far more disease than gastric cancer alone—and policy models should reflect that reality.

Vonoprazan based dual therapy of H.Pylori infection - Front. Med.,2026

The study titled "Vonoprazan-based dual therapy for H. pylori eradication" published in *Frontiers in Medicine* in 2026 systematically evaluates the efficacy and safety of Vonoprazan-based high-dose dual therapy (VPZ-HDDT) compared to proton pump inhibitor-based high-dose dual therapy (PPI-HDDT) for Helicobacter pylori (H. pylori) eradication as a first-line treatment. Below is a detailed summary of the study findings, including an explanation of Vonoprazan and the ideal dual therapy for H. pylori eradication. --- ### **What is Vonoprazan?** Vonoprazan (VPZ) is a novel potassium-competitive acid blocker (P-CAB) that has emerged as a highly effective acid-suppressing agent. Unlike traditional proton pump inhibitors (PPIs), Vonoprazan exhibits: - **Rapid onset of action**: It begins suppressing gastric acid secretion quickly. - **Potent acid inhibition**: It provides stronger acid suppression compared to PPIs. - **Long-lasting effect**: It maintains a stable, high pH environment in the stomach for an extended period. These properties make Vonoprazan particularly suitable for enhancing the effectiveness of H. pylori eradication therapies, as adequate acid suppression is critical for the success of such treatments. --- ### **What is the Ideal Dual Therapy for H. pylori Eradication?** The ideal dual therapy for H. pylori eradication involves: 1. **High-dose acid suppression**: To maintain a consistently high gastric pH, which enhances the efficacy of antibiotics. 2. **Amoxicillin**: A broad-spectrum antibiotic with low resistance rates that targets H. pylori. 3. **Simplified regimen**: A two-drug regimen (high-dose dual therapy) is preferred over triple or quadruple therapies due to reduced complexity, fewer side effects, and better patient compliance. Vonoprazan-based high-dose dual therapy (VPZ-HDDT) includes: - Vonoprazan: Provides potent and stable acid suppression. - Amoxicillin: Administered at a high dose (3,000 mg/day) to maximize its antibacterial activity. This dual therapy regimen is designed to improve eradication rates while minimizing adverse effects and ensuring high patient compliance. ### **Study Summary** - **Efficacy**: VPZ-HDDT demonstrated superior H. pylori eradication rates compared to PPI-HDDT, making it a more effective first-line treatment option. - **Safety**: Both regimens had comparable safety profiles, with no significant differences in adverse event rates. - **Compliance**: High compliance was observed in both groups, indicating that patients tolerated both regimens well. ### **Key Takeaway** Vonoprazan-based high-dose dual therapy (VPZ-HDDT) is a highly effective and safe first-line treatment for H. pylori eradication, outperforming traditional PPI-based dual therapy in terms of eradication rates while maintaining comparable safety and compliance. This novel approach has the potential to become the new standard for H. pylori management.