Gastro-oesophageal reflux disease (GORD) is among the most commonly diagnosed gastrointestinal disorders, with a substantial impact on quality of life, mental health, sleep and healthcare costs. Although proton pump inhibitors (PPIs) remain first-line therapy, a sizeable minority of patients are PPI-dependent or PPI-refractory and many wish to avoid lifelong pharmacotherapy without committing to laparoscopic fundoplication. Endoscopic antireflux therapies (EARTs) bridge this therapeutic gap. The currently relevant modalities—transoral incisionless fundoplication (TIF V.2.0) and concomitant TIF with hiatal hernia repair (cTIF), endoscopic full-thickness plication (GERD-X), the mucosal interventions antireflux mucosectomy (ARMS) and anti-reflux mucosal ablation (ARMA) and radiofrequency ablation (Stretta)—work through distinct mechanisms but share the goal of reinforcing the gastro-oesophageal junction. The 2025 American Society for Gastrointestinal Endoscopy (ASGE) guideline now formally endorses TIF and cTIF as evidence-based alternatives to chronic medical therapy in selected patients. The first sham-controlled randomised controlled trials of ARMA, published in 2026, have refined our understanding of its niche: ARMA appears effective in reflux-predominant GORD characterised by an acid exposure time (AET) <6% with >80 reflux episodes per 24 hours but provides no benefit over sham in conventional acid-predominant disease. Magnetic sphincter augmentation (LINX) has matured as a minimally invasive surgical alternative. This review synthesises the contemporary evidence using Lyon Consensus V.2.0 phenotyping as the framework for patient selection, discusses training, safety and cost considerations and offers a practical algorithm for choosing among EARTs and identifying patients best referred for surgery.

Endoscopic ultrasound (EUS)-guided drainage with metal stents is a standard therapy for walled-off necrosis (WON). However, some patients require re-interventions such as stent unclogging, necrosectomy or percutaneous drainage. This study aimed at identifying predictors of re-intervention to facilitate risk stratification and optimize management. This study included consecutive patients who underwent EUS-guided WON drainage with metal stents between January 2023 and December 2024 at a tertiary referral center. Demographic, clinical and radiological data was collected prospectively. Multi-variate logistic regression identified independent predictors of re-intervention. Model performance was evaluated using receiver operating characteristic (ROC) curve, calibration plot and decision curve analysis. Model’s diagnostic performance was evaluated in the validation cohort. Of 500 patients (83.2

Background:Endoscopic sleeve gastroplasty (ESG) and semaglutide are established therapies for obesity. However, comparative real-world data remain limited. We compared the effectiveness and safety of ESG versus oral semaglutide 14 mg in adults with obesity. Methods:In a real-world retrospective comparative cohort study between January 2024 and April 2025, adults aged 18-65 years with body mass index (BMI) ≥30, or ≥27 kg/m2 with obesity-related comorbidity, treated with either ESG or oral semaglutide 14mg daily, and having 6-months' follow-up were included. Primary endpoint was percentage total body weight loss (%TBWL) at 6 months. Secondary outcomes included treatment responder rates, adverse events, and 12-month weight outcomes. Analyses included Welch's two-sample t-tests, analysis of covariance adjusted for age, sex, baseline BMI, and diabetes, inverse probability of treatment weighting (IPTW), and 1:1 propensity score matching. Results:150 patients were included (ESG n=50; semaglutide n=100). Baseline characteristics were broadly similar between groups. At 6 months, mean %TBWL was significantly higher with ESG than semaglutide (12.72±5.67% vs 8.67±3.84%, P=0.0001) that remained after covariate adjustment (adjusted mean difference 4.04%, P=0.0001), IPTW analysis (P<0.001), and propensity-matched analysis (P=0.021). Responder rates ≥10%TBWL were achieved in 70% with ESG versus 43% with semaglutide (relative risk [RR] 0.62, 95%CI 0.46-0.82, P=0.0009), and ≥15%TBWL in 36% versus 7% (RR 0.20, 95%CI 0.09-0.44, P=0.0006). There were no major adverse events. At 12 months, mean %TBWL was 11.92±6.93 with ESG and 10.91±4.66 with semaglutide (P=0.41). During follow-up, 18 patients discontinued semaglutide and 5 ESG patients initiated semaglutide. Conclusions:ESG was associated with greater short-term weight loss and higher responder rates than oral semaglutide 14mg. At 12 months, weight loss was sustained in both groups without significant between-group difference. These preliminary findings should be interpreted with caution in absence of randomized trial design.

INTRODUCTION:Chronic pain causes an imbalance of autonomic function, often indicated by reductions in parasympathetic heart rate variability (HRV) indices. This study aimed to investigate HRV measures among patients with chronic pancreatitis (CP), and healthy controls (HCs), and the influence of diabetes on these parameters. METHODS:HRV measures, which are time and frequency-derived non-invasive measures of autonomic function, were obtained from the electrocardiography (ECG) recordings. Moreover, deceleration capacity, and periodic repolarization dynamics were assessed as measures of parasympathetic and sympathetic activity. RESULTS:A total of 141 participants (38 pain-free CP, 53 painful CP, and 50 healthy controls) were analysed. Painful CP patients exhibited more pronounced parasympathetic reductions assessed with the root mean square of successive differences between normal beats (14.5 ms IQR 11.5-22 versus 21.8 ms IQR 17.6-32.4; P=0.01) and high frequency content (118.2 ms² versus 273.4 ms²; P=0.007) in comparison to pain-free CP. Moreover, there was a decreased standard deviation of normal-to-normal interbeat intervals (31.6±18.7 ms versus 39.9±18.5 ms; P=0.04), and low frequency content (158.9 ms² versus 480.4 ms²; P=0.003) indicating altered sympathovagal balance. Furthermore, the mean RR interval was greater in non-diabetic CP patients (830.5±144.2 ms) compared to those with diabetes (770.7±139.4 ms; P=0.05). CONCLUSIONS:Chronic pancreatitis, particularly when painful, is associated with significant autonomic dysregulation, characterized by a pronounced reduction in parasympathetic activity as measured by HRV compared to pain-free patients.

BACKGROUND:Adequate gastric mucosal visibility (GMV) is essential for high quality upper gastrointestinal (GI) endoscopy. Simethicone and N-acetylcysteine (NAC) are commonly used to improve mucosal visibility, but the optimal timing of administration remains uncertain. OBJECTIVE:This double-blinded randomized controlled trial (RCT) evaluated the optimal interval between premedication (simethicone + NAC) and endoscopy for achieving adequate GMV. DESIGN:In this RCT, adults undergoing elective upper GI endoscopy were randomized to four groups: placebo (Group 1), premedication to endoscopy interval of 10-20 (Group 2), 21-30 (Group 3), or > 30 min (Group 4). GMV was scored in four gastric regions (antrum, distal body, proximal body, fundus) on a 4-point scale (range 4-16). The primary outcome was adequate GMV (total score < 7). Secondary outcomes included median total GMV score, region-wise mucosal visibility scores, lesion detection rate, and predictors of adequate GMV. RESULTS:A total of 1200 adults were randomized to four groups. Adequate GMV was significantly more frequent in Groups 3 (64.7%) and 4 (66.7%) than in placebo (2.7%) or Group 2 (25.0%). Subgroup analysis within Group 4 demonstrated a declining trend after 50 min. ROC analysis suggested an optimal cut-off of 25 min in predicting adequate GMV with area under the curve of 0.80. In region-wise analysis, mean visibility scores were lowest in antrum and distal body. There was no significant difference in the detection of gastric lesions across study groups (p = 0.913). No serious adverse events related to premedication were observed. CONCLUSION:Premedication with simethicone and NAC significantly improves GMV. The improvement becomes optimal at 20-30 min after ingestion and is consistently maintained up to 50 min. TRIAL REGISTRATION:ClinicalTrials.gov identifier: NCT06581783.

BACKGROUND AND AIMS: Chronic pancreatitis (CP) is associated with several systemic metabolic abnormalities including diabetes. While the colonic microbiota and its association with diabetes in CP have been reported, the specific composition of the small intestinal microbiota and its function in CP remains poorly understood. In this pilot study, we primarily aimed to characterize the jejunal microbiota in patients with CP and explore potential associations with diabetes. METHODS: Jejunal aspirates were collected in a RNAlater-containing sterile container from 29 patients with CP and 10 controls. The samples were then snap lysed followed by metagenomic DNA extraction. Next-generation sequencing was performed for the variable region 3-4 of the 16SrDNA in Illumina MiSeq. After quality control, microbial profiling and functional analysis were conducted using standard bioinformatics pipelines. We also evaluated tight junction integrity in jejunal biopsy samples using immunofluorescence. Furthermore, we assessed for plasma and stool metabolites. RESULTS: Patients with CP exhibited higher abundances of Prevotella vespertina, Prevotella oris, and Prevotella salivae, while controls demonstrated higher abundances of Prevotella scopos, Veillonella, Rothia, and Lachnospiraceae. Immunofluorescence showed decreased expression of the tight junction protein occludin in the jejunal mucosa of CP diabetic (CPD) patients compared to endoscopic controls (EC) (p.corr. CPD-EC = 0.012). No differences were seen between CP nondiabetic and endoscopic controls, and between the CP subgroups (CPND-EC = 0.29 and CPD-CPND = 1 respectively). Overall, there were significant plasma metabolomic abnormalities in patients with CP and a trend toward reduction of butyrate in the stool samples of the CP patients with diabetes. CONCLUSION: Our observations suggest alterations in the jejunal microbiota and mucosal barrier function in CP. These were associated with lower fecal butyrate. This may contribute to the pathogenesis of associated metabolic complications in CP. Further largescale longitudinal and mechanistic studies are needed to validate our findings.

Diagnosing hepatopancreatobiliary (HPB) malignancies remains challenging. Conventional imaging often lacks sensitivity for occult nodal and distant metastases, and FDG PET/CT has variable performance due to low uptake in several tumour subtypes and false-positive uptake in inflammation. Fibroblast activation protein inhibitor (FAPI) PET/CT has emerged as a promising alternative. This study compared the diagnostic accuracy of FDG PET/CT, FAPI PET/CT, and a dual-tracer approach in suspected HPB malignancies. This retrospective analysis included patients who underwent both [18F]FDG and [68Ga]Ga-FAPI-46 PET/CT for suspected HPB cancer, including cholangiocarcinoma, gallbladder carcinoma, pancreatic carcinoma, periampullary carcinoma, and hepatocellular carcinoma. Histopathology and/or clinical follow-up served as reference standard. FDG PET/CT classification used an SUVmax cut-off derived from receiver-operating characteristic analysis, while FAPI PET/CT classification followed expert clinical interpretation. Sensitivity, specificity, and accuracy metrics were compared using paired statistics. 176 patients were included. FAPI PET/CT demonstrated higher sensitivity than FDG PET/CT (93.0

BACKGROUND:Pain is the predominant symptom of chronic pancreatitis (CP). Pancreatic quantitative sensory testing (P-QST) provides a semi-objective assessment of pain processing, but has not been previously reported for Indian patients. This study aimed to evaluate pain characteristics using P-QST in Indian patients with CP. METHODS:Patients with painful CP and age- and sex-matched healthy controls (HCs) from two tertiary centers in northern (All India Institute of Medical Sciences, AIIMS) and southern India (Asian Institute of Gastroenterology, AIG) were included. P-QST assessed temporal summation (spinal hyperexcitability), pressure pain detection (pPDT), and tolerance thresholds (pPTT) across five dermatomes, tolerance to tonic cold pain, and conditioned pain modulation (descending pain inhibition). P-QST parameters were compared between CP and HC subgroups, stratified by center, and inter-center differences were evaluated. RESULTS:A total of 451 participants (251 CP, 200 HCs) were enrolled. TS scores were comparable between groups. Patients with CP had lower pPDT and pPTT sums than HCs at both centers (AIG: 2513 vs 2717 kPa, P = 0.006; 2966 vs 3337 kPa, P < 0.001; AIIMS: 1666 vs 1870 kPa, P < 0.001; 2355 vs 3033 kPa, P=<0.001). Cold pressor endurance time was shorter in CP (AIG: 54 vs 74 s, P < 0.001; AIIMS: 103 vs 114 s, P = 0.013). CPM responses were higher in CP (AIG: 5% vs 0%, P = 0.002; AIIMS: 5% vs 3%, P = 0.014) CONCLUSION: P-QST showed consistent, widespread hyperalgesia in Indian patients with painful CP, providing a window of opportunity to identify central sensitization and validating its clinical utility in assessing central pain modulation across diverse populations.

Background/objectives Pancreatitis is associated with choledochal cyst (CDC). We aimed to investigate the occurrence of acute and chronic pancreatitis in a cohort of pediatric and adult patients with CDC and the predictive factors for pancreatitis. Methods We conducted a retrospective cohort study of 654 consecutive patients who underwent choledochal cyst excision between July 2004 and July 2024 at a tertiary care center. Patients were classified as having acute pancreatitis (AP), chronic pancreatitis (CP), or no pancreatitis (NP) based on preoperative clinical, biochemical, and imaging criteria. Outcomes were compared between pediatric (<18 years) and adult (≥18 years) patients. Multivariable logistic regression was used to identify factors independently associated with AP and CP. Results Pancreatitis was present in 151 patients (23.1%): 93 (14.2%) had AP and 58 (8.9%) had CP. AP was significantly more frequent in pediatric patients (18.99% vs. 11.11%, p = 0.006). Adults had significantly longer duration of symptoms and biliary interventions. On multivariate analysis, pediatric age (<18 years) was independently associated with a higher likelihood of AP (odds ratio [OR] 2.05, p = 0.002). Pancreas divisum was independently associated with CP (OR 3.69, p = 0.002). Pancreatitis recurrence after CDC excision was 6.9% and 7.7% in the AP and CP groups which might be an under-estimation because of low follow-up (55.6%; median 96.5 months), Conclusions Acute pancreatitis predominates in pediatric patients. Apart from a higher prevalence of pancreas divisum, no predictive factors were found for CP. This should be interpreted cautiously because of retrospective non standardized imaging assessment.

Among patients with pancreatic cancer and biliary obstruction planned for pancreaticoduodenectomy, preoperative biliary drainage (PBD) may be considered during surgical delays. Higher complication rates have been reported for PBD using plastic stents versus early surgery. PBD with a self-expanding metal stent (SEMS) has not been compared with early surgery in a randomized controlled trial (RCT). We conducted a noninferiority RCT comparing PBD using a SEMS versus early surgery at 11 centers in 9 countries. We enrolled patients with resectable pancreatic or periampullary cancer and serum total bilirubin level ≥ 5.8 mg/dL, scheduled for primary resection. Primary endpoint was the proportion of patients reporting ≥ 1 serious adverse event (SAE) 120 days post-randomization. Secondary endpoints included rate of SEMS insertion, rate of curative-intent resection, and all-cause mortality. Among 284 patients, 144 were randomized to PBD and 140 to early surgery. In the modified intention-to-treat primary endpoint analysis, ≥ 1 SAE(s) occurred in 29.0