Stefano Siboni

Objective: We aimed to validate individual endoscopic parameters against clinical and functional testing and to build a simple classification of fundoplication integrity. Summary Background Data: Endoscopy is the main tool to assess the gastroesophageal valve after antireflux surgery (ARS), but existing classifications are complex and have never been validated against objective pathophysiologic data. Methods: This was a single-center, two-phase cohort study of adults undergoing endoscopy, high-resolution manometry (HRM), and reflux monitoring after ARS. Retroflexed videoclips were reviewed blinded to functional results. In the development cohort (2018–2024), endoscopic parameters were tested against pathologic GERD (Lyon 2.0 criteria); those correlating with reflux were included in the classification and the population was stratified according to the number of impaired mechanisms (0–3). In the second phase, the classification was validated prospectively (2024–2026). Results: Of 122 patients, 73 formed the development and 49 the validation cohort. Three parameters were associated with pathologic GERD: intrathoracic valve, disrupted valve, and visible hiatus. Clinical, manometric, and reflux metrics worsened stepwise with the number of impaired mechanisms, and pathologic GERD rose from 11.8% to 37.5% to 85.7%. The new classification discriminated pathologic GERD with an area under the curve of 0.860 in the development and 0.870 in the validation cohort (0.869 overall). Conclusions: A simple endoscopic classification based on valve location, disruption, and hiatal opening reliably identifies fundoplication failure and correlates with symptoms, manometric features, and reflux burden.

Background: Several high‐resolution manometry (HRM) metrics of esophagogastric junction (EGJ) competence exist, but they have never been compared head‐to‐head in one cohort against a uniform gastroesophageal reflux disease (GERD) definition. We aimed to assess whether any anatomical or pressure metric outperforms the others. Methods: Consecutive patients undergoing endoscopy, HRM, and ambulatory reflux monitoring for suspected GERD between December 2022 and December 2025 were studied. GERD was defined by the Lyon 2.0 criteria. All EGJ metrics were recalculated de novo by a single blinded reader. Paired AUC differences were tested with the DeLong method and interpreted against a pre‐specified equivalence margin of ΔAUC 0.05. Results: Of 429 patients (48.3% male; median age 52 years), 212 (49.4%) had GERD. Every metric differed between groups (all p < 0.001) and correlated weakly to moderately with acid exposure time and mean nocturnal baseline impedance. Among anatomical metrics, EGJ morphology (2017 Consensus) had the highest AUC (0.714); LES intra‐abdominal length, hiatal hernia, and Akimoto morphology were equivalent (95% CI of ΔAUC within ±0.05), whereas LES total length performed worse (ΔAUC 0.095, 95% CI 0.034–0.155). Among pressure metrics, EGJ‐CI at IGP + 2 mmHg had the highest AUC (0.692), and six of seven comparators were equivalent. Comparisons between hiatal hernia sizing methods and for LESPI were inconclusive. Conclusions: Anatomical and pressure HRM metrics of EGJ competence are equivalent within a 0.05 AUC margin and all provide only moderate discrimination for GERD. None can be preferred on diagnostic grounds, so the simplest and fastest to calculate may reasonably be chosen.

Introduction: Gastroesophageal reflux disease (GERD) with erosive esophagitis is driven by antireflux barrier (ARB) dysfunction, yet a comprehensive high-resolution manometry (HRM) assessment across Los Angeles (LA) grades is lacking. This study evaluates HRM metrics in patients with erosive esophagitis to validate Lyon 2.0 consensus criteria, hypothesizing that LA grade B esophagitis shares manometric features with severe GERD (LA grades C-D) and that HRM can stratify LA grade A patients for objective GERD risk. Methods: A retrospective multicenter study (July 2022 to July 2025) enrolled 254 patients with GERD symptoms and erosive esophagitis (LA grade A: 145, B: 84, C-D: 25) across 6 centers. Patients underwent off-PPI endoscopy, HRM, and pH monitoring. HRM assessed esophagogastric junction (EGJ) morphology, EGJ-contractile integral (EGJ-CI), ineffective esophageal motility (IEM), straight leg raise (SLR), and Milan Score. Pathologic GERD was defined per Lyon 2.0 criteria. Results: LA grades B and C-D showed a higher rate of hiatal hernia, positive SLR, and lower EGJ-CI compared with LA grade A ( P P <0.001). Reflux monitoring confirmed pathologic GERD in 96% (B) and 100% (C-D) versus 50% (A) based on pH and impedance criteria. In LA grade A, patients with ≥2 disrupted ARB mechanisms (67.5%) had higher GERD rates than those with intact ARB (29.2%). Discussion: HRM supports Lyon 2.0 inclusion of LA grade B as definitive GERD, with manometric profiles similar to C-D. In LA grade A, compromised ARB identifies higher GERD risk, guiding therapy escalation.

Background: Primary motor esophagogastric junction outflow obstruction (EGJOO) is an esophageal motility disorder identified by high‐resolution manometry (HRM) in the absence of an underlying structural or mechanical cause of obstruction. The clinical significance, management, and prognosis of primary motor EGJOO remain uncertain. This clinical practice update provides expert guidance on the evaluation and management of EGJOO, with particular emphasis on determining when the condition is “actionable”—that is, likely to benefit from lower esophageal sphincter (LES)‐directed therapies. Methods: With the endorsement of the European Society of Neurogastroenterology and Motility, an 11‐member international Working Group developed recommendation statements on EGJOO, focusing on the diagnosis and management of actionable primary motor EGJOO. Statements were developed based on available literature evidence and presented at virtual meetings. Each statement was voted upon by the Working Group, and statements reaching ≥ 80% agreement were included as recommendations. Results: Twelve statements reached the agreement threshold. In summary, the Working Group agrees that actionable primary motor EGJOO should be defined by the coexistence of clinical symptoms, a characteristic HRM pattern, and non‐manometric corroborative tests, including endoscopy, barium esophagogram, and functional lumen imaging probe panometry, in the absence of secondary causes. Patients with actionable primary motor EGJOO may receive medical, endoscopic, and/or surgical treatment, based on level of confidence in the diagnosis, while those without do not require LES‐directed invasive intervention. Conclusions: This clinical practice update represents an evidence and expert opinion‐based consensus on the most appropriate diagnostic and therapeutic workup of actionable primary motor EGJOO.

Background: High‐resolution manometry (HRM) is increasingly used to assess risk of gastroesophageal reflux disease (GERD). The Milan Score (MS) integrates four HRM variables—EGJ morphology, EGJ contractile integral (EGJ‐CI), ineffective esophageal motility (IEM), and straight leg raise (SLR) response—to predict pathological esophageal acid exposure. The inter‐observer reproducibility of the MS and its components has never been formally assessed. Methods: A total of 50 consecutive HRM plots from patients undergoing evaluation for suspected GERD at a tertiary referral center were distributed to a multicenter pool of esophageal experts for blind review. Participants assessed EGJ type, EGJ‐CI, IEM, and SLR response; the MS and corresponding GERD risk were automatically calculated. Inter‐observer variability was evaluated using Fleiss' κ for categorical variables and Kendall's coefficient for continuous variables. MS accuracy was assessed by comparing calculated scores against MII‐pH results. Results: Twenty‐three esophageal experts from 16 international institutions reviewed all 50 plots. Agreement was fair for EGJ morphology ( κ = 0.321), moderate for SLR ( W = 0.531), and good for IEM ( κ = 0.638), EGJ‐CI ( W = 0.675) and the final MS ( W = 0.641). Median plot‐level concordance between MS and pH‐impedance study was 71.74% [IQR 51.08%]; median reader accuracy for Milan Score was 64% [IQR 12%], ranging from 54% to 80%. Conclusions: Inter‐observer variability of the Milan Score is good across a diverse international cohort of esophageal experts, supporting its reproducibility as a clinical tool. However, agreement for individual parameters was heterogeneous, and the assessment of EGJ morphology and the SLR maneuver achieved only fair‐to‐moderate agreement, highlighting the need for improved standardization.

Background and Aim: In 2024, a novel high‐resolution manometry (HRM) metric termed the Milan Score was introduced to quantify anti‐reflux barrier disruption and estimate the probability of pathologic gastroesophageal reflux disease (GERD). This composite score incorporates oesophagogastric junction (EGJ) barrier metrics, oesophageal motor function and response to the straight leg raise (SLR) manoeuvre. Prior validations relied on acid exposure time (AET) > 6% on 24‐h pH‐impedance studies, making the outcome susceptible to day‐to‐day variability. The aim of this study is to validate the effectiveness of the Milan Score in predicting GERD using 96‐h wireless pH‐monitoring. Methods: Data from consecutive adults with GERD symptoms undergoing HRM and 96‐h wireless pH‐monitoring (2023–2025) at IRCCS Policlinico San Donato (Italy) and Washington University in St. Louis (USA) were retrospectively collected. Milan Score was calculated automatically from HRM metrics. pH studies followed Lyon Consensus 2.0 criteria, defining conclusive GERD as AET > 6% on ≥ 2 days. Diagnostic performance was evaluated by receiver operator characteristics (ROC) analysis. Results: Among the 90 included patients (age 54 years, 59% females, BMI 25 kg/m ² ), 48 had conclusive GERD. Hiatal hernia prevalence (65% vs. 35%, p = 0.006) and median SLR‐induced intra‐oesophageal pressure increase (14 vs. 3 mmHg, p < 0.001) were higher in GERD patients. Positive Milan Score was found in 65% of GERD vs. 19% of non‐GERD group ( p < 0.001). Milan Score values increased with higher number of positive pH days. ROC yielded AUC of 0.812 for conclusive GERD (95% CI: 0.718–0.895, optimal threshold 151.84, sensitivity 60.4%, specificity 92.9%). Conclusions: Abnormal Milan Score reliably predicts pathologic reflux per Lyon Consensus 2.0 on 96‐h wireless pH‐monitoring, with performance similar to 24‐h pH‐impedance. This validation strengthens evidence for the Milan Score in GERD diagnosis.

Gastroesophageal reflux disease (GERD) is driven by anti-reflux barrier (ARB) disruption, requiring precise endoscopic tools to guide diagnosis and management. The Hill classification, based solely on flap valve (FV), lacks precision. The American Foregut Society (AFS) classification, integrating hiatal hernia length (L), hiatal opening diameter (D), and FV (F), offers a comprehensive approach to phenotype esophago-gastric junction (EGJ) dysfunction. This study aims to assess the superiority of the AFS classification over the Hill and to weight the single AFS components contribution. A retrospective analysis of adult patients evaluated with upper-GI endoscopy (EGD), high-resolution manometry, and reflux monitoring study for GERD symptoms at our Institution (2022–2025) was performed. GERD was defined by Lyon 2.0 criteria. EGJ was graded using AFS and Hill classifications. GERD prevalence was compared across AFS and Hill grades and by the number of disrupted AFS components. Logistic regression assessed individual AFS component contributions. Of 249 patients (median age 52 years, 47% male, BMI 23.9 kg/m2), 127 had GERD. At least one AFS component was disrupted in 71.9% of the patients. GERD prevalence differed significantly across AFS grades 1–2 vs. 3 and 3 vs. 4, unlike Hill grades, where 2 and 3 overlapped. Patients with 1 and 2 impaired components were significantly different from those with 3 and 4. Pathologic D (OR = 2.537) and F (OR = 3.336) were independent GERD predictors. ROC analysis confirmed AFS superiority over Hill (AUC 0.750 vs. 0.653, P < 0.001). The AFS classification enhances EGD diagnostic yield, outperforming Hill in EGJ phenotyping. The AFS improves patient stratification for pathophysiological testing and tailored therapies, offering a practical tool for GERD management.

Background & Aims: The diagnosis and follow‐up of eosinophilic oesophagitis (EoE) currently rely on repeated upper endoscopies (EGD) with biopsies, which are invasive, resource‐intensive and environmentally costly. Non‐invasive biomarkers for EoE are needed. We investigated the role of blood eosinophils and lymphocytes in the management of EoE. Methods: This was a prospective study conducted at four EoE referral centres. Consecutive adults undergoing EGD with biopsies for known or suspected EoE were enrolled. Based on oesophageal peak eosinophil count (PEC) and clinical history, patients were divided into EoE (histologically active or in remission) and non‐EoE dysphagia (NED). Prior to the EGD, a full blood count was obtained. Clinical, endoscopic and histologic findings were recorded. Receiver operating characteristic curve analysis was used to assess the predictive ability of blood biomarkers (AUC). Results: We enrolled 209 patients (123 EoE and 86 NED). For the diagnosis of EoE, an absolute eosinophil count (AEC) of 155 eosinophils/mm ³ had an AUC of 85%. For the assessment of histological disease activity, an AEC of 325 eosinophils/mm ³ had an AUC of 70.5% for the identification of histological remission following treatment. AEC showed a positive correlation with PEC on histology and the EoE endoscopic reference score with Spearman's Rho of 0.4 ( p < 0.0001). Conclusion: Eosinophil absolute and relative counts in the peripheral blood could be used in the initial assessment of patients presenting with dysphagia to accurately differentiate EoE from NED and to predict histological remission of EoE.