ENDOSCOPIC CLASSIFICATION OF FUNDOPLICATION INTEGRITY PREDICTS PATHOLOGIC REFLUX

ENDOSCOPIC CLASSIFICATION OF FUNDOPLICATION INTEGRITY PREDICTS PATHOLOGIC REFLUX: DEVELOPMENT AND PROSPECTIVE VALIDATION

This single-center, two-phase cohort study aimed to develop and validate a simple endoscopic classification of fundoplication integrity after anti-reflux surgery (ARS - Nissen or Toupet fundoplication). Consecutive adult patients undergoing endoscopy, high-resolution manometry (HRM), and reflux monitoring after ARS were included. Retroflexed endoscopic videoclips were reviewed blinded to clinical and functional results. In the development cohort (2018-2024, n=73), individual endoscopic parameters were tested against pathologic GERD (Lyon 2.0 criteria). Three parameters significantly correlated with pathologic reflux: (1) intrathoracic valve location, (2) disrupted valve (deep anterior and/or posterior grooves), and (3) visible hiatal opening. Patients were stratified according to the number of impaired mechanisms (0-3). Symptom burden, manometric abnormalities, and reflux metrics worsened progressively with increasing impairment. The rate of pathologic GERD rose from 11.8% (0 mechanisms) to 37.5% (1-2 mechanisms) to 85.7% (3 mechanisms). The classification was then prospectively validated in an independent cohort (2024-2026, n=49), reproducing the same stepwise correlation. The number of impaired mechanisms showed excellent discriminatory capacity for pathologic GERD (AUC 0.860 in development, 0.870 in validation; overall AUC 0.869). This simple endoscopic classification, based on only three objective parameters, reliably identifies fundoplication failure and correlates with symptoms and objective pathophysiologic data. It has the potential to standardize endoscopic reporting after ARS.

Study Overview

• Status: Completed
• Conditions: Gastro Esophageal Reflux

Detailed Description

Background and Rationale Gastroesophageal reflux disease (GERD) is highly prevalent. Although medical therapy is first-line treatment, a significant proportion of patients have incomplete symptom control or require long-term medication. Anti-reflux surgery (ARS), primarily laparoscopic Nissen or Toupet fundoplication, re-establishes the anti-reflux barrier by recreating the gastroesophageal valve and repairing the hiatal defect. Endoscopy is the most common and often the only test performed after ARS. However, existing endoscopic classifications are complex, poorly standardized, and have never been validated against objective functional testing (HRM and reflux monitoring). This study was designed to identify which endoscopic parameters truly correlate with pathologic reflux and to create a simple, clinically meaningful classification.Study Design Single-center, two-phase cohort study. Development phase (retrospective, April 2018 - April 2024): classification was built.

Validation phase (prospective, May 2024 - April 2026): independent validation of the classification.

Inclusion Criteria Adults (18-90 years) who underwent Nissen or Toupet fundoplication for GERD or large hiatal hernia Completion of post-operative esophagogastroduodenoscopy (EGD) with adequate retroflexed videoclip, high-resolution manometry (HRM), and reflux monitoring (MII-pH or wireless pH) Both primary and redo procedures included

Exclusion Criteria Other foregut operations (Dor, Collis, magnetic sphincter augmentation, bariatric surgery) Insufficient quality of endoscopic videoclips Missing HRM or reflux monitoring

Endpoints Primary endpoint: Association between the new endoscopic classification (number of impaired mechanisms: 0-3) and pathologic GERD according to Lyon 2.0 criteria. Secondary endpoints: Correlation with individual symptoms and validated questionnaires (GERD-Q, GERD-HRQL, RSI, FOSS) Correlation with HRM parameters (LES pressure/length, EGJ-CI, Padova Consensus criteria for disruption/herniation, SLR maneuver) Correlation with reflux monitoring parameters (AET, MNBI, reflux episodes, symptom-reflux association)

Endoscopic Assessment All retroflexed videoclips were reviewed blinded to clinical and functional data by an experienced foregut surgeon. The following parameters were evaluated: Valve location: intra-abdominal vs intrathoracic (relative to diaphragmatic crura) Valve integrity: depth of anterior and posterior grooves (0-2 each). Groove sum <2 = disrupted valve Hiatal opening: visible (separated crura) vs not visible Valve lip thickness: thick vs thin (exploratory) Presence of para-esophageal hernia

Definition of Pathologic GERD (Lyon 2.0) AET >6%, or AET 4-6% + at least one adjunctive criterion (MNBI <1500 Ω, positive SI/SAP, >80 reflux episodes), or De novo Barrett's esophagus or LA grade B-D esophagitis

Statistical Analysis Continuous variables expressed as median [IQR], compared with Mann-Whitney or Kruskal-Wallis tests. Categorical variables compared with χ² or Fisher exact test. Odds ratios for association with pathologic GERD. ROC curves and AUC for discriminatory capacity of the classification. DeLong test for comparison of ROC curves.

• Study Type: Observational
• Enrollment (Actual): 153

Contacts and Locations

Study Locations

• Italy
  • Milan
    • San Donato Milanese, Milan, Italy, 20097
      • IRCCS Policlinico San Donato

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients who underwent anti-reflux surgery and a complete manometric, reflux monitoring and endoscopic assessment

Description

Inclusion Criteria:

• Adults (18-90 years) who underwent Nissen or Toupet fundoplication for GERD or large hiatal hernia Completion of post-operative esophagogastroduodenoscopy (EGD) with adequate retroflexed videoclip, high-resolution manometry (HRM), and reflux monitoring (MII-pH or wireless pH) Both primary and redo procedures included

Exclusion Criteria:

• Other foregut operations (Dor, Collis, magnetic sphincter augmentation, bariatric surgery) Insufficient quality of endoscopic videoclips Missing HRM or reflux monitoring

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
Normal fundoplication; Patients with 0 impaired mechanisms of ARB restoration
Partially impaired fundoplication; Patients with 1-2 impaired mechanisms of ARB restoration
Fully impaired fundoplication; Patients with 3 impaired mechanisms of ARB restoration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
acid exposure time	time of pH<4 during the pH monitoring test	during pH impedance monitoring

Collaborators and Investigators

• Sponsor: IRCCS Policlinico S. Donato

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2018
• Primary Completion (Actual): April 1, 2026
• Study Completion (Actual): July 1, 2026

Study Registration Dates

• First Submitted: July 19, 2026
• First Submitted That Met QC Criteria: July 19, 2026
• First Posted (Actual): July 23, 2026

Study Record Updates

• Last Update Posted (Actual): July 23, 2026
• Last Update Submitted That Met QC Criteria: July 19, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: endoscopy; anti-reflux surgery; pH study
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Esophageal Diseases; Esophageal Motility Disorders; Deglutition Disorders; Gastroesophageal Reflux
• Other Study ID Numbers: EndoARS

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No