What is the best next step for a male patient with gastroesophageal reflux disease (GORD) on proton pump inhibitor (PPI) therapy, who has only mild improvement in symptoms after 8 weeks of increased doses and lifestyle modifications, and has esophagitis without Barrett's esophagus on esophagogastroduodenoscopy (OGD)?

Management of Refractory GORD with Persistent Symptoms Despite PPI Therapy

The best important next step for this male patient with GORD who has persistent symptoms despite increased PPI doses and lifestyle modifications for 8 weeks, with esophagitis but no Barrett's on OGD, is ambulatory pH monitoring (option D).

Rationale for Ambulatory pH Monitoring

When patients with GORD fail to respond adequately to optimized PPI therapy, further diagnostic testing is essential to guide appropriate management. According to the Asia-Pacific consensus guidelines, after ascertaining medication compliance, functional testing including ambulatory pH monitoring is strongly recommended to better categorize the underlying pathophysiology and target therapy 1.

The American Gastroenterological Association (AGA) clinical practice update specifically states that if troublesome GORD symptoms do not respond adequately to a PPI trial and endoscopy shows no erosive reflux disease (Los Angeles B or greater) or long-segment Barrett's esophagus, clinicians should perform prolonged wireless pH monitoring off medication to confirm and phenotype GORD 1.

Why pH Monitoring is Superior to Other Options:

1. Diagnostic Value: Ambulatory pH monitoring can identify:

   • Whether pathological reflux is present (found in approximately 25% of patients with refractory GORD symptoms) 1
   • If there is insufficient acid suppression despite PPI therapy
   • If symptoms are related to weakly acidic/non-acidic reflux
   • If the patient has a functional disorder rather than true GORD

2. Guides Treatment Decision: pH monitoring results directly inform the next therapeutic steps:

   • Confirms if ongoing symptoms are truly reflux-related
   • Determines if surgical intervention would be beneficial
   • Identifies if alternative diagnoses should be considered

Why Other Options Are Less Appropriate

A. Repeat Endoscopy in 6 months

• Not indicated when initial endoscopy has already documented esophagitis
• Would not provide additional information to guide immediate management
• Delays appropriate treatment for a patient with ongoing symptoms

B. Nissen Fundoplication

• Surgery is only recommended for patients with objectively documented gastroesophageal reflux failing medical therapy 1
• The AGA states that lack of response to PPI therapy predicts poor response to anti-reflux surgery 2
• pH monitoring is required before considering surgery to confirm that symptoms are related to reflux 1

C. Esophageal Manometry

• While useful for evaluating motility disorders, it is not the first-line test for refractory GORD
• Should be considered after pH monitoring if a motility disorder is suspected
• Would not directly address the question of whether ongoing symptoms are related to acid reflux

Implementation of pH Monitoring

The preferred method is prolonged wireless pH monitoring (96-hour preferred if available) performed off PPI therapy 1:

1. Preparation: Discontinue PPI for 2-4 weeks before testing when possible
2. Procedure: Wireless pH capsule placed 6 cm proximal to the squamocolumnar junction
3. Duration: 96-hour monitoring provides better diagnostic yield than 24-hour monitoring by accounting for day-to-day variability 3

Interpretation of Results:

• No GORD: Acid exposure time (AET) <4.0% on all days
• Conclusive GORD: AET ≥6.0% on 2+ days
• Borderline GORD: AET ≥4.0% but not meeting conclusive criteria

Next Steps Based on pH Monitoring Results

1. If pH monitoring confirms GORD:

   • Optimize PPI therapy (switch to more potent PPI or twice daily dosing)
   • Consider adding adjunctive medications (H2RAs, alginates, baclofen)
   • Evaluate for surgical intervention if medical therapy fails

2. If pH monitoring is normal:

   • Consider functional esophageal disorder
   • Taper and discontinue PPI
   • Consider neuromodulators or cognitive behavioral therapy

3. If pH monitoring shows borderline results:

   • Optimize PPI to lowest effective dose
   • Consider on-demand therapy
   • Focus on aggressive lifestyle modifications

Conclusion

Ambulatory pH monitoring is the critical next step that will guide appropriate management for this patient with refractory GORD symptoms despite optimized medical therapy. This approach is supported by multiple high-quality guidelines and will provide the necessary information to determine whether continued medical therapy, surgical intervention, or an alternative diagnosis should be pursued.