What is the next step for a 55-year-old with long-standing Gastroesophageal Reflux Disease (GERD) who is a 20 pack-year smoker that quit five years ago, presenting with minimal relief and persistent symptoms after using over-the-counter Proton Pump Inhibitor (PPI) for the last two months?

Next Step Management for PPI-Refractory GERD

This 55-year-old man with persistent GERD symptoms after 2 months of over-the-counter PPI requires upper endoscopy, as he meets clear criteria for refractory disease and has multiple risk factors for Barrett esophagus and esophageal adenocarcinoma. 1

Primary Recommendation: Upper Endoscopy

Upper endoscopy is indicated because typical GERD symptoms persist despite what appears to be an adequate therapeutic trial. 1, 2 The American College of Physicians explicitly states that endoscopy should be performed when symptoms persist after 4-8 weeks of twice-daily PPI therapy. 1

Critical First Step Before Endoscopy

Before proceeding to endoscopy, you must optimize PPI therapy, as over-the-counter PPIs are typically once-daily dosing and may not represent adequate treatment:

• Escalate to prescription-strength PPI twice daily (any PPI: omeprazole 20mg, esomeprazole 40mg, lansoprazole 30mg, or equivalent) taken 30-60 minutes before meals for 4-8 weeks. 1
• If symptoms persist after this optimized regimen, then endoscopy is definitively indicated. 1, 2

Additional Justification for Endoscopy in This Patient

This patient has multiple high-risk features that independently support endoscopy:

• Male over 50 years old with chronic GERD (described as "long-standing") 1, 2
• 20 pack-year smoking history (tobacco use is an established risk factor for Barrett esophagus and esophageal adenocarcinoma) 1, 2
• Chronic GERD symptoms likely exceeding 5 years (implied by "long-standing") 1, 2

The American College of Physicians specifically recommends considering screening endoscopy in men over 50 with chronic GERD symptoms (>5 years duration) plus additional risk factors including tobacco use. 1, 2

What the Endoscopy Will Accomplish

The endoscopy serves multiple critical purposes:

• Rule out esophageal adenocarcinoma in this high-risk patient 1, 2
• Screen for Barrett esophagus, which occurs in patients with chronic reflux and requires surveillance 1, 2
• Identify severe erosive esophagitis that may require documented healing 1, 2
• Detect alternative diagnoses such as eosinophilic esophagitis, achalasia, strictures, or other causes of refractory symptoms 3

Common Pitfall to Avoid

Do not continue empiric PPI therapy indefinitely without objective evaluation. 4 Approximately 25-42% of patients on once-daily PPI and 10-20% on twice-daily PPI have persistent symptoms. 3 Many of these patients have conditions other than GERD causing their symptoms, including functional heartburn, eosinophilic esophagitis, achalasia, or other esophageal disorders. 3

The persistence of symptoms despite PPI therapy should prompt investigation rather than dose escalation beyond twice-daily or prolonged empiric treatment. 1, 3

If Endoscopy is Negative

If the initial screening endoscopy shows no Barrett esophagus, esophageal adenocarcinoma, or severe esophagitis, recurrent periodic endoscopy is not indicated. 1, 2 At that point, consider:

• Esophageal pH monitoring or impedance-pH monitoring to confirm true reflux versus functional symptoms 3
• Esophageal manometry to evaluate motility disorders 3
• Re-evaluation of the diagnosis as symptoms may be due to non-GERD causes 3