What are the current guidelines for diagnosing and treating a gastric ulcer, including history, endoscopic evaluation, Helicobacter pylori testing, appropriate proton pump inhibitor therapy, eradication regimens, and follow‑up recommendations?

Guidelines for Diagnosing and Treating Gastric Ulcer

Diagnostic Approach

All patients with suspected gastric ulcer require upper endoscopy with multiple biopsies to confirm the diagnosis, exclude malignancy, and test for Helicobacter pylori infection. 1

Endoscopic Evaluation

• Perform upper endoscopy to visualize the ulcer, assess size and location, and obtain targeted biopsies from the ulcer margin and base to exclude gastric carcinoma or lymphoma. 2
• Take additional biopsies from both the antrum and body (at least two from each site) for H. pylori testing via histology and rapid urease test. 2
• Document ulcer size precisely, as ulcers ≥1.5 cm require extended acid suppression beyond eradication therapy alone. 3

H. pylori Testing

• Test all gastric ulcer patients for H. pylori using endoscopic biopsy-based methods (histology plus rapid urease test) at the time of initial endoscopy. 2, 4
• Critical pitfall: During active bleeding, biopsy-based tests show 25-55% false-negative rates; if initial testing is negative in a bleeding ulcer, repeat testing after stabilization is mandatory. 1
• For non-invasive confirmation after treatment, use urea breath test (88-95% sensitivity, 95-100% specificity) or monoclonal stool antigen test (94% sensitivity, 92% specificity). 1, 5
• Never use serology to confirm eradication, as antibodies persist for months to years after successful treatment. 1

NSAID History

• Document current and recent NSAID use, including aspirin and COX-2 inhibitors, as this determines management strategy. 6
• Discontinue NSAIDs immediately if medically feasible. 1

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Treatment Strategy

Initiate high-dose proton pump inhibitor therapy immediately upon diagnosis and start H. pylori eradication therapy as soon as oral feeding is tolerated; delaying treatment reduces compliance and increases loss to follow-up. 1, 5

First-Line Eradication Regimen

Use 14-day bismuth quadruple therapy as the preferred first-line regimen:

• Esomeprazole or rabeprazole 40 mg twice daily
• Bismuth subsalicylate 262 mg four times daily
• Metronidazole 500 mg three to four times daily
• Tetracycline 500 mg four times daily 5

This regimen achieves 80-90% eradication rates even in areas with high clarithromycin resistance, and bismuth shows no documented bacterial resistance. 5

Alternative First-Line Regimen (if bismuth unavailable)

• Use 14-day concomitant quadruple therapy only if local clarithromycin resistance is documented <15%:
  • Esomeprazole or rabeprazole 40 mg twice daily
  • Amoxicillin 1000 mg twice daily
  • Clarithromycin 500 mg twice daily
  • Metronidazole 500 mg twice daily 5

Critical point: A 14-day course is mandatory; extending from 7 to 14 days improves eradication rates by approximately 5%. 5

Proton Pump Inhibitor Duration

The duration of PPI therapy depends on ulcer size and eradication success:

• For ulcers <1.0 cm: One-week triple therapy heals 89% of ulcers without additional acid suppression. 3
• For ulcers 1.0-1.5 cm: Continue PPI for 4-6 weeks total to ensure complete healing. 4, 3
• For ulcers ≥1.5 cm: Continue full-dose PPI until endoscopic healing is confirmed, as short-term eradication therapy alone heals only 5% of large ulcers. 3
• After successful eradication is confirmed: Continue PPI until repeat endoscopy documents complete ulcer healing. 1

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Follow-Up and Confirmation of Eradication

All gastric ulcer patients require both confirmation of H. pylori eradication and endoscopic verification of ulcer healing. 2

Test of Cure

• Perform urea breath test or monoclonal stool antigen test at least 4 weeks after completing eradication therapy. 1, 5
• Discontinue PPI at least 2 weeks before testing to avoid false-negative results. 1, 5
• If eradication fails, initiate second-line therapy with levofloxacin triple therapy (levofloxacin 500 mg once daily, amoxicillin 1000 mg twice daily, PPI 40 mg twice daily) for 14 days, avoiding antibiotics used previously. 2, 5

Mandatory Repeat Endoscopy

• Perform repeat endoscopy at 6 weeks post-diagnosis to confirm complete ulcer healing and exclude malignancy, as some gastric malignancies are only detected during or after the healing process. 2, 1
• Obtain multiple biopsies from the ulcer site even if it appears healed, as histological assessment is required to exclude dysplasia or carcinoma. 2
• Repeat endoscopy is non-negotiable for gastric ulcers, unlike duodenal ulcers where it may be omitted after successful eradication. 1, 4

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Special Populations and Scenarios

H. pylori-Negative Gastric Ulcer

• If H. pylori testing is negative and the patient is not taking NSAIDs, treat with full-dose PPI for 4-8 weeks and perform careful endoscopic follow-up to exclude malignancy (carcinoma, lymphoma) or non-peptic disease (Crohn's disease). 6
• These patients represent a small minority and require heightened vigilance for alternative diagnoses. 6

NSAID-Associated Gastric Ulcer

• If NSAIDs cannot be discontinued, consider maintenance therapy with prostaglandins or potent antisecretory drugs after ulcer healing. 6
• If the patient is also H. pylori-positive, eradicate the infection first, as successful eradication reduces rebleeding risk from 26% to near-zero. 1, 5

Bleeding Gastric Ulcer

• Initiate high-dose intravenous PPI (80 mg bolus followed by continuous infusion) immediately, but do not delay urgent endoscopy. 1
• Start eradication therapy as soon as oral feeding resumes after stabilization; waiting until discharge dramatically reduces compliance. 1
• Confirm eradication in all complicated ulcers, as successful eradication is significantly more effective than PPI therapy alone in preventing rebleeding. 1

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Critical Pitfalls to Avoid

• Do not skip repeat endoscopy in gastric ulcer patients: Some malignancies are only detectable after initial healing, and histological confirmation of benign healing is mandatory. 2
• Do not use 7-day eradication regimens: All regimens must be 14 days to optimize success rates. 5
• Do not postpone eradication therapy: Start treatment immediately when oral feeding resumes; delaying reduces compliance and increases loss to follow-up. 1, 5
• Do not rely on symptom resolution alone: Gastric ulcers require endoscopic and histological confirmation of healing regardless of symptom improvement. 2
• Do not test for eradication while the patient is on PPI: Stop PPI at least 2 weeks before testing to avoid false-negative results. 1, 5
• Do not use serology to confirm eradication: Antibodies remain positive for months to years after successful treatment. 1