A 38-year-old woman on chronic ibuprofen therapy for rheumatoid arthritis develops epigastric pain and dyspepsia. Upper endoscopy shows a 1.5 cm antral ulcer with clean base and no active bleeding. Rapid urease test is negative. Which investigation is most appropriate to confirm the diagnosis and exclude malignancy?

## Investigation of Choice for Gastric Ulcer Confirmation and Malignancy Exclusion ### Clinical Context This patient presents with a gastric ulcer in the setting of NSAID use and negative H. pylori testing (rapid urease test negative). The critical issue is that **gastric ulcers carry a risk of malignancy**, and biopsies are mandatory to exclude gastric cancer, even in the presence of a benign-appearing ulcer. **Key Point:** All gastric ulcers require multiple biopsies from the ulcer edge and surrounding mucosa to exclude malignancy. This is a cardinal rule in gastric ulcer management and differs from duodenal ulcers, where malignancy is exceptionally rare. ### Why Repeat Endoscopy with Biopsies? **High-Yield:** Gastric ulcers can be associated with gastric adenocarcinoma (intestinal type). Even endoscopically benign-appearing ulcers may harbor malignancy. Current guidelines mandate biopsies from: - Ulcer edge (4 quadrants) - Surrounding mucosa - Any suspicious areas **Clinical Pearl:** The initial endoscopy may have missed biopsies. Repeat endoscopy with targeted biopsies is the standard of care for any gastric ulcer, regardless of H. pylori status or NSAID exposure. ### Comparison of Investigations | Investigation | Role in Gastric Ulcer | Why Not Chosen Here | |---|---|---| | **Repeat endoscopy + biopsies** | Gold standard for confirming diagnosis and excluding malignancy | **CORRECT** — Mandatory for all gastric ulcers | | **Serum pepsinogen I/II** | Marker of gastric mucosal atrophy; used in H. pylori screening programs in endemic regions | Does not exclude malignancy; not standard for individual ulcer assessment | | **Fasting serum gastrin** | Diagnostic for Zollinger-Ellison syndrome or atrophic gastritis | Not indicated; no clinical suspicion for ZES; H. pylori already ruled out | | **Stool antigen test** | Confirms H. pylori if urease test was falsely negative | Rapid urease test was already performed; stool antigen adds no new information if negative | **Warning:** Do not rely on endoscopic appearance alone to exclude malignancy in gastric ulcers. Even ulcers with clean bases can harbor cancer. Biopsies are non-negotiable. **Mnemonic — Gastric vs. Duodenal Ulcer Management:** **GUM** = **G**astric ulcers need biopsies (Malignancy risk), **D**uodenal ulcers don't (Duodenal cancer is rare).