What is the next step in evaluation and management for a 32‑year‑old woman with lifelong epigastric pain relieved by fasting, worsened by meals and lying down, with weight loss and fatigue?

Evaluation and Management of Lifelong Epigastric Pain with Weight Loss

This 32-year-old woman with alarm features—significant weight loss (30 pounds over 3 years), worsening symptoms, and food-related pain—requires urgent upper endoscopy with biopsy to exclude gastric malignancy and peptic ulcer disease, followed by CT imaging if endoscopy is unrevealing. 1, 2, 3

Immediate Diagnostic Priorities

Endoscopy is Mandatory

• The British Society of Gastroenterology mandates 2-week-wait endoscopy for dyspepsia with weight loss in patients ≥25 years. 1 This patient at age 32 with 30-pound weight loss over 3 years clearly meets this threshold.

• Endoscopy must include systematic biopsies of any gastric ulcers to exclude adenocarcinoma, as ulceroproliferative lesions can represent malignancy. 3 Never assume benign disease without tissue diagnosis.

• The pattern of pain worsened by eating with significant weight loss raises concern for gastric outlet obstruction, peptic ulcer disease, or gastric malignancy—all requiring endoscopic evaluation. 2, 3

Consider CT Imaging

• The British Society of Gastroenterology recommends urgent CT scan for abdominal pain with weight loss in patients ≥60 years, but given this patient's severe constitutional symptoms and lifelong history, CT abdomen/pelvis should be obtained if endoscopy is negative. 1, 2

• CT can identify chronic mesenteric ischemia (pain after meals, weight loss, "food fear") or median arcuate ligament syndrome (postprandial pain in young women). 1 The classic triad of postprandial pain, weight loss, and food avoidance suggests mesenteric vascular insufficiency.

• Superior mesenteric artery syndrome should be considered given the combination of epigastric pain, early satiety, and significant weight loss. 4

Baseline Laboratory and Non-Invasive Testing

While arranging endoscopy, obtain:

• Complete blood count to assess for anemia (suggesting chronic blood loss from ulcer or malignancy). 1, 2

• H. pylori testing via stool antigen or urea breath test, as eradication eliminates peptic ulcer mortality risk. 2, 5

• Coeliac serology if there are overlapping IBS-type symptoms (though not prominent in this case). 1

Empiric Treatment Pending Results

• Initiate full-dose PPI therapy (omeprazole 40 mg once daily, 30-60 minutes before meals) for 4-8 weeks while awaiting endoscopy. 2, 3 This addresses potential peptic ulcer disease or severe erosive esophagitis.

• Do NOT delay endoscopy based on PPI response. The presence of alarm features (weight loss, progressive symptoms) mandates visualization regardless of symptomatic improvement. 1, 2

Critical Differential Considerations

Why This is NOT Functional Dyspepsia

• Functional dyspepsia requires exclusion of structural disease at endoscopy and typically does not present with this degree of weight loss. 1

• The lifelong history since age 3 is unusual but does not exclude serious acquired pathology developing over the past 6 years when symptoms worsened dramatically. 1

• Pain relieved by fasting and worsened by eating is more consistent with peptic ulcer disease, gastric outlet obstruction, or mesenteric ischemia than typical functional dyspepsia. 1, 5

Mesenteric Ischemia Warrants Specific Attention

• Chronic mesenteric ischemia classically presents with postprandial pain, food fear, and weight loss in the setting of atherosclerotic disease. 1 While more common in older patients, younger patients with risk factors or anatomic variants (median arcuate ligament syndrome) can present similarly.

• If CT angiography demonstrates celiac artery compression by the median arcuate ligament with patent SMA and IMA, mesenteric angiography in lateral projection during inspiration and expiration is indicated. 1

• Surgical median arcuate ligament release provides symptomatic relief in 84.6% of appropriately selected patients. 1

Common Pitfalls to Avoid

• Never attribute persistent epigastric symptoms with significant weight loss to functional dyspepsia without first excluding malignancy. 2 The positive predictive value of weight loss for gastro-oesophageal cancer is ≥3% in this age group with alarm features. 3

• Do not dismiss the possibility of cardiac ischemia—obtain ECG to exclude atypical angina, especially given pain worsened by exertion (eating). 2, 6

• Delay of endoscopy in patients with alarm features leads to missed serious pathology and poorer outcomes. 1, 2

• The brief relief from an "acid watcher diet" does not exclude serious pathology and may simply reflect reduced gastric acid exposure or decreased mechanical irritation. 7

Algorithmic Approach

1. Order urgent upper endoscopy with biopsy (within 2 weeks). 1, 3
2. Start omeprazole 40 mg daily before breakfast. 2, 3
3. Obtain H. pylori testing, CBC, and comprehensive metabolic panel. 1, 2
4. If endoscopy negative, proceed to CT angiography of abdomen/pelvis to evaluate for mesenteric ischemia, median arcuate ligament syndrome, or other structural causes. 1, 2
5. If CT angiography suggests vascular compression, obtain mesenteric angiography with lateral views during respiration. 1
6. If all imaging negative, consider gastric emptying study and carbohydrate breath testing for malabsorption syndromes. 2

Follow-Up Strategy

• Re-evaluate after endoscopy results. If peptic ulcer disease is found, optimize PPI to high-dose therapy and treat H. pylori if positive. 2, 5

• If gastric ulcer is identified, repeat endoscopy in 8-12 weeks to document healing and re-biopsy to definitively exclude malignancy. 3

• If all testing is negative, functional dyspepsia becomes a diagnosis of exclusion, but given the severity and chronicity, consider referral to a tertiary center for specialized motility testing. 2