Key Facts

Barrett oesophagus is a premalignant condition where the normal stratified squamous epithelium of the distal oesophagus is replaced by specialised intestinal metaplasia (columnar epithelium with goblet cells). It is the major risk factor for oesophageal adenocarcinoma.

Epidemiology

Barrett oesophagus affects 1-2% of the general population but is found in 3-5% of patients undergoing OGD for GORD. Male predominance (3:1). Mean age at diagnosis is 55-65 years. Prevalence is increasing in parallel with rising GORD and obesity rates. Oesophageal adenocarcinoma incidence has increased 6-fold over the past 40 years in the UK.

Aetiology

• Chronic GORD (>5 years): most important risk factor
• Central obesity: independently increases risk (visceral fat, intra-abdominal pressure)
• Male sex: 3:1 predominance
• Smoking: ~2x risk
• Family history: 7-10x risk if first-degree relative with Barrett/adenocarcinoma
• Protective factors: H. pylori infection (reduces acid output), aspirin/NSAIDs (anti-inflammatory)

Pathophysiology

Chronic acid and bile exposure causes injury-repair cycles in the oesophageal squamous epithelium. Under the influence of transcription factors (CDX2), squamous epithelium undergoes metaplastic transformation to intestinal-type columnar epithelium with goblet cells. This represents an adaptive response to chronic acid exposure. The metaplasia-dysplasia-carcinoma sequence follows: intestinal metaplasia → low-grade dysplasia → high-grade dysplasia → intramucosal carcinoma → invasive adenocarcinoma. Genomic instability (TP53 mutations, aneuploidy) drives malignant progression.

Typical Presentation

• Often discovered incidentally at OGD for GORD symptoms
• Chronic heartburn and regurgitation (>5 years)
• May be completely asymptomatic
• Barrett itself does not cause specific symptoms — symptoms relate to underlying GORD

Findings at OGD

• Salmon-pink tongues or circumferential segments of columnar mucosa extending above the gastro-oesophageal junction
• Described using Prague classification (C and M measurements)

Red Flags

• Progressive dysphagia (stricture or malignancy)
• Weight loss (adenocarcinoma)
• GI bleeding (ulceration within Barrett segment)
• Iron deficiency anaemia
• Nodularity or irregularity within Barrett segment (possible dysplasia/cancer)

Bedside

• OGD with systematic biopsies: gold standard diagnosis
  • Seattle protocol: 4-quadrant biopsies every 2 cm in non-dysplastic Barrett, every 1 cm if dysplasia suspected
  • Prague classification: record C (circumferential) and M (maximal) extent
• High-resolution endoscopy with NBI/chromoendoscopy: improved dysplasia detection

Bloods

• FBC: iron deficiency anaemia (chronic blood loss)
• LFTs, U&Es: baseline

Imaging

• CT thorax/abdomen: staging if adenocarcinoma diagnosed
• Endoscopic ultrasound (EUS): T-staging of early cancers, lymph node assessment
• PET-CT: M-staging for oesophageal adenocarcinoma

Special Tests

• Histopathology: presence of goblet cells (intestinal metaplasia) confirms Barrett oesophagus in UK
• Dysplasia grading: must be confirmed by two expert GI pathologists
• Cytosponge (TFF3 test): emerging non-endoscopic screening tool — swallowed sponge collects cells; TFF3 positivity detects Barrett with ~80% sensitivity (BEST3 trial)

Non-pharmacological

• Endoscopic surveillance programme (BSG guideline):
  • No dysplasia, <3 cm: OGD every 5 years
  • No dysplasia, ≥3 cm: OGD every 3 years
  • Low-grade dysplasia (confirmed): endoscopic ablation (preferred) OR 6-monthly surveillance
  • High-grade dysplasia: endoscopic treatment (RFA, EMR/ESD)
• Lifestyle measures: weight loss, GORD management as above

Pharmacological

• Lifelong PPI: all Barrett patients should be on once-daily PPI (e.g. omeprazole 20 mg OD) regardless of symptoms — may reduce progression risk
• Aspirin: emerging chemopreventive evidence (AspECT trial — combination of high-dose PPI + aspirin reduced composite endpoint of mortality, cancer, and HGD in Barrett); not yet standard of care

Surgical/Interventional

• Radiofrequency ablation (RFA): first-line treatment for flat dysplastic Barrett (LGD and HGD); eradicates Barrett epithelium; ~90% complete eradication of dysplasia
• Endoscopic mucosal resection (EMR): for visible lesions/nodularity within Barrett segment; allows histological assessment and treatment
• Endoscopic submucosal dissection (ESD): for larger early lesions; en-bloc resection
• Oesophagectomy: for invasive adenocarcinoma (T1b+) or when endoscopic treatment not feasible
• Cryotherapy: emerging alternative ablative technique

Referral Criteria

• All Barrett oesophagus to gastroenterology for surveillance programme entry
• Dysplasia to specialist Barrett centre for MDT discussion and endoscopic treatment
• Adenocarcinoma to upper GI cancer MDT

Non-dysplastic Barrett carries a 0.3-0.5% annual risk of progression to adenocarcinoma. LGD has ~0.7% annual progression risk but is over-diagnosed (up to 70% downgraded on expert review). HGD has ~10% annual cancer risk and warrants treatment. After successful RFA, recurrence of intestinal metaplasia occurs in ~10% per year, necessitating ongoing surveillance. Overall, most Barrett patients die of causes unrelated to oesophageal cancer.

BSG Barrett Surveillance Schedule

Dysplasia-Carcinoma Sequence