GastroenterologyTier 2Disease (DEADMAN)

Barrett’s oesophagus

Description

Metaplasia: normal squamous epithelium of the distal oesophagus replaced by columnar epithelium containing GOBLET CELLS (intestinal metaplasia)
- *Goblet cells are required for the diagnosis in Australia/US (UK/Japan accept columnar metaplasia without them*)
Endoscopic + histological diagnosis - both are needed
- Salmon-pink columnar mucosa extending >=1 cm above the gastro-oesophageal junction, AND intestinal metaplasia on biopsy
The only recognised precursor of oesophageal ADENOCARCINOMA

Prague C&M classification

C = circumferential extent (cm), M = maximal extent (cm)
Short segment <3 cm; long segment >=3 cm - length correlates with cancer risk

~1-2% of adults; 5-15% of those with chronic reflux symptoms
M>F ~2:1; Caucasian >> Asian, African
Mean age at diagnosis ~55
Progression to adenocarcinoma ~0.1-0.5%/yr (non-dysplastic)
- Far lower than historically taught - most patients die WITH Barrett's, not OF it
Oesophageal adenocarcinoma incidence rising sharply in Western countries

Chronic acid + bile reflux -> squamous injury -> columnar metaplasia (a more acid-resistant epithelium)
Progression: metaplasia -> low-grade dysplasia -> high-grade dysplasia -> adenocarcinoma
- TP53 loss is the key early molecular event; CDKN2A, aneuploidy
Risk factors:
- Chronic GORD >5 yr, central obesity (independent of reflux - visceral adipose, inc IL-6/leptin), male, age >50, smoking, Caucasian, FDR with Barrett's or oesophageal adenocarcinoma, hiatus hernia
*Helicobacter pylori is PROTECTIVE* (atrophic gastritis -> less acid)

Endoscopy

Adequate acid suppression first - inflammation mimics dysplasia; re-scope after 8 weeks of PPI if there is severe oesophagitis
Seattle protocol: 4-quadrant biopsies every 2 cm (every 1 cm if known/suspected dysplasia), plus targeted biopsies of any visible lesion
Two GI pathologists must confirm dysplasia, at least one expert
- Inter-observer agreement for low-grade dysplasia is poor - most "LGD" is downgraded on expert review
Advanced imaging: narrow-band imaging, acetic acid chromoendoscopy
Irregular Z-line / <1 cm columnar mucosa is NOT Barrett's - do not biopsy or label it

Histology grades

Grade	Meaning
Non-dysplastic IM	Goblet cells, no dysplasia
Indefinite for dysplasia	Usually inflammation - optimise PPI, re-scope 3-6 months
Low-grade dysplasia	Nuclear atypia confined to base; confirm with 2nd pathologist and repeat at 6 months
High-grade dysplasia	Full-thickness atypia, no invasion - *~40% harbour occult adenocarcinoma*
Intramucosal adenocarcinoma	Invasion into lamina propria, above muscularis mucosae

A. Antireflux therapy - everyone

PPI once daily long term - chemopreventive (AspECT); dose to symptom control
Aspirin + PPI reduced progression/death in AspECT - consider if other cardiovascular indication
Weight loss, smoking cessation, head-of-bed elevation
Antireflux surgery does NOT remove the need for surveillance and does not cause regression

B. Surveillance interval - set by dysplasia grade

Histology	Interval
No dysplasia	Endoscopy every 3-5 years (5 yr if short segment, 3 yr if long)
Indefinite	Optimise PPI, repeat 3-6 months
Low-grade dysplasia	Repeat at 6 months; if it persists -> ablation, or 1-yearly surveillance
High-grade dysplasia	Endoscopic therapy (or intensive 3-monthly surveillance if unfit)

*~40% of persistent low-grade dysplasia progresses to high-grade - hence the shift toward ablating confirmed, persistent LGD (SURF trial)*
Incident high-grade dysplasia carries a substantial risk of coexisting cancer - treat, do not watch

C. Endoscopic therapy

EMR or ESD FIRST for any visible/nodular lesion - it both stages (depth, differentiation, lymphovascular invasion) and treats
Then radiofrequency ablation of the remaining flat Barrett's segment to prevent metachronous lesions
Cryotherapy as an alternative
Surveillance continues after successful ablation (3, 6, 12 months then yearly) - recurrence ~10%/yr

D. Oesophagectomy

Submucosal (T1b) invasion, lymphovascular invasion, poor differentiation, or failed endoscopic therapy
High-volume centres only - morbidity is substantial

Who to endoscope in the first place

Chronic GORD PLUS >=3 risk factors (age >50, male, Caucasian, obesity, smoking, family history)
*Population screening of all reflux patients is NOT recommended*

Most non-dysplastic Barrett's never progresses - 0.1-0.5%/yr to adenocarcinoma
Risk rises with segment length, dysplasia grade, male sex, age, smoking
HGD -> cancer ~6-10%/yr untreated
RFA achieves complete eradication of dysplasia in ~80-90% and of intestinal metaplasia in ~70-80%
- Complications: stricture ~5-10%, bleeding, chest pain
- *Buried glands beneath neosquamous epithelium* - a theoretical but real reason surveillance continues
Oesophageal adenocarcinoma: 5-yr survival ~20% overall, but >90% if found as HGD/intramucosal - the entire justification for surveillance
Surveillance has never been shown in an RCT to reduce mortality - a genuine exam controversy

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