Barrett’s oesophagus: Current controversies

Table 1 Modified Vienna Criteria

Category	Description
1	No dysplasia
2	Indefinite for dysplasia
3	Low-grade intraepithelial neoplasia (low-grade adenoma/dysplasia)
4	High-grade intraepithelial neoplasia (high-grade adenoma/dysplasia, non-invasive carcinoma, or suspicion of invasive carcinoma)
5	Invasive epithelial neoplasia (intramucosal carcinoma, submucosal carcinoma, or beyond)

Table 2 The Wilson-Jungner criteria for appraising the validity of a screening programme

The Wilson-Jungner Screening Criteria	Achieved for Barrett’s oesophagus?
The condition being screened for should be an important health problem	+
The natural history of the condition should be well understood	+/-
There should be a detectable early stage	+
Treatment at an early stage should be of more benefit than at a later stage	+
A suitable test should be devised for the early stage	+
The test should be acceptable	+
Intervals for repeating the test should be determined	+/-
Adequate health service provision should be made for the extra clinical workload resulting from screening	+
The risks, both physical and psychological, should be less than the benefits	+
The costs should be balanced against the benefits	-

Table 3 Studies investigating chemoprevention in Barrett’s oesophagus

Ref.	Type	Sample size	Chemo-prevention	Effect on risk	Overall
Nguyen et al[113], 2010	Cohort	812	NSAID and aspirin	Filled NSAID/aspirin prescriptions were associated with a reduced risk of oesophageal adenocarcinoma (adjusted incidence density ratio, 0.64; 95%CI: 0.42-0.97)	Reduces risk
				Filled statin prescriptions were associated with a reduction in EAC risk (0.55; 95%CI: 0.36-0.86)
Corley et al[115], 2003	Meta-analysis of 9 studies	1813	NSAID and aspirin	Protective association between any use of aspirin/NSAID and oesophageal adenocarcinoma (OR = 0.57; 95%CI: 0.47-0.71)	Reduces risk
				Intermittent (OR = 0.82; CI: 0.67-0.99) and frequent medication use were protective (OR = 0.54; 95%CI: 0.43-0.67)
				Any use was protective against both oesophageal adenocarcinoma (OR = 0.67; 95%CI: 0.51-0.87) and squamous cell carcinoma (OR = 0.58; 95%CI: 0.43-0.78)
Alexandre et al[116], 2012	Meta-analysis of 2 studies	1382	Statin	Pooled effect size of 0.53 (95%CI: 0.36-0.78, P = 0.001, I2 = 0%) for risk of oesophageal adenocarcinoma with prior statin use	Reduces risk
Alexandre et al[116], 2012	Meta-analysis of 3 studies	35214	Statin	Pooled effect size of 0.86 (95%CI: 0.78-0.94, P = 0.001, I2 = 0%) for risk of oesophageal adenocarcinoma wth prior statin use	Reduces risk
Beales et al[117], 2012	Case-control	85	Statin	Regular statin use was associated with a significantly lower incidence of oesophageal adenocarcinoma (OR = 0.45, 95%CI: 0.24-0.84)	Reduces risk
				After NSAID/aspirin confounding correction: OR = 0.57, 95%CI: 0.28-0.94
Heath et al[121], 2007	Randomised control trial	100	NSAID (celecoxib)	No difference in the proportion of biopsy samples with dysplasia or cancer between treatment groups in either the low-grade (median change with celecoxib = -0.09); or high-grade (median change with celecoxib = 0.12) stratum	No effect
Singh et al[123], 2013	Meta-analysis of 13 studies	9285	Statin	A 28% reduction in the risk of oesophageal adenocarcinoma among patients who took statins (adjusted OR = 0.72; 95%CI: 0.60-0.86)	Reduces risk

NSAID: Non-steroidal anti-inflammatory drug.

Table 4 Summary of molecular biomarkers predicting malignant progression

Biomarker	Phase	Sample size	End-point
Biomarker panels
8-gene methylation panel	3	195	High grade dysplasia/adenocarcinoma
DNA content abnormalities and loss of heterozygosity	4	243	Adenocarcinoma
Expert low grade dysplasia, aneuploidy, Aspergillus oryzae lectin	3	380	Adenocarcinoma
DNA content abnormalities
Aneupolidy/tetraploidy	4	322	Adenocarcinoma
Tumour suppressor loci
p53 loss of heterozygosity	4	256	Adenocarcinoma
p53 staining	4	48	High grade dysplasia/adenocarcinoma
Epigenetics
P16 methylation	3	53	HD/adenocarcinoma
Proliferation
Mcm2	3	27	Adenocarcinoma
Clonal diversity
Clonal diversity measures	4	239	Adenocarcinoma
Cell cycle markers
Cyclin A	3	48	High grade dysplasia/adenocarcinoma
Cyclin D1	3	307	Adenocarcinoma
Serum biomarkers
Leukocyte telomere length	4	300	Adenocarcinoma
Selenoprotein P	4	361	Adenocarcinoma