What are the risk factors for progression from non-dysplastic BO to high-grade dysplasia or adenocarcinoma?
What are the risk factors for progression from non-dysplastic BO to high-grade dysplasia or adenocarcinoma?
Many observational studies have attempted to define the rate of progression from non-dysplastic Barrett’s Oesophagus to states of low- or high-grade dysplasia, or adenocarcinoma. There is emerging consensus from large-scale, population-based cohort studies and meta-analyses that the rate of progression to cancer among patients with non-dysplastic Barrett’s Oesophagus is in the range of 1 to 5 per 1000 per year (i.e. 0.1% to 0.5%). A subset of studies has further attempted to identify those factors which modify the rate of progression to dysplasia or cancer. The quality of these ‘modifying factor studies’ has been uneven, with the majority of studies suffering from one or more of the following limitations: small sample sizes and low statistical power; retrospective exposure assessment; high rates of loss to follow-up; selection bias (single institution referral centres); inadequate confounder control. To date, no randomised controlled trials have been published which have tested whether any factors modify the rate of progression to cancer, although at least one is in the field. These elements of study quality must be borne in mind when assessing the evidence base. Wherever possible, estimates from higher quality studies have been used in the summaries below.
Patient factors associated with rate of progression from BO to high-grade dysplasia or adenocarcinoma
Some studies but not all report significantly increased rates of progression with increasing age. There is consistent evidence that the rates of progression to cancer are significantly higher in men than women, with most estimates converging on two-fold higher rates among men. Rates of progression appear to be about two-fold higher among ever smokers than never smokers. A number of studies have assessed whether progression rates are modified by measures of obesity with no evidence of an effect. One study has assessed biochemical analytes, and reported significantly higher rates of progression to cancer among those with higher HOMA scores and higher leptin levels.
Endoscopic factors associated with rate of progression from non-dysplastic BO to high-grade dysplasia or adenocarcinoma
Longer segments of columnar mucosa in Barrett’s Oesophagus have been consistently associated with higher rates of progression to cancer. Endoscopic features that have been associated with significantly increased rates of progression in some studies include the presence of nodules, ulceration and strictures. Such areas of abnormality are likely to harbour high-grade dysplasia or adenocarcinoma, and as such require further investigation (see also What are the endoscopic features of neoplasia (dysplasia and early cancer) within a BO segment?)
Histologic factors associated with rate of progression from non-dysplastic BO to high-grade dysplasia or adenocarcinoma
For non-dysplastic Barrett’s Oesophagus, there are no histological features that have been reliably associated with risk of progression. Markers of cellular atypia such as aneuploidy appear to confer higher risks of progression to cancer, although these are frequently associated with dysplasia.
Pharmacologic factors associated with rate of progression from non-dysplastic BO to high-grade dysplasia or adenocarcinoma
There is evidence from observational studies that several classes of medications significantly reduce the rate of progression to cancer among patients with Barrett’s Oesophagus, including non-steroidal anti-inflammatory drugs (NSAIDs), proton-pump inhibitors (acid suppressant medications) and statins (HMG co-A reductase inhibitors which act to lower serum cholesterol). However, it is important to note that no randomised trials have yet reported on these associations, although at least one such trial is currently underway.
Evidence summary and recommendations
|Factors that have been associated with an increased rate of progression from non-dysplastic BO to high-grade dyplasia or adenocarcinoma in observational studies include those relating to the patient (age, sex, smoking), endoscopic appearance (greater segment length), and histology (aneuploidy).||III-2||, , , , |
|There is observational evidence that regular users of proton-pump inhibitors, non-steroidal anti-inflammatory drugs, and statins, may have lower rates of progression from BO to neoplasia. These findings await confirmation from randomised controlled trials.||II, III-2, III-3||, , , , |
A clinical assessment of a patient’s future risk of high-grade dysplasia or adenocarcinoma in the setting of non-dysplastic Barrett’s Oesophagus should consider their:
Issues requiring more clinical research study
- Do medications reduce the rate of progression to cancer? Is chemoprevention possible?
- Are there any dietary factors that reduce the rate of progression from BO to cancer?
- Does obesity modify the rate of progression to cancer?
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