Recent Developments in Understanding Paediatric Barrett's Oesophagus

ABSTRACT

Barrett’s oesophagus (BO) is an acquired pre-malignant condition in which metaplastic columnar epithelium replaces the normal squamous mucosa as a consequence of chronic gastro-oesophageal reflux. The pre-malignant quality of BO is demonstrated in untreated adults with BO which are at risk of Barrett-associated adenoacarcinoma (BAA).

This review addresses the epidemiological, clinical, endoscopic and histological features of paediatric BO. Recent molecular developments and future directions that might lead to a better understanding of this condition are also discussed.

A recent estimate of the prevalence of columnar lined BO in the paediatric population in South Yorkshire (England) found this to be 0.0024% among all children in this geographical area, 0.8% in those children referred for endoscopy and 5.5% in the subgroup of children with GORD. BO was more prevalent in males than in females and risk factors were identified.

Investigations in adult patients with BO have suggested that a key event that leads to the evolution of multiple aneuploid populations and to progression from metaplasia → dysplasia → adenocarcinoma is associated with a multistep process of genetic instability, which leads to a clonal expansion of the abnormal population. Genomic instability has not yet been demonstrated in paediatric BO.

Strong contenders for early events in neoplastic progression in BO include loss of p16 tumour suppressor function, HER2 amplification, loss of function of TP 53 and O6 methylguanine methyl transferase (MGMT) promotor gene silencing.

A clear genetic progression route has not yet emerged for BO. Nevertheless, many of the common abnormalities found in Barrett’s associated adenocarcinoma have been shown to be present in BO adjacent to carcinoma

Keywords:

Barrett’s oesophagus, gastro-oesophageal reflux disease, intestinal metaplasia, genomic instability, molecular abnormalities.