result in the retention of food in the oesophagus, which is then decomposed bybacteria releasing various chemical irritants.
Nonepidermolytic palmoplantar keratoderma (tylosis) is the only recognisedfamilial syndrome that predisposes patients to oesophageal SCC. It is a rareautosomal dominant disorder, in which a genetic abnormality occurs atchromosome 17q25. It may confer up to 95% risk of oesophageal SCC inafflicted individuals by the age of 70.
The precise molecular pathogenesis of oesophageal SCC remains incompletelydefined. However it has been shown that the loss of tumour suppressor genesincluding p53 and p16/INK4A is involved.
SCC begins as a lesion, usually inthe middle third of the oesophagus referred to as squamous dysplasia. Similar lesions occurring at other sites in the body are referred to as intraepithelialneoplasia or carcinoma. The lesion first appears as small, grey-white, plaque-likethickenings which over months to years grow into tumour masses. Such massesmay be polypoid or exophytic and protrude into and obstruct the lumen of theoesophagus. Symptomatic tumours are generally very large at diagnosis andhave already invaded the oesophageal wall.
AC of the oesophagus is strongly linked to gastroesophageal reflux disease(GORD). Persistent reflux symptoms lead to an eightfold increase in the risk of AC development.
Up to 10% of AC malignancies may be attributable to drugswhich relax the gastroesophageal sphincter, hence increasing reflux, such asanticholinergic agents, aminophyllines and beta-blockers.
The frequent use of antacids or histamine H
antagonists are also associated with an increased risk.
It has been postulated that the increasing prevalence of obesity in the developedworld is adding to the rising incidence of oesophageal AC.
It is believed thatobesity increases the occurrence of GORD due to an increase in intra-abdominalpressure.
A study published in 2008 suggests that abdominal obesity increasesthe risk of oesophageal AC independent of BMI and that this association was notsignificantly mediated by the presence of GORD symptoms.
The conclusiondrawn from this study suggests that since metabolic products of intra-abdominalfat, such as IGF and leptin are associated with malignancies through pro-neoplastic changes at the cellular level; that it is in fact these compounds whichinfluence cancer development. The metabolic products of intra-abdominal fatmay directly influence AC development or may modify the risk after injury fromother factors such as GORD.
Oesophageal AC typically arises in a background of Barrett’s oesophagus; acondition characterised by an abnormal change in the cells of the distal portion of the oesophagus. Columnar epithelium more typically seen in the stomach or intestine extends proximally from the gastroesophageal junction and replaces thesquamous cell epithelium which normally lines the oesophagus. Chronic GORDis thought to be the main cause of Barrett metaplasia due to acid exposure.