**3. Definition and clinical significance of Barrett's dysplasia**

Dysplasia is defined as "an unequivocal neoplastic alteration of epithelium which has the potential to progress to invasive malignancy but remains confined within the basement membrane of the epithelium within which it arose." (Shaheen and Ransohoff, 2002; Riddell et al., 1983) Dysplasia is classified as either low grade (LGD), or high grade (HGD) (often also termed high-grade intraepithelial neoplasia HGIN)), based on its histological appearances. As already described, HGD has a higher malignant potential than LGD and malignant transformation classically occurs through a stepwise progression of pathology from metaplastic Barrett's oesophagus, to LGD, then HGD, and finally invasive adenocarcinoma.

Understanding the pathogenesis and natural history of Barrett's oesophagus is key to understanding the malignant potential and clinical significance of the various dysplastic stages. Surveillance studies have shown that the risk of developing adenocarcinoma varies between 0.4% and 1% per year (in the US and UK respectively). However, it is clear from cohort studies that not all Barrett's oesophagus progresses to dysplasia. In fact, in most longterm studies fewer than 10% of patients show evidence of progressive disease. (Schnell et al., 2001a) Patients with Barrett's oesophagus are thought to have a lifetime risk of developing oesophageal adenocarcinoma of 3-14% (approximately 0.5-1% per year following diagnosis). (Shaheen et al., 2000; Drewitz et al., 1997) (Jankowski et al., 2000; Spechler et al., 2010; Shaheen and Richter, 2009; Jankowski et al., 2002) This represents an increased risk of 30-100 fold compared to the general population. However, cancer rates in excess of 10% per year have been described in patients with HGD. (Shaheen and Richter, 2009)

Several studies have also noted regression of disease in patients treated with acid suppression, and even complete resolution has been described. Similarly there is some data suggesting that anti-reflux surgery can improve the histological appearance of Barrett's oesophagus, although it is not currently recommended for this purpose. (BSG Working Party, 2005).
