The role of H-pylori infection in the development of CLO and its progression to AC is still very controversial and thus will not be discussed in any detail here. Vieth et al, (2000) 36 have shown that patients who have GORD and are infected with H-pylori have no increased risk of developing either CLO or AC and they concluded that since H-pylori infection is significantly less frequent in patients with GORD than in patients with non-ulcer dyspepsia it is possible that H-pylori infection may have a protective effect. There is certainly an increase in CLO in the USA and Europe concomitant with a decline in the prevalence of infection with H-pylori in these populations, and this and the effect of therapy with proton pump inhibitors are discussed in reviews by Sharma (2001) 37 and Koop (2002) 38.

There are a number of studies showing the basic characteristics of CLO patients and some of these are summarised in Table 1.

Most European studies, from the UK and The Netherlands, show a male predominance of CLO, whereas the studies from Australia and Chile do not, and all but three of these studies have fewer than 300 CLO patients. The mean age at diagnosis is over 60 years in Europe, but 50.8 years and 53.0 years respectively in Australia and Chile. It is not possible at this stage to speculate as to the reason for this. In all but one study the mean age at diagnosis was greater for females than males by almost a decade. In an analysis of CLO from a single UK centre over 15 years it was found that prevalence rose incrementally from age 20–29 years, from 0.16% in males and 0% in females, to a maximum at age 70–79 years, of 4.89% in males and 3.75% in females. Although there was a steep rise in prevalence with age in both sexes, it was slower in females between the ages of 20–59 than in males, and this was reflected in a 10-year delay in the onset of CLO in females. One could speculate that premenopausal females are protected to some degree against the development of CLO by their hormones 47.

There are very few studies on lifestyle factors and CLO thus making it impossible to say anything concrete at this stage. The available evidence suggests that neither alcohol consumption nor tobacco use have an effect (Table 2). One study 50 found the past smoking to be moderately connected with CLO development, possibly as a result of the effect of smoking on promoting gastroesophageal reflux. Another study 48 suggested a role for obesity in young CLO patients. In this context it is of interest that CLO occurs as a complication of long standing GORD 20 which, itself, is a complication of obesity.

Because of growing concern about the rise in the incidence of both AC and CLO The UK National Barrett's Oesophagus Registry (UKBOR) was established in June 1996. The aims of the Registry were to establish a national database of all cases of CLO in the UK in order to learn more about the aetiology, epidemiology and natural history of CLO and to provide a co-ordinating infrastructure for prospective studies. The primary aim being the identification of those sub-groups of CLO most at risk of developing AC so that targeted surveillance strategies can be implemented. This is the world's first such registry, and was set up as a joint initiative of the Oesophageal Section of the British Society of Gastroenterology and the European Cancer Prevention Organization (ECP) 51. Since then almost 9500 CLO patients have been registered from 42 hospitals nationwide. In the following section we give an overview of the data, for the UK, from studying UKBOR patients.

The results of studies using the expanding UKBOR database are summarised in table 3.

AC occurs almost exclusively in white males. In the USA, AC occurs in 2.5 per 100,000 males and 0.3 per 100,000 females, giving a M: F ratio of 8:1 56. In the UK, where there are several epidemiological differences from the USA, the M: F ratio is 3–4:1 33. Obesity is a risk factor in several series, the risk being proportional to the degree of obesity, with an odds ratio (OR) of 3.0 in the fourth quartile of the BMI range 5859. There is an increasing incidence of genetic factors in the genesis of both CLO and AC, familial cases of both having been documented, and reflux is more prevalent among siblings than spouse controls for both CLO and AC 60.

Whilst is it accepted that gastro-oesophageal reflux disease (GORD) is a precursor lesion of CLO and CLO is a pre-malignant lesion. A Swedish population-based study showed chronic, long-standing GORD to be a risk factor for AC independent of CLO, with an overall OR of 7.7 for chronic GORD and 43.5 for severe GORD of more than 20 years duration 61. Despite the fact that over 90% of CLO patients have a hiatal hernia (HH), the presence of an HH was found to be a risk factor for AC in two case-controlled studies with multi-variate analysis, the risk being proportional to the HH length 6263. In terms of reflux parameters, those with AC had higher levels of acid exposure (mean % TT pH < 4, 20 v 16) and lower resting lower oesophageal sphincter pressure (LOSP) (mean LOSP 6 v 10 mmHg) than those with uncomplicated CLO 63. The combination of duodeno-gastric reflux (DGR) and GORD appears to be a strong risk factor, culminating in oesophageal exposure to alkaline duodenal contents. An increased risk of AC following partial gastrectomy has been documented for some time 39 and measurement of duodenal content reflux by Bilitec monitoring has shown a progressive increase in those refluxers developing CLO, and those CLO patients developing AC 64.

Dietary factors have been studied extensively, with conflicting evidence of low fruit intake as a risk factor 58 although one study has demonstrated increased AC risk in females with dietary deficiencies of vitamins A, C, E and folate 65. More recent studies have postulated that dietary nitrate present in fertilisers may be a risk factor 66.

Smoking and alcohol ingestion have been studied extensively as putative risk factors with conflicting results. Few series have reported smoking as a risk factor with an OR of around 2.5, but proportional to the extent and duration of exposure 6567, although some failed to find increased risk 3235. In most series alcohol was not a risk factor 616367 whilst in one series which studies wine consumption, it had a protective effect 68.

Drugs, which relax the LOS, such as nitro-glycerine, aminophylline, anticholinergics and calcium channel blockers, have been found to increase risk with an OR of 3.8 in several studies 5969. The effect of acid-suppressing drugs is controversial, with an OR of 3–4 in two series 6170, but two series showing no increased risk 6971.

Several series have reported infection with H. pylori as a negative risk factor, particularly the CagA strain 7072.

Many series document increasing risk of AC with increasing length of Barrett's segment, particularly so when the segment length exceeds 6 cm 626367. As a consequence, it is generally assumed that the AC risk in short segment CLO (SSBO) is relatively low. However, in a study conducted by the UKBOR which looked at AC risk in 625 patients, 27% of whom had SSBO, the greatest risk in segments >6 cm was confirmed, but, somewhat surprisingly, the risk in SSBO was three times higher than that in CLO segments between 3–6 cm in length 55.

The most important risk factor of all in CLO is the presence of dysplasia, and particularly high-grade dysplasia (HGD) in the presence of which between 16–59% develop AC 7374. Within HGD, the presence of a raised lesion, ulceration and multifocality of HGD all increase the risk of AC. Multifocality of HGD is associated with an OR of 5.4 of AC, the corresponding figure for a raised lesion being 3.8. If HGD is complicated by ulceration, 80% develop AC 7273747576. In of low-grade dysplasia (LGD) overall risk is less than that with HGD at 5–28% 7273. However, the diagnosis of LGD is very subjective with significant inter-observer variation, but it has been shown that where two pathologists agree a diagnosis of LGD, the incidence of AC is 41% and when three agree, its 80% 75.

The challenge for the future is to develop identifiers of high-risk comparable to dysplasia and its complications, but at a much earlier stage in the process of genomic instability and the principal hope lies in the identification of appropriate molecular markers.

There is plenty of patient data to suggest that gastro-oesophageal reflux has an important role to play in the development of metaplasia in the distal oesophagus 8020. Three theories have emerged: (1) transdifferentiation of stem cells from the basal squamous cells, migration of (2) submucosal gland cells or (3) gastric cells to colonise the damaged squamous mucosa. Nevertheless, very little evidence is available to test these hypotheses or to determine the signalling pathways implicated in the metaplastic process. The lack of reliable animal or in vitro models does not facilitate the research.

The morphological characterisation of CLO when compared to other glandular epithelia such as gastric and duodenal mucosa is complex. Barrett's oesophagus is a mosaic of three main types of columnar epithelium: a junctional zone of gastric cardia type epithelium, a gastric fundic type and a columnar epithelium with intestinal features characterised by goblet cells (sometimes termed specialised intestinal metaplasia) 6. In 1996 Spechler suggested that there should be an alternative classification for the metaplasia depending on the presence or absence of specialised intestinal metaplasia since it is the intestinal metaplasia type which confers the highest risk for malignancy 8111. Intestinal metaplasia is classified in several ways depending on how strongly it resembles the small intestinal epithelium 8283. Metaplasia which is very similar to the small intestine is referred to as complete, whereas that which differs from it is termed incomplete. The complete type (or type 1) should contain absorptive cells that do not secrete mucus, have a well-defined brush border containing enzymes such as disaccharides. There may also be occasional paneth cells. In contrast, incomplete intestinal metaplasia (types 11 and 111/11B, which is more common) is composed mainly of 'intermediate' columnar cells that secrete mucus. It also contains goblet cells that secrete sulphomucins, sialomucins or both. The clinical relevance of these histopathological subtypes in terms of predicting cancer risk is not clear and does not currently contribute to the diagnosis or patient management. CLO is also regarded to be a hyperproliferative epithelium, although a review of the literature is somewhat conflicting 8485868788. The proliferative status may be important in determining the likelihood of cancer progression.

The products of the ras family (H, K and N) of oncogenes are believed to modulate cell growth by abrogation of cell growth requirements 108. Investigators were unable to identify c-ras mutations in dysplastic and non-dysplastic CLO mucosal biopsy or in cancer samples 95109. Mutations of codon 12 of the k-ras gene were found to be rare in CLO but increased in frequency along the progression to AC 110111. Amplification of k- and h-ras were only seen in established AC, suggesting that this is a late event in carcinogenesis 112.

The oncogenes c-myc, c-fos and c-jun encode for nuclear proteins involved in transcriptional regulation. Transient growth factor stimulation of those oncogenes can lead to a sustained increase in cell proliferation 113. Amplification of c-myc was only seen in dysplastic CLO and the percentage of cases with amplification increased with progression to AC 114115, nevertheless an increase in c-myc protein expression was seen in CLO and increased with progression to AC 116. As CLO becomes malignant, there is a shift of localisation of c-myc and c-jun from the nucleus to a more diffuse cytoplasmic localisation 95116.

The diverse abnormalities in oncogenes will result in abnormal epithelial cell proliferation independent of the usual growth requirements.

Expression of Cyclooxygenase-2 (cox-2) and inducible nitric oxide (iNOS) and mediators of were shown to be high in CLO and low grade dysplasia when compared to normal squamous oesophagus, gastric mucosa and adenocarcinoma 117118119120121. Cox-2 expression was shown to be higher in the distal end of the oesophagus, where AC tends to occur, when compared to the proximal end 122. Furthermore, Cox-2 stimulation was shown to induce proliferation in an in vivo system 124. This suggests an early involvement in the carcinogenesis process by stimulation of mucosal proliferation.

Gastro-oesophageal refluxate, the major factor associated with the development of CLO contains bile salts and hydrochloric acid. In vitro studies in AC adenocarcinoma cell lines, demonstrated that proliferation could be induced through involvement of the sodium-hydrogen exchanger (Na⁺-H⁺), a major acid-extruder in CLO cells, as well as via activation of the p38^MAPK, p44^ERK1 and Jun-N-terminal kinase (JNK) enzymes 124125. Pulsatile acid exposure of cell lines was shown to suppress apoptosis via the p53 pathway and to stimulate proliferation possibly through the MAP kinase pathway 126. Cox-2 expression was also induced by acid and bile salts in ex vivo experiments 127128 in a protein kinase C (PKC) dependant manner. As well as this in vitro work, ex vivo studies have also suggested a hyerproliferative effect of acid and bile exposure on the Barrett's epithelium 129130. This has implications for the use of reflux-suppressive therapies in patients with CLO. However, it should be remembered that the induction of the mitogen gastrin in response to proton pump inhibitor therapy might induce proliferation of the CLO mucosa via the cholecystokinin (CCK2) receptor 131.

Passage of cells through the restriction point controlling the G1/S phase transition is a key element of proliferation (Figure 1). This checkpoint, also called the restriction point, is tightly controlled by a plethora of inhibitors of cell cycle progression and molecules inducing apoptosis such as p53. Aberrant expression of regulatory proteins may lead to uncontrolled progression through the cell cycle, instead of the normal cell cycle arrest, which is necessary for processes such as DNA repair.

Hyperproliferation has been associated with progression from CLO to AC 848586132. For a tissue to become hyperproliferative, the individual cells have to progress in uncontrolled fashion through the restriction point. Amplification and overexpression of cyclin D1 133134135, decreased expression and loss of heterozygosity (LOH) of Rb 136137138 and increased expression cyclin E 139 as well as accumulation of mutant p53 140141142143144145146147148149 as CLO progresses to AC suggest that the G1/S transition control system is overridden. Furthermore, inactivating hyperphosphorylation 150151152153 or deletion of p16 154, a cyclin cyclin D1/CDK complex inhibitor, seems to be a common feature of CLO carcinogenesis. p27 is inactivated in AC and tumours lacking p27 have a more aggressive behaviour 155.

Flow cytometry studies showed that G2/M phase accumulation is found early in the progression 156. Results implicating cyclin B1 (expressed in G2 phase of the cell cycle to regulate entry into mitosis) overexpression in the progression to cancer, confirmed this first study 157.

Further to an increase in p53 expression, apoptosis may be avoided in the progression from CLO to AC via abnormal Bcl-2 and Bax expression 119158159160161162. The expression profile of p21^(cip1/waf1) is subject to controversy 158159163164 but p21^(cip1/waf1) does not seem to inhibit proliferation in the context of CLO carcinogenesis.

Angiogenesis, characterised by the stimulation of migration and proliferation of capillary endothelial cells creating new vasculature, is an important mechanism by which metastases occur. Acid and basic fibroblast growth factors (respectively FGF1 and FGF2) and vascular endothelium growth factor (VEGF) are key players in this process 165. FGF 1 and 2 expression was shown be increased as CLO progresses to AC 166167168. In AC, VEGF expression correlated with the level of the vasculature, which in turn correlated with the presence of lymph nodes and distant metastasis. It has been mentioned that the salmon-pink colour of the CLO mucosa could be due to the increased presence of blood vessels when compared to normal squamous epithelium 170171.

The calcium-dependant cadherin-catenin membrane bound complex is a key factor for maintaining epithelial integrity, cell polarisation and cell-cell adhesion. Loss of cell-cell interaction resulting from down-regulation of E-cadherin may trigger and facilitate metastasis 171. Many reports have commented on the increasingly low levels of E-cadherin (protein and mRNA level) and α- and β-catenin in the progression from normal squamous epithelium to adenocarcinoma 172173174175176. This trend of down-regulation was shown to correlate with poorer survival, invasion, and metastasis 172 as well as with the stage and grade of the cancer 173. Interestingly, a subset of patients was shown to have nuclear localisation of the E-cadherin-β-catenin complex 173174177178. A recent study demonstrated that tumour necrosis factor alpha (TNFα) induces c-myc expression via β-catenin 116. The role of the nuclear E-cadherin-β-catenin complex in this system is not clear and further investigation is warranted.

The adenomatous polyposis coli gene (APC) product is a binding partner for the catenin and links trans-membrane cadherins to the actin filaments of the cellular cytoskeleton. APC gene alterations are highly specific to gastrointestinal carcinogenesis. Alterations in the APC gene were detected in dysplastic CLO and associated AC but not in non-dysplastic CLO and normal mucosa 154179180. Hypermethylation of the APC locus was found in the majority of AC 181. Hence, molecular changes in the dysplasia carcinoma sequence set the stage for invasion and metastases to occur.

The large number of molecular alterations that occur in Barrett's carcinogenesis are gradually being documented although the sequence by which these abnormalities occur seems to be non-linear and complex 182. Most of the studies that have been carried out to date are descriptive. Unfortunately, it has proved hard to develop models for dynamic studies although progress is being made 130183. Work is still needed in order to understand the driving forces behind Barrett's carcinogenesis so that progress can be made in identifying clinically useful diagnostic markers and novel therapeutic strategies.

This clearly has theoretical advantages, being the least invasive form of long-term therapy, particularly as Barrett's oesophagus is predominantly a disease of the elderly, the mean age being around 63 33. Although the development of squamous islands following PPI therapy is well recognised, circumferential regression of the columnarised segment is rare, a meta-analysis of six subsequent series showing no evidence of regression 184. Several studies report the difficulty of normalising oesophageal acid exposure in Barrett's patients, even using doses equivalent to Omeprazole 80 mg daily and even when amelioration of symptoms, if present, has occurred 185186187. This is likely to relate to the pathophysiology of this group of patients previously alluded to and the consequences of incomplete acid suppression is a matter of concern in this group of patients, since it has been shown that Barrett's oesophagus cells in culture exhibit a greater degree of proliferation and de-differentiation when exposed to intermittent pulse acid exposure compared to no acid exposure and even continuous acid exposure 130. It is, therefore, possible that inadequate levels of acid suppression may have contributed to the rising incidence of adenocarcinoma of the oesophagus and gastric cardia 188189. It has been recommended to try to overcome this problem that an H2 receptor antagonist should be added at night, possibly combined with a prokinetic agent and that the dose of PPI should be titrated against the level of oesophageal acid exposure on 24 hr pH monitoring in order to optimise the effect of acid suppression therapy 185. There remains, however, the problem of abnormal duodenal juice exposure, which although reduced as measured by Bilitec monitoring, on PPI therapy, presumably due to a volume-reduction effect, such exposure is normalised in less than 50% of patients 190.

While endoscopy is considered to offer a relatively poor return in assessing uncomplicated symptomatic GORD and lack of impact in altering medical treatment 191, it offers a useful therapeutic option for mucosal ablation of metaplastic epithelium and putative regeneration of squamous lining 192. It could be argued that ablative techniques should be reserved for areas of dysplastic change only and certainly further studies are needed to define the indications, efficacy and relative safety of the various modalities of treatment.

Ablative modalities can be divided into thermal and non-thermal. Thermal methods involve coagulation and vaporisation of epithelium using an Nd-YAG or GaAIAs semi-conductor diode laser. A more recent and less expensive option involves the use of the Argon plasma coagulator (APC) 194. While the learning curve is shorter for the use of APC, care must be taken to limit the depth of thermal injury to prevent undue stricture formation and perforation by penetrating through the deeper layers with all forms of thermal therapy. Photodynamic therapy (PDT) produces a cytotoxic action via the release of singlet oxygen when light of a specific wavelength is directed onto the tissue sensitised by the uptake of a photosensitising drug. The pro-drug, 5 aminolaevulinic acid, which converts to protoporphyin IV, the last step in the haem biosynthetic pathway, is selectively taken up by the mucosa and has yielded promising results as an agent for PDT in the treatment of Barrett's metaplasia and dysplasia 195. Since ALA is confined to the mucosa, stricture formation does not occur but this complication has been found in excess of 30% of cases treated by PDT where mTHPC or Photofrin have been used as photosensitisers 196. Development in the light delivery systems and new generations of photosensitises are likely to improve the uptake of PDT. Endoscopic ablation techniques, performed in a reflux-free environment using either high dose PPI therapy or fundoplication result in squamous re-epithelialisation in 50–80% of patients, although residual islands of columnar metaplasia remain in 20–60% depending on the depth of injury 192193194195196.

There remains doubt as to the status of islands of columnar metaplasia covered by squamous regeneration following the use of ablative techniques and it is recommended that endoscopic ablation techniques should only be performed in the context of prospective randomised trials.

Fundoplication has the theoretical advantage of being able to correct lower oesophageal sphincter failure and the frequently associated hiatal hernia and producing complete and continuous control of abnormal acid and duodenal juice exposure in 80–90% of patients. Two studies have demonstrated a greater degree of symptom control and healing of associated strictures and a lower incidence of new strictures after fundoplication compared to acid suppression therapy 198199. There are considerably more reports of regression following anti-reflux surgery, although regression is rarely complete and occurs in only 10–44% of patients 198199200201202203. However, it is perhaps of greater importance what is happening at cellular level rather than whether or not macroscopic regression occurs.

The effect of successful anti-reflux surgery on the incidence of AC is unknown and indeed adenocarcinoma has been reported after successful anti-reflux surgery 201. It is theoretically possible that anti-reflux surgery may be effective in preventing adenocarcinoma if performed sufficiently early in the sequence of genomic instability, but that a point may be reached beyond which no form of treatment can prevent the development of AC. This concept is supported by the findings of a study from the Mayo Clinic in which 113 patients with CLO were followed up for up to 18 years after anti-reflux surgery. Although 3 patients developed AC, these were all in the first 3.3 years, after which no carcinomas developed 204. The incidence of AC in this series was 1:274 patient years of follow up, considerably less than the mean of 1:80 patient years of follow up reported from surveillance series of patients on acid suppression therapy 205.

Notwithstanding the apparent theoretical advantages of fundoplication over acid-suppression therapy, which need to be confirmed by randomised control trials, it should be remembered that CLO is a condition largely of old age and only approximately 50% of patients will be below the age of 70 and fit for consideration of surgery. However, it should certainly be considered in younger patients and particularly those with risk factors for development of AC, such as those with a long history, early age at diagnosis, Barrett's segment greater than 7 cm and documented pathological alkaline exposure.

Both screening and surveillance have been advocated for CLO in an attempt to reduce the mortality from AC. Screening refers to a programme to identify individuals with CLO who have not previously been diagnosed. Surveillance refers to the follow-up of patients with known Barrett's oesophagus. Surveillance programmes only review a small proportion of the population at risk since only a minority of patients with Barrett's oesophagus are clinically diagnosed 25.

At the current time there are no randomised controlled trials examining the clinical benefit or cost-effectiveness of endoscopic screening for Barrett's oesophagus in either the general population or in patients with reflux disease. In the future non-endoscopic screening programmes targeted at individuals at highest risk for developing AC may be possible. For this to become a reality we will need to depend on molecular epidemiological studies to identify predictive markers with high sensitivity and specificity and technological developments to implement this, in an ethically acceptable and cost-effective manner. Since the majority of the data at the current time pertains to surveillance.

Most patients with AC present with dysphagia, and despite advances in multimodal treatment the five-year survival rates of symptomatic oesophageal carcinomas remain less than 10% 206207. Since the major determinant of outcome is the stage of the cancer at presentation 208, early detection of AC is essential in order to significantly improve survival rates. The identification of a multistage process of cancer development, akin to that described in colon carcinogenesis, provides the rationale for endoscopic surveillance in patients with diagnosed CLO 7778209210211. Several studies have shown a significant improvement in the 5-year survival of patients with surveillance-detected adenocarcinoma 212213214, although these studies are generally limited by their small sample size.

There have been no large studies, which have compared the life expectancy of patients with Barrett's with the general population. The only report in the literature suggests that the actuarial survival of patients with Barrett's oesophagus is no different from general population 215. The flagging study in progress by the UK Barrett's Oesophagus Registry will address this question in a large population.

The value of surveillance hinges on the actual risk of cancer in patients with CLO 216. A meta-analysis of 25 studies conducted between 1984 and 1998 demonstrated that the number of incident cancers ranged from 1 in 35 to 1 in 441 patient years of follow-up, with a mean cancer incidence in these studies of 1 in 138 patient years 217. The wide variation in cancer incidence may be as a result of the retrospective nature of the studies, diagnostic variation, surveillance protocol variation (number of biopsies), variation in outcome data (death, dysplasia or cancer), and publication bias (negative studies tend not to be published).

At the current time the histopathological assessment of dysplasia is used to predict the likelihood of cancer development. In a recently reported retrospective cohort study of 79 patients with high-grade dysplasia 4.5 (5%) had cancer at 1 year and 12 (16%) had cancer on follow-up (mean 7.3 years) 73. However, concern has been expressed about the over-diagnosis of dysplasia in this cohort. Another group demonstrated that the likelihood of cancer was dependent on the extent of high-grade dysplasia (focal or diffuse) 74, although this has not been confirmed in a subsequent study 218. These studies are hampered by the subjectivity of the diagnosis of dysplasia and hence more specific markers of malignant potential are badly needed 219, (see section on molecular pathogenesis). When deciding on the merits of surveillance programmes it should be borne in mind that 40% of patients with high-grade dysplasia have been found to harbour foci of carcinoma in their resection specimen 220. The practical problems associated with surveillance are summarised in Table 9.

From an economic point of if the incidence is 1% 2–3 yearly surveillance endoscopy would be cost-effective; whereas if the incidence is 0.5% 4–5 yearly would be recommended 221222. As a result of the apparent geographical variations in cancer incidence (e.g. UK versus USA) different surveillance intervals may be recommended.

There is a wide variation in the surveillance protocols undertaken in the UK. Surveillance was conducted in Leicester from 1984 to 1999, 143 out of 409 patients were eligible for surveillance using their diagnostic criteria with a 70 year age cut-off and in 1999 only 8 were still in the programme. Quadrantic biopsies were taken from the midpoint of the Barrett's segment rather than every 2 cm along the Barrett's length according to the Seattle protocol 223. Over the 15 years 5/143 developed carcinoma – 2 had a stricture at the time enrolment, 2 were programme defaulters and hence the programme itself only identified one subject 44. This study is probably more informative about the practical difficulties in administering such a programme, rather then being informative about the value of surveillance itself. Implementation of a rigorous surveillance protocol In an East London hospital (Oldchurch, UK) in line with the Seattle guidelines, for patients with specialised intestinal metaplasia who were fit enough for surveillance (no age cut off) significantly increased the yield of high-grade dysplasia and cancer detection 224.

The World Health Organisation has criteria for screening/surveillance and it is not clear to what extent Barrett's oesophagus currently meets these criteria. In order to address these questions a prospective randomised controlled trial of surveillance versus no surveillance is required. Such a study would require 10 yr study with 5,000 patients and the ethical considerations of a no-surveillance arm would have to be carefully considered 222. At the current time the American College of Gastroenterology have made clear recommendations for screening and surveillance based on the best available evidence 225. The British Society of Gastroenterology is currently in the process of drawing up their guidelines (Prof. Tony Watson is Chairman of the Working Group). It is certainly clear that we need an international consensus on our definition(s) of Barrett's oesophagus and dysplasia so that the outcomes of surveillance protocols can be usefully compared.