Pathophysiological characteristics of the various forms of gastro-oesophageal reflux disease: Spectrum disease or distinct phenotypic presentations?

BACKGROUND: The traditional approach to gastro-oesophageal reflux disease as a spectrum disease has recently been criticised and the distinct phenotypic presentations model has been proposed. AIM: To evaluate the main pathophysiological characteristics of various gastro-oesophageal reflux disease presentations. METHODS: Oesophageal manometry and 24-h pH-monitoring were performed in a gastro-oesophageal reflux disease series collected in a 7-year period. RESULTS: Four hundred and twenty-one subjects were studied. Mean total percentage acid reflux time was significantly higher in long-segment Barrett's oesophagus and in ulcerative oesophagitis than in all the other gastro-oesophageal reflux disease groups, whilst in short-segment Barrett's oesophagus results were quite similar to those found in non-erosive reflux disease and in erosive reflux disease. Patients with ulcerative oesophagitis and long-segment Barrett's oesophagus were older than all the other gastro-oesophageal reflux disease groups. The mean lower oesophageal sphincter pressure was significantly reduced in non-erosive reflux disease, erosive reflux disease, ulcerative oesophagitis, short-segment Barrett's oesophagus and long-segment Barrett's oesophagus as compared with functional heartburn and hypersensitive oesophagus and with controls. CONCLUSIONS: In keeping with the spectrum model of gastro-oesophageal reflux disease, severity of acid reflux increases from non-erosive reflux disease through erosive reflux disease up to ulcerative oesophagitis and long-segment Barrett's oesophagus. Ulcerative oesophagitis and long-segment Barrett's oesophagus could represent an advanced step in the natural history of gastro-oesophageal reflux disease. Our results do not confirm the distinct phenotypic presentations hypothesis.     

Risk of oesophageal cancer in Barrett's oesophagus and gastro-oesophageal reflux

BACKGROUND AND AIMS: While patients with Barrett's oesophagus develop oesophageal adenocarcinoma more frequently than the general population, it has controversially been suggested that gastro-oesophageal reflux (GORD) itself is a more important determinant of risk. In order to assess the validity of this suggestion, we examined the risk of oesophageal cancer in patients with Barrett's and with GORD compared with the general population in a community based cohort study. METHODS: Cohorts of patients with Barrett's (n = 1677), oesophagitis (n = 6392), and simple reflux (n = 6328), and a reference cohort (n = 13416) were selected from the General Practice Research Database. The last three cohorts were matched to the Barrett's cohort by general practitioner practice, age, and sex. Cox's regression analysis was used to calculate relative risks for oesophageal cancer. Standardised incidence ratio methodology was used to estimate the relative risks for oesophageal adenocarcinoma. RESULTS: A total of 137 oesophageal cancers were identified, of which 94 prevalent cases were excluded. The hazard ratios for oesophageal cancer were 10.6 (5.1-22.0), 2.2 (0.9-5.2), and 1.7 (0.7-4.5) in the Barrett's, oesophagitis, and reflux cohorts compared with the reference cohort, respectively. The corresponding relative risks for oesophageal adenocarcinoma were 29.8 (9.6-106), 4.5 (1.04-19.6), and 3.1 (0.6-14.2). CONCLUSION: Barrett's oesophagus increases the risk of oesophageal cancer approximately 10 times and oesophageal adenocarcinoma approximately 30 times compared with the general population. There is only a modestly increased risk of oesophageal cancer in patients with reflux who have no record of Barrett's oesophagus. Our findings therefore do not support the suggestion that gastro-oesophageal reflux disease itself predisposes to cancer.     

Barrett's oesophagus: the new endoscopic modalities have a future

Barrett's oesophagus is defined as the replacement of squamous oesophageal epithelium by intestinal metaplasia in the distal oesophagus. It is a fairly frequent complication of gastro-oesophageal reflux disease (GORD): 5-10% of patients with GORD suffer from Barrett's oesophagus. GORD is essential for the development of Barrett's oesophagus.1 Intestinal metaplasia is a premalignant lesion that may further develop into dysplasia and lead to adenocarcinoma of the oesophagus. The latter now accounts for almost 50% of oesophageal cancer cases in western countries, and the largest increase in its incidence was recorded during the past two decades. Patients with Barrett's oesophagus have a 2-25% risk of developing mild to severe dysplasia and a 2-5% risk of having adenocarcinoma: 30-150 times higher than the risk in the general population. Forty to fifty per cent of Barrett's oesophagus patients with severe dysplasia would present adenocarcinoma within 5 years.     

Risk factors for Barrett＇s oesophagus and oesophageal adenocarcinoma： Results from the FINBAR study

AIM:To investigate risk factors associated with Barrett's oesophagus and oesophageal adenocarcinoma.METHODS:This all-Ireland population-based case-control study recruited 224 Barrett's oesophagus patients,227 oesophageal adenocarcinoma patients and 260 controls.All participants underwent a structured interview with information obtained about potential lifestyle and environmental risk factors.RESULTS:Gastro-oesophageal reflux was associated with Barrett's [OR 12.0(95% CI 7.64-18.7)] and oesophageal adenocarcinoma [OR 3.48(95% CI 2.25-5.41)].Oesophageal adenocarcinoma patients were more likely than controls to be ex-or current smokers [OR 1.72(95% CI 1.06-2.81)and OR 4.84(95% CI 2.72-8.61)respectively] and to have a high body mass index [OR 2.69(95% CI 1.62-4.46)].No significant associations were observed between these risk factors and Barrett's oesophagus.Fruit but not vegetables were negatively associated with oesophageal adenocarcinoma [OR 0.50(95% CI 0.30-0.86)].CONCLUSION:A high body mass index,a diet low in fruit and cigarette smoking may be involved in the progression from Barrett's oesophagus to oesophageal adenocarcinoma.     

Secular trends in the epidemiology and outcome of Barrett's oesophagus in Olmsted County, Minnesota

BACKGROUND: The incidence of oesophageal adenocarcinoma has increased greatly. Barrett's oesophagus is a known risk factor. AIMS: To identify changes in the incidence, prevalence, and outcome of Barrett's oesophagus in a defined population. SUBJECTS: Residents of Olmsted County, Minnesota, with clinically diagnosed Barrett's oesophagus, or oesophageal or oesophagogastric junction adenocarcinoma. METHODS: Cases were identified using the Rochester Epidemiology Project medical records linkage system. Records were reviewed with follow up to 1 January 1998. RESULTS: The incidence of clinically diagnosed Barrett's oesophagus (>3 cm) increased 28-fold from 0.37/100 000 person years in 1965-69 to 10.5/100 000 in 1995-97. Of note, gastroscopic examinations increased 22-fold in this same time period. The prevalence of diagnosed Barrett's oesophagus increased from 22.6 (95% confidence interval (CI) 11.7-33.6) per 100 000 in 1987 to 82.6/100 000 in 1998. The prevalence of short segment Barrett's oesophagus (<3 cm) in 1998 was 33.4/ 100 000. Patients with Barrett's oesophagus had shorter than expected survival but only one patient with Barrett's oesophagus died from adenocarcinoma. Only four of 64 adenocarcinomas occurred in patients with previously known Barrett's oesophagus. CONCLUSIONS: The incidence and prevalence of clinically diagnosed Barrett's oesophagus have increased in parallel with the increased use of endoscopy. We infer that the true population prevalence of Barrett's oesophagus has not changed greatly, although the incidence of oesophageal adenocarcinoma increased 10-fold. Many adenocarcinomas occurred in patients without a previous diagnosis of Barrett's oesophagus, suggesting that many people with this condition remain undiagnosed in the community.     

Should patients with Barrett's oesophagus be kept under surveillance? The case against

Barrett's oesophagus, or columnar metaplasia of the oesophagus, is a known risk factor for adenocarcinoma of the oesophagus. Barrett's oesophagus is thought to be the result of longstanding gastro-oesophageal reflux disease, a very common diagnosis in the United States and other western countries. Because Barrett's oesophagus is a transition state between a common complaint and a devastating illness, endoscopic screening and surveillance strategies are commonly employed. However, neither screening nor surveillance strategies have been proven to reduce mortality from oesophageal adenocarcinoma. We address the multifaceted case against surveillance for oesophageal adenocarcinoma. The overall incidence of oesophageal adenocarcinoma is very low, especially compared to other cancers where surveillance is used. The pace of progression from Barrett's to adenocarcinoma is not known. There is a lack of evidence supporting surveillance programmes. There are drawbacks to endoscopic surveillance for dysplasia and adenocarcinoma in patients with established Barrett's oesophagus that include sampling error, inconsistent pathologic interpretation of biopsies, and cost. Taken individually or together, these limitations make a strong case against surveillance endoscopy in Barrett's oesophagus.     

Intra-oesophageal acid suppression in complicated gastro-oesophageal reflux disease: esomeprazole versus lansoprazole

BACKGROUND: Acid suppression is the mainstay of therapy in gastro-oesophageal reflux disease. Esomeprazole 40 mg is more effective than lansoprazole 30 mg in healing mucosal lesions in severe erosive reflux oesophagitis. However, data comparing esomeprazole with lansoprazole in patients with complications of gastro-oesophageal reflux disease, such as ulcerative reflux oesophagitis and Barrett's oesophagus, are lacking. AIM: To compare the efficacy of esomeprazole and lansoprazole at their standard dosages in suppressing oesophageal acid exposure in complicated gastro-oesophageal reflux disease. METHODS: Thirty patients with complicated gastro-oesophageal reflux disease (7 with ulcerative reflux oesophagitis and 23 with Barrett's oesophagus), randomly assigned to receive 40 mg esomeprazole (n=16) or 30 mg lansoprazole (n=14) once daily, underwent oesophageal 24-h pH monitoring while on therapy. Total, upright diurnal and supine nocturnal percentage acid reflux time were assessed. RESULTS: Esomeprazole was significantly more effective than lansoprazole in decreasing oesophageal acid exposure. Normalisation of both total and supine nocturnal percentage acid reflux time was obtained in 12 of 16 (75%) patients treated with esomeprazole but only in 4 of 14 (28%) cases treated with lansoprazole (p=0.026). CONCLUSIONS: Normalisation of oesophageal acid exposure can be achieved in the majority of complicated gastro-oesophageal reflux disease cases with esomeprazole 40 mg once daily.     

Toxic bile acids in gastro-oesophageal reflux disease: influence of gastric acidity

BACKGROUND: Bile acid toxicity has been shown in the gastric, colonic, and hepatic tissues; the effect on oesophageal mucosa is less well known. AIMS: To determine the spectrum of bile acids refluxing in patients with gastro-oesophageal reflux disease and its relation to oesophageal pH using a new technique of combined oesophageal aspiration and pH monitoring. METHODS: Ten asymptomatic subjects and 30 patients with symptoms of gastro-oesophageal reflux disease (minimal mucosal injury, erosive oesophagitis (grade 2 or 3 Savary-Miller), Barrett's oesophagus/stricture; n=10 in each group) underwent 15 hour continuous oesophageal aspiration with simultaneous pH monitoring. Bile acid assay of the oesophageal samples was performed using modified high performance liquid chromatography. RESULTS: The peak bile acid concentration and DeMeester acid scores were significantly higher in the patients with oesophagitis (median bile acid concentration 124 micromol/l; acid score 20.2) and Barrett's oesophagus/stricture (181 micromol/l; 43. 3) than patients with minimal injury (14 micromol/l; 12.5) or controls (0 micromol/l; 11.1). The predominant bile acids detected were cholic, taurocholic, and glycocholic acids but there was a significantly greater proportion of secondary bile acids, deoxycholic and taurodeoxycholic acids, in patients with erosive oesophagitis and Barrett's oesophagus/stricture. Although bile acid reflux episodes occurred at variable pH, a temporal relation existed between reflux of taurine conjugates and oesophageal acid exposure (r=0.58, p=0.009). CONCLUSION: Toxic secondary bile acid fractions have been detected in patients with extensive mucosal damage. Mixed reflux is more harmful than acid reflux alone with possible toxic synergism existing between the taurine conjugates and acid.     

Pathophysiological characteristics of long- and short-segment Barrett's oesophagus

BACKGROUND: Depending on the length of the segment of columnar epithelium in the distal oesophagus, Barrett's oesophagus can be divided into long-segment and short-segment Barrett's oesophagus. This article describes the pathophysiological characteristics of both forms of Barrett's oesophagus. METHODS: Review of the literature. RESULTS: Although there is some disagreement, ours and most other studies suggest that long-segment columnar-lined oesophagus is causally linked to chronic gastro-oesophageal reflux and that this from of Barrett's oesophagus is characterized by lower oesophageal sphincter tone, reduced oesophageal contractility and increased acid reflux. Short-segment Barrett's oesophagus is also associated with acid reflux, but the degree of oesophageal acid exposure and the level of other pathophysiological alterations seem to be lower. CONCLUSION: Pathophysiological abnormalities appear to be more prominent in long-segment Barrett's oesophagus than in short-segment Barrett's oesophagus.     

Barrett oesophagus and adenocarcinoma: an overview of epidemiologic, conceptual and clinical issues.

A steady increase in the incidence of adenocarcinoma of the oesophagus and oesophagogastric junction has been observed in Western countries. Patients with distinctive-type Barrett oesophagus are predisposed to developing adenocarcinoma of the oesophagus. Distinctive-type Barrett oesophagus is defined by the presence of intestinal-like goblet cells anywhere in the oesophagus. Adenocarcinomas of the oesophagogastric junction may be associated with short segments of intestinal-type columnar epithelium in the distal oesophagus. Prognosis after surgical resection for cancer of the oesophagus or oesophagogastric junction is strongly affected by the extent of the disease at the time of diagnosis. The identification of Barrett oesophagus as a premalignant condition, the recognition of a stepwise neoplastic progression, along with the poor survival rates of advanced oesophageal adenocarcinoma have initiated the practice of endoscopic biopsy surveillance for patients with Barrett oesophagus. There is supporting evidence that endoscopic biopsy surveillance of Barrett oesophagus permits detection of malignancy at an early stage with favourable results after oesophageal resection. Endoscopic treatment modalities should at this time not be generally adopted in the management of patients with early invasive adenocarcinoma of the oesophagus or oesophagogastric junction.     

Evaluation of the magnitude of gastro-oesophageal reflux in Barrett's oesophagus.

A manometric study to determine the role of gastro-oesophageal reflux in Barrett's oesophagus was performed on 20 patients with Barrett's oesophagus and 53 patients with reflux oesophagitis without Barrett's oesophagus (25 with mild oesophagitis and 28 with severe oesophagitis). For the same reason, the 20 patients with Barrett's oesophagus also underwent 24 hour continuous oesophageal pH monitoring, and the results obtained were compared with those of 20 oesophagitis patients without Barrett's oesophagus (10 with mild oesophagitis and 10 with severe oesophagitis). The manometric results show that the motor changes found in the Barrett's group are specific but similar to the motor dysfunction associated with reflux oesophagitis. Motor anomalies are probably related more to the inflammatory process in the oesophageal wall than to the metaplastic changes themselves. The pH monitoring results show that while reflux in the Barrett's oesophagus patients was greater overall than in the oesophagitis group without Barrett's oesophagus, the changes are similar when the results are compared with the severe oesophagitis group. In conclusion there are other factors besides gastro-oesophageal reflux involved in the pathogenesis of Barrett's oesophagus.     

Prevalence of short-segment Barrett's epithelium

BACKGROUND/AIMS: The incidence of adenocarcinoma of the oesophagus has increased. Its major risk factor is Barrett's epithelium of which the sine qua non is microscopically diagnosed intestinal metaplasia. Short segment Barrett's epithelium may often be overlooked during routine endoscopy. In routine biopsies taken from normal-appearing mucosa of the distal oesophagus, the reported rates of short segment Barrett's epithelium in the distal oesophagus reached 36%. We compared these rates with the results obtained in a community hospital in Israel. METHODS: Consecutive patients undergoing oesophagogastroduodenoscopy were enrolled. Biopsy specimens taken from cardia, oesophagogastric junction and 2 cm above the oesophagogastric junction were stained with haematoxylin & eosin and Alcian blue. RESULTS: There were 112 study patients (mean age +/- SD 48. 9+/-18.3 years, 51.8% males). Nine (8.04%) patients had intestinal metaplasia (according to specimen from 2 cm above oesophagogastric junction), and symptoms of gastro-oesophageal reflux were found in only four (44.4%) of them. Of these nine patients, six (6.66%) had normal-appearing mucosa and three (3.33%) had macroscopic Barrett's epithelium. Alcian blue staining revealed two patients with intestinal metaplasia that haematoxylin & eosin staining had missed. CONCLUSION: We found an 8% prevalence of intestinal metaplasia compared to 18-36% reported in the literature. We also determined that the added advantage of routine biopsy was 5.4%.     

Bile reflux gastritis and Barrett's oesophagus: further evidence of a role for duodenogastro-oesophageal reflux?

BACKGROUND: There is increasing evidence that reflux of bile plays a part in the pathogenesis of Barrett's oesophagus. Bile injury to the gastric mucosa results in a "chemical" gastritis in which oedema and intestinal metaplasia are prominent. AIM: To determine if patients with Barrett's oesophagus have more bile related changes in antral mucosa than patients with uncomplicated gastro-oesophageal reflux disease (GORD) or non-ulcer dyspepsia (NUD). PATIENTS AND METHODS: Patients were identified by a retrospective search of pathology records and those with a clinically confirmed diagnosis of either Barrett's oesophagus or reflux oesophagitis who had oesophageal and gastric biopsies taken at the same endoscopy and had no evidence of Helicobacter pylori infection entered the study. Control biopsies were taken from H pylori negative NUD patients. Antral biopsies were examined "blind" to clinical group and graded for a series of histological features from which the "reflux gastritis score" (RGS) and "bile reflux index" (BRI) could be calculated. The reproducibility of these histological scores was tested by a second pathologist. RESULTS: There were 100 patients with Barrett's, 61 with GORD, and 50 with NUD. The RGSs did not differ between groups. BRI values in the Barrett's group were significantly higher than those in GORD subjects (p=0.014) which in turn were higher than those in NUD patients (p=0.037). Similarly, the frequency of high BRI values (>14) was significantly greater in the Barrett's group (29/100; 29%) than in the GORD (9/61; 14.8%) or NUD (4/50; 8%) group. However, agreement on BRI values was "poor", indicating limited applicability of this approach. CONCLUSION: Patients with Barrett's oesophagus have more evidence of bile related gastritis than subjects with uncomplicated GORD or NUD. The presence of bile in the refluxate could be a factor in both the development of "specialised" intestinal metaplasia and malignancy in the oesophagus.     

Role of acid and bile reflux in development of specialised intestinal metaplasia in distal oesophagus

BACKGROUND: Barrett's oesophagus is defined as specialised intestinal metaplasia in the distal oesophagus, regardless of extension. AIM: To study distal oesophagus function, and acid and bile exposure in patients with Long Segment (>3 cm), Short Segment (1 to 2 cm) and Ultra-short Segment (<1 cm) Barrett's Oesophagus, and in patients with gastro-oesophageal reflux disease without intestinal metaplasia. PATIENTS: Study population comprised 17 patients with Long, 8 with Short, 9 with Ultra-Short Segment Barrett's oesophagus, 32 with reflux disease and 12 healthy volunteers. METHODS: Patients were evaluated by manometry and by 24-hour pH and bile monitoring. RESULTS: Patients with intestinal metaplasia had greater acid exposure of the distal oesophagus than healthy volunteers. Patients with Long Segment Barrett's oesophagus had a longer history of symptoms, worse lower oesophageal sphincter pressures and longer bile and acid exposure than the other patients. Long Segment Barrett's oesophagus was predicted by low oesophageal pressure and increased bile exposure, age and male sex. CONCLUSION: Acid exposure in the distal oesophagus is probably the aetiological factor behind intestinal metaplasia, but a severely damaged antireflux barrier and bile in the refluxate are necessary for Long Segment Barrett's Oesophagus to develop.     

Are screening and surveillance for Barrett's oesophagus really worthwhile?

Oesophageal adenocarcinoma has a low incidence and still remains an uncommon cancer; however, it has been on the rise over the past 20 years. Barrett's oesophagus, a complication of gastro-oesophageal reflux disease, is the only known precursor of this adenocarcinoma. It can often be asymptomatic and probably goes undiagnosed in the majority of the population. There are no direct data supporting the practice of screening for Barrett's oesophagus and oesophageal adenocarcinoma among the general population or even in patients with chronic reflux symptoms. However, many argue that the detection of neoplasms at a curable state in a high risk population can perhaps justify screening endoscopy. No prospective, controlled trials have been conducted to support the effectiveness of surveillance, but some indirect evidence does exist. The cost effectiveness of surveillance programmes needs to be further assessed in prospective studies. Ultimately, the use of better tools to diagnose Barrett's oesophagus and dysplasia and the identification of high risk groups for progression to oesophageal adenocarcinoma could potentially make screening and surveillance a cost effective practice.     

K-ras codon 12 mutations in Barrett's oesophagus and adenocarcinomas of the oesophagus and oesophagogastric junction

BACKGROUND: Activation of the ras oncogene is commonly found in gastrointestinal tract cancers, but the role of ras in the development and progression of Barrett's oesophagus and associated cancers is uncertain. METHODS: The frequency of K-ras codon 12 point mutations was assessed in 52 paraffin-embedded tissues from 44 patients with oesophageal pathology. The specimens were classified pathologically as follows: adenocarcinoma of the oesophagus or oesophagogastric junction (n = 23), Barrett's high-grade dysplasia (n = 5), low-grade dysplasia (n = 14), intestinal metaplasia (n = 4), normal oesophagus (n = 5) or normal stomach (n = 1). DNA was extracted from three consecutive sections of each paraffin block and mutations at bases 1 and 2 of K-ras codon 12 were identified using a novel restriction endonuclease-mediated selective polymerase chain reaction method. RESULTS: Mutations were found in 7 of 23 (30.4%) adenocarcinomas and in 2 of 5 (40%) high-grade dysplasia specimens. No mutations were found in specimens of low-grade dysplasia, intestinal metaplasia without dysplasia, or normal oesophagus and stomach. There were no significant associations between the presence of mutations and clinicopathologic features in the patients with cancer. One patient who progressed from low-grade to high-grade dysplasia was found to have developed mutant K-ras in the course of this transformation. CONCLUSION: These results suggest that K-ras codon 12 mutations may occur frequently in patients with Barrett's oesophagus with high-grade dysplasia or adenocarcinoma of the oesophagus or oesophagogastric junction. K-ras mutation may be a late event in the Barrett's metaplasia-dysplasia-adenocarcinoma sequence.     

Neuromuscular function of the human lower oesophageal sphincter in reflux disease and Barrett's oesophagus

BACKGROUND: Columnar lined (Barrett's) oesophagus is often considered a sequel to chronic severe reflux disease. Aberrant lower oesophageal sphincter (LOS) motility associated with Barrett's oesophagus includes reduced basal LOS pressures. The aim of this study was to characterise neuromuscular function of the LOS in normal (squamous cell carcinoma (SCC) with uninvolved LOS) and reflux affected (Barrett's) oesophagus in vitro. METHODS: Strips of LOS muscle were prepared at biopsy following oesophagectomy from 16 patients with SCC and seven patients with oesophageal adenocarcinoma and Barrett's oesophagus associated with a history of reflux disease. LOS smooth muscle responses were recorded in response to electrical field stimulation (EFS), potassium chloride (KCl), DMPP, isoprenaline, capsaicin, bethanechol, and tachykinins. RESULTS: Basal LOS tone and LOS relaxations in response to isoprenaline, EFS, and DMPP were not significantly altered in the Barrett's group. After tetrodotoxin pretreatment, responses to KCl and DMPP were significantly reduced in the SCC but not in Barrett's LOS. Maximal contraction in response to bethanechol was significantly decreased in Barrett's LOS while substance P and NK-2 receptor mediated contraction was unaltered. Capsaicin, NK-1, and NK-3 receptor agonists exerted negligible effects on LOS tone. CONCLUSIONS: LOS muscle strips from patients with reflux associated Barrett's oesophagus exhibit a reduction in cholinergic muscle contraction while retaining similar features of basal tone, responses to tachykinins, and inhibitory muscle and neural function. Enteric inhibitory neurones in LOS muscle strips from patients with reflux associated Barrett's oesophagus display resistance to axonal sodium channel blockade. No evidence for functional NK-1 or NK-3 receptors or capsaicin sensitive axon collateral reflexes was observed in the human LOS.     

Oesophageal disorders: future developments

Elicitation of the characteristic symptom patterns remains the primary approach to the diagnosis of gastro-oesophageal reflux disease, and this may be enhanced by developments in the use of high-resolution endoscopy and oesophageal biopsy. For future therapy, proton pump inhibitors and anti-reflux surgery may compete with reversible acid pump blockers, reflux inhibitor drugs and diverse luminally delivered physical anti-reflux therapies. Short-segment Barrett's oesophagus is known to be highly prevalent, but its impact on the risk of adenocarcinoma remains poorly defined. Biomarkers for Barrett's oesophagus have been proposed to aid in the stratification of cancer risk, and cytology may assume more importance in the future. Endoscopic surveillance for Barrett's oesophagus is widely practised, but more data are needed to demonstrate cost-effectiveness and a positive impact on mortality. Animal and limited human studies suggest that chemoprevention may become an important strategy in reducing the risk of adenocarcinoma. The ablation of Barrett's epithelium results in a reversal of Barrett's epithelium, albeit with an uncertain long-term outcome.     

Should patients with Barrett's oesophagus be kept under surveillance? The case for

Oesophageal adenocarcinoma is associated with high mortality rates and its incidence is increasing more rapidly than any other gastrointestinal cancer in the Western world. Several factors, including gastro-oesophageal reflux disease, smoking, alcohol and male gender, are associated with oesophageal adenocarcinoma but none can be used to identify accurately those individuals who will develop adenocarcinoma. It is generally accepted that oesophageal adenocarcinoma arises predominantly in Barrett's oesophagus and it is arguable that Barrett's oesophagus is currently the only clinically useful predictor of oesophageal adenocarcinoma. Surveillance - periodic testing to detect adenocarcinoma or its precursor, high grade dysplasia - is widely recommended for patients with Barrett's oesophagus with the aim of reducing mortality from oesophageal adenocarcinoma. The annual incidence of oesophageal adenocarcinoma in patients with Barrett's oesophagus is 0.5%-1.0% although there is marked variation between studies, attributable variously to publication bias, concurrent acid suppression therapy and differences in patient characteristics. There is limited evidence that surveillance reduces the incidence of oesophageal adenocarcinoma or consequent mortality and the cause of death for patients undergoing surveillance is often unrelated to oesophageal disease. There are, nonetheless, observational studies which suggest that surveillance is associated with earlier detection of malignancy and a reduction in mortality; in addition, data from modelling studies suggest that surveillance can be cost-effective. Furthermore, the advent of new, non-surgical treatments (endoscopic mucosal resection, photodynamic therapy, argon plasma coagulation) for high grade dysplasia and early cancer has reduced the risks associated with therapy for disease detected during surveillance. Surveillance programs have high drop out rates and, for patients who continue surveillance, adherence to standard, published protocols is highly variable. The establishment of specialist Barrett's oesophagus surveillance programs, with coordinator support, has considerable potential to improve adherence to current guidelines, pending the acquisition and publication of data from ongoing studies of chemoprophylaxis and surveillance in the management of Barrett's oesophagus. In consequence, although there is a paucity of data providing unequivocal demonstration of benefit, there is no proof that surveillance is ineffective. It is, therefore, appropriate to offer surveillance for Barrett's oesophagus in accordance with locally-applicable published guidelines after a full informed discussion of the risks and benefits of surveillance and therapy; continued participation should be reviewed regularly to accommodate changes in the patient's health and expectations.