Barrett's oesophagus: results from a 13-year surveillance programme

OBJECTIVES: To review the results of a 13-year surveillance programme of patients with Barrett's oesophagus to determine the incidence of adenocarcinoma. Although the risk of cancer in Barrett's oesophagus is well established, the magnitude of this risk is still controversial. DESIGN: Records of all patients with histologically confirmed Barrett's oesophagus in our 13-year surveillance programme were examined retrospectively. SETTING: Integrated gastroenterology and gastrointestinal surgical service in a large teaching hospital. PARTICIPANTS: During the study period, 597 patients had a diagnosis of Barrett's oesophagus; of these, 357 entered a yearly endoscopy and biopsy surveillance programme. MAIN OUTCOME MEASURES: The development of oesophageal adenocarcinoma. RESULTS: After a mean follow-up of 43 months, 12 patients, all with specialized epithelium, developed adenocarcinoma (11 men), an incidence for men of one cancer per 69 patient-years; and for women, one cancer per 537 patient-years follow-up (P < 0.01). If only patients with specialized mucosa were included the incidence of cancer was one per 95 patient-years of follow-up (men, one per 61 patient-years; women, one per 468 patient-years). CONCLUSIONS: Whilst the role of screening patients with Barrett's oesophagus remains controversial, this study supports the routine surveillance of male patients with specialized epithelium.     

Cost-effectiveness of Barrett's oesophagus screening and surveillance

Endoscopic screening and surveillance of patients with Barrett's oesophagus to detect oesophageal cancer at earlier stages is contentious. As a consequence, their cost-effectiveness is also debatable. Current health economic evidence shows mixed results for demonstrating their value, mainly due to varied assumptions around progression rates to cancer, quality of life and treatment pathways. No randomized controlled trial exists to definitively support the efficacy of surveillance programs and one is unlikely to be undertaken. Contemporary treatment, cost and epidemiological data to contribute to cost-effectiveness analyses are needed. Risk assessment to stratify patients at low- or high-risk of developing cancer should improve cost-effectiveness outcomes as higher gains will be seen for those at higher risk, and medical resource use will be avoided in those at lower risk. Rapidly changing technologies for imaging, biomarker testing and less-invasive endoscopic treatments also promise to lower health system costs and avoid adverse events in patients.     

New developments in the endoscopic surveillance of Barrett's oesophagus

Patients with a Barrett's oesophagus are at risk for developing an adenocarcinoma of the distal oesophagus. Therefore, many patients undergo endoscopic surveillance to detect dysplasia and/or cancer at an early and curable stage. However, early neoplastic lesions are difficult to identify with standard endoscopy. In addition, the low incidence of these lesions, currently estimated at 0.5% per year, reduces the cost effectiveness of the surveillance strategy. New developments, aimed at improving the efficacy of Barrett's surveillance, focus on two areas: 1) improvement of the endoscopic detection of early neoplastic lesions; and 2) the use of alternative techniques for tissue sampling combined with molecular markers to identify patients at risk for malignant degeneration.     

A surveillance programme for Barrett's oesophagus in a UK general hospital

BACKGROUND: Surveillance programmes for oesophageal cancer in patients with Barrett's columnar-lined oesophagus have reported varying efficacies. AIM: To review the effectiveness of an endoscopic surveillance programme for patients with Barrett's oesophagus in a UK general hospital. METHODS: Patients with Barrett's oesophagus (> or =3 cm histologically proven columnar-lined oesophagus) were identified from endoscopic and histological records and outcomes recorded when surveillance was performed with 2-yearly endoscopies and quadrantic biopsies at 3 cm intervals. RESULTS: One hundred and twenty-one patients (24%) entered the surveillance programme (mean age 60.2 years, 69.5% men, mean length of Barrett's mucosa 7.5 cm) of 505 patients identified with Barrett's oesophagus. Two hundred and five endoscopies were performed over a mean follow-up of 3.5 years. Five cases of high-grade dysplasia and two cases of adenocarcinoma were detected during the surveillance. One patient with high-grade dysplasia refused surgery and died of oesophageal carcinoma. The other six patients underwent oesophagectomy and five of the six resected specimens showed early (Tis to T2, N0) adenocarcinoma. All six patients remained well and tumour free at 24 months. No interval oesophageal cancers occurred. CONCLUSION: This surveillance programme for classical Barrett's oesophagus was effective with six cancers being detected early and treated. The detection rate was 1/71 patient-years of surveillance. Endoscopic workload was not excessive and no interval cancers occurred.     

Adenocarcinoma in Barrett's oesophagus: an overrated risk.

Barrett's oesophagus is a risk factor for the development of oesophageal cancer and for this reason annual endoscopic surveillance has been proposed. In this retrospective study of all patients with Barrett's oesophagus diagnosed in a 12 year period carcinoma had developed in only four patients. The incidence of oesophageal cancer in this series was one in 170 patient years, which means a 30-fold increase compared with the general population. The survival of patients with Barrett's oesophagus was not different, however, from an age and sex matched control population. It is concluded that systematic endoscopic surveillance of patients with Barrett's oesophagus is not indicated.     

Barrett's oesophagus: Current controversies

Oesophageal adenocarcinoma is rapidly increasing in Western countries. This tumour frequently presents late in its course with metastatic disease and has a very poor prognosis. Barrett's oesophagus is an acquired condition whereby the native squamous mucosa of the lower oesophagus is replaced by columnar epithelium following prolonged gastro-oesophageal reflux and is the recognised precursor lesion for oesophageal adenocarcinoma. There are multiple national and society guidelines regarding screening,surveillance and management of Barrett's oesophagus,however all are limited regarding a clear evidence base for a well-demonstrated benefit and cost-effectiveness of surveillance,and robust risk stratification for patients to best use resources. Currently the accepted risk factors upon which surveillance intervals and interventions are based are Barrett's segment length and histological interpretation of the systematic biopsies. Further patient risk factors including other demographic features,smoking,gender,obesity,ethnicity,patient age,biomarkers and endoscopic adjuncts remain under consideration and are discussed in full. Recent evidence has been published to support earlier endoscopic intervention by means of ablation of the metaplastic Barrett's segment when the earliest signs of dysplasia are detected. Further work should concentrate on establishing better risk stratification and primary and secondary preventative strategies to reduce the risk of adenocarcinoma of the oesophagus.     

Surveillance in Barrett's oesophagus: a critical reappraisal

BACKGROUND: Current recommendations are for endoscopic surveillance of patients with Barrett's oesophagus to detect dysplasia and to diagnose carcinoma at an early and possibly treatable stage. However, observations suggest that these current practice guidelines are thwarted by many factors often not taken into account. These observations stem from general surveillance aspects as well from specific data on Barrett's oesophagus. This review therefore aims at discussing data on the current surveillance strategy in conjunction with general surveillance aspects relevant for their interpretation. METHODS: Literature survey of published articles. RESULTS: A critical reappraisal of the literature shows that the current surveillance strategy is hampered by multiple problems with the marker dysplasia, cost-ineffectiveness, an overrated cancer risk and an astonishing lack of prospective, randomized data showing a clear benefit in terms of a greater life expectancy. Moreover, the decisive study is unlikely ever to be performed because of the large number of patients needed and the required length of follow-up. As a result, protocols are being carried out that have never been critically tested prior to large-scale clinical implementation. CONCLUSIONS: Although these findings should not lead to therapeutic nihilism, the data raise the issue of whether or not surveillance protocols should be restricted to specialized referral centres with particular research efforts aimed at improving existing and developing new techniques that lack most of the described pitfalls and problems. Since it is foreseen that matters will not change rapidly in the (near) future, the clinician has no other choice than to rely on individually tailored arguments to survey taking into account for example family history, age and anxiety about potential long-term effects.     

Impact of endoscopic biopsy surveillance of Barrett's oesophagus on pathological stage and clinical outcome of Barrett's carcinoma

BACKGROUND: The efficacy of endoscopic biopsy surveillance of Barrett's oesophagus in reducing mortality from oesophageal cancer has not been confirmed. AIMS: To investigate the impact of endoscopic biopsy surveillance on pathological stage and clinical outcome of Barrett's carcinoma. METHODS: A clinicopathological comparison was made between patients who initially presented with oesophageal adenocarcinoma (n = 54), and those in whom the cancer had been detected during surveillance of Barrett's oesophagus (n = 16). RESULTS: The surveyed patients were known to have Barrett's oesophagus for a median period of 42 months (range 6-144 months). Prior to the detection of adenocarcinoma or high grade dysplasia, 13 to 16 patients (81%) were previously found to have low grade dysplasia. Surgical pathology showed that surveyed patients had significantly earlier stages than non-surveyed patients (p = 0.0001). Only one surveyed patient (6%) versus 34 non-surveyed patients (63%) had nodal involvement (p = 0.0001). Two year survival was 85.9% for surveyed patients and 43.3% for non-surveyed patients (p = 0.0029). CONCLUSIONS: The temporal course of histological progression in our surveyed patients supports the theory that adenocarcinoma in Barrett's oesophagus develops through stages of increasing severity of dysplasia. Endoscopic biopsy surveillance of Barrett's oesophagus permits detection of malignancy at an early and curable stage, thereby potentially reducing mortality from oesophageal adenocarcinoma.     

Definition of Barrett's oesophagus

Barrett's oesophagus is the eponym applied to the columnar epithelium-lined lower oesophagus. In 1976, Paull et al. described three types of columnar epithelia lining the distal oesophagus: a junctional or cardiac-type epithelium, a gastric fundic-type epithelium and a distinctive type of intestinal metaplasia referred to as specialized columnar epithelium. Even the normal oesophagus can be lined by 2 cm of columnar epithelium. To avoid the problem of false-positive diagnoses, arbitrary criteria for the extent of oesophageal columnar lining necessary to include patients in studies of Barrett's oesophagus were established in the early 1980s. The latter criteria require a circumferential segment of columnar lined epithelium of 2 or 3 cm in length. There are, however, a number of technical and conceptual problems related to this approach. The traditional definition excludes shorter segments and tongues of columnar lined epithelium. Only the specialized columnar epithelium defined by intestinal type goblet cells carries an inherent risk of malignancy. Therefore, a number of investigators currently define Barrett's oesophagus as any amount of columnar mucosa in the lower esophagus that has histologic evidence of goblet cells (highlighted in biopsies using the alcian blue pH 2.5 stain). Recently, short segments of specialized intestinal metaplasia in the distal oesophagus ("short segment Barrett's oesophagus") have attracted considerable attention. It has also become clear that intestinal metaplasia can occur at a normally located gastro-oesophageal junction. The etiology and clinical significance (in terms of possible relationship to the adenocarcinoma of the cardia) of this "intestinal metaplasia of the gastric cardia" and its potential relationship to Barrett's oesophagus are not yet completely understood.     

Development of pseudo-achondroplasia over a 30-year period in an adult patient

Summary We studied the clinical and radiological developments in a pseudoachondroplasia patient over a period of 30 years.     

Risk factors for Barrett's oesophagus: a population-based approach

OBJECTIVE: Given its often subclinical course, Barrett's oesophagus (BO) hardly lends itself to epidemiologically stringent evaluations. The objective of this study was to investigate risk factors for incident BO diagnosed in a defined population in southeast Sweden while paying particular attention to epidemiological aspects of the study design. MATERIAL AND METHODS: Consecutive patients (aged 18-79 years) who were endoscoped with new indications at units exclusively responsible for all gastroscopies in defined catchment area populations were invited to take part in the study. Biopsies were taken above and immediately below the gastro-oesophageal junction, and exposure information was collected through self-administered questionnaires. Endoscopy-room-based cross-sectional data from 604 patients were supplemented with exposure data from 160 population controls. Associations, expressed as odds ratios (ORs), were modelled by means of multivariable logistic regression. RESULTS: In the comparison with population controls, reflux symptoms and smoking indicated a 10.7- and 3.3-fold risk, respectively, for BO (95% confidence interval (CI) 3.5-33.4 and 1.1-9.9, respectively). Body mass was unrelated to risk. In the cross-sectional analysis among endoscopy-room patients, reflux symptoms were associated with an OR of 2.0 (95% CI 0.8-5.0). This association was, however, modified by the subjunctional presence of Helicobacter pylori; although the infection was not in itself significantly connected with risk, a combination of reflux symptoms and H. pylori infection was linked to an almost 5-fold risk (95% CI 1.4-16.5) as compared with the absence of both factors. The BO prevalence increased by 5% per year of age (95% CI 1-9%). CONCLUSIONS: Reflux is the predominant risk factor for BO, and proximal gastric colonization of H. pylori seems to amplify this risk.     

Anaerobic bacteremia: decreasing rate over a 15-year period

At the Mayo Clinic, the number of cases of anaerobic bacteremia decreased 45% between 1974 and 1988. In addition, the percentage of blood cultures positive for anaerobes decreased significantly even though the total number of blood cultures performed increased. The number of anaerobic bacteremias per 100,000 patient-days also declined over the 15-year period. Organisms of the Bacteroides fragilis group ranked third in frequency with respect to other organisms that caused aerobic and anaerobic bacteremia in 1974 but ranked only seventh in 1988 and caused slightly less than one-half of the anaerobic bacteremias. The mechanisms responsible for these changes are unclear but might relate to earlier recognition and treatment of localized anaerobic infection, widespread preoperative use of agents prior to bowel surgery, and use of broad-spectrum antimicrobial regimens that include agents with activity against anaerobes.     

Endoscopic treatment of Barrett's oesophagus

Barrett's oesophagus develops as a consequence of severe gastro-oesophageal reflux. The importance of Barrett's oesophagus lies in the small risk of developing high-grade dysplasia and subsequent adenocarcinoma. Because of poor treatment results in patients with advanced adenocarcinoma, surveillance of patients with Barrett's oesophagus for the development of dysplasia, although not uncontroversial, is widely practised in the gastroenterological community. The aim of surveillance is to detect adenocarcinoma in an early stadium where surgical cure is possible. In recent years several endoscopic treatments for both high-grade dysplasia and intramucosal adenocarcinoma have been developed. In this review some basic aspects of Barrett's oesophagus are discussed together with endoscopic treatments such as endoscopic mucosal resection, local thermal treatments and photodynamic therapy. Although surgical resection is probably the treatment of choice in fit patients, local endoscopic treatments should be considered in patients with high-grade dysplasia or intramucosal carcinoma who are unfit or unwilling to have surgery.