Motion All patients with GERD should be offered once in a lifetime endoscopy : Arguments for the motion

This article was originally presented at a symposium entitled, "Controversies in Gastroenterology", sponsored by Axcan Pharma, Toronto, Ontario, April 8-10, 2002 Division of Gastroenterology, McMaster University, Hamilton, Ontario Correspondence: Dr David Armstrong, Division of Gastroenterology, HSC-4W8, McMaster University Medical Centre, 1200 Main Street West, Hamilton, Ontario L8N 3Z5. Telephone 905-521-2100 ext 76404, fax 905-521-4958, e-mail armstro@mcmaster.ca D Armstrong. Motion  All patients with GERD should be offered once in a lifetime endoscopy: Arguments for the motion. Can J Gastroenterol 2002;16(8):549-551.


THE ROLE OF ENDOSCOPY IN GASTROESOPHAGEAL REFLUX DISEASE
Since its introduction, endoscopy has been crucial to the management of gastroesophageal reflux disease (GERD), although its specific role has continued to evolve as understanding of the disease has changed over the years.Fibreoptic endoscopy allows safe, detailed inspection of the upper gastrointestinal tract and accurate identification of distal esophageal erosions, which are the most typical lesions of reflux esophagitis (1).
The identification of esophageal erosions and their healing in response to treatment were the basis of many of the seminal trials in GERD, shifting the emphasis from symptomatic therapy to the healing of esophageal erosions.For many physicians, erosive esophagitis has become synonymous with GERD, and endoscopy has, therefore, been the investigation of choice for the diagnosis of GERD.Endoscopy has also improved the opportunities to identify and, on occasion, treat complications of reflux disease, such as hemorrhage, ulceration, stricturing and Barrett's esophagus (BE) (1,2).With these developments, greater emphasis has been placed on refining the diagnosis of GERD, so that therapy can be tailored to disease severity and to facilitate the management of the acute complications of reflux disease.Even though it is increasingly apparent that BE is a premalignant lesion, the identification of this abnormality was not the primary aim of endoscopic examination.
Endoscopy continues to have a major role in the investigation of patients with alarm features, such as dysphagia, odynophagia, bleeding, weight loss, severe atypical symptoms or failure to respond to optimal medical therapy.It has recently been recognized, however, that endoscopy-negative reflux disease (ENRD) accounts for a large proportion (over one-half in some studies) of patients with GERD (3).Moreover, esophageal pH monitoring has not lived up to its diagnostic promise, particularly in patients with ENRD.Increasingly, GERD is diagnosed based on the presence of typical reflux symptoms (heartburn and regurgitation) that resolve with acid-suppression therapy.A number of consensus panels have endorsed this approach, and the use of empirical therapy for patients with typical symptoms and no alarm features (4,5).

THE RELATIONSHIP BETWEEN GERD AND BE AND CANCER
If the primary role of endoscopy is not to diagnose GERD, is there then still a place for this procedure in its management?I will argue that endoscopy indeed remains important in the management of GERD, because severe GERD predisposes patients to both BE and esophageal adenocarcinoma (EAC).In brief, the evidence to be reviewed shows that BE occurs in a significant proportion of patients with GERD (10% to 15%) and that it is a major risk factor for the development of adenocarcinoma.Furthermore, the occurrence of reflux symptoms, possibly even without Barrett's metaplasia, is also a risk factor for the development of cancer.
The incidence of reflux-associated EAC is increasing, while that of squamous cell esophageal carcinoma is decreasing (6,7).EAC is now the eighth most prevalent cancer in the world.The reasons for this prevalence are not known, but a population-based study from Sweden found that symptomatic GERD was a significant risk factor (8). Subjects with reflux symptoms at least once per week had a relative risk of EAC of 7.7, compared with persons without such symptoms, and the risk was even greater for those with chronic, frequent and severe symptoms (odds ratio 43.5).Other risk factors for EAC include obesity, smoking and, in women, decreased fruit intake (9)(10)(11).
The prevalence of GERD in the general population is 10% to 40% (12)(13)(14).Of patients with severe enough symptoms to warrant endoscopy, 40% to 60% have erosive esophagitis, and 10% to 15% have BE.Winters et al (15) reported that approximately 12% of persons who undergo endoscopy for reflux symptoms have BE, but estimates decrease by at least one-half if stricter criteria for the diagnosis of BE (such as the presence of specialized intestinal epithelium) are used (16).The population prevalence of erosive esophagitis is approximately 2% and that of BE is approximately 0.4% (17).
There is considerable debate about the BE patient's risk of developing EAC, with estimates ranging from 0.2% to 2.9% per year (18).Because of publication bias, however, the risk may be overestimated (18,19).Because it presents late in its course, EAC has a very poor prognosis, with fiveyear survival rates of less than 10% (20).

SCREENING FOR BE
Recent guidelines from the American College of Gastroenterology recommend endoscopy for patients over the age of 50 years who have long-standing symptomatic gastroesophageal reflux (21), but there are limited outcomes data to support this policy.
The significance of short-segment BE (less than 3 cm) and of small intestinal metaplasia at the esophagogastric junction remains unclear.These lesions appear to be much more prevalent than classical long-segment BE (6% for short-segment BE, 5.6% for small intestinal metaplasia at the esophagogastric junction and 1.6% for long-segment BE) (22).Some investigators have suggested that patients with short-segment BE could be followed expectantly.Although dysplasia and cancer are most prevalent in patients with long-segment BE (31%), they are not rare among cases of short-segment BE (10%) or esophagogastric junction-specialized intestinal metaplasia (6.4%) (22).
In accordance with principles outlined by the World Health Organization, surveillance is predicated on the availability of suitable therapy for the disease in question or its precursor (23).For a patient who is otherwise fit, esophagectomy offers the possibility of improved long term survival or even cure for patients with high-grade dysplasia or early cancer.Although diagnosis and treatment are far from ideal, improved diagnostic techniques (such as photodynamic therapy and laser ablation) offer new promise.
Endoscopy is the technique of choice for identifying esophagitis, while the diagnosis of BE requires (targeted) biopsy to identify areas of intestinal metaplasia (5).Because inflammation and mucosal regeneration can induce changes that are difficult to distinguish histologically from dysplasia, endoscopy and biopsy should be performed while the patient is taking sufficient antisecretory medication to relieve symptoms and minimize esophageal damage (21).
Some physicians have argued that cancer surveillance is too costly to be applied to all patients with GERD.Moreover, surveillance will not prevent all esophageal cancers.Nevertheless, unless early indicators of possible malignancy are sought, all endoscopic evaluations for reflux disease might as well be avoided until alarm features develop, with the knowledge that most malignancies will, by then, be incurable.Even though the presence of severe reflux symptoms has been identified as a risk factor for EAC (8), endoscopy with biopsies is the only available means of determining whether an individual patient has an increased risk of esophageal malignancy and merits long term follow-up.

CONCLUSIONS
'Once in a lifetime' endoscopy should be the standard of care for patients over 60 years of age who have severe, prolonged, frequent GERD symptoms and who are willing to proceed with surgery, if necessary.Endoscopy should be undertaken earlier if clinically warranted, for example, if alarm symptoms or diagnostic confusion are present.The endoscopic appearances should be fully recorded, and biopsies should be taken if BE is suspected endoscopically.It should be emphasized that 'once in a lifetime' endoscopy is not synonymous with either 'surveillance endoscopy' for BE, which depends on additional criteria, or 'screening endoscopy', which would be used to look for BE in the general population.According to published guidelines (24,25), surveillance should be undertaken in patients whose risk of developing malignancy is greater than 0.5% per year.