A survey of Canadian gastroenterologists about the management of Barrett ’ s esophagus

1Medical student; 2Department of Surgery; 3Division of Anatomical Pathology; 4Division of Gastroenterology, Dalhousie University, Halifax, Nova Scotia Correspondence: Dr Sander Veldhuyzen van Zanten, Dalhousie University, Division of Gastroenterology, Room 928, Centennial Building, Victoria General Site, Queen Elizabeth II Health Sciences Centre, Halifax, Nova Scotia B4H 2Y9. Telephone 902-473-1499, fax 902-473-5548, e-mail zanten@is.dal.ca Received for publication October 18, 2002. Accepted February 12, 2003 L MacNeil-Covin, AG Casson, D Malatjalian, S Veldhuyzen van Zanten. A survey of Canadian gastroenterologists about the management of Barrett’s esophagus. Can J Gastroenterol 2003;17(5):313-317.

Over the past 30 years the incidence of primary esophageal adenocarcinoma has increased steadily (4), especially in white males (4,11,12).The prognosis for invasive esophageal adenocarcinoma is poor, and despite advances in multimodality therapy, five-year survival generally remains below 10% (13).However, in selected surgical series, overall five-year survival may approach 30% following resection of early stage disease (14,15), or for tumours with favourable biology (16).This observation underlies the rationale for endoscopic surveillance (17), with the hope that early detection will improve long term survival.Currently, there is consensus that patients diagnosed with BE should enter an endoscopic surveillance program.However, the optimal frequency with which endoscopy and biopsy should be repeated is not known.
A number of guidelines for managing BE have been proposed (Table 1), with the following considerations: frequency of surveillance for patients with BE without dysplasia, and for low grade and high grade dysplasia; the timing of surgical referral; the role of alternative therapies; and standardization of biopsy protocols (18)(19)(20)(21).None of these guidelines is based on prospective randomized studies.
The aim of the present study was to determine practice patterns of Canadian gastroenterologists for screening patients with BE and to compare those results with the published guidelines.A secondary objective was to determine whether gastroenterologists perform a 'once in a lifetime' endoscopy in patients who have long standing GERD.

METHODS
A two-page survey was developed, pretested using five gastroenterologists, and mailed with a self-addressed return envelope to active members of the Canadian Association of Gastroenterologists (CAG).The survey focused on endoscopic surveillance practices for patients with BE without dysplasia, with low grade dysplasia and with high grade dysplasia.Physicians were also asked about their biopsy techniques and whether they support a 'once in a lifetime' endoscopy for patients with chronic GERD.Surveys were sent out in English only.The survey was anonymous and included the following questions: practice setting (university or community); number of years in practice; and the number of patients seen with high grade dysplasia and esophageal adenocarcinoma.Physicians were asked to complete the survey without having to rely on patient charts.In the analysis the proportion of respondents who followed recommended guidelines is reported.

RESULTS
Surveys were mailed to 476 members of the CAG.From 80 surveys, it could not be determined whether the CAG members were in active clinical practice, which left 396 possible responders.It is estimated that at least 25% of CAG members are nonphysicians but the database does not contain that information.A total of 203 (51%) surveys were returned.One hundred sixty-five of the 203 responders were practising gastroenterologists, and their responses were used in the analysis.If nonphysician CAG members are excluded the response rate is 65% (203 of 297).Of the 38 excluded from analysis, 18 responders were pediatric gastroenterologists not dealing with BE, eight did not perform endoscopy, seven were retired, three were full-time researchers, one was a radiologist and one was a surgeon who did not perform endoscopy.Of the 165 responders 52 (32%) were from Western Canada (British Columbia, Alberta, Manitoba, Saskatchewan), 67 were from Ontario (41%), 25 were from Quebec (15%), 20 were from Eastern Canada (12%) (Newfoundland, Prince Edward Island, Nova Scotia, New Brunswick) and three (1%) were from an unknown location.

Physician characteristics
The number of years in practice was distributed as follows (Table 2): 31% less than 10 years, 33% 11 to 20 years and 35% greater than 20 years.Fifty per cent of gastroenterologists were in community practice, and the remaining 50% indicated they had either full-time or part-time university-based practices.Most of the respondents (82%) indicated they see more than five patients with BE every year.When asked about the total number of patients with BE with high grade dysplasia seen over the course of their practice, most of the respondents (85%) indicated they had seen less than five cases.Similarly, the number of esophageal adenocarcinomas seen by physicians was also reported to be low.Dividing the estimated number of cancer cases by the number of years in practice, it can be estimated that physicians see on average one patient with esophageal adenocarcinoma each year.

Endoscopic surveillance intervals
Surveillance intervals varied depending on whether patients with BE had no, low grade or high grade dysplasia (Table 3).For patients with BE without dysplasia, 62% of gastroenterologists indicated they would perform endoscopy every two years; 19% indicated they would perform yearly endoscopy and the remaining 19% at intervals every three years or greater.The frequency of surveillance for patients with low grade dysplasia was reported to be six-monthly (55%), yearly (35%), or less than six months (10%).For patients with high grade dysplasia, 56 gastroenterologists reported they would continue surveillance with a frequency of every three months or less (70%), or every six months (30%).Computer cohort five years ↑ life expectancy similar to common medical intervention *Biopsies taken from all 4 quadrants.This technique was repeated every 1 or 2 cm along the length of Barrett's Esophagus (q 1 cm, 2 cm).Symbols (<3 cm, >3 cm) refer to the visible length of Barrett's Esophagus.ACG American College of Gastroenterology; SFED French Society of Digestive Endoscopy.NOTE: The ACG guidelines have recently been updated (27).They do not specify the initial interval of endoscopies after the diagnosis Barrett's esophagus is made.The updated guideline states that the screening interval can be increased to three years after two consecutive endoscopies did not detect dyspepsia

Management of patients with high grade dysplasia
Three selections were given in the survey for the management of patients with high grade dysplasia: continued surveillance, esophageal resection or other (alternative) therapy.As responders were able to check multiple options there is overlap for the following percentages.However, most respondents indicated a preference for esophageal resection (81%), followed by continued surveillance (34%), and other therapies, such as mucosal ablation, laser or photodynamic therapy (32%); 20% would consider all three options.
'Once in a lifetime' endoscopy for patients with chronic GERD This component of the survey posed two questions about 'once in a lifetime' endoscopy for patients with chronic GERD (Table 5).Seventy-six per cent of gastroenterologists indicated support for 'once in a lifetime' endoscopy.In response to the second question about criteria used to determine when a person should have the endoscopy, 61% indicated duration of symptoms (greater than five years); 40% said they would use age (greater than 50 years); and 33% indicated other criteria, including medication use.

DISCUSSION
The present survey found that Canadian gastroenterologists regularly perform endoscopic surveillance of patients with BE, and the majority follow published guidelines (18-21).
Comparable surveys have been performed in other countries with similar results (22)(23)(24)(25).All reported that the majority of physicians follow published guidelines, but found considerable variation with surveillance interval and biopsy protocols.
In the present survey, the majority of respondents (62%) carried out endoscopic surveillance every two years for patients with BE without dysplasia, as recommended by Canadian guidelines (19), although 19% of respondents performed yearly screening.Given the low potential for cancer progression in patients with BE, adhering to the published guidelines would likely result in substantial savings to the Canadian health care system.Furthermore, recent data suggest that the screening interval perhaps can be increased to three years if dysplasia is not seen at two endoscopic intervals (26).
The American College of Gastroenterology (ACG) recommends that surveillance endoscopies are performed in patients in whom a diagnosis of Barrett's esophagus is made (18).However, the guidelines are vague in that they do not state the screening interval.Recently, the ACG guidelines have been updated (27).They still do not specify an initial screening interval after the diagnosis of Barrett's esophagus is made.However, the new guidelines state that the interval can be three years after two consecutive endosocopies that did not find any evidence of dysplasia on histology.The present survey was conducted before the updated guidelines were published.At the moment the recommendations for screening intervals are being evaluated.It seems likely that in the future the screening intervals will increase in patients who have no evidence of dysplasia.It is interesting that the guidelines do not take ethnicity into account.It is well established that especially white males are at the highest risk for developing Barrett's esophagus.
There are no prospective randomized controlled clinical trials to help determine the optimal endoscopic interval.Current guidelines (18)(19)(20)(21)    have not been proven to be more beneficial than every two years.Whether screening patients with BE with regular endoscopy is cost effective is also unproven, although it is the current standard of practice.One recent prospective study (28) evaluated 143 patients with BE undergoing yearly screening over 10 years, and found that only one cancer was detected as a result of the surveillance program.Esophageal adenocarcinomas developed in a total of five individuals, but was detected during an unscheduled endoscopy for worsening symptoms in two patients, and in two patients who had defaulted from the program.
An economic study of endoscopic screening for BE found that yearly endoscopies would cost an estimated US$62,000 (in 1988) and 78 h of lost work-days to discover one cancer during the screening process (9).The authors recommended screening every two years to reduce cost.A more recent economic modelling study found that yearly surveillance was the best choice if only length of life is considered (21).However, when quality of life and life expectancy were both considered, two to three year intervals were recommended (21).
There is concern that the risk of developing adenocarcinoma has been overestimated and, consequently, the intervals between endoscopies can be increased.A study by Shaheen et al. (10), which looked at 27 publications, found that reporting a higher risk of cancer was related to study size, the definition of BE, and the nature of the study (retrospective versus prospective), supporting publication bias.
Esophageal adenocarcinoma progresses through well defined histological stages, described as the metaplasia-dysplasiacarcinoma sequence (29,30).The increased risk of developing cancer in patients with low grade dysplasia is reflected in the published guidelines that recommend surveillance increase to every six months.After one year without worsening histology, the surveillance can extend to yearly intervals (18)(19)(20).The concern about low grade dysplasia progressing to malignancy is reflected in this survey, with 55% of respondents screening every six months, and 35% performing yearly screening for patients with low grade dysplasia.
The published guidelines recommend that patients with confirmed high grade dysplasia, who are surgically fit, undergo esophageal resection (18)(19)(20)(21).Approximately 50% of patients with high grade dysplasia will be found to have unsuspected invasive adenocarcinoma (31,32).Recent studies have suggested that surgery can be delayed in patients with high grade dysplasia although this is not the current standard of care (32,(33)(34)(35)(36).The majority (81%) of Canadian gastroenterologists indicate that they refer patients with high grade dysplasia for surgery.Although some physicians reported continued surveillance of patients with high grade dysplasia, or alternative therapy, there is overlap with these numbers because 11 of 165 (7%) respondents checked all three options, suggesting that these options are patient-dependent.For example, an elderly person who is medically at high risk for surgery may be referred for endoscopic ablation therapy.
Detection of high grade dysplasia and unsuspected adenocarcinoma are the main reasons for standardized biopsy protocols (36,37).Most guidelines recommend four-quadrant biopsies at 2 cm intervals (18)(19)(20).Boyer and Robaszkiewiez (20) recommend 1 cm intervals for BE segments shorter than 3 cm.Biopsy protocols were quite variable in this survey, ranging from four-quadrants every 2 cm (46%) to 15% of respondents who said they did not follow any biopsy protocol.It is likely that this in part is due to patients with short segment BE where a standardized biopsy protocol is not possible.
Although the ACG recommends that patients with chronic GERD should have an endoscopy to screen for BE (18), no timing was specified.This survey demonstrates that Canadian gastroenterologists agreed with this statement, as 76% said they believe in 'once in a lifetime' endoscopy for patients with chronic GERD.They also indicated that criteria for endoscopy   should include duration of symptoms (61%) and age (40%).However, the optimal timing and criteria for 'once in a lifetime' endoscopy warrants further critical study before evidence based recommendations can be given.Large forceps biopsies are recommended to get adequate biopsy samples.The results of the present survey may not reflect the opinions of all Canadian gastroenterologists as the response was 68%.However, we found that the majority of Canadian gastroenterologists who responded to the survey followed the published guidelines, and indicated support for a 'once in a lifetime' endoscopy.Future advances in understanding the molecular pathogenesis of BE and esophageal adenocarcinoma may further modify endoscopic surveillance for this disease in the future (38).

Survey: Management of Barrett's esophagus Can
base their recommendations on cohort and retrospective studies.Yearly endoscopic screenings J Gastroenterol Vol 17 No 5 May 2003 315

TABLE 3 Endoscopic surveillance intervals used in the physicians' practices*
*Some physicians did not respond to all questions.BE Barrett's esophagus; HGD High grade dysplasia; LGD Low grade dysplasia

TABLE 5 Physician's opinions of once in a lifetime endoscopies for patients with longstanding gastroesophageal reflux disease
) Do you believe that in all patients with a convincing history of heartburn and acid regurgitation, endoscopy should be performed to detect Barrett's esophagus? A