EPIDEMIOLOGY OF COLUMNAR-LINED ESOPHAGUS AND ADENOCARCINOMA

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This article uses the term Barrett's esophagus (BE) to describe the columnar-lined esophagus. Most available information on the epidemiology of BE relates to longer segments defined on the basis of the extent of columnar lining. Often a BE has been defined by the presence of 3 cm or more of columnar lining, and this definition is used here. A BE of this length is usually recognized at endoscopy. The red columnar epithelium in the lower esophagus contrasts with the pink squamous epithelium that normally lines the entire organ. Biopsies show intestinal metaplasia containing goblet cells. This is the epithelial type in which adenocarcinoma of the esophagus usually arises. Short segments and tongues of intestinal metaplasia, which may be related to adenocarcinoma of the esophagogastric junction, are discussed separately.

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GASTROESOPHAGEAL REFLUX DISEASE AND BARRETT'S ESOPHAGUS

BE is associated with reflux, with many patients having heartburn and sour regurgitation. Most have a weak lower esophageal sphincter and exhibit more severe reflux of acid and bile than patients with uncomplicated esophagitis.12 BE may result from reflux-induced damage to the normal squamous epithelium, with its subsequent replacement by more acid-resistant columnar epithelium.

PREVALENCE OF REFLUX SYMPTOMS IN THE GENERAL POPULATION

Gastroesophageal reflux symptoms are common. Population-based studies29, 39, 53, 54 reported that 4% to 9% of adults experience daily heartburn. An additional 10% to 15% of persons in these studies had heartburn at least once a week. Thus, about 7% of adults in the general population have heartburn every day, and about 20% have heartburn at least on a weekly basis.

PREVALENCE OF BARRETT'S ESOPHAGUS IN PATIENTS WITH REFLUX

Earlier, retrospective reports showed BE in 8% to 20% of patients having endoscopy for reflux.50 In these reports, the indications for endoscopy were usually not stated. Prospective studies provide firmer data. Winters and colleagues59 found a columnar-lined esophagus, 3 cm or longer, in 12 (12%) of 97 patients with reflux symptoms. Only 6 (6%) patients had intestinal metaplasia on biopsy, and the diagnosis of BE is uncertain without this confirmation. Mann and co-workers36 found a

PREVALENCE OF BARRETT'S ESOPHAGUS IN PATIENTS HAVING ENDOSCOPY

The prevalence of BE in patients having endoscopy for any clinical indication, not just reflux, was reviewed in a previous Gastroenterology Clinics and was 0.3% to 2%.42 In a multicenter study from Italy, BE was found in 0.74% of 14,898 subjects having endoscopy.24 The author found BE in 0.73% of 51,311 patients having endoscopy at the Mayo Clinic.8 The true number was almost certainly higher because cases in which the length was not recorded were excluded. In another report,11 a consistent

PREVALENCE OF BARRETT'S ESOPHAGUS IN THE GENERAL POPULATION

The author and colleagues11 estimated the prevalence of BE in Olmsted County, Minnesota, by two different methods. All Mayo Clinic and other medical care provider records were reviewed to find patients living in the county with BE diagnosed by endoscopy and biopsy. This gave a clinically diagnosed prevalence of 22.6 cases per 100,000 population. The author also looked for evidence of BE in Mayo Clinic autopsies. Seven cases were found in 733 consecutive autopsies (about 1%). Adjusting for age

PREVALENCE OF BARRETT'S ESOPHAGUS RELATED TO AGE AND SEX

BE is an acquired condition, often diagnosed in older patients. When the diagnosis is made, it is usually unknown how long the disorder has been present in that individual. The author found the prevalence of BE was about 1% both in autopsy study and in patients having endoscopy for all indications. The latter group should, therefore, be somewhat representative of the general population. Thus, the author examined the age and sex distribution of 377 patients with proven BE in a series of 51,311

FAMILIAL BARRETT'S ESOPHAGUS

Identical twins with BE have been noted.21 There are several reports of families with multiple members having BE16, 17, 18, 30 and sometimes esophageal adenocarcinoma, occurring in successive generations. Other family members had reflux disease without BE. The observations are consistent with an autosomal dominant liability to reflux in these families.

INCREASING INCIDENCE OF ADENOCARCINOMA

There has been a striking change in the frequency of the different histologic types of esophageal cancer. The esophagus is normally lined with squamous epithelium, and until recent years, most esophageal cancers were squamous carcinomas. From 1926 to 1976, four large surgical series reported that only 0.8% to 3.7% of esophageal cancers were adenocarcinomas.5, 43, 55, 58 In later surgical series, with patients seen during 1979 to 1992, 54% to 68% of cancers were adenocarcinomas.20, 44, 45

ADENOCARCINOMA, AGE, SEX, AND RACE

The age-specific incidence rate for esophageal adenocarcinoma increases with age. For men, the rates were 0.1 per 100,000, age 30 to 39; 0.6, age 40 to 49; 1.8, age 50 to 59; 3.0, age 60 to 69; and 3.9, age 70 to 79.60 Esophageal adenocarcinoma is most common in white men.4, 48, 60 In 1988 to 1990, the annual incidence per 100,000 was 2.5 for white men and 0.3 for white women. The incidence was less in African-Americans, 0.6 in men and 0.2 in women.4 Adenocarcinoma of the cardia is also more

CHANGING PATTERN OF GASTRIC ADENOCARCINOMA

An increasing proportion of gastric adenocarcinomas is located in the cardia.2, 22 Comparing the 5-year periods 1960 to 1964 and 1984 to 1988, the incidence of gastric antral carcinoma fell from 10 to 4.5 per 100,000, whereas the incidence of cardia tumors rose from 2.8 to 5.2 per 100,000.47 Adenocarcinomas of the esophagogastric junction (cardia) and esophagus show similar histology,33 white male predominance, and rising incidence. These two cancers may represent variations of a single

GASTROESOPHAGEAL REFLUX DISEASE AND ADENOCARCINOMA

Chow and associates13 compared 196 patients with adenocarcinoma of the esophagus or cardia with 196 matched controls. Cancer in both locations was associated with a past history of esophageal reflux, hiatal hernia, esophagitis, or dysphagia, with odds ratios between 2 and 5. The cancer risk to the individual with gastroesophageal reflux disease is small, however, because gastroesophageal reflux disease is so common. BE is the probable intermediate stage between gastroesophageal reflux disease

SMOKING, ALCOHOL, AND ADENOCARCINOMA

Two large studies compared men with adenocarcinomas of the esophagus and cardia with controls.6, 32 In both studies, smoking and drinking alcohol were associated with adenocarcinoma. Smoking and drinking have been found more prevalent in patients with adenocarcinoma compared to uncomplicated BE in some reports but not all.23, 34, 37

Tobacco and alcohol are more strongly associated with squamous cell cancer of the esophagus than with adenocarcinoma, and although they are probable etiologic

INCIDENCE OF ADENOCARCINOMA IN PATIENTS WITH BARRETT'S ESOPHAGUS

Many reports of patients with BE, followed up to determine their subsequent risk of developing cancer, are available.10, 51 Tytgat56 reviewed 18 series from the literature. The median incidence in patients with BE was about 1 cancer per 100 patient-years of follow-up. The esophageal cancer risk was about 40 times higher than the general population. The mean duration of follow-up exceeded 5 years in only 2 of the 18 series, and this might not truly reflect the long-term risk. A longer follow-up

PREVALENCE OF BARRETT'S ESOPHAGUS IN PATIENTS WITH ADENOCARCINOMA

In earlier reports, BE was found in 58% to 86% of cases of adenocarcinoma of the esophagus,25, 35 35% of cases of adenocarcinoma of the cardia,35 and 64% of cases including adenocarcinoma in both locations.26 Clark and associates15 found histologic evidence of intestinal metaplasia in 42% of adenocarcinomas of the cardia and in 79% of esophageal adenocarcinomas. The author and colleagues9 found a BE (≥3 cm in length) in eight of nine (89%) cases with esophageal adenocarcinoma, the other case

PREVALENCE OF INTESTINAL METAPLASIA AT THE ESOPHAGOGASTRIC JUNCTION

Most of the columnar epithelium in a BE is of the intestinal metaplastic type, with goblet cells.40 Most adenocarcinomas of the esophagus are found in this type of epithelium, which appears to predispose to malignancy. Short segments and tongues of intestinal metaplasia may be found with adenocarcinoma of the esophagogastric junction.26, 49 Studies have shown a high prevalence of small areas of intestinal metaplasia at the esophagogastric junction. Spechler and colleagues52 took biopsy

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    Address reprint requests to Alan J. Cameron, MD, Mayo Clinic, 200 First Street SW, Rochester, MN 55905

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    From the Division of Gastroenterology, Mayo Clinic, Rochester, Minnesota

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