Barrett’s esophagus is a common condition affecting the esophagus and its management remains controversial in the medical community. Barrett’s is considered a pre-cancer and clearly elevates the risk of esophageal adenocarcinoma in carriers of this condition. In this post, we will attempt to summarize the risk factors associated with Barrett’s esophagus, who should undergo screening, and how is Barrett’s treated. Most importantly, who is at most risk for developing esophageal cancer and what can we do to prevent that from happening.
Barrett’s esophagus is a condition named for the late Norman Rupert Barrett, an influential esophageal surgeon who was born in Adelaide, Australia in 1903. Barrett worked for most of his career as a consultant surgeon at St. Thomas’ Hospital in London. He was a pioneer in the field of thoracic surgery and a charismatic academic leader who served for more than 25 years as editor of Thorax. By all accounts, Norman Barrett was an outstanding surgeon, scholar, and teacher. However, Norman Barrett was not the first to describe the condition that now bears his name; in fact, his original contentions about the nature and pathogenesis of the condition were incorrect.
Credit for describing the columnar-lined esophagus probably should go to Wilder Tileston, a pathologist who, while working in Boston in 1906, described 3 cases of “peptic ulcer of the oesophagus,” and noted “the close resemblance of the mucous membrane about the ulcer to that normally found in the stomach.” Tileston wrote that “the first requisite for the formation of the peptic ulcer of the esophagus is an insufficiency of the cardia” (i.e. gastroesophageal reflux). Thus, almost a half-century before Barrett, Tileston described the columnar-lined esophagus and correctly attributed the pathogenesis of the associated ulceration to gastroesophageal refluxReference: Gastroenterology. 2010 Mar; 138(3): 854–869
Barrett’s is caused by injury to the esophageal lining due to acid, bile, and other stomach contents that have refluxed into the esophagus. The lining of the lower esophagus bears the brunt of this injury and not surprisingly, this is where Barrett’s esophagus get started. It is believed that several years of uncontrolled acid reflux causes small mutations in cell DNA. Over time, these DNA mutations lead to the formation of Barrett’s esophagus and in some cases, esophageal cancer.
Barrett’s esophagus is a silent disease, there are no warning signs. The individual most likely to acquire this condition is anyone with a long history of heartburn.
Barrett’s esophagus is usually discovered during endoscopic examinations of middle-aged and older adults whose mean age at the time of diagnosis is approximately 55 years . Although Barrett’s esophagus can affect children, it rarely occurs before the age of five . This observation supports the contention that Barrett’s esophagus is an acquired condition, not a congenital one.
Barrett’s can be detected using a lighted fiber optic scope to directly view the esophageal lining. Barrett’s can be seen easily as an area of salmon colored mucosa rather than the usual light pink coloration. Biopsies of the esophageal lining can confirm the presence of Barrett’s. These biopsies, taken at the time of endoscopy reveal that the esophageal lining has developed an unusual cell shape – rather than the normal squamous cell which is flat, the cell has become tall and columnar with evidence of mucus production. A special stain called Alcian blue is useful for detecting the presence of this mucus, also called goblet cells. Barrett’s is also called intestinal metaplasia. This is a laboratory term used to describe an occurrence when cells transform to a new shape.
Studies on Barrett’s…
Estimates of the prevalence of Barrett’s esophagus in the general population have varied widely ranging from 0.4 to more than 20 percent depending in part upon the population studied and the definitions used [3-7]. The male to female ratio is approximately 2:1 . The following studies illustrate the range of findings:
- A study from Sweden estimated that Barrett’s esophagus was present in 1.6 percent of the general population . Applying these prevalence estimates to the United States would translate into about 3.3 million individuals with Barrett’s esophagus .
- 44 percent of patients lacked “troublesome heartburn and/or acid regurgitation during the past three months,” suggesting that screening programs based upon reflux symptoms alone may be inadequate to identify patients with Barrett’s esophagus.
- In a study conducted in the United States, the prevalence of Barrett’s esophagus was 6.8 percent among 961 patients undergoing a colonoscopy .
- Among 556 patients who had never had heartburn, the prevalence was 5.6 percent.
- Among 384 subjects with a history of heartburn, the prevalence was 8.3 percent.
- Most cases were “short-segment.”
- Long-segment Barrett’s was especially uncommon in those without a history of heartburn.
- Among patients who have endoscopic examinations because of chronic GERD symptoms, long-segment Barrett’s esophagus can be found in 3 to 5 percent.
- Whereas 10 to 15 percent have short-segment Barrett’s esophagus.
- In a meta-analysis of 51 studies that included 453,157 individuals, the pooled prevalence of histologically confirmed Barrett’s esophagus was 1.3 percent, of which 82 percent was short-segment Barrett’s esophagus .
- Obesity is a risk factor for gastroesophageal reflux disease (GERD) and may be a risk factor for Barrett’s esophagus [18,19]. A 2009 meta-analysis that included 11 observational studies demonstrated a small increase in the risk of Barrett’s esophagus in patients with a body mass index (BMI) >30 kg/m2 as compared with patients with a BMI <30 kg/m2 (OR 1.4, 95% CI 1.1-1.6) . However, other studies have suggested that rather than BMI, abdominal obesity as measured by a high waist to hip ratio (≥0.9 in males and ≥0.85 in females) is associated with an increase in risk of Barrett’s esophagus [19-22].
- A study of 40 patients who had subtotal esophagectomy with esophagogastrostomy, an operation frequently complicated by severe reflux esophagitis in the esophageal remnant, supports the notion that cardiac-type epithelium is metaplastic . Endoscopic examinations performed at a median of 36 months postoperatively showed that 19 of the 40 patients had developed columnar metaplasia in the esophageal remnant (10 cardiac-type epithelium, 9 intestinal metaplasia).
- Seven patients who had serial endoscopic examinations showed progression from cardiac-type epithelium on the initial postoperative endoscopy to specialized intestinal metaplasia on subsequent studies. The median time to the development of cardiac-type epithelium was 14 months, whereas specialized intestinal metaplasia was found at a median of 27 months postoperatively. These findings suggest that cardiac epithelium is not only metaplastic, but also the precursor of intestinal metaplasia in the esophagus.
Differences between long- and short-segment Barrett’s
As discussed above, the prevalence of short-segment Barrett’s esophagus is substantially higher than long-segment Barrett’s esophagus. Both conditions are diagnosed most frequently in patients age 55 years and older, and are predominantly seen in male Caucasians.
Studies have shown that patients with long and short-segment Barrett’s were predominantly male and white. Patients with short-segment Barrett’s had a shorter history of heartburn and many had no GERD symptoms at all. In contrast, those with intestinal metaplasia of the GEJ had a similar gender distribution and were more likely to be infected by Helicobacter pylori.
The degree and mechanism of acid exposure in patients with short- and long-segment Barrett’s esophagus suggest that patients who develop long-segment Barrett’s were predisposed to more severe reflux :
Patients with long-segment Barrett’s tend to have:
- Upright and supine reflux in contrast to those with short-segment Barrett’s who have predominantly upright reflux.
- Proximal esophageal acid exposure is more common in patients with long-segment Barrett’s.
- The risk of adenocarcinoma has been estimated to be 2 to 15 times higher in patients with long-segment Barrett’s.
Patients with short-segment Barrett’s tend to have:
- Higher LES pressures
- Higher distal esophageal peristaltic amplitudes
- A lower incidence of dysplasia since less mucosa is involved [3,49,50].
Endoscopic Screenings Showing the Findings of Barrett’s Esophagus
The Importance of Screening Patients with GERD
More than 40 percent of patients with esophageal adenocarcinoma have no history of heartburn [54,56]. Thus, any screening program that targets only patients with heartburn can have only limited impact on cancer mortality rates and there is little evidence that these programs have prevented deaths from esophageal adenocarcinoma. In published series of patients found to have these tumors, fewer than 5 percent were known to have had Barrett’s esophagus before they presented with symptoms of esophageal cancer .
The impact of the incidence of esophageal adenocarcinoma on screening was evaluated using a Markov model based upon age- and sex-specific incidences of esophageal adenocarcinoma in American non-Hispanic whites with GERD symptoms . The study noted that the overall incidence of esophageal adenocarcinoma is low, but increases with age:
- For men between the ages of 30 and 80 years, the incidence ranged from 0.1 to 15.4/100,000 for those without GERD or with GERD less than once per week, and from 0.4 to 75.9/100,000 for those with GERD at least once per week.
- For women between the ages of 30 and 80 years, the rates were lower, ranging from 0 to 2.3/100,000 for those without GERD or with GERD less than once per week, and from 0 to 11.2/100,000 for those with GERD at least once per week.
- The incidence of esophageal adenocarcinoma for men without GERD was higher than the incidence for women with GERD at any given age (eg, at age 60 years the incidence in men without GERD was 7.0/100,000 and the incidence in women with GERD was 3.9/100,000).
Barrett’s esophagus is usually discovered during endoscopic examinations of middle-aged and older adults whose mean age at the time of diagnosis is approximately 55 years. The specialized intestinal columnar metaplasia typical of Barrett’s esophagus causes no symptoms. Most patients are seen initially for symptoms of associated gastroesophageal reflux disease (GERD), such as heartburn, regurgitation, and dysphagia.
Two criteria must be fulfilled to make a diagnosis of Barrett’s esophagus:
- The endoscopist must document that columnar epithelium lines the distal esophagus.
- Histologic examination of biopsy specimens from that columnar epithelium must reveal specialized intestinal metaplasia. Some data suggests that gastric cardiac-type epithelium in the esophagus also might predispose to cancer and thus might be considered “Barrett’s esophagus,” but most authorities still require the presence of specialized intestinal metaplasia for an unequivocal diagnosis.