How can I be sure that the patient has Barrett’s esophagus?

The majority of patients diagnosed with Barrett’s esophagus have symptoms of gastroesophageal reflux disease such as heartburn and/or acid regurgitation. The prevalence of Barrett’s esophagus in patients with chronic gastroesophageal reflux disease is estimated to be approximately 10% to 15%. However, patients with Barrett’s esophagus can be asymptomatic with some cohorts reporting that up to 55% of these patients are asymptomatic. In addition, prior cohort studies of asymptomatic patients have reported the prevalence of Barrett’s esophagus in asymptomatic patients to be 5% to 15%.

The cost-effectiveness of endoscopic screening for Barrett’s esophagus has been limited due to several factors, including the cost of endoscopy, lack of reliable predictors for Barrett’s esophagus, and limited data supporting mortality reductions from Barrett’s esophagus screening. As a result, screening the general population for Barrett’s esophagus is not recommended.

Current guidelines recommend an individualized approach to screening with a focus on screening high-risk individuals. Caucasian male patients over the age of 40, with longstanding gastroesophageal reflux symptoms are suspected to be the highest risk group at this time.

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A tabular or chart listing of features and signs and symptoms

Frequency and duration of gastroesophageal symptoms have been found to be reliable predictors for Barrett’s esophagus; however, severity of gastroesophageal reflux disease symptoms has not been proven to be a reliable predictor.

Several other risk factors have been identified, including advanced age, male gender, Caucasian race, presence of a hiatal hernia, obesity, family history of Barrett’s esophagus, history of tobacco use, and history of alcohol use.

How can I confirm the diagnosis?

Esophagogastroduodenoscopy is considered the “gold standard” test for the diagnosis of Barrett’s esophagus. Endoscopically, Barrett’s esophagus appears as columnar-lined epithelium (pink/salmon color) that results in displacement of the squamocolumnar junction proximal to the gastroesophageal junction (
Figure 1). If columnar-lined epithelium is seen proximal to the gastroesophageal junction, then multiple biopsies of the columnar-lined epithelium should be taken to evaluate for intestinal metaplasia and dysplasia (
Figure 2).

Intestinal metaplasia is the presumed precursor lesion for esophageal adenocarcinoma, and its presence of biopsies confers an increased risk for the development of cancer. However, it remains uncertain whether the presence of columnar-lined epithelium proximal to the gastroesophageal junction without histologically confirmed intestinal metaplasia carries an increased risk for esophageal adenocarcinoma. As a result, debate continues as to the exact criteria needed to diagnose Barrett’s esophagus: presence of columnar-lined epithelium proximal to the gastroesophageal junction versus presence of intestinal metaplasia on biopsies. At this time, U.S. guidelines recommend that the diagnosis of Barrett’s esophagus requires the presence of histologically confirmed intestinal metaplasia.

It can be difficult for an endoscopist to diagnose Barrett’s esophagus of less than 1 cm in length and to differentiate this from intestinal metaplasia of the cardia, which does not have the same risk for neoplastic progression. The Prague Classification System uses both the extent of circumferential (C) columnar-lined epithelium and the maximum length (M). Studies examining this system have found good inter-observer reliability, and it is the recommended classification system for Barrett’s esophagus.

In addition, the presence of severe erosive esophagitis (Los Angeles grade C and D) can inhibit endoscopic visualization of the distal esophagus, making it difficult to diagnose Barrett’s esophagus. As a result, these patients should undergo a repeat endoscopy once the erosive esophagitis has healed to evaluate for underlying Barrett’s esophagus.

What other diseases, conditions, or complications should I look for in patients with Barrett’s esphagus?

Patients with Barrett’s esophagus may also be found to have erosive esophagitis and hiatal hernias – the two most common conditions associated with Barrett’s esophagus. Additional studies have suggested that patients with Barrett’s esophagus may have an increased risk for adenomatous colon polyps and colon cancer, although these studies need additional confirmation.

The major complication of Barrett’s esophagus is neoplastic progression to esophageal adenocarcinoma. The metaplastic change of Barrett’s esophagus is thought to be a response to long-standing gastroesophageal reflux disease, in which bile and acid cause inflammation of the esophageal mucosa. Consequently, the normal squamous cell mucosa is replaced by columnar mucosa. As inflammation continues, neoplastic transformation proceeds through a stepwise progression from Barrett’s esophagus with no dysplasia to low-grade dysplasia to high-grade dysplasia and, finally, esophageal adenocarcinoma.

The rate of progression from nondysplastic Barrett’s esophagus to esophageal adenocarcinoma and from low-grade dysplasia to esophageal adenocarcinoma have been found to be as low as 0.25% and 0.44% per year, respectively. Patients with high-grade dysplasia have a 6% chance of progressing to esophageal adenocarcinoma within 1 year and up to a 10% to 20% chance of having coexisting esophageal adenocarcinoma at the time of diagnosis.

What is the right therapy for the patient with Barrett’s esophagus?

Following acid suppressive therapy (specifically proton-pump inhibitors) to control any coexisting reflux symptoms or erosive esophagitis, management of Barrett’s esophagus patients depends on the degree of dysplasia found during upper endoscopy. Those with no dysplasia or low-grade dysplasia should undergo endoscopic surveillance at routine intervals. Patients with high-grade dysplasia or esophageal adenocarcinoma should undergo either endoscopic or surgical therapy to treat the entire Barrett’s esophagus segment.

See Figure 3 for a recommended strategy for managing patients with Barrett’s esophagus.

What is the most effective initial therapy?

Patients should undergo upper endoscopy to assess the degree of dysplasia present once reflux symptoms are controlled and erosive esophagitis has healed, as the presence of inflammation in the distal esophagus can interfere with histological assessment of dysplasia.

Adequate time should be taken to examine the Barrett’s esophagus segment using the best quality endoscopes available to detect subtle lesions that may harbor dysplasia, preferably high-definition white light endoscopy.

Current guidelines recommend four quadrant biopsies every 2 cm of the Barrett’s esophagus segment, along with additional biopsies of any visible lesions (Seattle Protocol). Biopsies should be obtained using large-capacity forceps and using the turn-and-suck technique. Specimens from each segment should be submitted to histopathology in separate jars so that future targeted biopsies can be obtained if any dysplasia is detected. As there is significant inter-observer variability in dysplasia grading, even among expert gastrointestinal pathologists, biopsies with dysplasia should be reviewed by at least two expert gastrointestinal pathologists.

Listing of usual initial therapeutic options, including guidelines for use, along with expected result of therapy.

Acid suppression therapy with proton-pump inhibitors should be used indefinitely to control any reflux symptoms and heal any coexisting erosive esophagitis. The dose should be titrated until reflux symptoms are controlled and/or erosive esophagitis is healed. While studies have revealed that proton-pump inhibitor therapy can decrease markers of proliferation and, perhaps, development of dysplasia, there has been no proven decrease in overall cancer risk. Patients should also be instructed on antireflux dietary and lifestyle modifications and obese patients should be counseled on the importance of weight loss.

In Barrett’s esophagus patients with no dysplasia or low-grade dysplasia, endoscopic surveillance should be performed at routine intervals based on the degree of dysplasia. Surveillance endoscopy should be performed when erosive esophagitis is healed and biopsies should be taken using the Seattle protocol. Biopsies should be obtained using large-capacity forceps and using the turn-and-suck technique. Specimens from each segment should be submitted to histopathology in separate jars so that future targeted biopsies can be obtained if any dysplasia is detected.

In Barrett’s esophagus patients with high-grade dysplasia or early cancer, diagnostic endoscopic mucosal resection should be performed to accurately stage the disease, as some cohorts have reported a change in diagnosis in as high as 50% of cases. Those with confirmed high-grade dysplasia or early cancer should be referred for either surgical resection or endoscopic eradication therapy.

A listing of a subset of second-line therapies, including guidelines for choosing and using these salvage therapies

Antireflux surgery can be considered an option for the management of coexisting gastroesophageal reflux symptoms; however, it is not recommended for the treatment of Barrett’s esophagus because there is no consistent evidence that it reduces the risk of neoplastic progression, and up to 20% of patients develop recurrent symptoms on long-term follow up.

Patients with high-grade dysplasia or early cancer (confirmed by two expert gastrointestinal pathologists) who are not candidates for surgery, should be evaluated for endoscopic eradication therapy. A variety of endoscopic therapies are available for these patients, including endoscopic mucosal resection (EMR), photodynamic therapy (PDT), and radiofrequency ablation (RFA). While all of these therapies have been found to be effective, there are no trials comparing the various techniques. In addition, long-term follow up is not yet available for all of the endoscopic therapies.

  • EMR can achieve dysplasia and cancer eradication rates of over 95% in patients with high-grade dysplasia or intramucosal adenocarcinoma. Major complications include post-procedure bleeding (19%) and stricture formation (12%).
  • In patients with high-grade dysplasia, PDT can achieve eradication of high-grade dysplasia in over 75% and a 50%reduction in cancer risk. However, its use is associated with an approximately 23% risk of stricture formation.
  • In patients with high-grade dysplasia, RFA has been found to have a dysplasia eradication rate of 81% and a 90% reduction in cancer risk. Major side effects include chest pain for up to 1 week after the procedure, and a 6% risk of stricture formation.

Listing of these, including any guidelines for monitoring side effects.

Major side effects from Barrett’s esophagus treatment are a result of endoscopic eradication therapy and include chest pain, bleeding, esophageal stricture, and perforation.

Patients undergoing endoscopic eradication therapy should remain on twice-a-day proton-pump inhibitors to heal esophageal ulcerations that occur after treatment.

Liquid antacid and topical anesthetic solutions are commonly given for heartburn and chest pain symptoms that commonly occur. Patients who develop signs of gastrointestinal bleeding or dysphagia suggestive of an esophageal stricture should undergo repeat upper endoscopy because the majority of these complications can be successfully managed endoscopically.

How should I monitor the patient with Barrett’s esophagus?

Patients without dysplasia on biopsies should have repeat endoscopy with biopsies performed within 1 year. If no dysplasia is found, patients should undergo continued surveillance, but the interval can be extended to every 3 to 5 years.

Patients with low-grade dysplasia should undergo repeat endoscopy in 6 months. If no dysplasia is found in these patients during the follow up examination, then endoscopy should be repeated every year until the patient has two consecutive endoscopies with no dysplasia. At this time, the surveillance interval can be increased further.

If there is persistent low-grade dysplasia on follow up examination, then repeat endoscopy should be performed in 6 months. Patients with high-grade dysplasia should not undergo endoscopic surveillance and should be referred for either surgical or endoscopic therapy.

The management and prognosis of esophageal cancer in Barrett’s esophagus patients is dependent on accurate staging of the tumor and associated metastases. While computed tomography and positron emission tomography are useful in detecting distant metastases, their accuracy in assessing local tumor invasion is poor.

Endoscopic ultrasound is the preferred method for obtaining accurate T and N staging and should be performed in patients with esophageal cancer without distant metastases. The presence/absence of submucosal invasion is an important predictor for lymph node metastases. Therefore, diagnostic endoscopic mucosal resection should be performed in all patients with no lymph node metastases by endoscopic ultrasound because it provides the most accurate assessment of tumor invasion and the opportunity for curative resection.

What’s the evidence?

Sharma, P. “Clinical practice: Barrett’s esophagus”. N Engl J Med. vol. 361. 2009. pp. 2548-56. (This is a key review article summarizing Barrett’s esophagus.)

Spechler, SJ, Sharma, P, Souza, RF. “American Gastroenterological Association: medical position statement on the management of Barrett’s esophagus”. Gastroenterology. vol. 140. 2011Mar. pp. 1084-91. (These are the guidelines from the American Gastroenterological Association for Barrett’s esophagus.)

Wang, KK, Sampliner, RE. “Updated guidelines 2008 for the diagnosis, surveillance, and therapy of Barrett’s esophagus”. Am J Gastroenterol. vol. 103. 2008. pp. 788-97. (These are the guidelines from the American College of Gastroenterology for Barrett’s esophagus.)

Wani, S, Falk, G, Hall, M. “Patients with nondysplastic Barrett’s esophagus have low risks for developing dysplasia or esophageal adenocarcinoma”. Clin Gastroenterol Hepatol. vol. 9. 2011. pp. 220-7. (This study illustrates the low rate of neoplastic progression of Barrett’s esophagus patients with no dysplasia.)

Wani, S, Falk, GW, Post, J. “Risk factors for progression of low-grade dysplasia in patients with Barrett’s esophagus”. Gastroenterology. 2011 Jun 29. (This study illustrates the low rate of neoplastic progression of Barrett’s esophagus patients with low-grade dysplasia.)

Wani, S, Mathur, SC, Curvers, WL. “Greater interobserver agreement by endoscopic mucosal resection than biopsy samples in Barrett’s dysplasia”. Clin Gastroenterol Hepatol . vol. 8. 2010. pp. 783-8. (This study reports on the inter-observer agreement in assessing biopsy and endoscopic mucosal resection specimens from patients with Barrett’s esophagus.)

Abrams, JA, Kapel, RC, Lindberg, GM. “Adherence to biopsy guidelines for Barrett’s esophagus surveillance in the community setting in the United States”. Clin Gastroenterol Hepatol. vol. 7. 2009. pp. 736-42. (This study illustrates the poor rate of adherence to Barrett’s esophagus surveillance recommendations and the impact on neoplasia detection.)

Sharma, P, Dent, J, Armstrong, D. “The development and validation of an endoscopic grading system for Barrett’s esophagus: the Prague C & M criteria”. Gastroenterology. vol. 131. 2006. pp. 1392-9. (This study reports on the development and validation of the Prague classification system.)

Moss, A, Bourke, MJ, Hourigan, LF. “Endoscopic resection for Barrett’s high-grade dysplasia and early esophageal adenocarcinoma: an essential staging procedure with long-term therapeutic benefit”. Am J Gastroenterol. vol. 105. 2010. pp. 1276-83. (This study illustrates the importance of diagnostic endoscopic mucosal resection in Barrett’s esophagus patients with high-grade dysplasia and early cancer.)

Shaheen, NJ, Sharma, P, Overholt, BF. “Radiofrequency ablation in Barrett’s esophagus with dysplasia”. N Engl J Med.. vol. 360. 2009. pp. 2277-88. (This study reports the results of a randomized placebo-controlled clinical trial of radiofrequency ablation for the treatment of Barrett’s esophagus with dysplasia.)

Chennat, J, Konda, VJ, Ross, AS. “Complete Barrett’s eradication endoscopic mucosal resection: an effective treatment modality for high-grade dysplasia and intramucosal carcinoma–an American single-center experience”. Am J Gastroenterol. vol. 104. 2009. pp. 2684-92. (This study reports the efficacy and safety of endoscopic mucosal resection for the treatment of Barrett’s esophagus with high-grade dysplasia and early cancer.)