BARRETT ESOPHAGUS

BARRETT ESOPHAGUS - Laura Goldman, MD
BASICS
DESCRIPTION
• Replacement of normal squamous epithelium of the distal esophagus with abnormal columnar epithelium as a consequence of gastric acid reflux
• Precursor of adenocarcinoma of the esophagus
• Divided into long (3 cm) and short segments (3 cm)
GENERAL PREVENTION
• Case-controlled studies have shown that aspirin, and NSAIDs may prevent esophageal cancer, but no randomized trials to date (1)[B]
• No evidence that gastric acid-suppression reduces cancer risk (medical or surgical) (1)[A]
• Epidemiological evidence that weight loss, cessation of smoking, and eating fruits and vegetables can decrease cancer risk (2)[C]
EPIDEMIOLOGY
• Most common in white men >55
• Uncommon in Blacks and Asians, Hispanics similar to Caucasians
• Can affect children, but rarely occurs before the age of 5
Prevalence
• Estimates vary widely in studies
- Most patients with Barrett esophagus are not diagnosed (3)[B]
- In patients without gastroesophageal reflux disease (GERD) symptoms 0-25%
- In patients with chronic GERD symptoms, 10%
RISK FACTORS
• Chronic GERD symptoms
• Male
• White
• Most frequent in 55-65 years of age
PATHOPHYSIOLOGY
• Reflux of gastric contents injures mature cells and triggers metaplastic transformation from squamous cells to more resistant columnar cells called specialized intestinal metaplasia
• Columnar cells have higher malignant potential than squamous cells
• Annual incidence of esophageal cancer in patients with Barrett's is 0.5% per year
• A few studies have demonstrated no difference in overall survival in patients with Barrett esophagus compared to the general population. One observational study showed only 4 of 409 patients affected died of esophageal cancer in 10 years. (3)[B]
• Cancers evolve through a sequence of DNA changes that can be recognized by the pathologist as dysplasia, categorized as low grade or high grade depending on severity of changes.
• Develops to full extent over a relatively short period of time, 1 year
ETIOLOGY
Caused by chronic reflux of gastric contents
ASSOCIATED CONDITIONS
• Esophageal cancer is the most rapidly increasing cancer in the United States, with 0.4% annual increase
• Specialized intestinal metaplasia may also be found in the esophagogastric junction, with lower incidence of cancer, but differentiating between this and Barrett's may be difficult.

DIAGNOSIS
SIGNS AND SYMPTOMS
• Barrett esophagus causes no symptoms
• Most patients seen for GERD symptoms
History
• Heartburn, regurgitation, and dysphagia are the most common symptoms of GERD.
• Less common include chest pain, odynophagia, chronic cough, water brash, globus sensation, laryngitis, and asthma
• Weight loss, anorexia, dysphagia, odynophagia, or bleeding may indicate complications of GERD or cancer
Physical Exam
Normal
TESTS
Upper endoscopy with random multiple biopsies is the only test recommended for diagnosis.
Lab
H. pylori testing not indicated; it does not infect the esophagus, and it does not increase the risk of Barrett's or esophageal cancer
Imaging
None
Diagnostic Procedures/Surgery
• Specialized intestinal metaplasia (reddish, velvety appearance) can be seen at endoscopy
• Multiple biopsies are taken of this area.
• Multiple experimental techniques to identify dysplasia have not been shown in studies to increase accuracy of diagnosis (dysplasia is not visible). (1)[A]
Pathological Findings
• Histologic examination must reveal specialized intestinal metaplasia (also called specialized columnar epithelium) to diagnose Barrett esophagus
• Biopsies may or may not demonstrate low-grade or high-grade dysplasia
DIFFERENTIAL DIAGNOSIS
• Erosive esophagitis may make biopsies inadequate, and repeat study after treatment may be necessary.
• Pathology may show 2 types of columnar epithelium that DO NOT have malignant potential: Cardiac epithelium and gastric-fundic type.
• Intraobserver agreement among experienced pathologists for low-grade dysplasia is 50%, while for high-grade dysplasia it is 85%; second expert pathologist opinion is recommended (4)[A]
TREATMENT
GENERAL MEASURES
• The goal of treatment is to control GERD symptoms and detect and treat dysplasia and cancer.
• The efficacy of treatments in reducing the number of deaths from cancer has not been established. (1)[A]
Diet
• Avoid foods that can cause reflux.
• Avoid other acidic foods if known to trigger symptons: Colas, red wine, orange juice
• Weight loss if obese
Activity
• Avoid supine position after eating; avoid tight fitting clothes.
• Smoking cessation
SPECIAL THERAPY
• Treatment of high-grade dysplasia is controversial.
• Esophagectomy is usually recommended. (4)[B] There are multiple endoscopic procedures now available, but none has been shown to decrease long-term risk of cancer. (5)[A] They may be considered in patients who are poor operative candidates (4,5)
- Photodynamic therapy (PDT) is available in some academic centers; efficacy is not established; cancer has been shown to recur after treatment and strictures occur in 40%. (1,5)
- Other endoscopic ablative procedures (thermal, photochemical, radiofrequency); again efficacy unknown and cancers have been reported post-treatment. (5)
- Endoscopic mucosal resection: Involves excision of mucosa down to submucosa; its efficacy is unknown; can be paired with PDT; remains experimental (1)[A]
- Intensive surveillance with endoscopy every 3-6 months and treatment of cancer if it arises; little data to support safety and efficacy (5)[A]
MEDICATION (DRUGS)
• Goal of therapy is the control of the symptoms of GERD (5)[A] and the maintenance of healed mucosa
• Therapy usually does not result in reversal of Barrett esophagus. (4)[A]
First Line
• Once a day proton-pump inhibitor (PPI) therapy for long-segment disease (5)[B]
• H2-receptor antagonist may be sufficient for short-segment disease (5)[B]
Second Line
• If once a day PPI does not control symptoms, b.i.d. dosing is recommended. (4)[A]
• If H2-receptor antagonist does not control symptoms, step-up to PPI. (4)[A]
SURGERY
• Fundoplication is an option to control GERD symptoms, but it has not been shown to reverse Barrett esophagus or decrease risk of cancer (5)[A]
• Esophagectomy is the only treatment of high-grade dysplasia that guarantees cancer-free survival (5)
• Mortality rate from esophagectomy is 8-23%, and 30-50% develop serious post-op complications
ALERT
Geriatric Considerations
If the patient is a poor operative candidate for PDT or other endoscopic ablative procedure, surveillance or no treatment may be preferable; treatment must be individualized.
FOLLOW-UP
• Surveillance is controversial; aim is to detect high-grade dysplasia or early carcinoma
• Only evidence to support improved survival in patients undergoing surveillance is from non-randomized, retrospective studies (1,3)
• Vast majority (96% in one study) of patients with adenocarcinoma of esophagus are NOT known to have Barrett esophagus before diagnosis of cancer (6)[B]
ALERT
Geriatric Considerations
Surveillance should only be done if there is reasonable life expectancy and ability to tolerate treatment of esophageal cancer (4)
DISPOSITION
• American College of Gastroenterology Guidelines for surveillance in Barrett esophagus (4)[C]
- If no dysplasia on 2 consecutive endoscopies with biopsies, 3-yr interval is appropriate
- If low-grade dysplasia, and repeat endoscopy again shows low-grade, yearly endoscopy until no dysplasia
- If high-grade, repeat Esophagogastroduodeno- scopy (EGD) w/biopsies to rule out cancer, expert pathologist confirmation; intervention or EGD every 3 months
Issues for Referral
• Patients should be treated with a PPI prior to endoscopy
• Diagnosis of high-grade dysplasia should be confirmed by a second expert pathologist. (4)[A]
• Patients considering esophagectomy should be referred to a high-volume institution; mortality and morbidity rates have been shown to be inversely related to volume. (4)[A]
PROGNOSIS
• Annual incidence of esophageal cancer in patients with Barrett esophagus is 0.5% per year.
• Low-grade dysplasia may be transient: 7% progress to cancer in 3-7 yrs
• High-grade progresses to cancer in 22% (3-7 yrs) (4)[B]
COMPLICATIONS
Same as GERD: Stricture, bleeding, ulceration
REFERENCES
1. Sampliner RE. Managing Barrett esophagus esophagus: What is new in 2005? Dis Esophagus. 2005;18:17-20.
2. Wang et al. AGA medical position statement: Role of gastroenterologist in the management of EsoCa Gastroenterology. 2005;128.
3. Sharma P, Sidorenko EI. Are Screening and surveillance for Barrett esophagus really worthwhile? Gut. 2005;54:27-32.
4. Sampliner RE and the Practice Parameters Committee of the American College of Gastroenterology. Updated guidelines for the diagnosis, surveillance, and therapy of Barrett Esophagus. Am J of Gastroenterology. 2002;97:1888-1895.
5. Spechler SJ. Barrett Esophagus. N Eng J Med. 2002;346:836-842.
6. Corley DA, Levin TR, et al. Surveillance and survival in Barrett's adenocarcinomas: A population based study. Gastroenterology. 2002;122:3:633-40.
ADDITIONAL READING
UpToDate Online 13.3 has an excellent evidence-based review.