Barrett’s esophagus (Intestinal metaplasia of the lower esophagus)

The metaplasia of esophageal squamous epithelium to columnar epithelium (Barrett’s esophagus) is a complication of severe reflux esophagitis, and it is a risk factor for esophageal adenocarcinoma. Metaplastic columnar epithelium develops during healing of erosive esophagitis with continued acid reflux because columnar epithelium is more resistant to acid-pepsin damage than is squamous epithelium. The metaplastic epithelium is a mosaic of different epithelial types, including goblet cells and columnar cells, which have features of both secretory and absorptive cells. Finding intestinal metaplasia with goblet cells in the esophagus is diagnostic of Barrett’s esophagus; this type of mucosa is thought to be at risk of cancer. Barrett’s esophagus is arbitrarily divided into long-segment (>1-4 cm) and short-segment (<1-4 cm) groups; long-segment disease is diagnosed in about 2% and short-segment disease in 8-14% of the GERD population.
The rate of cancer development is 1% per year in long-segment disease, a 30- to 125-fold increased risk as compared to the general population. Short-segment Barrett’s esophagus may also progress to cancer, but the actual risk in these cases is unclear.

Currently, patients with HGD can be treated with esophagectomy, endoscopic mucosal resection, or photodynamic therapy with HGD. Close endoscopic follow-up (every 3-4 months) is recommended in all patients with HGD. In LGD, follow-up endoscopy is recommended at 5 and 10 months initially and yearly thereafter, as long as LGD persists. Patients with Barrett’s esophagus without dysplasia should have two examinations within the first year and subsequently every 3-4 years. Acid suppression and fundoplication are indicated when active esophagitis is also present. Established metaplasia does not regress with antisecretory treatment.
EPIDEMIOLOGY & DEMOGRAPHICS
* Male predominance with a 4:2 ratio of men to women;
* Mean age of onset is 42 yr with a mean age of diagnosis of 52 to 62 years;
* Occurs more frequently in Caucasians and Hispanics than in African-Americans with a ratio of 8-20:1;
* Mean prevalence of 10% in patients undergoing endoscopy for symptoms of GERD.
PHYSICAL FINDINGS & CLINICAL PRESENTATION
Symptoms:
* Chronic (>6 year) heartburn;
* Asymptomatic, incidental finding;
* Dysphagia for solid food;
* Less frequent: chest pain, hematemesis, or melena.
Physical findings:
* Nonspecific;
* Ranges from epigastric tenderness on palpation to completely normal.
ETIOLOGY
* Metaplasia is thought to be secondary to irritation of esophageal lining secondary to chronic gastro-esophageal reflux.
* Because not all individuals with GERD develop Barrett’s esophagus, there is probably also a genetic propensity for the disease.
DIAGNOSIS
DIFFERENTIAL DIAGNOSIS
* GERD, uncomplicated;
* Erosive esophagitis;
* Gastritis;
* Hiatal hernia;
* Peptic ulcer disease;
* Angina;
* Malignancy;
* Stricture.
DIAGNOSTIC CRITERIA: CONTROVERSIAL
* Long segment;
* Short segment;
* Junctional intestinal metaplasia.
DIAGNOSTIC TESTS
* Endoscopy with biopsy necessary for diagnosis;
* Histologic hallmark is intestinal metaplasia in esophagus;
* Upper GI with barium may reveal ulcer crater in esophagus; however, UGI is nonspecific and insensitive for the diagnosis;
* Screening for H. pylori infection in patients with GERD and Barrett’s esophagus is not recommended.
TREATMENT
NONPHARMACOLOGIC THERAPY
Same as treatment for GERD alone for symptoms of acid reflux (life-style modifications and pharmacologic therapy).

     Barrett’s intestinal metaplasia progresses to adenocarcinoma through dysplastic stages, including low-grade dysplasia (LGD) and high-grade dysplasia (HGD). The sequence of disease progression is variable and inconsistent. Sampling error is a major problem in monitoring progression of the disease by mucosal biopsies. Therefore, optical methods of recognizing dysplasia during the endoscopy (laser-induced fluorescence spectroscopy, optical coherence tomography) are being developed. Moreover, an intense search for molecular markers of neoplastic progression is ongoing.
     Barrett’s esophagus can also lead to chronic peptic ulcer of the esophagus with high (midesophageal) and long strictures. Barrett’s esophagus is more common in obese white men; its incidence increases with age. Usefulness of routine endoscopic population screening for Barrett’s esophagus has not been established. However, a one-time esophagoscopy is recommended in patients with persistent GERD symptoms at age 50-55, particularly in white males. Over 92% of patients with esophageal adenocarcinoma are diagnosed during their first visit to a physician. When Barrett’s esophagus is identified for the first time, no effort should be spared to exclude the presence of concurrent dysplasia or carcinoma. This effort may require a follow-up endoscopic study after aggressive treatment of esophagitis, with multiple esophageal mucosal biopsies.
     The frequency of surveillance endoscopies in patients with established Barrett’s esophagus depends on the initial endoscopic findings. HGD is often associated with concurrent carcinoma and progresses to cancer in about 25% of the cases.

ACUTE GENERAL Rx
* Proton pump inhibitors (PPIs) are most effective;
* Adequate system control of GERD in patients with Barrett’s esophagus may control symptoms and adequate acid suppression may impede the progression to dysplasia.
* If asymptomatic and incidentally found to have Barrett’s esophagus, medication is unnecessary.
CHRONIC Rx
* Laser ablation, photodynamic therapy, endoscopic mucosal resection.
* Surgery for: (1) management of GERD and associated sequelae or (2) cancer or precursor lesions.
SCREENING
* GERD highly prevalent in general population;
* Only 4% to 10% of patients with reflux symptoms develop Barrett’s esophagus;
* ACG recommends that patients with Barrett’s undergo surveillance endoscopy and biopsy at intervals determined by the presence and grade of dysplasia, with a range of every 6 months to 3 years;
* Patients should be treated aggressively for GERD before surveillance.
DISPOSITION
* Overall, 40 to 60 times increased risk of adenocarcinoma of the esophagus in patients with Barrett’s esophagus than in general population;
* This risk corresponds to 600 cancers per year per 110,000 persons with Barrett’s esophagus;
* Specifics of frequency of monitoring is controversial, no prospective controlled studies to prove that surveillance increases life expectancy;
* Usual recommendation is periodic surveillance by endoscopy and biopsy for detection of carcinoma or high-grade dysplasia;
* Current generally accepted follow-up recommendations for patients with Barrett’s esophagus (no dysplasia) include endoscopy every 3 years and q6 months (x2), then once/year for those with low-grade dysplasia.