eMedicine Specialties > Gastroenterology > Esophagus

Barrett Esophagus and Barrett Ulcer: Treatment & Medication

Author: Mark H Johnston, MD, Associate Professor of Medicine, Uniformed Services University of Health Sciences; Consulting Staff, Lancaster Gastroenterology Inc
Coauthor(s): John A Eastone, MD, Gastroenterology Fellow, Bethesda and Walter Reed Army Medical Center; Instructor, Department of Internal Medicine, F Edward Herbert School of Medicine, Uniformed Services University of the Health Sciences
Contributor Information and Disclosures

Updated: Jun 1, 2009

Treatment

Medical Care

The diagnosis of Barrett esophagus does not lead to specific therapy. Little evidence supports the assumption that antisecretory agents or antireflux surgery prevents the occurrence of adenocarcinoma or leads to regression of Barrett esophagus. Haag et al conducted a comprehensive MEDLINE search in 1999 to determine the effect of medical, surgical, and ablative therapy in producing regression of Barrett esophagus (see Ablative therapy for Barrett esophagus below).⁹

In the early-to-mid 1980s, histamine 2 (H2)-receptor antagonists were the most commonly prescribed agents for treatment of GERD. A number of studies were conducted with either cimetidine or ranitidine, and none documented regression of Barrett esophagus. In the late 1980s, proton pump inhibitors (PPIs) were introduced and proved to be much more efficacious at reducing gastric acid secretion. The supposition that better acid suppression could induce Barrett esophagus regression was met with optimism. Studies to date, however, have been inconclusive. Only 2 of 7 investigators demonstrated some regression. Most were unable to detect any regression, despite documentation of complete normalization of esophageal pH by pH testing.

Currently, the indication for medical therapy in Barrett esophagus is the same as that for GERD—control of symptoms and healing of esophageal mucosa. An important, as yet unanswered, question is whether abolishing acid completely with high-dose PPIs decreases the risk for adenocarcinoma of the esophagus and warrants the cost and possible adverse effects of this therapy.

In addition to acid, the reflux of pancreatic and biliary secretions into the esophagus has been implicated in the pathogenesis of Barrett esophagus. Because medications are effective only at reducing the acid component, surgical therapy may have an advantage. While studies have shown surgery to be efficacious in the control of GERD symptoms, the results regarding Barrett esophagus regression are inconclusive. No good evidence indicates that surgical therapy provides regression in Barrett esophagus. Thus, antireflux surgery is not indicated for eradication of Barrett esophagus, but it certainly is reasonable for appropriate patients who desire surgery for control of GERD symptoms.

• Barrett esophagus screening and surveillance
• • The Practice Parameters Committee of the AmericanCollege of Gastroenterology recommends that patients with long-standing GERD symptoms (>5 y), particularly those aged 50 years or older, have an upper endoscopy to detect or screen for Barrett esophagus. Once identified, patients with Barrett esophagus should undergo periodic surveillance endoscopy to identify histological markers for increased cancer risk (dysplasia) or cancer that is at an earlier stage and is amenable to therapy. Preliminary data suggest that surveillance endoscopy does just that. Still, esophageal cancer is an uncommon cause of death.
  • In a cohort study of patients with Barrett esophagus not undergoing surveillance, only 2.5% of 155 patients died as a result of esophageal cancer, with a mean of 9 years follow-up. Patients with Barrett esophagus should be considered candidates for surveillance only if a potential to prolong life expectancy exists and only if they are eligible for therapy when dysplasia or early cancer is detected. Age and comorbidity are important factors to consider.
  • The goal of surveillance is the detection of dysplasia or early cancer. Currently, dysplasia is the best histological marker for cancer risk. The appropriate surveillance interval is based on published data on the natural history of dysplasia and primarily is a function of the grade of dysplasia. Surveillance involves repeated upper endoscopy with systematic 4-quadrant biopsies at 2-cm intervals along the entire length of the segment of Barrett esophagus, with additional biopsy of any mucosal abnormalities.
  • Patients with Barrett esophagus in whom dysplasia is lacking for 2 consecutive yearly endoscopies may be extended to follow-up at 3-year intervals. Patients with persistent low-grade dysplasia on repeat endoscopy should undergo surveillance every 6 months for 2 cycles; if no progression of disease is noted, surveillance may be extended to yearly follow-up. Management of high-grade dysplasia is more controversial.
  • Observer variation is a problem in the grading of dysplasia, and the first step in management of a patient with high-grade dysplasia always is confirmation of the diagnosis by a pathologist who is an expert at reading esophageal biopsies. The surgical literature suggests that as many as 40% of patients who undergo esophagectomy for high-grade dysplasia have concomitant cancer in the resected specimen.
  • Currently, 2 alternatives for management of high-grade dysplasia exist. One is surveillance endoscopy, with intensive biopsy at 3-month intervals until cancer is detected. The other is surgical resection.
  • Because dysplasia and cancer are patchy and cannot be visualized endoscopically, the diagnosis is difficult with even the most intensive surveillance. Current research is focused on developing endoscopic techniques that would highlight dysplastic tissue to allow directed biopsy and also finding surrogate cellular markers and the like that might help predict which patients will develop cancer in the absence of biopsy-proven dysplasia.
• Ablative therapy for Barrett esophagus
• The goal of ablative therapy is to destroy the Barrett epithelium to a sufficient depth to eliminate the intestinal metaplasia and allow regrowth of squamous epithelium. A number of modalities have been tried, usually in combination with medical or surgical therapy because successful ablation appears to require an anacid environment.
• Human studies have been performed with photodynamic therapy (PDT), argon plasma coagulation (APC), multipolar electrocoagulation (MPEC), heater probes, and various forms of lasers, endoscopic mucosal resection (EMR), cryotherapy, and radiofrequency ablation.
• Ablative therapy is emerging as a viable alternative to surgical resection or esophagectomy for patients with high-grade dysplasia in Barrett esophagus. A recent study by Prasad found that the 5-year survival rate of patients with high-grade dysplasia in Barrett esophagus who were treated with PDT and EMR comparable to that of patients treated with esophagectomy.¹⁰ Shaheen et al demonstrated that radiofrequency ablation was associated with a high rate of complete eradication of both dysplasia and intestinal metaplasia and a reduced risk of disease progression in patients with dysplastic Barrett esophagus.¹¹ Complete eradication occurred in 90.5% of patients with low-grade dysplasia compared with 22.7% of those in the control group (P <0.001). Among patients with high-grade dysplasia, complete eradication occurred in 81% in the ablation group, whereas complete eradication occurred in only 19% in the control group (P <0.001).¹¹ Patients in the ablation group had less disease progression (3.6% vs 16.3%, P = 0.03) and fewer cancers (1.2% vs 9.3%, P = 0.045). In this study, radiofrequency ablation showed a high success rate for complete eradication of dysplasia and intestinal metaplasia in patients with Barrett esophagus.¹¹
• PDT involves the use of a photosensitizing agent that accumulates in tissue and induces local necrosis by means of production of intracellular free radicals following exposure to light at a certain wavelength. Typically, a hematoporphyrin is used as the photosensitizing agent because it has a greater affinity for neoplastic tissue.
• Also, 5-aminolevulinic acid (ALA), which induces endogenous protoporphyrin IX and has selectivity for the mucosa over deeper submucosal layers, has been used. The results have been promising for regression of Barrett esophagus, as well as for treatment of dysplasia and superficial carcinoma.
• Overholt et al treated 100 patients, 73 with high-grade dysplasia and 13 with superficial adenocarcinoma.¹² Ablation of Barrett esophagus with regeneration of squamous epithelium reportedly was accomplished in 75-80% of patients.¹² Other studies have shown similar response rates, but Barrett epithelium beneath the superficial squamous layer has been observed, indicating that deeper-placed pluripotent cells may be preserved. Additionally, PDT is an expensive and time-consuming endeavor, and early use was complicated by esophageal stricture requiring dilation in 58% of patients.
• APC is a method of contact-free high-frequency current coagulation in which the burning of tissue stops as soon as the area is ablated. One study using high-power APC was reported to result in complete restoration of squamous mucosa in 33 out of 33 patients after a mean of 1.96 sessions. The major complication was chest pain and odynophagia, which occurred in 57.5% of patients and lasted 3-10 days. Only 3 patients experienced stricture, which was treated easily with dilation. Only 1 endoscopic, as well as histologic, recurrence was observed at 10.6-months mean follow-up, but this was in a patient with an ineffective Nissan fundoplication.
• Other studies have been less encouraging, with persistence of residual foci of Barrett epithelium under the neosquamous lining in 22-29%, and deep esophageal ulceration with massive bleeding, perforation, and even death has been reported.
• MPEC is a method in which the mucosa is ablated by direct contact with an electrocautery probe. Sampliner et al (1996) used this technique to treat 10 patients with LSBE, using half of the patient's own esophagus as an internal control.¹³ All 10 patients had the treated segment eliminated by visual and biopsy criteria at 6 months, with the untreated segment unchanged despite acid suppression. Treatment took an average of 2.5 sessions, and 5 patients had complications in 75 total sessions (2 transient odynophagia, 1 transient dysphagia, 1 chest pain, and 1 upper gastrointestinal bleed).
• Lasers have been used in numerous small studies for eradication of Barrett esophagus. Results were less consistent with this modality than those listed above. Studies that demonstrated full or partial regression endoscopically were confounded by the persistence of glandular elements beneath the neosquamous epithelium in as many as one third of cases.
• Relatively new to the scene of endoscopic ablation is balloon-based, bipolar radiofrequency ablation (Stellartech Research Coagulation System; BARRx, Inc, Sunnyvale, Calif). This technique requires the use of sizing balloons to determine the inner diameter of the targeted portion of the esophagus. This is followed by placement of a balloon-based electrode with a 3-cm long treatment area that incorporates tightly spaced, bipolar electrodes that alternate in polarity. The electrode is then attached to a radiofrequency generator and a preselected amount of energy is delivered in less than 1 second at 350 W.
• One of the newer ablative techniques is low-pressure cryospray ablation using liquid nitrogen pioneered at the author's institution.
• The components of the low-pressure spray cryoablation device are as follows: liquid nitrogen tank; electronic console for monitoring and controlling cryogen release; dual foot pedal for controlling cryogen release and heating of the catheter; and the catheter, which is a multilayered, 7-9F, open-tipped catheter for spray of supercold nitrogen gas through an upper endoscope.
• The mechanism of injury is unique relative to the other ablative techniques. Cryoablation induces apoptosis, causes cryonecrosis at supercold temperatures (-76°C to -196°C), results in transient ischemia, and can cause immune stimulation. The Barrett epithelium is resistant to apoptosis and, therefore, may be uniquely suited for treatment by cryoablation.
• A pilot study at the author's institution using cryoablation in Barrett esophagus with degrees of dysplasia ranging from no dysplasia to multifocal high-grade dysplasia achieved complete endoscopic reversal of Barrett esophagus in 78% of cases, with no subsquamous SIM or dysplasia at 6-month follow-up. These results will need confirmation at other institutions.

Surgical Care

Antireflux surgeries, such as a Nissen fundoplication, have not been shown to reverse the outcome of Barrett esophagus. Surgery seems to play no role in preventing the progression of Barrett esophagus to cancer. However, when high-grade dysplasia is discovered and confirmed by a second pathologist, esophagectomy is the standard of care.

Diet

The diet for patients with Barrett esophagus is the same as that recommended for patients with GERD. Patients should avoid fried or fatty foods, chocolate, peppermint, alcohol, coffee, carbonated beverages, citrus fruits or juices, tomato sauce, ketchup, mustard, vinegar, aspirin, or other nonsteroidal anti-inflammatory drugs (NSAIDs). They also should decrease the size of portions at mealtime, avoid eating 3 hours prior to bedtime, elevate the head of the bed 6 inches, lose weight (if overweight), and stop smoking.

Medication

Treatment of Barrett esophagus should be the same as that of GERD. However, most authorities agree that it should be used with a proton pump inhibitor versus an H2-receptor antagonist due to the relative acid insensitivity of patients with Barrett esophagus.

H2-receptor antagonists

These agents are reversible competitive blockers of histamine at the H2 receptors, particularly those in the gastric parietal cells, where they inhibit acid secretion. The H2 antagonists are highly selective, do not affect the H1 receptors, and are not anticholinergic agents.

Ranitidine (Zantac)

Inhibits histamine stimulation of the H2 receptor in gastric parietal cells, which reduces gastric acid secretion, gastric volume, and hydrogen concentrations.
Indicated in acid/peptic disorder, erosive esophagitis, gastrointestinal hypersecretion, mastocytosis, gastroesophageal reflux, peptic ulcer, and Zollinger-Ellison syndrome.

Famotidine (Pepcid)

Competitively inhibits histamine at H2 receptor of gastric parietal cells, resulting in reduced gastric acid secretion, gastric volume, and hydrogen concentrations.

Nizatidine (Axid)

Competitively inhibits histamine at the H2 receptor of the gastric parietal cells, resulting in reduced gastric acid secretion, gastric volume, and hydrogen concentrations.

Proton pump inhibitors

Inhibit gastric acid secretion by inhibition of the H⁺/K⁺ -ATPase enzyme system in the gastric parietal cells. These agents are used in cases of severe esophagitis and in patients not responding to H2 antagonist therapy.

Omeprazole (Prilosec)

Decreases gastric acid secretion by inhibiting parietal cell H⁺ and K⁺ pump.

Lansoprazole (Prevacid)

Inhibits gastric acid secretion. Used for as long as 8 wk to treat all grades of erosive esophagitis.

Esomeprazole (Nexium)

S-isomer of omeprazole. Inhibits gastric acid secretion by inhibiting H⁺/K⁺ -ATPase enzyme system at secretory surface of gastric parietal cells.

Photosensitizers

These agents are used with photodynamic therapy (PDT). Upon light absorption, photosensitizer transform to a short-lived singlet state followed by a transition to the reactive triplet state. When in the triplet state, produces reactive free radicals in the presence of oxygen, which react with cell membranes, causing direct damage to the mitochondria, endoplasmic reticulum, and/or plasma membranes.

Porfimer (Photofrin)

Indicated to treat high-grade dysplasia in Barrett esophagus. Elicits a photosensitizing effect used in the photodynamic therapy (PDT).

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