eMedicine Specialties > Gastroenterology > Esophagus
Barrett Esophagus and Barrett Ulcer
Updated: Jun 1, 2009
Introduction
Background
The definition of Barrett esophagus (BE) has evolved considerably over the past 100 years. In 1906, Tileston, a pathologist, described several patients with "peptic ulcer of the oesophagus" in which the epithelium around the ulcer closely resembled that normally found in the stomach. The debate for the next 4 decades centered on the anatomical origin of this mucosal anomaly. Many investigators, including Barrett in his treatise published in 1950, supported the view that this ulcerated columnar-lined organ was, in fact, the stomach tethered within the chest by a congenitally short esophagus.1
In 1953, Allison and Johnstone argued that the columnar organ was more likely esophagus because the intrathoracic region lacked a peritoneal covering, contained submucosal glands and muscularis propria characteristic of the esophagus, and could harbor islands of squamous cells within the columnar segment.2 In 1957, Barrett agreed and suggested that the condition that bears his name be referred to as "lower esophagus lined by columnar epithelium."3 For the next 2 decades, descriptions of the histology of Barrett esophagus varied considerably from acid-secreting, fundic-type epithelium to intestinal-type epithelium with goblet cells.
Finally, in 1976, Paull et al published a report on the histologic spectrum of Barrett esophagus in which they used manometric guidance for their biopsies.4 These patients had 1 or a combination of 3 types of columnar epithelium—a gastric fundic-type, a junctional type, and a distinctive type of intestinal metaplasia the investigators called "specialized columnar epithelium." This specialized intestinal metaplasia (SIM), complete with goblet cells, has become the sine qua non for the diagnosis of Barrett esophagus.
While the histologic lesion became clearly evident, the endoscopic definition of Barrett esophagus has continued to change over the past 25 years. Many people believed that the distal esophagus could contain a normal region of columnar mucosa. In addition, determining the exact location of the esophagogastric junction (EGJ) in patients with Barrett esophagus often is difficult. To avoid false-positive diagnoses, investigators selected arbitrary lengths of columnar-lined esophagus to establish a diagnosis for their studies. Eventually, community endoscopists embraced this practice and biopsy of this so-called normal distal columnar-lined esophagus was avoided.
The last 10 years have brought convincing evidence that SIM, the hallmark histologic lesion of Barrett esophagus, predisposes to dysplasia and cancer regardless of the endoscopic location. Thus, the definition of Barrett esophagus currently is the finding of SIM anywhere within the tubular esophagus.
Pathophysiology
Barrett esophagus is well recognized as a complication of gastroesophageal reflux disease (GERD). Patients with GERD who develop Barrett esophagus tend to have a combination of clinical features, including hiatal hernia, reduced lower esophageal sphincter (LES) pressures, delayed esophageal acid clearance time, and duodenogastric reflux (as documented by the presence of bile in the esophageal lumen). First understanding the pathogenesis of GERD is necessary to understand the relationship between GERD and Barrett esophagus. Esophageal defense mechanisms against the noxious substances in the refluxate include an antireflux barrier, an efficient clearing mechanism, and epithelial defense factors. The antireflux barrier is a high-pressure zone at the EGJ that is generated by tonic contraction of the LES coupled with extrinsic compression by the right crus of the diaphragm. The phrenoesophageal ligament, intra-abdominal location of the LES, and maintenance of an acute angle of entry into the stomach help to reinforce this barrier.
This system is imperfect due to the existence of physiologic transient LES relaxations (TLESR). TLESR occur primarily after meals but in the absence of a preceding swallow. Studies indicate that about 95% of reflux episodes in healthy controls occur during the TLESR. Most reflux in patients with GERD occurs via this same mechanism. The duration of esophageal acidification, and not the frequency, correlates best with presence of erosive esophagitis.
A healthy individual clears the esophagus through various means, including gravity, bicarbonate secretion from the salivary and esophageal glands, and peristalsis. Dysfunctional esophageal motility with failed or weak peristalsis is a contributing factor in 34-48% of patients with GERD.
An acid (pH <4) contact time of 1-2 hours per day is considered normal in the distal esophagus. This physiologic reflux occurs in completely asymptomatic individuals. The esophagus, therefore, must have additional local means of protection. The esophagus is composed of a thick epithelial layer, with cells joined by tight junctions with lipid-rich intercellular spaces. This arrangement resists the diffusion of noxious substances by limiting entry of H+ into both cells and intercellular spaces. In addition, scattered submucosal glands in the distal esophagus that secrete bicarbonate and have an adequate blood supply to deliver bicarbonate and remove H+ help to maintain tissue acid-base balance.
The aggressors in the GERD battle reside in the refluxate. Mucosal injury depends on the pH of the refluxate and the duration of contact with the esophageal mucosa. Lower pH of the refluxate and extended contact with the esophagus increases the time required for intraesophageal pH to return to normal and increases the risk for mucosal injury.
Prolonged exposure of the esophagus to the refluxate can erode the esophageal mucosa, promote inflammatory cell infiltrate, and ultimately cause epithelial necrosis. This chronic damage is believed to promote the replacement of healthy esophageal epithelium with the metaplastic columnar cells, the cellular origin of which remains unknown. This likely is an adaptive response of the esophagus, which, if not for the increased risk of cancer, would have been beneficial. GERD symptoms and strictures are less common in the columnarized segment.
Interestingly, the features of GERD in relation to long-segment Barrett esophagus (LSBE >3 cm) and short-segment Barrett esophagus (SSBE <3 cm) are quite different. Patients with LSBE tend to have a longer duration of reflux symptoms, and, when undergoing 24-hour esophageal pH monitoring, they have severe, combined patterns of reflux (both supine and erect) and low LES pressures. They also tend to be less sensitive to direct acid exposure. On the other hand, patients with SSBE are more sensitive to acid exposure but have had symptoms for a shorter duration, with normal LES pressures and only upright reflux on 24-hour esophageal pH testing.
Current clinical practice guidelines recommend screening for Barrett esophagus in patients with GERD when the patients have had long-standing symptoms (>5 y), especially in those older than 50 years.
Epidemiology
The average age of patients with Barrett esophagus is 55-65 years. More than 80% are white males, with some studies indicating a higher prevalence of smoking, alcohol intake, and obesity.
Estimates of the prevalence of Barrett esophagus vary considerably and range from 0.9-10% of the general adult population. One of the more recent studies from Sweden by Ronkainen and colleagues estimates the prevalence to be approximately 2% in the adult population.5 This particular study is believed to be one of the more reliable because of the means by which epidemiological data can be assessed in Sweden. In US population terms, this prevalence would equate to approximately 3 million adults with Barrett esophagus.
The prevalence of LSBE in patients undergoing endoscopy for any clinical indication has been reported at 0.3-2% but is much higher, 8-20%, in patients with symptoms of GERD. A study conducted at the Mayo Clinic showed an autopsy prevalence about 17 times higher than a clinically matched population, suggesting that most cases of LSBE are asymptomatic and thus unrecognized. In patients undergoing endoscopy, the prevalence of SSBE ranges from 5-30%. The combined prevalence of SSBE and cardia-SIM is 7-8 times greater than LSBE, but the prevalence of dysplasia and cancer is much less.
Frequency
United States
Cameron (1997) estimated the prevalence of LSBE in the general US population to be 376 cases per 100,000 population.6
International
The frequency of Barrett esophagus internationally probably parallels that in the United States by ethnicity.
In a Swedish study, Ronkainen (2005) estimates the overall prevalence of Barrett esophagus (SSBE and LSBE) to be 1.6% in the adult population.5
Mortality/Morbidity
The most significant morbidity associated with Barrett esophagus is the development of adenocarcinoma in the esophagus. The incidence of esophageal adenocarcinoma is rising faster than any other cancer in the United States. From 1926-1976, 4 large surgical series reported that only 0.8-3.7% of esophageal cancers were adenocarcinomas. From 1979-1992, this increased to 54-68%.
In 1991, Blot et al reported their findings in a review of data from the Surveillance, Epidemiology, and End Results program of the National Cancer Institute.7 The incidence of esophageal adenocarcinoma in 1988-1990 was 3 times that in 1976-1978. In Olmstead County, Minnesota, Pera et al (1993) conducted a population-based study and found that the incidence of esophageal adenocarcinoma rose from 0.13 cases per 100,000 person-years in 1935-1971 to 0.74 cases per 100,000 person-years in 1974-1989.8 The incidence of adenocarcinoma of the cardia rose from 0.25 to 1.34 cases per 100,000 person-years in the same time period, an increase of more than 5-fold for both locations. Patients with LSBE have the greatest risk for development of dysplasia and adenocarcinoma of the esophagus.
Studies report the prevalence of dysplasia in LSBE at 20-35%, SSBE at 6-8%, and cardia-SIM at 0-6%, with the prevalence of adenocarcinoma being 7-15 times greater in LSBE versus SSBE and cardia-SIM. However, the total number of patients with SSBE and cardia-SIM is 7-8 times that of LSBE. Thus, even with a higher prevalence of dysplasia and cancer in the LSBE population, a greater total number of patients are likely to develop cancer from within the SSBE and EGJ-SIM group.
Race
Barrett esophagus primarily affects white people. It is rare in people of African ancestry, at this time.
Sex
Barrett esophagus is found in both men and women, with a 2:1 male-to-female ratio.
Age
The average age of patients with demonstrated Barrett esophagus is 55-65 years.
Clinical
History
The classic history for a patient with Barrett esophagus is a middle-aged (55 y) white man with a chronic history of GER, for example, pyrosis, acid regurgitation, and, occasionally, dysphagia. Although this is a classic history, some patients may deny any symptoms.
Physical
No unique physical examination characteristics are evident in patients with Barrett esophagus other than those that would be found in patients with chronic GERD.
Causes
GERD is the primary etiology of Barrett esophagus.
Differential Diagnoses
Esophagitis
Gastroesophageal Reflux Disease
Workup
Imaging Studies
- When high-grade dysplasia or cancer is found on surveillance endoscopy, endoscopic ultrasound (EUS) is advisable to evaluate for surgical resectability.
Procedures
- The standard diagnostic test or study for Barrett esophagus is an upper endoscopy. In cases of erosive esophagitis, a healing of the mucosa is required first to ensure lack of Barrett mucosa underneath the inflammation.
- Esophagogastroduodenoscopy (EGD) is the procedure of choice for the diagnosis of Barrett esophagus. The diagnosis requires biopsy confirmation of SIM in the esophagus. An upper gastrointestinal series (UGI) or barium swallow cannot reliably establish the diagnosis of Barrett esophagus.
Histologic Findings
The presence of specialized intestinal metaplasia in the esophagus is required for the diagnosis of Barrett esophagus.
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.
Dosing
Adult
150 mg PO bid
Pediatric
Not established
Interactions
May decrease effects of ketoconazole and itraconazole; may alter serum levels of ferrous sulfate, diazepam, nondepolarizing muscle relaxants, and oxaprozin
Contraindications
Documented hypersensitivity
Precautions
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Caution in renal or liver impairment; CrCl <10 mL/min, administer half dose
Famotidine (Pepcid)
Competitively inhibits histamine at H2 receptor of gastric parietal cells, resulting in reduced gastric acid secretion, gastric volume, and hydrogen concentrations.
Dosing
Adult
40 mg/d PO bid for 4-8 wk
Pediatric
Not established; suggested dose is 1-2 mg/kg/d PO/IV divided q6h; not to exceed 40 mg/dose
Interactions
May decrease effects of ketoconazole and itraconazole
Contraindications
Documented hypersensitivity
Precautions
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
If changes in renal function occur during therapy, consider adjusting dose or discontinuing treatment
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.
Dosing
Adult
300 mg PO hs or 150 mg bid
Pediatric
Not established
Interactions
None reported
Contraindications
Documented hypersensitivity
Precautions
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in renal or liver impairment; if changes in renal function occur during therapy, consider adjusting dose or discontinuing treatment
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.
Dosing
Adult
20 mg PO qd; up to 40 mg qd
Pediatric
Not established
Interactions
May decrease effects of itraconazole and ketoconazole; may increase toxicity of warfarin (increased plasma levels of warfarin are observed only with high doses)
Contraindications
Documented hypersensitivity
Precautions
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Bioavailability may increase in elderly people; adjust dose in hepatic impairment, half-life can increase as much as 4-fold
Lansoprazole (Prevacid)
Inhibits gastric acid secretion. Used for as long as 8 wk to treat all grades of erosive esophagitis.
Dosing
Adult
30 mg PO qd for 4-8 wk
Pediatric
Not established
Interactions
May decrease effects of ketoconazole and itraconazole; may increase theophylline clearance
Contraindications
Documented hypersensitivity
Precautions
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Consider adjusting dose in liver impairment
Esomeprazole (Nexium)
S-isomer of omeprazole. Inhibits gastric acid secretion by inhibiting H+/K+ -ATPase enzyme system at secretory surface of gastric parietal cells.
Dosing
Adult
20-40 mg PO qd
Pediatric
Not established
Interactions
Concurrent use with amoxicillin or clarithromycin may increase plasma levels of esomeprazole; may reduce absorption of dapsone; may increase levels of diazepam and GI absorption of digoxin; may decrease absorption of iron, ketoconazole, and itraconazole
Contraindications
Documented hypersensitivity
Precautions
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Symptomatic relief with PPIs may mask symptoms of gastric malignancy
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).
Dosing
Adult
2 mg/kg IV infused over 3-5 min; may repeat treatment courses separated by at least 30 d, not to exceed a total of 3 treatment courses
Pediatric
Not established
Interactions
Allow sufficient time between radiotherapy treatment to ensure inflammation has decreased; coadministration with other photosensitizing agents (eg, tetracycline, sulfonamides; hypoglycemic agents, thiazides) may increase photosensitivity risk; coadministration with drugs that inhibit oxygen species or free radicals (eg, DMSO, beta-carotene, ethanol, mannitol), allopurinol, calcium channel blockers, glucocorticoids, or prostaglandin synthesis inhibitors may decrease effect
Contraindications
Documented hypersensitivity to porphyrins; tracheoesophageal or bronchoesophageal fistula; tumors eroding into a major blood vessel
Precautions
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Use extravasation precautions; treatment-induced inflammation may obstruct main airway or cause chest pain; esophageal varices (increases bleeding risk); ocular sensitivity; monitor for respiratory distress
Follow-up
Prognosis
- Most patients with Barrett esophagus will not develop esophageal cancer and will die of other causes, as in the general population. The risk of progression to adenocarcinoma of the esophagus is estimated at approximately 0.5% per year in patients without dysplasia on initial surveillance biopsies. Why only some people with GERD develop Barrett esophagus also is not clear.
Miscellaneous
Medicolegal Pitfalls
- The association of chronic GERD with Barrett esophagus and its inherent risk of progression to adenocarcinoma of the esophagus is established. Consequently, any patient aged 50 years or older, male or female, with a history of chronic GERD should have at least a 1-time upper endoscopy to screen for Barrett esophagus. Failure to recommend endoscopy or at least to discuss the cancer risk in this situation could lead to litigation, should such a diagnosis be missed.
Multimedia
Media file 1: Barrett esophagus (BE). The salmon-pink area has specialized intestinal metaplasia. The white area is squamous epithelium.
Media file 2: Cryoablation of esophageal lining in Barrett esophagus (BE). This is one of the newest experimental ablative therapies for the esophagus performed at the author's laboratory.
Media file 3: Blistering of the esophageal mucosal layer after cryoablation in Barrett esophagus (BE).
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Keywords
Barrett esophagus, Barrett's esophagus, BE, Barrett's ulcer, specialized intestinal metaplasia, SIM, goblet cells, columnar lined esophagus, columnar-lined esophagus, Barrett's metaplasia, Barrett metaplasia, esophageal carcinoma, chronic gastroesophageal reflux, chronic GER, gastroesophageal reflux disease, GERD
Contributor Information and Disclosures
Author
Mark H Johnston, MD, Associate Professor of Medicine, Uniformed Services University of Health Sciences; Consulting Staff, Lancaster Gastroenterology Inc
Mark H Johnston, MD is a member of the following medical societies: American College of Gastroenterology, American College of Physicians, American Gastroenterological Association, and Christian Medical & Dental Society
Disclosure: Nothing to disclose.
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
John A Eastone, MD is a member of the following medical societies: American Association for the Study of Liver Diseases, American College of Gastroenterology, American College of Physicians-American Society of Internal Medicine, American Gastroenterological Association, and American Society for Gastrointestinal Endoscopy
Disclosure: Nothing to disclose.
Medical Editor
Ronnie Fass, MD, Director of GI Motility Laboratory, Tucson VA Medical Center, Associate Professor, Department of Internal Medicine, Division of Gastroenterology, University of Arizona School of Medicine
Ronnie Fass, MD is a member of the following medical societies: American College of Gastroenterology, American College of Physicians-American Society of Internal Medicine, American Gastroenterological Association, American Motility Society, American Society for Gastrointestinal Endoscopy, and Israel Medical Association
Disclosure: Nothing to disclose.
Pharmacy Editor
Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment
Managing Editor
James L Achord, MD, Professor Emeritus, Department of Medicine, Division of Digestive Diseases, University of Mississippi School of Medicine
James L Achord, MD is a member of the following medical societies: American Association for the Study of Liver Diseases, American College of Gastroenterology, American College of Physicians, American Gastroenterological Association, American Medical Association, American Society for Gastrointestinal Endoscopy, Mississippi State Medical Association, New York Academy of Sciences, Sigma Xi, and Southern Medical Association
Disclosure: Nothing to disclose.
CME Editor
Alex J Mechaber, MD, FACP, Associate Dean for Undergraduate Medical Education, Associate Professor of Medicine, University of Miami Miller School of Medicine
Alex J Mechaber, MD, FACP is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians-American Society of Internal Medicine, and Society of General Internal Medicine
Disclosure: Nothing to disclose.
Chief Editor
Julian Katz, MD, Clinical Professor of Medicine, Drexel University College of Medicine; Consulting Staff, Department of Medicine, Section of Gastroenterology and Hepatology, Hospital of the Medical College of Pennsylvania
Julian Katz, MD is a member of the following medical societies: American College of Gastroenterology, American College of Physicians, American Gastroenterological Association, American Geriatrics Society, American Medical Association, American Society for Gastrointestinal Endoscopy, American Society of Law Medicine and Ethics, American Trauma Society, Association of American Medical Colleges, and Physicians for Social Responsibility
Disclosure: Nothing to disclose.
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