AUTHOR AND EDITOR INFORMATION

Section 1 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

INTRODUCTION

Section 2 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

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 BE 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 BE 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 BE.

While the histologic lesion became clearly evident, the endoscopic definition of BE 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 BE 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 BE, predisposes to dysplasia and cancer regardless of the endoscopic location. Thus, the definition of BE currently is the finding of SIM anywhere within the tubular esophagus.

Pathophysiology

BE is well recognized as a complication of gastroesophageal reflux disease (GERD). Patients with GERD who develop BE 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 BE. 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 BE (LSBE >3 cm) and short-segment BE (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 BE 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 BE 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 BE 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 BE.

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 BE internationally probably parallels that in the United States by ethnicity.

In a Swedish study, Ronkainen (2005) estimates the overall prevalence of BE (SSBE and LSBE) to be 1.6% in the adult population.⁵

Mortality/Morbidity

The most significant morbidity associated with BE 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

BE primarily affects white people. It is rare in people of African ancestry, at this time.

Sex

BE is found in both men and women, with a 2:1 male-to-female ratio.

Age

The average age of patients with demonstrated BE is 55-65 years.

CLINICAL

Section 3 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

History

The classic history for a patient with BE 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 BE other than those that would be found in patients with chronic GERD.

Causes

GERD is the primary etiology of BE.

DIFFERENTIALS

Section 4 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

WORKUP

Section 5 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

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 BE 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 BE. The diagnosis requires biopsy confirmation of SIM in the esophagus. An upper gastrointestinal series (UGI) or barium swallow cannot reliably establish the diagnosis of BE.

Histologic Findings

The presence of specialized intestinal metaplasia in the esophagus is required for the diagnosis of BE.

TREATMENT

Section 6 of 11  

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• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Medical Care

The diagnosis of BE 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 BE. Haag et al conducted a comprehensive MEDLINE search in 1999 to determine the effect of medical, surgical, and ablative therapy in producing regression of BE (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 BE. 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 BE 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 BE 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 BE. 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 BE regression are inconclusive. No good evidence indicates that surgical therapy provides regression in BE. Thus, antireflux surgery is not indicated for eradication of BE, 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 American College 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 BE. Once identified, patients with BE 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 BE 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 BE 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 BE, with additional biopsy of any mucosal abnormalities.
  • Patients with BE 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 BE.  A recent study by Prasad found that the 5-year survival rate of patients with high-grade dysplasia in BE who were treated with PDT and EMR comparable to that of patients treated with esophagectomy.¹⁰
  • 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 BE, 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.¹¹ Ablation of BE with regeneration of squamous epithelium reportedly was accomplished in 75-80% of patients.¹¹ 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.¹² 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 BE. 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 BE with degrees of dysplasia ranging from no dysplasia to multifocal high-grade dysplasia achieved complete endoscopic reversal of BE 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 BE. Surgery seems to play no role in preventing the progression of BE 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 BE 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

Section 7 of 11  

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• References

Treatment of BE 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 BE.

Drug Category: 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.

Drug Category: 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.

Drug Category: 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.

FOLLOW-UP

Section 8 of 11  

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• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Prognosis

• Most patients with BE 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 BE also is not clear.

MISCELLANEOUS

Section 9 of 11  

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• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Medical/Legal Pitfalls

• The association of chronic GERD with BE 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 BE. 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

Section 10 of 11  

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• Workup
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• Follow-up
• Miscellaneous
• Multimedia
• References

Media file 1:  Barrett esophagus (BE). The salmon-pink area has specialized intestinal metaplasia. The white area is squamous epithelium.
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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.
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Media file 3:  Blistering of the esophageal mucosal layer after cryoablation in Barrett esophagus (BE).
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Media type:  Photo

REFERENCES

Section 11 of 11

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

1. Barrett NR. Chronic peptic ulcer of the oesophagus and 'oesophagitis'. Br J Surg. Oct 1950;38(150):175-82. [Medline].
2. Allison PR, Johnstone AS. The oesophagus lined with gastric mucous membrane. Thorax. Jun 1953;8(2):87-101. [Medline].
3. Barrett NR. The lower esophagus lined by columnar epithelium. Surgery. Jun 1957;41(6):881-94. [Medline].
4. Paull A, Trier JS, Dalton MD, Camp RC, Loeb P, Goyal RK. The histologic spectrum of Barrett's esophagus. N Engl J Med. Aug 26 1976;295(9):476-80. [Medline].
5. Ronkainen J, Aro P, Storskrubb T, Johansson SE, Lind T, Bolling-Sternevald E, et al. Prevalence of Barrett's esophagus in the general population: an endoscopic study. Gastroenterology. Dec 2005;129(6):1825-31. [Medline].
6. Cameron AJ. Epidemiology of columnar-lined esophagus and adenocarcinoma. Gastroenterol Clin North Am. Sep 1997;26(3):487-94. [Medline].
7. Blot WJ, Devesa SS, Kneller RW, Fraumeni JF Jr. Rising incidence of adenocarcinoma of the esophagus and gastric cardia. JAMA. Mar 13 1991;265(10):1287-9. [Medline].
8. Pera M, Cameron AJ, Trastek VF, Carpenter HA, Zinsmeister AR. Increasing incidence of adenocarcinoma of the esophagus and esophagogastric junction. Gastroenterology. Feb 1993;104(2):510-3. [Medline].
9. Haag S, Nandurkar S, Talley NJ. Regression of Barrett's esophagus: the role of acid suppression, surgery, and ablative methods. Gastrointest Endosc. Aug 1999;50(2):229-40. [Medline].
10. Prasad GA, Wang KK, Buttar NS, Wongkeesong LM, Krishnadath KK, Nichols FC 3rd, et al. Long-term survival following endoscopic and surgical treatment of high-grade dysplasia in Barrett's esophagus. Gastroenterology. Apr 2007;132(4):1226-33. [Medline].
11. Overholt BF, Panjehpour M, Haydek JM. Photodynamic therapy for Barrett's esophagus: follow-up in 100 patients. Gastrointest Endosc. Jan 1999;49(1):1-7. [Medline].
12. Sampliner RE, Fennerty B, Garewal HS. Reversal of Barrett's esophagus with acid suppression and multipolar electrocoagulation: preliminary results. Gastrointest Endosc. Nov 1996;44(5):532-5. [Medline].
13. Bremner RM, Mason RJ, Bremner CG, DeMeester TR, Chandrasoma P, Peters JH, et al. Ultrasonic epithelial ablation of the lower esophagus without stricture formation. A new technique for Barrett's ablation. Surg Endosc. Apr 1998;12(4):342-6; discussion 346-7. [Medline].
14. Dodds WJ, Dent J, Hogan WJ, Helm JF, Hauser R, Patel GK, et al. Mechanisms of gastroesophageal reflux in patients with reflux esophagitis. N Engl J Med. Dec 16 1982;307(25):1547-52. [Medline].
15. Johnston CM, Schoenfeld LP, Mysore JV, Dubois A. Endoscopic spray cryotherapy: a new technique for mucosal ablation in the esophagus. Gastrointest Endosc. Jul 1999;50(1):86-92. [Medline].
16. Kahrilas PJ, Dodds WJ, Hogan WJ, Kern M, Arndorfer RC, Reece A. Esophageal peristaltic dysfunction in peptic esophagitis. Gastroenterology. Oct 1986;91(4):897-904. [Medline].
17. Pereira-Lima JC, Busnello JV, Saul C, Toneloto EB, Lopes CV, Rynkowski CB, et al. High power setting argon plasma coagulation for the eradication of Barrett's esophagus. Am J Gastroenterol. Jul 2000;95(7):1661-8. [Medline].
18. Sampliner RE. Ablative therapies for the columnar-lined esophagus. Gastroenterol Clin North Am. Sep 1997;26(3):685-94. [Medline].
19. Sampliner RE. Practice guidelines on the diagnosis, surveillance, and therapy of Barrett's esophagus. The Practice Parameters Committee of the American College of Gastroenterology. Am J Gastroenterol. Jul 1998;93(7):1028-32. [Medline].
20. Spechler SJ, Goyal RK. The columnar-lined esophagus, intestinal metaplasia, and Norman Barrett. Gastroenterology. Feb 1996;110(2):614-21. [Medline].
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22. Wong RKH. Barrett's esophagus. Pract Gastroenterol. 2000;24:15-35.

Article Last Updated: Mar 7, 2008