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Background: Obesity has been linked to gastro-oesophageal reflux disease symptoms and oesophageal adenocarcinoma; however, there is no published evidence for an association with Barrett's oesophagus., Aim: To investigate the association between obesity and Barrett's oesophagus., Methods: We conducted a retrospective cross-sectional study of patients who underwent upper endoscopy at the Southern Arizona Veteran's Affairs Healthcare System between 1998 and 2004. We examined male patients without malignancy, with available information on weight and height. Based on endoscopic and histological findings, patients were classified as cases with Barrett's oesophagus or non-cases without Barrett's oesophagus. Multivariable logistic regression analysis was conducted to examine the association of body mass index and obesity with Barrett's oesophagus and Barrett's oesophagus length while adjusting for age and race., Results: There were 65 cases with Barrett's oesophagus and 385 non-cases without Barrett's oesophagus. The mean body mass index was significantly higher in cases than in non-cases (29.8 vs. 28.0, P = 0.03). Cases had significantly greater mean weight than controls (206 lb vs. 190,P = 0.005). The proportions of cases with body mass index 25-30 and body mass index > or =30 were greater than those in non-cases (44.6% vs. 37.7%) and (40.0% vs. 33.5%), respectively (P = 0.08). In the multivariable logistic regression model adjusting for race and age, when compared with body mass index < 25, the odds ratio was 2.43 (95% confidence interval: 1.12-5.31) for body mass index 25-30 and 2.46 (1.11-5.44) for body mass index > or =30. When examined as a continuous variable the adjusted odd ratio for each five-point increase in body mass index was 1.35 (95% confidence interval: 1.06-1.71, P = 0.01). The association between weight and Barrett's oesophagus was also statistically significant (adjusted odd ratio for each 10 pound increase = 1.10, 1.03-1.17, P =0.002). Among the 65 cases of Barrett's oesophagus, there was no correlation between the length of Barrett's oesophagus at the time of diagnosis and the body mass index (correlation coefficient = 0.03, P = 0.79)., Conclusion: This retrospective cross-sectional study in male veterans shows that overweight is associated with a two-and-half-fold increased risk of Barrett's oesophagus. Larger studies of the underlying mechanism are warranted to better understand how and why obese patients are at greater risk for Barrett's oesophagus.

Background: Barrett's oesophagus patients may continue to have abnormal oesophageal acid exposure on proton pump inhibitor therapy. The effect of factors such as Barrett's oesophagus length, hiatal hernia size and Helicobacter pylori infection on intra-oesophageal pH in Barrett's oesophagus patients has not been adequately studied., Aim: To evaluate oesophageal acid exposure in a large Barrett's oesophagus population on b.d. proton pump inhibitor therapy and determine clinical factors predicting normalization of intra-oesophageal pH on therapy., Methods: Barrett's oesophagus patients were studied using 24 h pH monitoring to evaluate intra-oesophageal acid suppression on b.d. dosing of rabeprazole., Results: Forty-six Barrett's oesophagus patients completed the study. Median total percentage time pH < 4 was 1.05% (range: 0-29.9%) in the entire group and respective values for upright and supine percentage time pH < 4 were 1.15% and 0%. However, 34 of the Barrett's oesophagus patients (73.9%) had a normal pH study (median total percentage time pH < 4: 0.2%) and 12 patients (26.1%) had an abnormal result (median total percentage time pH < 4: 9.3%). There were no significant differences between patients with a normal and abnormal 24 h pH result with respect to age, Barrett's oesophagus length, hiatal hernia size and presence of H. pylori infection., Conclusions: Approximately 25% of Barrett's oesophagus patients continue to have abnormal total intra-oesophageal pH profiles despite b.d. proton pump inhibitor therapy. Factors such as age, Barrett's oesophagus length and hiatal hernia size cannot be used to predict persistent abnormal intra-oesophageal pH on proton pump inhibitor.

Background & Aims: Gastroesophageal reflux disease (GERD) is prevalent worldwide. Until recently patients and physicians have had a choice between long-term medical therapy, usually in the form of proton pump inhibitors (PPIs), or surgical fundoplication. During the past several years, endoscopic antireflux therapies have been approved for GERD patients to potentially obviate the risks of surgery and avoid long-term medication use. The objective of this review was to critically evaluate existing literature on endoscopic antireflux therapies with regards to efficacy and safety., Methods: A review of human studies by using Pub Med was performed., Results: Injectable LES implants, endoscopically placed gastric plications, and radio frequency energy application to the LES comprise the 3 modes of antireflux therapies. These techniques received approval by the Food and Drug Administration on the basis of symptomatic evidence supplied by numerous uncontrolled trials. As a group, these techniques have demonstrated efficacy less than medical and surgical options, and yet they carry a rare but significant risk of serious complications and even death., Conclusions: The field is still evolving at this stage, and there is a need for more randomized sham and placebo-controlled trials to better define the subjective and objective outcomes of these endoscopic procedures. At this time endoscopic antireflux procedures should be used with caution after discussing risks and benefits with the patient.

The definition of BE has evolved over time. BE is the key premalignant lesion for developing EAC. The epidemiology and pathophysiology of BE is outlined, and risk factors for BE and EAC are reviewed. GERD plays a crucial role in the pathophysiology and the clinical identification of BE. Endoscopy with biopsy is the best tool for diagnosing and surveying patients with BE. Detection of early neoplasia is the present approach to reduce EAC mortality. Novel technology should assist in the early detection of dysplasia to enable targeted therapy. Effective chemopreventive strategies may reduce the risk of progression to EAC.

Background and Aims: Barrett's esophagus (BE) is a premalignant lesion of the distal esophagus in which squamous epithelial cells are replaced by metaplastic intestinal-like columnar epithelium that contains goblet cells. The factors that contribute to the progression from normal squamous mucosa to BE, Barrett's dysplasia, and adenocarcinoma are not well understood at the molecular level. Since reflux of bile acids is associated with BE development, we speculate that cells with an apoptosis-resistant phenotype are selected after long-term repeated exposure to pulses of bile acids. This will result in the survival of cells with unrepaired DNA damage, and a consequent increase in genomic instability leading to cancer progression. The major goal of this study is to compare sensitivity to apoptosis induced by the bile acid, deoxycholate (DOC), a known inducer of apoptosis, in normal esophageal squamous epithelium, normal colon epithelium, and BE., Methods: Thirteen patients with a confirmed diagnosis of BE and four patients who had undergone clinically indicated colectomy were included in the present study. Freshly obtained biopsies were incubated with control medium or medium supplemented with 1 mM DOC for 3 h and then evaluated for apoptotic changes using transmission electron microscopy and immunohistochemical staining for two apoptotic markers, cleaved caspase 3 and cleaved cytokeratin 18., Results: Our results indicate that BE is resistant to apoptosis induced by DOC compared to esophageal squamous epithelium and normal colon epithelium. In addition, electron micrographs revealed mitochondrial swelling in squamous epithelial cells treated ex vivo with DOC, which was absent in epithelial cells of BE. Formation of swollen mitochondria is an early marker of apoptotic cell death. Altogether, the data indicate that reduced apoptosis capability in BE tissue may contribute to progression to esophageal adenocarcinoma.

The new developments in the management of Barrett's esophagus in 2005 result in refinements of decision making. New techniques including magnification endoscopy have been used for real-time recognition of intestinal metaplasia but are not yet validated. The finding of BE in patients lacking GERD symptoms highlights the problems of developing screening criteria for the general population. Many experimental optical techniques are pushing the optical recognition of dysplasia to real time. Availability, cost and validation remain barriers to clinical application. Endoscopic mucosal resection is being more widely applied resulting in more accurate staging of patients with early adenocarcinoma of the esophagus and helping to define patients amenable to endoscopic therapy. The approval of photodynamic therapy for the treatment of high grade dysplasia adds to the non-operative therapeutic arsenal. The impact of medical therapy of GERD and anti-reflux surgery on the development of esophageal adenocarcinoma is disappointing. Technological developments and emerging efforts in chemoprevention offer promise for the future.

Treatment for Barrett's esophagus (BE) has consisted of medical treatment (acid suppression medications), surgery (fundoplication) and endoscopic ablative techniques (photodynamic therapy, argon plasma coagulation and multipolar electrocoagulation). Despite the large number of clinical trials of the efficacy of different therapeutic modalities, there is a paucity of published randomized controlled trials. The aim of this review is to evaluate the published randomized therapeutic trials in patients with BE. A comprehensive MEDLINE search was performed to review randomized clinical trials of different therapeutic modalities in BE. Only eight randomized studies have been published. The eight randomized studies reviewed include: two trials that evaluated medical and surgical therapy; two placebo controlled trials for photodynamic therapy (PDT); one placebo controlled trial comparing argon plasma coagulation (APC) versus surveillance; two trials comparing PDT versus APC; and one trial comparing APC versus multipolar electrocoagulation (MPEC). All the studies are prospective, however only one study is double-blinded. Each study has a small sample size, uses a different population of BE patients (dysplasia versus no dysplasia, short segment BE versus long segment BE), has different defined endpoints (endoscopic ablation of BE, number of treatments required for endoscopic ablation of BE, and elimination of high grade dysplasia) and the methodology for the treatment modalities is different among the studies. Though the data to support the use of endoscopic ablative techniques in the treatment of BE are promising, more rigorous double-blind and larger, well designed randomized studies are required to draw any definitive conclusions.

Background and Aims: Esophageal acid exposure is important in the pathogenesis of Barrett's esophagus (BE), and possibly in the progression of BE to dysplasia and carcinoma. The aim of this study is to compare the development of dysplasia in BE patients treated with or without proton pump inhibitor (PPI) or histamine 2-receptor antagonist (H2RA)., Methods: We analyzed prospectively collected data by a single endoscopist on patients with BE in a VA (Veterans Affairs) setting over a 20-yr time period (1981-2000). A pathologist used standard criteria to diagnose BE/dysplasia. Pharmacy information after 1994 was retrieved from a computerized database, and from research files for the period before that. The receipt and the duration of H2RA and/or PPI use was compared between those with and without dysplasia. The incidence of dysplasia was examined in a Kaplan-Meier survival analysis stratified by PPI treatment status, and the risk of dysplasia was examined in a Cox multiple regression analysis controlling for demographic features, length of BE, and the year of BE diagnosis., Results: We analyzed data for 236 unique veteran patients with a mean age at BE diagnosis of 61.5 yr, 86% Caucasian, and 98% male. During 1,170 patient-yr of follow-up, 56 patients developed dysplasia giving an annual incidence rate of 4.7%. Of those, 14 had high-grade dysplasia. The cumulative incidence of dysplasia was significantly lower among patients who received PPI after BE diagnosis than in those who received no therapy or H2RA; log rank test (p < 0.001). Furthermore, among those on PPIs, a longer duration of use was associated with less frequent occurrence of dysplasia. In multivariate analysis, the use of PPI after BE diagnosis was independently associated with reduced risk of dysplasia, hazards ratio: 0.25 (95% CI 0.13-0.47), p < 0.0001. Longer segments of BE and Caucasian race were other independent risk factors for developing dysplasia. In general, similar findings were observed when only cases with high-grade dysplasia were analyzed., Conclusions: These results indicate that PPI therapy is associated with a significant reduction in the risk of developing dysplasia in patients with BE. However, more studies are required to confirm this finding.

Background: The length of Barrett's oesophagus seems to correlate well with indicators of severe gastro-oesophageal reflux disease. However, it remains unknown whether prior acid suppressive therapy affects the length of newly diagnosed Barrett's oesophagus., Methods: A retrospective analysis of a well-characterized large cohort of patients with Barrett's oesophagus diagnosed between 1981 and 2000., Aim: To compare the length of Barrett's oesophagus between patients who received acid suppressive therapy prior to their diagnosis to those who did not receive such therapy. Pharmacy records were obtained from Department of the Veterans Affairs computerized records and prospectively collected research records. We further examined the association between prior use of acid suppressive therapy and the length of Barrett's oesophagus in correlation analyses, as well as multivariate linear regression analyses while adjusting for differences in year of diagnosis, age, gender, ethnicity, and the presence of intestinal metaplasia of the gastric cardia. Results : There were 340 patients with Barrett's oesophagus first diagnosed between 1981 and 2000. The average length of Barrett's oesophagus at the time of first diagnosis was 4.4 cm (range: 0.5-16). Of all patients, 139 (41%) had prior use of histamine-2 receptor antagonists, or proton-pump inhibitors (41 used both), and 201 (59%) used neither prior to the diagnosis of Barrett's oesophagus. The mean length of Barrett's oesophagus was significantly shorter in patients with prior use of proton-pump inhibitors (3.4 cm) or proton-pump inhibitors and histamine-2 receptor antagonists (3.1 cm) when compared to those with none of these medications (4.8 cm). In the multivariate linear regression model, the prior use of proton-pump inhibitors or either proton-pump inhibitors or histamine-2 receptor antagonists was an independent predictor of shorter length of Barrett's oesophagus (P = 0.0396)., Conclusions: The use of acid suppressive therapy among patients is associated with a reduction in the eventual length of newly diagnosed Barrett's oesophagus with gastro-oesophageal reflux disease. This finding is independent of the year of diagnosis or demographic features of patients. Further studies are required to confirm this finding.

Background & Aims: Secular trends in the length of newly diagnosed Barrett's esophagus (BE) are unknown. We have anecdotally noticed less frequent new diagnoses of long segments of BE., Methods: This is a retrospective analysis of prospectively collected information on a well-characterized large cohort of patients with documented BE that was diagnosed between 1981 and 2000 at Southern Arizona Department of Veterans Affairs Health Care System. We examined temporal changes in the length of BE at the time of diagnosis (frequency and proportions). We conducted correlation analyses, as well as multivariate linear regression analyses, to examine the association between year of diagnosis and BE length while adjusting for temporal differences in age, sex, ethnicity, previous use of antisecretory therapy, and the presence of intestinal metaplasia (IM) of the gastric cardia., Results: There were 340 patients with BE first diagnosed between 1981 and 2000. All cases were defined by the presence of areas of salmon-colored mucosa in the lower end of the tubular esophagus and IM in biopsy specimens obtained from these areas on at least 2 endoscopic examinations. There were no significant changes over time in mean age of patients with BE (61 yr) or proportion of white patients (84%). The mean length of BE at the time of first diagnosis declined progressively over time. In the earliest period (1981-1985), mean BE length was 6 +/- 3.8 cm, whereas mean BE length in 1996-2000 was 3.6 +/- 2.9 cm. This observation was explained not only by more frequent diagnoses of short BE, but also by less frequent diagnoses of long BE (> or =3 cm). There was a strong inverse correlation between BE length at the time of diagnosis and year of diagnosis (Pearson's correlation coefficient, -0.29; P <0.0001). In the multivariate linear regression model, a more recent year of BE diagnosis was an independent predictor of shorter BE length (P <0.0001). Similar results were obtained in analyses restricted to veteran patients or those with BE > or = 3 cm., Conclusions: There has been a progressive decline in the length of newly diagnosed BE as a result of an increase in short-segment BE, but, curiously, also because of a decline in long-segment BE (> or =3 cm). These changes cannot be explained fully by changes in demographic features of patients, previous therapy, or the increasing emphasis on IM of the gastric cardia. The role of referral bias and/or temporal changes in the definitions cannot be excluded.

Objectives: Accurate measurements of Barrett's esophagus length are important in clinical follow-up as well as in studies of therapeutic intervention in Barrett's esophagus. Our aim was to evaluate both the inter- and intraobserver reliability in measuring Barrett's length during two consecutive endoscopies by either the same or different experienced endoscopists. The relationship between Barrett's mucosa length and the absolute change in Barrett's length measurements on a follow-up endoscopy was also evaluated., Methods: A total of 96 Barrett's patients underwent two consecutive endoscopies. The diagnosis of Barrett's esophagus was confirmed by the presence of intestinal metaplasia on biopsy. The Barrett's esophagus length was carefully measured and recorded during the two endoscopies. Procedures were performed by only two experienced endoscopists, who were not aware of previous endoscopic measurements. Only patients with long-segment (> or =3 cm) Barrett's esophagus were included in this study., Results: The 55 patients who had their consecutive endoscopies performed by the same endoscopist had a mean 1.6-cm difference between the two measurements as compared to 1.4 cm in the 41 patients who had their endoscopies performed by different endoscopists (p = 0.3). The agreement between the two Barrett's length measurements was high in both groups, although it was slightly higher for endoscopies performed by the same endoscopist (r = 0.79 vs r = 0.67). Linear regression analysis of the absolute change in Barrett's length between the two endoscopic measurements and Barrett's mucosa length demonstrated a significant relationship (r = 0.28, p = 0.005). For every 1-cm increase in the mean length of Barrett's mucosa, a 0.15-cm increase in the absolute difference between two consecutive endoscopic measurements of Barrett's length was observed., Conclusions: Consecutive measurements of Barrett's length performed by different experienced endoscopists or by the same experienced endoscopist demonstrated a high degree of agreement. A range of variability in Barrett's length measurement was determined (+/-1.4-1.6 cm). True regression or progression of Barrett's mucosa should be considered only if the change is greater than the range of variability. In addition, endoscopists should be well aware that the longer the Barrett's mucosa the greater the absolute difference in Barrett's length measurement on follow-up endoscopy.

The ultimate goal of therapy in patients with Barrett's esophagus (BE) is to reduce the risk of developing adenocarcinoma of the esophagus. Neither pharmacologic nor surgical therapy has been documented to reduce this risk. There is preliminary evidence that many forms of mucosal ablation combined with acid reduction therapy result in restitution of normal squamous epithelium in patients with BE. Acid reduction can be accomplished with high-dose proton pump inhibitor therapy or antireflux surgery. Endoscopic ablation can be accomplished with photodynamic therapy, laser, multipolar electrocoagulation, a heater probe, and argon plasma coagulation. These techniques require further study so the complication rates can be compared. The success of reversing BE must be evaluated in a standard way utilizing large-capacity biopsy forceps through a therapeutic endoscope. Ideally, patients at high risk of developing adenocarcinoma of the esophagus can be treated with ablation therapy and followed to document a reduction in the development of adenocarcinoma of the esophagus. A validated biomarker would help select high risk patients appropriate for reversal therapy. Currently, patients who are at prohibitive risk for surgery or who refuse surgery are candidates for combination therapy including mucosal ablation to reverse their BE. This therapy offers the promise of less morbidity and greater quality of life than resection.

Studies show Barrett's esophagus prevalence increases with age, while mean length of Barrett's esophagus is unchanged. Few data are available about the relationship between age and length on the development of dysplasia. Our aim was to assess age and length as risk factors for dysplasia. Consecutive patients with Barrett's esophagus were enrolled in a multicenter study establishing a tissue bank of Barrett's esophagus patients 1994 and 1998. Demographics, length of Barrett's esophagus (centimeters), and histology were recorded. Risk factors for dysplasia were assessed, including patient age, gender, and length of Barrett's esophagus. Statistical analysis was performed comparing prevalence of dysplasia (which included the presence of any carcinoma and high- or low-grade dysplasia) to age and length. In all, 309 patients were studied [278 (90%) male and 31 (10%) female]: 5 had adenocarcinoma of the esophagus, 11 had high-grade dysplasia, and 29 had low-grade dysplasia. Patients with Barrett's esophagus without dysplasia were younger than those with dysplasia [62 +/- 0.8 years vs 67 +/- 1.7 years (mean +/- SEM, P = 0.02)]. The risk of dysplasia increased by 3.3%/yr of age. Mean length of Barrett's esophagus in patients with Barrett's alone vs dysplasia was 4.0 +/- 0.2 cm vs 5.4 +/- 0.4 cm (P = 0.003). Patients with Barrett's esophagus length > or = 3 cm had a significantly greater prevalence of dysplasia compared to length < 3 cm (23% vs 9%, P = 0.0001). The risk of dysplasia increased by 14%/cm of increased length. Multivariate analysis showed age and length to be independent risk factors. In conclusions: prevalence of dysplasia is strongly associated with age and length of Barrett's esophagus. These preliminary results can be used to develop a strategy for screening/surveillance based on age and length of Barrett's epithelium.

Multipolar electrocoagulation (MPEC) is a readily available technique that can be applied for endoscopic ablation of Barrett's esophagus. MPEC, in combination with high dose proton pump inhibitor therapy or antireflux surgery, results in normal squamous epithelium in most patients without major adverse effects. The ultimate clinical role of MPEC has not been determined but may be adjunctive to other techniques in appropriately selected patients at high risk for neoplastic progression.

Background: The presence of intestinal metaplasia (IM) in the columnar lined distal oesophagus defines Barrett's oesophagus with the risk of future malignant transformation. The distribution of both IM and dysplasia (low grade (LGD) and high grade (HGD)) within the columnar lined oesophagus is patchy and mosaic requiring random biopsies. Techniques that could help target areas of high yield within Barrett's mucosa would be helpful., Aim: To study the utility of high magnification chromoendoscopy (MCE) in the detection of IM, LGD, and HGD in patients with Barrett's oesophagus., Methods: Consecutive patients detected with columnar mucosa in the distal oesophagus were studied using an Olympus magnification endoscope (GIF-Q16OZ, 115x). The distal oesophagus was sprayed with indigo carmine solution and the oesophageal columnar mucosa patterns were noted under high magnification and targeted for biopsy. All biopsies were read by pathologists blinded to the endoscopic findings., Results: Eighty patients with suspected Barrett's oesophagus (that is, columnar lined distal oesophagus) were studied: mean age 62.7 years (range 35-81). Mean length of columnar mucosa was 3.7 cm (range 0.5-17). Three types of mucosal patterns were noted within the columnar mucosa after spraying indigo carmine and using MCE: ridged/villous pattern, circular pattern, and irregular/distorted pattern. The yield of IM on target biopsies according to the patterns was: ridged/villous 57/62 (97%) and circular 2/12 (17%). Six patients had an irregular/distorted pattern and all had HGD on biopsy (6/6 (100%)). Eighteen patients had LGD on target biopsies; all had the ridged/villous pattern. All patients with long segment Barrett's were identified using MCE whereas 23/28 patients (82%) with short segment Barrett's had the ridged/villous pattern., Conclusions: MCE helps visually identify areas with IM and HGD having specific patterns but not patients with LGD (appear similar to IM). MCE may be a useful clinical tool for the increased detection of patients with IM as well as for surveillance of patients for the detection of HGD. If these preliminary results are validated, MCE would help identify high yield areas, potentially eliminating the need for random biopsies.

Barrett's oesophagus is a change in the lining of the distal oesophagus recognised at endoscopy and documented to have intestinal metaplasia by biopsy. It is thought that it is an acquired condition resulting from chronic gastro-oesophageal reflux disease (GORD). Barrett's oesophagus has the potential to progress to adenocarcinoma of the oesophagus. Evidence to support the association between Barrett's oesophagus and GORD appears to be strong but circumstantial. The intermediate steps that lead from GORD to Barrett's oesophagus are speculative and the timeline for the development of this condition remains obscure. It has yet to be demonstrated that erosive oesophagitis is a necessary intermediate step for the development of Barrett's oesophagus. In spite of effective therapy, documentation that medical or surgical therapy prevents Barrett's oesophagus is lacking. The goal of screening for Barrett's oesophagus is ultimately to improve the survival of patients with adenocarcinoma of the oesophagus. This goal has not been achieved and the evidence-based criteria for screening remain to be defined. Medical and surgical therapy of Barrett's oesophagus is effective in controlling reflux, although not proven to prevent neoplastic progression of the at risk mucosa. Endoscopic techniques of mucosal injury have been applied as alternatives to oesophagectomy in efforts to prevent progression to cancer. Surveillance endoscopy and biopsy is the currently accepted method aimed at early intervention and improved survival for oesophageal adenocarcinoma. A working surveillance protocol to accomplish this is proposed based on dysplasia grade. If no dysplasia is found and confirmed with subsequent endoscopy and biopsy, a 3-year interval is recommended. If only low grade dysplasia is confirmed, then annual endoscopy until no dysplasia is recognised is recommended. On the basis of defined risk factors, high grade dysplasia can lead to intense surveillance every 3 months or an intervention. Future developments in understanding the biology of Barrett's oesophagus and in therapeutic interventions will provide an opportunity for more effective screening, surveillance and prevention of neoplastic progression.

A number of publications have provided valuable insight into and data on the epidemiology, pathogenesis, diagnosis, risk factor evaluation, and treatment of patients with Barrett esophagus. Although the incidence of esophageal adenocarcinoma has rapidly increased over the past two decades, it is not clear whether there has been a parallel increase in the frequency of Barrett esophagus. The issue of surveillance endoscopy in patients with Barrett esophagus remains controversial; prospective data are still lacking. Bile reflux plays an important role in the pathogenesis of Barrett esophagus; however, this usually occurs in the presence of acid. Newer technology and techniques, including chromoendoscopy, magnification endoscopy, optical coherence tomography, and spectroscopy, have opened the field by providing a more accurate and "nonbiopsy" diagnosis of intestinal metaplasia and dysplasia. The field of biomarkers remains continues to expand and is providing insight into risk stratification of patients with Barrett esophagus. The exact role of acid suppression in patients with this premalignant disease remains controversial, and endoscopic therapies appear promising.

Objectives: Several previous studies have shown that malignant progression in Barrett's metaplasia (BM) occurs even in patients treated with fundoplication or acid suppression therapy (AST). The aim of this study was to test the hypothesis that AST may not alter malignant progression in BM if key genes involved in DNA repair and cell cycle control, particularly p53, are defective., Methods: Initial and follow-up biopsies from 21 patients with BM treated with AST and observed for 1-13 yr were entered in the study. All biopsies were graded for dysplasia and evaluated for p53 protein accumulation and oxidative DNA damage by immunohiostochemistry, using antibodies to p53 and to 8-hydroxydeoxyguanosine, respectively. DNA ploidy was determined using image analysis. Statistical analysis was performed using Kaplan-Meier curves, log rank test, and multivariate regression., Results: Patients with p53 positive initial biopsies were more likely to have progression in dysplasia grade (p = 0.022) and DNA ploidy status (p = 0.023) than those with p53 negative biopsies. In eight patients AST resulted in significant reduction in oxidative DNA damage in the five patients with p53-negative initial biopsies, but not the three with p53 positive ones (p = 0.0007)., Conclusions: We conclude that failure of AST to alter malignant progression in BM may be due, at least in part, to defects in DNA repair and cell cycle control resulting from p53 gene mutation, present before AST treatment. Although AST may be effective in preventing further DNA damage, it is unlikely to alter progression in genetically unstable cells.

Objective: Gastroesophageal reflux disease (GERD) plays a major role in the development of Barrett's esophagus. Recently, we demonstrated that duration of esophageal acid exposure in the distal esophagus correlates with the length of Barrett's mucosa. The aim of this study was to determine whether there is a relationship between the rate of the change in acid exposure along the esophagus and the length of Barrett's esophagus., Methods: A total of 17 patients (16 men and one woman; mean age 66 +/- 15 yr, range 41-83 yr) with varying lengths of biopsy-proven Barrett's esophagus were recruited prospectively into the study. Ambulatory 24-h esophageal pH monitoring was performed using a commercially available pH probe with four sensors located 5 cm apart. For each patient, a least squares regression line of the fraction of the study that the pH was <4 against the height of the sensor above the lower esophageal sphincter was fit. The slope of the regression line was used to represent the rate of change in acid exposure. Linear regression analysis was conducted to analyze the relationship between the rate of change in acid exposure and the length of Barrett's mucosa., Results: The mean Barrett's length was 5 +/- 3 cm (range 1-11 cm). Linear regression demonstrated a statistically significant relationship between the rate of change in acid exposure and the length of Barrett's esophagus for the 24-h duration of the study, as well as for the fraction of the study that patients were in the upright position (p = 0.0096 and 0.0076, respectively). For the supine position, the relationship did not reach statistical significance (p = 0.095)., Conclusions: We demonstrated a significant relationship between the rate of change in acid exposure and the length of Barrett's mucosa. Thus, as the rate at which recorded acid exposure values increases from the proximal to distal esophagus, the length of Barrett's esophagus significantly increases (for percent total time and upright position).

The treatment of patients with Barrett's esophagus is similar to that of any patient with underlying gastroesophageal reflux disease (GERD). The treatment of reflux includes medical and surgical therapy. A key component of medical therapy is the use of a proton pump inhibitor to treat the underlying GERD. The major controversy is whether the end point of therapy should be the control of reflux symptoms or the control of esophageal pH. When controlling reflux symptoms with proton pump inhibitor therapy, it is important to eliminate all of the symptoms of reflux. An alternative to medical therapy is surgical fundoplication, which is currently performed laparoscopically. Fundoplication may be indicated when a patient has persistent regurgitation even while on proton pump inhibitor therapy. An individual patient also may choose fundoplication, preferring surgical intervention to taking medication long term on a daily basis. Patients with Barrett's esophagus also have the risk of the developing of adenocarcinoma of the esophagus. Therefore, there is an additional goal in the therapy for individuals with Barrett's to prevent progression to adenocarcinoma. The standard approach to the issue of the premalignant nature of Barrett's esophagus is surveillance endoscopy with biopsy in order to detect dysplasia, a cytologic and architectural histologic change. Dysplasia is the first step in the neoplastic process, an early stage offering the opportunity of intervention and longer-term survival.

Dysplasia in a patient who has Barrett's esophagus (BE) is the first step in the neoplastic process. The grade of dysplasia correlates with the likelihood of developing adenocarcinoma of the esophagus during follow-up surveillance endoscopy and biopsy. Surveillance intervals are proposed based on the existing data of the likelihood of developing adenocarcinoma. In the future these intervals will be refined as a result of better definition of the risk factors the development of adenocarcinoma of the esophagus. Risk stratification of the individual patients by age, gender, grade of dysplasia, length of BE, length of hiatal hernia, and presence of genetic mutations will be possible.

Objective: Normalization of esophageal acid exposure had been assumed to be necessary for the reversal of Barrett's esophagus with endoscopic therapy. This assumption is examined by evaluating the esophageal pH in a group of patients undergoing reversal therapy with fixed high-dose proton pump inhibitor therapy and endoscopic multipolar electrocoagulation (MPEC)., Methods: Patients with Barrett's esophagus of 2-6 cm in length were treated with omeprazole (40 mg b.i.d.). They underwent 24-h esophageal pH monitoring 5 cm above the upper margin of the lower esophageal sphincter determined by a water-perfused catheter. They then underwent MPEC therapy to an endpoint of elimination of Barrett's (reversal) by both endoscopy and biopsy 6 months after the last MPEC session or failure to achieve visual (endoscopic) reversal after six treatment sessions., Results: Twenty patients had 24-h pH testing and reached a reversal endpoint. Three patients had abnormal pH tests, two total and supine and one supine only. These patients had documented reversal. The remaining 17 patients had normal pH testing but five failed reversal therapy., Conclusion: Barrett's esophagus can be completely reversed with endoscopic therapy despite abnormal esophageal acid exposure. Also, patients can fail reversal even with normal esophageal acid exposure. The necessary reduction of esophageal acid exposure for reversal therapy has yet to be defined.

Background: Barrett's oesophagus is associated with an increased risk of the development of oesophageal adenocarcinoma. Endoscopic surveillance every 2-5 years has been recommended to prevent death from adenocarcinoma., Aim: To assess the cost-effectiveness of this strategy., Methods: The incremental cost-effectiveness of surveillance (as compared to no surveillance) was analysed with a computer model of a Markov process., Results: Compared to no surveillance, the incremental cost-effectiveness of bi-annual endoscopy is 16,695 dollars per life-year saved. Surveillance is less cost-effective if the incidence rate of oesophageal adenocarcinoma is low and the 5-year survival rate is high. For surveillance to be cost-effective, there should be little reduction in health-related quality of life following surgical oesophagectomy to prevent death. Moreover, endoscopic surveillance and oesophagectomy need to be efficacious in reliably diagnosing high-grade dysplasia and preventing deaths from cancer. If such ideal conditions of surveillance are not met, the cost per life-year saved could rise five-fold., Conclusions: Endoscopic surveillance of patients with Barrett's oesophagus may be a cost-effective means to prevent death from oesophageal adenocarcinoma.

Background: Surveillance of patients with Barrett esophagus (BE) is recommended to detect dysplasia and early cancer. In 1998, practice guidelines for the surveillance of patients with BE were developed under the auspices of the American College of Gastroenterology (ACG). Our objective is to assess physicians' awareness of agreement with and adherence to these guidelines., Methods: A national prospective cohort study of practicing gastroenterologists who completed a self-administered questionnaire containing case studies prior to the release of the guidelines and another survey 18 months later. Analysis of adherence to the guidelines was done using the McNemar chi(2) test., Results: Of the 154 gastroenterologists (66%) who responded to the follow-up survey, more than half (55%) were aware of the guidelines, and members of the ACG were more likely to know of their existence than nonmembers (61% vs 38%; P =.01). Overall, about 27% of physicians reported practicing in accordance with the guidelines at baseline; adherence increased modestly to 38% in the 18-month follow-up (P =.04) and was inversely related to fee-for-service reimbursement. Awareness was not associated with an increased likelihood of adherence, but agreement with the guidelines was strongly correlated with adherence (P<.001). The most frequent reasons for disagreement were concerns about liability, cancer risk, and inadequate evidence., Conclusions: Awareness of the guidelines published by the ACG was low. Guideline awareness did not predict adherence. Improvement in guideline adherence will require steps beyond mere dissemination and promotion. Addressing disagreements about liability, disease risk, and scientific evidence as well as restructuring payment incentives may help achieve optimal practice.

Objective: Short segment Barrett's esophagus (SSBE) is defined by the presence of intestinal metaplasia in biopsies obtained from mucosa with an appearance suggestive of Barrett's that extends <3 cm into the esophagus. It has been suggested that this lesion may represent a stage in an ongoing process of Barrett's esophagus progression. If so, then the prevalence of SSBE would be expected to decrease with advancing age, and patients followed over time should exhibit an increase in the extent of columnar-lined esophagus. The aim of this study was to determine whether SSBE length progresses or regresses over time by following a prospective cohort and by assessing the relationship between age and the length, as well as prevalence of SSBE., Methods: The study included consecutive patients who were evaluated prospectively by an upper endoscopy and were found to have SSBE between October, 1983, and December, 1999, at the Southern Arizona VA Health Care System. All patients underwent a systematic biopsy protocol, and a designated pathologist who reviewed all specimens confirmed the diagnosis of Barrett's esophagus. Patients were subsequently interviewed for demographic information. In those patients who were enrolled into our surveillance program, SSBE length was remeasured and intestinal metaplasia reconfirmed on follow-up endoscopies., Results: Of 343 patients with endoscopically proven Barrett's esophagus, 116 (33.8%) were found to have SSBE. Almost all were male (97.4%) and white (85.3%), with a mean age of 60.1+/-1.0 yr. The prevalence of SSBE increased with age and reached a plateau during the seventh decade of life. One-way analysis of variance showed that there was no significant difference in the mean length of SSBE among the various age groups (p = 0.84). This trend was maintained when only the white group was assessed. Follow-up endoscopies were performed in 57 patients, revealing a mean interval of 64 months to the latest endoscopy, with no significant difference in SSBE length between the first and last endoscopy (p = 0.16)., Conclusions: The prevalence of SSBE increases with age until the seventh decade of life. Finding that SSBE length does not change across the various age groups and during a 64-month mean follow-up, suggests that SSBE does not progress over time.

There continues to be great interest in Barrett esophagus, the premalignant lesion for adenocarcinoma of the esophagus and the esophagogastric junction. There were several publications this past year related to the epidemiology, pathogenesis, new methods for detection, biomarkers for stratifying patients by risk, and the treatment of patients with Barrett esophagus. Patients with intestinal metaplasia in short lengths of columnar mucosa in the distal esophagus (ie, short-segment Barrett esophagus) appear to be distinct from those with intestinal metaplasia in the gastric cardia. The reported risk of cancer in patients with Barrett esophagus is probably subject to publication bias, with small series reporting a higher incidence of cancer. New methods for the diagnosis and detection of intestinal metaplasia and dysplasia are being evaluated and may, in future, help in obtaining more accurate screening and more focused surveillance of patients with Barrett esophagus. The validation of biomarkers may help us to risk stratify patients at high risk for cancer development. Endoscopic mucosal resection appears to be a safe and effective technique for the resection and accurate diagnosis of dysplastic or cancerous areas within Barrett esophagus.

The previous paradigm that Barrett's is an irreversible premalignant lesion has recently been challenged by a proliferation of reports documenting elimination of Barrett's by a variety of endoscopic techniques. Whether Barrett's is entirely eliminated is unknown as endoscopic biopsy samples the surface of the epithelium only. Numerous reports document underlying specialised columnar epithelium in many of these trials. Until now there have been no reports of pathological examination of the entire oesophagus as a specimen. This case documents complete elimination of intestinal metaplasia from the oesophagus and supports the biological plausibility of these research techniques.

Background: The presence of extensions of squamous epithelium into the proximal stomach in patients undergoing routine upper endoscopy has recently been described. The factors that may favor development of squamous epithelium within the proximal stomach remain unknown., Methods: Patients with Barrett's esophagus who agreed to undergo ablation of Barrett's epithelium by using multipolar electrocoagulation were included. Patients were treated with a high dose of a proton pump inhibitor. The columnar-appearing mucosa was systematically treated. Occasionally, thermal injury was inadvertently induced in the proximal stomach. On endoscopy performed 4 to 6 weeks after treatment, the presence of squamous epithelium extending into the proximal stomach was documented. The use of Lugol's stain assisted in confirming the squamous nature of the abnormal tissue, which was confirmed histologically by cytokeratin immunohistochemistry., Results: The 12 patients included in the study had a mean length of Barrett's epithelium of 3.8 +/- 0.7 cm. Patients were treated with omeprazole, mean dose 66 +/- 6.0 mg, and had a mean percent total time that the pH was less than 4 of 1.9 +/- 0.8. The mean length and width of gastric squamous extensions were 1.7 +/- 0.2 cm and 0.8 +/- 0.1 cm, respectively. None of the squamous extensions into the stomach were documented before mucosal ablation. The extensions stained positively for cytokeratin 13 and negatively for cytokeratin 8, thereby confirming their squamous nature., Conclusions: Thermal injury to the proximal stomach in patients undergoing ablation of Barrett's epithelium and profound acid suppression results in repair by squamous epithelium. Recognition of this lesion is essential because it may lead to confusion as to the location of the esophagogastric junction in subsequent endoscopic evaluations.

Background: Helicobacter pylori infection has been linked with the development of gastric adenocarcinoma and its precursor lesion, intestinal metaplasia (IM). The presence of gastric IM is not associated with symptoms, which makes identification of individuals with this lesion difficult. It is not clear whether eradication of H. pylori infection leads to reversal of gastric IM or the potential decrease in the risk of cancer in these patients., Goals: The purpose of this pilot study was to define the prevalence of gastric IM in a population at high risk for gastric cancer (Southwestern Hispanics), examine the ability of noninvasive testing to identify individuals with the lesion, and determine whether eradication of H. pylori infection reverses gastric IM in this population., Study: Subjects from the Tucson metropolitan area were recruited, and baseline data, including the presence of upper gastrointestinal (UGI) symptoms, urinary sodium, and serum pepsinogen levels, were obtained. Upper endoscopy was performed and six gastric biopsies from specific anatomic sites were obtained, followed by methylene blue staining with targeted biopsies from blue-stained mucosa. Biopsies were evaluated for the presence of H. pylori infection and gastric IM. A subset of patients with gastric IM were treated to eradicate H. pylori infection. Follow-up exams with methylene blue staining, including biopsies for histology and rapid urease testing, were performed for up to 48 months., Results: There were 84 subjects with a mean age of 53.0 years; 24 (29%) had gastric IM and 65 (77%) had H. pylori. There was no significant association between gastric IM and age, gender, UGI symptoms, H. pylori, or urine sodium. There was an association identified between gastric IM and a decreased pepsinogen I:II ratio (p = 0.03). Of the 11 individuals with gastric IM treated for H. pylori infection, 9 had successful therapy and underwent at least 2 follow-up examinations. The mean length of follow-up was 3.3 years. Eight of the nine (89%) had gastric IM identified histologically at the final endoscopic exam., Conclusions: H. pylori infection and gastric IM are frequent findings in Southwestern Hispanics, a high-risk population for gastric cancer. Noninvasive testing is not clinically useful in distinguishing individuals within this group who harbor gastric IM. Although eradication of H. pylori infection may lead to a decrease in the amount of gastric IM in some individuals, the lesion may be detected in the majority of individuals after more than 3 years of follow-up. These data suggest that therapy for H. pylori may not eliminate the risk of gastric cancer once IM has developed.

Background: Barrett's esophagus is a metaplastic change in the esophageal lining with an increased risk for adenocarcinoma. Multiple endoscopic techniques have been applied in an effort to reverse Barrett's. This is a multicenter trial defining the efficacy and safety of multipolar electrocoagulation combined with high-dose acid inhibition., Methods: Patients with a 2- to 6-cm segment of Barrett's esophagus without dysplasia were enrolled at 3 centers. They were treated with omeprazole 40 mg twice daily and then with up to 6 sessions with electrocoagulation aimed at eliminating all the endoscopically apparent Barrett's. Four quadrant large-capacity biopsies every 2 cm were centrally assessed for residual intestinal metaplasia., Results: Fifty-eight patients reached the endpoint of failure of visual reversal of Barrett's after 6 treatment sessions or a 6-month follow-up after the last session. Eighty-five percent had visual reversal and 78% both visual and histologic reversal. Four patients had histologic evidence of residual intestinal metaplasia. Transient esophageal symptoms were common. One patient developed a stricture requiring dilation and one required overnight hospitalization for chest pain., Conclusions: The majority of patients with 2 to 6 cm of nondysplastic Barrett's esophagus can be safely reversed with this combination therapy. Long-term follow-up will be necessary to document the durability of the new squamous epithelium.

Barrett esophagus is defined by the metaplasia of existing squamous mucosa into a specialized intestinal-type mucosa. The importance of this metaplasia is the association of this condition with the development of adenocarcinoma of the esophagus. Elimination of the metaplastic mucosa may decrease the cancer risk. Currently, several forms of therapy have evolved with the goal of replacing the specialized mucosa with normal squamous mucosa. These proposed treatments include photodynamic therapy and thermal techniques. The effectiveness of photodynamic therapy varies depending on the pharmaceutical photosensitizer used and the wavelength of light applied to activate the drug. Thermal techniques include multipolar coagulation, argon plasma coagulation, KTP:YAG laser therapy, Nd:YAG laser therapy, and argon laser therapy. Finally, mucosal resection has been attempted through the endoscope to remove large areas of the Barrett mucosa. All of these ablative strategies attempt to destroy the metaplastic mucosa and promote the regrowth of squamous epithelium. These therapies have demonstrated the ability to "reverse" the metaplasia to varying degrees, but a decrease in cancer risk has not been demonstrated conclusively with any of these treatment methods.

Background: Gastro-oesophageal reflux disease (GORD) plays a major role in the development of Barrett's oesophagus. However, it has yet to be elucidated what factors determine the length of Barrett's mucosa in each individual patient., Aims: To determine if there is a correlation between oesophageal acid exposure and the length of Barrett's mucosa. We also compared the extent of oesophageal acid exposure between patients with short segment (SSBE) and long segment (LSBE) Barrett's oesophagus., Methods: Twenty seven patients with Barrett's oesophagus were recruited prospectively into the study from the outpatient gastroenterology clinic at the Southern Arizona VA Health Care System. Diagnosis of Barrett's oesophagus and its anatomical characteristics were determined during upper endoscopy. Ambulatory 24 hour oesophageal pH monitoring assessed the extent of oesophageal acid exposure., Results: There was a significant correlation between per cent total time pH less than 4 and length of Barrett's mucosa (r=0.6234, p=0.0005). In addition, there was a significant correlation between per cent upright and supine time pH less than 4 and length of Barrett's mucosa (r=0.5847, p=0.0014 and r=0.6265 p=0.0006, respectively). Patients with SSBE had significantly less oesophageal acid exposure than patients with LSBE, in terms of both per cent total time and per cent supine time pH less than 4 (p<0.05)., Conclusions: The length of Barrett's mucosa correlated with the duration of oesophageal acid exposure. Patients with LSBE experienced significantly more oesophageal acid exposure than patients with SSBE. Duration of oesophageal acid exposure appears to be an important contributing factor in determining the length of Barrett's mucosa.

There is no dispute that Barrett's esophagus (BE) is associated with an increased risk of esophageal adenocarcinoma. Detecting these cancers early can improve patient survival. But should screening be used to detect BE, or should a surveillance program monitor those already diagnosed with BE for neoplastic changes? Endoscopy and endoscopic biopsy are the only tools available for such screening and surveillance, and the cost effectiveness of either approach must be considered. Two possible solutions are discussed. First, screening could be limited to patients considered at high risk for BE and associated adenocarcinoma. With this approach, more precise risk stratification would be required. The second possible approach is to combine screening for high-risk patients and surveillance for those already diagnosed with BE. Additional outcomes data are needed to determine how often and for what length of time endoscopic surveillance should continue in a patient after several examinations are negative for adenocarcinoma.

Objectives: Inflammation of the gastric cardia, i.e., "carditis," has been associated with Helicobacter pylori (H. pylori) infection; however, some investigators believe carditis to be a histological marker for gastroesophageal reflux disease. The aim of this study was to investigate the role of H. pylori eradication on the grade of carditis scored according to the updated Sydney classification., Methods: Consecutive patients presenting for upper endoscopy underwent systematic gastric biopsies (eight antral, 12 corpus, and four cardia). Patients with H. pylori infection and carditis were identified and followed prospectively before and after H. pylori treatment. At pretreatment and, on average, 2 yr after eradication of H. pylori, the degree of inflammation in the gastric cardia and H. pylori status were blindly assessed by a single pathologist., Results: A total of 31 patients with H. pylori infection and carditis were identified. The mean age was 70 yr (range: 37-81 yr); all were male. Four were African-American and 27 were Caucasian. All patients were treated with standard anti-H. pylori therapy, including a proton pump inhibitor in combination with two antibiotics for 2 wk. Eradication of H. pylori was successful in 23 patients (group I), whereas eight patients had persistent infection (group II). Patients were followed after eradication therapy for a mean of 23.2 months (range: 6-48 months). After eradication therapy, there was a significant decrease (p < 0.0001) in the carditis scores (activity and inflammation scores) in group I, whereas the scores remained unchanged in group II patients. In both groups, there were no significant changes in the degree of intestinal metaplasia or atrophy. There were four patients with intestinal metaplasia, and one with atrophy., Conclusions: There is a dramatic improvement in the degree of inflammation and activity scores in the gastric cardia of patients with successful H. pylori eradication compared to those with persistent infection. By fulfilling one of Koch's postulates (i.e., improvement in the disease after cure of the possible etiological organism), these data support H. pylori as being the etiological agent for carditis in this group of patients.

Although significant advances have been made in our understanding of Barrett's esophagus (BE), several questions remain. The answers will affect the way BE is defined, identified, monitored, and treated. This paper reviews the current definition of BE, the rationale for surveillance and risk stratification, the possible role of p53 mutations in adenocarcinoma, and the relationships among metaplasia, dysplasia, and adenocarcinoma.

Objective: The present study aimed to assess the cost-effectiveness of endoscopic screening in patients with gastroesophageal reflux disease (GERD) to rule out high-grade dysplasia of Barrett's esophagus., Methods: Using an incremental cost-effectiveness ratio as outcome measure, the cost-effectiveness of endoscopic screening was compared to not screening in a decision tree. It was assumed that GERD patients at age 60 yr undergo a one-time endoscopy with esophageal biopsies, targeting abnormal-appearing epithelium. Positive biopsies with respect to high-grade dysplasia or early esophageal adenocarcinoma result in esophagectomy. Transition rates were estimated from U.S. cancer statistics, as well as published data of endoscopic sensitivity, specificity, and surgical outcome. Costs of screening and cancer care were estimated from Medicare reimbursement data from the perspective of a third-party-payor., Results: Compared with no screening, screening endoscopy cost $24,700 per life-year saved. The cost-effectiveness of screening is quite sensitive to the prevalence of Barrett's esophagus, high-grade dysplasia, and adenocarcinoma, as well as the sensitivity, specificity, and cost of screening endoscopy. A small drop in the health-related quality of life associated with postsurgical states markedly reduced the effectiveness of screening. Simultaneous variations of the prevalence, specificity, and health-related quality of life can easily change screening endoscopy from a life-saving into a life-losing strategy., Conclusions: Under favorable conditions, general screening by endoscopy of all patients with reflux symptoms to prevent death from esophageal adenocarcinoma may represent a cost-effective strategy; however, such conditions may be difficult to meet.

Barrett esophagus continues to intrigue investigators and clinicians alike as the new millennium begins. A large number of publications in the past year have discussed issues of epidemiology, prevalence, detection, and treatment of Barrett esophagus. Chronic symptoms of gastroesophageal reflux were identified as a strong risk for esophageal adenocarcinoma. The relative frequency of short and long Barrett and cardia intestinal metaplasia in patients who undergo upper endoscopy have been better defined. Biomarkers in patients with Barrett may eventually be helpful in identifying those at high risk for the development of neoplasia. High-dose proton pump inhibition to the point of near elimination of esophageal acid exposure remains disappointing in its impact on the surface area of Barrett. Finally, the developments in endoscopic therapy for patients with Barrett esophagus continue to be promising.

Objective: Recent studies have found a relatively high prevalence of gastric cardia intestinal metaplasia in individuals presenting for elective upper endoscopy. It has been hypothesized that this lesion may be a precursor of gastric cardia cancer. Our objective was to identify the incidence of dysplasia in patients with gastric cardia intestinal metaplasia., Methods: Twenty-eight patients who had previously been identified with cardia intestinal metaplasia had follow-up examinations performed. None of the patients had dysplasia at the time of diagnosis. All had an examination at 1 yr, and 20 patients had an examination at 3 yr after diagnosis. During follow-up examinations all patients underwent vital staining with methylene blue to help identify areas of intestinal metaplasia in the cardia. Two to four biopsies were taken from blue-stained mucosa. Histological specimens were stained using a combination of hematoxylin and eosin with Alcian blue at pH 2.5., Results: There were 27 men and one woman with a mean age of 69.8 yr (range, 48-83 yr). The mean length of follow-up was 2.5 yr (range, 12-46 months). Only one patient was diagnosed with dysplasia (low-grade) during the study, for an incidence of 1.4% per yr., Conclusions: The prevalence (0%) and incidence (1.4%/yr) of dysplasia in cardia intestinal metaplasia are low. Although further studies are needed, screening and surveillance for gastric cardia intestinal metaplasia is unlikely to be clinically useful for the prevention of gastric cardia cancer.

Background: Normalization of oesophageal acid exposure using high dose proton pump inhibitors in patients who are candidates for ablation therapy has been suggested to be essential for successful Barrett's reversal. However, the success rate for achieving pH normalization has not been determined., Methods: Patients with Barrett's oesophagus (2-6 cm in length) who were found to be eligible for ablation therapy using multipolar electrocoagulation were included in this prospective study. Patients underwent an upper endoscopy to determine Barrett's length and other anatomic characteristics. Biopsies were obtained to rule out dysplasia. Subsequently, patients were treated with omeprazole 40 mg b.d. Twenty-four hour oesophageal pH monitoring was performed after a mean period of 8.4 +/- 0.6 days of therapy., Results: Twenty-five patients were enrolled into the study. The pH test was abnormal in four (16%) of the study subjects. An additional two (8%) patients had abnormal supine percentage time with pH less than 4. There was no significant difference in oesophageal acid control between patients with long vs. short segment Barrett's oesophagus. Elderly (> 60 years) patients tended to have less acid control than younger (

Background: Ambulatory 24-h oesophageal pH monitoring and a short course of high dose omeprazole can be used as diagnostic modalities for GERD. However, comparative studies of the diagnostic accuracy and reliability of both strategies have not been performed., Aim: To compare the omeprazole test to ambulatory 24-h oesophageal pH monitoring in diagnosing GERD in symptomatic patients using endoscopically proven erosive oesophagitis as a gold standard., Methods: Patients with heartburn underwent an upper endoscopy. Only those with erosive oesophagitis were included in the study. Subsequently, patients underwent ambulatory 24-h oesophageal pH monitoring and an 'omeprazole test.' Daily symptoms were recorded during the first week (baseline) and repeated during the second week on therapy (omeprazole 40 mg in the morning and 20 mg in the evening)., Results: Thirty-five patients were included in the study. The omeprazole test was significantly more sensitive in diagnosing GERD than total acid contact time on 24-h oesophageal pH monitoring (83% vs. 60%; P < 0.03). However, the sensitivity of the pH test increased to 80% after adding patients with a positive symptom index, and patients with abnormal acid exposure in the supine or erect positions despite normal total acid contact time. Patients with a normal pH test were significantly younger (49 +/- 2.6 years) than those with abnormal test (59 +/- 1.8; P=0.002)., Conclusions: In this study an omeprazole test was at least as sensitive as ambulatory 24-h oesophageal pH monitoring in diagnosing GERD in patients with erosive oesophagitis.

Background: Omeprazole was replaced by lansoprazole as the only proton pump inhibitor on the Veterans Affairs (VA) formulary in February 1997. We aimed to assess the clinical and fiscal impact of this conversion at two VA hospitals., Methods: We identified lansoprazole intolerant patients using pharmacy databases. We reviewed medical records to obtain data regarding reasons for lansoprazole intolerance. The costs of the formulary change and the savings to the VA were calculated., Results: A total of 3833 patients required long-term proton pump inhibitor therapy; 2224 (58%) were started on lansoprazole and 1479 (39%) were converted from omeprazole to lansoprazole. The remaining 130 (3.4%) patients were never converted from omeprazole to lansoprazole. Of the 3833 patients, 325 (8.5%) currently receive omeprazole therapy; of these, 195 out of 3703 (5.3%) patients are true lansoprazole failures; 172 of these 195 patients completed the study. Most (87%) of the lansoprazole intolerant patients received prior omeprazole. Discontinuation of lansoprazole was due to poor symptom control in 69% and/or side-effects (22%) including diarrhoea (10%), abdominal pain (5%), or hives (1%). The 1-year cost of managing lansoprazole failure in 195 patients was $61 690. However, the savings to the VA during the same time period, which totalled $321 360, more than offset the costs associated with the conversion., Conclusions: Lansoprazole intolerance requiring omeprazole conversion occurred in 5% of veterans on proton pump inhibitor therapy for chronic gastro-oesophageal reflux disease (GERD) symptoms and in 10% of patients with prior omeprazole success. The VA realized substantial cost savings in association with the formulary change.

Background and Study Aims: The presence of squamous epithelium in the stomach has been rarely noted in the past with only sporadic case reports of squamous cell carcinoma of the stomach and a variety of other pathological processes. We report the documentation, over a period of 9 months, of squamous epithelium extending beyond the esophagogastric junction and into the proximal stomach in 16 patients who underwent upper endoscopy., Patients and Methods: This newly recognized mucosal abnormality was systematically identified by both antegrade and retrograde views of the esophagogastric junction during routine upper endoscopy. Other associated mucosal abnormalities were also evaluated (Barrett's esophagus, erosive esophagitis, etc.). Biopsies were obtained from the distal esophagus, cardia, antrum and the squamous extension. Additionally, all patients underwent a detailed interview., Results: Of the patients, 14 were Caucasian and two Hispanic; all were males, with a mean age 61.2+/-4.2. Indications for upper endoscopy included dysphagia, Barrett's esophagus surveillance, failure of antireflux treatment and anemia. Heartburn was reported by 12 patients (75%). None of the patients reported a history of corrosive injury, foreign body ingestion or surgery. A total of 12 patients had a solitary tongue of squamous cell extension, three had two tongues and in addition, two had squamous islands. Hiatal hernia was present in all patients, Barrett's esophagus in six (37.5 %), and esophageal stricture in four., Conclusion: Squamous cell extension into the proximal stomach is a newly recognized mucosal abnormality with presently unknown clinical significance. This mucosal abnormality may represent an esophageal mucosal response to proximal gastric injury.

The goals of treatment of Barrett's esophagus (BE) include relieving reflux symptoms, healing inflammatory lesions, and preventing esophageal adenocarcinoma. Reduction of acid reflux is believed to prevent progression of BE. A critical question is whether or not regression of BE occurs in response to therapy with proton pump inhibitors. The natural history of BE is altered both by the use of medications (over-the-counter or prescribed) and by endoscopic surveillance with periodic biopsies. Regression occurs when the length and surface area of BE decreases, along with the emergence of islands of squamous epithelium in the BE segment. However, the extent of regression is difficult to assess because intestinal metaplasia may underlie the islands of squamous epithelial regrowth. Sampling by endoscopic biopsy is useful in ruling out progression of BE to dysplasia or adenocarcinoma; however, complete regression of the lesion cannot be definitively proven by this technique. To date, published clinical trials of proton pump inhibitor therapy in patients with BE provide evidence of increases in squamous islands in the BE segment, but do not provide convincing data in support of complete regression of BE. In a review of prospective studies of the treatment of BE with proton pump inhibitors (PPIs) (with or without surgery), only 3 of 123 patients had apparent complete reversal of BE. This article reviews the current understanding of regression in BE following treatment with PPIs.