Endoscopic ablative therapy for Barrett's esophagus: current status.
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Barrett Esophagus↗
Biomedical subjects
Richard E Sampliner
Publications and source records attributed to Richard E Sampliner.
Is the length of newly diagnosed Barrett's esophagus decreasing? The experience of a VA Health Care System.
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.
Age Distribution↗
Prevention of adenocarcinoma by reversing Barrett's esophagus with mucosal ablation.
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.
Adenocarcinoma↗
Multipolar electrocoagulation.
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.
Barrett Esophagus↗
Risk factors for dysplasia in patients with Barrett's esophagus (BE): results from a multicenter consortium.
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.
Adenocarcinoma↗
Long-term endoscopic surveillance of Barrett's esophagus.
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Adenocarcinoma↗
Progression or regression of Barrett's esophagus--is it all in the eye of the beholder?
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.
Barrett Esophagus↗
Barrett's oesophagus: optimal strategies for prevention and treatment.
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.
Adenocarcinoma↗
Appearance and prognosis of dysplasia in Barrett's esophagus.
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.
Adenocarcinoma↗
Impact of esophageal acid exposure on the endoscopic reversal of Barrett's esophagus.
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.
Adult↗
Relationship between rate of change in acid exposure along the esophagus and length of Barrett's epithelium.
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).
Adult↗
Acid suppression therapy may not alter malignant progression in Barrett's metaplasia showing p53 protein accumulation.
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.
Barrett Esophagus↗
Updated guidelines for the diagnosis, surveillance, and therapy of Barrett's esophagus.
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Barrett Esophagus↗