Barrett's esophagus: prevalence-incidence and etiology-origins.

Although the prevalence of Barrett's esophagus (BE) is rising no data exist for racial minorities on prevalence in the general population. Minorities have a lower prevalence than Caucasians, and yet age, smoking, abdominal obesity, and Helicobacter pylori are all risk factors. Metabolic changes induced by adipocytokines and the apparently strong association between obesity, central adiposity, and BE may lead to reconsideration of some aspects of the natural history of BE. There is lack of experimental evidence on acid sensitivity and BE, which is hyposensitive compared to esophageal reflux disease. Reactive nitrogen and oxygen species lead to impaired expression of tumor suppressor genes, which can lead to cancer development; thus, antioxidants may be protective. Gastroesophageal reflux disease may be considered an immune-mediated disease starting at the submucosal layer; the cytokine profile of the mucosal immune response may explain the different outcome of gastroesophageal reflux.

Barrett's esophagus: endoscopic treatments II.

The following on endoscopic treatments of Barrett's esophagus includes commentaries on animal experiments on cryotherapy; indications for cryotherapy, choice of dosimetry, number of sessions, and role in Barrett's esophagus and adenocarcinoma; recent technical developments of RFA technology and long-term effects; the comparative effects of diverse ablation procedures and the rate of recurrence following treatment; and the indications for treatment of dysplasia and the role of radiofrequency ablation.

Barrett's esophagus: treatments of adenocarcinomas II.

The following topics are explored in this collection of commentaries on treatments of adenocarcinomas related to Barrett's esophagus: the importance of intraoperative frozen sections of the margins for the detection of high dysplasia; the preferable way for sentinel node dissection; the current role of robotic surgery and of video-endoscopic approach; the value of the Siewert's classification of adenocarcinomas; the indications of two-step esophagectomy; the evaluation of pathological complete response; the role of PET scan in staging and response assessment; the role of p53 in the selection of adenocarcinomas patients; chemotherapy regimens for adenocarcinomas; the use of monoclonal antibodies in the control of cell proliferation; he attempt to define a stage-specific strategy, and the possible indications of selective therapy; and changes in mortality rates from esophageal cancer.

Barrett's esophagus: natural history.

The following on the natural history of Barrett's esophagus (BE) includes commentary on histological sequences of the development of Barrett mucosa; the transformation of esophageal cells from squamous to columnar phenotype; the stages of natural history of dysplasia; the difficulties of predicting progression of dysplasia to adenocarcinoma; the preferable biopsy protocols; the role of Helicobacter pylori infection and gastric atrophy in the risk of BE; the value of decrease of proton pump inhibitor efficacy following eradication of H. pylori; the place of antireflux surgery in the natural history of BE; the newest procedures for the endoscopic detection of early neoplasia; and the essential importance of a good understanding of the natural history for the best management of high-grade dysplasia.

Randomized phase II trial of sulindac, atorvastatin, and prebiotic dietary fiber for colorectal cancer chemoprevention.

Sulindac, atorvastatin, or prebiotic dietary fiber may reduce colorectal cancer (CRC) risk. However, clinical trial data are currently limited. We conducted a randomized, phase II chemoprevention trial involving subjects 40 years or older, with previously resected colon cancer or multiple/advanced colorectal adenomas. Magnification chromoendoscopy (MCE) was performed to identify and characterize rectal aberrant crypt foci (ACF); eligibility criteria required five or more rectal ACFs at baseline. Intervention assignments were as follows: (a) atorvastatin 20 mg qd; (b) sulindac 150 mg bid; (c) oligofructose-enriched inulin (as ORAFTI®Synergy1) 6 gm bid; or (d) control (maltodextrin) 6 gm bid, for 6 months. Percent change in rectal ACF number (%ΔACF) within arm was the primary endpoint. Secondary endpoints included changes in proliferation (Ki67) and apoptosis (caspase-3), as measured from normal mucosa biopsy samples. Among 85 eligible randomized subjects, 76 (86%) completed the trial per protocol. The median (range) of rectal ACF was 9 (5-34) and 8 (0-37) at baseline and postintervention, respectively. The median (SD) for %ΔACF was 5.6 (-69% to 143%), -18.6 (-83% to 160%), -3.6 (-88% to 83%), and -10.0 (-100% to 117%) in the atorvastatin, sulindac, ORAFTI®Synergy1 and control arms, respectively. Neither within-arm (P = 0.12-0.59) nor between-arm (P = 0.30-0.92) comparisons of %ΔACF were statistically significant. The active and control interventions also seemed to have similar effects on mucosal proliferation and apoptosis (P > 0.05 for each comparison). Data from this multicenter, phase II trial do not provide convincing evidence of CRC risk reduction from 6-month interventions with atorvastatin, sulindac, or ORAFTI®Synergy1, although statistical power was limited by the relatively small sample size.

Non-cardiac chest pain: the long-term natural history and comparison with gastroesophageal reflux disease.

OBJECTIVES: The source of most cases of non-cardiac chest pain (NCCP) is thought to be the esophagus. We reasoned that if the origin of NCCP is truly esophageal and not cardiac, the characteristics and survival of individuals with NCCP should be similar to those of individuals with benign esophageal disease, such as gastroesophageal reflux disease (GERD). The aim of this study was to compare the characteristics, natural history, and long-term survival of two well-defined groups, NCCP patients and GERD patients. METHODS: From 1984 to 1996, patients with NCCP were referred for endoscopy by the cardiology service after a coronary angiography done for chest pain was reported by the cardiologist as negative. Patients with GERD were referred for endoscopy for one of the usual symptoms of acid reflux. The baseline endoscopy and referrals occurred in the pre-proton pump inhibitor (PPI) era, before and during the availability of only the histamine receptor antagonists (HRAs). Thus, the endoscopic findings reflected the untreated natural state of the gastrointestinal mucosa. Endoscopic exams, esophageal biopsy, endoscopic anatomy mapping, and data verification were carried out in the endoscopy lab by one of three endoscopists using predefined criteria. All results were recorded both by hand and by entry into a database storage program. Patients were followed by their primary care providers in their usual outpatient general medicine clinics. The Veterans Affairs Decentralized Hospital Computer Program (VA DHCP) storage system provided access to mortality data as well as details of all prescriptions filled since 1985. RESULTS: During the 12-year enrollment period, 1,218 patients in the GERD group and 161 in the NCCP group were referred for endoscopy. The follow-up period ranged from 1-22 years (mean 9.8 years). The groups were similar in age, gender, smoking and alcohol habits, and use of aspirin and NSAIDs (non-steroidal anti-inflammatory drugs) (P=NS), but there was a greater proportion of blacks in the NCCP group (P<0.003). In every parameter, NCCP patients had a significantly lower prevalence of GERD-related findings such as endoscopic esophagitis (P<0.0001), Barrett's metaplasia (P=0.02), the development of esophageal adenocarcinoma, and hiatal hernia presence (P=0.0001). In patients with hiatal hernia, the size of the hernia was similar in both groups (P=0.94). In the NCCP group compared with the GERD group, there was a significantly higher prevalence of cardiac factors, such as coronary artery disease (P=0.03), and there was a trend toward greater cardiac clinic enrollment (P=0.08) and cardiac medication usage (P=0.06). The amount and duration of anti-GERD therapy, such as HRAs and PPIs, were significantly less in the NCCP group (P=0.0001 for PPIs and P=0.0002 for HRAs). The diagnosis of NCCP disappeared from the electronic hospital record in 96% of patients within 2 years of follow-up. There was no significant difference in survival between the GERD and NCCP groups (hazard ratio=1.1; CI=0.8-1.5); however, longer duration of follow-up in those with a greater number of events may make a difference in survival. CONCLUSIONS: NCCP in most patients seems to be a short-lived event requiring extensive medical evaluation and having clinical characteristics significantly different from those associated with GERD. Patients with NCCP, confirmed by the absence of angiogram-documented coronary artery disease, who are referred for diagnostic endoscopy, have an excellent long-term benign prognosis, similar to patients with GERD.

Modeling using baseline characteristics in a small multicenter clinical trial for Barrett's esophagus.

OBJECTIVE: Utilizing data obtained during a multicenter investigation, this paper illustrates how the use of covariates and careful modeling techniques can be useful in assessing whether a negative outcome from a small multicenter clinical trial could be due to imbalance in baseline characteristics. The Chemoprevention for Barrett's Esophagus Trial (CBET) was a phase IIb, multicenter, randomized, placebo-controlled trial of celecoxib in patients with Barrett's esophagus. The primary outcomes for the original study were the proportion of biopsy samples exhibiting dysplasia in the celecoxib and placebo groups. The secondary and tertiary outcomes included histologic change and measurements of biologically relevant markers, including COX-1 and -2 mRNA, prostanoid levels, and methylation of tumor suppressor genes p16, APC, and E-cadherin. The original study reported no significant differences in primary, secondary or tertiary outcomes. In this paper, we focus on the results of one of the secondary measures, quantitative endoscopy (QE). DESIGN: The study utilizes data from 56 patients in the CBET for whom baseline (BL) QE and one-year follow-up QE (F04) studies were performed. Of these, 29 were treated with celecoxib (200 mg twice daily for a minimum of 48 weeks) and 27 received the placebo. These patients are segmented as to the presence or absence of circumferential, tongues or islands of Barrett's. MEASUREMENTS: The response of interest is total affected area at one year (Total F04); affected area at baseline (Total BL) is used as a covariate. RESULTS: Controlling for complexity and clinic, there is a significant treatment effect. In addition, there is significant evidence that the area of Barrett's involvement decreased for patients in the treatment group. CONCLUSIONS: That there was a decrease for the celecoxib over the placebo group adds to the body of evidence that relates COX-2 specific inhibitors and cancer incidence.

Quantitative endoscopy in the chemoprevention of Barrett's Esophagus Trial.

The Chemoprevention for Barrett's Esophagus Trial (CBET) was a phase IIb, multicenter, randomized, placebo-controlled trial of celecoxib in patients with Barrett's esophagus. The overall outcome of the study was that there were no significant differences in primary, secondary, or tertiary outcomes. The purpose of the current study is to focus on results related to the method of measuring lesion size called quantitative endoscopy (QE). The design includes a review of a total number of studies and then restricts analyses to the four clinics that enrolled more than four patients each for whom a baseline and 1-year QE study was performed, comparing intra- and inter-patient and clinic differences in Barrett's esophagus. Measurements include the number of total QEs and adverse events, changes in areas from baseline to 1 year and other intervals, classification of Barrett's lesion type with respect to patients, clinics, and treatment. A total of 309 QE studies were completed with no adverse events. Differences in surface area measurements over time for a particular patient are smaller than the differences for randomly selected patients. The complexity mix (as defined by the mix of circumferential, tongues, and islands) of the Barrett's lesions varied with different clinics. In conclusion, QE is an efficient, safe, and accurate way to measure the area of Barrett's lesions variation between different clinical sites may be attributable to a subtle type of selection bias at the individual clinics rather than to regional differences.

Five-year colon surveillance after screening colonoscopy.

BACKGROUND & AIMS: Outcomes of colon surveillance after colorectal cancer screening with colonoscopy are uncertain. We conducted a prospective study to measure incidence of advanced neoplasia in patients within 5.5 years of screening colonoscopy. METHODS: Three thousand one hundred twenty-one asymptomatic subjects, age 50 to 75 years, had screening colonoscopy between 1994 and 1997 in the Department of Veterans Affairs. One thousand one hundred seventy-one subjects with neoplasia and 501 neoplasia-free controls were assigned to colonoscopic surveillance over 5 years. Cohorts were defined by baseline findings. Relative risks for advanced neoplasia within 5.5 years were calculated. Advanced neoplasia was defined as tubular adenoma greater than > or =10 mm, adenoma with villous histology, adenoma with high-grade dysplasia, or invasive cancer. RESULTS: Eight hundred ninety-five (76.4%) patients with neoplasia and 298 subjects (59.5%) without neoplasia at baseline had colonoscopy within 5.5 years; 2.4% of patients with no neoplasia had interval advanced neoplasia. The relative risk in patients with baseline neoplasia was 1.92 (95% CI: 0.83-4.42) with 1 or 2 tubular adenomas <10 mm, 5.01 (95% CI: 2.10-11.96) with 3 or more tubular adenomas <10 mm, 6.40 (95% CI: 2.74-14.94) with tubular adenoma > or =10 mm, 6.05 (95% CI: 2.48-14.71) for villous adenoma, and 6.87 (95% CI: 2.61-18.07) for adenoma with high-grade dysplasia. CONCLUSIONS: There is a strong association between results of baseline screening colonoscopy and rate of serious incident lesions during 5.5 years of surveillance. Patients with 1 or 2 tubular adenomas less than 10 mm represent a low-risk group compared with other patients with colon neoplasia.

The long-term natural history of gastroesophageal reflux disease.

INTRODUCTION: Long-term gastric acid suppression has been suggested as a means to prevent complications of reflux esophagitis. We report on the 20-year follow-up of 2,306 patients with at least two endoscopic examinations who were taking no antisecretory medication before baseline endoscopy and whose long-term treatment was determined by reflux symptoms. METHODS: From 1979 through 1998, endoscopy and biopsy were performed in the Hines Veterans Affairs Hospital endoscopy clinic by three endoscopists. Antireflux treatment was symptom-driven, and endoscopies were repeated mostly for symptomatic recurrence due to cessation of therapy. RESULTS: Of 4,633 patients undergoing endoscopy for reflux symptoms, 2,306 had at least one follow-up endoscopy and biopsy. Over a mean follow-up period of 7.6 years (range, 1-20 years), the esophageal mucosa of 67% of patients remained unchanged, that of 21% improved, and that of 11% worsened. Esophageal stricture requiring dilation developed from a normal baseline mucosa in one of 1,313 patients (0.08%) and from an erosive baseline mucosa in 18 of 957 patients (1.9%). The overall incidence of stricture in patients with gastroesophageal reflux (GER) disease was <1/1,000 per year. Nonsteroidal anti-inflammatory drug (NSAID) consumption was associated with less mucosal improvement (odds ration [OR] = 0.67; confidence interval [CI] = 0.46-0.98). Use of histamine-2 receptor antagonists (H2RAs) and proton pump inhibitors (PPIs) was associated with mucosal improvement (OR for PPIs = 1.49; CI = 1.14-2.17). Cohn's kappa was 42%, confirming the results that demonstrate stability of esophageal mucosal disease in the majority of patients. CONCLUSIONS: Symptom-driven treatment of GER disease after a thorough endoscopic examination to exclude premalignant or malignant esophageal mucosal disease is practical and safe for the vast majority of patients with uncomplicated GER symptoms.

Treatment of patients with persistent heartburn symptoms: a double-blind, randomized trial.

BACKGROUND & AIMS: Common treatment practices in patients who continue to be symptomatic on proton pump inhibitor once-daily treatment include either increasing the dosage or the use of supplemental medication. This trial's purpose was to compare 2 therapeutic strategies, increasing the proton pump inhibitor dosage to twice daily versus switching to another proton pump inhibitor, in patients with persistent heartburn while receiving standard-dose proton pump inhibitor therapy. METHODS: This multicenter, randomized, double-blind, double-dummy trial included patients with persistent heartburn symptoms while receiving therapy with lansoprazole 30 mg once daily. Patients were randomly assigned to treatment for 8 weeks with either single-dose esomeprazole (40 mg once daily) (n = 138) or lansoprazole 30 mg twice daily (n = 144). The primary efficacy variable was the percentage of heartburn-free days from day 8 to the end of treatment. RESULTS: Single-dose esomeprazole was at least as effective as twice-daily lansoprazole for the primary end point of percentage of heartburn-free days during the study period (54.4% and 57.5%, respectively). Symptom scores improved from baseline in similar numbers of patients for heartburn (83.3% of patients in each group), acid regurgitation (76.8% vs 72.9%, P = .58), and epigastric pain (67.4% vs 61.1%, P = .32), and rescue antacid use was also similar (0.4 tablets/day vs 0.5 tablets/day, P = .50). CONCLUSIONS: Switching patients with persistent heartburn on a standard-dose proton pump inhibitor to a different proton pump inhibitor was as effective as increasing the proton pump inhibitor dosage to twice daily for controlling heartburn symptoms.

The spectrum of pulmonary symptoms due to gastroesophageal reflux.

Most asthmatics have GER, and the evidence is strong that GER plays an important role in some patients who have asthma. Despite sophisticated study methods and technologically advanced diagnostic tests, the results of published studies on mechanisms have failed to provide a diagnostic test with a degree of certainty great enough to identify which patients have GER-induced or GER-exacerbated asthma and which patients will respond to antireflux therapy. The difficulties involved in establishing a definite cause-and-effect relationship between GER and asthma are real. Even positive results on such direct tests as sputum inspection and scintigraphic monitoring, both of which establish reflux into the tracheobronchial tree, do not necessarily establish cause or effect and cannot be used to predict outcomes. Ambulatory esophageal pH testing can suggest, but cannot prove, the diagnosis of GER-induced asthma, and pH testing cannot be relied on safely to make clinical decisions. A trial of a proton pump inhibitor (PPI) is indicated to assess if asthma improves subjectively and objectively, but the dose must be high enough to prevent even silent esophageal acid exposure, and the duration must be long enough to allow for detection of even subtle trends in subjective and objective respiratory improvement. Antireflux surgery remains a therapeutic option and should not be withheld if GER is a reasonable suspect in asthma exacerbations. Although strong opinions have been voiced as to whether or not a good response to PPI therapy predicts a good response to antireflux surgery, the opinions, although logical, are based on personal experience and gut feelings; a good PPI response may not necessarily predict a good surgery response. Opinions suggesting that a poor response to PPI predicts a poor response to antireflux surgery also may seem logical but are not based on clinical data; a poor PPI response may not necessarily predict a poor antireflux surgery response. When the method is found that predicts which patients who have GER and asthma will respond to antireflux treatment, the results could be profound: fewer hospitalizations for respiratory complications, less pulmonary morbidity and mortality, less need for pulmonary medications, less time lost from work, fewer visits to physicians' offices, and less illness associated with corticosteroid therapy. For the present, however, clinical judgment and good sense still are our best friends. It is not unreasonable to urge patients to alter their lifestyle: the huge volume, calorie-dense, high-fat meals eaten before bedtime are not likely to prevent GER or add to their life expectancy.

Asthmatics have more nocturnal gasping and reflux symptoms than nonasthmatics, and they are related to bedtime eating.

OBJECTIVES: Certain pulmonary diseases are now recognized as possible complications of gastroesophageal reflux (GER) disease. To further clarify the relationship between GER and asthma, we determined the prevalence, nature, and patterns of reflux symptoms in consecutive asthmatics and a well-defined patient population control group. METHODS: Two hundred and sixty-one asthmatic outpatients with well-documented asthma were interviewed in person using an extensive questionnaire. To avoid selection bias, we (a) used no selection criteria other than asthma, (b) interviewed every identified asthmatic from either the outpatient general medical clinic or pulmonary clinic (and excluded the gastroenterology clinic), and (c) excluded asthmatics referred because of gastrointestinal symptoms. A control group comprised 218 consecutive outpatients chosen from the same general medical clinics in which the asthmatics were enrolled. Interviews were conducted by one of two investigators. RESULTS: The control and asthmatic groups were similar with regard to age, gender, ethnicity, and consumption of tobacco and alcohol. There were major significant differences between the asthmatics and controls with regard to the age of onset of pulmonary and reflux symptoms, prevalence of eating before bedtime, prevalence of reflux symptoms, the quality of reflux symptoms, and the factors that promote and relieve reflux symptoms. Heartburn, regurgitation, and dysphagia were present in 71%, 45%, and 22% of asthmatics compared with 51%, 30%, and 5% of controls (p < 0.001). Three times as many asthmatics as controls had heartburn occurring throughout the day and night (OR; 95% CI: 19.5; 4.5-85.7), and three times as many asthmatics as controls had sudden nocturnal awakening with reflux symptoms and reflux-associated pulmonary symptoms that occurred simultaneously with the reflux symptoms (p < 0.001). Within the asthma group, reflux symptoms were similar in those who required and those who did not require continuous bronchodilator therapy. In these asthmatics, however, those requiring continuous bronchodilator therapy (more severe asthma) developed pulmonary and GER symptoms at a significantly older age. Eating before bedtime was recognized by significantly more asthmatics than controls as a promoter of serious nocturnal GER symptoms (4.5; 2.7-7.7). In terms of patient awareness, one-third of the asthmatics with heartburn had previously considered a relationship between their reflux symptoms and their asthma. CONCLUSION: Compared to nonasthmatics, asthmatics have significantly more frequent and more severe day and night GER symptoms and significantly more of the pulmonary symptoms (nocturnal suffocation, cough, or wheezing) so often attributed to GER. The habit of eating before bedtime appears in asthmatics to have serious and life-threatening consequences.

Asthmatics with gastroesophageal reflux: long term results of a randomized trial of medical and surgical antireflux therapies.

OBJECTIVE: In short term studies, asthma symptoms and pulmonary function have been reported to improve during and after medical treatment or surgical correction of gastroesophageal reflux (GER). In this study, we aimed to determine whether prolonged treatment of GER altered the long term natural history of asthma in asthmatics with GER. METHODS: A total of 62 patients with both GER and asthma entered a randomized study of antireflux treatments for at least 2 yr: 24 controls (antacids as needed); 22 medical (ranitidine 150 mg t.i.d.); and 16 surgical (Nissen fundoplication). Asthma was defined as a previous diagnosis of asthma with discrete attacks of wheezing and 20% reversibility in airway disease. GER was defined as an abnormal ambulatory 24-h esophageal pH test and macroscopic or microscopic evidence of GER disease. Overall clinical status, asthma symptom scores, and pulmonary medication requirements were recorded monthly. Peak expiratory flow rates were recorded up to seven times per day for 1 wk of each month throughout the years. Pulmonary function, esophageal manometry, and endoscopy with biopsy were repeated yearly. RESULTS: The 62 patients were followed for up to 19.1 yr. In the surgical group, but not in the medical or control groups, there was an immediate and sustained reduction in acute nocturnal exacerbations of wheezing, coughing, and dyspnea. By the end of 2 yr, improvement, marked improvement, or cure in the overall asthma status occurred in 74.9% of the surgical group, 9.1% of the medical group and 4.2% of the control group, whereas the overall status worsened in 47.8% of the control group, 36.4% of the medical group, and 12.5% of the surgical group (p < 0.001, surgical vs medical and control). The mean asthma symptom score of the surgical group improved 43%, compared with less than 10% in the medical and control groups (p = 0.0009). As determined by changes in peak expiratory flow rates, there was no statistically significant difference in pulmonary function during the 2-yr period or during regularly scheduled follow-up. There was no difference in medication requirements among the groups. There was no difference between the groups in overall survival. CONCLUSION: In patients with both GER and asthma, antireflux surgery (but not medical therapy with ranitidine 150 mg t.i.d.) has minimal effect on pulmonary function, pulmonary medication requirements, or survival, but significantly improves asthma symptoms and overall clinical status.

Persistent gastroesophageal reflux disease symptoms on standard proton-pump inhibitor therapy.

Eight patients with refractory GERD symptoms were controlled over a mean of 15.4 years only by the addition of a benzodiazepine to once-daily or twice-daily PPI therapy. In selected patients with refractory GERD, as defined by continued reflux symptoms despite twice-daily PPIs, the addition of a benzodiazepine to the PPI regimen may provide additional control of GERD symptoms.

Acid reflux is a poor predictor for severity of erosive reflux esophagitis.

It is unknown which factors determine the severity of mucosal damage in gastroesophageal reflux disease (GERD). Our aim was to test whether the amount of esophageal acid exposure could predict the severity of esophageal injury in erosive reflux esophagitis. A total of 644 outpatients with symptomatic GERD underwent an esophagogastroduodenoscopy followed by esophageal manometry and 24-h pH monitoring. GERD was graded according to the endoscopic severity of mucosal damage as no erosions, single erosions, confluent erosions, esophageal ulcers, and strictures. A multiple linear regression was used to assess the joint influences of demographic characteristics, social habits, endoscopic anatomy, and various parameters of esophageal function tests on the severity of erosive reflux disease. No clear-cut association between the amount of acid reflux and the severity of erosive reflux esophagitis could be established. All individual parameters of esophageal pH monitoring, such as upright or supine acid contact time, frequency of all or only long reflux episodes, and an overall summary score of pH-metry, revealed no or only a weak correlation with the severity grade of erosive reflux esophagitis. Similarly, the pressure of the lower esophageal sphincter was only slightly more decreased in patients with extensive erosive esophagitis as compared to subjects without esophageal erosions. In the multiple linear regression, the presence of hiatus hernia was a stronger predictor of disease severity than any of the other parameters. In conclusion, factors other than exposure of the esophageal mucosa to acid must contribute to the development of erosive esophagitis.

Hiatal hernia size, Barrett's length, and severity of acid reflux are all risk factors for esophageal adenocarcinoma.

OBJECTIVE: The reasons for the development of dysplasia and adenocarcinoma in Barrett's mucosa are not well understood. The aims of this study were to characterize risk factors for the transition from Barrett's esophagus without dysplasia to Barrett's esophagus with high-grade dysplasia or esophageal adenocarcinoma. METHODS: A group of 131 patients with high-grade dysplasia or esophageal adenocarcinoma were selected as case subjects. A first population of 2170 patients without gastroesophageal reflux disease (GERD) and a second population of 1189 patients with Barrett's esophagus served as two control groups. Logistic regression analyses were used to compare the risk factors associated with the occurrence of high-grade dysplasia or esophageal adenocarcinoma. RESULTS: Patients with high-grade dysplasia or esophageal adenocarcinoma shared many characteristics with other forms of severe GERD, such as older age, male gender, and white ethnicity. The length of Barrett's esophagus and the size of hiatus hernia increased the risk for both conditions. Subjects with high-grade dysplasia and adenocarcinoma had more severe acid reflux than patients with other forms of GERD. Smoking and alcohol consumption did not affect the risk for developing high-grade dysplasia or adenocarcinoma in patients with Barrett's esophagus. CONCLUSIONS: High-grade dysplasia and esophageal adenocarcinoma seem to stem from an extreme and unfavorable constellation of all risk factors that are generally held responsible for the development of GERD and Barrett's esophagus.