Thomas G. Schnell

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 Barretts mucosa are not well understood. The aims of this study were to characterize risk factors for the transition from Barretts esophagus without dysplasia to Barretts 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 Barretts 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 Barretts 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 Barretts 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 Barretts esophagus.

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.

Hiatal hernia and acid reflux frequency predict presence and length of Barrett's esophagus.

One third of the general population may experience reflux symptoms, yet only a small fraction of patients with gastroesophageal reflux disease (GERD) have Barretts esophagus. The aim of the present study was to compare the characteristics of GERD patients with and without Barretts esophagus and identify potential risk factors for the appearance of Barretts esophagus in reflux disease. Outpatients from a gastroenterology clinic who underwent upper gastrointestinal endoscopy, esophageal manometry, and 24-hr pH monitoring were recruited into a case-control study. A total of 256 case subjects with endoscopically and histologically proven Barretts esophagus were compared to a control group of 229 subjects with nonerosive reflux disease. As compared to nonerosive reflux disease, Barretts esophagus was strongly associated with more reflux episodes. Barretts esophagus occurred more frequently among subjects with hiatus hernia and among subjects who consumed large amounts of alcohol or cigarettes. Frequent reflux episodes, hiatus hernia, smoking, and alcohol consumption were also risk factors for an increased length of Barretts mucosa. Total esophageal mucosal acid contact time at pH < 4 was a significant risk factor for the length but not the presence of Barretts esophagus. Intake of aspirin or NSAIDs was similar in patients with and without Barretts esophagus. In conclusion, in comparison with nonerosive reflux disease, Barretts esophagus is characterized by risk factors usually indicative of severe types of GERD. Mechanisms in addition to acid reflux must contribute to the development of Barretts esophagus.

The importance of hiatal hernia in reflux esophagitis compared with lower esophageal sphincter pressure or smoking.

The characteristics of gastroesophageal reflux disease have not been adequately defined. To determine the influence on the esophageal mucosa of hiatal hernia, lower esophageal sphincter pressure, acid reflux, and cigarettes and alcohol, we studied the reflux parameters, smoking habits, and alcohol consumption of 184 healthy, ambulatory outpatients who received endoscopy as the initial diagnostic procedure for workup of gastroesophageal reflux. Patients received endoscopic and histologic evaluations of the esophageal mucosa, prolonged ambulatory esophageal pH monitoring, and esophageal manometric determinations. Structural analysis was used to test the plausibility of various clinical theories concerning the most important factors contributing to the development of esophagitis. Statistical analyses revealed the following: (a) the lower esophageal sphincter pressure, acid contact time, and frequency of reflux episodes were highly associated with the presence of a hiatal hernia (p less than 0.003 for all parameters); (b) individuals with esophagitis had 16.5 times as many hiatal hernias as found in normal, healthy people; (c) cigarette smoking was not correlated with esophagitis but was significantly associated with increased lower esophageal sphincter pressure (r = 0.18; p less than 0.03); and (d) smoking was also not associated with increased acid contact time or increased frequency of reflux episodes. We conclude that (a) the presence of a hiatal hernia, not the pressure of the lower esophageal sphincter, is the most important predictor of reflux frequency, acid contact time, and esophagitis; (b) a decreased lower esophageal sphincter pressure, as suggested by structural analysis, is unlikely to be the cause of increased reflux episodes or esophagitis; and (c) if smoking and lower esophageal sphincter pressure are factors in the development of esophagitis, they damage the esophageal mucosa by mechanisms other than increased frequency of reflux episodes or increased acid contact time.

New occurrence and recurrence of neoplasms within 5 years of a screening colonoscopy

OBJECTIVE:The fear that colorectal adenomas were missed on initial colonoscopy or that new adenomas have developed is often a rationale for repeating a colonoscopic examination. The aim of this study was to delineate risk factors associated with recurrence of colorectal adenomas after an initial baseline screening colonoscopy.METHODS:The study population comprised 875 subjects who underwent a baseline screening colonoscopy followed by a second examination 1–5 yr later. Multiple logistic regression was used to assess the influence of potential risk factors on the occurrence or recurrence of colorectal adenomas, the strength of the influence being expressed as an OR with a 95% CI.RESULTS:Colorectal adenomas were detected in 484 of all patients (55%) at baseline colonoscopy. Within a 1- to 5-yr time interval, 181 patients (37%) had recurrent adenomas (adenomas were removed during the first colonoscopy) and 73 patients (19%) had newly developed adenomas (adenomas were absent on the first colonoscopy). The occurrence of adenomas at baseline screening colonoscopy was the only factor associated with an increased risk for the recurrence of adenomas at follow-up (OR = 2.51, 95% CI = 1.77–3.55). Recurrence was associated with multiple baseline adenomas (4.45, 2.98–6.64) and baseline adenomas larger than 1 cm (2.62, 1.99–3.11). Recurrence was not associated with histology type or family history of colorectal cancer. There was a significant trend for adenomas to recur in the same proximal or distal segment as the baseline adenomas (p = 0.02).CONCLUSIONS:Colon adenomas tend to recur with greater frequency if the adenomas removed at baseline were either large or multiple. Although patients with large adenomas or multiple adenomas at baseline screening colonoscopy are at a 2.6- to 4.5-fold risk for recurrence of adenomas, the rate of de novo adenoma formation in patients without baseline adenomas may be large enough to warrant repeat colonoscopy at some time in the future. The exact timing of the follow-up colonoscopy needs to be determined.

Risk factors for erosive reflux esophagitis: a case-control study

OBJECTIVES:It is presently not fully understood which risk factors contribute to the occurrence of reflux esophagitis and how such factors might influence the severity of the disease. The aim of this study was to delineate the clinical epidemiology of erosive reflux esophagitis.METHODS:Outpatients from a medicine and gastroenterology clinic who underwent upper GI endoscopy were recruited into a case-control study. A total of 1533 patients with and 3428 patients without endoscopically diagnosed reflux esophagitis were categorized as case and control subjects, respectively. Using multivariate logistic regressions for statistical analysis, the presence of esophageal erosions, ulcers or strictures, served as three separate outcome variables. Demographic characteristics, intake of nonsteroidal anti-inflammatory drugs (NSAIDs), consumption of alcohol and cigarettes, and the presence of hiatus hernia or peptic ulcer served as predictor variables.RESULTS:Erosive reflux esophagitis tended to occur more frequently in Caucasian male patients. Hiatus hernia was associated with a strong risk for developing esophageal erosions, ulcers, and strictures. Although statistical significance was demonstrated only for esophageal erosions, in all grades of reflux esophagitis alike, gastric and duodenal ulcer exerted a protective influence. Consumption of NSAIDs increased the risk for esophageal ulcers only. Smoking and alcohol were not associated with an increased risk of developing any type of erosive reflux esophagitis.CONCLUSIONS:The results stress the critical role played by hiatus hernia in all grades of erosive reflux esophagitis. NSAIDs may act through a mechanism of topically induced esophageal injury. Our data also suggest that the presence of either gastric or duodenal ulcer exerts a protective influence against the development of reflux disease.

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). Cohns 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.

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.

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), Barretts 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.

Risk factors of oesophagitis in arthritic patients.

Background The risk factors that precipitate the occurrence of oesophageal mucosal injury in patients on continuous nonsteroidal anti-inflammatory drug (NSAID) therapy are unknown. Methods Outpatients who regularly consumed NSAIDs for osteoarthritis were recruited from a rheumatology clinic into a prospective case–control study. All patients answered a structured interview and underwent upper gastrointestinal endoscopy. Results Of 450 eligible patients, 195 (43%) consented to be interviewed and undergo upper gastrointestinal endoscopy. Oesophagitis was diagnosed in 41 of these 195 patients (21%). The occurrence of gastric or duodenal ulcer in individual patients did not predict the concomitant damage of the oesophageal mucosa. Young age (odds ratio: 1.79 per decade of life; 95% confidence interval: 1.11–2.86) and hiatus hernia (odds ratio: 3.72; 95% confidence interval: 1.63–8.49) both increased the risk of developing oesophagitis. When questioned, all oesophagitis patients revealed at least one gastrointestinal symptom, heartburn being named most frequently (odds ratio: 4.78; 95% confidence interval: 2.04–11.17). The type of anti-inflammatory medication, the use of alcohol and the use of nicotine were not associated with any significant risk for erosive oesophagitis. Conclusions Patients on chronic NSAID therapy for rheumatological disease suffer frequently from erosive oesophagitis. While the risk may be higher in patients with a pre-existing tendency for gastro-oesophageal reflux, any concomitant history of NSAID-induced peptic ulcer disease does not add to the risk. Erosive oesophagitis should be considered especially in patients on NSAIDs who complain of heartburn.