Maximal acid reflux control for Barrett's oesophagus: feasible and effective

The treatment of patients with Barrett's oesophagus is controversial. Debate exists regarding the use and value of high dose acid suppression as the standard of practice. Despite prolonged use of high dose proton pump inhibitors (40 mg omeprazole, 60 mg lansoprazole), most studies have shown no convincing evidence of significant regression of Barrett's length. These studies, however, have used fixed doses of proton pump inhibitors and did not regularly document control of oesophageal acid exposure. AIM: To determine whether regression of Barrett's epithelium can be achieved with documented maximal acid suppression. METHODS: We have prospectively followed nine patients with Barrett's oesophagus (eight male; mean age 60 years) for more than 1 year. They were all treated using medical therapy with pH monitoring documenting oesophageal acid exposure over 24 h < 1.6% of the time, and with two or more esophagogastroduodenoscopies performed by the same endoscopist. RESULTS: Acid control was individually tailored and achieved with proton pump inhibitor b.d. (omeprazole 20 mg or lansoprazole 30 mg) and ranitidine at bedtime (HS) (Ran) if necessary. All nine patients (100%) showed some evidence of regression. All nine patients (100%) showed a decrease in Barrett's length (mean 2 cm, range 1-3 cm). Six out of nine (66.67%) patients showed evidence of squamous islands on the last oesophagogastroduodenoscopy. The mean total distal oesophageal acid exposure was 0.38% (range: 0-1.5%). The mean follow-up of patients was 54 months (range: 13-118 months). CONCLUSIONS: Consistent and individually tailored maximal acid suppression documented by pH-metry is achievable and may result in decreased length and development of squamous islands in patients with Barrett's epithelium. This approach should be further evaluated as potentially the preferred medical treatment for these patients.     

Review article: Barrett's oesophagus, dysplasia and pharmacologic acid suppression

Barrett's oesophagus, a significant complication of gastro-oesophageal reflux disease (GERD), is the single most important risk factor for oesophageal adenocarcinoma. The strong association between Barrett's oesophagus and chronic GERD suggests that abnormal oesophageal acid exposure plays an important role in this condition. The progression of Barrett's oesophagus from specialized intestinal metaplasia to dysplasia and finally invasive carcinoma is incompletely understood, but increased and disordered proliferation is a key cellular event. In ex vivo organ culture experiments, cell proliferation is increased after exposure to short pulses of acid, whilst proliferation is reduced in Barrett's oesophagus specimens taken from patients with oesophageal acid exposure normalized by antisecretory therapy. In long-term clinical studies, consistent and profound intra-oesophageal acid suppression with proton pump inhibitors decreases cell proliferation and increases differentiation in Barrett's oesophagus, but the clinical importance of such favourable effects on these surrogate markers is not clear. In clinical practice, proton pump inhibitors relieve symptoms and induce partial regression to squamous epithelium, but abnormal oesophageal acid exposure and the risk for dysplasia or adenocarcinoma persist in many patients. The ability of proton pump inhibitors to suppress acid profoundly and consistently may be critical in the long-term management of Barrett's oesophagus.     

Failure of oesophageal acid control in candidates for Barrett's oesophagus reversal on a very high dose of proton pump inhibitor

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 (相似文献   

Lack of predictors of normalization of oesophageal acid exposure in 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.     

Oesophageal and gastric pH profiles in patients with gastro-oesophageal reflux disease and Barrett's oesophagus treated with proton pump inhibitors

BACKGROUND: Acid plays a significant role in the development of gastro-oesophageal reflux symptoms and tissue damage. It is generally assumed that acid suppressive therapy with proton pump inhibitors improves or eliminates symptoms of gastro-oesophageal reflux disease by normalizing intra-oesophageal pH. However, the degree of acid suppression induced by proton pump inhibitor therapy in patients with gastro-oesophageal reflux disease and/or Barrett's oesophagus has not been adequately studied. AIM: To assess the efficacy of proton pump inhibitors in normalizing intra-oesophageal and intra-gastric pH in patients with gastro-oesophageal reflux disease with and without Barrett's oesophagus who have been rendered symptom-free by acid-suppressive therapy. METHODS: Patients with gastro-oesophageal reflux disease and Barrett's oesophagus were prospectively evaluated by dual sensor 24-h pH monitoring while receiving proton pump inhibitor therapy for complete control of gastro-oesophageal reflux disease symptoms. Analyses and comparisons of intra-oesophageal and intra-gastric pH profiles on therapy were then made. RESULTS: One hundred and ten patients, 98 men and 12 women, with gastro-oesophageal reflux disease (n = 62) and/or Barrett's oesophagus (n = 48), were studied. All tolerated proton pump inhibitors well and were asymptomatic at the time of the study. Thirty-six (58%) patients with gastro-oesophageal reflux disease and 24 (50%) patients with Barrett's oesophagus (P = 0.4) normalized their intra-oesophageal pH profiles on proton pump inhibitors. Compared with patients with gastro-oesophageal reflux disease, patients with Barrett's oesophagus were more likely to have higher degree of pathologic acid reflux despite proton pump inhibitor therapy (DeMeester score 50.5 +/- 8.2 vs. 31.4 +/- 4.6, P = 0.03) and exhibited less intra-gastric acid suppression (% total pH < 4.0: 53.9 +/- 2.7 vs. 39.9 +/- 2.6, P = 0.0004), particularly supine (% pH < 4.0: 62.1 +/- 3.4 vs. 44.8 +/- 3.4, P = 0.0006). CONCLUSIONS: Gastro-oesophageal reflux disease patients with or without Barrett's oesophagus continue to exhibit pathologic gastro-oesophageal reflux disease and low intra-gastric pH despite proton pump inhibitor therapy that accomplishes complete reflux symptom control. Further, intra-oesophageal and intra-gastric pH control is significantly more difficult to achieve in patients with Barrett's oesophagus. These findings may have significant therapeutic implications.     

Persistence and adherence to proton pump inhibitors in daily clinical practice

BACKGROUND: Proton pump inhibitors are widely used, but little is known about the usage pattern in different indications. AIM: To analyse proton pump inhibitor usage patterns in the general population. METHODS: A cohort of 16 311 incident proton pump inhibitor users was identified in the Integrated Primary Care Information database, a Dutch general practice research database. Persistence and adherence were calculated by indication. Risk factors were identified by logistic regression analysis. RESULTS: One-year persistence was 31% in patients using proton pump inhibitors for gastro-oesophageal reflux. Persistence was higher in oesophagitis grade A/B (54%), grade C/D (73%) and Barrett's oesophagus (72%), compared to patients with only reflux symptoms (27%). Approximately 25% of patients with non-reflux dyspepsia or Helicobacter pylori-associated indications used proton pump inhibitors for more than 6 months. Half of all patients used proton pump inhibitors <80% of time indicating intermittent use, which was independent of indication. Exception were patients with Barrett's oesophagus, who were most adherent. CONCLUSIONS: A substantial proportion of patients with indications not requiring long-term treatment use proton pump inhibitors for an extended period. Half of the patients used proton pump inhibitors on-demand or intermittently. Such usage pattern is probably sufficient for most patients, but may be inadequate if proton pump inhibitors are used for serious diseases, such as severe oesophagitis or Barrett's oesophagus.     

Clinical experience of patients undergoing photodynamic therapy for Barrett's dysplasia or cancer

INTRODUCTION: Barrett's oesophagus is the most important risk factor in the increase in incidence of oesophageal adenocarcinoma. Photodynamic therapy using porfimer sodium is the only approved endoscopic treatment for use in patients with Barrett's high-grade dysplasia. AIM: To determine clinical characteristics, endoscopic findings and treatment complications in Barrett's high-grade dysplasia patients undergoing photodynamic therapy. METHODS: We reviewed our experience using porfimer sodium photodynamic therapy to treat patients with Barrett's oesophagus and high-grade dysplasia or mucosal carcinoma. Data collected included patients characteristics, presentation symptoms, endoscopic findings, subsequent use of surveillance endoscopy and outcome after photodynamic therapy. RESULTS: Since 1997, 102 patients with Barrett's high-grade dysplasia (69 patients) or mucosal adenocarcinoma (33 patients) have been treated with photodynamic therapy using porfimer sodium as an alternative to oesophagectomy (median series follow-up time = 1.6 years). Almost half (46%) of patients had high-grade dysplasia or carcinoma detected on their first endoscopy and the remainder (54%) were found during surveillance of known Barrett's oesophagus. Symptoms typically associated with oesophageal disease were only found in 29 of 47 (62%) patients in whom dysplasia/carcinoma was detected on the initial endoscopy - chest pain in 13 patients, dysphagia in nine patients and chronic gastro-oesophageal disease in seven patients. Comparison of endoscopic characteristics found the median Barrett's glandular segment length was significantly shorter in adenocarcinoma patients (median 3 cm; range: 1-12) vs. Barrett's high-grade dysplasia patients (median 5 cm; range: 1-16, P < 0.001). Overall treatment results found complete ablation of glandular epithelium with one course of photodynamic therapy in most patients (56%). Stricture requiring dilation occurred in 20 patients (20%) was the most common serious adverse event. Photodynamic therapy failed to ablate dysplasia or carcinoma in four patients and subsequent oesophagectomy was curative in three of these patients. CONCLUSIONS: Approximately 40% of newly diagnosed patients with Barrett's associated dysplasia or carcinoma had no oesophageal symptoms and had carcinoma associated with short segment (3 cm or less). Photodynamic therapy is a highly effective, safe and minimally invasive first-line treatment for patients with Barrett's dysplasia and mucosal adenocarcinoma.     

Daily use of non-steroidal anti-inflammatory drugs is less frequent in patients with Barrett's oesophagus who develop an oesophageal adenocarcinoma

BACKGROUND: Non-steroidal anti-inflammatory drugs use may protect against development of oesophageal adenocarcinoma. AIM: To define the consequences of non-steroidal anti-inflammatory drugs use in patients with Barrett's oesophagus. METHODS: Records of all Barrett's oesophagus/oesophageal adenocarcinoma patients examined in Blackpool-Wyre-Fylde area were reviewed. All surviving patients completed validated questionnaires. RESULTS: Use of non-steroidal anti-inflammatory drugs of any type and at any frequency was more prevalent in Barrett's oesophagus patients [147 (38%) Barrett's oesophagus vs. 30 (26%) oesophageal adenocarcinoma, P = 0.02]. Daily use of non-steroidal anti-inflammatory drugs was more prevalent in Barrett's oesophagus patients [88 (23%) Barrett's oesophagus vs. 14 (12%) oesophageal adenocarcinoma, P = 0.02], due to more prevalent consumption of non-aspirin non-steroidal anti-inflammatory drugs [48 (13%) Barrett's oesophagus vs. four (4%) oesophageal adenocarcinoma, P = 0.009]. There was no difference between the two groups in usage of either daily low-dose aspirin or of occasional non-steroidal anti-inflammatory drugs. In logistic regression analysis any use of non-steroidal anti-inflammatory drugs [odds ratio (OR) = 0571 (95% CI: 0.359-0.909), P = 0.018] and daily use of non-aspirin non-steroidal anti-inflammatory drugs [OR = 0.297 (95% CI: 0.097-0.911), P = 0.034] were significant protective factors. Non-steroidal anti-inflammatory drugs use did not affect the survival of oesophageal adenocarcinoma patients. Oesophageal adenocarcinoma and Barrett's oesophagus consuming non-steroidal anti-inflammatory drugs did not differ in upper gastrointestinal bleeding [26 (15%) non-steroidal anti-inflammatory drugs consumers vs. 29 (9%) non-consumers, P = 0.08], oesophageal ulcers [31 (18%) non-steroidal anti-inflammatory drug consumers vs. 49 (15%) non-consumers, P = 0.43] or stricturing [19 (11%) non-steroidal anti-inflammatory drug consumers vs. 41 (13%) non-consumers, P = 0.58]. CONCLUSIONS: (i) Daily use of non-steroidal anti-inflammatory drugs is more prevalent in Barrett's oesophagus than oesophageal adenocarcinoma patients, because of a more prevalent use of non-aspirin non-steroidal anti-inflammatory drugs. (ii) Use of non-steroidal anti-inflammatory drugs in Barrett's oesophagus patients is safe if acid suppression is adequate.     

Dilemmas in managing Barrett's oesophagus

In the UK, oesophageal adenocarcinoma accounts for over 7,000 deaths per year and its incidence is rising. One risk factor for this cancer is Barrett's oesophagus. In this condition, reflux of acid and duodenal fluid leads to replacement of the normal stratified squamous epithelium with a columnar epithelium. This new epithelium includes areas of intestinal metaplasia that may develop into dysplasia and ultimately carcinoma. Of people with Barrett's oesophagus, about 1% per year develop adenocarcinoma, around 30-125 times the rate in the general population. This carcinoma is asymptomatic until locally advanced, and has a poor prognosis unless detected early. So it has been suggested that people with reflux should be screened for Barrett's oesophagus, and those with the condition should be kept under surveillance to detect dysplasia or adenocarcinoma in the early stages. Here we discuss the problems in managing patients with Barrett's oesophagus.     

Test and treat or treat and test in reflux disease?

The role of diagnostic testing in reflux disease is in evolution. There is little question that patients with dysphagia, bleeding or other 'alarm' symptoms, should undergo early endoscopy. A substantial proportion of patients presenting with reflux symptoms have endoscopy negative reflux disease. pH testing is both inconvenient and lacks the sensitivity and specificity required for a 'gold standard'. Empirical trials of therapy using proton pump inhibitors have shown that a trial of treatment may be the most accurate way of diagnosing gastro-oesophageal reflux disease (GERD) and may the optimal strategy from a cost-effectiveness standpoint. On the other hand, the increasing rate of oesophageal adenocarcinoma has raised questions about the possible value of screening endoscopy to determine if Barrett's oesophagus is present. The role of endoscopic testing in the average patient is therefore shifting from a diagnostic modality to one that helps manage risk by identifying Barrett's oesophagus.     

Review article: approaches to Barrett's oesophagus treatment-the role of proton pump inhibitors and other interventions

Despite implementation of screening and surveillance strategies, a significantly large number of patients with Barrett's oesophagus remain undiagnosed. In those who are identified, the management options include acid reduction therapies with proton pump inhibitors or anti-reflux surgery. Endoscopic ablative therapies have also been attempted. In addition to having inherent procedure-related risks with ablative therapies, these alternatives may be limited by high rates of failure, need for continued acid suppressive therapy, metaplasia persistence under otherwise normal appearing tissue, need for procedural expertise, and continued risk for adenocarcinoma development. Therefore, a widely applicable chemoprevention strategy that cost-effectively reduces the rate of progression from oesophagitis to adenocarcinoma in high-risk patients and perhaps those at lower rates of risk is highly desirable. The AspECT trial currently underway is seeking to determine the effects of high- and low-dose proton pump inhibitor therapy with and without low-dose aspirin as Barrett's oesophagus chemoprevention.     

Effect of proton pump inhibitors on markers of risk for high-grade dysplasia and oesophageal cancer in Barrett's oesophagus

Background  It has been shown that the presence on diagnosis of endoscopic macroscopic markers indicates a high‐risk group for Barrett’s oesophagus. Aim  To determine whether proton pump inhibitor therapy prior to diagnosis of Barrett’s oesophagus influences markers for risk development of subsequent high‐grade dysplasia/adenocarcinoma. Methods  A review of all patients with Barrett’s oesophagus entering a surveillance programme was undertaken. Five hundred and two patients diagnosed with Barrett’s oesophagus were assessed on diagnosis for endoscopic macroscopic markers or low‐grade dysplasia. Subsequent development of high‐grade dysplasia/adenocarcinoma was documented. The relationship between the initiation of proton pump inhibitor therapy prior to the diagnosis of BE and the presence of macroscopic markers or low‐grade dysplasia at entry was determined. Results  Fourteen patients developed high‐grade dysplasia/adenocarcinoma during surveillance. Patients who entered without prior proton pump inhibitor therapy were 3.4 times (95% CI: 1.98–5.85) more likely to have a macroscopic marker or low‐grade dysplasia than those patients already on a proton pump inhibitor. Conclusions  Use of proton pump inhibitor therapy prior to diagnosis of Barrett’s oesophagus significantly reduced the presence of markers used to stratify patient risk. Widespread use of proton pump inhibitors will confound surveillance strategies for patients with Barrett’s oesophagus based on entry characteristics but is justified because of the lower risk of neoplastic progression.     

The prescribing of acid suppressants prior to the endoscopic diagnosis of Barrett's oesophagus and oesophagitis

BACKGROUND: There has been a dramatic rise in incidences of Barrett's oesophagus and oesophageal adenocarcinoma. It has been suggested that the introduction and use of acid suppression therapy may be a factor in the rising incidences of Barrett's oesophagus and oesophageal adenocarcinoma. METHODS: This was a record linkage study, using a prescribing database and an endoscopy database. Patients who had undergone their first endoscopy during the period 1992-1995 and received the diagnosis of Barrett's oesophagus or oesophagitis were identified. The prescribing of acid suppressants was compared for the 3 years prior to endoscopy, between those with Barrett's oesophagus and those with oesophagitis. RESULTS: There was no significant difference between the Barrett's patients and the oesophagitis patients in the proportion that had been exposed to acid suppression therapy (53.4% vs. 51.7%, P=0.704). The mean number of days of prescribing among those who had been exposed to acid suppression therapy was higher in the Barrett's group (340.5 vs. 237.0 days, P=0.001). CONCLUSIONS: Patients with Barrett's oesophagus have received more acid suppressant therapy prior to diagnosis. The reasons for this are not clear. However, 46.6% of Barrett's patients have not been exposed to acid suppressant therapy.     

Cyclo-oxygenase-2 expression in Barrett's oesophageal carcinogenesis: an immunohistochemical study

BACKGROUND: The incidence of Barrett's oesophageal adenocarcinoma is increasing more rapidly than any other malignancy in industrialized countries. Cyclo-oxygenase-2 appears to play an important role in gastrointestinal carcinogenesis. Previous studies on cyclo-oxygenase-2 expression in Barrett's oesophageal carcinogenesis have utilized tissue samples obtained from different patients. We sought a definitive comparison of cyclo-oxygenase-2 expression in the sequence of Barrett's metaplasia-dysplasia-adenocarcinoma within the same patients. METHODS: Paraffin-embedded oesophago-gastrectomy specimens from 20 patients, containing successive stages of Barrett's metaplasia, high-grade dysplasia and adenocarcinoma, were analysed for cyclo-oxygenase-2 expression by immunohistochemistry. RESULTS: Cyclo-oxygenase-2 was constitutively expressed in the basal layers of cells in the adjacent normal squamous oesophageal epithelium, but a higher cyclo-oxygenase-2 expression was observed in Barrett's metaplasia. A further increase in cyclo-oxygenase-2 expression was detected in high-grade dysplasia, but cyclo-oxygenase-2 was decreased in adenocarcinoma tissue, regardless of its stage or level of differentiation. CONCLUSIONS: Cyclo-oxygenase-2 expression is progressively increased when squamous oesophageal epithelium develops into Barrett's metaplastic epithelium and then into high-grade dysplasia, but appears to decrease when adenocarcinoma develops. These findings may be significant for an effective chemo-prevention strategy with selective cyclo-oxygenase-2 inhibitors.     

Influence of pantoprazole on oesophageal motility, and bile and acid reflux in patients with oesophagitis

BACKGROUND: Reflux of duodeno-gastric juice into the oesophagus appears to be involved in the pathogenesis of both reflux oesophagitis and oesophageal adenocarcinoma. Although proton pump inhibitors have been shown to decrease acid reflux and heal oesophagitis, their effect on biliary reflux and motility is less clear. AIM: To investigate whether pantoprazole also reduces bile reflux and whether this is paralleled by a change in oesophageal motility. METHODS: Combined 24-h measurements of intraoesophageal bilirubin concentration, pH and pressure were performed in 18 symptomatic patients with endoscopically proven reflux oesophagitis before and on day 28 of treatment with pantoprazole, 40 mg/day, under standardized conditions. A reflux symptom score was determined initially and every 2 weeks thereafter. After 56 days on medication, a control endoscopy was performed. RESULTS: The symptom score and the acid and bile reflux improved significantly, whereas the motility parameters did not change during the study period. Helicobacter pylori-positive patients had a significantly higher bile reflux time (32.1 +/- 4.3%) than H. pylori-negative patients (16.3 +/- 3.1%) (P=0.009). The endoscopic healing rate was 89%. The cough symptoms disappeared in three of four patients. CONCLUSIONS: The proton pump inhibitor pantoprazole decreases both acid and bile reflux. The decrease of bile reflux cannot be explained by increased oesophageal clearance as oesophageal motility did not improve with therapy. Interestingly, H. pylori infection of the stomach was associated with higher levels of oesophageal bile reflux.     

Lansoprazole heals erosive reflux oesophagitis in patients with Barrett's oesophagus

Background : Barrett's oesophagus is thought to be a complication of severe gastro-oesophageal reflux.
Aim : To determine whether the proton pump inhibitor, lansoprazole, is effective in healing erosive reflux oesophagitis in patients with Barrett's oesophagus.
Methods : An 8-week, randomized, double-blind study was conducted using patients with both erosive reflux oesophagitis and Barrett's oesophagus. Erosive reflux oesophagitis was defined as grades 2–4 oesophagitis; Barrett's oesophagus, as specialized columnar epithelium obtained by biopsy from the tubular oesophagus; and healing, as a return to grade 0 or 1 oesophageal mucosa (complete re-epithelialization). One-hundred and five (105) patients from one centre were randomized to receive either lansoprazole 30 mg daily or ranitidine 150 mg twice daily. Unhealed or symptomatic lansoprazole patients at week 4 were randomized to receive the same 30 mg dose daily or an increased dose of 60 mg daily. Endoscopy was performed at baseline and at weeks 2, 4, 6 and 8.
Results : The treatment groups were similar in regards to baseline characteristics, erosive reflux oesophagitis grades and length of Barrett's oesophagus. At each 2-week interval, lansoprazole patients had significantly greater healing rates and less day and night heartburn and regurgitation than ranitidine patients. There were no significant differences between treatment groups in antacid use, quality of life parameters, or rate of reported adverse events. Median values for fasting serum gastrin levels remained within the normal range for both groups.
Conclusion : In patients with both Barrett's oesophagus and erosive reflux oesophagitis, lansoprazole is significantly more effective than ranitidine in relieving reflux symptoms and healing erosive reflux oesophagitis.     

Medical decision analysis of endoscopic surveillance of Barrett's oesophagus to prevent oesophageal adenocarcinoma

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.     

The role of the hiatus hernia in gastro-oesophageal reflux disease

A sliding hiatus hernia disrupts both the anatomy and physiology of the normal antireflux mechanism. It reduces lower oesophageal sphincter length and pressure, and impairs the augmenting effects of the diaphragmatic crus. It is associated with decreased oesophageal peristalsis, increases the cross-sectional area of the oesophago-gastric junction, and acts as a reservoir allowing reflux from the hernia sac into the oesophagus during swallowing. The overall effect is that of increased oesophageal acid exposure. The presence of a hiatus hernia is associated with symptoms of gastro-oesophageal reflux, increased prevalence and severity of reflux oesophagitis, as well as Barrett's oesophagus and oesophageal adenocarcinoma. The efficacy of treatment with proton pump inhibitors is reduced. Our view on the significance of the sliding hiatus hernia in gastro-oesophageal reflux disease has changed enormously in recent decades. It was initially thought that a hiatus hernia had to be present for reflux oesophagitis to occur. Subsequently, the hiatus hernia was considered an incidental finding of little consequence. We now appreciate that the hiatus hernia has major patho-physiological effects favouring gastro-oesophageal reflux and hence contributing to oesophageal mucosal injury, particularly in patients with severe gastro-oesophageal reflux disease.     

Approaches to endoscopic‐negative reflux disease: part of the GERD spectrum or a unique acid‐related disorder?

Endoscopic-negative reflux disease (ENRD) is the most common presentation of gastro-oesophageal reflux disease (GERD)-affecting up to 70% of these individuals. In the last three decades therapeutic studies have focused solely on the treatment of patients with erosive oesophagitis. However, more recent studies have shifted our attention to defining, understanding and treating those with ENRD. GERD has traditionally been approached as a spectrum with ENRD at the mild end and complicated GERD (i.e. patients with erosive oesophagitis, stricture and Barrett's oesophagus) being at the other end, suggesting that patients' disease may progress over time along the spectrum. Current data indicate that ENRD should be approached as a unique entity rather than a part of the GERD spectrum and that over time only a few patients with ENRD will develop GERD-related complications. Patients with ENRD are a heterogenous group of patients with different aetiologies for their heartburn symptoms, including motor events, reflux of acidic or nonacidic gastric contents, minute changes in intraesophageal pH (pH < 4), mucosal hypersensitivity, and emotional or psychological abnormalities. By dropping the spectrum concept, which emphasizes oesophageal mucosal injury, we can focus our attention on the specific mechanisms that lead to symptom generation in each of the three unique groups of GERD (ENRD, erosive oesophagitis and Barrett's oesophagus) and on the specific therapeutic modalities that benefit each of these individual groups. Acid suppressive therapy with proton pump inhibitors is highly effective in healing erosions and controlling symptoms in those with erosive oesophagitis. In those with ENRD the resolution or control of heartburn with proton pump inhibitor therapy is greater than that with placebo or H2 receptor antagonist, but not as consistent nor as impressive as the results observed in studies of patients with erosive oesophagitis. By considering the mechanisms involved in ENRD symptom generation, future studies that include high-dose proton pump inhibitors, promotility agents (alone or in combination with proton pump inhibitors), transient lower oesophageal sphincter reducers, or pain modulators (e.g. tricyclic antidepressant agents) may prove beneficial.     

Potent gastric acid inhibition in the management of Barrett's oesophagus

Barrett's oesophagus is the consequence of excessive and prolonged gastro-oesophageal reflux. The therapeutic objectives in Barrett's oesophagus include the reduction of gastro-oesophageal reflux in order to relieve symptoms and the prevention of the biologic progression to adenocarcinoma. The first objective may be achieved with standard proton pump inhibitor (PPI) therapy, which is the base of the medical therapy in this type of patients, but this therapy has been found not to be associated with normalization of the intraluminal pH of the oesophagus in many patients with Barrett's oesophagus. This condition seems to be necessary in order to reduce mucosal cell proliferation in some studies. Therefore, it has been proposed that patients with Barrett's oesophagus need profound acid inhibition with high-dose PPI. This therapeutic approach provides symptom relief, but there is no direct evidence that it is associated with Barrett's oesophagus regression or progression to adenocarcinoma. Nevertheless, recent and preliminary data suggest that long-term PPI therapy may reduce the risk of developing disease progression. Profound acid inhibition is also combined with endoscopy ablative or resection therapy in patients with Barrett's oesophagus. This therapeutic approach should be still regarded as experimental and more data are needed before its therapeutic role in patients with Barrett's oesophagus is established.