What is the optimal medical therapy for Barrett's esophagus?

The development of Barrett's esophagus (BE) in patients with gastroesophageal reflux disease (GERD) is troubling because of its known association with esophageal cancer. When evaluated clinically, patients with BE have the severest form of GERD and require aggressive therapy to control esophageal acid exposure. Both hypotension of the lower esophageal sphincter and the extent of esophageal acid exposure are major contributors to severe GERD and its complications. It is hypothesized that better control of acid will improve outcomes for BE patients. While it is clear that therapy (medical or surgical) for reflux rarely if ever results in total regression of BE, there are some limited data to support improvement in BE with control of reflux. Current medical choices include prokinetic agents, histamine type-2 receptor antagonists, and proton pump inhibitors. In the future, genetic markers may be used in identifying BE patients at the greatest risk for histologic progression, and chemoprevention with cyclooxygenase-2 inhibitors may be a therapeutic option. This paper will review the rationale for and results of medical antireflux therapy in patients with BE.     

Role of acid suppression in the development and progression of dysplasia in patients with Barrett's esophagus

Barrett's esophagus (BE) usually develops in patients with gastroesophageal reflux disease and therefore it has been suggested that esophageal acid exposure plays an import role in the initiation of BE and its progression towards esophageal adenocarcinoma (EAC). The mechanisms whereby acid exposure causes BE are not completely revealed and the potential role of esophageal acid exposure in carcinogenesis is unclear as well. Since acid exposure is thought to play an important role in the progression of BE, therapies aimed at preventing the development of EAC have primarily focused on pharmacological and surgical acid suppression. In clinical practice, acid suppression is effective in relieving reflux symptoms and decreases esophageal acid exposure in most patients. However, in some individuals, pathological acid exposure persists and these patients continue to be at risk for developing dysplasia or EAC. To date, published trials suggest that acid suppression is able to prevent the development and progression of dysplasia in patients with BE, but definite and compelling proof is still lacking. This article reviews the mechanisms of acid-induced carcinogenesis in BE and the role of acid suppression in the prevention of neoplastic progression.     

Comparison of esophageal acid exposure distribution along the esophagus among the different gastroesophageal reflux disease (GERD) groups

BACKGROUND: Patients with nonerosive reflux disease (NERD) have the lowest esophageal acid exposure profile compared with the other gastroesophageal reflux disease (GERD) groups. AIM: To compare lower esophageal acid exposure recordings 1 cm above the lower esophageal sphincter (LES) with those 6 cm above the LES as well as to determine the characteristics of esophageal acid exposure along the esophagus among the different GERD groups. METHODS: Patients with classic heartburn symptoms were enrolled into the study. Patients were evaluated by a demographics questionnaire and the validated GERD Symptom Checklist. Upper endoscopy was performed to evaluate the presence of esophageal erosions and Barrett's esophagus (BE). Ambulatory pH testing was performed using a commercially available 4-sensor pH probe with sensors located 5 cm apart. The distal sensor was placed 1 cm above the LES. RESULTS: Sixty-four patients completed the study. Of those, 21 patients had NERD, 20 had erosive esophagitis (EE), and 23 had BE. All patient groups demonstrated greater esophageal acid exposure 1 cm above the LES than 6 cm above the LES. In NERD and EE, this phenomenon was primarily a result of a higher mean percentage of upright time with pH <4. Unlike patients with EE and BE, those with NERD had very little variation in esophageal acid exposure throughout the esophagus (total and supine). CONCLUSIONS: ALL GERD groups demonstrated significant greater esophageal acid exposure at the very distal portion of the esophagus, primarily as a result of short upright reflux events. Unlike erosive esophagitis and BE, NERD patients demonstrate a more homogenous acid distribution along the esophagus.     

Esophageal Bacteria and Barrett's Esophagus: A Preliminary Report

The objective of this study was to investigate if esophageal bacteria are associated with Barrett's esophagus (BE). This study was comprised of a retrospective (Part 1) and a subsequent prospective (Part 2) study. In Part 1, Gram stains were performed on esophageal biopsy specimens obtained in 47 patients. Bacteria were quantitated from 0 to 4. In Part 2, Gram stains and cultured bacterial counts of esophageal biopsies were obtained in 18 GERD patients (9 with BE and 9 without BE). Part 1 results were as follows. Bacteria were found in 37 of 47 esophageal biopsies. Quantitative bacterial stain scores for BE (2.5 +/- 0.2) were higher than for non-BE (1.5 +/- 0.3; P = 0.02). The quantitative bacterial stain scores correlated with increasing severity of dysplasia (r = 0.37, P = 0.028). In Part 2, bacteria were found in 8 of 18 esophageal biopsies by Gram stain (6 of 9 patients with BE vs. 2 of 9 non-BE). The distal esophageal bacterial stain scores in BE patients (1.6 +/- 0.5) were higher than in those without BE (0.4 +/- 0.3; P = 0.07). Patients on proton pump inhibitors tended to have higher bacterial stain scores (1.2 +/- 0.4) than patients who were not (0.7 +/- 0.3; P = 0.45). Bacterial colony counts were similar in patients with BE compared to those without BE. In conclusion, bacteria in esophageal biopsies were detected more often in BE than non-BE. Increasing bacterial stain scores were associated with metaplasia and increasing dysplasia. Esophageal bacteria, possibly related to stasis or gastric acid suppression therapy, may play a role in the pathogenesis of BE and dysplasia.     

Esophageal acid exposure at pH ≤ 2 is more common in Barrett''s esophagus patients and is associated with oxidative stress

Barrett's esophagus (BE) patients demonstrate a higher distal esophageal acid exposure profile than other gastroesophageal reflux disease patients. Cellular oxidative stress has been proposed to contribute to the development of BE and esophageal adenocarcinoma. However, a relationship between low esophageal pH and oxidative stress has yet to be elucidated. The aim of this study was to determine the duration of low pH exposure in the esophagus of BE patients compared to those with erosive esophagitis (EE) and to test if brief exposure to low pH leads to the induction of reactive oxygen species (ROS). Seventy-three patients with BE or EE were evaluated by 24-hour esophageal pH monitoring and the percentage of time during which there was exposure to pH < or = 4 and pH < or = 2 was recorded. In vitro, Seg-1 and Het-1A cells were evaluated after brief exposure to pH4 or pH2 by flow cytometry and fluorescent microscopy for the production of ROS. BE patients demonstrated a significantly higher exposure to low pH values (pH < or = 2) than EE patients. The mean percent total time, duration and mean number of reflux episodes at pH < or = 2 were 2.8 +/- 0.53%, 28.8 +/- 3.6 seconds and 79 +/- 11.4 episodes in BE patients, whereas in EE patients they were significantly less, 1.16 +/- 0.3%, 15.6 +/- 1.2 seconds and 48.3 +/- 8.8 episodes, respectively (P < 0.05). In vitro experiments indicate that esophageal cells, when exposed to pH 2, produce ROS. In vitro studies using brief pH 2 exposure are biologically relevant to the clinical situation. Our studies indicate that such exposure induces oxidative stress. This stress may cause DNA damage, mutations and progression to cancer.     

Capsaicin induction of esophageal symptoms in different phenotypes of gastroesophageal reflux disease

"Background: Type 1 vanilloid receptors (TRPV1) have been described on esophageal afferent sensitive neurons. Stimulation of TRPV1 receptors with capsaicin may induce heartburn. Capsaicin is the pungent component of chili and the most extensively studied TRPV1 agonist. Objectives: To investigate the effect of esophageal stimulation with intraesophageal capsaicin administration on induction of esophageal symptoms and on esophageal chemo-sensitization to acid in different gastroesophageal reflux disease (GERD) phenotypes. Methods: Healthy volunteers and patients with GERD (non-erosive [NERD], erosive GERD [EE] and Barrett's esophagus [BE]) were prospectively studied. All subjects were randomized to receive either intraesophageal perfusion capsaicin or saline 0.9%. Thirty minutes after saline or capsaicin infusion an acid perfusion test of HCl was performed. A week later, a crossover phase with capsaicin versus saline was performed. Five symptoms were evaluated every 5 min during the first 30 minutes after capsaicin, saline, and acid perfusion: chest burning, chest pain, heartburn, epigastric burning, and epigastric pain Results: 17 healthy subjects and 31 GERD patients (10 NERD, 11 EE, and 10 BE) were included. Twenty- eight (90%) of GERD and 6 (35%) of healthy subjects had esophageal symptoms after capsaicin perfusion. Mean for the 5 evaluated symptoms induced by capsaicin was significantly higher in the GERD group compared to the control group. The highest symptom severity was in the erosive subgroup. Capsaicin decreased the 5 symptoms induced by acid perfusion in both healthy volunteers and GERD patients. Total score of esophageal symptom severity (produced by acid perfusion) was significantly reduced by capsaicin infusion in the BE group. Conclusions: Capsaicin induces esophageal and gastric symptoms in healthy volunteers and GERD patients. Capsaicin reduces esophageal chemosensitivity to acid, especially in patients with BE. "     

Antireflux surgery, highly selective vagotomy and duodenal switch procedure: post-operative evaluation in patients with complicated and non-complicated Barrett's esophagus.

Antireflux surgery, highly selective vagotomy (HSV) and Roux-en-Y duodenojejunostomy have been suggested for control of pathophysiological factors involved in patients with Barrett's esophagus (BE). The aim of this study was to evaluate prospectively the results of this technique in patients with complicated (n = 21) and noncomplicated (n=45) BE. Complete evaluation of esophageal function, endoscopic histologic and clinical control was carried out before and 2 years after surgery. Post-operative results show recurrence of ulcer in patients with complicated BE, but no recurrence in patients with non-complicated BE. Preoperative esophageal ulcer and stricture were present in 85.3% and 14.3%, respectively, of patients with complicated BE. In this group, recurrence of these complications was 38.1% and 9.5% respectively. The technique offers excellent results in patients with non-complicated BE. However, in patients with complicated BE, the recurrence rate is higher, mainly because of the persistence of acid reflux into the esophagus.     

Nonerosive reflux disease

Nonerosive reflux disease (NERD) is the most common phenotype of gastroesophageal reflux disease. By definition, patients with NERD have typical reflux symptoms caused by the intraesophageal reflux of gastric contents but have no visible esophageal mucosal injury. This is in contrast to patients with erosive reflux disease (ERD) or Barrett's esophagus (BE) who have obvious esophageal mucosal injury on endosco-py. Only 50% of patients with NERD have pathologic esophageal acid exposure as detected on 24-h pH monitoring. NERD patients with physiologic esophageal acid exposure and good temporal correlation of symptoms with reflux events are considered to have esophageal hypersensitivity, while patients with no symptom-reflux correlation are considered to have functional heartburn. It is possible yet uncommon for NERD to progress to severe ERD (i.e. LA Grade C or D) or BE. Patients with NERD and pathologic esophageal acid exposure have motor dysfunction and acid reflux abnormalities that are similar to patients with ERD and BE, whereas NERD patients with physiologic esophageal acid exposure have minimal abnormalities and are not much different than healthy controls. The pathological feature most indicative of NERD is the presence of dilated intercellular spaces within squamous epithelium, an ultrastructural abnormality readily identified on transmission electron microscopy but also on light microscopy. A symptomatic response to an empiric trial of high-dose proton pump inhibitor (PPI) therapy is a simple and useful strategy to establish the diagnosis of NERD, although histology and pH monitoring may be useful in confirming the diagnosis. Patients with NERD suffer similar decrements in quality of life as do patients with erosive esophagitis. Therapy is aimed at eliminating or reducing symptoms and improving quality of life. PPIs are the most effective agents for the treatment of NERD although they are less effective in providing symptom relief than in patients with erosive esophagitis. Laparoscopic antireflux surgery is an effective therapy for selected patients with NERD and outcomes are better when performed in high volume centers.     

反流性食管炎、Barrett食管的食管动力学研究

目的 探讨反流性食管炎(RE)、Barrett食管(BE)的动力学改变。方法 经内镜检查3 400例患者,分 RE、BE、对照组,进行症状调查、食管测压、食管24h pH检测,并行统计学分析。结果 RE与BE组间除吞咽不适外,烧心感、反酸及胸骨后疼痛的症状评分均为RE组大于BE组,且差异有显著性意义。部分RE、BE、对照组间食管运动功能比较,食管下括约肌静息压等差异均无显著性意义。食管24 h pH检测DeMeester评分、pH<4总时间、pH<4时间的百分比等 RE、BE组高于对照组,差异有显著性意义,但RE、BE组间差别无显著性意义。结论 食管反流症状与食管黏膜的内镜下表现不一致;食管组织化生与食管运动功能间无相关。     

Acid suppression and reepithelialization after ablation of Barrett's esophagus

The role of acid reflux in the development of esophageal columnar epithelium was first described in the early 1970s in the canine esophageal reflux model. In the presence of acid reflux, columnar epithelium developed at the site of induced esophageal mucosal injury. When reflux was suppressed, most epithelium reverted back to squamous mucosa. Similar findings in human patients with Barrett's esophagus (BE) who were treated with laser ablation were first described in 1993. While acid suppression with antireflux surgery or proton pump inhibitors (PPIs) has proven insufficient to completely reverse BE, ablation of the lesion followed by acid suppression may be a promising option. Although at least one report disputes the importance of complete acid suppression following mucosal ablation of BE, most investigators use full-dose PPI therapy following ablation, in the belief that full acid suppression provides an environment that allows the esophageal progenitor cell to develop squamous mucosa. This article provides a review of the literature to date regarding ablative therapies and acid suppression for patients with BE.     

胆汁酸在Barrett食管和食管腺癌发病中的作用

目的探讨胆汁酸在Barrett食管(BE)及食管腺癌(EAC)发病中的作用,为预防、治疗BE、EAC的发生提供参考依据。 方法选取2017年8月10日至2020年10月30日于茌平区人民医院就诊,反流性疾病问卷评分>12分的患者,对其行无痛胃镜检查,镜下胃液留取及食管下段(胃食管结合部上1 cm处)黏膜组织活检,进行胃液、食管下段黏膜胆汁酸浓度检测。 结果所检患者胃液中均检测到不同浓度的胆汁酸,且BE、EAC患者胃液及食管下段黏膜组织总胆汁酸浓度较非糜烂性反流病(NERD)、反流性食管炎(RE)患者胃液及食管下段黏膜组织总胆汁酸浓度明显升高(P值均<0.05)。 结论胆汁酸在BE、EAC患者胃液及食管下段黏膜组织中的浓度较无Barrett食管的胃食管反流病患者的浓度明显升高,提示胆汁反流可能与胃食管结合部黏膜细胞恶性转化相关,抑制胆汁反流可能成为预防BE、EAC发生的必要干预措施。     

Barrett&rsquo;s esophagus in 2016: From pathophysiology to treatment

Esophageal complications caused by gastroesophageal reflux disease (GERD) include reflux esophagitis and Barrett’s esophagus (BE). BE is a premalignant condition with an increased risk of developing esophageal adenocarcinoma (EAC). The carcinogenic sequence may progress through several steps, from normal esophageal mucosa through BE to EAC. A recent advent of functional esophageal testing (particularly multichannel intraluminal impedance and pH monitoring) has helped to improve our knowledge about GERD pathophysiology, including its complications. Those findings (when properly confirmed) might help to predict BE neoplastic progression. Over the last few decades, the incidence of EAC has continued to rise in Western populations. However, only a minority of BE patients develop EAC, opening the debate regarding the cost-effectiveness of current screening/surveillance strategies. Thus, major efforts in clinical and research practice are focused on new methods for optimal risk assessment that can stratify BE patients at low or high risk of developing EAC, which should improve the cost effectiveness of screening/surveillance programs and consequently significantly affect health-care costs. Furthermore, the area of BE therapeutic management is rapidly evolving. Endoscopic eradication therapies have been shown to be effective, and new therapeutic options for BE and EAC have emerged. The aim of the present review article is to highlight the status of screening/surveillance programs and the current progress of BE therapy. Moreover, we discuss the recent introduction of novel esophageal pathophysiological exams that have improved the knowledge of the mechanisms linking GERD to BE.     

Barrett食管、糜烂性食管炎和非糜烂性反流病食管酸暴露及食管动力学分析

目的分析胃食管反流病(GERD)三种亚型Barrett食管(BE)、糜烂性食管炎(EE)和非糜烂性反流病(NERD)患者食管24 h pH监测与高分辨率食管测压结果,探讨不同亚型胃食管反流病食管酸暴露及动力学变化特点。 方法收集2015年12月至2017年12月,新疆维吾尔自治区人民医院接受住院治疗的90例GERD患者的临床资料,其中BE组28例、EE组35例、NERD组27例,通过食管24 h pH监测结果评价患食管酸暴露及反流特点,高分辨率食管测压检查评价食管动力学特点。 结果3组患者年龄及身体质量指数(BMI)等一般资料比较,差异无统计学意义(P>0.05);EE组患者24 h食管pH监测中pH≤4(酸反流)、40.05);3组Demeester评分比较,差异无统计学意义(P>0.05);LES长度3组无明显差异,BE组LES静息压及残余压较EE组和NERD组稍高,但差异无统计学意义(P均>0.05);3组在食管远端收缩积分比较,差异无统计学意义(P>0.05)。 结论食管测酸检查在GERD临床亚型的鉴别方面并无显著差别;Barrett食管、糜烂性食管炎、非糜烂性反流病均存在抗反流屏障功能减退,但不同程度的食管粘膜损伤对食管动力学的影响并无差异。     

Acid and bile reflux in erosive reflux disease, non-erosive reflux disease and Barrett's esophagus

BACKGROUND/AIMS: Gastroesophageal reflux disease (GERD) may occur with acid, bile or in a mixed form. Endoscopic injury and mucosal metaplasia are a known sequlae to pathological GERD. The aim of the study was to determine the contribution of acid and duodenogastroesophageal reflux (DGER) to endoscopic severity in patients with GERD and Barrett's esophagus. METHODS: Ninety-one patients complaining of reflux symptoms were studied with upper gastrointestinal endoscopy and graded to non-erosive reflux disease (NERD), erosive reflux disease (ERD) and Barrett's esophagus (BE). Esophageal manometry and simultaneous ambulatory 24-h esophageal pH and bilirubin monitoring (Bilitec 2000) were done to all patients. RESULTS: Seventy one patients (78.0%) had ERD (Savary-Miller (grade I-III), 11 patients (12.1%) had NERD and 9 patients (9.9%) had BE suspected endoscopically and diagnosed by histological esophageal biopsy. Combined 24-h esophageal bilirubin and pH monitoring revealed that 39 patients (42.9%) had mixed acid and bile reflux, 16 (17.6%) had pathological acid reflux only, 18 (19.8%) had bile reflux only and 18 patients (19.8%) had no evidence of abnormal reflux. The percentage of the total time of bilirubin absorbance above 0.14, in 71 patients with ERD was (8.18 +/- 11.28%), and in 9 patients with BE was (15.48 +/- 30.48%) which was significantly greater than that in 11 patients with NERD (4.48 +/- 8.99%), p < 0.05 and p = 0.01 respectively. All BE patients had abnormal esophageal bile reflux (3 bile alone and 6 mixed bile and acid); 44 of 71 patients (61.97%) with ERD had abnormal esophageal bile reflux (13 bile alone and 31 mixed bile and acid); meanwhile 15 of them (21.2%) had abnormal acid exposure alone. Of the 11 patients with NERD, 4 patients (36.4%) had abnormal esophageal bile reflux, 2 of them mixed with acid. CONCLUSIONS: The Bilitec method reliably identifies the presence of bilirubin and quantitatively detects duodenogastroesophageal reflux of bile. Mixed reflux (acid and bile) is the chief pattern of reflux in GERD patients in this study. Bile reflux either alone or mixed with acid reflux contributes to the severity of erosive and non-erosive reflux disease as well as to Barrett's esophagus.     

Trends in Barrett's esophagus diagnosis in Southern Europe: implications for surveillance

The incidence of Barrett's esophagus (BE) and esophageal adenocarcinoma has increased in Western countries in recent decades. The aim of this study is to describe the changes in incidence and prevalence of BE diagnosis, dysplasia, and adenocarcinoma development in BE patients in a South‐European Mediterranean area. Retrospective population‐based analyses of endoscopy and pathology reports from 1976 to 2001 was performed. Data from patients with diagnosis of BE and/or esophageal carcinoma were collected. The study period was divided in four quartiles for statistical calculations; parametric and nonparametric tests were used. A 6.9‐fold increase was found in the diagnosis of long‐segment BE from the first to the fourth quartile, and a 9.3‐fold increase in short‐segment BE from 1995 to 2000, in contrast to a much smaller increase of 1.9‐fold increase in the number of upper gastrointestinal endoscopies. The adjusted incidence of BE diagnosis increased from 0.73 to 9.73 cases/100 000 (first to fourth quartile, respectively) and the adjusted prevalence from 6.51 to 76.04 cases/100 000 (1985–2001). The incidence of dysplasia was 2.13% per year (95% confidence interval: 0.05–11.3%) ? 1.78% for low‐grade dysplasia and 0.36% for high‐grade dysplasia – giving a total incidence of 1 per 47 patient‐years. The incidence of adenocarcinoma during follow‐up was 0.48% per year (95% confidence interval: 0.006–2.62%), for an incidence of 1 per 210 patient‐years. Nineteen patients with BE (14 long‐segment BE, 5 short‐segment BE) were diagnosed with esophageal adenocarcinoma, with eight being diagnosed during endoscopic surveillance. Only 14 (8%) adenocarcinoma patients diagnosed during the study period had a history of BE. BE diagnosis has dramatically increased over recent decades in our population, unrelated to an increase in endoscopies. Progression to low‐grade dysplasia and adenocarcinoma is rare. Surveillance may have a low impact on the survival of adenocarcinoma patients in Southern Europe.     

Prevalence of Barrett's esophagus in systemic sclerosis

OBJECTIVE: The esophagus is the most commonly affected gastrointestinal area in systemic sclerosis (SSc). Patients with SSc frequently develop gastroesophageal reflux, esophageal injury, and sometimes, intestinal metaplasia, or Barrett's esophagus (BE), which may increase the risk of esophageal adenocarcinoma. This study sought to determine the prevalence of BE and esophageal adenocarcinoma in a cohort of SSc patients. METHODS: One hundred ten SSc patients who were receiving long-term treatment with proton-pump inhibitors (PPIs) were assessed systematically by esophageal manometry and endoscopy. Esophageal biopsies were performed when macroscopic abnormalities were detected, and BE was diagnosed histologically. RESULTS: Among the 110 patients, 14 had BE (12.7%). None of the patients with BE had adenocarcinoma, but 3 of the 14 patients (21%) had dysplasia on esophageal biopsy. Similar proportions of patients with and without BE had abnormal peristalsis and decreased lower esophageal sphincter pressure. No association between BE and other disease characteristics was demonstrated. CONCLUSION: In this study, 12.7% of SSc patients who had been treated with PPIs for long periods had BE, similar to the prevalence in patients with gastroesophageal reflux disease. Although none of the patients had esophageal adenocarcinoma, patients with BE should be followed up closely, particularly patients with dysplasic BE. Long-term prospective studies are warranted to determine the phenotype of SSc patients at high risk of developing dysplasia or esophageal adenocarcinoma.     

Cyclooxygenase 2 expression in Barrett's esophagus and adenocarcinoma: Ex vivo induction by bile salts and acid exposure

BACKGROUND & AIMS: Barrett's esophagus (BE) results from chronic, severe gastroesophageal reflux and predisposes to esophageal adenocarcinoma. Cyclooxygenase (COX)-2 is involved in chronic inflammation and epithelial cell growth. We investigated COX-2 expression in BE and esophageal adenocarcinoma to explore a potential relation between COX-2 expression and metaplasia or carcinogenesis. METHODS: Endoscopic mucosal biopsy specimens of Barrett's intestinal metaplasia (n = 30), Barrett's dysplasia (n = 11), and esophageal adenocarcinoma (n = 5) were compared with normal esophagus (n = 46) and duodenum (n = 46) and analyzed by Western blotting and immunohistochemistry. RESULTS: Immunoblots revealed constitutive expression of COX-2 in normal esophagus and duodenum. COX-2 protein expression was significantly higher in patients with Barrett's metaplasia, dysplasia, and adenocarcinoma compared with normal squamous esophageal or columnar duodenal epithelia and was heterogenous in different regions of the BE surface. Immunohistochemistry revealed prominent staining in the glands of BE, dysplasia, and adenocarcinoma and faint staining in the basal layers of squamous esophagus and the surface of the duodenum. In response to pulses of acid or bile salts in an ex vivo organ culture system, COX-2 expression increased significantly in BE tissues, and this effect was attenuated by the selective COX-2 inhibitor NS-398. CONCLUSIONS: The results show COX-2 expression in normal esophagus, which increases significantly in BE and esophageal adenocarcinoma. COX-2 is regulated ex vivo by exposure to acid or bile salts.     

Patients with multiple endocrine neoplasia type 1 with gastrinomas have an increased risk of severe esophageal disease including stricture and the premalignant condition, Barrett's esophagus

CONTEXT: Multiple endocrine neoplasia type 1 (MEN1) patients frequently develop Zollinger-Ellison syndrome (MEN1/ZES). Although esophageal reflux symptoms are common in these patients, little is known about long-term occurrence of severe peptic esophageal disease including strictures and Barrett's esophagus (BE). OBJECTIVE: The objective of the study was to prospectively analyze the frequency of severe peptic esophageal disease in ZES patients with and without MEN1. SETTING: The study was conducted at a tertiary care research center. PATIENTS: Two hundred ninety-five patients (80 = MEN1/ZES, 215 = sporadic ZES) participated in a prospective study. INTERVENTIONS AND OUTCOME MEASURES: Assessment of MEN1, acid hypersecretion, upper gastrointestinal endoscopy/biopsies, and tumor status were measured initially and at each follow-up. Esophageal manometry was performed in 89 patients. Frequency and type of esophageal disease were correlated with clinical/laboratory/tumoral features of ZES/MEN1. RESULTS: In MEN1/ZES patients, esophageal stricture was 3-fold higher, BE 5-fold higher, and dysplasia 8-fold higher, and one patient died of esophageal adenocarcinoma. Esophageal symptoms were more frequent or severe in MEN1/ZES, but known risk factors for severe esophageal disease and ZES-specific features did not differ between MEN1/ZES and sporadic ZES. In MEN1/ZES, the onset of ZES was 10 yr earlier, and H2-antagonists were used longer and at lower doses. MEN1/ZES patients with esophageal disease differed from those without in that ZES diagnosis was delayed longer, esophageal symptoms were more frequent or severe, hiatal hernias were more frequent, esophagitis or pyloric scarring was more common, basal acid output was higher, and hyperparathyroidism was underdiagnosed. CONCLUSIONS: This study shows that MEN1/ZES patients have a higher incidence of severe esophageal disease including the premalignant condition BE and identifies factors important for their pathogenesis that need to be incorporated into their long-term treatment.     

Barrett's esophagus in patients with symptomatic reflux esophagitis

We evaluated the frequency with which Barrett's esophagus (BE) occurs in patients with symptomatic reflux esophagitis, and compared the clinical endoscopic and manometric features of patients with Barrett's esophagus with those of patients who had non-Barrett's esophagitis (NBE). The effect of 6 months' medical treatment on BE patients was reevaluated by repeating manometry, endoscopy, and biopsy. Esophageal manometry was performed by perfusion technique and endoscopic biopsies were obtained. There were 180 patients; 20 (11%) were found to have BE. The vast majority of BE patients were caucasians. BE patients had symptoms of gastroesophageal reflux for a longer time than did NBE patients. Mean lower esophageal sphincter pressure in BE patients was lower than that in NBE patients. On medical treatment, the severity of esophagitis as judged by endoscopic criteria in BE patients was reduced, but there was no increase in lower esophageal sphincter pressure and no regression of the columnar epithelium.     

Epidemiology and significance of Barrett's esophagus

Barrett's esophagus (BE) is of interest because of its recognized association with esophageal adenocarcinoma. While BE develops in a minority of patients with gastroesophageal reflux disease, its diagnosis has markedly increased over the last 30 years. Although a concurrent increase in the number of endoscopies performed annually has improved the ability to diagnose BE, the increase in prevalence appears to be a true finding. Conflicting data in the literature confound an accurate assessment of the risk for adenocarcinoma in patients with BE. Certain factors associated with BE also hold for esophageal adenocarcinoma: greater severity of reflux symptoms, specific pattern of symptoms (particularly nocturnal), longer duration of symptoms, white race, and male gender. One report has suggested a 45-fold increase in cancer risk for patients with frequent, severe and long-standing heartburn symptoms. New cases of esophageal adenocarcinoma are also increasing, especially in white males, with over 6,000 new cases diagnosed in 1995. BE can progress to esophageal dysplasia and adenocarcinoma; hence, early diagnosis and surveillance of BE and treatment of high-grade dysplasia leads to improved survival. The reported risk of developing cancer in BE ranges from 0.4 to 1.9%/year of follow-up. Most recent studies have tended to report rates of 0.5%/year or lower. Despite these data and concerns, at least two actuarial studies have suggested that the risk of death in patients with BE does not differ from that of a control population. This review of the literature focuses on the epidemiology of BE and the associated incidence of its sequelae.