Distribution of Tn antigen recognized by an anti-Tn monoclonal antibody (MLS128) in normal and malignant tissues of the digestive tract

Alterations in the normal glycosylation process are often associated with oncogenic transformation. Using an anti-Tn monoclonal antibody, MLS128, we have investigated the immunohistochemical localization of Tn antigen in normal and malignant tissues of the digestive tract. In normal tissues, MLS128 was immunoreactive with the squamous epithelium of the esophagus and was weakly reactive with the columnar epithelia of the stomach, duodenum, colon, bile duct and pancreatic duct. In malignant, tissues, positive immunostaining was detected with high frequency (75%–100%) in carcinomas of the esophagus, stomach colon, biliary tract and pancreas, whereas 2 of 11 (18%) hepatocellular carcinomas were positive. Tn antigen was detected in the upper two-thirds of the normal squamous epithelium, and was often detected in squamous cell carcinomas with cancer pearls (keratinization). These results suggest that the expression of Tn antigen is related to the differentiation of squamous epithelium, or to keratinization. In normal columnar epithelial cells, Tn antigen was localized mainly to the Golgi area. This intracellular localization was preserved in well-differentiated papillary adenocarcinomas of the colon, but was lost in most cases of tubular adenocarcinomas.     

Cervical inlet patch-optical coherence tomography imaging and clinical significance

AIM: To demonstrate the feasibility of optical coherence tomography (OCT) imaging in differentiating cervical inlet patch (CIP) from normal esophagus, Barrett’s esophagus (BE), normal stomach and duodenum.METHODS: This study was conducted at the Veterans Affairs Boston Healthcare System (VABHS). Patients undergoing standard esophagogastroduodenoscopy at VABHS, including one patient with CIP, one representative patient with BE and three representative normal subjects were included. White light video endoscopy was performed and endoscopic 3D-OCT images were obtained in each patient using a prototype OCT system. The OCT imaging probe passes through the working channel of the endoscope to enable simultaneous video endoscopy and 3D-OCT examination of the human gastrointestinal (GI) tract. Standard hematoxylin and eosin (H and E) histology was performed on biopsy or endoscopic mucosal resection specimens in order to compare and validate the 3D-OCT data.RESULTS: CIP was observed from a 68-year old male with gastroesophageal reflux disease. The CIP region appeared as a pink circular lesion in the upper esophagus under white light endoscopy. OCT imaging over the CIP region showed columnar epithelium structure, which clearly contrasted the squamous epithelium structure from adjacent normal esophagus. 3D-OCT images obtained from other representative patients demonstrated distinctive patterns of the normal esophagus, BE, normal stomach, and normal duodenum bulb. Microstructures, such as squamous epithelium, lamina propria, muscularis mucosa, muscularis propria, esophageal glands, Barrett’s glands, gastric mucosa, gastric glands, and intestinal mucosal villi were clearly observed with OCT and matched with H and E histology. These results demonstrated the feasibility of using OCT to evaluate GI tissue morphology in situ and in real-time.CONCLUSION: We demonstrate in situ evaluation of CIP microstructures using 3D-OCT, which may be a useful tool for future diagnosis and follow-up of patients with CIP.     

Assessment of proliferation of squamous, Barrett''s and gastric mucosa in patients with columnar lined Barrett''s oesophagus.

There is no satisfactory biomarker yet available for predicting the likelihood of premalignant changes or carcinoma developing in Barrett's or columnar lined oesophagus. In this study we have evaluated the proliferation of squamous epithelium, columnar epithelium from columnar lined oesophagus and gastric columnar epithelium from 23 Barrett's patients using positive immunoreactivity with the mouse monoclonal antibody Ki67 (which recognises an antigen associated with proliferative cells) with a view to using this parameter as a biomarker. Squamous epithelium had significantly higher Ki67 immunostaining as compared with columnar epithelium from columnar lined oesophagus (when examining the tissue with greater than 15% cells staining positive for Ki67, Fisher's exact test p = 0.004) but there was no difference found between the epithelium from the columnar lined oesophagus and gastric columnar epithelium. There was no correlation between histological inflammation and Ki67 immunoreactivity of Barrett's mucosa, and the Ki67 immunostaining of two patients with dysplasia was no different from the rest of the group. There was, however, a significant correlation between the Ki67 immunoreactivity of columnar epithelium from columnar lined oesophagus and columnar epithelium from the stomach (correlation coefficient = 0.44, p = 0.03) suggesting that epithelium from columnar lined oesophagus behaves in a similar fashion to gastric epithelium.     

Variable pathologic interpretation of columnar lined esophagus by general pathologists in community practice.

BACKGROUND: Pathologic interpretation of biopsy specimens of columnar lined esophagus guides subsequent endoscopic surveillance and/or surgical intervention. The aim of this study was to evaluate pathologic interpretation of columnar lined esophagus by general pathologists in community practice. METHODS: Five histologic slides representing different types of columnar lined esophagus were submitted for review by 20 randomly selected general pathologists in community practice. There were three cases with intestinal metaplasia (one with no dysplasia, one with low-grade dysplasia, and one with high-grade dysplasia) and two cases of gastric metaplasia (one fundic-type and one cardia-type). RESULTS: High-grade dysplasia was identified as such by 30% of pathologists and was called invasive adenocarcinoma by 20%, low-grade dysplasia by 30%, and moderate dysplasia by the remaining 20%. Low-grade dysplasia was identified as such by 35% of pathologists and was called high-grade dysplasia by 20%, moderate dysplasia by 20%, and no dysplasia by 25%. Specialized columnar epithelium with no dysplasia was identified as such by 35%, called low-grade dysplasia by 35%, moderate dysplasia by 15%, indeterminate for dysplasia by 10%, and invasive adenocarcinoma by 5%. Gastric metaplasia without specialized columnar epithelium was identified as Barrett's esophagus in 38% of cases. CONCLUSIONS:Pathologic interpretation of columnar lined esophagus by community pathologists may be subject to marked interobserver variation. The term Barrett's esophagus is often used to describe columnar lined esophagus without goblet cells. Because this finding is not clearly associated with an increased risk of cancer, these data support recent suggestions that the term Barrett's esophagus be abandoned. Interpretations of both high-grade and low-grade dysplasia should be considered for review by experts in esophageal pathology.     

On the origin of cardiac mucosa： A histological and immunohistocheroical study of cytokeratin expression patterns in the developing esophagogastric junction region and stomach

AIM To examine the fetal and neonatal esophagogastric junction region (EGJ) histologically for the presence of an equivalent to adult cardiac mucosa (CM); to study the expression patterns of all cytokeratins (CK) relevant to the EGJ during gestation; to compare the CK profile of the gestational and the adult EGJ; and to determine the degree of development in the adult EGJ histology and CK profile during gestation. METHODS: Forty-eight fetal autopsy specimens of the EGJ were step-sectioned and stained with hematoxylin and eosin (H&E) to select sections showing the mucosal lining. Immunohistochemistry for CK5, 7, 8, 13, 18, 19, and 20 was performed. Antibody staining was then graded for location, intensity, and degree. RESULTS: The distal esophagus was lined by simple columnar epithelium from 12-wk gestational age (GA). The proximal part of this segment consisted of mucusproducing epithelium, devoid of parietal cells. CK5 and 13 were present exclusively in multilayered epithelia and CK8, 18, and 19 predominantly in simple columnar epithelium. There were no differences in the frequencies of the coordinate CK7+/20+ and the CK7-/20-immunophenotypes between different locations. The prevalence of the CK7+/20-immunophenotype decreased, and that of the CK7-/ 20+ immunophenotype increased significantly from the distal esophagus to the distal stomach. CONCLUSION: Fetal columnar-lined lower esophagus (fetal CLE) may be the equivalent and precursor of the short segments of columnar epithelium found in the distal esophagus of some normal adult subjects. Esophageal simple columnar epithelium without parietal cells (ESN) may be the precursor of adult CM. The similarities between the fetal and adult EGJ and stomach CK expression patterns support the conclusion that adult CM has an identifiable precursor in the fetus. This would then indicate that at least a part of the adult CM has a congenital origin.     

Distinct immunohistochemical findings in columnar epithelium of esophageal inlet patch and of Barrett's esophagus

Immunohistochemistry was performed on biopsies of columnar mucosa from 11 patients with Barrett's esophagus and 11 patients with columnar mucosa in the cranial esophagus, the inlet patch. Both epithelia contained endocrine cells, immunoreactive to antisera against serotonin, glucagon, somatostatin, and pancreatic polypeptide; the specialized mucosa of Barrett's esophagus contained, in addition, neurotensin-immunoreactive cells, and in the mucosa of an inlet patch we found a gastrin cell. These findings are not compatible with some of the current theories on the origin of these epithelia. The mucosa of the inlet patch has been considered to consist of heterotopic gastric mucosa. The mucosa of the adult human stomach, however, does not contain glucagon cells. These cells are only present in the early embryonic stomach, and they disappear during embryonogenesis. According to our findings, the mucosa of the inlet patch therefore represents embryonic gastric mucosa. The specialized columnar epithelium of Barrett's esophagus has been considered to have evolved from gastric mucous neck cells. However, although glucagon cells are a feature of the embryonic stomach, neurotensin-immunoreactive cells have not been found in the gastric mucosa. Our study suggests that the specialized columnar epithelium of Barrett's esophagus originates from a very immature multipotent gastrointestinal stem cell.This investigation was supported by a grant of the Deutsche Forschungsgemeinschaft Fe 127/5-7.     

Definition of the Barrett esophagus--results of an endoscopic study with biopsy

There are two different definitions of Barrett's esophagus, a precancerous condition. The first requires circumferentially lining of the lower esophagus with columnar epithelium, the second adds tongue-like projections extending up into the squamous epithelium more than 2 cm. Carcinomas, which develop in a Barrett's esophagus almost ever are associated with metaplasia of the specialized columnar type. Endoscopic-bioptical examinations of columnar lined projections were done with 26 patients altogether. Histologically 8 patients showed metaplasia of the specialized columnar type. These results show that columnar lined projections of the specialized type are part of Barrett's esophagus.     

Diagnosis of Barrett's esophagus by pertechnetate radionuclide

In Barrett's esophagus the normal stratified squamous epithelium of esophagus is replaced by columnar epithelium and other chracteristics of gastric mucosa. Barrett's esophagus has an increased tendency to bleed and is more prone to undergo malignant change. There are many procedures used to diagnose this entity, but only by serial and multiple esophageal mucosal biopsies can the diagnosis be confirmed. Harper et al (8) demonstrated an early and intense uptake of 99m Tc pertechnetate by the stomach in animals. Since the Barrett's esophagus is lined by gastric mucosa, pertechnetate scintigraphy was used as a screening procedure. The criteria for a positive scan was an area of increased uptake of technetium extending above the normal dense uptake of stomach configuration. Pertechnetate scintigraphy was performed in 4 patients with Barrett's esophagus and 6 controls with only one false negative result. Thus pertechnetate scintigraphy is a rapid, safe, and atraumatic screening procedure.     

Definition of Barrett's oesophagus

Barrett's oesophagus is the eponym applied to the columnar epithelium-lined lower oesophagus. In 1976, Paull et al. described three types of columnar epithelia lining the distal oesophagus: a junctional or cardiac-type epithelium, a gastric fundic-type epithelium and a distinctive type of intestinal metaplasia referred to as specialized columnar epithelium. Even the normal oesophagus can be lined by 2 cm of columnar epithelium. To avoid the problem of false-positive diagnoses, arbitrary criteria for the extent of oesophageal columnar lining necessary to include patients in studies of Barrett's oesophagus were established in the early 1980s. The latter criteria require a circumferential segment of columnar lined epithelium of 2 or 3 cm in length. There are, however, a number of technical and conceptual problems related to this approach. The traditional definition excludes shorter segments and tongues of columnar lined epithelium. Only the specialized columnar epithelium defined by intestinal type goblet cells carries an inherent risk of malignancy. Therefore, a number of investigators currently define Barrett's oesophagus as any amount of columnar mucosa in the lower esophagus that has histologic evidence of goblet cells (highlighted in biopsies using the alcian blue pH 2.5 stain). Recently, short segments of specialized intestinal metaplasia in the distal oesophagus ("short segment Barrett's oesophagus") have attracted considerable attention. It has also become clear that intestinal metaplasia can occur at a normally located gastro-oesophageal junction. The etiology and clinical significance (in terms of possible relationship to the adenocarcinoma of the cardia) of this "intestinal metaplasia of the gastric cardia" and its potential relationship to Barrett's oesophagus are not yet completely understood.     

门诊护理干预对提高老年糖尿病病人生活质量评价分析

[目的]调查研究门诊护理干预对老年糖尿病病人生活质量的影响。[方法]采用随机法将50例老年糖尿病病人分为观察组和对照组各25例,两组病人采用相同的治疗方案,观察组采用门诊护理方法,对照组采用常规的护理方案进行护理。[结果]观察组在实施护理后的情绪明显好转,对疾病护理后的焦虑程度为35.56分±9.05分,与对照组的52.25分±7.12分比较,差异具有统计学意义(P<0.05)。两组病人的心率与血压状况相比存在较大的差异性(P<0.05)。[结论]通过门诊护理干预,可以有效提高老年糖尿病病人的生活质量,提高战胜疾病的信心。     

Upper esophageal web due to a ring formed by a squamocolumnar junction with ectopic gastric mucosa (another explanation of the Paterson-Kelly,Plummer-Vinson syndrome)

A patient is presented with Barrett's esophagus (lower esophagus lined with columnar epithelium) who also has a band of columnar epithelium in the upper esophagus separated from that below by normal squamous epithelium in the midesophagus. The upper most squamocolumnar junction coincided with or formed a mucosal ring as seen at endoscopy. This ring, which was first seen on barium swallow, has the radiographic appearance of that associated with the Paterson-Kelly syndrome. This patient's unique findings may provide further insight into the etiology of upper esophageal webs or rings (Paterson-Kelly syndrome).     

Immunohistochemical Analysis of Distribution of RON Receptor Tyrosine Kinase in Human Digestive Organs

The immunohistochemical distribution of RON receptor tyrosine kinase in digestive organs of both human fetus and adult, including the esophagus, stomach, duodenum, small intestine, colon, rectum, liver, gallbladder, pancreas, and spleen, was investigated semiquantitively using an affinity-purified rabbit polyclonal antibody. RON was observed to be widely distributed throughout various digestive organs and cell types in humans. The immunoreactivity for RON was observed in the epithelium of the esophagus, small intestine, colon, hepatocytes, Kupffer cells, and splenic macrophages both in the adult and the fetus, suggesting that the MSP/RON signaling pathway possesses the proper biological properties to possibly be involved in morphogenesis or differentiation of cells in these organs and cell types. Several organs differed in immunoreactivity between adult and fetus. No immunoreactive cells were found in the pancreas of adults; however, immunoreactivity was observed in acinar cells and in some of the duct or ductular cells and endocrine cells of the islet of the fetus. Similarly, immunoreactivity was not observed in gastric mucosa except in the intestinal metaplastic cells in adults; however, immunoreactivity was found in the foveolar epithelium of the stomach of the fetus. Although the biological significance of RON in malignancy is unclear, the presence of RON immunoreactivity in the fetus and it lack in the adult may indicate that RON is a oncofetal substance in human pancreas and stomach.     

Juvenile polyposis syndrome

Juvenile polyposis syndrome is a rare autosomal dominant syndrome characterized by multiple distinct juvenile polyps in the gastrointestinal tract and an increased risk of colorectal cancer.The cumulative life-time risk of colorectal cancer is 39% and the relative risk is 34.Juvenile polyps have a distinctive histology characterized by an abundance of edematous lamina propria with inflammatory cells and cystically dilated glands lined by cuboidal to columnar epithelium with reactive changes.Clinically,juven...     

Prospective evaluation of multilayered epithelium in Barrett's esophagus

OBJECTIVE: We recently identified a distinctive type of multilayered epithelium in two patients with Barrett's esophagus, which shows morphological characteristics of both squamous and columnar epithelium. This study was performed to prospectively evaluate the prevalence of multilayered epithelium in patients with Barrett's esophagus. METHODS: Mucosal biopsies were obtained from the squamocolumnar junction (Z-line) of 58 patients with endoscopic evidence of esophageal columnar epithelium and from the gastroesophageal junction in 21 patients without endoscopic evidence of esophageal columnar epithelium. Specimens were evaluated for the presence of multilayered epithelium and goblet cells. RESULTS: Twenty-four of 58 (41%) of the patients with endoscopic evidence of esophageal columnar epithelium had multilayered epithelium compared with only one of 21 patients (5%) in the control group (p = 0.005). Of the 58 patients in the study group, 43 had goblet cell metaplasia and 15 did not (p < 0.001). Only patients with goblet cell metaplasia had multilayered epithelium. Shorter lengths of columnar epithelium were noted in the 24 patients with goblet cells and multilayered epithelium compared with the 19 patients with goblet cells and no multilayered epithelium (p < 0.05). CONCLUSIONS: Multilayered epithelium is strongly associated with goblet cell metaplasia in patients with endoscopic evidence of esophageal columnar epithelium. These data support the hypothesis that multilayered epithelium may represent a transitional stage in the development of Barrett's esophagus.     

Use of a Novel Monoclonal Antibody in Diagnosis of Barrett's Esophagus

A novel monoclonal antibody (MAbDAS-1), that specifically reacts with colonic but not small intestinal epithelium, recognizes specialized columnar epithelium (SCE) in the esophagus. The frequency of its reactivity in biopsy specimens of patients with endoscopically suspected Barrett's Esophagus (BE) is examined. Fifty-two biopsy specimens of the distal esophagus from 38 patients were tested by immunoperoxidase method using MAbDAS-1. Fifty-four samples of cardia-type mucosa biopsied from the stomach were used as controls. Results were compared with histology and Alcian blue/high iron diamine (AB/HID). Of the 52 specimens, 29 had glandular epithelium and the rest had only squamous epithelium. Ten were diagnosed to have SCE by histology. All 10 samples reacted with MAbDAS-1 and with Alcian blue. Of the remaining 19 specimens, five also reacted with MAbDAS-1. None of the squamous epithelium and cardia specimens reacted with MAbDAS-1. MAbDAS-1 may detect intestinal metaplasia of the esophagus of colonic phenotype in the absence of histological evidence of SCE.     

Adenocarcinoma arising in Barrett's esophagus after total gastrectomy

A 64-yr-old Japanese male who underwent a partial gastrectomy for a duodenal ulcer at the age of 21, a total resection of the remnant stomach for a stomal ulcer at age 25, and in whom Barrett's esophagus was diagnosed at age 47, was found to have a tumor at the distal esophagus and was operated on by thoracic esophagectomy. The tumor was a well to moderately differentiated adenocarcinoma invading down to the muscularis propria. The entire esophageal mucosa in the resected specimen was lined by columnar epithelium. This tumor was thought to derive from the Barrett's esophageal epithelium.     

Prevalence and topography of intestinal metaplasia in columnar lined esophagus

OBJECTIVES: Barrett's mucosa is considered as a mosaic of three epithelial types but little is known about the topography of intestinal metaplasia in columnar lined esophagus. The aims of the study were to determine the prevalence of intestinal metaplasia within long and short segments of columnar lined esophagus and to analyze the distribution of the intestinal metaplasia within long segments of Barrett's esophagus. PATIENTS AND METHODS: The study was performed on the initial endoscopy carried out among 112 patients enrolled in an endoscopic surveillance program. Seventy-two patients with columnar mucosa extending more than 3 cm into the esophagus (group I) and 40 patients with a short segment of columnar mucosa (group II) had multiple biopsies according to a standardized protocol. 1163 biopsies were analyzed on the whole: 949 biopsies in group I and 214 biopsies in group II. RESULTS: Intestinal metaplasia was identified among 650 (68.5%) and 50 (23.4%) biopsies in groups I and II respectively (P<10-7). The proportion of biopsies with foci of intestinal metaplasia increased significantly with the length of the columnar mucosa. The diagnosis of Barrett's esophagus was confirmed in 100% of the patients in group I and in 45% of the patients in group II. In long segments of Barrett's esophagus, intestinal metaplasia was more frequently observed in the 2 upper thirds of the columnar mucosa that in the lower third (P<10-7). Detailed mapping of the distribution of epithelial types within the columnar lined esophagus identified three patterns of distribution of intestinal metaplasia within long segments of Barrett's esophagus: unifocal, multifocal and diffuse, in 5%, 56% and 39% of the patients respectively. Dysplasia was present in 15% of patients with long segments of Barrett's esophagus and 11% of patients with short segments (NS). CONCLUSION: The distribution of intestinal metaplasia within columnar lined esophagus is heterogeneous and three distinct patterns can be identified: unifocal, multifocal and diffuse. Considering the risk of sampling error, the current recommendations concerning the biopsy protocols are mandatory until the validation of new techniques such as chromoendoscopy or magnifying endoscopy.     

Cell kinetic study on histogenesis of Barrett's esophagus using rat reflux model

BACKGROUND: To elucidate the histogenesis of Barrett's esophagus and esophageal adenocarcinoma, we designed a duodeno-gastric reflux model in which normal stomach function and normal nutritional status are retained. METHODS: Male Wistar rats were used in the experiment. The esophago-gastric junction was side-to-side anastomosed to a loop of jejunum about 3 cm distal to Treitz's ligament. The animals were not exposed to any known carcinogens during the experiment. Sequential morphological changes were studied for up to 50 weeks after surgery. Serial sections were made and stained with hematoxylin and eosin (H&E). In addition, immunohistochemical staining for bromodeoxyuridine (BrdU) was performed along with histochemical staining for mucins using paradoxical concanavalin A (ConA), galactose oxidase Schiff (GOS), and high-iron diamine-alcian blue (HID-AB). RESULTS: Severe esophagitis with squamous cell hyperplasia was noted in all animals after surgery. At week 20 after surgery, glandular metaplastic cells positive for ConA first appeared within the basal cell layer of esophageal squamous cell epithelium, and then GOS-positive cells and HID-AB goblet cells appeared. This is a characteristic of the specialized columnar epithelium of Barrett's esophagus. We detected esophageal adenocarcinomas in 1 out of 8 subjects at week 40 and in 3 out of 8 subjects at week 50 after surgery. CONCLUSIONS: Reflux of duodenal contents causes specialized columnar epithelium of Barrett's esophagus and esophageal adenocarcinoma. As part of the sequence of events leading to the development of Barrett's esophagus, pyloric-foveolar metaplasia was observed followed by the appearance of intestinal goblet cells. The pyloric-foveolar metaplasia appears to be associated with chronic mucosal damage and regeneration. This multiplastic cell lineage is referred to as 'gut-regenerative cell lineage' (GRCL).     

BARRETT'S ESOPHAGUS: CLINICAL, ENDOSCOPIC, AND HISTOLOGIC SPECTRUM IN FIFTY PATIENTS

Abstract The columnar lined (Barrett's) esophagus is an acquired condition resulting from chronic gastroesophageal reflux. The clinical spectrum of 50 consecutive cases of endoscopically consistent, histologically proven Barrett's esophagus was reviewed. The mean age of patients was 65.9 ± 12.4 (SD) years with only four patients younger than 50 years. The predominant presenting symptoms were dysphagia, heartburn, and regurgitation. At endoscopy, the columnar lined segment extended over 6.5 ± 3.0 cm of the lower esophagus. Specialised columnar (intestinal) epithelium was the most frequent histological type identified. Radiologic or endoscopic evidence of a hiatal hernia was present in the majority. Complications were present at endoscopy in 38 (76%) patients. Reflux esophagitis (56%) was present at the area of the squamo-columnar junction. Stricture formation (38%) and ulceration (36%) were located either at the squamo-columnar junction or more distally within the columnar epithelium. Two patients (4%) had adenocarcinoma arising in a segment of Barrett's esophagus at presentation. Treatment included physical measures, dilatation, and cimetidine. Bougienage in 20 patients was successful in alleviating dysphagia but multiple treatment sessions were often necessary. Although esophagitis readily resolved with cimetidine therapy, ulceration was generally resistant to medical therapy. Indeed, by two months, healing was achieved in only five of 12 patients. Endoscopic surveillance of 12 patients who received cimetidine (1 g/day) for at least 12 months showed no regression of the metaplastic mucosa.     

Pathophysiology and treatment of Barrett’s esophagus

Gastroesophageal reflux disease (GERD) affects an estimated 20% of the population in the United States. About 10%-15% of patients with GERD develop Barrett’s esophagus, which can progress to adenocarcinoma, currently the most prevalent type of esophageal cancer. The esophagus is normally lined by squamous mucosa, therefore, it is clear that for adenocarcinoma to develop, there must be a sequence of events that result in transformation of the normal squamous mucosa into columnar epithelium. This sequence begins with gastroesophageal reflux, and with continued injury metaplastic columnar epithelium develops. This article reviews the pathophysiology of Barrett’s esophagus and implications for its treatment. The effect of medical and surgical therapy of Barrett’s esophagus is compared.