Visible Columnar-lined Esophagus Research Articles

Intestinal Metaplasia of the Cardia is Associated With Barrett Esophagus and Esophageal Adenocarcinoma

The cardia, defined as the area distal to the endoscopic gastro-esophageal junction (GEJ), is rarely subject to biopsy in patients with gastro-esophageal reflux disease (GERD). In this study we examine the clinical significance of intestinal metaplasia (IM) found in a biopsy of the cardia. The epithelia in biopsies taken 1 cm distal to the endoscopic GEJ in 963 patients undergoing esophago-gastroduodenoscopy were classified into cardiac mucosa (CM) with IM, CM without IM, oxyntocardiac mucosa (OCM) and gastric oxyntic mucosa. The associations of these mucosal types with visible columnar lined esophagus (CLE) without IM, CLE with IM, and esophageal neoplasia proximal and within 2 cm distal to the endoscopic GEJ were determined. Cardiac mucosa with IM in a biopsy 1 cm distal to the endoscopic GEJ was present in 18 (21%) of the 86 patients with all visible CLE ( P < .01), in 16 (22%) of the 74 patients with visible CLE with IM (Barrett esophagus) ( P < .01), and in 12 (22%) of the 55 patients with neoplasia proximal and within 2 cm distal to the endoscopic GEJ ( P = .01). All other epithelial types had no such associations. The significant association of CM with IM in the cardia with visible CLE, visible CLE with IM, and esophageal neoplasia proximal and within 2 cm distal to the endoscopic GEJ indicates that CM with IM 1 cm distal to the endoscopic GEJ is a likely precursor of these entities. Identification of precursor lesions of CLE and esophageal neoplasia has the potential to stimulate new methods aimed at preventing Barrett esophagus and esophageal adenocarcinoma.

Functional performance in late-onset GM2 gangliosidosis (Tay-Sachs and Sandhoff diseases), longitudinal data over 3 consecutive years

Anatomically, the normal state in the human adult is an esophagus that is entirely tubular and has a sharp transition to the saccular stomach where it forms an acute angle of His. Histologically, the normal esophagus is lined entirely by stratified squamous epithelium, transitioning at the gastroesophageal junction to gastric oxyntic epithelium, which lines the entire proximal stomach. Cardiac epithelium is normally absent. Its presence indicates the abnormal state of the dilated distal esophagus that results from damage to the abdominal segment of the lower esophageal sphincter. It is the early stage of gastroesophageal reflux disease (GERD) that is presently ignored and mistaken as normal proximal stomach. This normal state is not recognized at present time by the myth that 1–4 mm of cardiac epithelium normally exists between the distal end of the squamous epithelium and the proximal limit of gastric oxyntic epithelium. Evidence that eradicates this myth includes the facts: (1) The cardiac epithelium is absent in some people. (2) The presence of cardiac epithelium in the dilated distal esophagus is associated with the presence of submucosal esophageal glands. (3) Its extent varies from 0 to <15 mm in persons without GERD and increases up to 30 mm in patients with GERD. (4) The presence of any cardiac epithelium is associated with abnormal acid exposure, reflux esophagitis, and manometric abnormalities in the lower esophageal sphincter. (5) Cardiac epithelium extends into the thoracic esophagus as visible columnar-lined esophagus (CLE) in patients with severe GERD associated with severe lower esophageal sphincter damage. (6) The morphologic, immunohistochemical, and molecular features of cardiac epithelium in the dilated distal esophagus and visible CLE are identical and different than those of distal gastric epithelium. Eradication of the myth that cardiac epithelium is normally absent is essential to the understanding of the pathologic changes associated with the earliest stage of GERD. Existence of the myth at present prevents this understanding.

Barrett's esophagus is frequently overdiagnosed in clinical practice: results of the Barrett's Esophagus Endoscopic Revision (BEER) study

The published prevalence of Barrett's esophagus (BE) varies from 0.9% to 25%, in part because of differences in the endoscopic interpretation of the disease. We studied the accuracy of diagnosis in 130 patients previously labeled as having BE. Our aim was to determine the interobserver consistency of endoscopic findings and assess the percentage of patients with confirmed BE versus those with a revised diagnosis. Patients previously diagnosed with BE of any length and due for surveillance endoscopy were eligible for study. After intensive consensus anatomic and endoscopic review, study patients underwent endoscopy and biopsy by 1 of 3 endoscopists. BE was defined as any length of columnar-lined esophagus with goblet cells. Patients were photographed/videotaped for review by the other 2 endoscopists, and BE was either confirmed or revised. Eighty-eight patients (67.7%) had confirmed BE, and 42 (32.3%) had their diagnosis revised to no BE (95% confidence interval, 24.4%-41.1%) because there was no visible columnar-lined esophagus proximal to the gastric folds or no goblet cells were found on biopsy. BE length, site of previous endoscopy, age, sex, and hiatal hernia size were predictors of revision. All 3 endoscopists agreed on all confirmed BE cases and 38 of 42 of those revised. Retrospective analysis, possible sampling error. BE is overdiagnosed in clinical practice with important implications for patient care including increased costs, reduced insurability, and psychological stress. The true BE cancer risk may also be underestimated. This study suggests the need for a better definition of the gastroesophageal junction, stricter accountability for BE diagnosis, and improved endoscopic education.

Columnar-Lined Esophagus Without Intestinal Metaplasia Has No Proven Risk of Adenocarcinoma

Intestinal metaplasia in the columnar-lined esophagus (CLE) has long been recognized as the most significant histologic risk indicator for esophageal adenocarcinoma. Recent concern has been expressed, however, that nonintestinalized metaplastic columnar epithelia (cardiac epithelium in the esophagus) may also indicate risk. Of 2586 consecutive patients undergoing endoscopy and biopsy in the Foregut Surgery Department, we selected (a) 214 patients with a visible CLE who had systemic 4-quadrant biopsies at 1 to 2 cm intervals, with the most proximal biopsy straddling the squamocolumnar junction, and (b) 109 patients without systematic biopsy who had dysplasia or adenocarcinoma. In the first group, 187 (87.4%) patients had intestinal metaplasia, and 27 (12.6%) had cardiac epithelium. Dysplasia or adenocarcinoma was present in 55 patients, all with intestinal metaplasia; its presence was significantly higher than in the cardiac epithelium group, none of whom had dysplasia or adenocarcinoma (P=0.01). In the second group with limited sampling, 49 had only tumor tissue in the biopsy. Of 60 patients with nontumor epithelium, only 34 (56.7%) had residual intestinal metaplasia. We conclude that systematic biopsies of CLE as described in this study separate patients into those with and without intestinal metaplasia in such a manner as to remove the possibility of false-negative diagnosis of intestinal metaplasia. When intestinal metaplasia is absent using this biopsy protocol, the patient is at no or extremely low risk for dysplasia and cancer. When biopsies have a lower level of sampling of the segment of CLE, the absence of intestinal metaplasia cannot be interpreted as a true negative for intestinal metaplasia. Inadequate sampling is a powerful reason why the near absolute association between intestinal metaplasia and adenocarcinoma is not seen in some studies.

The Dilated Distal Esophagus

Present management algorithms for patients with gastroesophageal reflux disease (GERD) limit endoscopy to patients with advanced disease. When endoscopy is performed, biopsy is limited to patients who have a visible columnar-lined esophagus. Biopsy is not recommended for patients whose endoscopy is normal. This algorithm results in the failure to evaluate patients with early stages of GERD at a pathologic level. We report 714 patients with normal endoscopic findings irrespective of symptoms who had adequate biopsies taken from the squamocolumnar junction and the area 1-cm distal to this from mucosa that had rugal folds. Concurrent biopsies were also taken from the gastric body and/or antrum. All patients had a gap between their esophageal squamous epithelium and gastric oxyntic mucosa in the junctional region composed of oxyntocardiac ± cardiac ± intestinal epithelia. A total of 643 (90.1%) patients had no significant pathology in the gastric antrum and/or body, indicating that the squamooxyntic gap was an isolated abnormality in this region in all but 71 (9.9%) patients. The gap contained only oxyntocardiac epithelium in 71 (9.9%) patients, cardiac mucosa without intestinal metaplasia in 482 (67.5%) patients, and intestinal metaplasia in 161 (22.6%) patients. The pathologic interpretation of biopsies taken from the gastroesophageal junction is confusing and has significant interobserver variation. This results from lack of agreement as to whether these biopsies originate in the proximal stomach ("gastric cardia") or in the esophagus. We provide evidence that the presence of oxyntocardiac ± cardiac ± intestinal epithelia in biopsies from patients who are endoscopically normal is diagnostic of a dilated GERD-damaged distal esophagus. The dilated distal esophagus is the pathologic manifestation of destruction of the abdominal segment of the lower esophageal sphincter. Its presence is the pathologic basis of early GERD, which is missed if patients who are endoscopically normal are not biopsied, as is the present recommendation. Its recognition allows for accurate and evidence-based interpretation of biopsies from this region and removes the present confusion and permits the development of a reproducible pathologic diagnostic method.

Histopathology of columnar-lined esophagus in patients with gastroesophageal reflux disease

The question of whether an endoscopically normal-appearing esophagogastric junction should be biopsied in patients with gastroesophageal reflux disease is controversial. We have addressed this issue using endoscopy and histopathology. A total of 114 consecutive patients (58 males) with symptoms of gastroesophageal reflux disease prospectively underwent endoscopy, including biopsy sampling from the esophagogastric junction. Endoscopically visible columnar-lined esophagus was defined by the presence of gastric-type mucosa above the level of the rise of the gastric folds. Histopathology was conducted using the Paull-Chandrasoma classification. Of the 114 patients, 85 (74.6%) had endoscopically visible columnar-lined esophagus of length < or =0.5 cm (n = 82), 1 cm (n = 2) and 7 cm (n = 1); 29 patients (25.4%) had a normal endoscopic junction. All patients had histopathologic columnar-lined esophagus. Intestinal metaplasia and low-grade dysplasia was identified in 26 (22.8%) and 5 (4.4%) individuals, respectively, and was not statistically different in endoscopically normal vs. abnormal junction (P = 0.408 for intestinal metaplasia, P = 0.775 for low grade dysplasia). Intestinal metaplasia was independent from endoscopic esophagitis (P = 0.398) and hiatal hernia (P = 0.405). Columnar-lined esophagus cannot be excluded by endoscopy. In patients with gastroesophageal reflux disease, biopsy sampling of normal-appearing junction is recommended for histopathologic exclusion of intestinal metaplasia and low-grade dysplasia.

Videoendoscopy and histopathology of the esophagogastric junction in patients with gastroesophageal reflux disease

During endoscopy the stomach is considered to rise at the level of the 'gastric' folds; however, anatomical studies have demonstrated that the proximal gastric folds may in fact be esophageal. This prospective study was designed to assess the histopathology of endoscopically visible proximal gastric folds in patients with gastroesophageal reflux disease. 35 consecutive patients (20 males) with gastroesophageal reflux disease underwent video endoscopy, including biopsy sampling from the endoscopically visible esophagogastric junction (0 cm, 0.5 cm and 1.0 cm distal to the rise of gastric folds and 0.5 cm and 1.0 cm proximal to it). Endoscopy was digitally recorded and reviewed for assignment of biopsy level. Columnar-lined esophagus and esophagitis were cataloged according to the Paull-Chandrasoma histopathologic classification and the Los Angeles endoscopic classification. Endoscopy: Normal endoscopic esophagogastric junction was seen in 11 (31%) patients and visible columnar-lined esophagus < or = 0.5 cm in 24 (69%). Columnar-lined esophagus extended 1.0 cm in 22.8% of patients and 0.5 cm in 51.4%, distal to the rise of the gastric folds. In all patients columnar-lined esophagus was interposed between squamous epithelium and gastric oxyntic mucosa. Thus, so-called gastric folds contained mucosa of esophageal origin in all patients. Intestinal metaplasia (Barrett esophagus) was detected in eight (22.9%) patients. Endoscopy cannot exclude histopathologic columnar-lined esophagus within gastric rugae. Thus, visible 'gastric' folds should not be used for definition of the esophagogastric junction but as a reference landmark for biopsy sampling during endoscopy.