Cytokeratin immunoreactivity patterns in short-segment Barrett's esophagus in Japanese patients

BACKGROUND: The origin of intestinal metaplasia at the esophagogastric junction has clinical importance. However, it can be difficult to differentiate between intestinal metaplasia of short-segment Barrett's esophagus and cardiac intestinal metaplasia due to Helicobacter pylori infection. Specific patterns of cytokeratin (CK)7 and CK20 have been detected in long-segment Barrett's esophagus. The aim of the present study was to assess the immunostaining patterns associated with short-segment Barrett's esophagus. AIMS: Paraffin-embedded biopsy specimens were prepared from 128 patients with intestinal metaplasia of long-segment Barrett's esophagus (n = 3), short-segment Barrett's esophagus without H. pylori infection (n = 22), short-segment Barrett's esophagus with H. pylori infection (n = 22), and cardiac mucosa (n = 49) and gastric mucosa from antrum and fundus (n = 44) with H. pylori infection. Sections were prepared and immunostained for CK7 and CK20. RESULT: A Barrett's CK7/20 pattern was present in all three patients (100%) with long-segment Barrett's esophagus, 21 of 22 patients (95%) with short-segment Barrett's esophagus without H. pylori infection, and six of 22 patients (27%) with short-segment Barrett's esophagus with H. pylori infection (P < 0.05). CONCLUSION: Intestinal metaplasia of short-segment Barrett's esophagus in patients without H. pylori infection is thought to be similar to that seen in long-segment Barrett's esophagus.     

Cytokeratin immunoreactivity patterns in the diagnosis of short-segment Barrett's esophagus

BACKGROUND & AIMS: The origin of intestinal metaplasia in short segments of columnar mucosa at the esophagogastric junction has clinical importance but can be difficult to determine at endoscopy. Cytokeratin (CK) 7 and 20 patterns are specific for long-segment Barrett's esophagus; however, their utility in short-segment Barrett's esophagus has not been assessed. METHODS: Endoscopic biopsy specimens from patients with long-segment Barrett's esophagus (n = 49), suspected short-segment Barrett's esophagus (n = 43), and gastric intestinal metaplasia (n = 26) were immunostained for CK7 and CK20. Comprehensive clinical data were obtained, including age, gender, and hiatal hernia and Helicobacter pylori status. RESULTS: A Barrett's CK7/20 pattern was present in 48 (98%) of 49 patients with long-segment Barrett's esophagus, 35 (82%) of 43 with suspected short-segment Barrett's esophagus, and 0 (0%) of 26 patients with gastric intestinal metaplasia. Patients with suspected short-segment Barrett's esophagus with a Barrett's CK7/20 pattern were clinically similar to those with long-segment Barrett's esophagus. In contrast, patients with suspected short-segment Barrett's esophagus with no Barrett's CK7/20 pattern were clinically similar to those with gastric intestinal metaplasia. CONCLUSIONS: A Barrett's CK7/20 pattern identifies a subset of patients with suspected short-segment Barrett's esophagus who have a patient profile similar to that seen in long-segment Barrett's esophagus. A Barrett's CK7/20 pattern is an objective marker of Barrett's mucosa that in conjunction with appropriate clinical and endoscopic data can be used by clinicians to better define patients with short-segment Barrett's esophagus.     

Characteristics of intestinal metaplasia in the gastric cardia

OBJECTIVE: Intestinal metaplasia of the gastroesophageal junction is frequently grouped together with Barrett's esophagus. The area of the gastroesophageal junction is comprised of the distal esophagus and the gastric cardia. The aim of the present study was to assess whether intestinal metaplasia in the distal esophagus and gastric cardia represent two different entities with a different set of risk factors. METHODS: Patients presenting for elective upper endoscopy were enrolled into a prospective study. The presence of gastritis and intestinal metaplasia was evaluated in gastric biopsies taken from the antrum, corpus, and cardia. Barrett's esophagus was defined by the presence of any length of columnar mucosa above the gastroesophageal junction. RESULTS: Of 302 patients, 50 patients had intestinal metaplasia of the gastric cardia, 73 Barrett's esophagus, and 116 erosive esophagitis. Men were more prone than women to develop Barrett's esophagus or erosive esophagitis. Both conditions were also more common among whites than nonwhites. Smoking was particularly common among patients with Barrett's esophagus. Patients with cardiac intestinal metaplasia did not share these demographic characteristics. The prevalence of daily reflux symptoms, erosive esophagitis, and Barrett's esophagus was similar among patients both with and without cardiac intestinal metaplasia. However, atrophy and intestinal metaplasia of the gastric antrum and corpus were found more frequently among patients with than without cardiac intestinal metaplasia. CONCLUSIONS: Intestinal metaplasia of the gastric cardia is different from Barrett's esophagus. Although cardiac intestinal metaplasia is closely associated with signs of gastritis in other parts of the stomach, gastroesophageal reflux disease does not seem to be a risk factor. A diagnosis of Barrett's esophagus should not be made based on the presence of intestinal metaplasia within the cardiac portion of the gastroesophageal junction.     

Short segment Barrett's esophagus and distal gastric intestinal metaplasia

BACKGROUND: Short segment Barrett's esophagus is defined by the presence of <3 cm of columnar-appearing mucosa in the distal esophagus with intestinal metaplasia on histophatological examination. Barrett's esophagus is a risk factor to develop adenocarcinoma of the esophagus. While Barrett's esophagus develops as a result of chronic gastroesophageal reflux disease, intestinal metaplasia in the gastric cardia is a consequence of chronic Helicobacter pylori infection and is associated with distal gastric intestinal metaplasia. It can be difficult to determine whether short-segment columnar epithelium with intestinal metaplasia are lining the esophagus (a condition called short segment Barrett's esophagus) or the proximal stomach (a condition called intestinal metaplasia of the gastric cardia). AIMS: To study the association of short segment Barrett's esophagus (length <3 cm) with gastric intestinal metaplasia (antrum or body) and infection by H. pylori. PATIENTS AND METHODS: Eight-nine patients with short segment columnar-appearing mucosa in the esophagus, length <3 cm, were studied. Symptoms of gastroesophageal reflux disease were recorded. Biopsies were obtained immediately below the squamous-columnar lining, from gastric antrum and gastric corpus for investigation of intestinal metaplasia and H. pylori. RESULTS: Forty-two from 89 (47.2%) patients were diagnosed with esophageal intestinal metaplasia by histopathology. The mean-age was significantly higher in the group with esophageal intestinal metaplasia. The two groups were similar in terms of gender (male: female), gastroesophageal reflux disease symptoms and H. pylori infection. Gastric intestinal metaplasia (antrum or body) was diagnosed in 21 from 42 (50.0%) patients in the group with esophageal intestinal metaplasia and 7 from 47 (14.9%) patients in the group with esophageal columnar appearing mucosa but without intestinal metaplasia. CONCLUSION: Intestinal metaplasia is a frequent finding in patients with <3 cm of columnar-appearing mucosa in the distal esophagus. In the present study, short segment intestinal metaplasia in the esophagus is associated with distal gastric intestinal metaplasia. Gastroesophageal reflux disease symptoms and H. pylori infection did not differ among the two groups studied.     

Immunohistochemical markers for Barrett's esophagus and associations to esophageal Z-line appearance

BACKGROUND: Data from previous studies on intestinal metaplasia at the gastroesophageal junction have been conflicting, which makes the diagnosis of Barrett's esophagus less obvious. This may partly be due to the lack of a reliable classification of the Z-line appearance. We previously proposed such a classification (the ZAP classification) that was shown to correlate with the prevalence of intestinal metaplasia. The use of different immunohistochemical techniques has increased in the study of intestinal metaplasia. In the present study our aim was to 1) evaluate the impact of different antibodies, namely cytokeratin (CK) 7, 13, and 20, CaCO3/73, and FBB2/29, in order to differentiate between Barrett's esophagus and cardia intestinal metaplasia, and 2) explore the staining patterns in different ZAP grades. METHODS: Thirty-nine specimens with intestinal metaplasia were compared--9 from Barrett's esophagus, 6 from cardia, and 24 from the Z-line. The Z-line specimens were evaluated with respect to ZAP grade. RESULTS: No differences were encountered regarding staining patterns for CK13 and CaCO3/73 in Barrett's esophagus and cardia. The staining pattern of CK7/20 was significantly different between Barrett's esophagus and cardia. CK7/20 showed a rising frequency of Barrett's esophagus staining pattern with rising ZAP grade. CONCLUSION: CK7/20 is a feasible marker for Barrett's esophagus. Intestinal metaplasia in different ZAP grades differs regarding expression of immunohistochemical markers.     

Helicobacter pylori infection, not gastroesophageal reflux, is the major cause of inflammation and intestinal metaplasia of gastric cardiac mucosa

OBJECTIVE: The etiology of inflammation below the normal Z-line is an area of intense debate. Some suggest this is the earliest change of chronic gastroesophageal reflux disease (GERD), whereas others indict Helicobacter pylori (H. pylori) as the main cause. The aim of this study was to evaluate the relationship among inflammation of gastric cardiac mucosa (carditis), H. pylori infection, and intestinal metaplasia in patients with GERD and Barrett's esophagus compared with age-matched controls. METHODS: Patients with GERD and Barrett's esophagus were compared with controls undergoing endoscopy for a variety of other conditions. Endoscopic biopsy specimens from the gastric cardia (obtained on retroflexed view), fundus, and antrum were evaluated for inflammation, H. pylori infection, and intestinal metaplasia. RESULTS: The prevalence of H. pylori infection did not significantly differ among the study populations: controls (42%), GERD (33%), and Barrett's esophagus (27%) (p = 0.20). However, the prevalence of carditis significantly decreased from the control group (30%) to those with GERD (23%) and Barrett's esophagus (11%) (p = 0.03). Overall, 42 of 51 (82%) patients with carditis had H. pylori; all had pangastritis. The prevalence of cardia intestinal metaplasia also significantly decreased from the control group (15%) to those with GERD (4%) and Barrett's esophagus (0%) (p = 0.003). Of 13 patients with cardia intestinal metaplasia, 12 had carditis, 10 had H. pylori infection, and seven had intestinal metaplasia elsewhere in the stomach. CONCLUSIONS: Inflammation of gastric cardiac mucosa decreases in prevalence from controls to patients with GERD and Barrett's esophagus and correlates strongly with H. pylori infection. Cardia intestinal metaplasia is associated with H. pylori-related cardiac inflammation and intestinal metaplasia elsewhere in the stomach.     

Comparative study of intestinal metaplasia and mucin staining at the cardia and esophagogastric junction in 225 symptomatic patients presenting for diagnostic open-access gastroscopy

Objective: Adenocarcinoma around the esophagogastric junction (EGJ) is increasing in incidence, and is frequently associated with areas of macroscopic or microscopic intestinal metaplasia (IM). The aim of this study was to define the incidence and type of metaplastic changes in the cardia and at the EGJ in symptomatic patients in whom there was no endoscopic columnar segment. Methods: Patients attending for open-access gastroscopy had three sets of endoscopic biopsies taken at 3-cm intervals, from cardia, EGJ, and distal esophagus. Hematoxylin and eosin, Alcian blue/PAS (AB/PAS), and high-iron diamine/Alcian blue (AB/HID) were used to define and characterize IM. Results: Of 225 patients, eight (4%) had carcinoma, eight (4%) had conventional long-segment Barrett's esophagus, 15 (7%) showed endoscopic short-segment Barrett's change, with no endoscopic Barrett's in 194 (86.2%). Of the latter, 34 (17.5%) had IM at the EGJ, and nine (4.6%) had IM at the cardia on hematoxylin and eosin. Acid mucin stains were positive at the EGJ in 135 (69.6%) and at the cardia in 75 (38.7%). Metaplasia at the EGJ was associated with sulphomucins (   p < 0.0001  ) and involved the surface glandular epithelium (   p < 0.0001  ) more frequently than the cardia. Metaplasia was not related to reflux symptoms, hiatus hernia, or endoscopic esophageal inflammation. Ninety percent of those with IM detectable by hematoxylin and eosin were taking acid suppression, compared with 72.8% overall. Conclusions: Intestinal metaplasia is very common at the esophagogastric junction and gastric cardia, with marked differences in incidence and characteristics of mucin staining between the two sites. The relationship of intestinal metaplasia to the development of carcinoma is yet to be determined.     

Does methylene blue detect intestinal metaplasia in Barrett's esophagus?

BACKGROUND: Methylene blue has been used to selectively stain areas of specialized intestinal metaplasia in Barrett's esophagus. The sensitivity, specificity, and negative and positive predictive values for the detection of specialized intestinal metaplasia by methylene blue chromoendoscopy were determined in patients with Barrett's esophagus. METHODS: Thirty patients with Barrett's esophagus underwent endoscopy with biopsy specimens obtained from areas that stained positive and negative with methylene blue. Histopathologic findings were compared with methylene blue chromoendoscopy findings. RESULTS: Two hundred ninety-two biopsy specimens (mean 9.7/patient) were obtained: 203 from stained and 89 from unstained areas. Sensitivity, specificity, and negative and positive predictive values for detection of specialized intestinal metaplasia were, respectively, 72%, 46%, 22%, and 89%. Comparing 187 biopsy specimens from patients with long-segment Barrett's esophagus with 105 specimens from patients with short-segment Barrett's esophagus, the sensitivity, specificity, and negative and positive predictive values were, respectively, 77% versus 63% (p = 0.044), 79% versus 21% (p < 0.002), 28% versus 14% (p = 0.219), and 97% versus 73% (p < 0.002). The odds ratio for detection of specialized intestinal metaplasia in stained areas was 12.40 in long-segment and 0.45 in short-segment Barrett's esophagus. CONCLUSIONS: Data from this study confirm the value of methylene blue chromoendoscopy for detection of specialized intestinal metaplasia in long-segment Barrett's esophagus, but not in short-segment Barrett's esophagus.     

Is intestinal metaplasia a necessary precursor lesion for adenocarcinomas of the distal esophagus,gastroesophageal junction and gastric cardia?

Adenocarcinoma of the distal esophagus and gastroesophageal junction are believed to arise in Barrett's esophagus with intestinal metaplasia. Whether adenocarcinoma can arise in columnar lined esophagus without intestinal metaplasia is in doubt. Whether adenocarcinoma of the gastric cardia arises in intestinal metaplasia of the gastric cardia is also in doubt. We aim to evaluate the relationship of size and stage of adenocarcinoma of the distal esophagus, gastroesophageal junction and gastric cardia to intestinal metaplasia and other types of columnar epithelium. Seventy-four patients who had esophagogastrectomy for adenocarcinomas in this region were examined histologically to assess the frequency of residual intestinal metaplasia in the surrounding epithelium. Tumors without residual intestinal metaplasia were evaluated for the presence of other columnar epithelia and correlated with tumor size and stage. Cardiac mucosa was present around all tumors. Residual intestinal metaplasia was present in 48 (65%) tumors, including 33/38 (87%) distal esophageal, 10/25 (45%) junctional and 5/11 (45%) gastric cardia tumors. The prevalence of intestinal metaplasia was 100% in all tumors that were less than 1 cm in maximum diameter and all intramucosal tumors. The prevalence of residual intestinal metaplasia decreased with increasing tumor size and stage. These data strongly support the contention that adenocarcinomas of this region, including those in the gastric cardia, arise in intestinal metaplastic epithelium. The absence of residual intestinal metaplasia in larger tumors is the result of tumor overgrowing the intestinal metaplasia from which it arose.     

The Use of Cytokeratin Stain to Distinguish Barrett’s Esophagus from Contiguous Tissues: A Systematic Review

Our objective was to systematically review the existing literature regarding the use of cytokeratin (CK) stain in differentiating Barrett’s esophagus (BE) from tissues of the gastric cardia, corpus, or antrum, with or without intestinal metaplasia (IM). Pubmed was searched for full publications in English (1983–2005) addressing the use of CK for differentiation of BE from contiguous tissues. Information was collected on the study sample, blinding, the methods used for CK staining, and for defining and applying the gold standard tests. Test characteristics were obtained or calculated. Sixteen studies (containing 46 comparisons) met the inclusion and exclusion criteria. Immunostaining for CK 7 and 20 was generally highly specific in distinguishing long-segment BE from antrum IM, fundus IM, or noncardiac gastric IM; 27 comparisons showed statistically significant differences. However, only 8 of 15 comparisons (6 of 12 studies) reported significant differences in CK staining patterns between BE and gastric cardia IM with a high sensitivity (89%–100%) and specificity (83%–100%) for long-segment BE and lower estimates for short-segment BE, while the other seven comparisons showed no significant differences and a very low sensitivity. Examination by a blinded pathologist was reported in five of six positive studies and in only one of six of the negative studies. In addition, variation in the patient populations, use of surgical resection versus endoscopic biopsies, and biopsy sampling technique in endoscopic studies may have accounted for these differences. Finally, two studies did not find significant differences in CK staining patterns between BE and normal cardiac mucosa. In conclusions, CK immunostaining has not performed well in differentiating BE, especially short-segment BE, from cardia IM. There seems to be a spectrum bias where the accuracy varies with different tested populations. CK immunostaining distinguished well between BE and IM in noncardiac segments of the stomach; however, these comparisons are not clinically relevant.     

Prospective Evaluation of Intestinal Metaplasia and Dysplasia Within the Cardia of Patients with Barrett's Esophagus

The prevalence of cardia versus noncardiagastric intestinal metaplasia in patients with Barrett'sesophagus was assessed prospectively. Four-quadrantbiopsies were obtained from the cardia from 119consecutive patients with Barrett's esophagus and 64control patients. Gastric surveillance biopsies wereobtained in 108 of the Barrett's patients and 58 controlpatients. There was a significantly greater prevalence of cardia intestinal metaplasia inshort-segment Barrett's (10.2%), but not traditionalBarrett's (3.3%), compared to control patients (0%) (P= 0.009). Dysplastic changes were significantly morefrequent in the metaplastic epithelium within theesophagus than in the cardia (P < 0.0001). Asignificantly greater prevalence of noncardia intestinalmetaplasia compared to cardia intestinal metaplasia wasfound in each of the three groups of patients;however, the prevalence of noncardia intestinalmetaplasia between short-segment, traditional, andcontrol patients was not significantly different. Cardiaintestinal metaplasia was an infrequent finding inpatients with Barrett's esophagus and appears to developindependently from that in the remainder of thestomach.     

Specialized intestinal metaplasia of the distal esophagus in gastroesophageal reflux disease: prevalence and clinico-demographic features

BACKGROUND: Specialized intestinal metaplasia can be categorized according endoscopic and histological findings in long segment Barrett, short segment Barrett and specialized intestinal metaplasia of cardia. Barrett's esophagus is an acquired disease that is found in about 10%-13% of patients undergoing endoscopy for symptoms of gastroesophageal reflux disease and it is well established as predisposing to esophageal adenocarcinoma. The columnar epithelium with goblet cells replaces the normal squamous epithelium. OBJECTIVE: To determine the prevalence and clinical-demographic characteristics of specialized intestinal metaplasia of distal esophagus in the gastroesophageal reflux disease. METHODS: From April to October 2002, 402 patients referred to upper endoscopy due gastroesophageal reflux disease were evaluated through of a symptom questionnaire about clinical and demographic features and submitted to upper endoscopy with four-quadrant biopsies 1 cm below escamocolumnar junction. RESULTS: Eighteen point four percent of patients had specialized intestinal metaplasia, 0.5% long segment Barrett esophagus, 3.2% short segment Barrett's esophagus and 14.7% specialized intestinal metaplasia of cardia. Patients with Barrett's esophagus showed a tendency to be male and specialized metaplasia of cardia to be female. All patients with Barrett's esophagus were white. There was not association between symptoms of gastroesophageal reflux disease and specialized intestinal metaplasia, but patients with Barrett's esophagus showed a tendency to have symptoms over 5 years and had more hiatal hernia and esophagitis. The use of alcohol and tobacco was not related to the presence of specialized intestinal metaplasia. CONCLUSIONS: Barrett's esophagus was more related to the male gender, gastroesophageal reflux disease symptoms for 5 years or longer, more intense esophagitis and hiatal hernia, but was not related to the use of tobacco and alcohol.     

Cytokeratin and CDX-2 expression in Barrett's esophagus

OBJECTIVE: Barrett's esophagus (BE) is a premalignant condition of the distal esophagus. For diagnostic purposes it is important to find biomarkers that can specifically identify BE, for instance to differentiate BE epithelial cells from gastric cardia epithelial cells in brush cytology specimens. The objective of this study was to determine the specificity of CDX-2 and a set of cytokeratins (CKs) as specific markers for BE as compared with normal squamous esophageal and gastric cardia tissue. MATERIAL AND METHODS: Immunohistochemistry (IHC) with specific antibodies against CDX-2, and a set of CKs was performed on fresh frozen consecutive tissue sections of normal squamous, gastric cardia and non-dysplastic BE of 80 patients. RESULTS: IHC results showed CK8, CK18 and CK20 expression in both BE and gastric cardia, while CK7 was seen in all BE but also in 26% of gastric cardia biopsies. CK10/13 was only expressed in normal squamous epithelium. CDX-2 nuclear staining was found in 87.5% of the BE biopsies, whereas normal squamous esophagus and cardia biopsies were negative. CONCLUSIONS: CDX-2 in combination with a set of CKs can be used as biomarkers to distinguish between BE and normal squamous esophagus. In order to distinguish BE from cardia tissue, a combination of CDX-2 and CK7 is most informative.     

Prevalence of Barrett's esophagus by endoscopy and histologic studies: a prospective evaluation of 306 control subjects and 376 patients with symptoms of gastroesophageal reflux

The classic endoscopic diagnosis of a Barrett's esophagus (BE) is based on the finding of > or =3 cm, of distal esophagus covered by specialized columnar epithelium. However, currently, it is based on the finding of intestinal metaplasia (IM) at the squamous-columnar mucosal junction, independent of its extent. The aim of this study was to determine the prevalence of Barrett's esophagus by endoscopic and histological findings in control subjects and in patients with symptoms of gastroesophageal reflux (GER). Three hundred and six control subjects and 376 patients with symptoms of gastroesophageal reflux were included in this prospective study. Patients with Barrett's esophagus were classified in three groups as follows. 1. Intestinal metaplasia at the cardia. When endoscopy showed non-Barrett's esophagus, but histological intestinal metaplasia was found. 2. Short-segment Barrett's esophagus. When <3 cm, was covered with tongues or finger-like or creeping substitution of distal esophagus. 3. Long-segment Barrett's esophagus. When > 3 cm, of distal esophagus was covered by specialized columnar epithelium. Two biopsies at the antrum, four biopsies at the squamous-columnar junction and one or two at the distal esophagus were taken. In control subjects, 1.6% showed histological IM at the esophagogastric junction. In patients with GER without esophagitis or with erosive esophagitis, IM was found in 18% and 10.7% respectively. 'Short-segment' Barrett's esophagus was three times more frequent than 'long-segment' Barrett's esophagus. Patients with Barrett's esophagus were significantly older than the other groups. The presence of complications or erosions, peptic ulcer or stricture were significantly more frequent among patients with 'long-segment' Barrett's esophagus (p < 0.0001). The prevalence of dysplasia was similar in all groups of patients with Barrett's esophagus. Complications such as ulcers, stricture and dysplasia were exclusively seen among patients with BE, whereas non-Barrett's patients did not exhibit these complications. In control subjects, IM can be found in a low percentage of cases. Among patients with symptoms of GER, the classic endoscopic diagnosis of a Barrett's esophagus can underestimate this condition in 80% of the cases. Patients with intestinal metaplasia at the cardia already present 17% of the cases with low-grade dysplasia. In all patients with symptoms of GER, systematic biopsies at the squamous-columnar junction should be taken.     

Comparative studies on epithelial lesions at gastric cardia and pyloric antrum in subjects from a high incidence area for esophageal cancer in Henan, China

AIM To investigate the pathogenesis of gastric cardia and the distal part of stomach cancer and to further characterize the histopathogenesis model for gastric cardia cancer from the high-risk population for esophageal cancer.METHODS Mass survey with endoscopic mucosa biopsy and histopathological examination were carried out on 226 subjects aged above 30 years. Three biopsies were collected one each from the middle part of the esophagus, the gastric cardia and the pyloric antrum. The biopsy tissue was fixed with 85% alcohol and paraffin-embedded.RESULTS The incidence of intestinal metaplasia and dysplasia at gastric cardia epithelium was higher than that at the pyloric antrum from the subjects in the same area. And there were high incidences of both esophageal and gastric cardia cancer, but a low incidence of gastric cancer at the distal part of the stomach.CONCLUSION There might be different etiology and pathogenesis of gastric cardia and pyloric cancer at the distal part of the stomach.     

Comparative studies on epithelial lesions at gastric cardia and pyloric antrum in subjects from a high incidence area for esophageal cancer in Henan, China

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Prevalence of short-segment Barrett's epithelium

BACKGROUND/AIMS: The incidence of adenocarcinoma of the oesophagus has increased. Its major risk factor is Barrett's epithelium of which the sine qua non is microscopically diagnosed intestinal metaplasia. Short segment Barrett's epithelium may often be overlooked during routine endoscopy. In routine biopsies taken from normal-appearing mucosa of the distal oesophagus, the reported rates of short segment Barrett's epithelium in the distal oesophagus reached 36%. We compared these rates with the results obtained in a community hospital in Israel. METHODS: Consecutive patients undergoing oesophagogastroduodenoscopy were enrolled. Biopsy specimens taken from cardia, oesophagogastric junction and 2 cm above the oesophagogastric junction were stained with haematoxylin & eosin and Alcian blue. RESULTS: There were 112 study patients (mean age +/- SD 48. 9+/-18.3 years, 51.8% males). Nine (8.04%) patients had intestinal metaplasia (according to specimen from 2 cm above oesophagogastric junction), and symptoms of gastro-oesophageal reflux were found in only four (44.4%) of them. Of these nine patients, six (6.66%) had normal-appearing mucosa and three (3.33%) had macroscopic Barrett's epithelium. Alcian blue staining revealed two patients with intestinal metaplasia that haematoxylin & eosin staining had missed. CONCLUSION: We found an 8% prevalence of intestinal metaplasia compared to 18-36% reported in the literature. We also determined that the added advantage of routine biopsy was 5.4%.     

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.     

Cytokeratin immunoreactivity of intestinal metaplasia at normal oesophagogastric junction indicates its aetiology

BACKGROUND AND AIMS: Cytokeratin (CK) 7 and 20 patterns are specific for long and short segments of Barrett's oesophagus but their use has not been assessed in intestinal metaplasia arising in macroscopically normal gastro-oesophageal junction (GOJ). PATIENTS AND METHODS: This study was carried out in a large prospective series of 254 patients who underwent upper endoscopy, had normal gastro-oesophageal anatomy, and who had biopsies of the antrum, fundus, cardia, GOJ, and lower oesophagus. Intestinal metaplasia of the GOJ was typed by histochemistry with high iron diamine-alcian blue staining and by immunohistochemistry using CK7 and CK20 antibodies. Results were correlated with clinical, endoscopic, and pathological data. RESULTS: Sixty (23.6%) of our patients presenting with a normal GOJ had intestinal metaplasia. The CK7/CK20 pattern identified two groups of patients: one highly correlated with Barrett's and the other with characteristics of Helicobacter pylori gastritis. The Barrett's type CK7/CK20 pattern was related to a high frequency of gastro-oesophageal reflux symptoms (p<0.02) and normal endoscopic appearance of the stomach (p<0.03). In contrast, the gastric type CK7/CK20 pattern was linked to atrophic (p<0.02) or erythematous (p<0.05) appearance of the stomach (p<0.03), high frequency of H pylori infection (p<0.04), antral inflammation (p<0.006) with atrophy (p<0.02), and intestinal metaplasia (p<0.02). CONCLUSION: In patients presenting with intestinal metaplasia in normal appearing GOJ, the cytokeratin pattern identifies two groups of patients, one with features identical to those of long segment Barrett's oesophagus and one with features seen in H pylori gastritis. These data may be used by clinicians and should result in improved endoscopic surveillance strategies targeted specifically at patients at increased risk of Barrett's oesophagus and thus cancer.     

Detection of intestinal metaplasia in Barrett's esophagus: an observational comparator study suggests the need for a minimum of eight biopsies

OBJECTIVES: Intestinal metaplasia (IM) and dysplasia in Barrett's esophagus are recognized surrogates for esophageal adenocarcinoma risk. While few would argue with the "hunt for dysplasia," there is a divide regarding the usefulness of the histological confirmation of intestinal metaplasia in endoscopically apparent long segment Barrett's esophagus. We aimed to assess the frequency of intestinal metaplasia in 125 consecutive patients with columnar-lined esophagus and to determine the optimal biopsy protocol to detect intestinal metaplasia. METHODS: Two-hundred ninety-six endoscopies were performed over a 4-yr period in Barrett's esophagus segments of mean length 4 cm (range 1-11 cm) at a single center and the resulting biopsies were analyzed retrospectively. Biopsies were all processed with routine hematoxylin and eosin (H&E) staining, and a subset (N=92) was subject to alcian blue/periodic-acid Schiff staining. RESULTS: Using H&E staining, we found that the optimum number of biopsies to diagnose intestinal metaplasia was 8 per endoscopy, mean 67.9% endoscopies having intestinal metaplasia. In contrast, if only four were taken the yield was 34.7% with intestinal metaplasia. Unless more than 16 biopsies were taken (100% yield of intestinal metaplasia), no additional significant detection was achieved. Using additional alcian blue/periodic-acid Schiff staining only had a marginal benefit, with 5.4% of new cases of intestinal metaplasia being identified. There is a proximal cephalo-caudal gradient of intestinal metaplasia, especially with increased chronological age, but doing repeat endoscopies on patients did not increase the detection of intestinal metaplasia. CONCLUSIONS: The data suggest that at least 8 random biopsies is the minimum to be taken and analyzed with conventional H&E staining to diagnose benign intestinal metaplasia. Taking more biopsies did not statistically increase the diagnosis of intestinal metaplasia except when greater than 16 were taken when 100% yield was obtained.