Gastric cardia intestinal metaplasia: biopsy follow-up of 85 patients.

BACKGROUND: Gastric cardia intestinal metaplasia (CIM), denoted by goblet cells is common. The frequency of persistent CIM is unknown. METHODS: 85 patients with CIM and follow-up endoscopies were prospectively identified during the time period of 10/6/94-12/21/97. The presence of goblet cells was the defining feature of CIM, other metaplastic cell types were not evaluated. AU 85 patients initially had biopsies that straddled the squamocolumnar junction (SCJ) showed CIM, an otherwise normal proximal stomach, lower esophagus, and squamocolumnar junction. The SCJ lay within the 2 cm of mucosa immediately proximal to the uppermost gastric fold and overlaid the junction of the tubular esophagus and the saccular dilatation of the stomach in all patients. The patients underwent endoscopy for many reasons. They were randomly identified based on the absence of a hiatal hernia and the presence of CIM. RESULTS: Ten of the 85 patients had CIM on repeat biopsy. Among patients with no CIM in the first repeat endoscopy, the degree of cardia inflammation decreased between the initial and first repeat endoscopy, whereas there was no change in the amount of inflammation among patients who had CIM in the first repeat endoscopy. The changes in mean inflammation score was significantly different between the two groups (P = .024). Twenty-two patients underwent a second repeat endoscopy and five had a third repeat endoscopy. Including all follow-up biopsies, six of the 85 patients (7%) had CIM. Four patients who did not have CIM on initial repeat endoscopy had CIM on their second repeat endoscopy, probably reflecting sampling issues. None of the biopsies had dysplasia. CONCLUSIONS: Cardia inflammation is a stimulus for cardia intestinal metaplasia, and a reduction in inflammation may allow the metaplastic mucosa to revert to normal.     

Histopathologic changes in gastroesophageal reflux disease. A study of 126 bioptic and autoptic cases

The histologic diagnosis of reflux esophagitis is still complicated by the lack of a consensus opinion on what is the normal mucosa in the area of the gastroesophageal junction (GEJ). Most authors consider GEJ as the junction between the squamous and the cardiac epithelium. The cardiac mucosa is composed of mucinous or mixed mucinous-oxyntic glands. These glands are in fact indistinguishable from metaplastic mucosa that arises in the distal esophagus in consequence of gastroesophageal reflux (GER). The cardiac mucosa shows invariably chronic inflammatory changes referred to as "carditis". The cause of "carditis" is GER and/or Helicobacter pylori (HP) infection. In our series of 120 endoscopic biopsies of the GEJ and distal esophagus the cardia type mucosa (CM) was always present. In 15 cases, it was accompanied by oxyntocardiac mucosa. Both mucosa types showed chronic inflammation that is after exclusion of HP infection regarded as a strong diagnostic sign of the gastroesophageal reflux disease (GERD). In two cases with clinical symptoms of GERD, a few HP were found on the CM. Therefore we diagnosed them as GERD with secondary HP infection. In 17 cases, CM displayed intestinal metaplasia (IM) predominantly of incomplete type and no dysplasia. This IM expressed MUC6 in the glandular zone of the mucosa like it did in the neighboring glands, whereas in the surface and foveolar epithelium the MUC6 was negative or only slightly and focally positive. On the other hand, IM in the surface and foveolar epithelium was reactive for MUC5AC. The positivity and distribution of CK7 and CK20 was very similar in the Barrett's mucosa, cardiac mucosa and antral mucosa. In one specimen of esophagus resected for adenocarcinoma, CM with incomplete IM was found in the vicinity of the tumor. Squamous metaplastic epithelium was often seen near the orifices of submucosal esophageal glands in these areas, indicating the metaplastic nature of the glandular mucosa in the distal esophagus. In the GEJ of 5 autopsy cases of children with spastic quadriplegia (age range 7-10 years) CM in a short segment (0.5-3 mm in length), probably of metaplastic origin was identified, showing chronic inactive inflammation.     

Pathology of the gastroesophageal junction

The gastroesophageal junction (GEJ) is a poorly defined anatomic area that represents the junction etween the distal esophagus and the proximal stomach (cardia). The true anatomic GEJ corresponds to the most proximal aspect of the gastric folds, which represents an endoscopically apparent transition oint in most individuals. Many, if not most, adults, particularly those with either physiologic or logic GERD, have a proximally displaced Z-line indicating that the histologic squamocolumnar nction (SCJ) is located above the anatomic GEJ. The histologic characteristics of short segments of columnar mucosa located above the anatomic GEJ in these individuals are similar to the gastric cardia, ng composed of either pure mucous glands or mixed mucous glands/oxyntic glands. Although controversial, some authors believe that the cardia is normally composed, at birth, of surface mucinous columnar epithelium and underlying oxyntic glands identical to the gastric corpus, whereas others maintain that the true anatomic cardia is normally composed of mucinous columnar epithelium with underlying mucous glands or mixed mucous and oxyntic glands. However, the preponderance of evidence supports the latter theory and that the length of mucosa composed of either mucous, or mixed mucous glands/oxyntic glands, increases with age and is presumed to be related to ongoing GERD. Inflammation of the true gastric cardia (carditis), which is most often due to H. pylori infection, is difficult to distinguish from columnar metaplasia of the distal esophagus secondary to GERD. From a pathologist's perspective, the differential diagnosis of true gastric carditis from esophageal columnar metaplasia of the distal esophagus in GEJ biopsies is difficult, but a variety of clinical, pathologic, and immunohistochemical methods can be used to help separate these two disorders. Nearly one-third of patients who present for upper GI endoscopy without endoscopic evidence of BE reveal foci of intestinal metaplasia in the GEJ. There are some studies to suggest that the risk of dysplasia and cancer is different in patients with intestinal metaplasia in the cardia related to H. pylori infection versus those with metaplastic columnar epithelium in the distal esophagus related to GERD. Chronic inflammation is generally considered the predominant underlying stimulus for the development of columnar metaplasia in the GEJ, regardless of the etiology. Columnar metaplasia and intestinal metaplasia in the distal esophagus represents a squamous to columnar cell transition and there is some evidence that this occurs through an intermediate, or transitional, phase of intestinalization termed multilayered epithelium. In contrast, intestinal metaplasia that develops in the true gastric cardia secondary to H. pylori infection represents a columnar to columnar metaplastic reaction. This review will focus on the clinical, pathologic, and pathogenetic aspects of GERD and H. pylori-induced inflammation of the GEJ region.     

The gastric cardia in gastro-oesophageal disease

BACKGROUND: There have been conflicting reports concerning the use of cardia biopsies in screening patients for gastro-oesophageal disease. AIM: To define the histopathological changes in the gastric cardia of patients with and without gastro-oesophageal disease. METHODS: Topographically mapped gastric biopsy specimens were obtained from patients with gastro-oesophageal disease and from controls. Biopsies were scored on a visual analogue scale of 0 to 5 for Helicobacter pylori, intestinal metaplasia, pancreatic metaplasia, foveolar hyperplasia, and active inflammation. The presence or absence of cardiac glands was recorded. RESULTS: Sixty-five patients with gastro-oesophageal disease and 71 controls were examined. Intestinal metaplasia was present in cardia biopsies of 10 patients with gastro-oesophageal disease and 11 controls. Only two patients with gastro-oesophageal disease and intestinal metaplasia in the cardia had no evidence of exposure to H pylori. Intestinal metaplasia was not found in the cardia of those with long segment Barrett's oesophagus. Carditis was strongly associated with active H pylori infection (p = 0.000) and resolved after treatment of the infection. A negative association was present between gastro-oesophageal disease and the presence of cardiac glands in cardiac biopsies (p = 0.003). Pancreatic metaplasia was found in 15 of 65 and foveolar hyperplasia in 19 of 65 cases but neither was related to gastro-oesophageal disease. CONCLUSION: Intestinal metaplasia in the cardia is uncommon in gastro-oesophageal disease in the absence of H pylori infection. With chronic H pylori infection the junction between the cardia and corpus expands in a cardia-corpal direction.     

The significance and etiology of intestinal metaplasia of the esophagogastric junction

Biopsies from the vicinity of the esophagogastric junction occasionally show foci of intestinal metaplasia. Whether these biopsies represent Barrett's esophagus in all cases is controversial and of clinical importance because patients with Barrett's esophagus are at significantly increased risk for developing esophageal adenocarcinoma. Recent evidence suggests that intestinal metaplasia of the gastric cardia is also quite common. Although prospective data are relatively sparse, it has been suggested that the risk of progressing to dysplasia and adenocarcinoma is significantly lower for intestinal metaplasia of the gastric cardia when compared with esophageal intestinal metaplasia (Barrett's esophagus). Immunohistochemical stains for cytokeratins 7 and 20 may be useful in more precisely localizing the site of intestinal metaplasia in biopsy specimens taken from the vicinity of the esophagogastric junction. Correlation of all clinical, endoscopic, histologic, and immunohistochemical data may be used by the gastroenterologist to determine the likely source of the intestinal metaplasia and whether the patient should be followed by endoscopic surveillance.     

Reflux esophagitis or Helicobacter infection? – Diagnostic value of the inflammatory pattern in metaplastic mucosa at the squamocolumnar junction

OBJECTIVES: Metaplastic glandular mucosa with goblet cells at the squamocolumnar junction is induced either by reflux or by Helicobacter infection. We investigated whether the accompanying inflammation may give information about the etiology of these metaplastic changes and whether there are further criteria which are helpful in differentiating Helicobacter-induced vs. reflux-caused metaplasia. METHODS: One hundred and nine patients with intestinal metaplasia diagnosed in biopsies obtained immediately below the Z-line were evaluated. Further biopsies were taken from the gastric body and antrum. Patients were diagnosed as having a normal Z-line, or as showing short tongues or segments of Barrett's esophagus endoscopically. Inflammation was graded according to the updated Sydney-system. Metaplasia was typed using Gomori's-aldehyde-fuchsin-Alcianblue staining. RESULTS: Compared to patients with Barrett's esophagus, the active (p=0.0002) and chronic inflammation (p=0.0004) at the squamocolumnar junction was higher in patients with a normal Z-line and frequently accompanied by lymphoid aggregates (p<0.0001) and regular cardia- (p=0.0044) and/or corpus-type glands (p=0.0004). Pseudogoblet cells were more frequent in Barrett's esophagus (p=0.0159). CONCLUSIONS: The endoscopic aspect of the Z-line, the inflammatory pattern, and the type of glands in biopsies from the squamocolumnar junction, as well as the presence of pseudogoblet cells are helpful tools in distinguishing Barrett's mucosa from Helicobacter-associated intestinal metaplasia.     

Does Cytokeratin7/20 immunoreactivity help to distinguish Barrett's esophagus from gastric intestinal metaplasia? Results of a prospective study of 75 patients

Barrett's esophagus is a recognized risk factor for the development of esophageal dysplasia and carcinoma. Unfortunately, gastric incomplete intestinal metaplasia arising in Short Segment Barrett's esophagus can be indistinguishable histologically on hematoxylin/eosin stains. Distinct patterns of CK 7 and CK 20 immunohistochemical expression have been demonstrated to be both highly sensitive and specific for Barrett's esophagus, but have not been found in gastric metaplasia. The aim of our study was to test whether immunostaining with CK 7/20 helps to distinguish between Barrett's epithelium and gastric incomplete metaplasia. Cases of long segment Barrett's esophagus, short segment Barrett's esophagus, and cases with a normal gastroesophageal junction, as well as specimens with gastric antral intestninal metaplasia, were examined: three patterns were defined. Barrett's pattern (superficial CK 20 staining; superficial and crypt CK 7 staining); gastric pattern (superficial and crypt staining of both markers); other patterns (different from Barrett and gastric types). Seventy-five patients were enrolled in this study, 26 with long segment Barrett's esophagus, 21 with short segment esophagus, 13 with intestinal metaplasia of the cardia, and 18 with antral intestinal metaplasia. The Barrett pattern showed a high specificity of 97%, but a sensitivity of only 30% in patients with short segment Barrett esophagus. Our results do not confirm the hypothesis that CK 7/20 immunostaining can be used for a reliable differentiation between incomplete intestinal metaplasia and Barrett's epithelium.     

Clinicopathological features of duodenal bulb biopsies and their relationship with upper gastrointestinal diseases

AimTo assess the prevalence of the lesions in duodenal bulb mucosa and the relationship between duodenal lesions and upper gastrointestinal diseases, including helicobacter pylori infection.MethodsClinical, endoscopic and pathological data of the cases with duodenal bulb and gastric mucosal biopsy from January 2005 to May 2017 were analyzed retrospectively.ResultsA total of 3540 patients were enrolled. The biopsy from protuberant lesions with endoscopic morphology are mostly duodenal gastric heterotopia or adenoma. The biopsy from duodenal ulcers are often observed in inflammatory changes and gastric metaplasia.Patients with gastric heterotopia had a significantly lower prevalence of chronic atrophic gastritis, intestinal metaplasia, and gastric ulcer; and much higher prevalence of gastroesophageal reflux disease and gastric fundic polyps.Patients with gastric metaplasia had been positively associated with gastroesophageal reflux disease, and negatively associated with gastric fundic polyps.There were positive correlation between helicobacter pylori infection and duodenal active inflammation, Brunner gland hyperplasia, gastric metaplasia and duodenal ulcer. However, Patients with gastric heterotopia in bulb had been negatively associated with helicobacter pylori infection.ConclusionsThe mucosa lesions in duodenal bulb were associated with concurrent gastric fundic gland polyps, gastroesophageal reflux disease, duodenal ulcer, and helicobacter pylori infection.     

The location and frequency of intestinal metaplasia at the esophagogastric junction in 223 consecutive autopsies: implications for patient treatment and preventive strategies in Barrett's esophagus.

The frequency of intestinal metaplasia at the esophagogastric junction is as high as 36% in endoscopy studies; the majority of cases (approximately 67%) occur in short segments of esophageal columnar mucosa. The validity of these studies has been questioned, however, because of heterogenous underlying diseases prompting endoscopy. To determine the frequency and origin of intestinal metaplasia at the esophagogastric junction, we histologically evaluated the entire esophagogastric junction for the presence of intestinal metaplasia using Alcian blue/periodic acid-Schiff mucin stains in 223 consecutive autopsies. Precise localization of the Z line in relation to the esophagogastric junction and tongues of esophageal columnar-appearing mucosa were noted in each case. Mean patient age was 47 years; 69% of patients were male, and 63% were white. Twenty five of 223 cases (11%) had intestinal metaplasia at the esophagogastric junction. Only 2 of 25 cases (8%) had intestinal metaplasia in the esophagus; the remaining 23 cases (92%) had intestinal metaplasia in the gastric cardia. Male gender, advanced age, white ethnic origin, and short tongues of esophageal columnar mucosa were not associated with gastric cardia intestinal metaplasia. An association of distal gastric intestinal metaplasia (P < .01) and chronic gastritis (P < .01) with gastric cardia intestinal metaplasia suggests a role for Helicobacter pylori infection in this process. The frequency of intestinal metaplasia at the esophagogastric junction in an unselected autopsy population is low (11%) even after exhaustive histologic evaluation using Alcian blue mucin stains. Furthermore, intestinal metaplasia is confined to the gastric cardia in more than 90% of cases with no association to male gender, white ethnic origin, advanced age, or the presence of short segments of esophageal columnar-appearing mucosa at endoscopy. These results demonstrate that caution is warranted when applying the findings of endoscopy studies to the development of preventive and screening strategies aimed at identifying Barrett's esophagus in an asymptomatic general population.     

Tumor necrosis factor alpha and apoptosis in Helicobacter pylori related progressive gastric damage: a possible mechanism of immune system involvement in epithelial turnover regulation

Helicobacter pylori (HP) related inflammation is mediated by tumour necrosis factor alpha (TNFalpha), which "in vitro" increases epithelial apoptosis in response to infection. In the early stages of HP gastritis, a raised epithelial apoptosis occurs; this phenomenon becomes less evident with progression towards intestinal metaplasia. Aim of our study was to analyze "in vivo" mucosal TNFalpha in relation to epithelial apoptosis in the progression of HP related histological damage. Antral biopsies from 20 HP positive patients were retrospectively studied: 10 with and 10 without intestinal metaplasia (IM and CG group respectively); samples of 10 dyspeptics with normal HP negative stomach (N) were used as control. The following parameters were evaluated by immunohistochemistry: 85 kDa caspase-cleaved fragment (p85) of human poly (ADP-ribose) polymerase (PARP) labelling index (LI) as marker of apoptosis and TNFalpha LI in stromal cells as marker of inflammatory response. Both epithelial apoptosis and mucosal TNFalpha expression were higher in chronic active gastritis compared to intestinal metaplasia and controls (PARP and TNFalpha LI: CG > IM > N; ANOVA & Student-Neumann-Keuls; p < 0.05 and p < 0.01, respectively). Pearson's coefficient showed a significant correlation between PARP and TNFalpha LI in IM and CG groups. Our data show that mucosal TNFalpha, similarly to what suggested "in vitro", may be related "in vivo" to epithelial apoptosis thus suggesting a possible mechanism for immune system involvement in the control of gastric epithelial turnover.     

Tumor Necrosis Factor Alpha and Apoptosis in Helicobacter pylori Related Progressive Gastric Damage: A Possible Mechanism of Immune System Involvement in Epithelial Turnover Regulation

Helicobacter pylori (HP) related inflammation is mediated by tumour necrosis factor alpha (TNFα), which “in vitro” increases epithelial apoptosis in response to infection. In the early stages of HP gastritis, a raised epithelial apoptosis occurs; this phenomenon becomes less evident with progression towards intestinal metaplasia. Aim of our study was to analyze “in vivo” mucosal TNFα in relation to epithelial apoptosis in the progression of HP related histological damage. Antral biopsies from 20 HP positive patients were retrospectively studied: 10 with and 10 without intestinal metaplasia (IM and CG group respectively); samples of 10 dyspeptics with normal HP negative stomach (N) were used as control. The following parameters were evaluated by immunohistochemistry: 85 kDa caspase-cleaved fragment (p85) of human poly (ADP-ribose) polymerase (PARP) labelling index (LI) as marker of apoptosis and TNFα LI in stromal cells as marker of inflammatory response. Both epithelial apoptosis and mucosal TNFα expression were higher in chronic active gastritis compared to intestinal metaplasia and controls (PARP and TNFα LI: CG>IM>N; ANOVA & Student-Neumann-Keuls; p<0.05 and p<0.01, respectively). Pearson' s coefficient showed a significant correlation between PARP and TNFα LI in IM and CG groups. Our data show that mucosal TNFα, similarly to what suggested “in vitro”, may be related “in vivo” to epithelial apoptosis thus suggesting a possible mechanism for immune system involvement in the control of gastric epithelial turnover.     

What is the role of cytokeratins in Barrett/cardia differentiation?

The importance of distinguishing between Barrett metaplasia and intestinal metaplasia of the gastric cardia is now accepted, and the management of each entity is quite different. Patients with Barrett metaplasia are enrolled in surveillance programs, consisting of periodic endoscopy and biopsy, because of the known risk of developing adenocarcinoma of the esophagus. Patients with intestinal metaplasia of the gastric cardia, however, are not currently enrolled in such programs, because this condition carries a low risk of developing adenocarcinoma of the gastric cardia. The distinction between both conditions by morphologic examination of routine histologic sections of endoscopic biopsies is extremely difficult if at all possible. A group of investigators proposed the use of immunostains for cytokeratin (CK) 7 and CK20 to overcome such difficulty. They concluded that the Barrett CK7/CK20 pattern was a highly sensitive and specific marker for Barrett metaplasia. Their observations, however, were not confirmed by other investigators. However, because it may be associated with premalignant lesions elsewhere in the gastric mucosa, we propose that intestinal metaplasia of the gastric cardia may have the same clinical implication as Barrett metaplasia.     

Endoscopic versus histological diagnosis of Barrett's esophagus: a cross-sectional survey

CONTEXT : Barrett's esophagus is a common pathological condition in patients with gastro-esophageal reflux disease. OBJECTIVE : The aim of this study was to compare endoscopic diagnosis versus histological confirmation. DESIGN : Cross-sectional. SETTING: Cancer Institute of the Imam Khomeini Hospital. MATERIAL AND METHODS : A total of 50 patients with a history of gastro-esophageal reflux were recruited and underwent upper endoscopy at this cross-sectional survey. Four-quadrant biopsy was taken from all suspected areas of intestinal metaplasia. Sections of blocks were stained with Mixed Alcian Blue (PH 2.5)/PAS and haematoxylin-eosin stainings for the diagnosis of intestinal metaplasia (complete vs. incomplete types) and goblet cell / columnar cell / dysplasia, respectively. Main outcome measure : The presence of Helicobacter pylori was assessed by Giemsa staining. RESULTS : There were 44 cases of short-segment Barrett's esophagus and 6 of long-segment Barretts esophagus by endoscopy. When examined by histologic examination, 12 patients with short-segment Barrett's esophagus and 4 with long-segment Barrett's esophagus had intestinal metaplasia. Haematoxylin-eosin staining diagnosed 12 cases of intestinal metaplasia, whereas mixed alcian blue/PAS was used to diagnose 16 cases (κ = 80%, p < 0.001). The positive predictive value in the diagnosis of goblet cell metaplasia and columnar cell metaplasia was 32% and 66%, respectively. Helicobacter pylori infection was observed in 10 cases of those with columnar cell metaplasia without goblet cells, while none of the patients with intestinal metaplasia were infected. CONCLUSION : Our findings suggest that biopsy taking is necessary in all patients with gastro-esophageal reflux disease, whose results suggest columnar cell lining in distal esophagus in endoscopy.     

Helicobacter pylori-induced changes in the gastric mucosa are associated with mitogen-activated protein kinase (MAPK) activation.

BACKGROUND: Gastric cancers are usually associated with and preceded by Helicobacter pylori (HP) infection, gastric atrophy, intestinal metaplasia, and dysplasia. HP infection alters cell kinetics of the gastric mucosa. Both proliferation and apoptosis are increased. Proinflammatory cytokines are responsible for some of these alterations. The mitogen-activated protein kinase (MAPK) signaling pathway has been implicated as a causative factor in these alterations based on in vitro studies. In this study, we investigated the effects of HP infection on gastric mucosal proliferation, apoptotic mechanisms, and the activation status of the MAPK signaling pathway at various stages of gastric carcinogenesis, especially intestinal metaplasia and dysplasia caused by HP infection. DESIGN: Stomach biopsies representing normal (n=20), HP+ (n=25), HP+ with intestinal metaplasia (n=25), HP+ with dysplasia (n=15) and gastric adenocarcinoma (n=30; 20 HP+ and 10 HP-) cases were selected. Cell proliferation was assessed by proliferating cell nuclear antigen immunostaining. Apoptosis and survival-related markers; cleaved caspase-3, and phospho-MAPK extracellular signal-regulated kinase (ERK) were detected by immunohistochemical methods. RESULTS: Proliferation index (proliferating cell nuclear antigen) and cleaved caspase-3 expression were higher in the HP+, HP+ with intestinal metaplasia, and HP+ with dysplasia groups than in normal controls (P<0.05). Cleaved caspase-3 activity was also high in the adenocarcinomas. Phospho-MAPK(ERK) expression was increased in the HP+, HP+ with intestinal metaplasia, HP+ with dysplasia and adenocarcinomas compared with the normal control group. Whereas HP- gastric carcinomas had a lower expression of phospho-MAPK. CONCLUSIONS: HP infection increases the proliferative rate of gastric foveolar cells in conjunction with an increased apoptotic rate and activation of MAPK(ERK). MAPK activation seems to be a significant and persistent event in the HP-induced neoplastic transformation.     

Incomplete intestinal metaplasia in the diagnosis of columnar lined esophagus (Barrett's esophagus)

To investigate the distribution and specificity of intestinal metaplasia (IM) in columnar lined esophagus (CLE), the authors reviewed biopsies of the hiatal hernia pouch (HHP) and esophagus from 17 patients with CLE (84 biopsies) and 10 controls (25 biopsies). The proximal margin of the gastric folds was used as an endoscopic landmark, corresponding to the gastroesophageal muscular junction (GEMJ). No biopsies obtained above the GEMJ in control patients showed columnar mucosa. No goblet cell metaplasia was seen in 21 biopsies of the HHP from patients with CLE or in 13 corresponding biopsies from controls. In contrast, alcian blue (AB) stains showed diffuse acid mucins in 3 of 21 biopsies of the HHP from patients with CLE and in 10 of 13 corresponding biopsies from controls, demonstrating that goblet cell metaplasia clearly distinguishes biopsies of CLE from the HHP (P less than 0.01), whereas small amounts of diffuse acid mucin on AB stains do not. IM evidenced by goblet cell metaplasia was frequently seen in biopsies only 2-3 cm above the GEMJ, and CLE was limited to that area in three patients, suggesting that the distal esophagus cannot be dismissed as a site for metaplastic and possibly premalignant mucosa. Adenocarcinoma was diagnosed during the course of the study in one patient with only 5 cm of columnar mucosa above the GEMJ.     

Pathologic anatomy of Barrett's esophagus

It is most substantiated to define Barrett's esophagus as intestinal metaplasia of esophageal cardiac mucosa irrespective of its association with the endoscopically detected esophageogastric junction, which develops as a result of gastroesophageal reflux. There is a need for further investigations of the specific features of the cardiac-type mucosa. During endoscopic study, it is important to be alert when identifying short and ultrashort Barrett's esophagus and to sample sufficient biopsy material. A pathologist must differentiate three major types of the cylindrical epithelium of the esophagus: cardiac, acid-producing cardiac, and intestinal metaplasia, by diagnosing Barrett's esophagus in the latter case. Patients with the esophageal cardiac mucosa should be referred to as a risk group for its development.     

Bile reflux and intestinal metaplasia in gastric mucosa.

AIM: To determine associations between enterogastric bile reflux and gastric mucosal pathology. METHOD: A retrospective study using fasting gastric juice bile acid measurements and antral or prestomal biopsy specimens from 350 patients, 66 of whom had previously undergone surgery that either bypassed or disrupted the pyloric sphincter. RESULTS: Bile reflux was positively associated with reactive gastritis and negatively with Helicobacter pylori density. After stratification for previous surgery, age, and H pylori status, the histological feature most strongly associated with bile reflux was intestinal metaplasia, including all its subtypes. The prevalence of intestinal metaplasia was greatest in patients with both H pylori infection and high bile acid concentrations. Bile reflux was also positively associated with the severity of glandular atrophy, chronic inflammation, lamina propria oedema and foveolar hyperplasia. CONCLUSIONS: Bile reflux is a cause of reactive gastritis. It modifies the features of H pylori associated chronic gastritis. The changes are not confined to patients who have had surgery to their stomachs. The positive associations with atrophy and intestinal metaplasia have implications for models of gastric carcinogenesis.     

Foveolar hyperplasia at the gastric cardia: prevalence and associations

AIMS: In the gastric antrum and body, foveolar hyperplasia is a feature of reactive gastritis resulting from--for example, duodenogastric bile reflux and the use of non-steroidal anti-inflammatory drugs (NSAIDs). The aim of this study was to examine the occurrence and clinical relevance of gastric cardiac foveolar hyperplasia. METHODS: The study population was drawn from a consecutive series of 1698 patients sent for upper gastrointestinal endoscopy. Only cases without chronic gastritis or Barrett's oesophagus were included. The final study population consisted of 307 patients. RESULTS: Foveolar hyperplasia was seen in the gastric cardiac mucosa in 31 (10%) patients with histologically normal stomach mucosa, but none had endoscopically noticeable hyperplastic polyps. Compared with patients without gastric cardiac hyperplasia, those with hyperplasia more often had chronic inflammation and complete intestinal metaplasia in the junctional biopsies (48% v 77% and 9% v 26%, respectively). Logistic regression analysis revealed that chronic cardiac inflammation (odds ratio (OR), 3.2; 95% confidence interval (CI), 1.3 to 7.8) and intestinal metaplasia of the complete type (OR, 2.8; 95% CI, 1.1 to 7.1) were independent risk factors for cardiac foveolar hyperplasia. In univariate analysis, endoscopic erosive oesophagitis (endoscopy positive gastro-oesophageal reflux disease) and the use of NSAIDs were not related to the presence of foveolar hyperplasia. CONCLUSIONS: Foveolar hyperplasia in the gastric cardiac mucosa occurs in patients with histologically normal non-gastritic stomachs and may develop as a consequence of chronic inflammation limited to the gastro-oesophageal junction ("junctitis"). It is not associated directly with endoscopy positive gastro-oesophageal reflux disease or the use of NSAIDs.