Barrett's Group Research Articles

Gastric Intestinal Metaplasia: Defining the Natural History

Introduction: The management of intestinal metaplasia (IM), a pre-malignant condition and precursor to dysplasia and gastric carcinoma (GCa), is problematic because of paucity of data on its natural history, especially for the United States (US) population, and because of variance in guidelines. We aim to study the natural history of IM in the US and to identify potential risk factors for progression to GCa. Methods: A cohort of 9,000 consecutive patients with histologically confirmed IM were identified, and a subset from 2003-2004 was selected for this pilot study. Clinical, endoscopic, and histologic data was extracted, including demographics, BMI, symptoms, tobacco pack years, alcohol use, NSAID use, H. pylori, Barrett's esophagus, GERD symptoms, PPI use, anemia, blood group, and family history of GCa. Fisher's Exact Test (2-Tail) and the non-parametric Wilcoxon 2-Sample Test were used for analysis. Results: We identified 200 patients, with statistically equal distribution between genders. The majority were Caucasian (81.4%), with average age of 68, and mean BMI of 26.5. The majority of patients were symptomatic (82%) leading to endoscopy, including symptoms of: pain (43%), reflux (30%), GI bleeding (11%), and concern for GCa (8%). Sixty-one percent of patients were smokers, 18.6% of patients had H. pylori and 80.8% demonstrated eradication after treatment. Of the patients with documented blood type the majority, 54% had type A. Eleven percent of patients had a family history of GCa. Patients were followed for a mean of 4.1 years, and of those with clinical follow-up, 7%, (14) developed GCa. Those that lived (6), had a mean age of 67.5, while eight passed away from GCa with mean age of 75.6, and all were men. Conclusion: We found no association with H. pylori, obesity, or alcohol consumption and IM, and all other studied parameters did not appear to correlate. Of patients followed, 4% passed away from GCa, in contrast to SEER database prediction of 2% of deaths in US in 2014 due to GCa. This represents a significant, increase in risk of GCa death development in IM. The difference in gender and age was statistically significant for those with mortality. The progression from IM to GCa occurred in the US population and it appears the patients with IM were at higher risk than the general population. More frequent and rigorous endoscopic surveillance may be necessary, especially in elderly men if the increased risk is confirmed in the remainder of our cohort and by other studies.

Expression of SOX9 and CDX2 in nongoblet columnar-lined esophagus predicts the detection of Barrett's esophagus during follow-up

The diagnosis of Barrett's esophagus in the United States requires both endoscopically evident columnar-lined esophagus and the presence of goblet cells by histology. Currently, there is no consensus on how patients with nongoblet columnar-lined esophagus should be followed. In this study, we investigated whether biomarkers can be used to predict the detection of goblet cells in follow-up biopsies. Patients with nongoblet columnar-lined esophagus were identified. In 13 of these cases, goblet cells were detected in subsequent follow-up endoscopic biopsies (Barrett's group). Additionally, 26 cases that remained negative for goblet cells in follow-up biopsies served as controls. Immunohistochemistry for CDX2, SOX9, BMP4, SHH, and MUC2 was performed on the initial biopsies and graded independently by at least two pathologists in a masked manner. CDX2 was positive in the nongoblet columnar epithelium of 7/13 cases in the Barrett's group and in 4/26 controls (sensitivity 54%, specificity of 85%, odds ratio (OR) 6.4). Strong and diffuse immunoreactivity for SOX9 was detected in 10/13 cases in the Barrett's group and in 1/26 controls (sensitivity 77%, specificity 96%, OR 83.3). Combining CDX2 and SOX9 as a panel increased sensitivity to 85%, although the specificity decreased to 85% (OR 30.3). SHH, BMP4, and MUC2 expression showed no significant difference between the Barrett's and control groups. In patients with nongoblet columnar-lined esophagus, SOX9 and CDX2 may be useful in identifying a subset of patients who have a higher risk of being diagnosed for Barrett's esophagus (developing goblet cells) and need closer follow-up.

The activities of acid DNase and 5'nucleotidase in erosive reflux esophagitis and Barrett's epithelium.

The study examines the relationship between activity of acid DNase and 5'nucleotidase (5'NT) and histological changes in reflux esophagitis. Thirty-three patients were examined, 15 of whom with mild esophagitis, 12 with severe esophagitis and 6 with Barrett's epithelium. Patients were classified into 3 groups, according to Ismail-Beigi histological criteria: mild esophagitis group (ME); severe esophagitis group (SE); Barrett's esophagitis group (BE). DNase and 5'NT levels were measured biochemically both in healthy and injured tissue samples. Difference of acid DNase and 5'NT activity in healthy tissue versus injured tissue samples was the lowest in ME group: 0.55±4.47 U/g for acid DNase and 11.56±37.11 U/g for 5'NT, the difference increased to 4.43±1.64 U/g for acid DNase and 105.57±54.11 U/g for 5'NT in the SE group, while 6.07±2.92 U/g for acid DNase and 109.83±14.02 U/g for 5'NT as the highest levels were measured in the BE group. Difference in BE group is statistically significantly higher (p <0.05) compared to the ME group, confirmed by ANOVA with Dunnett's post hoc test. The study shows significant decrease of apotosis level that is detectable even before metaplasia was morphologically defined.

PWE-019 Mitochondrial instability is elevated in Barrett's oesophagus and dimethyloxalylglycine has a potential role in reversing this dysfunction

IntroductionDeoxycholic acid (DCA), a component of bile, has been associated with the development and progression of Barrett's oesophagus (BO). In addition, the “mutator-phenotype hypothesis” states benign cells with high rates...

PTU-167 The role of proton pump inhibitors in patients with Barrett's oesophagus following laparoscopic fundoplication can only be determined after the level of residual reflux has been quantified

IntroductionLaparoscopic fundoplication is carried out for pathological Gastro Oesophageal Reflux in patients with and without Barrett's oesophagus. It has been suggested that in patients with Barrett's, only those patients with...

The gene expression profile of cardia intestinal metaplasia is similar to that of Barrett's esophagus, not gastric intestinal metaplasia

The etiology and significance of cardia intestinal metaplasia (CIM) is disputed. CIM may represent a form of Barrett's esophagus due to reflux or could reflect generalized gastric intestinal metaplasia due to Helicobacter pylori. The aim of this study was to utilize gene expression data to compare CIM to Barrett's and gastric intestinal metaplasia. Endoscopic biopsies were classified by endoscopic and histologic criteria as CIM (n= 33), Barrett's (n= 25), or gastric intestinal metaplasia of the antrum or body (n= 18). The squamocolumnar and gastroesophageal junctions were aligned in CIM patients and patients with diffuse gastric intestinal metaplasia were excluded. H. pylori was tested for in the biopsies of all patients. After laser-capture microdissection, quantitative reverse transcription-polymerase chain reaction (RT-PCR) was used to measure the mRNA expression of a panel of nine genes that has been shown to differentiate Barrett's from other foregut mucosa. Cluster analysis with linear discriminant analysis of the expression data was used to classify each sample into groups based solely on similarity of gene expression. Cluster analysis was performed for three groups (CIM vs. Barrett's vs. gastric intestinal metaplasia) and two groups (CIM + Barrett's vs. gastric intestinal metaplasia). There was no difference in H. pylori infection among groups (P= 0.66). Clustering into three groups resulted in frequent misclassification between CIM and Barrett's while misclassification of gastric intestinal metaplasia was uncommon. The CIM and Barrett's groups were then combined for two group clustering and linear discriminant analysis correctly predicted 95% of CIM and Barrett's samples and 83% of gastric intestinal metaplasia samples based on gene expression alone. In conclusion, the gene expression profiles of CIM and Barrett's esophagus were similar in 95% of biopsies and differed significantly from that of gastric intestinal metaplasia. The indistinguishable gene expression profile of CIM and BE suggests that they may share a common etiology in the majority of patients with a similar biology, and calls into question the perception that CIM is an innocuous process.

Multilayered Epithelium May Be Found in Patients With Barrett’s Epithelium and Dysplasia or Adenocarcinoma

To determine if multilayered epithelium (MLE) is a useful prognostic indicator for a benign natural history of Barrett's epithelium, we evaluated endoscopic biopsies from patients with Barrett's epithelium without and with dysplasia and/or adenocarcinoma and from non-Barrett's controls for the presence of MLE. MLE was found in 6% of non-Barrett's controls, 30% of Barrett's patients with no dysplasia, and 14% of Barrett's patients with dysplasia and/or adenocarcinoma. MLE was significantly associated with shorter lengths of Barrett's epithelium in both Barrett's groups. Three of 5 photodynamic therapy patients were noted to develop MLE after therapy. MLE may be found in patients with dysplasia and/or adenocarcinoma and after photodynamic therapy; its presence is not useful as a prognostic indicator for a more benign course of Barrett's. This study confirms that MLE is significantly associated with shorter lengths of Barrett's epithelium.

Survivin, a potential biomarker in the development of Barrett's adenocarcinoma

Survivin, a member of the inhibitor-of-apoptosis family, is reported to be overexpressed in esophageal cancer but no data are available about its status in the metaplastic/dysplastic sequence. The aim of this study was to measure survivin gene expression in normal squamous/columnar epithelium and in the various stages of development of Barrett's adenocarcinoma. Endoscopic biopsy or operative specimen samples from 5 tissue types were analyzed: (1) squamous epithelium from 3 cm above the gastroesophageal junction in patients with a negative pH study and no histologic injury (n = 17, pH- control); (2) antral tissue from patients with no evidence of Barrett's, dysplasia, or cancer (n = 29, antral control); (3) specialized intestinal metaplasia from patients with Barrett's esophagus (n = 16; Barrett's group); (4) low- or high-grade dysplasia (n = 12, dysplasia group), and (5) adenocarcinoma (n = 45 cancer group). After laser-capture microdissection cellular RNA was extracted from each tissue and reverse transcribed to complementary DNA. Expression levels of survivin were measured by reverse-transcription polymerase chain reaction. Survivin gene expression was greater in columnar (antral) compared with squamous (pH-) control tissues (P = .03). Expression in quiescent Barrett's epithelium was similar to both control tissues. Expression levels in dysplastic epithelium were greater than in squamous control (P = .01) and Barrett's tissues (P = .04), but not higher than columnar control tissues, whereas expression in adenocarcinoma was greater than all tissues except dysplasia (P < .001). Survivin expression may be a biomarker in the development of Barrett's adenocarcinoma that is able to distinguish between quiescent Barrett's, dysplastic Barrett's, and Barrett's adenocarcinoma.

CLINICAL, PHYSICAL AND DEMOGRAPHIC FACTORS CAN PREDICT THE LENGTH OF BARRETTʼS ESOPHAGUS

Purpose: The increased risk for cancer in patients with Barrett's esophagus is often cited as a driving force for endoscopic evaluation of patients with gastroesophageal reflux disease (GERD). Long-segment Barrett's esophagus (LSBE) conveys an increased risk for cancer compared to short-segment Barrett's (SSBE), but clinical factors that distinguish these patients are less well characterized. The aim of our study is to evaluate clinical and epidemio-logic factors that may help distinguish patients with GERD, SSBE and LSBE in a geographically and racially diverse group of patients. Methods: We prospectively evaluated patients with endoscopic and histo-logically confirmed SSBE (<3 cm) and LSBE (>3 cm), as well as a GERD cohort. Demographic and clinical features, medication usage, endoscopic appearance and histologic samples from 112 GERD, 40 SSBE and 45 LSBE patients from 2 sites were compared. Results: There was a higher percentage of men in the LSBE group as compared to the SSBE (p <0.025) and GERD group (p <0.05). There was a higher percentage of Caucasians in the Barrett's groups; but this difference was significant only when comparing LSBE to GERD patients (p <0.01). LSBE patients were taller than patients in the SSBE (p <0.025) and GERD groups (P <0.005). This remained significant even when adjusting for gender differences. LSBE patients were more likely to have gained weight in the preceding year than SSBE (p <0.025) and GERD patients (p <0.01). There was a trend towards a higher weight in the LSBE group over the SSBE and GERD groups although this was not statistically significant. Interestingly, the average BMI was 30 kg/m2 in all three groups. LSBE patients were more likely to have heartburn symptoms for greater than 10 years than SSBE (p <0.05) or GERD (p <0.01) patients, but neither severity of heartburn or frequency of symptoms was significantly different between the three groups. Overall, there was no significant differences between the SSBE and GERD patients. Age, tobacco or alcohol use, previous esophagitis, hiatal hernia or PUD, medical history or medication were not distinguishing factors between any of the groups. Conclusions: While several clinical, demographic and physical characteristics distinguish LSBE patients from those with SSBE and uncomplicated GERD, we found no differences between SSBE and GERD patients. Thus, clinical factors cannot be used as discriminative factors in designing screening guidelines.

Colonization with cagA-positive Helicobacter pylori strains in intestinal metaplasia of the esophagus and the esophagogastric junction.

Recent studies indicate that colonization with cagA-positive Helicobacter pylori (H. pylori) strains may protect against gastroesophageal reflux disease (GERD) and its complications, but the role of cagA in the etiology of Barrett's esophagus has so far been poorly investigated. The pathogenesis of intestinal metaplasia (IM) at an endoscopically normal esophagogastric junction (EGJ) is still unclear, and the role of the H. pylori virulence factor cagA in it has not been investigated. The aim of our study was to assess the relationship between H. pylori and cagA-positive H. pylori in particular and IM at an endoscopically normal EGJ and Barrett's esophagus. Serum samples were obtained from 62 patients without IM, 43 patients with IM at an endoscopically normal junction, and 51 patients with Barrett's esophagus. IM was defined as presence of goblet cells with positive staining with Alcian blue. The prevalence of H. pylori and cagA was investigated by assessment of IgG antibody levels as determined by ELISA. The overall H. pylori prevalence was 59% (92/156), and the cagA prevalence was 29% (46/156). Although 63% (39/62) of IM negative subjects and 74% (32/43) of those with IM at the junction were H. pylori positive, only 41% (21/51) of Barrett's patients tested positive. The differences between the IM negative and the Barrett's group (p = 0.02) and between IM at the junction and Barrett's were significant (p = 0.002). The relative cagA prevalence (percentage with cagA positivity and H. pylori positivity) was 56% (22/39) in patients who were IM negative, 59% (19/32) in those with IM at the junction, and 24% (5/21) in those with Barrett's. The prevalence of anti-CagA was significantly lower in patients with Barrett's esophagus compared with patients who were IM negative (p = 0.002) and those who had IM at the junction (p < 0.001). No difference in cagA prevalence was seen between the latter groups. These findings are in line with the concept that H. pylori and cagA-positive strains in particular protect against the development of Barrett's esophagus. In contrast, our findings do not support the theory that IM at an endoscopically normal esophagogastric junction is associated with H. pylori or cagA-positive strains. IM at the junction and Barrett's esophagus seem to have different etiologies.

Outcome of esophageal adenocarcinoma detected during endoscopic biopsy surveillance for Barrett's esophagus.

In an attempt to reduce mortality from esophageal adenocarcinoma, it has been recommended to enroll patients with Barrett's esophagus in endoscopic surveillance programs in order to detect malignant degeneration at an early and possibly curable stage. The aim of this study was to assess the impact of endoscopic biopsy surveillance on outcome of Barrett's adenocarcinoma. Between November 1992 and June 2000, 312 patients with histologically proven esophageal adenocarcinoma were referred to our department. Ninety-seven of these patients had Barrett's adenocarcinoma. In 12 (12.2%) patients, cancer was discovered during endoscopic surveillance for Barrett's metaplasia. The prevalence of gastroesophageal reflux disease in the Barrett's group was 38.8% versus 8% (p < 0.01) in non-Barrett's patients. In the surveyed group, there were 9 (75%) early stage tumors (Tis-1/N0) versus 9 (10.6%, p < 0.01) in the nonsurveyed patients. Three of 5 surveyed patients operated on for high-grade dysplasia proved to have invasive carcinoma in the esophagectomy specimen. All surveyed patients were alive at a median follow-up of 48 months; the median survival in the nonsurveyed group was 24 +/- 3 months (p < 0.01). Endoscopic surveillance of Barrett's esophagus provides early detection of malignant degeneration and a better long-term survival than in nonsurveyed patients.

Bile reflux gastritis and Barrett's oesophagus: further evidence of a role for duodenogastro-oesophageal reflux?

BACKGROUNDThere is increasing evidence that reflux of bile plays a part in the pathogenesis of Barrett's oesophagus. Bile injury to the gastric mucosa results in a “chemical” gastritis in which...

The prescribing of acid suppressants prior to the endoscopic diagnosis of Barrett's oesophagus and oesophagitis.

There has been a dramatic rise in incidences of Barrett's oesophagus and oesophageal adenocarcinoma. It has been suggested that the introduction and use of acid suppression therapy may be a factor in the rising incidences of Barrett's oesophagus and oesophageal adenocarcinoma. This was a record linkage study, using a prescribing database and an endoscopy database. Patients who had undergone their first endoscopy during the period 1992-1995 and received the diagnosis of Barrett's oesophagus or oesophagitis were identified. The prescribing of acid suppressants was compared for the 3 years prior to endoscopy, between those with Barrett's oesophagus and those with oesophagitis. There was no significant difference between the Barrett's patients and the oesophagitis patients in the proportion that had been exposed to acid suppression therapy (53.4% vs. 51.7%, P=0.704). The mean number of days of prescribing among those who had been exposed to acid suppression therapy was higher in the Barrett's group (340.5 vs. 237.0 days, P=0.001). Patients with Barrett's oesophagus have received more acid suppressant therapy prior to diagnosis. The reasons for this are not clear. However, 46.6% of Barrett's patients have not been exposed to acid suppressant therapy.

Neuromuscular function of the human lower oesophageal sphincter in reflux disease and Barrett's oesophagus

BACKGROUNDColumnar lined (Barrett's) oesophagus is often considered a sequel to chronic severe reflux disease. Aberrant lower oesophageal sphincter (LOS) motility associated with Barrett's oesophagus includes reduced basal LOS pressures. The...

Symptoms are a poor indication of severity of reflux in Barrett's oesophagus

AIMS: Patients with Barrett's oesophagus have increased acid and duodenogastric reflux and impaired motility compared with non-Barrett's patients with reflux disease. Impaired sensitivity to acid infusion and distension have also been described, but the relationship of this visceral response to symptoms is unclear. A symptom index was used to compare Barrett's and non-Barrett's patients with reflux. METHODS: Patients with reflux (DeMeester score above 14) were studied with 24-h pH monitoring and manometry. An event marker recorded symptom events. An event was positive if it corresponded to a period greater than 10 s within 2 min either side of the drop in pH. The symptom index was calculated as the number of symptoms with pH less than 4/total number of symptoms x 100. RESULTS: Eighteen patients with Barrett's oesophagus were compared with 58 non-Barrett's patients with significant reflux. CONCLUSIONS: Patients with Barrett's oesophagus have a low symptom index compared with non-Barrett's patients with reflux disease. This occurs despite a near 100 per cent increase in acid exposure in the Barrett's group. Symptoms are thus no guide to the severity of reflux in patients with Barrett's oesophagus. Proof of efficacy of therapeutic modalities may need physiological rather than symptom-based confirmation.

Prevalence of Helicobacter pylori infection in 160 patients with Barrett's oesophagus or Barrett's adenocarcinoma.

The role of Helicobacter pylori infection in the development of Barrett's oesophagus and its complications is uncertain. The aim of the present study was to determine the importance of H. pylori infection in this disease by comparing the frequency of oesophageal and gastric H. pylori infection in a group of patients with Barrett's oesophagus or adenocarcinoma, with the frequency of infection in a control group without Barrett's disease. The study group included 160 patients (123 male, 37 female; mean age: 61.2 years) who were classified (according to the highest grade pathological lesion in the oesophagus) as having Barrett's intestinal metaplasia (IM; 88 patients), Barrett's oesophagus with low-grade dysplasia (LGD; 28 patients), high-grade dysplasia (HGD; five patients), Barrett's indefinite for dysplasia (n = 4), and Barrett's adenocarcinoma (33 patients). A total of 91 of these patients had gastric antral specimens available for study. The control group consisted of 214 consecutive, prospectively enrolled symptomatic patients (122 male, 92 female; mean age: 57.2 years) who underwent upper gastrointestinal endoscopy and in whom Barrett's oesophagus or Barrett's adenocarcinoma was not found. A modified Warthin-Starry method was used to detect H. pylori infection. Oesophageal H. pylori infection was found in eight of 160 (5%) patients with Barrett's oesophagus or Barrett's adenocarcinoma. Holicobacter pylori organisms in the oesophagus were found only on non-intestinalized cardiac or oxyntocardiac mucosa. All patients with oesophageal H. pylori infection and an antral biopsy available for study had antral H. pylori infection. Gastric antral H. pylori infection was significantly less prevalent in patients in the Barrett's study group (15/91, 16.5%) than in the non-Barrett's control group (67/214, 31.3%; Fisher's exact test, P = 0.01). Patients from the control group with an endoscopic diagnosis of duodenal ulcer, gastric ulcer, gastritis, or duodenitis had a significantly higher prevalence of infection compared with the Barrett's group, but there was no difference in the infection prevalence in patients in the Barrett's group and patients with reflux oesophagitis, hiatal hernia, no endoscopic abnormality, or any other diagnosis. Oesophageal H. pylori infection is uncommon in patients with Barrett's IM, dysplasia, or adenocarcinoma, and may be restricted to non-intestinalized columnar epithelium. Gastric H. pylori infection may have a protective effect for the development of Barrett's oesophagus.

Barrett's esophagus and the presence of Helicobacter pylori.

Although the role of Helicobacter pylori in the pathogenesis of peptic ulcer disease and antral gastritis has been well documented, the role of H. pylori in esophageal disease has not been clearly defined. To clarify this issue, we analyzed 141 patients with histologically confirmed esophageal disease. The study group consisted of 82 patients with Barrett's esophagus, 19 with adenocarcinoma of the esophagus arising in columnar epithelium and 40 patients with reflux esophagitis without columnar metaplasia of the esophagus. In each of these cases the presence or absence of H. pylori was assessed histologically. H. pylori was present in 19 of 82 patients (23%) with Barrett's esophagus, but was absent in all patients with adenocarcinoma of the esophagus and in patients with reflux esophagitis without Barrett's metaplasia. H. pylori was found only in areas of gastric type metaplasia in the patients with Barrett's esophagus. All of the 19 Barrett's esophagus group with H. pylori had chronic inflammation, and in 16 the inflammation was severe. H. pylori was significantly associated with severity of inflammation in patients with Barrett's esophagus (p < 0.001). Members of the Barrett's group with evidence of moderate to severe dysplasia were negative for H. pylori. These data confirm that the presence of gastric type mucosa within the esophagus is a prerequisite for H. pylori colonization, and that H. pylori may contribute to the severity of inflammation in Barrett's epithelium.

Morphological characterization of the squamocolumnar junction of the esophagus in patients with and without Barrett's epithelium

Barrett's esophagus is a metaplastic condition in which the normal stratified squamous epithelium of the distal esophagus is replaced by columnar epithelium. Our group has previously characterized a unique surface cell (the "distinctive cell") at the junction of squamous and Barrett's epithelium. This cell is notable for the simultaneous presence on its surface of both squamous and columnar cell features. The aims of our present study were, first, to evaluate prospectively the frequency with which Barrett's patients have the distinctive cell at the squamo-Barrett's junction; second, to further elucidate the characteristics of the distinctive cell; and third, to perform a combined morphological study of the squamo-Barrett's junction using scanning electron microscopy followed by transmission and light microscopy. We divided study patients into two groups: Group I consisted of Barrett's patients and group II of non-Barrett's control patients. Of eight group I Barrett's patients with junctional biopsies, three were noted to have the distinctive cell (37.5%). In contrast, this cell was not observed in any of the group II control patients. Biopsies in control patients as well as Barrett's patients without the distinctive cell revealed abrupt squamogastric or squamo-Barrett's junctions by scanning electron microscopy and light microscopy. In contrast, biopsies from the Barrett's patients with the distinctive cell revealed junctions that were not abrupt and had the distinctive cells overlying normal squamous epithelium. By scanning electron microscopy, the distinctive cells were flattened, polygonal cells with surface microvilli (a columnar cell feature) and were demarcated from one another by shallow depressions, or by intercellular ridges (a squamous cell feature). By transmission electron microscopy, the distinctive cells were cuboidal in shape with abundant apical microvilli and secretory vesicles. We have confirmed that distinctive cells are present in some Barrett's patients. This cell is a morphologic hybrid, sharing features of both squamous and columnar cells, and may be analogous to hybrid cells identified in other locations that undergo metaplasia (eg, the human cervix). Its origin may be the result of transformation of multipotential basal cells of squamous epithelial origin. We hypothesize that the distinctive cells may represent an intermediate stage in the development of Barrett's epithelium.

Barrett’s esophagus and adenocarcinoma of the esophagus and gastroesophageal junction

Since 1985, 57 patients with adenocarcinoma of the esophagus and gastroesophageal (GE) junction have undergone surgical resection. In this group, 16 of the tumors arose in a Barrett's esophagus. There was a significant predilection toward white men above the age of 55 (15/16; 94%) in this subgroup. The mean proximal extent of abnormal columnar involvement was 5.4 cm above the gastroesophageal junction (range 2.5 to 11 cm). The mean location of the neoplasm centered in the distal esophagus 1.8 +/- 0.5 cm above the gastroesophageal junction. During the same time period, 30 patients with Barrett's esophagus were seen without associated adenocarcinoma. There were no statistical differences in the proximal extent of columnar involvement or the presence of reflux symptoms between the two groups. There were no significant differences in age, smoking history, and alcohol consumption between patients with benign or malignant Barrett's esophagus as compared to those with adenocarcinoma of the gastroesophageal junction not associated with Barrett's mucosa. The marked male predominance seen in the group with malignant Barrett's esophagus was in contrast to the benign cases (16/30; 53%) but was similar to the adenocarcinoma group, without recognized Barrett's esophagus (38/41; 93%). The mean location of the tumor in the latter was 0.9 +/- 1.2 cm above the gastroesophageal junction and was comparable to the location in the group with Barrett's adenocarcinoma. The 4-year survival rate of patients in the non-Barrett's adenocarcinoma group is approximately 30%. Of those with Barrett's adenocarcinoma, the present 4-year survival rate is 60%. The demographic and morphometric similarities between the Barrett's and non-Barrett's adenocarcinoma groups may be of primary importance in determining the true clinical prevalence of Barrett's adenocarcinoma. Our findings suggest that the sensitivity of endoscopic surveillance may be improved if biopsy specimens are concentrated within the distal 3 cm of the esophagus and the esophagogastric junction. Finally, the reason for the current difference in survival between the Barrett's and non-Barrett's adenocarcinoma groups is uncertain but may be related to endoscopic surveillance permitting earlier diagnosis and treatment.

Barrett's esophagus in children and young adults

Since few data are available on epidemiologic features of Barrett's esophagus in young persons, we reviewed the case records of patients undergoing esophageal biopsies at Children's Hospital, Boston, from 1982 through 1986. There were 1423 esophageal biopsies obtained from 1173 patients, and histological evidence of esophagitis was present in 397 cases; Barrett's epithelium was diagnosed in 10 patients (0.9% of total and 2.5% of esophagitis cases). Specialized columnar epithelium was present in seven of these 10 patients. The mean age of those with Barrett's epithelium was 19.0 +/- 7.9 years (range 3.7-27 years) compared to 8.7 +/- 6.7 years (range 4 days to 31 years) for all patients biopsied (P less than 0.0001); 80% (8/10) of the Barrett's cases were male compared to 54% of all cases. The relative importance of the possible risk factors was assessed by comparing the 10 patients with Barrett's with the 541 patients that had esophageal biopsies in calendar years 1984-1985. Mental retardation, a risk factor not previously described for young persons with Barrett's esophagitis, was present in 70% (7/10) of the Barrett's patients but in only 15% of all patients biopsied (P less than 0.0002). The frequency of mental retardation was also higher, but not significantly so (P greater than 0.07), in patients with biopsies that were positive for esophagitis (19%) than in those with normal biopsies (14%). No significant differences were found between the Barrett's group and all patients biopsied in regards to racial origin, prior stricture, or fundoplication.