W1297

Cardia-Type Mucosa Is the Predominant Type of Metaplasia in Columnar Lined Lower Esophagus Ulrich Peitz, Michad Vieth, Andreas Leodoher, Stefan Kahl, Albert Roessner, Peter Malfertheiner

Only specialized intestinal metaplasia (SIM) within segments of columnar epithelium lined lower esophagus (CLE) is acknowledged to car D, an increased m k for esophageal adenocarci- noma. However, the prevalence of SIM in endoscopically identified CLE varies The question is raised whether otber types of metaplasia within CLE are of any significance. Aim: To access the type of metaplasia in CLE Patients and methods: In 306 consecutive patients undergoing upper intestinal endoscopy for dyspeptic or reflux symptoms, the endoscopic and histological findings of the esophagogastric junction were compared. CLE was defined as any dislocation of the squamocolumnar junction (SCJ) proximal to the esophagogastric junction (EGJ), whether in shape of tongues, islets or circular areas. EGJ was identitled by the upper border of the gastric folds and the lower border of the palisade veins. The endoscopic appearance of the SCJ was grouped according to the length of CLE: no CLE (group 1); CLE < l c m (group 2); CLE <3cm (group 3); and CLE ~3cm (group 4). Biopsies were obtained from EGJ and separately from CLE Histological slides were stained with H&E and Gomori s aldehyde fnchsin for differentiation of complete type intestinal metaplasia and S1M. Results: See table, Conclusions: In CLE, three different types of mucosa are found histologically: cardia-, fundus- and SlM-type. The frequency of S1M (Barrett's mncosa) correlates with the length of CLE. The most frequent type of mucosa in short segments of CLE is cardia-type, but also long segments still contain this mncosa in half of the cases. This suggests that cardia-type mucosa is a metaplasia induced by gastroesophageal reflux and ma t' precede SIM The prognosis of CLE with cardia-type nretaplasia, but without SIM should to be determined.

Histological type of metaldasla dependent on endoscoldc appeareance

.h,to,~w Endoscopy Biopsy fundus, cardia- complete intestinal

Group Site n type t y p e n~.aplasla SIM EGJ 110 42% 54% 18% 1%

2.4 EGJ 198 36% 55% 12% 9% 2 CLE <lcm 123 15% 55% 4% 29% 3 CLE .,:3cm 52 11% 66% 0% 36% 4 CLE ~'3cm 21 8% 47% 0% 83%

W1298

Relation of Hiatal Hernia Size with Length of Barrett 's Esophagus David Desilets, Brian Nathanson, Farhad Navab

Introduction: It has been shown that the severity of esophagins and presence of Barrett's epithelium is related to prolonged acid exposure. One factor leading to recurrent episodes ot acid exposure is re-reflux t~com a hiatal hernia. Both presence and progression of Barrett's epithelium has been related to hiatal hernia size (Gastroentero11999;116:227, AJGastmenerol 1999;94:3413). In this study we provide evidence suggesting a relationship between hiatal hernia size with Barrett's esophagus length. Methods: A cohort of 82 patients with Barrett's esophagus was studied to determine differences between 39 patients with short-segment (SSBE) measured as < 3cm and 43 with long-segment Barrett's esophagus (LSBE), as > 3cm in length. BE was diagnosed endoscopically and confirnred by presence of intestinal metaplasia above the sqnamo-columnar junction on endoscopic biopsies. The cohort included 64 males and 18 temales. Results: A hiatal hernia was present m all patients except one male with SSBE The mean size of hiatal hernia in males and females with SSBE was 3,07 and 2.5 cm and in LSBE 4.2 and 4.7 cm. Hiatal hernia size was larger in patients with LSBE (mean 4.3 cm, SD 1.34) than in SSBE (2.95 cm, SD 1.28), p < 0.0001. A linear regression analysis suggested that there was a relationship between Barrett's length and hiatal hernia size (BE length = 0.04 + 0.851 hernia size, p = 0.000 R2 = 0.249). lxgistic regression showed an odds ratio of 2.28 for LSBE for each 1 cm increase in hiatal hernia size. Risk tactors such as current or prior alcohol use, current or prior tobacco use and a wight gain of 5 lb in prior 5 yr did not appear to influence the length of BE. The finding of a stricture or an ulcer during endoscopy was more common in LSBE compare with SSBE 9/43 vs 1/ 39 p<0,001. Presence of high-grade dysplasia or adenocarcinoma con~lated with LSBE. Conclusion: The results suggest that the presence of a hiatal hernia is an important pathogenic tactor in development of Barrett's esophagus. In our population hiatal hernia size positively correlated with length of Barrett's epithelium. Higher levels of recurrent re-relfiix from a larger hiatal hernia may be a pathogenic factor in determining the initial length of Bar- rett's epithelium.

W1299

Early Results of Multiple Biomarkers in Barrett's Using Immunohistochemistry and Laser Scanning Cytometry james H. Sul, Dennis M Jensen, Jian Y. Rao

Background: The management of the increased cancer risk in Barretts's esophagus (BE) centers around surveillance tor dysplasia or cancer, largely with random biopsy. The diagnosis of dysplasia results in increased surveillance. However, interobserver variation ranges from 86% tur high grade dysplasia to < 70% for low grade or indefinite. There is a need for objectwe biomarkers to reduce costs and improve management. We have a long-term goal of evaluating ~he use of biomarkers as an adjunct to histology or as a primary risk-stratifying modality. We present our preliminary results using both immunohistochemistry (IHC) and a new objective tool, laser scanning cytometry (LSC). Methods: 16 p.atients with BE were collected. 5 patients had IHC for Cyclin D1, Cox lI, and HSP 27 and immunofluorescence for DNA content using LSC. 11 patients had both IHC for p53 and immunofluorescence for p53 with LSC. All sections were graded prior to the study and a blinded pathologist

using 0-4 grading read the IHC. An intensity score (INS) was calculated by adding the grades for each slide and dividing by the total number of slides by grade. The LSC score is the percentage of ceils above a predetermined intensity level as calibrated by controls, Resuhs: See table 1. (SBM = Standard Error of the Mean) Using LSC, the score for p53 was 4.8 (SEM 2.7), 5,2 (SEM 1.9) and 4.9 (SEM 1.2) for BE, LGD and HGD. P values comparing means were not significant. LSC scores comparing DNA content were 8.9 (SEM 4.2), 63.3 (SEM 16.6), and 68.9 (SEM 13,4) for BE, LGD and HGD. Tire P value for LGD or HGD vs BE was significant at p<0.001 but not for HGD vs LGD. Conclusions: No marker showed any striking relationship between visual grading and staining by IHC. There was a slight linear increase in the 1NS by histology for Cox II. There was a rise in INS between BE and both LGD and HGD for HSP 27 and p53 but no difference in 1NS between LGD and HGD. Interpretations using IHC remain difficuh due to variability. LSC appears promising in objective quantification as LSC percentages and p53 INS appeared to correlate. LSC measuring increased DNA content, show promise as an alternative to flow cytometry for measuring DNA ploidy as it utilizes paraffin-embedded tissue instead of fresh tissue.

PoslOve Staining by Immunohistochemlstry and INS by Biomarker

Cox n INS Ojclin DI INS HSP 27 INS p53 INS BE 4,'$ (67%) 0.4 1/6 (17%) 0.3 5~ (83%) 1.67 4/7 (573',) 1.1

LGD 4/8 (50%) 0.6 5/8 (63%) 1.4 8/8(100%) 2.88 9/10 (90%) 2.3

HGD 4/5 (80%) 1.0 2,'5 (40%} 0.4 5/5(100%) 2.00 4/5 (80%) 1.8

W1300

Prevalance of Barrett's Esophagus in Patients without Reflux or Reflux-Related Symptoms Sanjay Nayyar, Bashar M Attar, Gijo Vettiankal, Frida Abrahamian

Barrett's esophagus was recently reported to be present in as high as 25% of as~mnptomatic patients while autopsy studies have shown a much lower rate of 0.9%. The aim of this study was to find the prevalence of Barrett's esophagus in patients who underwent endoscopy for indications other than GERD related symptoms. Methodology: We evaluated 260 consecutive patients (group 1) who had Esophagogastmduodenoscopy (EGD) for indications other than GERD and compared them to a control group of 180 patients (group ll) who underwent EGD for symptoms of heartburn and/or regurgitation for a minimum of 3 months in a retrospective review.Exclusion criteria for group l patients included patients who had a W ~'mptoms of heartburn, regurgitation, dysphagia, GI bleeding or h/o prior gastric surgeD'. Demographic data of group I patients revealed 109(419%)African-Americans, 73(28%)His- panics, 46(17J%)Cancasians,and 32(12.3%)Asians. The range of age was 38-81 years. In the control arm (group 1I) of 180 patients there were 64(35.5%) African-Americans, 72(40%)Hispanics, 22(16,7%)Caucasians and 14(7 8%)Asians.The range of the ages was 38-71 years. Results: In the non-GERD patients(group I),four(1.5%) patients had endoscopic appearance suggestive of SSBE(sbort segment Barrett's esophagus) but on staining with alcian blue, only 2(0.77%) had intestinal metaplasia and theretore qualified as SSBE.In the control group(grouplI), fourteen patients had endoscopic appearance of Barrett's esophagus (12 SSBE and 2 LSBE).Both patients with LSBE had intestinal metaplasia on alcian blue staining, with one patient having low-grade dysplasia. Eight patients out of 12 with endoscopic appearance of SSBE had intestinal metaplasia on alcian blue staining on histology, One patient was found to have adenocarcinoma of the distal esophagus in the patients in the control arm. Thus, 11(6. ] %) patients presented with Barrett's esophagus/esophageal adeno- carcinoma in the control group. Conclusion: In a general population with mLxed ethnicity, Barrett's esophagus was only detected in 0.77% of the patients who had endoscopy for non- GERD related indications.

W1301

RANK is Expressed As a Late Event During Malignant Progression in Barrett's Metaplasia Rebecca Yorke, Anas Younes, Mmni Chirala, Mamoun Younes

Activation of Receptor Activator of Nuclear Factor kappaB (RANK) induces several several survival signals including nuclear factor kappaB (NB-kappaB) and activation and upregulation of Bcl-xL. 1"he aim of this work is to determine whether RANK is expressed in esophageal adenocarcinoma (EA) and its precursor, Barrett metaplasia (BM). Sections of tbrmalin-fixed and paraffin-embedded tissue from 23 esophagectomy specimens showing EA and BM with and without dysplasia were stained for RANK using standard immunoperoxtdase technique, and the percent of positive cells was recorded. All 23 EA cases (100%) showed strong RANK immunoreactivity. This was detected in >75% of the cancer cells in 21 (91%) cases and in 11-50% of the cancer cells in 2 (9%) of the cases. In high grade dysplasia ti'om 8 cases RANK was detected in >50% of the dysplastic cells in 3 (37%) case, in 11-50% of the cells in one (12%) case, in 1-10% of the cells in 3 (40%) cases, and was completely negative in one (12%) case. RANK was not detected in any (0%) of 17 Barrett metaplasia ND, or any (0%) of 9 LGD. These results indicate that RANK is expressed as a late event during nralignant progression in BM It remains to be determined whether interfering with RANK signaling affects survival of EA cells. Supported by National Institutes of Health grant R01 C~81570-02.

W1302

Predictors of Progression to Cancer in Barrett's Esophagus (BE): Endoscopic Lesions Ar/sing from Barrett's Epithelium Are Not Independently Associated with Increased Risk Michael M. Owens, Patricia Blount, Gary Longton, Peter Rabinovitch, Brian J. Reid

Background: It has been suggested that endoscopic lesions such as nodules or ulcers arising in BE may indicate increased risk of present or future adenocarcinoma. However, few large clinical trials or observational data sets exist to support the use of this data in surveillance

A-643 AGA Abstracts