confirmation of specialized intestinal metaplasia (SIM). Patients with endoscopic BE and noSIM on histopathology confirmed by two expert pathologists received a follow up EGD withbiopsies within 1 year of the index endoscopy. The follow-up endoscopy and review ofhistopathology from targeted biopsies was carried out in the same manner as the indexendoscopy. We examined multiple predictive variables (clinical, demographic and the endos-copist identity) and three possible outcomes (definite BE "endoscopic BE plus SIM in targetedbiopsies", endoscopic BE only "endoscopic BE with no SIM" or no BE) on repeat EGD.Results: A total of 1844 patients underwent EGD; 344 had suspected BE on endoscopyincluding 237 with definite BE (146 (62%) short ,3 cm segment and 91 (38%) longsegment). 107 patients had endoscopic only BE [101 (94%) short segment and 6 (6%) longsegment)., 80 underwent a repeat EGD with biopsies within 1 year of the index EGD ofwhich 96% were men with an age distribution of 40-49 (14%), 50-59 (26%), 60-69 (46%)and .70 years (14%). 70% (56 of 80 patients) had endoscopic BE confirmed at repeat EGDand 23 (29%) had biopsies confirming SIM. The mean length of BE on the index EGD wasslightly longer among patients with definite BE than those with endoscopic only BE and noBE on the repeat EGD; 1.6 cm (SD 1.3), 1.5 cm (SD 1.4) and 1.4 cm (SD 1.2), respectively.The majority (96%) confirmed BE on repeat EGD had short segment BE ( ,3 cm). Patientgender, age, race, BMI, presence or duration of GERD symptoms or size of hiatal herniawere not significantly associated with a positive biopsy for BE on repeat EGD (p .0.1),and nor was the identity of the endoscopist. Conclusion: The majority of patients withendoscopic only BE had biopsies negative for SIM on repeat EGD. The results of this studyaffirms the withholding of a diagnosis of BE for individuals with endoscopic only BE.

Mo1901

Goblet-Cell Density and Differentiation in Barrett's Esophagus Correlate WithIncreased Esophageal-Adenocarcinoma Development in HumansRaphael J. Schellnegger, Martina Schernhammer, Michael Vieth, Roland M. Schmid,Michael Quante

Introduction: Barrett's esophagus (BE) is a premalignant condition, characterized by a meta-plastic change from squamous to columnar intestinal-type epithelium. To include patientswith endoscopic BE into surveillance, specialized intestinal metaplasia (IM) with goblet cells(GC) needs to be confirmed. However incidence-rates for EAC within these patients arevery low. Nevertheless the overall incidence of EAC raises and correlates with an insufficienthistological dysplasia assessment as well as observer errors. Therefore re-diagnostic is doneassuming patient compliance and financial resources. Recent studies also suggest that a lackof GC in chronic inflammation could be associated with EAC. Using a novel mouse modelfor BE we suggested that chronic-inflammation induces migration of Lgr5+ stem cells fromgastric cardia to migrate into the esophagus and give rise to BE. Notch-signaling inhibitionresulted in IM differentiation and risk reduction for EAC, suggesting that GC differentiationcould be protective in this environment. Methods: To transfer the results from the mousemodel to humans we analyzed a correlation of GC-density, stem cell- and differentiationmarkers with disease progression in a retrospective cohort of BE, LG/HGD and EAC patients.100 samples were analyzed and on biopsies PAS/HE-staining as well as Immunohistochemis-try for Dclk1, Lgr5, Tff2 and Notch was performed. Quantification was done in 10xmagnifica-tion as a ratio of crypt numbers containing GC or positive immunostaining in correlationwith the histological diagnosis. Results: Analyzing the different stages our data suggests thatnon-dysplastic BE is associated with higher GC density as well as active Notch-signaling.Furthermore Tff2, expressed in progenitor cells of the columnar lined esophagus (CLE), isassociated with lower GC density. Lgr5, a known stem cell marker of the cardia, not presentin the esophagus, and Dclk1, a proposed stem cell marker of the gut that correlates withinflammation, are associated with dysplasia or EAC andwith less GC differentiation. Moreoveradjacent to EAC no GC could be observed. Summary: To predict malignant transformationbetter diagnostics than todays are needed to determine high-risk patients. Transferring theinsights from the mouse model to the human shows a significant correlation of GC-densityand GC differentiation dependent markers with the stage of BE. Our data suggests thatsimilar to the mouse, in humans Notch-signaling regulates GC differentiation and less GCcorrelates with increased malignant transformation. It remains to be analyzed in an ongoingprospective trail, if these markers and the GC ratio can predict cancer risk for an individualpatient with BE over time. Nevertheless specific testing of biopsies for the described markerscould be used to improve surveillance programs to be more effective.

Mo1902

Patient Preferences for Endoscopic Assessment of Gastroesophageal Refluxand Barrett's EsophagusJason Egginton, Kelly T. Dunagan, Nilay D. Shah, Christopher Blevins, KarthikRagunathan, Cadman L. Leggett, Prasad G. Iyer

BACKGROUND. Barrett's esophagus (BE), a well-known complication of GER, is the strongestknown precursor of esophageal adenocarcinoma (EAC). Thus, identifying effective screeningapproaches for the early detection of BE are highly desired. Current impediments to BEscreening include 1) the inability to utilize sedated endoscopy (sEGD) effectively in popula-tions and 2) current GER-based paradigms for detecting BE. PURPOSE. As part of a largercomparative effectiveness study of uTNE versus sEGD, we sought to measure the short-term patient preferences associatedwith each test strategy. PATIENTS. Patients were identifiedusing age- and gender-stratified random samples of Olmsted County, Minnesota residents,having no history of BE, and .50 years of age. These patients were randomly assigned toreceive Clinic uTNE, Mobile uTNE, or sEGD. METHODS. Beginning May 2011, an endo-scopic tolerability questionnaire was administered on the telephone 24 hours (+2 days) afterall procedures by a trained interviewer. The instrument assessed side effects, discomfort andsensations such as choking and anxiety, all on a 0-10 scale (10=worst). A "waiting trade-off" (WTO) was used to evaluate the preferences in the three test strategy cohorts: in-clinicsEGD; in-clinic uTNE; or mobile community vehicle uTNE. A difference was calculatedbetween the period a patient was willing to wait for a test result and treatment after ahypothetical "ideal" test and the choice to undergo screening for the arm the patient wasenrolled into. RESULTS. A total of 160 participants have completed the clinic uTNE (n=56), mobile uTNE (n=73), or sEGD (n=31) and the 24h telephone interview thus far. For

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reported minor procedural side effects—such as sore throat, gas, reflux or headache— 38%for clinic uTNE, 32% for mobile uTNE, 42% for sEGD. Mean pain score for each proceduretype (10=worst): 2.9, 1.7, 0.1 respectively. The mean patient tolerability score for eachprocedure overall, with 0 signifying an "ideal" medical procedure: 2.1, 1.9, 0.5 respectively.For mean time trade-off measures of disutility for clinic uTNE was 8 days waiting for results;for mobile uTNE, 7 days; and for sEGD, 6 days. DISCUSSION. Though all three endoscopicassessment types were generally well tolerated by patients, mobile uTNE outperformed itsin-house counterpart on measures of side effects, comfort, tolerability and time-trade offs.While mobile uTNE also appears promising in this light in comparison to sEGD, particularlyin terms of missed hours (likely due to sedation) and lower likelihood of immediate sideeffects, sEGD appears to remain the patient gold standard in terms of pain avoidance andoverall tolerability.

Mo1903

Molecular Effect of Acid and Bile Suppression on Progression of Be toNeoplasiaManisha Bajpai, Kiron M. Das

INTRODUCTION:Acid and bile are implicated in development of columnar metaplasia orBarrett's epithelium (BE) at the gastro-esophageal junction in patients with gastroesophagealreflux disease (GERD). Proton pump inhibitors (PPIs) may prevent progression of BE toneoplasia and may even induce healing by suppressing the acidic pH of stomach and hencethe refluxate. However, molecular effect of acid suppression on the esophageal epitheliumremains elusive. We developed an in-vitro BE carcinogenesis model (BEC) after exposureof telomerase immortalized benign BE cells (BAR-T) to acid and bile at pH4 (B4), 5min/day for 60wks (IJC, 2011). This model can be divided into four stages BEC-0-Week(W)(naive), BEC-20W (karyotype change), BEC-40W (change in shape and loss of contactinhibition) and BEC-60W (foci formation in soft agar) resembling pathological progressionof BE to esophageal adenocarcinoma (IJC,2011). Earlier we observed that growing BEC-20W cells for additional 20 wks in the absence of further B4 exposure prevented changein cell morphology and clumping (loss of contact inhibition) normally seen at BEC-40Wcells. We investigated the molecular basis of this observation, in the present study. AIM:To study the effect of discontinuation of B4 exposure (for 20 weeks) on BEC-20W cellsfocusing on transcript levels of genes involved in metaplastic differentiation (CDX2, NFkB),mucosal healing (TFF3), inflammation (IL-8), apoptosis p53 and Casp3 and proliferation(Ki-67). METHOD: BEC-20W cells were grown in special growth medium (IJC, 2011) anddivided into two groups, one group stimulated with B4 for 5mins everyday and anothergroup left unstimulated for another 20 wks. Transcript levels of genes were evaluated atthe end of 20wks by quantitative RT-PCR analysis (results are average of three independentexperiments). RESULTS: BEC-20W cells after 20 wks of culture without B4 showed markedsuppression of CDX2, NFkB (table) and IL8. These unstimulated cells also had higherlevels of TFF3, Casp3 and p53 transcripts compared to their B4 treated counterparts. Theproliferation marker Ki-67 was however not affected by acid suppression. CONCLUSIONS:We observed suppression of metaplastic differentiation, inflammation and induction ofmucosal healing bio-markers that may prevent disease progression. Increased apoptosis andp53 induction may indicate reinstatement of DNA damage response pathways. Since acidand bile are known to cause DNA damage in BE we did not see any change in proliferationmarker after B4 removal perhaps because BAR-T cells are intestinal (CK7+ and CK8/18+)and colonic (mAbDas-1+) phenotype and acid suppression has been reported to reduceproliferation of gastric phenotype. This study demonstrate a molecular basis for acid andbile suppression an effective therapeutic strategy during early stages of BE (represented byBEC-20W).Effect of acid and bile removal on the neoplastic progression of BE in-vitro: unstimulatedover B4 stimulated BEC-20W cells

Mo1904

Comparative Acceptance of TransNasal Esophagoscopy vs. Esophageal CapsuleEndoscopy for Barrett's Esophagus ScreeningBronia Alashkar, Ashley L. Faulx, Gerard A. Isenberg, Katarina B. Greer, Richard Pulice,Ashley Hepner, Yngve Falck-Ytter, Amitabh Chak

Background: Endoscopic screening for Barrett's esophagus (BE) is controversial. The AGAdoes not recommend screening for BE because sedated EGD is costly, invasive, and thereis insufficient evidence to support its effectiveness. Objectives: To assess the feasibility ofimplementing less invasive, inexpensive office-based methods for BE screening by comparingthe acceptance of unsedated transnasal esophagoscopy (TNE) and esophageal capsule endos-copy (ECE), in a VA clinic. Methods: We identified approximately 600 veterans betweenthe age of 40-85 who had no upper endoscopy in the previous 10 years and invited themto participate in an unsedated screening procedure for BE regardless of whether they hadGERD symptoms. 147 patients accepted BE screening. Patients were then randomly assignedusing sealed envelopes to either ECE (n=73) or TNE (n=74). The assigned procedure wasthen explained. All subjects completed a previously validated acceptability questionnaire (orNon completion for those who refused the assigned screening). Anxiety and nervousnessbefore and during the procedure were assessed using a 10-point Likert scale. Pain, gagging,choking, and overall intolerance scores were also measured following the assigned procedure.Results: The majority of the enrolled subjects (141/147, 95.9%) were men, 76 (51.7 %)were African American and 69 (46.9 %) white, 2 were Hispanic. There were no significantdifferences in age, BMI, education, gender or race between the two study groups. Five (6%)of 74 subjects assigned to TNE refused TNE after randomization, whereas 1 (1.3%) of 73subjects refused ECE after randomization. Subjects completing the TNE, reported moreanxiety before (median score 2 vs. 1, p=0.001) and during (median 2 vs. 1, p , 0.001) theprocedure compared to those who completed the ECE. The TNE exam was also associatedwith higher pain (median score 2 vs. 1, p ,0.001), higher gagging (median score 2 vs. 1,

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sp,0.001), and higher intolerability (median score 1 vs. 1, p ,0.001). The Z-line was fullyvisualized in 58/69 (84%) who completed TNE and 8 subjects with ZAP grade II or higherwere referred for sedated EGD. The Z-line was fully visualized in 67/72 (93%) who completedECE and 3 subjects with ZAP grade II or higher were referred for EGD. BE was confirmedby biopsy in 2/69 (2.8%) TNE subjects and 2/72 (2.7 %) ECE subjects. BE was present in4/69 (5.8%) white and 0/76 (0%) African American subjects. Conclusions: Both TNE andECE were feasible in the clinic setting and helped identify BE overall in 2.8% of this VApopulation. Screening was effective only in whites and had no yield in African Americans.Given the nearly equal acceptability and yield, cost considerations and availability of equip-ment and personnel should guide which non-invasive modality should be utilized for BEscreening. Supported by an ARRA grant and BETRNet.

Mo1905

Has There Been a Change in the Prevalence of Be or Patient CharacteristicsThat May Be Contributing to the Increasing EAC Incidence?Vijay Kanakadandi, Maria Giacchino, Srinivas Gaddam, Ajay Bansal, Amit Rastogi, AprilD. Higbee, Neil Gupta, Prateek Sharma

Background: The incidence of esophageal adenocarcinoma (EAC) has increased six fold overthe last few decades. It would be important to ascertain if there has been a change in theprevalence of BE (i.e. increase) or patient characteristics (i.e. increasing BE length, morehiatus hernia, increasing BMI etc) that may be contributing to the increasing EAC incidence.Aim: To evaluate for changes in the prevalence and characteristics of patients with newlydiagnosed BE over the last 15 years in a large multicenter cohort. Methods: Patients presentingto the endoscopy unit for their index endoscopy for evaluation of GERD symptoms wereenrolled in this prospective cohort study. Patients were asked to complete a validated GERDquestionnaire (GERQ) that documents the onset of GERD symptoms (heartburn and acidregurgitation) and grades the frequency and severity of symptoms experienced over the pastyear. Demographic information such as body mass index (BMI), smoking history, use ofPPIs and aspirin/NSAIDs were recorded. Endoscopic details including length of BE, presenceand size of hiatal hernia (HH) were recorded. Patients were divided into 5 groups dependingon the time of index endoscopy- those presenting before 2001, 2001-2003, 2004-2006,2007-2009 and 2010 to date. Age, BMI, smoking status, prevalence and size of hiatal hernia(HH), prevalence and size of BE were calculated for each of those groups. Logistic regressionanalysis was used to calculate the p-value for trend. Results: Of a total of 1097 consecutiveGERD patients presenting for their index EGD, 1024 were male (93.3%), 910 (83.6%) wereCaucasian, and 850 (78.2%) were smokers. The overall prevalence of BE was 15.5 %, themean length of BE (SD) was 1.99 (2.5) cm, the mean BMI was 29.7 (5.7) kg/m2and meanage at presentation was 57.1 (12.7) years. There was no statistically significant trend (eitherincrease or decrease) in the prevalence of BE among these GERD patients on their indexendoscopy and remained stable over time (Table). Similarly, there was no significant differ-ence in BE patient characteristics (age, gender, BE length) and potential risk factors associatedwith BE (smoking, BMI ,presence and size of hiatal hernia) over the past 15 years. A gradualincrease in the use of PPI use was noted during the time period. Conclusions: In a largeprospective cohort of GERD patients, the prevalence of BE at index endoscopy , BE patientcharacteristics (age, gender, BE length) and risk factors associated with BE (smoking, BMI,hiatal hernia) have remained stable over the last 15 years. Additional factors should beevaluated in order to explain the increasing incidence of EAC.Time Trend Analysis for Characteristics of BE

Mo1906

Obstructive Sleep Apnea Is a Risk Factor for Barrett's EsophagusCadman L. Leggett, Emmanuel C. Gorospe, Andrew D. Calvin, William S. Harmsen, AlanR. Zinsmeister, Sean Caples, Virend K. Somers, Kenneth K. Wang, Lori S. Lutzke, PrasadG. Iyer

Background: Patients with obstructive sleep apnea (OSA) and Barrett's esophagus (BE) sharecommon risk factors including central obesity and gastroesophageal reflux (GER) symptoms.It is unclear if OSA increases the risk of BE independent of reflux and BMI. Aim: To examinewhether OSA is associated with an increased risk of BE using a clinic-based case controlstudy. Methods: We searched the clinic database of a large, academic, integrated healthcaresystem from Jan. 2000 to Nov. 2011 and identified patients who had undergone both aformal polysomnogram and an upper endoscopy. Participants were subdivided into fourgroups by the presence (+) or absence (-) of a diagnosis of BE and OSA (-BE/-OSA, +BE/-OSA, -BE/+OSA, +BE/+OSA) and randomly matched in a 1:2 ratio on age, gender and BMI.BE was diagnosed based on endoscopic identification of columnar epithelium and histologicalevidence of intestinal metaplasia confirmed by an expert gastrointestinal pathologist. Presenceand severity of esophagitis was recorded as well as history of GER and use of acid-suppressionmedications. The diagnosis and severity of OSA was confirmed by the apnea-hypopneaindex (AHI) and SleepMedicine evaluation record. Univariate andmultiple variable regressionmodels were used to assess the association between BE and OSA. Results: 264 patients wereincluded in the study of which 36 were identified as (+BE/-OSA), 74 as (-BE/-OSA), 74 as

S-690AGA Abstracts

(+BE/+OSA) and 78 as (-BE/+OSA). There was no significant association of the +BE/+OSAgroup with baseline characteristics (age, gender, race, BMI and smoking history) (table 1).The overall mean (SD) age was 61(13), 72% were males, 99% were Caucasian. A total of172(66%) patients had a history of tobacco use. In patients with BE the mean segmentlength was 3(2.6) cm. Overall, 137(52%) patients had a hiatal hernia with a mean lengthof 3.10 cm. In the 110 patients with BE, 74 had no dysplasia, 24 had low-grade dysplasia,8 had high-grade dysplasia and 4 had cancer. Patients with OSA had a mean AHI score of24.7(21.9) of which 89 (59%) had moderate to severe OSA (AHI>20). 148(56%) patientshad GER symptoms requiring acid-suppression medications. Endoscopic evidence of esopha-gitis was present in 21 patients (LA class A=14, B=6, C=1). Multiple variable logistic regressionadjusting for age, gender, BMI, GER diagnosis, and use of acid-suppression medicationsindicated OSA was associated with a 80% increased risk of BE relative to subjects withoutOSA (OR 1.80, 95%CI 1.02-3.10, p=0.04) (table 2). This association was dose-dependentsuggesting an increased risk for BE per 10 unit increase in AHI (OR 1.14, 95% CI 0.99-1.3, p=0.05). Conclusion: Subjects with OSA are at higher risk of BE independent of GERand BMI. This risk is higher with increased OSA severity with a 14% increase in risk of BEfor every 10 unit increase in AHI score.Baseline Characteristics

Multiple variable logistic model for BE Risk Factors

Mo1907

Dietary Intake of Fat, Animal Products and Advanced Glycation End-Productsand the Risk of Barrett's EsophagusLi Jiao, Liang Chen, Jennifer R. Kramer, Massimo Rugge, Paola Parente, GordanaVerstovsek, Abeer Alsarraj, Hashem El-Serag

OBJECTIVES: Diet is a potentially modifiable risk factor for Barrett's esophagus (BE).Advanced glycation end-products (AGEs) are found in high quantity in high-fat foods andmeats cooked at high temperature and have been shown to contribute to chronic inflammationand oxidative stress in humans. We investigated the associations between dietary intake offat, meat and other animal products, and AGEs, and risk of BE. METHODS: This is a case-control study in a single VA Medical Center conducted between 2008 and 2011. Diet inthe past one year was assessed by using a validated self-administered Block food frequencyquestionnaire (FFQ). The daily intake value of N ε-(carboxymethyl)lysine (CML), a majortype of AGEs, was derived from the FFQ using a published dietary AGEs database. Detailedclinical and lifestyle factors were also collected by personal interview. Multivariate logisticregression models were used to estimate the odds ratio (OR) and its 95% confidence interval(CI) for BE. The covariates included age, energy intake, sex, race/ethnicity, smoking status,alcohol consumption, waist to hip ratio (WHR), use of aspirin or proton pump inhibitor,frequency of gastroesophageal reflux (GER) symptoms, and physical activity. Stratified analy-sis was conducted according to WHR and frequency of GER symptoms. RESULTS: A totalof 151 cases with histologically confirmed BE and 777 controls without BE completed theFFQ. Intake of CML-AGE was significantly correlated with intake of saturated fat (r= 0.53)and total meats (r = 0.61). The multivariate OR (95% CI) of BE was 1.86 (1.06-3.24) forsaturated fat intake, 1.57 (0.90 -2.73) for total meat intake, and 1.50 (0.89-2.53) for CML-AGE intake, when the highest tertile was compared with the lowest. When CML-AGE wasadjusted in the models, the association for saturated fat was attenuated to 1.75 (95% CI:0.92-3.32), and that for total meat intake to 1.39 (95% CI: 0.72-2.69). Similarly, theadjustment of saturated fat attenuated the association for CML-AGE to 1.26 (95% CI: 0.69-2.29). The positive associations between CML-AGE and risk of BE was stronger in the studysubjects with a higher WHR (OR = 1.82, 95% CI: 0.94-3.52) or with frequent GER symptoms(. 1 time per month) (OR = 2.69, 95% CI: 1.12-6.42). Dietary intakes of total fat, monounsa-turated fat, polyunsaturated fat, trans fat, cholesterol, omega-3, egg, or dairy products werenot associated with risk of BE. CONCLUSIONS: Higher intakes of saturated fat and potentiallytotal meat and CML-AGE were associated with an increased risk of BE. CML-AGE mayexplain some of the effects of saturated fat and meat intake. The association between CML-AGE and risk of BE seems to be modified by abdominal obesity and GER symptoms.The interrelationship between CML-AGE and saturated fat and their contributions to BEdevelopment warrants further investigation.