M1095 Optical Analysis of Squamous Cells Predicts the Presence of Esophageal Dysplasia and Adenocarcinoma via Partial-Wave Spectroscopic Microscopy

a delay in subspecialist referral once cholestasis is identified. This study suggests that a more uniform approach to the management of prolonged neonatal jaundice is needed to expedite the diagnosis of BA.

(IGFBP1) and insulin growth factor binding protein-3 (IGFBP3) were measured in 45 nondysplastic, 8 low grade dysplasia (LGD), 14 high grade dysplasia (HGD), and 9 EAC subjects. Insulin resistance was estimated through homeostatic model assessment (HOMA). Body mass index (BMI) and waist-hip ratio were calculated. Immunohistochemistry (IHC) was performed on paraffin embedded tissue derived from BE cases using rabbit monoclonal antibodies to p-mTOR and p-AKT, mouse monoclonal antibody to Ki-67, and rabbit polyclonal antibody to p-IRS1. IHC results were reviewed by an expert pathologist blinded to patient's BMI and results of systemic serum assays. Intensity of staining was classified as weak or strong. Chi-square and Fisher's exact tests were used to assess differences in staining intensity across all variables of interest. Strength of association between p-IRS1 and p-AKT, p-mTOR, and Ki-67 was measured by Spearman correlation coefficient. RESULTS: Eighteen of 38 (47%) BE, 4/8 (50%) LGD, 10/14 (71%) HGD, and 7/9 (78%) EAC cases showed strong staining for p-IRS1. A significantly higher proportion of HGD/EAC subjects showed p-IRS1 staining when compared to BE/LGD subjects, 48% vs. 74%, p < 0.05. p-IRS1 immunostaining was highly correlated with strong immunostaining of the downstream mediators p-AKT and p-mTOR (Spearman correlation coefficient = 0.60 for p-IRS1/p-AKT and p-IRS1/p-mTOR, p < 0.01) and the proliferation marker Ki-67 (Spearman correlation coefficient=0.47, p=0.02). Systemic levels of insulin, IGF-1, or IGF-2 were not associated with tissue immunostaining of p-IRS1. CONCLUSIONS: Activation of the insulin/IGF pathway in BE is associated with cellular proliferation and appears to play a role in the progression from metaplasia to cancer. Activation of the insulin/IGF pathway at the tissue level is likely complex and does not have a simple association with systemic measures of insulin or IGF.

AGA Abstracts

M1091 Is There a Way to Implement Guidelines Into Clinical Practice? Wolfgang Kruis Aim: It has been described that adherence to treatment guidelines is limited and a wide variability exists regarding prescription of standard drugs such as mesalazine for ulcerative colitis (UC). The effectiveness of measures for implementation of new therapeutic standards is unclear. The aim of this project was to analyse previous therapeutic management in UC outpatients and to observe the influence of a simple strategy such as systematic documentation on prescription behaviour. Materials and methods: Medication was prescribed at the discretion of the participating gastroenterologists. Mesalazine treatment of UC patients was prospectively and systematically documented in 107 private gastroenterology practices between 9/2007 and 7/2008. Data management and statistical analysis were performed externally. Results: Complete data were obtained from a total of 360 UC patients (median age 43 yrs, 14-83 yrs; 49.2% females). 203/360 patients (56.3%) had active UC. 35% of these patients were newly diagnosed; 29% were known to have UC, but had been without any maintenance treatment, while 36% were on maintenance therapy before flaring (72.6% oral mesalazine, 24.7% rectal mesalazine, 32.9% steroids, 20.5% azathioprine [multiple entries]). The acute flare was treated with oral mesalazine alone in 70% (median dose 3.0 g/d [1.5-5.0 g/d]) and with oral/rectal mesalazine combination therapy in 30% (median rectal dose 1.6 g/d [0.25-10.0 g/d]). Patients received mesalazine in 1-4 doses per day. Granule preparations were taken mostly twice daily, tablets three times per day. Once daily dosing was recommended in 6% of the new prescriptions at baseline (10/2007). This percentage increased to 47% after 8 months. 157/360 of the documented patients (43.7%) were in remission. Maintenance treatment comprised oral mesalazine alone in 88% of the patients (median dose 2.1g/d [1.04.0 g/d]) and oral/rectal mesalazine combination in 12% (median rectal dose 0.8g/d [0.252.0 g/d]). Once daily dosing was recommended in 17% of the new prescriptions at baseline (10/2007), this percentage increased to 58% after 8 months. 20% of participating gastroenterologists reported basing their treatment decision on relevant new study data. Conclusion: In this prospective observational study, mesalazine was used in a patient-personalized approach and, moreover, in contrast to previous publications, for the most part according to guidelines. New study results were rapidly implemented into daily treatment decisions. A simple measure such as systematic documentation may have significant beneficial effects on treatment quality.

M1094 Meta-Analysis of the Association of Gastroesophageal Reflux Disease With Barrett's Esophagus: NO Association With Short Segment Barrett's Esophagus Justin B. Taylor, Joel H. Rubenstein Background: Esophageal adenocarcinoma is associated with Barrett's esophagus (BE), a metaplastic change thought to be due to gastroesophageal reflux disease (GERD). Current preventive efforts rely on screening of individuals with GERD symptoms. However, some recent studies have found a high prevalence of BE in patients without GERD, and others have found little or no association with GERD. We hypothesized that high quality study designs show less association of GERD with BE, and that GERD is only weakly associated with short segment BE. Methods: We performed a systematic literature search in multiple online electronic databases regardless of language. Eligible studies required visualization of columnar mucosa and histologic confirmation of intestinal metaplasia, and GERD symptoms ascertained by questionnaire or interview. The highest quality design was defined a priori by both cases and controls identified among unselected research volunteers (“research design”) rather than by patients selected for endoscopy for clinical indications (“clinical design”) which introduces selection and ascertainment bias. A priori, heterogeneity was defined by Cochrane's Q p < 0.20, and Inconsistency Index, I2 (25% low, 50% moderate, 75% high). Results: Systematic review identified 13,392 citations, and 108 articles were reviewed, resulting in 26 studies meeting eligibility. The summary odds ratio (OR) for the association of GERD with BE from all studies was 3.41 (95% CI 3.09-3.76), but the results were very heterogeneous (p = 0.0001; I2 = 87%). When stratified by BE length and sampling design, the studies with clinical design demonstrated substantial, but heterogeneous, association with short segment BE (OR = 1.96, 95% CI=1.35-2.84; p = 0.02; I2 = 60%) and greater and homogeneous association with long segment BE (OR = 2.96; 95% CI 1.69-5.19; p = 0.25; I2 = 25%). In the research design, stratifying by length of BE resolved the heterogeneity and demonstrated a strong association with long segment BE (OR = 4.92; 95% CI 2.01-12.0; p = 0.30; I2 = 19%) but no association with short segment BE (OR = 1.15; 95% CI 0.764-1.73; p = 0.84; I2 = 0%). Funnel plots demonstrated evidence for bias against publication of small negative studies. Conclusions: In the highest quality studies, GERD symptoms are not associated with short segment BE, but increase the odds of long segment BE by 5-fold. GERD symptoms can serve as a reliable predictor of long segment BE, but not short segment BE. If short segment BE is considered worthy of identification, then current screening practices do not select patients at risk for endoscopy, and other methods of selection for screening need to be developed.

M1092 Typical Gastroesophageal Reflux Disease: Just Heartburn and Regurgitation? Fermin Mearin, Julio Ponce, Marta Ponce, Agustín Balboa, Miguel A. Gonzalez, Javier Zapardiel Heartburn and regurgitation are considered to be the typical gastroesophageal reflux disease (GERD) symptoms but in many patients other symptoms coexist. Aim: To evaluate the association among dyspeptic and supraesophageal symptoms with typical GERD symptoms, and to investigate its repercussion in quality of life and therapeutic response. Methods: We conducted a prospective, multicentre, observational study that included 301 patients attended in gastroenterology offices for typical GERD symptoms (heartburn and/or regurgitation). A directed interview was performed to identify upper digestive symptoms. Symptoms severity were quantified by specific symptom scores and visual analogue scales. Quality of life was evaluated by two different questionnaires (SF-12 and QoLRAD). Patients were treated with proton pump inhibitors (PPI) according to the Spanish Association Gastroenterology clinical practice guideline recommendations. Results: 99% of the patients complained of heartburn (78% nocturnal heartburn), 86% of regurgitation and 85% of both; 1% only suffered regurgitation. Dyspeptic symptoms were associated in 91% of the cases and supraesophageal symptoms in 58%. The symptoms were severe/extremely severe in 56% for heartburn, 35% for regurgitation and 34% for nocturnal heartburn. One in every 6 patients had dysphagia: 14% of them severe/extremely severe. 52% of the patients chose heartburn as the most bothersome symptom, 20% thoracic pain, 8% regurgitation, 6% epigastric pain and 3% nocturnal heartburn. Thus, the most bothersome symptom was a typical one from GERD in 64%, a supraesophageal one in 23% or a dyspeptic one in 10%. Presence of supraesophageal and/or dyspeptic symptoms was associated with worse quality of life (according to SF-12 and QoLRAD). After treatment 93% of the patients had not heartburn and 87% not regurgitation. Response rate was significantly higher (p