Tu1564 Indefinite Dysplasia in Barrett's Esophagus Confers a Similar Risk of Progression to High Grade Dysplasia or Esophageal Adenocarcinoma As Low Grade Dysplasia

Abstract

circumferential CBE-EMR for Barrett’s esophagus with HGD or IMC and subsequently developed post-EMR esophageal strictures requiring endoscopic balloon dilation. Archived formalin fixed paraffin embedded (FFPE) specimens of pinch biopsies were obtained of the esophageal stricture within one month of EMR. Each specimen was reviewed by an expert pathologist to ensure no residual Barrett’s esophagus or dysplasia. Total RNA from 70mm of FFPE tissue was extracted and miRNA expression profiling was completed with miRCURY LNA microRNA Arrays (Exiqon A/S, Denmark). Controls were five age, gender and race matched patients with a normal endoscopic and histologic squamocolumnar junction. Results: The mean age was 63.6 yrs (SD)+/-7.1 for the CBE-EMR group and 65.1+/5.9 yrs for controls; 4/5 CBE-EMR patients had tobacco exposure history as compared to 3/5 of the control patients. The average time from index CBE-EMR to post-EMR tissue procurement was 14.6 days. The average number of EMR specimens was 5.6, average BE length was 2.0 cm and 2/5 received triamcinolone for stricture prophylaxis at the time of index CBE-EMR. miRNA profiling revealed four (miR-205, miR-203a, and miR125b-5p and miR-23c) differentially expressed miRNA candidates (adjusted p-value !0.05). Of these, three (miRs-205, -203a, and -125b-5p) have been previously reported to be involved with the process of post-injury/inflammation scarring and fibrosis, including epithelial-to-mesenchymal transition. Conclusion: miRNAs are differentially expressed in post-EMR stricture tissue during the acute response to wound healing. Our study identified three miRNAs previously established in postinjury/inflammation scarring and fibrosis. This data supports the continued investigation of the role of miRNAs in the development of post-EMR strictures including serving as predictive biomarkers and possibly targets of miRNA based therapeutics. Tu1564 Indefinite Dysplasia in Barrett’s Esophagus Confers a Similar Risk of Progression to High Grade Dysplasia or Esophageal Adenocarcinoma As Low Grade Dysplasia Jonathan K. Callaway*, Vishnu Teja Kommineni, Allon Kahn, Rahul Pannala, Michael D. Crowell, George E. Burdick, Marcelo F. Vela, David E. Fleischer, Francisco C. Ramirez Mayo Clinic, Phoenix, AZ Background: It has been well established that patients with Barrett’s esophagus (BE) are at increased risk for esophageal adenocarcinoma (EAC). Traditionally, both lowgrade dysplasia (LGD) and high-grade dysplasia (HGD) are considered dysplastic degrees each conferring an increasingly higher risk. Indefinite (IND) dysplasia in BE is still commonly reported but its risk to progression, if any, has not yet been established. Aim: To evaluate a large cohort of patients with known BE to determine the risk of progression to HGD or EAC in patients with IND. Methods: Study Design: Retrospective review of endoscopic databases. Setting: Endoscopy unit at a tertiary academic medical center. Population: Patients with endoscopic and histologic diagnosis of BE on at least 2 separate occasions. Only patients with documented IND without prior or concomitant dysplasia were analyzed. Outcomes: Progression to HGD or EAC. Comparison groups: Patients with no prior dysplasia (ND) or LGD. Study period: 2002-2010. Statistical analysis: Proportional data were compared using the Fisher’s exact test; Logistic regression was used to identify any contributing factors. Data are presented as mean (SD). Results: A total of 848 patients with known BE underwent upper endoscopy. Among these, 79 patients met inclusion criteria, with a mean follow up of 84.8 months. 13 (16.7%) patients with IND progressed to HGD or EAC by an average of 55.2 (SD 62.3) months. This was statistically significant when compared to patients with no dysplasia (ND) on initial biopsy (pZ 0.032), but no different when compared to those with LGD (pZ 0.4283). The time to progression to HGD/EAC was not statistically different between the IND group and, the ND or LGD groups. RFA was used in 32 patients with IND and of these, 4 (12.5%) progressed to HGD or EAC, whereas, of the 46 patients without RFA treatment, 9 (19.6%) progressed (p Z n.s.). Table 1 illustrates the distribution of patient’s progression according to their histological presentation. Sex, RFA treatment or long vs short segment BE did not influence progression to HGD/EAC in the IND group (pZ 0.72, 0.54 and 1.0 respectively). Conclusion: In this large cohort, patients with IND at initial biopsy had the same risk of developing HGD or EAC as those with LGD at presentation. The risk was independent of gender, RFA treatment or length of BE segment. This study suggest patients with IND should be carefully followed to detect development of higher grades of dysplasia or adenocarcinoma and, should be considered for endoscopic therapy as with LGD and HGD.