AGA Abstracts
to similar pathways in both blacks and white patients: cancer, organismal injury and abnormalities, organismal development, cellular movement and FXR/RXR activation. Conclusion GERD to BE transition is molecularly similar between blacks and white patients. Our results argue that surveillance intervals in BE patients should not be different based on race.
Su1052 GENOMIC TESTING OF ENDOSCOPIC BIOPSIES AID IN THE IDENTIFICATION OF BARRETT'S ESOPHAGUS PATIENTS WHO PROGRESS TO DYSPLASIA Antonia R. Sepulveda, Elena Komissarova, Sarawut Kongkarnka, Richard A. Friedman, Jon M. Davison, Gary W. Falk, Ming-ming Xu, Julian A. Abrams, Timothy C. Wang, Jorge L. Sepulveda Background: Patients with Barrett's intestinal metaplasia (BIM) may sequentially progress to low-grade dysplasia (LGD), high-grade dysplasia (HGD) and eventually esophageal adenocarcinoma (EAC). Genomic alterations have been reported in pre-dysplastic BIM. Our hypothesis is that testing random pre-neoplastic BIM for gene copy number alterations (CNAs) and selected targeted genomic mutations using routine clinical endoscopic biopsies obtained before development of dysplasia/EAC (B-BIMP), may be used for prediction of progression to dysplasia/EAC in patients with Barrett's esophagus (BE) undergoing surveillance. Methods: We tested 17 B-BIMP patients endoscopically sampled at least 1 year before progression to dysplasia/EAC and 35 control patients with BIM that never progressed to HGD/EAC with at least 2 years of follow-up (BIM-NP). Formalin-fixed paraffin-embedded (FFPE) biopsy tissues were used for DNA extraction. Next generation sequencing (NGS) was performed with the TruSeq (Illumina) and AmpliSeq (IonTorrent) cancer panels to interrogate mutational hotspots within 48/50 cancer genes. Sequencing data were analyzed with NextGENe software (SoftGenetics) and with a pipeline using the Integrative Genomics Viewer platform. Highresolution OncoScanTM FFPE Express 2.0 SNP Arrays (Affymetrix) were used to analyze whole-genome copy number changes and copy-neutral loss of heterozygosity. Results: 46 patients had results by NGS (30 BIM-NP and 16 B-BIMP) and 24 patients had SNP-array results (10 BIM-NP and 14 B-BIMP). Mutations detected by NGS were present in 4/16 (25%) B-BIMP (3 in CDKN2A, 3 in TP53, and 1 in APC) and in 3/30 (10%) BIM-NP (2 in CDKN2A and 1 in TP53). The most frequent copy number genomic alterations in preneoplastic B-BIMP affected the FHIT and CDKN2A genes. Focal deletion of exon 5 of FHIT was found in 57% of B-BIMP but none of the BIM-NP (p=.0128). Copy number alterations in chromosome 9p involving the CDKN2A gene were found in 79% of B-BIMP and 30% of BIM-NP (p=.050). Heterozygous deletions in other chromosomes were found in 29% of B-BIMP but not in BIM-NP. Together, CNAs in FHIT, CDKN2A, and/or other heterozygous deletions were present in 100% of B-BIMP vs. 30% of BIM-NP. No TP53 CNAs were found in B-BIMP, suggesting this alteration is a late event. Conclusions: CNA analysis of endoscopic biopsies obtained before development of dysplasia/EAC (B-BIMP) by SNP arrays was highly sensitive to predict progression to dysplasia/EGD. NGS analysis with an amplicon panel had low prevalence of mutations in BE non-progressors. Further studies with larger patient numbers are warranted to determine the optimum combination of genomic markers of BIM progression. Genomic alterations detectable in BE may serve as biomarkers to improve detection of dysplasia and EAC through risk stratification of BE patients for surveillance.
Su1054 INFLUENCE OF PERSISTENT LGD ON PROGRESSION IN PATIENTS WITH BARRETT'S ESOPHAGUS Christopher H. Blevins, Ross Dierkhising, Fouad Otaki, Michele L. Johnson, Naveen Prasad Gopalakrishnan Ravikumar, Navtej S. Buttar, David A. Katzka, Prasad G. Iyer Background: Some patients with Barrett's Esophagus (BE) and confirmed low-grade dysplasia (LGD) at the time of diagnosis do not demonstrate LGD on subsequent exams whereas others have persistent or recurrent LGD on these follow-up exams. Data from Europe suggests that patients with LGD on more than one endoscopic exam have a higher risk of progressing to high-grade dysplasia (HGD) or intra-mucosal cancer (IMC). Aim: To determine if confirmed LGD on multiple surveillance exams increases the risk for progression to HGD or EAC in our population. Methods: 223 patients with confirmed BE with LGD at the time of diagnosis were studied from our multicenter prospective esophageal adenocarcinoma and Barrett's Esophagus (EABE) registry. The primary outcome was dysplasia progression defined as detection as HGD or IMC at a time greater than 12 months after the index BE diagnosis. Patients were excluded if they did not have at least two surveillance endoscopies or were diagnosed with HGD/IMC. Patients were then divided into those that had ≥2 endoscopies (EGDs) with LGD and those with just one EGD with LGD. HGD/IMC incidence curves were calculated using landmark Kaplan-Meier methods. A Cox model was used to estimate the association between number of EGDs with LGD and progression to HGD/IMC. Results: The median follow-up time was 7.3 years with a median of 6 EGDs (range 2-27). Fourteen patients progressed in the entire cohort. Over the course of 1 year after the index EGD, 173 patients had just 1 EGD showing LGD and 50 patients had ≥1 EGD showing LGD. The landmark cumulative incidence rates of HGD/IMC were 3.0%, 8.2% and 9.7% at years 3, 7 and 11 after the index EGD in the group with just 1 EGD with LGD in the first year. The landmark incidence rate of HGD/IMC was 2.2%, 14.6% and 18.9% at years 3, 7 and 11 after the index EGD in the group that had ≥1 EGD with LGD in the first year. [Figure 1] The hazard ratio for progressing to HGD/IMC comparing patients with ≥1 EGD with LGD vs 1 was 2.0 (P=0.12). Conclusion: In our large cohort of patients with a confirmed diagnosis of BE and LGD, the risk of progression to HGD and/or IMC was two times higher in those that have more than one surveillance exam that demonstrated LGD when compared to those with just one exam with LGD, although the P value was not statistically significant due to the low number of patients that progressed.
Su1053 NEOPLASTIC PROGRESSION IN PATIENTS WITH SHORT SEGMENT BARRETT'S ESOPHAGUS: LONG-TERM FOLLOW-UP OF OVER A 1000 PATIENTS IN A MULTI-CENTER CONSORTIUM Sreekar Vennelaganti, Sravanthi Parasa, Prashanth Vennalaganti, Srinivas Gaddam, Manon Spaander, Sophie H. van Olphen, Prashanthi N. Thota, Kevin F. Kennedy, Fouad J. Moawad, Marco J. Bruno, John J. Vargo, Sharad Mathur, Brooks D. Cash, Richard Sampliner, Neil Gupta, Gary W. Falk, Ajay Bansal, Patrick E. Young, David A. Lieberman, Prateek Sharma Background and aims: Rates of progression of non-dysplastic Barrett's esophagus (NDBE) to high-grade dysplasia/esophageal adenocarcinoma (HGD/EAC) is known to vary based on length of the BE segment. Methods: The Barrett's esophagus study trial (BEST) is a multicenter outcome project of a large cohort of BE patients. Only patients who were diagnosed with intestinal metaplasia (IM) without dysplasia on index endoscopy were included in this analysis. All cases of low-grade dysplasia (LGD), HGD/EAC that were detected within one year of diagnosing NDBE were considered prevalent cases and were excluded from the analysis. Patient demographics, co-morbid conditions, medication use, endoscopy results and time of HGD/EAC were recorded. Continuous variables were compared using Student's T-test and categorical variables were compared using chi-square test. Hazards ratio (HR) was calculated after adjusting for other variables such as age, race, gender, smoking, PPI use, aspirin use or statin use and BMI. Results: A total of 2065 patients with NDBE were identified (mean age 57.6 years, male 82%, Caucasians 89%). The mean length of BE in the entire cohort was 3.5cm ± 3.0 and 74% patients had a hiatus hernia. 1004 patients had a BE length of <3 cm (short BE) while 1061 had BE ≥ 3 cm (Table). The annual progression rate of short (<3 cm) and long (≥3 cm) NDBE to EAC was 0.05% vs. 0.25% p =.001 respectively. Similarly, for a combined end point of HGD/EAC, annual progression rates were significantly lower in short BE compared to long BE (0.19% vs. 0.67% p <.001). The average time to progression of NDBE to HGD/EAC was 5 years when BE length was <3 cm and 5.9 years when BE length was ≥3 cm. Overall, the risk of progression to HGD/EAC was significantly lower among short vs long BE patients after adjusting for multiple variables; HR: 0.37 (95% CI 0.18, 0.78; p=0.009) Conclusion: The results of our study show that patients with short segment BE (<3 cms length and without dysplasia at baseline) have extremely low rates of progression to EAC (0.05% annually) and even for a combined end point of HGD/EAC (0.19% annually). We suggest that surveilllance, if considered, in this patient population should not be earlier than every 5 years.
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Figure 1: Landmark Kaplan-Meier curve comparing progression to HGD/IMC between those with only one EGD showing LGD versus those with ≥1 EGD showing LGD.
AGA Abstracts
Su1055 ACCEPTABILITY OF TISSUE COLLECTION BY CYTOSPONGE IN U.S. PATIENTS WITH BARRETT'S ESOPHAGUS Audrey O. Chang, Cary C. Cotton, Swathi Eluri, Athidi Guthikonda, Ryan D. Madanick, RoseMary Beitia, Susan E. Moist, Evan S. Dellon, Rebecca C. Fitzgerald, Nicholas J. Shaheen Background: Barrett's esophagus (BE) is a common precancerous condition of the esophagus diagnosed by biopsy of endoscopically visible lesions. Patients with BE undergo serial endoscopic exams for surveillance. The Cytosponge is a less invasive and cost-effective alternative to endoscopy and could be used both to screen for BE, and perhaps to survey prevalent BE. Aim: To assess the acceptability and tolerability of the Cytosponge assay in BE patients at a United States (US) tertiary care medical center. Methods: This is a crosssectional study of adult BE patients presenting for routine care surveillance endoscopy of current BE or following endoscopic ablation of BE, at the University of North Carolina Hospitals. The Cytosponge is an ingestible gelatin capsule attached to a string that is swallowed. Tissue is sampled as the liberated sponge is withdrawn from the esophagus. Seven days after the Cytosponge assay, subjects completed an assessment of acceptability measured with the Impact of Events Scale (validated to assess the distress associated with a specific life event, includes measures of intrusiveness and any avoidance responses to the event). The scale ranges from 0-75 with lower score corresponding to lower impact of the event. Tolerability was measured with a visual analogue scale (VAS) given immediately after the procedure, ranging from 0 being no pain and 100 being the worst pain ever felt by the patient. We fit linear models of the VAS score as a function of baseline characteristics and reported the estimate with 95% confidence limits (CL). Follow-up data regarding procedure preference (propofol-sedated endoscopy vs. Cytosponge), procedure ratings (0=unacceptable, 10=Take the test again without hesitation), and adverse events were collected. Results: In a sample of 108 subjects, 74% were men with 44% aged 60-69 years (Table). 107 (99%) subjects successfully swallowed the Cytosponge. The Cytosponge was well tolerated with an average VAS score of 18.0 out of 100 (Figure) and a procedure rating of 9.1 out of 10. Of the responding participants, 94% (n=102) reported willingness to repeat the Cytosponge assay and 47% (n=51) preferred Cytosponge to propofol-sedated endoscopy. On the Impact of Events Scale, 61% reported a score of 0 in terms of reported distress from the event. The procedure caused less discomfort among patients with greater body mass index (BMI). For every unit increase in BMI the VAS score decreased by 0.58 (95% CL 0.04 - 1.12). There were no serious adverse events and the most commonly reported complication was sore throat after the procedure in 16% of the participants (n=17). Conclusion: This is the first study to examine and report acceptability and tolerability outcomes of the Cytosponge in a US cohort with BE. In patients with BE, the Cytosponge assay was well accepted and tolerated with no significant adverse events. Baseline Characteristics and Tolerability Characteristics Patients Barrett's Esophagus Who Underwent the Cytosponge Assay
Distribution of Visual Analog Score for Discomfort Associated with the Cytosponge. Score ranges from 0-100 with 0 being no pain and 100 being the worst pain ever felt by the patient.
Su1056 SLEEVE GASTRECTOMY IS A RISK FACTOR FOR BARRETT'S ESOPHAGUS: A SYSTEMATIC REVIEW AND META-ANALYSIS Scott Smukalla, Max Pitman, Abraham Khan, Violeta Popov, Christopher C. Thompson Introduction: Laparoscopic sleeve gastrectomy (LSG) accounted for approximately 50% of weight loss procedures performed in the US in 2013 compared to 9.3% in 2010.Nevertheless, little is known about its long-term safety and effectiveness. Anecdotal reports have shown a subjective increase in the incidence of gastro-esophageal reflux after LSG. Aim: To assess the impact of LSG on the incidence of Barrett's esophagus (BE) and esophagitis postoperatively in studies that report endoscopic data before and after LSG. Methods: MEDLINE, Embase, and Web of Science were searched from inception through November 2016 with the mesh terms "endoscopy", "bariatric surgery", "sleeve gastrectomy". Dual extraction and quality assessment of studies using the Newcastle-Ottawa scale were performed independently by two authors. Inclusion criteria were retrospective and prospective studies reporting endoscopic outcomes both before and after LSG that were done per protocol in most participants regardless of symptoms. Primary outcomes included the pooled event rate and 95% confidence interval (95% CI) for incidence of BE, hiatal hernia, esophagitis and dilated cardia after LSG, and odds ratios comparing rates of these conditions before and after surgery, using random effects meta-analysis for all outcomes. Results: 1100 citations were identified; 82 studies were reviewed by full text. 6 prospective and 1 retrospective study including 869 subjects were analyzed. The average time to follow-up was 15 months (range 1 month to 5 years), ages ranged from 17 to 64 years, and 75% of the patients were female. After LSG, 37% of patients developed endoscopic esophagitis, event rate 0.37 (95% CI 0.2, 0.57), I^2=95%, Tau^2=1.4, 8 studies, 803 patients; 12% had new hiatal hernia, event rate 0.12 (95% CI 0.02, 0.41); and 27% developed dilated cardia (95% CI 0.11, 0.53). The pooled incidence of new onset BE was 4%, event rate 0.4 (95% CI 0.01, 0.14). The odds ratio for new onset BE after LSG compared to pre-surgery was 2.3 (95% CI 1.7, 3.04), I^2=0%, Tau^2=0% (Figure 1), and the pooled odds ratio for erosive esophagitis was 2.7 (95% CI 1.8, 4.2) (Figure 2). 46% of patients included had GERD symptoms post-operatively. Conclusion: LSG significantly increases the risk of developing BE, with new incidence of BE in 4% of patients 15 months after surgery, and esophagitis in 37% of patients evaluated with per protocol endoscopies regardless of symptoms. Based on these findings, screening for BE after LSG should be considered for all patients at pre-specified intervals, and more studies are needed to better understand these results.
Figure 1: Odds Ratio for incidence of Barretts esophagus after sleeve gastrectomy compared to before surgery, I sq= 0%, tau sq=0%
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AGA Abstracts