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Sa1818 African Americans Do Not Develop Barrett's Esophagus Following Erosive Esophagitis
AGA Abstracts
presented as mean + standard deviation, Median (25th, 75th percentiles) or N (%).Time of follow-up was defined as time between baseline endoscopy and diagnosis of HGD/EAC or last endoscopy if no progression. Univariate and multivariate Cox regression was performed to evaluate the association between BMI and progression. A multivariate analysis was performed with LGD group, gender, baseline BMI and BMI change. Results: There were a total of 1239 with BE who had BMI within 1 year of upper endoscopy. Mean age was 60.6 ±13 yrs. 76% were men and 94.7% were Caucasian. Average BMI was 29.8 ± 6 kg/m2. The mean length of Barrett's segment was 3 ±3.4 cm and hiatal hernia size was 1.9 ±2cm. 363 patients met the inclusion criteria. Of these patients, 261 were in no dysplasia group and 102 in LGD group. The mean follow up was 31.6+26 months. During follow up, there were 10 cases of HGD and 4 cases of EAC in no dysplasia group and 18 cases of HGD and 11 cases of EAC in LGD group. There was no evidence to suggest that BMI or BMI change was associated with progression to HGD/EAC in subjects with no dysplasia at baseline (Table 1). However, in patients with LGD as baseline, there was a trend toward significance between lower baseline BMI and hazard of progression (Table 2). For every one unit increase in baseline BMI, the hazard of progression decreases by 7% (p=0.061). This remained so after adjusting for gender and change in BMI (p=0.056). Conclusions: Higher BMI is not associated with increased risk of progression of dysplasia in patients with BE with no dysplasia at baseline. However in LGD patients, increase in BMI was associated with a trend towards lower risk of progression. This is an unexpected finding and warrants validation in further studies. 1. BMI and Progression of Dysplasia in Patients with No Dysplasia at Baseline
Figure 1. Kaplan-Meier Curves of EAC Incidence by Baseline Pathology Sa1816 Influence of Body Mass Index (BMI) on the Prevalence of Dysplasia in Barrett's Esophagus (BE) Prashanthi N. Thota, Madhusudhan R. Sanaka, Prabhdeep Singh, Mangesh R. Pagadala, Rocio Lopez Background/Aims: Increased body mass index (BMI) has been reported to be a risk factor associated with gastroesophageal reflux disease (GERD), BE and esophageal adenocarcinoma (EAC). However, it is not known if it influences the prevalence of dysplasia in BE. Our aim was to estimate the prevalence of various degrees of dysplasia in different BMI groups of patients with BE. Methods: Patients who underwent upper endoscopy and were found to have endoscopic evidence of BE confirmed by presence of intestinal metaplasia on histology from January 2000 to December 2012 at Cleveland Clinic were reviewed. Patients who had BMI values available within one year of upper endoscopy were included in the analysis. BMI levels were classified as following groups: <25, 25-27.4, 27.5-29.9, 30-34.9, 35-39.9 and ≥40. Patient demographics and endoscopic findings such as length of BE, dysplasia in BE and size of hiatal hernia were reviewed. Dysplasia was classified as no dysplasia, low grade dysplasia (LGD), high grade dysplasia (HGD) and EAC. Indefinite for dysplasia was included under LGD group. Data were presented as mean + standard deviation, Median (25th, 75th percentiles) or N (%). Jonckheere-Terpstra test was used to assess differences between the groups. Results: Among a total of 2370 patients, 1239 were included in the analysis. Mean age was 60.6 ±13 yrs. 76% were men and 94.7% were Caucasian. Average BMI was 29.8 ± 6 kg/m2. The time between EGD and BMI measurement ranged between 0-12 months with a mean of 1.3 months. There were 228 (18.4%) in group with BMI<25, 236(19%) in BMI group25-27.4, 262(21.1%) in BMI 27.5 - 29.9, 303 (24.5%) in BMI 3034.9, 126(10.2%) in BMI 35-39.9 and 86(6.8% ) in BMI ≥40. The mean length of Barrett's segment was 3 ± 3.4 cm and hiatal hernia size was 1.9 ±2 cm. The histological findings were no dysplasia in 732 (59.1%), LGD in 159 (12.8%), HGD in 149(12%) and EAC in 199 (16.1%) patients. Lower BMI groups had lower prevalence of dysplasia while patients in higher BMI groups had higher prevalence of dysplasia (p=0.002). These findings are presented in Table 1. Conclusions: Our study found that prevalence of degree of dysplasia varies by BMI. Increased BMI was associated with higher prevalence of dysplasia. These findings have important clinical implications since BMI is a modifiable risk factor. BMI and Degree of Dysplasia
Values presented as mean ± SD or N (column%) Hazard Ratios and p-values correspond to univariate Cox regression analysis 2. BMI and Progression of Dysplasia in Patients with LGD at Baseline
Values presented as Mean ± Sd or N (column%) Hazard Ratios and p-values correspond to univariate Cox regression analysis Sa1818 African Americans Do Not Develop Barrett's Esophagus Following Erosive Esophagitis Ahmad AlKaddour, Camille McGaw, Rama Hritani, Carlos Palacio, Juan C. Munoz, Kenneth J. Vega
Values presented as N (column %) P-value corresponds to Jonckeere-Terpstra test
Introduction: Barrett's esophagus (BE) is a metaplastic alteration of the distal esophageal epithelium to specialized intestinal epithelium (SIM), which is present in 8% to 20% of patients with chronic GERD and is the primary risk factor for development of esophageal adenocarcinoma. Erosive esophagitis (EE) is a likely intermediate step, representing reflux related esophageal injury with potential development of BE upon healing. Previous data indicate that circumstance occurs in 9-12% of individuals following EE. Limited data exists evaluating this situation in African Americans. The aim of this study is to determine if ethnic variation occurs in BE formation following EE on index endoscopy for any indication at the University of Florida-Jacksonville College of Medicine. Methods: A retrospective review of upper endoscopies (EGD) was performed between January 1st, 2008 and December 31st, 2012. Inclusion criteria were erosive esophagitis on index endoscopy, follow-up endoscopy at minimum of 6 weeks later and ethnicity of either non-Hispanic white (nHw) or African American (AA). Exclusion criteria were age <18 years of age, no repeat EGD following EE on index endoscopy and patients with known BE, UGI malignancy or head and neck cancer at index endoscopy. Data collected included age, gender, BMI, dates of index and repeat EGD, presence of esophagitis and grade (LA classification) if present, medication use (aspirin, NSAID, statin, proton pump inhibitor), length of BE (long ( > 3 cm) or short (< 3 cm) segment) as well as presence of dysplasia and grade (low, indeterminate or high) if present. Results: A total of 10515 patients had upper endoscopy during the 5 year study period;
Sa1817 Effect of Body Mass Index on Progression of Dysplasia in Barrett's Esophagus Prashanthi N. Thota, Madhusudhan R. Sanaka, Prabhdeep Singh, Mangesh R. Pagadala, Rocio Lopez Background/Aims: Increased body mass index (BMI) is associated with Barrett's esophagus (BE) and esophageal adenocacinoma (EAC). It is not known if a change in BMI would affect the progression of dysplasia in Barrett's. Our aim was to study the effect of BMI on progression of dysplasia in BE to high grade dysplasia (HGD) or esophageal adenocarcinoma (EAC). Methods: Patients who underwent upper endoscopy and were found to have BE from January 2000 to December 2012 at Cleveland Clinic were reviewed. Patients in whom BMI values were available within one year of upper endoscopy were included in the analysis. Patients with HGD/EAC at baseline, or with no follow-up BMI or biopsies were excluded. BMI levels were classified into following groups: <25, 25-27.4, 27.5-29.9, 30-34.9, 35-39.9 and ≥40. Degree of dysplasia was classified into 4 groups: no dysplasia, low grade dyspasia (LGD), high grade dysplasia (HGD) and EAC. Patient demographics and endoscopic findings such as length of BE, degree of dysplasia in BE, and size of hiatal hernia were reviewed. Data are
AGA Abstracts
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a sensitivity and specificity of 95% and 90%, respectively. Conclusions: Extensive reagent and analytical performance studies were conducted to evaluate the reliability and reproducibility of a gene test panel (ENGAUGE™-GI-Barrett's Esophagus) for Barrett's esophagus samples. Results indicate that this test produces clinically robust and reproducible results under typical experimental and CLIA-level conditions. Sa1821 The Association of Obesity and Barrett's Esophagus, A Meta-Analysis Mohammad H. Shakhatreh, Lior H. Katz, Mohammed Elfaramawi, Hashem El-Serag, Lori A. Fischbach Introduction: Multiple studies have examined the association between overweight, obesity and Barrett's esophagus (BE). We aimed to examine the association of obesity with BE in a meta-analysis. Methods: We searched conference abstracts as well as Ovid and Pubmed from the inception of each database through the end of 2012. We included studies if BE was considered an outcome, there were at least 4 BE patients in the case group, sufficient information was provided to estimate a relative measure of effect (i.e., odds ratio (OR), risk ratio, etc.), the study was published in English or Spanish, was an original study and used the individual as the unit of analysis. We examined the distribution of the measures of effect using visual and tabular displays and tests of homogeneity to reveal systematic variation in the risk estimates of obesity on Barrett's esophagus across studies. Furthermore, we investigated potential publication bias by using funnel plots. We conducted a meta-regression analysis to identify factors that influence variation in the estimated risk estimates across studies within the pool of available data and to define subgroups for which the effect of obesity on BE did not show observable residual heterogeneity in the measure of effect across studies. Results: We found 26 eligible studies examining the association of obesity as defined by Body Mass Index (BMI) ≥30, with BE (Figure 1). In the random-effects meta-analysis model, patients who were obese were 33% more likely to have BE (OR 1.33, 95%CI 1.206-1.467). However, significant heterogeneity (I2: 44.35, p=0.008) was detected overall. Meta-regression analysis revealed that the majority (76%) of the heterogeneity was explained by whether or not the article was a peer-reviewed full-text article (vs. abstract), whether the authors intended to examine obesity as the primary causal risk factor for BE, and whether or not obvious selection bias was observed. In a subset analysis including only the 7 studies which were peer-reviewed full-text articles, where the authors intended to examine obesity as a causal risk factor for BE and with no obvious selection bias (Figure 2), there was no longer significant heterogeneity (I2=12.17, p=0.335), but the risk estimate remained about the same (OR 1.31, 95%CI 1.13-1.53). Conclusion: In a meta-analysis of studies examining the association of obesity (BMI≥30) with BE, we found that obese patients are about 33% more likely to have BE than those who are not obese.
Sa1819 Computer-Assisted Analysis of Esophageal Brush Biopsies Increase the Effectiveness of Screening and Surveillance for Short Segment Barrett's Esophagus DaeWon Kim, Daniel S. Oh, Steven R. DeMeester, Christina L. Greene, Stephanie G. Worrell, Jeffrey A. Hagen BACKGROUND Traditionally, screening and surveillance for Barrett's Esophagus (BE) has been done by endoscopic 4-quadrant forceps biopsies which are analyzed by light microscopy. Recently, a novel endoscopic brush has been developed to allow broader sampling of the esophageal mucosa. The clusters of cells collected are screened by a computerized algorithm to identify intestinal metaplasia (IM) and dysplasia, which are confirmed by a cytopathologist. The aim of this study was to determine whether this approach has additive value over standard endoscopic biopsies for screening and surveillance of BE. METHODS A retrospective review was performed to identify patients who had both 4-quadrant forceps biopsies (FB) and single brush biopsies (BB) for screening and surveillance of BE between 8/17/2012 and 10/11/2013. Results of each technique were matched by location and used to categorize patients regarding the presence of IM and degree of dysplasia. The additional diagnostic yield of the BB technique was determined and the number needed to treat (NNT) was calculated. RESULTS 133 patients received both 4-quadrant forceps biopsies and single brush biopsies. Forceps biopsy detected IM in 56 patients and low grade dysplasia (LGD) in 2. Brush biopsy missed IM in 22 patients and LGD in 2. However, BB detected IM in an additional 8 patients, all of whom had < 3 cm columnar mucosa. Among the 113 patients with < 3 cm columnar mucosa, the additional yield of BB was 7% (8/113) for a NNT of 15. The EGD was done for screening in 60, surveillance without previous endoscopic therapy in 34, and surveillance during endoscopic therapy in 19 patients. In the screening group, the addition of BB increased IM detection by 8.3% (5/60) compared to FB for a NNT of 12 patients. No screening patient had dysplasia. In the surveillance without endoscopic therapy group, the addition of BB detected IM in an additional 5.9% (2/34) compared to FB for a NNT of 17 patients. No dysplasia was identified by either technique. In the surveillance after endoscopic therapy group, BB increased detection of residual or recurrent IM by 5.3% (1/19) compared to FB for a NNT of 19 patients. In 1 patient BB showed IM while FB showed low grade dysplasia. CONCLUSION The addition of computer-assisted analysis of brush biopsy to standard forceps biopsy for screening and surveillance of BE was useful only when there was < 3 cm columnar mucosa. In this setting, the addition of BB to standard FB appears to have significant additive value in detecting BE, with one additional case of BE detected for every 15 procedures. However, a single BB should not replace standard 4-quadrant FB since the BB technique missed 16.5% (22/133) of BE detected by FB in all patients. The use of multiple brushes to increase yield in long segment BE requires further study. Sa1820 Analytical Validation of a Novel Multi-Gene Assay for Patients With Barrett's Esophagus Vivek Yellore, Stephen J. Meltzer, Yulan Cheng, James Stover Background: A previously developed multi-gene methylation-specific PCR assay (ENGAUGE™-GI-Barrett's Esophagus) was analytically validated for the stratification of risk of progression to high-grade dysplasia (HGD) or esophageal adenocarcinoma (EAC) in patients with Barrett's esophagus (BE). We validated the performance of this assay with respect to PCR amplification efficiency, precision, linearity, as well as limits of detection and quantification in a clinical reference laboratory environment. We designed this study to determine the assay's reproducibility and robustness in sections taken from formalinfixed paraffin-embedded (FFPE) tissue blocks. Methods: Tissues from twenty patients were studied. Extracted DNA was assayed for 8 BE progression-related genes (HPP1, p16, RUNX3, CDH13, TAC1, NELL1, AKAP12, and SST) and 1 reference gene (β-Actin) using methylationspecific PCR on an ABI ViiA™ 7 Real-Time PCR System using well-characterized primer and probe sets. All reactions were performed in triplicate with both positive and negative controls for each gene, and detection thresholds for each gene were chosen by receiveroperator curve analysis. Methylation of each gene was normalized relative to a reference gene. Unsupervised clustering and components analysis were performed to examine the variance and correlation of gene methylation profiles amongst patients and sections within FFPE blocks. Sensitivity and Specificity were also calculated. Results: Acceptable performance ranges were defined for each gene. Amplification efficiencies for the 8 assay genes averaged 96.5% (range, 86.4-107.1%) and 92.6% (range, 84.3-102.2%) for the reference gene. All genes responded linearly to at least a 1000-fold DNA concentration range, with an average accuracy of 0.2% and CV's averaging 2.0% for the reference gene and 4.5% for the assay genes. Analytical study SD's were less than 0.5 methylation units and took into account variability contributed by instruments, reagents, and day-to-day baseline variation. Extraction of total DNA yielded high-quality DNA ranging from 100 to 500 ng per sample. In all cases, samples were classified correctly, demonstrating high reproducibility in the classification for repeated tests on the same sample. Unsupervised clustering and principal components analyses revealed a strong correlation between blocks from the same patient, as well as between tumor samples from the same block. For identifying BE progressors, the assay had
Figure 1. Forest plot of 26 studies examining the association of obesity (BMI≥30) with Barrett's Esophagus
Figure 2. Forest plot of 7 homogenous studies examining the association of obesity (BMI≥30) and Barrett's Esophagus
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AGA Abstracts
AGA Abstracts
1316 were reported to have esophagitis. One hundred twenty nine (129) had repeat upper endoscopy at least 6 weeks from the index procedure and were either nHw or AA comprising the study group. Ethnic distribution was as follows: 58% nHw (n=75) and 42% AA (n=54). Gender distribution, BMI and age were similar between groups. BE was present in 8% (n= 6) of the nHw group while no AA had BE on repeat EGD (p<0.04). There was no difference between groups regarding, presence of reflux symptoms, long or short segment BE, dysplasia, presence of esophagitis or grade and medication use (aspirin, NSAID, statin or proton pump inhibitor). Conclusion: African Americans did not progress to BE following EE, while nonHispanic whites were found to have BE at similar rates seen previously in the literature. Medication use, BMI, severity of esophagitis or symptom presence did not impact this result. Other etiologies for this outcome (variation in stem cell presence or additional mucosal factors) must be investigated to illustrate factors decreasing BE presence in AA.
presented as mean + standard deviation, Median (25th, 75th percentiles) or N (%).Time of follow-up was defined as time between baseline endoscopy and diagnosis of HGD/EAC or last endoscopy if no progression. Univariate and multivariate Cox regression was performed to evaluate the association between BMI and progression. A multivariate analysis was performed with LGD group, gender, baseline BMI and BMI change. Results: There were a total of 1239 with BE who had BMI within 1 year of upper endoscopy. Mean age was 60.6 ±13 yrs. 76% were men and 94.7% were Caucasian. Average BMI was 29.8 ± 6 kg/m2. The mean length of Barrett's segment was 3 ±3.4 cm and hiatal hernia size was 1.9 ±2cm. 363 patients met the inclusion criteria. Of these patients, 261 were in no dysplasia group and 102 in LGD group. The mean follow up was 31.6+26 months. During follow up, there were 10 cases of HGD and 4 cases of EAC in no dysplasia group and 18 cases of HGD and 11 cases of EAC in LGD group. There was no evidence to suggest that BMI or BMI change was associated with progression to HGD/EAC in subjects with no dysplasia at baseline (Table 1). However, in patients with LGD as baseline, there was a trend toward significance between lower baseline BMI and hazard of progression (Table 2). For every one unit increase in baseline BMI, the hazard of progression decreases by 7% (p=0.061). This remained so after adjusting for gender and change in BMI (p=0.056). Conclusions: Higher BMI is not associated with increased risk of progression of dysplasia in patients with BE with no dysplasia at baseline. However in LGD patients, increase in BMI was associated with a trend towards lower risk of progression. This is an unexpected finding and warrants validation in further studies. 1. BMI and Progression of Dysplasia in Patients with No Dysplasia at Baseline
Figure 1. Kaplan-Meier Curves of EAC Incidence by Baseline Pathology Sa1816 Influence of Body Mass Index (BMI) on the Prevalence of Dysplasia in Barrett's Esophagus (BE) Prashanthi N. Thota, Madhusudhan R. Sanaka, Prabhdeep Singh, Mangesh R. Pagadala, Rocio Lopez Background/Aims: Increased body mass index (BMI) has been reported to be a risk factor associated with gastroesophageal reflux disease (GERD), BE and esophageal adenocarcinoma (EAC). However, it is not known if it influences the prevalence of dysplasia in BE. Our aim was to estimate the prevalence of various degrees of dysplasia in different BMI groups of patients with BE. Methods: Patients who underwent upper endoscopy and were found to have endoscopic evidence of BE confirmed by presence of intestinal metaplasia on histology from January 2000 to December 2012 at Cleveland Clinic were reviewed. Patients who had BMI values available within one year of upper endoscopy were included in the analysis. BMI levels were classified as following groups: <25, 25-27.4, 27.5-29.9, 30-34.9, 35-39.9 and ≥40. Patient demographics and endoscopic findings such as length of BE, dysplasia in BE and size of hiatal hernia were reviewed. Dysplasia was classified as no dysplasia, low grade dysplasia (LGD), high grade dysplasia (HGD) and EAC. Indefinite for dysplasia was included under LGD group. Data were presented as mean + standard deviation, Median (25th, 75th percentiles) or N (%). Jonckheere-Terpstra test was used to assess differences between the groups. Results: Among a total of 2370 patients, 1239 were included in the analysis. Mean age was 60.6 ±13 yrs. 76% were men and 94.7% were Caucasian. Average BMI was 29.8 ± 6 kg/m2. The time between EGD and BMI measurement ranged between 0-12 months with a mean of 1.3 months. There were 228 (18.4%) in group with BMI<25, 236(19%) in BMI group25-27.4, 262(21.1%) in BMI 27.5 - 29.9, 303 (24.5%) in BMI 3034.9, 126(10.2%) in BMI 35-39.9 and 86(6.8% ) in BMI ≥40. The mean length of Barrett's segment was 3 ± 3.4 cm and hiatal hernia size was 1.9 ±2 cm. The histological findings were no dysplasia in 732 (59.1%), LGD in 159 (12.8%), HGD in 149(12%) and EAC in 199 (16.1%) patients. Lower BMI groups had lower prevalence of dysplasia while patients in higher BMI groups had higher prevalence of dysplasia (p=0.002). These findings are presented in Table 1. Conclusions: Our study found that prevalence of degree of dysplasia varies by BMI. Increased BMI was associated with higher prevalence of dysplasia. These findings have important clinical implications since BMI is a modifiable risk factor. BMI and Degree of Dysplasia
Values presented as mean ± SD or N (column%) Hazard Ratios and p-values correspond to univariate Cox regression analysis 2. BMI and Progression of Dysplasia in Patients with LGD at Baseline
Values presented as Mean ± Sd or N (column%) Hazard Ratios and p-values correspond to univariate Cox regression analysis Sa1818 African Americans Do Not Develop Barrett's Esophagus Following Erosive Esophagitis Ahmad AlKaddour, Camille McGaw, Rama Hritani, Carlos Palacio, Juan C. Munoz, Kenneth J. Vega
Values presented as N (column %) P-value corresponds to Jonckeere-Terpstra test
Introduction: Barrett's esophagus (BE) is a metaplastic alteration of the distal esophageal epithelium to specialized intestinal epithelium (SIM), which is present in 8% to 20% of patients with chronic GERD and is the primary risk factor for development of esophageal adenocarcinoma. Erosive esophagitis (EE) is a likely intermediate step, representing reflux related esophageal injury with potential development of BE upon healing. Previous data indicate that circumstance occurs in 9-12% of individuals following EE. Limited data exists evaluating this situation in African Americans. The aim of this study is to determine if ethnic variation occurs in BE formation following EE on index endoscopy for any indication at the University of Florida-Jacksonville College of Medicine. Methods: A retrospective review of upper endoscopies (EGD) was performed between January 1st, 2008 and December 31st, 2012. Inclusion criteria were erosive esophagitis on index endoscopy, follow-up endoscopy at minimum of 6 weeks later and ethnicity of either non-Hispanic white (nHw) or African American (AA). Exclusion criteria were age <18 years of age, no repeat EGD following EE on index endoscopy and patients with known BE, UGI malignancy or head and neck cancer at index endoscopy. Data collected included age, gender, BMI, dates of index and repeat EGD, presence of esophagitis and grade (LA classification) if present, medication use (aspirin, NSAID, statin, proton pump inhibitor), length of BE (long ( > 3 cm) or short (< 3 cm) segment) as well as presence of dysplasia and grade (low, indeterminate or high) if present. Results: A total of 10515 patients had upper endoscopy during the 5 year study period;
Sa1817 Effect of Body Mass Index on Progression of Dysplasia in Barrett's Esophagus Prashanthi N. Thota, Madhusudhan R. Sanaka, Prabhdeep Singh, Mangesh R. Pagadala, Rocio Lopez Background/Aims: Increased body mass index (BMI) is associated with Barrett's esophagus (BE) and esophageal adenocacinoma (EAC). It is not known if a change in BMI would affect the progression of dysplasia in Barrett's. Our aim was to study the effect of BMI on progression of dysplasia in BE to high grade dysplasia (HGD) or esophageal adenocarcinoma (EAC). Methods: Patients who underwent upper endoscopy and were found to have BE from January 2000 to December 2012 at Cleveland Clinic were reviewed. Patients in whom BMI values were available within one year of upper endoscopy were included in the analysis. Patients with HGD/EAC at baseline, or with no follow-up BMI or biopsies were excluded. BMI levels were classified into following groups: <25, 25-27.4, 27.5-29.9, 30-34.9, 35-39.9 and ≥40. Degree of dysplasia was classified into 4 groups: no dysplasia, low grade dyspasia (LGD), high grade dysplasia (HGD) and EAC. Patient demographics and endoscopic findings such as length of BE, degree of dysplasia in BE, and size of hiatal hernia were reviewed. Data are
AGA Abstracts
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a sensitivity and specificity of 95% and 90%, respectively. Conclusions: Extensive reagent and analytical performance studies were conducted to evaluate the reliability and reproducibility of a gene test panel (ENGAUGE™-GI-Barrett's Esophagus) for Barrett's esophagus samples. Results indicate that this test produces clinically robust and reproducible results under typical experimental and CLIA-level conditions. Sa1821 The Association of Obesity and Barrett's Esophagus, A Meta-Analysis Mohammad H. Shakhatreh, Lior H. Katz, Mohammed Elfaramawi, Hashem El-Serag, Lori A. Fischbach Introduction: Multiple studies have examined the association between overweight, obesity and Barrett's esophagus (BE). We aimed to examine the association of obesity with BE in a meta-analysis. Methods: We searched conference abstracts as well as Ovid and Pubmed from the inception of each database through the end of 2012. We included studies if BE was considered an outcome, there were at least 4 BE patients in the case group, sufficient information was provided to estimate a relative measure of effect (i.e., odds ratio (OR), risk ratio, etc.), the study was published in English or Spanish, was an original study and used the individual as the unit of analysis. We examined the distribution of the measures of effect using visual and tabular displays and tests of homogeneity to reveal systematic variation in the risk estimates of obesity on Barrett's esophagus across studies. Furthermore, we investigated potential publication bias by using funnel plots. We conducted a meta-regression analysis to identify factors that influence variation in the estimated risk estimates across studies within the pool of available data and to define subgroups for which the effect of obesity on BE did not show observable residual heterogeneity in the measure of effect across studies. Results: We found 26 eligible studies examining the association of obesity as defined by Body Mass Index (BMI) ≥30, with BE (Figure 1). In the random-effects meta-analysis model, patients who were obese were 33% more likely to have BE (OR 1.33, 95%CI 1.206-1.467). However, significant heterogeneity (I2: 44.35, p=0.008) was detected overall. Meta-regression analysis revealed that the majority (76%) of the heterogeneity was explained by whether or not the article was a peer-reviewed full-text article (vs. abstract), whether the authors intended to examine obesity as the primary causal risk factor for BE, and whether or not obvious selection bias was observed. In a subset analysis including only the 7 studies which were peer-reviewed full-text articles, where the authors intended to examine obesity as a causal risk factor for BE and with no obvious selection bias (Figure 2), there was no longer significant heterogeneity (I2=12.17, p=0.335), but the risk estimate remained about the same (OR 1.31, 95%CI 1.13-1.53). Conclusion: In a meta-analysis of studies examining the association of obesity (BMI≥30) with BE, we found that obese patients are about 33% more likely to have BE than those who are not obese.
Sa1819 Computer-Assisted Analysis of Esophageal Brush Biopsies Increase the Effectiveness of Screening and Surveillance for Short Segment Barrett's Esophagus DaeWon Kim, Daniel S. Oh, Steven R. DeMeester, Christina L. Greene, Stephanie G. Worrell, Jeffrey A. Hagen BACKGROUND Traditionally, screening and surveillance for Barrett's Esophagus (BE) has been done by endoscopic 4-quadrant forceps biopsies which are analyzed by light microscopy. Recently, a novel endoscopic brush has been developed to allow broader sampling of the esophageal mucosa. The clusters of cells collected are screened by a computerized algorithm to identify intestinal metaplasia (IM) and dysplasia, which are confirmed by a cytopathologist. The aim of this study was to determine whether this approach has additive value over standard endoscopic biopsies for screening and surveillance of BE. METHODS A retrospective review was performed to identify patients who had both 4-quadrant forceps biopsies (FB) and single brush biopsies (BB) for screening and surveillance of BE between 8/17/2012 and 10/11/2013. Results of each technique were matched by location and used to categorize patients regarding the presence of IM and degree of dysplasia. The additional diagnostic yield of the BB technique was determined and the number needed to treat (NNT) was calculated. RESULTS 133 patients received both 4-quadrant forceps biopsies and single brush biopsies. Forceps biopsy detected IM in 56 patients and low grade dysplasia (LGD) in 2. Brush biopsy missed IM in 22 patients and LGD in 2. However, BB detected IM in an additional 8 patients, all of whom had < 3 cm columnar mucosa. Among the 113 patients with < 3 cm columnar mucosa, the additional yield of BB was 7% (8/113) for a NNT of 15. The EGD was done for screening in 60, surveillance without previous endoscopic therapy in 34, and surveillance during endoscopic therapy in 19 patients. In the screening group, the addition of BB increased IM detection by 8.3% (5/60) compared to FB for a NNT of 12 patients. No screening patient had dysplasia. In the surveillance without endoscopic therapy group, the addition of BB detected IM in an additional 5.9% (2/34) compared to FB for a NNT of 17 patients. No dysplasia was identified by either technique. In the surveillance after endoscopic therapy group, BB increased detection of residual or recurrent IM by 5.3% (1/19) compared to FB for a NNT of 19 patients. In 1 patient BB showed IM while FB showed low grade dysplasia. CONCLUSION The addition of computer-assisted analysis of brush biopsy to standard forceps biopsy for screening and surveillance of BE was useful only when there was < 3 cm columnar mucosa. In this setting, the addition of BB to standard FB appears to have significant additive value in detecting BE, with one additional case of BE detected for every 15 procedures. However, a single BB should not replace standard 4-quadrant FB since the BB technique missed 16.5% (22/133) of BE detected by FB in all patients. The use of multiple brushes to increase yield in long segment BE requires further study. Sa1820 Analytical Validation of a Novel Multi-Gene Assay for Patients With Barrett's Esophagus Vivek Yellore, Stephen J. Meltzer, Yulan Cheng, James Stover Background: A previously developed multi-gene methylation-specific PCR assay (ENGAUGE™-GI-Barrett's Esophagus) was analytically validated for the stratification of risk of progression to high-grade dysplasia (HGD) or esophageal adenocarcinoma (EAC) in patients with Barrett's esophagus (BE). We validated the performance of this assay with respect to PCR amplification efficiency, precision, linearity, as well as limits of detection and quantification in a clinical reference laboratory environment. We designed this study to determine the assay's reproducibility and robustness in sections taken from formalinfixed paraffin-embedded (FFPE) tissue blocks. Methods: Tissues from twenty patients were studied. Extracted DNA was assayed for 8 BE progression-related genes (HPP1, p16, RUNX3, CDH13, TAC1, NELL1, AKAP12, and SST) and 1 reference gene (β-Actin) using methylationspecific PCR on an ABI ViiA™ 7 Real-Time PCR System using well-characterized primer and probe sets. All reactions were performed in triplicate with both positive and negative controls for each gene, and detection thresholds for each gene were chosen by receiveroperator curve analysis. Methylation of each gene was normalized relative to a reference gene. Unsupervised clustering and components analysis were performed to examine the variance and correlation of gene methylation profiles amongst patients and sections within FFPE blocks. Sensitivity and Specificity were also calculated. Results: Acceptable performance ranges were defined for each gene. Amplification efficiencies for the 8 assay genes averaged 96.5% (range, 86.4-107.1%) and 92.6% (range, 84.3-102.2%) for the reference gene. All genes responded linearly to at least a 1000-fold DNA concentration range, with an average accuracy of 0.2% and CV's averaging 2.0% for the reference gene and 4.5% for the assay genes. Analytical study SD's were less than 0.5 methylation units and took into account variability contributed by instruments, reagents, and day-to-day baseline variation. Extraction of total DNA yielded high-quality DNA ranging from 100 to 500 ng per sample. In all cases, samples were classified correctly, demonstrating high reproducibility in the classification for repeated tests on the same sample. Unsupervised clustering and principal components analyses revealed a strong correlation between blocks from the same patient, as well as between tumor samples from the same block. For identifying BE progressors, the assay had
Figure 1. Forest plot of 26 studies examining the association of obesity (BMI≥30) with Barrett's Esophagus
Figure 2. Forest plot of 7 homogenous studies examining the association of obesity (BMI≥30) and Barrett's Esophagus
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AGA Abstracts
AGA Abstracts
1316 were reported to have esophagitis. One hundred twenty nine (129) had repeat upper endoscopy at least 6 weeks from the index procedure and were either nHw or AA comprising the study group. Ethnic distribution was as follows: 58% nHw (n=75) and 42% AA (n=54). Gender distribution, BMI and age were similar between groups. BE was present in 8% (n= 6) of the nHw group while no AA had BE on repeat EGD (p<0.04). There was no difference between groups regarding, presence of reflux symptoms, long or short segment BE, dysplasia, presence of esophagitis or grade and medication use (aspirin, NSAID, statin or proton pump inhibitor). Conclusion: African Americans did not progress to BE following EE, while nonHispanic whites were found to have BE at similar rates seen previously in the literature. Medication use, BMI, severity of esophagitis or symptom presence did not impact this result. Other etiologies for this outcome (variation in stem cell presence or additional mucosal factors) must be investigated to illustrate factors decreasing BE presence in AA.