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Mo1927 Complete Remission of Intestinal Metaplasia After One Radiofrequency Ablation Session
Mo1926
AGA Abstracts
Effects of Vitamin D Supplementation on Barrett's Esophagus Linda C. Cummings, Joseph Willis, Gregory S. Cooper, Beth Bednarchik, Sanford Markowitz, Amitabh Chak Background: Vitamin D directly or indirectly controls genes that regulate proliferation, apoptosis, and differentiation. We have previously reported that calcitriol, the active form of vitamin D, inhibits the growth of esophageal adenocarcinoma cell lines. Vitamin D deficiency is also associated with insulin resistance and increased risk for esophageal cancer. The goals of this study were to assess the effects of vitamin D supplementation on Barrett's esophagus (BE) patients with or without dysplasia. We hypothesized that vitamin D supplementation may have beneficial effects including improvement of dysplasia and insulin resistance in BE. Methods: Patients with long-segment or short-segment BE with or without high grade dysplasia (HGD) were treated with vitamin D3 (cholecalciferol) 50,000 international units weekly for 2 weeks (HGD) or 12 weeks (no dysplasia or low grade dysplasia). BE biopsies and blood samples were obtained before and after vitamin D3 supplementation. Biopsies were stained with hematoxylin and eosin and reviewed by an expert pathologist blinded to study arm. Serum 25-hydroxyvitamin D, insulin, and glucose levels were assessed to characterize vitamin D status and to estimate insulin resistance (IR) by the Homeostatic Model Assessment (HOMA). Results: Among the first 10 evaluable study subjects, 7 had BE with no or low grade dysplasia and 3 had high grade dysplasia. 6 patients had longsegment BE and 4 had short-segment. The mean age was 65.6 years (standard deviation, 9.6 years); 3 women and 7 men were enrolled. Baseline serum 25-hydroxyvitamin D levels ranged from 14.1 ng/mL (deficient) to 60.9 ng/mL (sufficient) with a median level of 35.4 ng/mL. Median baseline HOMA-IR was 4.27. After vitamin D supplemention, 25hydroxyvitamin D levels rose significantly (p , 0.001) with a median increase of 35.2 ng/ mL among patients with no or low grade dysplasia. Among patients with HGD with 2 weeks of supplementation, 2 had small increments in serum 25-hydroxyvitamin D levels of 13.3 and 14.2 ng/mL, while no change occurred in 1 patient. On pathologic review, regression to low grade dysplasia after vitamin D supplementation occurred in 2 of 3 HGD subjects. There was no significant change in insulin resistance after vitamin D supplementation. Vitamin D supplementation was well tolerated. Conclusion: Regression to low grade dysplasia occurred in 2 of 3 high grade dysplasia subjects. Baseline Vitamin D status of BE patients was generally sufficient. Treatment with 12 weeks of vitamin D supplementation resulted in marked increases in serum 25-hydroxyvitamin D levels compared with 2 weeks. These changes occurred independent of effects on insulin resistance. These findings support the hypothesis that vitamin D supplementation may have beneficial effects in Barrett's esophagus and warrant further investigation.
FIGURE 1: (A) Cross-sectional view using VLE of a segment of BE previously treated with RFA. (B) Neosquamous epithelium is characterized by a layered structure that is absent in (C) specialized intestinal metaplasia. Measurements of NSE thickness (red double arrow) were taken at four quadrants (Q1-4) along each centimeter of the pre-RFA BE segment. Quadrants that contained both NSE and SIM were excluded from measurement (gray rectangle involving Q2 and Q3). Mo1925 Cellular Senescence and P16ink4a Immunohistochemistry Predicts Response to Radiofrequency Ablation (RFA) for Barrett's Esophagus (BE) With Highgrade Dysplasia (HGD) Joshua D. Penfield, Cadman L. Leggett, Marlys Anderson, Lori S. Lutzke, Tsung-Teh Wu, Alan R. Zinsmeister, Prasad G. Iyer, Kenneth K. Wang BACKGROUND: Cellular senescence is a state of permanent cell growth arrest that occurs as a response to neoplastic stimuli and appears to prevent progression of neoplasia. The presence of markers of senescence in BE with HGD prior to ablative therapy may predict response to RFA, as escape from senescence promotes aggressive behavior of dysplastic cells. As identification of senescence in paraffin-embedded tissue is difficult to achieve with standard methods, we chose biomarkers that were compatible. We hypothesized that there would be a difference in senescence biomarkers and stem cells between patients who responded and those who did not respond to RFA. AIM: To evaluate whether senescence biomarkers can predict response to RFA by using immunohistochemistry against the tumor suppressor protein p16INK4a, the nuclear DNA damage response marker γ-H2Ax and the intestinal stem cell marker LGR5 in biopsy tissue from BE patients with HGD prior to RFA. METHODS: All patients referred for untreated BE with HGD were reviewed. Patients with pre-RFA esophageal biopsies, two RFA treatment sessions and surveillance biopsies 3 months post-RFA were identified. From this group, patients were selected as either persistent HGD [non-responders (NR)] or neosquamous re-epithelialization [responders (R)]. Pre-RFA tissue was then stained with p16INK4a, γ-H2Ax and LGR5. Slides were reviewed by an experienced GI pathologist blinded to the status of the patients. An intensity-weighted scoring system was used. RESULTS: Forty five patients (R:25, NR:20) fulfilled inclusion criteria. Baseline characteristics are shown in table 1. Using a logistic model to predict RFA response, mean cell count of γ-H2Ax (R:110 vs. NR:76, p.0.05) and LGR5 (R:10 vs. NR:13, p .0.05) were not significantly associated with response to RFA. Decreased intensity of p16INK4a in preRFA tissue was associated with persistent HGD post-RFA (OR=2.78, 95% CI 1.16-6.66; p= 0.02). CONCLUSION: In our cohort of patients, p16INK4a intensity was associated with RFA response as patients with decreased expression of this tumor suppressor protein on pre-RFA tissue were more likely to have persistent HGD post-RFA. This is likely due to a decreased senescence response in pre-RFA tissue that promotes resistance to ablation. Table 1: Patient demographics
Mo1927 Complete Remission of Intestinal Metaplasia After One Radiofrequency Ablation Session Bashar J. Qumseya, Waseem J. David, Edgar C. Aranda-Michel, Lois L. Hemminger, Michael B. Wallace, Herbert C. Wolfsen Background: Radiofrequency ablation (RFA) is the most commonly used for treatment of Barrett's esophagus (BE) with the goal of achieving complete remission from intestinal metaplasia (CRIM). Endoscopic mucosal resection (EMR) is used in conjunction with RFA to remove nodular and other suspicious areas. Impact of EMR on CRIM is uncertain with potential to improve CRIM by removal of nodular/thick tissue which is difficult to ablate by RFA, but also potential to worsen RFA by inducing stenosis and altered esophageal geometry. Aims: To assess the effect of one treatment with RFA with/without EMR on the rate of CRIM among patients with BE. Methods: This was a retrospective, observational study using large RFA database in a tertiary referral center. The primary outcome was the rate of CRIM after the first RFA session compared between patients who had RFA alone vs. RFA with EMR. A secondary outcome was the achievement of complete remission from dysplasia (CRD) downgrade in pathology from baseline. Chi-square or Fisher's exact tests where used to assess differences between proportions. Multivariable logistic regression analysis was used to assess the association between the primary outcome (CRIM) and predictor variables. Results: 215 patients underwent RFA for BE between May 2005 and June 2012. Of those 23% (49) has nondysplastic BE (NDBE), 6.5% (14) were indefinite for dysplasia (IFD), 29% (63) has low-grade dysplasia (LGD), 36% (77) had high-grade dysplasia (HGD), and 5.5% (12) had adenocarcinoma (AC). Most patients (91%) were males. Half of all patients (50%) had a history of ever having EMR. However, a minority of patients (11%) had EMR to remove nodules within 3 months of initiating RFA. Pathology on follow up EGD based on baseline pathology is summarized in Figure 1. Overall 36% [29-42%] achieved CRIM after one RFA treatment. Among 166 patients with BE and dysplasia, 46% (76) achieved complete remission of dysplasia (CRD) after one session of RFA. In a univariate analysis there was no significant difference in the rate of CRIM after the first RFA between patients who had RFA with EMR or RFA alone (50% vs. 34%, p=0.17). In a multivariable logistic regression analysis when controlling for age, gender, and BE length, RFA with EMR showed a trend toward more CRIM (OR 2.5 [0.96 - 6.6], p=0.06) when compared to RFA alone, but this did not achieve statistical significance. Conclusion: Many patients can achieve CRIM after one RFA treatment. Use of EMR to remove nodules before RFA may be associated with higher rates of CRIM after RFA. Larger studies are needed to confirm this association.
Figure 1: A) and B) Representative images of p16INK4a immunohistochemistry on pre-RFA biopsy tissue from patients with subsequent complete neosquamous re-epithelialization postRFA. C) and D) Representative images of p16INK4a on pre-RFA biopsy tissue from patients with subsequent persistent HGD post-RFA.
AGA Abstracts
S-696
Mo1928 Factors Associated With Recurrence of Barrett's Esophagus After Completion of Radiofrequency Ablation Peter Shue, Rahul Kataria, Murali Pathikonda, Frank K. Friedenberg, Rebecca Thomas, Michael S. Smith Background: Despite the efficacy of radiofrequency ablation (RFA) in eradicating Barrett's esophagus (BE), prior studies have reported recurrence of intestinal metaplasia (IM) and dysplasia after complete remission (CR) is achieved. There is limited data on factors that predict recurrence. Our aim was to identify factors associated with the recurrence of IM and/or dysplasia after CR is achieved with RFA. Methods: All BE patients at a single academic medical center who received RFA from January 2009-October 2012 were identified. Patients were included in the analysis if they achieved CR of IM, defined by the absence of endoscopic and histologic evidence of Barrett's metaplasia on initial post-ablation endoscopy, and had a minimum of two surveillance endoscopies at least three months apart. Surveillance biopsies were obtained using a modified Seattle protocol. Clinical, demographic and endoscopic data were collected. Univariate analysis using Pearson-Chi square for categorical variables and independent sample t-test for continuous variables was performed. Results: Forty-two patients (15 with non-dysplastic BE (NDBE); 13 with low grade dysplasia (LGD), 12 with high grade dysplasia (HGD) and 2 with intramucosal carcinoma) met criteria. This cohort was 71% male with a median age of 61 years (IQR 53-70). The median BE length was 3.5 cm (IQR 1-5). A median of 3 ablations (IQR 2-4) were required to achieve CR of IM, with a median follow-up period of 14 months (IQR 11-22.5). The overall IM recurrence rate was 26.2% (n=11). Recurrence was seen in 5 (33.3%) patients with NDBE, 4 (30.1%) with LGD, and 2 (18.0%) with HGD. The difference in recurrence rates between dysplasia grades was not significant (p=0.681). The median time to recurrence was 12 months (IQR 9-20). There was no recurrence of dysplasia. Twenty-eight (66.7%) patients had a smoking history. Among these smokers, 11 (39.3%) recurred. No recurrence was seen among non-smokers. The difference in recurrence rate between smokers and non-smokers was significant (p = .006). However, there was no significant difference when comparing former to active smokers (p= 0.12). Patients with recurrence had a significantly lower body mass index (BMI) compared to patients who did not recur (25.3 kgm-2 vs 29.8 kgm-2, p=0.002). Other parameters such as age, gender, race, alcohol consumption, family history of BE or esophageal cancer, initial BE length, hiatal hernia size and presence of gastroesophageal reflux symptoms were not significantly associated with recurrence. Conclusion: Recurrence after achieving CR of IM with RFA was 26.2%. These recurrences were seen exclusively in smokers, suggesting that smoking may be a risk factor. Surprisingly, patients with recurrence had a lower BMI, which may indicate that obesity is not a predisposing factor. Further studies are needed to understand these associations.
Mo1930 Beneficial Effect of Ursodeoxycholic Acid (UDCA) and Its Derivative UDCACpa in Attenuation of Functional Impairment of Esophageal Mucosa in Rat Model of Barrett's Esophagus Jolanta Majka, Rafal Pabianczyk, Gracjana Krzysiek-Maczka, Agata Ptak-Belowska, Slawomir Kwiecien, Anne-Marie Byrne, Dermot P. Kelleher, John Gilmer, Tomasz Brzozowski
Mo1929 Effect of Site Volume on Eradication of Barrett's Esophagus (BE): Results From the U.S. RFA Registry Sarina Pasricha, William J. Bulsiewicz, V. Raman Muthusamy, Srinadh Komanduri, Herbert C. Wolfsen, Ron E. Pruitt, Atilla Ertan, Gary W. Chmielewski, Nicholas J. Shaheen
Barrett,s esophagus (BE) is a pre-malignant condition in which squamous epithelium is replaced by metaplastic columnar epithelium, but the pathogenesis of this disorder should be elucidated. The secondary bile acid deoxycholic acid (DCA) contributes to the development of BE and implicated in progression of BE to adenocarcinoma, whereas UDCA has shown some protection in BE epithelial cell line in vitro. We studied effect of treatment with DCA, UDCA and the novel derivative UDCA (UDCA-CPA) on esophageal mucosal damage in rats prepared with esophagogastroduodenal anastomosis (EGDA). EGDA rats were randomly divided into 4 groups treated i.g. daily with: 1) vehicle (saline),2) DCA (20 mg/kg), 3) UDCA (40 mg/kg) or UDCA-CPA (40 mg/kg). At 8 and 12 weeks esophageal damage was evaluated by macroscopic and histological lesion index (LI), esophageal blood flow (EBF), MPO activity and malonylodialdehyde (MDA) content. mucosal expression of mRNA for caudal-related homebox gene family Cdx1 and Cdx2, COX-2, VEGF, NF κB and proinflammatory cytokines IL-1β and TNF-α was analyzed by RT-PCR. Chronic esophagitis developed in all EGDA animals and a significant decrease in EBF was observed. MPO activity and MDA content was elevated and an overexpression of Cdx2 and COX-2 were observed. In EGDA rats, extensive esophageal ulcerations, development of columnar epithelium, formation of mucus glands in squamous epithelium and intestinal metaplasia were observed. Treatment with DCA significantly enhanced LI, MPO activity and MDA content. Expression of IL-1 β and TNF-α mRNA and plasma concentration were elevated compared to vehicle. EGDA animals treated with UDCA or UDCA-CPA, exhibited significantly less macro- and microscopic esophageal injury and fewer animals developed columnar epithelium and intestinal metaplasia. Expression of NFκB was negligible in sham-control animals but strongly upregulated in esophageal mucosa of EGDA rats treated with DCA, but not in those treated with
Background: Radiofrequency ablation (RFA) may require multiple sessions for complete eradication of Barrett's esophagus (BE). The impact of case volume on safety and efficacy outcomes associated with RFA is unclear. Methods: The U.S. Barrett's RFA Patient Registry is a multi-center prospective study of patients undergoing RFA for BE from 2007 to 2012. We collected demographic data, pre- and post- treatment histology, endoscopic findings, number of RFA sessions, ablation outcomes (including complete eradication of intestinal metaplasia (CEIM), and complete eradication of dysplasia (CED)), and complications (stricture, bleeding, hospitalization). Our safety cohort consisted of patients treated with RFA, while our efficacy cohort was restricted to subjects who had a biopsy performed 12 months or more after initial treatment. We examined the effect of center volume at the time of an individual's enrollment by examining safety and efficacy outcomes based upon the number of patients treated at a center prior to an individual's enrollment in 4 patient groups (Patients 1-10, 11-20, 21-30, and more than 30). The effect of center experience on stricture, bleeding, hospitalization, and CEIM was assessed using logistic regression adjusting for age, gender, race, BE length, and presence of pretreatment dysplasia. The effect of center experience on total treatment sessions to achieve CEIM was examined using linear regression, controlling for BE length. Results: Among 5,530 patients, the number of patients treated prior to enrollment at a site was not significantly associated with the risk of stricture, GI bleeding, perforation or hospitalization (p. 0.05)(see table). There was, however, a trend toward lower rates of hospitalization with added case volume. In a multivariate logistic regression model, the odds of hospitalization decreased by 1% for each patient previously treated at
S-697
AGA Abstracts
AGA Abstracts
the center (OR 0.99, p=0.02). Center experience was not independently associated with stricture or GI bleed after controlling for age, gender, race, BE length and pre-treatment dysplasia. Among 2936 patients included in the efficacy analysis, degree of center experience at the time of an individual's treatment session was significantly associated with improvements in CEIM rate (p= 0.001) (see table), however this association dissolved in multivariable analysis after controlling for age, gender, race, length and pre-treatment dysplasia(p=0.30). Patient volume did not impact CED rates. However, case volume was independently associated with the number of treatment sessions needed to achieve CEIM, after controlling for BE length (p = 0.02; see figure). Conclusions: Increased site case volume was associated with lower hospitalization rates and fewer treatments needed to achieve CEIM but did not significantly affect rates of stricture, bleeding, or the efficacy of treatment. Safety and efficacy of RFA based on center experience prior to treatment:
AGA Abstracts
Effects of Vitamin D Supplementation on Barrett's Esophagus Linda C. Cummings, Joseph Willis, Gregory S. Cooper, Beth Bednarchik, Sanford Markowitz, Amitabh Chak Background: Vitamin D directly or indirectly controls genes that regulate proliferation, apoptosis, and differentiation. We have previously reported that calcitriol, the active form of vitamin D, inhibits the growth of esophageal adenocarcinoma cell lines. Vitamin D deficiency is also associated with insulin resistance and increased risk for esophageal cancer. The goals of this study were to assess the effects of vitamin D supplementation on Barrett's esophagus (BE) patients with or without dysplasia. We hypothesized that vitamin D supplementation may have beneficial effects including improvement of dysplasia and insulin resistance in BE. Methods: Patients with long-segment or short-segment BE with or without high grade dysplasia (HGD) were treated with vitamin D3 (cholecalciferol) 50,000 international units weekly for 2 weeks (HGD) or 12 weeks (no dysplasia or low grade dysplasia). BE biopsies and blood samples were obtained before and after vitamin D3 supplementation. Biopsies were stained with hematoxylin and eosin and reviewed by an expert pathologist blinded to study arm. Serum 25-hydroxyvitamin D, insulin, and glucose levels were assessed to characterize vitamin D status and to estimate insulin resistance (IR) by the Homeostatic Model Assessment (HOMA). Results: Among the first 10 evaluable study subjects, 7 had BE with no or low grade dysplasia and 3 had high grade dysplasia. 6 patients had longsegment BE and 4 had short-segment. The mean age was 65.6 years (standard deviation, 9.6 years); 3 women and 7 men were enrolled. Baseline serum 25-hydroxyvitamin D levels ranged from 14.1 ng/mL (deficient) to 60.9 ng/mL (sufficient) with a median level of 35.4 ng/mL. Median baseline HOMA-IR was 4.27. After vitamin D supplemention, 25hydroxyvitamin D levels rose significantly (p , 0.001) with a median increase of 35.2 ng/ mL among patients with no or low grade dysplasia. Among patients with HGD with 2 weeks of supplementation, 2 had small increments in serum 25-hydroxyvitamin D levels of 13.3 and 14.2 ng/mL, while no change occurred in 1 patient. On pathologic review, regression to low grade dysplasia after vitamin D supplementation occurred in 2 of 3 HGD subjects. There was no significant change in insulin resistance after vitamin D supplementation. Vitamin D supplementation was well tolerated. Conclusion: Regression to low grade dysplasia occurred in 2 of 3 high grade dysplasia subjects. Baseline Vitamin D status of BE patients was generally sufficient. Treatment with 12 weeks of vitamin D supplementation resulted in marked increases in serum 25-hydroxyvitamin D levels compared with 2 weeks. These changes occurred independent of effects on insulin resistance. These findings support the hypothesis that vitamin D supplementation may have beneficial effects in Barrett's esophagus and warrant further investigation.
FIGURE 1: (A) Cross-sectional view using VLE of a segment of BE previously treated with RFA. (B) Neosquamous epithelium is characterized by a layered structure that is absent in (C) specialized intestinal metaplasia. Measurements of NSE thickness (red double arrow) were taken at four quadrants (Q1-4) along each centimeter of the pre-RFA BE segment. Quadrants that contained both NSE and SIM were excluded from measurement (gray rectangle involving Q2 and Q3). Mo1925 Cellular Senescence and P16ink4a Immunohistochemistry Predicts Response to Radiofrequency Ablation (RFA) for Barrett's Esophagus (BE) With Highgrade Dysplasia (HGD) Joshua D. Penfield, Cadman L. Leggett, Marlys Anderson, Lori S. Lutzke, Tsung-Teh Wu, Alan R. Zinsmeister, Prasad G. Iyer, Kenneth K. Wang BACKGROUND: Cellular senescence is a state of permanent cell growth arrest that occurs as a response to neoplastic stimuli and appears to prevent progression of neoplasia. The presence of markers of senescence in BE with HGD prior to ablative therapy may predict response to RFA, as escape from senescence promotes aggressive behavior of dysplastic cells. As identification of senescence in paraffin-embedded tissue is difficult to achieve with standard methods, we chose biomarkers that were compatible. We hypothesized that there would be a difference in senescence biomarkers and stem cells between patients who responded and those who did not respond to RFA. AIM: To evaluate whether senescence biomarkers can predict response to RFA by using immunohistochemistry against the tumor suppressor protein p16INK4a, the nuclear DNA damage response marker γ-H2Ax and the intestinal stem cell marker LGR5 in biopsy tissue from BE patients with HGD prior to RFA. METHODS: All patients referred for untreated BE with HGD were reviewed. Patients with pre-RFA esophageal biopsies, two RFA treatment sessions and surveillance biopsies 3 months post-RFA were identified. From this group, patients were selected as either persistent HGD [non-responders (NR)] or neosquamous re-epithelialization [responders (R)]. Pre-RFA tissue was then stained with p16INK4a, γ-H2Ax and LGR5. Slides were reviewed by an experienced GI pathologist blinded to the status of the patients. An intensity-weighted scoring system was used. RESULTS: Forty five patients (R:25, NR:20) fulfilled inclusion criteria. Baseline characteristics are shown in table 1. Using a logistic model to predict RFA response, mean cell count of γ-H2Ax (R:110 vs. NR:76, p.0.05) and LGR5 (R:10 vs. NR:13, p .0.05) were not significantly associated with response to RFA. Decreased intensity of p16INK4a in preRFA tissue was associated with persistent HGD post-RFA (OR=2.78, 95% CI 1.16-6.66; p= 0.02). CONCLUSION: In our cohort of patients, p16INK4a intensity was associated with RFA response as patients with decreased expression of this tumor suppressor protein on pre-RFA tissue were more likely to have persistent HGD post-RFA. This is likely due to a decreased senescence response in pre-RFA tissue that promotes resistance to ablation. Table 1: Patient demographics
Mo1927 Complete Remission of Intestinal Metaplasia After One Radiofrequency Ablation Session Bashar J. Qumseya, Waseem J. David, Edgar C. Aranda-Michel, Lois L. Hemminger, Michael B. Wallace, Herbert C. Wolfsen Background: Radiofrequency ablation (RFA) is the most commonly used for treatment of Barrett's esophagus (BE) with the goal of achieving complete remission from intestinal metaplasia (CRIM). Endoscopic mucosal resection (EMR) is used in conjunction with RFA to remove nodular and other suspicious areas. Impact of EMR on CRIM is uncertain with potential to improve CRIM by removal of nodular/thick tissue which is difficult to ablate by RFA, but also potential to worsen RFA by inducing stenosis and altered esophageal geometry. Aims: To assess the effect of one treatment with RFA with/without EMR on the rate of CRIM among patients with BE. Methods: This was a retrospective, observational study using large RFA database in a tertiary referral center. The primary outcome was the rate of CRIM after the first RFA session compared between patients who had RFA alone vs. RFA with EMR. A secondary outcome was the achievement of complete remission from dysplasia (CRD) downgrade in pathology from baseline. Chi-square or Fisher's exact tests where used to assess differences between proportions. Multivariable logistic regression analysis was used to assess the association between the primary outcome (CRIM) and predictor variables. Results: 215 patients underwent RFA for BE between May 2005 and June 2012. Of those 23% (49) has nondysplastic BE (NDBE), 6.5% (14) were indefinite for dysplasia (IFD), 29% (63) has low-grade dysplasia (LGD), 36% (77) had high-grade dysplasia (HGD), and 5.5% (12) had adenocarcinoma (AC). Most patients (91%) were males. Half of all patients (50%) had a history of ever having EMR. However, a minority of patients (11%) had EMR to remove nodules within 3 months of initiating RFA. Pathology on follow up EGD based on baseline pathology is summarized in Figure 1. Overall 36% [29-42%] achieved CRIM after one RFA treatment. Among 166 patients with BE and dysplasia, 46% (76) achieved complete remission of dysplasia (CRD) after one session of RFA. In a univariate analysis there was no significant difference in the rate of CRIM after the first RFA between patients who had RFA with EMR or RFA alone (50% vs. 34%, p=0.17). In a multivariable logistic regression analysis when controlling for age, gender, and BE length, RFA with EMR showed a trend toward more CRIM (OR 2.5 [0.96 - 6.6], p=0.06) when compared to RFA alone, but this did not achieve statistical significance. Conclusion: Many patients can achieve CRIM after one RFA treatment. Use of EMR to remove nodules before RFA may be associated with higher rates of CRIM after RFA. Larger studies are needed to confirm this association.
Figure 1: A) and B) Representative images of p16INK4a immunohistochemistry on pre-RFA biopsy tissue from patients with subsequent complete neosquamous re-epithelialization postRFA. C) and D) Representative images of p16INK4a on pre-RFA biopsy tissue from patients with subsequent persistent HGD post-RFA.
AGA Abstracts
S-696
Mo1928 Factors Associated With Recurrence of Barrett's Esophagus After Completion of Radiofrequency Ablation Peter Shue, Rahul Kataria, Murali Pathikonda, Frank K. Friedenberg, Rebecca Thomas, Michael S. Smith Background: Despite the efficacy of radiofrequency ablation (RFA) in eradicating Barrett's esophagus (BE), prior studies have reported recurrence of intestinal metaplasia (IM) and dysplasia after complete remission (CR) is achieved. There is limited data on factors that predict recurrence. Our aim was to identify factors associated with the recurrence of IM and/or dysplasia after CR is achieved with RFA. Methods: All BE patients at a single academic medical center who received RFA from January 2009-October 2012 were identified. Patients were included in the analysis if they achieved CR of IM, defined by the absence of endoscopic and histologic evidence of Barrett's metaplasia on initial post-ablation endoscopy, and had a minimum of two surveillance endoscopies at least three months apart. Surveillance biopsies were obtained using a modified Seattle protocol. Clinical, demographic and endoscopic data were collected. Univariate analysis using Pearson-Chi square for categorical variables and independent sample t-test for continuous variables was performed. Results: Forty-two patients (15 with non-dysplastic BE (NDBE); 13 with low grade dysplasia (LGD), 12 with high grade dysplasia (HGD) and 2 with intramucosal carcinoma) met criteria. This cohort was 71% male with a median age of 61 years (IQR 53-70). The median BE length was 3.5 cm (IQR 1-5). A median of 3 ablations (IQR 2-4) were required to achieve CR of IM, with a median follow-up period of 14 months (IQR 11-22.5). The overall IM recurrence rate was 26.2% (n=11). Recurrence was seen in 5 (33.3%) patients with NDBE, 4 (30.1%) with LGD, and 2 (18.0%) with HGD. The difference in recurrence rates between dysplasia grades was not significant (p=0.681). The median time to recurrence was 12 months (IQR 9-20). There was no recurrence of dysplasia. Twenty-eight (66.7%) patients had a smoking history. Among these smokers, 11 (39.3%) recurred. No recurrence was seen among non-smokers. The difference in recurrence rate between smokers and non-smokers was significant (p = .006). However, there was no significant difference when comparing former to active smokers (p= 0.12). Patients with recurrence had a significantly lower body mass index (BMI) compared to patients who did not recur (25.3 kgm-2 vs 29.8 kgm-2, p=0.002). Other parameters such as age, gender, race, alcohol consumption, family history of BE or esophageal cancer, initial BE length, hiatal hernia size and presence of gastroesophageal reflux symptoms were not significantly associated with recurrence. Conclusion: Recurrence after achieving CR of IM with RFA was 26.2%. These recurrences were seen exclusively in smokers, suggesting that smoking may be a risk factor. Surprisingly, patients with recurrence had a lower BMI, which may indicate that obesity is not a predisposing factor. Further studies are needed to understand these associations.
Mo1930 Beneficial Effect of Ursodeoxycholic Acid (UDCA) and Its Derivative UDCACpa in Attenuation of Functional Impairment of Esophageal Mucosa in Rat Model of Barrett's Esophagus Jolanta Majka, Rafal Pabianczyk, Gracjana Krzysiek-Maczka, Agata Ptak-Belowska, Slawomir Kwiecien, Anne-Marie Byrne, Dermot P. Kelleher, John Gilmer, Tomasz Brzozowski
Mo1929 Effect of Site Volume on Eradication of Barrett's Esophagus (BE): Results From the U.S. RFA Registry Sarina Pasricha, William J. Bulsiewicz, V. Raman Muthusamy, Srinadh Komanduri, Herbert C. Wolfsen, Ron E. Pruitt, Atilla Ertan, Gary W. Chmielewski, Nicholas J. Shaheen
Barrett,s esophagus (BE) is a pre-malignant condition in which squamous epithelium is replaced by metaplastic columnar epithelium, but the pathogenesis of this disorder should be elucidated. The secondary bile acid deoxycholic acid (DCA) contributes to the development of BE and implicated in progression of BE to adenocarcinoma, whereas UDCA has shown some protection in BE epithelial cell line in vitro. We studied effect of treatment with DCA, UDCA and the novel derivative UDCA (UDCA-CPA) on esophageal mucosal damage in rats prepared with esophagogastroduodenal anastomosis (EGDA). EGDA rats were randomly divided into 4 groups treated i.g. daily with: 1) vehicle (saline),2) DCA (20 mg/kg), 3) UDCA (40 mg/kg) or UDCA-CPA (40 mg/kg). At 8 and 12 weeks esophageal damage was evaluated by macroscopic and histological lesion index (LI), esophageal blood flow (EBF), MPO activity and malonylodialdehyde (MDA) content. mucosal expression of mRNA for caudal-related homebox gene family Cdx1 and Cdx2, COX-2, VEGF, NF κB and proinflammatory cytokines IL-1β and TNF-α was analyzed by RT-PCR. Chronic esophagitis developed in all EGDA animals and a significant decrease in EBF was observed. MPO activity and MDA content was elevated and an overexpression of Cdx2 and COX-2 were observed. In EGDA rats, extensive esophageal ulcerations, development of columnar epithelium, formation of mucus glands in squamous epithelium and intestinal metaplasia were observed. Treatment with DCA significantly enhanced LI, MPO activity and MDA content. Expression of IL-1 β and TNF-α mRNA and plasma concentration were elevated compared to vehicle. EGDA animals treated with UDCA or UDCA-CPA, exhibited significantly less macro- and microscopic esophageal injury and fewer animals developed columnar epithelium and intestinal metaplasia. Expression of NFκB was negligible in sham-control animals but strongly upregulated in esophageal mucosa of EGDA rats treated with DCA, but not in those treated with
Background: Radiofrequency ablation (RFA) may require multiple sessions for complete eradication of Barrett's esophagus (BE). The impact of case volume on safety and efficacy outcomes associated with RFA is unclear. Methods: The U.S. Barrett's RFA Patient Registry is a multi-center prospective study of patients undergoing RFA for BE from 2007 to 2012. We collected demographic data, pre- and post- treatment histology, endoscopic findings, number of RFA sessions, ablation outcomes (including complete eradication of intestinal metaplasia (CEIM), and complete eradication of dysplasia (CED)), and complications (stricture, bleeding, hospitalization). Our safety cohort consisted of patients treated with RFA, while our efficacy cohort was restricted to subjects who had a biopsy performed 12 months or more after initial treatment. We examined the effect of center volume at the time of an individual's enrollment by examining safety and efficacy outcomes based upon the number of patients treated at a center prior to an individual's enrollment in 4 patient groups (Patients 1-10, 11-20, 21-30, and more than 30). The effect of center experience on stricture, bleeding, hospitalization, and CEIM was assessed using logistic regression adjusting for age, gender, race, BE length, and presence of pretreatment dysplasia. The effect of center experience on total treatment sessions to achieve CEIM was examined using linear regression, controlling for BE length. Results: Among 5,530 patients, the number of patients treated prior to enrollment at a site was not significantly associated with the risk of stricture, GI bleeding, perforation or hospitalization (p. 0.05)(see table). There was, however, a trend toward lower rates of hospitalization with added case volume. In a multivariate logistic regression model, the odds of hospitalization decreased by 1% for each patient previously treated at
S-697
AGA Abstracts
AGA Abstracts
the center (OR 0.99, p=0.02). Center experience was not independently associated with stricture or GI bleed after controlling for age, gender, race, BE length and pre-treatment dysplasia. Among 2936 patients included in the efficacy analysis, degree of center experience at the time of an individual's treatment session was significantly associated with improvements in CEIM rate (p= 0.001) (see table), however this association dissolved in multivariable analysis after controlling for age, gender, race, length and pre-treatment dysplasia(p=0.30). Patient volume did not impact CED rates. However, case volume was independently associated with the number of treatment sessions needed to achieve CEIM, after controlling for BE length (p = 0.02; see figure). Conclusions: Increased site case volume was associated with lower hospitalization rates and fewer treatments needed to achieve CEIM but did not significantly affect rates of stricture, bleeding, or the efficacy of treatment. Safety and efficacy of RFA based on center experience prior to treatment: