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Su1127 Association of Schatzki Rings With Eosinophilic Esophagitis in Adults
Unless noted, listed as number of cases (% of included EGDs in the year). Statistical analyses performed using one-way ANOVA. Post-hoc Tukey analysis is not shown in the table. † Including manometric abnormalities of diffuse esophageal spasm, nutcracker esophagus, aperistalsis. ‡Including anastomotic strictures and marginal ulcers as well as symptomatic Type III para-esophageal hernias after prior surgical intervention. ¥Including ALS, multiple sclerosis, CVA and traumatic brain injury. Su1125 Tumor Suppressive Gene p-53 and Cell Proliferation Marker KI-67 in Children With Eosinophilic Esophagitis Awni Al-Subu, Krista L. Denning, Jenna Maynard, Pamela Thompson, Sarah E. Wellman, Yoram Elitsur
*p<0.5 vs Baseline, #p<0.5 vs IL-13 alone,&p<0.5 vs IL-4 alone Su1127
Eosinophilic esophagitis (EoE) has been recognized as a chronic disease of the esophagus in children and adults. Chronic inflammation of the esophagus may lead to malignant transformation of cells. Malignant or pre-malignant (dysplasia) conditions of the esophagus in EoE has not been reported. p53, a mutated intracellular oncogene marker, and Ki-67, a nuclear antigen associated with cell proliferation, were found to be increased in patients with Barrett's esophagus and esophageal cancer. Aim: To evaluate the presence of p53 and Ki-67 in children with EoE. Materials: Esophageal biopsies of children with EoE (Test Group), children with GERD (Control 1), adults with EoE (Control 2), adults with esophageal cancer (Control 3), and children with normal esophagus (Control 4), comprised our patient population. The immunreactivity of monoclonal oncogene p53 (DAKO, DO-7) and monoclonal Ki-67 cell marker (DAKO, Clone MIB-1) were utilized. Immunoreactivity of p53 was considered positive when at least 10% of the cells stained positive (Wang 1993). Ki-67 immunoreactivity was calculated as a percentage of positive cells per at least 500 cells (Feith 2004). Results: A total of 50 esophageal biopsies were available, 25 children with EoE, 15 children with GERD, 15 children with normal esophagus, 3 adults with EoE, and 2 adults with esophageal cancer. p53 was negative in normal mucosa but was Ki-67 positive in the basal layer (proliferative zone). Adult biopsies with esophageal cancer were positive for both markers. Immunoreactivity of p53 and Ki-67 was significantly higher in EoE vs. normal esophagus (Table). Conclusion: Oncogene p53 and Ki-67 immunoreactivity were higher in the EoE compared to the GERD and the normal group. Our data suggested an active cell proliferation in the esophagus of children with EoE and GERD. Whether the positive immunoreactivity of p53 in EoE children represents a real genetic mutation or false positive results is yet to be resolved (Rice 1994). Oncogene immunoreactivity in EoE
Association of Schatzki Rings With Eosinophilic Esophagitis in Adults Mazer R. Ally, Corinne L. Maydonovitch, Roy K. Wong, Fouad J. Moawad Introduction: Schatzki rings (SR) and Eosinophilic Esophagitis (EoE) are the two most common causes for dysphagia in adults. The pathogenesis of these entities is not completely understood, although both may be related to an underlying chronic inflammatory process. Aim: To demonstrate whether an association exists between EoE and SR. Methods: A retrospective review of adult EoE patients enrolled in a registry from 2006-2011 was performed. All patients had biopsy confirmed EoE defined as > 15 eosinophils per high power field. Patients with coexisting SR were identified and a descriptive analysis was performed comparing EoE patients with and without SR. Clinical and histological characteristics were reviewed. Statistical analysis using Fisher's exact test was used to analyze the data. Results: A total of 226 patients [mean age (SD), 41 (12) years; 80% Caucasian; 85% male] were identified, in which 80 patients (36.3 %) had a SR. EoE patients with SR were older (>65yrs) than patients without SR (44.4% vs. 39.0%, p=0.001). There were no significant differences between race or gender in patients with and without SR. There was no significant difference in patients with allergic rhinitis, asthma, dermatitis or food allergies. With endoscopic findings seen in EoE, concentric rings were more commonly associated in patients with SR (79% vs. 65%, p=0.033), however there was no difference seen with longitudinal furrows, plaques or coexisting erosive esophagitits. Patients with dysphagia or food impactions were more likely to have SR compared to patients without these symptoms, however this was not significant (38% vs. 24%, p=0.109). Of patients who underwent dilation, 46% had a SR compared to 22% without a SR (p<0.001). Hiatal hernia was more common in EoE patients with SR compared to EoE patients without SR (54% vs. 23%, p<0.001) and more commonly associated with reflux symptoms (48% vs. 19%, p=0.037). Conclusion: More than one-third of patients with EoE had SR and these patients were twice as likely to undergo an esophageal dilation. SR is often associated with GERD, however this data suggests that SR can be seen in other inflammatory esophageal disorders such as EoE. Su1128
* EoE vs. GERD; # EoE vs. Normal. Efficacy of Elimination Diet Based on Food Sensitisation Skin Testing for Adult Eosinophilic Esophagitis Javier Molina-Infante, Elisa Martin-Noguerol, Gema Vinagre Rodriguez, Moises Hernandez Alonso, Jesus M. Gonzalez-Santiago, Carmen Martinez-Alcala, Manuela Alvarado-Arenas, Soledad Jimenez-Timon, Sergio L. Porcel-Carreño, Javier Hernandez-Arbeiza
Su1126 Omeprazole Blocksth2-Cytokine-Stimulated Secretion of Eotaxin-3 in Esophageal Squamous Cells From Patients With EoE and From Patients With GERD Edaire Cheng, Xi Zhang, Xiaofang Huo, Chunhua Yu, Qiuyang Zhang, Stuart J. Spechler, Rhonda F. Souza
BACKGROUND&AIMS Dietary exclusion is an effective therapy in children given a diagnosis of eosinophilic esophagitis (EoE). However, no data are available for adults. We aimed to evaluate food sensitisation in patients with suspected EoE and to assess the efficacy of elimination diet based on allergy skin testing for EoE patients. METHODS Evaluation by different skin tests, including prick testing and fresh food prick-prick testing and atopy patch testing, was carried out in 30 patients presenting with clinical (disphagia/food impaction), endoscopic (rings, narrow caliber, exudates, furrows) and histological (≥15 eo/HPF) data
Introduction: In patients who have GERD with esophageal eosinophilia, it has been assumed that PPI therapy decreases that eosinophilia by decreasing acid reflux. Recently, it has been recognized that patients who have typical EoE symptoms and esophageal eosinophilia with
S-431
AGA Abstracts
AGA Abstracts
no evidence of GERD also can respond to PPI therapy. The mechanism underlying this “PPI-responsive esophageal eosinophilia” is not known. In earlier studies, we showed that Th2 cytokines (IL-13 and IL-4) activate the eotaxin-3 promoter and induce the secretion of eotaxin-3 (a potent eosinophil chemoattractant) in telomerase-immortalized esophageal squamous epithelial cell lines from patients with GERD or EoE. Now, we have studied the effects of Th2 cytokines on eotaxin-3 production in primary cultures of esophageal squamous cells from patients with GERD or EoE. To explore acid-independent effects of PPIs on esophageal eosinophilia, we have studied the effects of omeprazole on cytokine-stimulated eotaxin-3 production in our GERD and EoE cell lines. Methods: Primary cultures of esophageal squamous cells derived from 9 patients with EoE and 6 patients with GERD were treated for 48 hours with either IL-13 (10 ng/ml) or IL-4 (1ng/ml). Eotaxin-3 transcriptional activity was measured by an eotaxin-3 promoter (-800bp) construct attached to a luciferase reporter, and eotaxin-3 protein secretion was determined by ELISA. In separate experiments, telomerase-immortalized esophageal squamous epithelial cell lines from two patients with EoE (EoE1-T and EoE2-T) and two patients with GERD (NES-G4T and NES-B10T) were treated for 48 hours with either IL-13 (50 ng/ml) or IL-4 (10 ng/ml) in the presence or absence of acid-activated omeprazole (50 μM). Results: In primary EoE and GERD cells, both IL-13 and IL-4 markedly increased eotaxin-3 promoter activity and protein secretion. There were no significant differences between the primary EoE and GERD cells in the degree of cytokine-induced promoter activation or in the levels of cytokine-stimulated protein secretion. IL-13 and IL-4 also caused significant increases in the secretion of eotaxin-3 by all 4 telomerase-immortalized cell lines (Table), although that stimulated secretion was more pronounced in the EoE than in the GERD cell lines. In all 4 cell lines, cytokine-stimulated eotaxin-3 secretion was reduced significantly by omeprazole. Conclusions: In primary esophageal squamous epithelial cells from patients with GERD or EoE, stimulation by Th2 cytokines causes a similar degree of activation of the eotaxin-3 promoter and similar increases in eotaxin-3 protein secretion. Omeprazole blocks that cytokine-stimulated eotaxin-3 secretion in GERD and in EoE esophageal squamous cell lines. These findings suggest that, in both GERD and EoE, PPIs might have eosinophil-reducing effects that are independent of their effects on acid reflux. Eotaxin-3 Protein Secretion (pg/ml/250K cells±SEM)
*p<0.5 vs Baseline, #p<0.5 vs IL-13 alone,&p<0.5 vs IL-4 alone Su1127
Eosinophilic esophagitis (EoE) has been recognized as a chronic disease of the esophagus in children and adults. Chronic inflammation of the esophagus may lead to malignant transformation of cells. Malignant or pre-malignant (dysplasia) conditions of the esophagus in EoE has not been reported. p53, a mutated intracellular oncogene marker, and Ki-67, a nuclear antigen associated with cell proliferation, were found to be increased in patients with Barrett's esophagus and esophageal cancer. Aim: To evaluate the presence of p53 and Ki-67 in children with EoE. Materials: Esophageal biopsies of children with EoE (Test Group), children with GERD (Control 1), adults with EoE (Control 2), adults with esophageal cancer (Control 3), and children with normal esophagus (Control 4), comprised our patient population. The immunreactivity of monoclonal oncogene p53 (DAKO, DO-7) and monoclonal Ki-67 cell marker (DAKO, Clone MIB-1) were utilized. Immunoreactivity of p53 was considered positive when at least 10% of the cells stained positive (Wang 1993). Ki-67 immunoreactivity was calculated as a percentage of positive cells per at least 500 cells (Feith 2004). Results: A total of 50 esophageal biopsies were available, 25 children with EoE, 15 children with GERD, 15 children with normal esophagus, 3 adults with EoE, and 2 adults with esophageal cancer. p53 was negative in normal mucosa but was Ki-67 positive in the basal layer (proliferative zone). Adult biopsies with esophageal cancer were positive for both markers. Immunoreactivity of p53 and Ki-67 was significantly higher in EoE vs. normal esophagus (Table). Conclusion: Oncogene p53 and Ki-67 immunoreactivity were higher in the EoE compared to the GERD and the normal group. Our data suggested an active cell proliferation in the esophagus of children with EoE and GERD. Whether the positive immunoreactivity of p53 in EoE children represents a real genetic mutation or false positive results is yet to be resolved (Rice 1994). Oncogene immunoreactivity in EoE
Association of Schatzki Rings With Eosinophilic Esophagitis in Adults Mazer R. Ally, Corinne L. Maydonovitch, Roy K. Wong, Fouad J. Moawad Introduction: Schatzki rings (SR) and Eosinophilic Esophagitis (EoE) are the two most common causes for dysphagia in adults. The pathogenesis of these entities is not completely understood, although both may be related to an underlying chronic inflammatory process. Aim: To demonstrate whether an association exists between EoE and SR. Methods: A retrospective review of adult EoE patients enrolled in a registry from 2006-2011 was performed. All patients had biopsy confirmed EoE defined as > 15 eosinophils per high power field. Patients with coexisting SR were identified and a descriptive analysis was performed comparing EoE patients with and without SR. Clinical and histological characteristics were reviewed. Statistical analysis using Fisher's exact test was used to analyze the data. Results: A total of 226 patients [mean age (SD), 41 (12) years; 80% Caucasian; 85% male] were identified, in which 80 patients (36.3 %) had a SR. EoE patients with SR were older (>65yrs) than patients without SR (44.4% vs. 39.0%, p=0.001). There were no significant differences between race or gender in patients with and without SR. There was no significant difference in patients with allergic rhinitis, asthma, dermatitis or food allergies. With endoscopic findings seen in EoE, concentric rings were more commonly associated in patients with SR (79% vs. 65%, p=0.033), however there was no difference seen with longitudinal furrows, plaques or coexisting erosive esophagitits. Patients with dysphagia or food impactions were more likely to have SR compared to patients without these symptoms, however this was not significant (38% vs. 24%, p=0.109). Of patients who underwent dilation, 46% had a SR compared to 22% without a SR (p<0.001). Hiatal hernia was more common in EoE patients with SR compared to EoE patients without SR (54% vs. 23%, p<0.001) and more commonly associated with reflux symptoms (48% vs. 19%, p=0.037). Conclusion: More than one-third of patients with EoE had SR and these patients were twice as likely to undergo an esophageal dilation. SR is often associated with GERD, however this data suggests that SR can be seen in other inflammatory esophageal disorders such as EoE. Su1128
* EoE vs. GERD; # EoE vs. Normal. Efficacy of Elimination Diet Based on Food Sensitisation Skin Testing for Adult Eosinophilic Esophagitis Javier Molina-Infante, Elisa Martin-Noguerol, Gema Vinagre Rodriguez, Moises Hernandez Alonso, Jesus M. Gonzalez-Santiago, Carmen Martinez-Alcala, Manuela Alvarado-Arenas, Soledad Jimenez-Timon, Sergio L. Porcel-Carreño, Javier Hernandez-Arbeiza
Su1126 Omeprazole Blocksth2-Cytokine-Stimulated Secretion of Eotaxin-3 in Esophageal Squamous Cells From Patients With EoE and From Patients With GERD Edaire Cheng, Xi Zhang, Xiaofang Huo, Chunhua Yu, Qiuyang Zhang, Stuart J. Spechler, Rhonda F. Souza
BACKGROUND&AIMS Dietary exclusion is an effective therapy in children given a diagnosis of eosinophilic esophagitis (EoE). However, no data are available for adults. We aimed to evaluate food sensitisation in patients with suspected EoE and to assess the efficacy of elimination diet based on allergy skin testing for EoE patients. METHODS Evaluation by different skin tests, including prick testing and fresh food prick-prick testing and atopy patch testing, was carried out in 30 patients presenting with clinical (disphagia/food impaction), endoscopic (rings, narrow caliber, exudates, furrows) and histological (≥15 eo/HPF) data
Introduction: In patients who have GERD with esophageal eosinophilia, it has been assumed that PPI therapy decreases that eosinophilia by decreasing acid reflux. Recently, it has been recognized that patients who have typical EoE symptoms and esophageal eosinophilia with
S-431
AGA Abstracts
AGA Abstracts
no evidence of GERD also can respond to PPI therapy. The mechanism underlying this “PPI-responsive esophageal eosinophilia” is not known. In earlier studies, we showed that Th2 cytokines (IL-13 and IL-4) activate the eotaxin-3 promoter and induce the secretion of eotaxin-3 (a potent eosinophil chemoattractant) in telomerase-immortalized esophageal squamous epithelial cell lines from patients with GERD or EoE. Now, we have studied the effects of Th2 cytokines on eotaxin-3 production in primary cultures of esophageal squamous cells from patients with GERD or EoE. To explore acid-independent effects of PPIs on esophageal eosinophilia, we have studied the effects of omeprazole on cytokine-stimulated eotaxin-3 production in our GERD and EoE cell lines. Methods: Primary cultures of esophageal squamous cells derived from 9 patients with EoE and 6 patients with GERD were treated for 48 hours with either IL-13 (10 ng/ml) or IL-4 (1ng/ml). Eotaxin-3 transcriptional activity was measured by an eotaxin-3 promoter (-800bp) construct attached to a luciferase reporter, and eotaxin-3 protein secretion was determined by ELISA. In separate experiments, telomerase-immortalized esophageal squamous epithelial cell lines from two patients with EoE (EoE1-T and EoE2-T) and two patients with GERD (NES-G4T and NES-B10T) were treated for 48 hours with either IL-13 (50 ng/ml) or IL-4 (10 ng/ml) in the presence or absence of acid-activated omeprazole (50 μM). Results: In primary EoE and GERD cells, both IL-13 and IL-4 markedly increased eotaxin-3 promoter activity and protein secretion. There were no significant differences between the primary EoE and GERD cells in the degree of cytokine-induced promoter activation or in the levels of cytokine-stimulated protein secretion. IL-13 and IL-4 also caused significant increases in the secretion of eotaxin-3 by all 4 telomerase-immortalized cell lines (Table), although that stimulated secretion was more pronounced in the EoE than in the GERD cell lines. In all 4 cell lines, cytokine-stimulated eotaxin-3 secretion was reduced significantly by omeprazole. Conclusions: In primary esophageal squamous epithelial cells from patients with GERD or EoE, stimulation by Th2 cytokines causes a similar degree of activation of the eotaxin-3 promoter and similar increases in eotaxin-3 protein secretion. Omeprazole blocks that cytokine-stimulated eotaxin-3 secretion in GERD and in EoE esophageal squamous cell lines. These findings suggest that, in both GERD and EoE, PPIs might have eosinophil-reducing effects that are independent of their effects on acid reflux. Eotaxin-3 Protein Secretion (pg/ml/250K cells±SEM)