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Sa1860 Serum Pepsinogens for Detection of Fundic Gastric Atrophy in Subjects With Autoimmune Thyroid Disease
support a role for metformin, at least as assessed by surrogate markers, for chemoprevention in patients with BE. Clinical trial registration number NCT01447927.
AGA Abstracts
Sa1860 Serum Pepsinogens for Detection of Fundic Gastric Atrophy in Subjects With Autoimmune Thyroid Disease Marino Venerito, Marcus Radünz, Kirsten Reschke, Peter R. Mertens, Francesco Di Mario, Peter Malfertheiner
Sa1858
Background: Autoimmune gastritis (AIG) leads to fundic gastric atrophy (FGA), a condition that increases the risk for gastric cancer. The prevalence of AIG is high among subjects with autoimmune thyroid disease (ATD). Aim: In this case-controlled study we evaluate the usefulness of serum pepsinogens for screening of FGA among subjects with ATD. Methods: Patients with known or newly diagnosed ATD (cases) and goitre (controls) presenting to the Department of Gastroenterology, Hepatology and Infectious Diseases and to the Department of Nephrology and Hypertension, Diabetes and Endocrinology of the Otto-von-Guericke University Hospital from October 2012 to October 2013 were enrolled in the study. Pepsinogen (PG)-I levels ≤ 25 μg/mL and PGI/II ratio ≤ 3 were indicative for FGA. Serum antiHelicobacter pylori (H. pylori) IgG antibody titers were also determined. Upper endoscopy was offered to subjects with serological FGA and histological FGA stage was assessed by OLGA. Results: 23 patients with ATD (17 with Hashimoto thyroiditis and 6 with Graves` disease), and 21 controls with goitre were enrolled. The majority of subjects were female, and subjects with ATD were younger than controls (mean age 56.6 ± 13.4 and 67.9 ± 12.8 years in cases and controls, respectively, p<0.05). Serological prevalence of H. pylori infection in cases and controls was 13.6% and 28.6%, respectively. Serological FGA was present only in cases with AITD (5/23, 21.8%). None of the patients with FGA had serological evidence of H. pylori Iinfection. One patient with serological FGA has not yet received endoscopy. In all other cases FGA was confirmed by histology. OLGA stage was II in 3 out of 4 cases and III in 1 case. Conclusions: Serum pepsinogens are useful for serological screening of FGA among patients with ATD and may have an impact on patient management.
High Prevalence of Barrett's Esophagus and Histological Inflammatory Changes in Patients With Esophageal Atresia Manon C. Spaander, Nicole W. van Beelen, Eleonore Dandrieu, Frédéric Gottrand, Laurent Michaud, Katharina Biermann, Marco J. Bruno, Rene M. Wijnen, Hanneke IJsselstijn Background After repair of esophageal atresia (EA) in newborns, gastroesophageal reflux (GER) is reported in 25-62% of cases during follow-up. The high incidence of GER and extended survival among individuals with repaired EA, raises concerns about the possibility of an increased risk of Barrett's esophagus and esophageal cancer. Incidence of Barrett's esophagus amongst adults in the general population is 2% and Barrett's is predominantly diagnosed in middle-aged males at an average of 55 years. In this multicenter follow-up study we assessed the prevalence of GER and Barrett's esophagus after EA repair. Methods EA can be classified according to the anatomic Gross classification: Type A: EA without tracheoesophageal fistula (TEF), type B: EA with proximal TEF, type C: EA with distal TEF (most common type) and type D: EA with proximal and distal TEF. Since 2011 all patients (age >16) that have a history of EA repair are invited for gastroscopy with random biopsies of the distal esophagus at the level of the gastro-esophageal junction (GEJ) and standard 4quadrant biopsies in case of Barrett's epithelium. All clinical, endoscopic and histological data are prospectively registered in a dedicated database. Results To date, a total of 74 patients (55% male) with a median age of 21 years (range 16-57 years) underwent a gastroscopy. Type of EA according to the Gross classification: type A was found in 6 (8%)patients, type C in 60 (81%) patients, type D in 4 (5%) and in 4 (5%) patients it was unknown. Twenty-four (32%) patients had a history of anti-reflux surgery, 8 patients (11%) used PPI and 24 patients (32%) had complaints of GER. Endoscopic findings were reflux esophagitis in 13 patients (18%), Barrett's esophagus in 14 patients (19%) with a maximal circumferential length of 4 cm, and inlet patch with gastric metaplasia in 6 patients (8%). In 42 patients (57%) no endoscopic abnormalities were found. Histology revealed Barrett's esophagus (BE) in 14 patients (19%), all without dysplasia, with a median age of 18 years (range 16- 51 years), 9 (64%) of whom were males. Chronic inflammation was seen in 36 (49%) patients and active esophagitis in 17 (23%). Inflammatory changes were absent in only 6 (8%) patients. One patient had developed squamous cell carcinoma (SCC) of the esophagus at the age of 44 years. Conclusion Almost all patients after EA repair have histological inflammatory abnormalities at the GEJ. The prevalence of Barrett' s esophagus is markedly increased after EA repair by almost a factor 10 and Barrett's is present at a much younger age compared to the general population. These observations may signify important and relevant clinical implications including the use of PPI after EA repair to mitigate development of (pre)neoplastic changes and life-long endoscopic follow-up to facilitate early diagnosis of clinically relevant lesions.
Sa1861 Antimicrobial Susceptibility and Virulence Factors in Two Populations in Contrast With Gastric Cancer Risk in Southwestern Colombia Alvaro J. Pazos, Luis E. Bravo, Mercedes . Figueroa BACKGROUND: The resistance of H. pylori to antibiotics used for its treatment focuses on the role of virulence and eradication of infection as a valid strategy for chemoprevention of gastric cancer (GC). It was reported that the infection for avirulent strains resistant to clarithromycin and amoxicillin are related to low rates of eradication. OBJECTIVE: To determine the association between the antibiotic susceptibility and virulence markers, depending on the type of gastritis in two Colombian populations with contrasting GC risk: Túquerres high risk and Tumaco: low risk. The hypothesis states that no virulent genotypes are associated with antibiotic resistance in patients with low risk of GC. METHODS: There were obtained gastric mucosal biopsies of 409 adult patients for histological evaluation, isolation of H. pylori antimicrobial susceptibility studies and determination of genotypes by PCR cagA and vacA virulence. The Fisher and χ2 allowed evaluating the relationship between sensitivity and virulence. RESULTS: The prevalence of resistance of H. pylori to amoxicillin and clarithromycin was significantly higher in Túquerres than Tumaco (22,8% and 20,5%) vs. (5,4% and 3,4%). The in vitro diagnosis of antimicrobial resistance does not predict the therapeutic failure of the H. pylori treatment (Kappa -0,037). CONCLUSIONS: There is a relationship between antibiotic resistance and virulence of the bacterium. The prevalence of resistance of H. pylori to clarithromycin and amoxicillin was significantly higher in nonvirulent isolates compared with virulent isolates.
Sa1859 Randomized Double Blind Placebo Controlled Phase II Trial of Barrett's Esophagus Chemoprevention With Metformin Amitabh Chak, Navtej Buttar, Nathan R. Foster, Drew K. Seisler, Norman E. Marcon, Robert E. Schoen, Marcia R. Cruz-Correa, Gary W. Falk, Prateek Sharma, Chin Hur, Anamay N. Sharma, Anushka Baruah, Sonia Chowdhury, Sarah Kossak, L. M. Rodriguez, Ellen Richmond, Sumithra Mandrekar, Paul J. Limburg
Sa1862
Background & Aims: Observational studies suggest that metformin is protective against obesity associated cancers. We conducted a randomized, double-blind, placebo-controlled, phase 2 trial to assess the effect of metformin (vs. placebo) in participants with Barrett's Esophagus (BE) with no dysplasia or low-grade dysplasia. Phosphorylated S6 kinase (pS6K1) was selected as a biomarker because this substrate of MTOR is a common molecular mediator of the insulin pathway as well as the AMPK pathway. The primary aim was to compare the percent change in the mean pS6K1 immunostaining from baseline to 12 weeks for metformin vs. placebo. Methods: Participants were recruited through the multicenter Cancer Prevention Network and randomly assigned to either metformin or placebo, where oral doses were given in an escalating fashion from 500 mg/day for week 1 up to 2000 mg/day by week 4 for a full 12 week intervention period. We collected esophageal biopsy specimens before and after the intervention period to determine the percent change in mean pS6K1 (the primary endpoint). Secondary endpoints compared baseline characteristics, agent adherence, adverse events (AEs), and changes in cell proliferation (Ki-67) and apoptosis (caspase-3) in the epithelium between intervention arms. The study yielded 84% power to detect at least a 35% decrease in the metformin arm as compared to placebo, using a 1-sided test with a significance level of 0.05. Results: Based on data from 74 participants, mean age = 58.7 years, 58 (78% ) men, 52 (70.3%) with circumferential BE > 5 cm, that were randomized and received study intervention (38-metformin, 36-placebo), baseline characteristics and agent adherence rates were similar between the 2 randomization arms. Treatment related AEs were similar for metformin vs. placebo (50% vs. 36%, p=0.25) and all but one AE were Grade 1 or 2. In the 69 participants that were evaluable for the primary endpoint, the percent change from baseline in tissue concentration of pS6K1 was similar for metformin vs. placebo (median = 1.4% vs. -14.7%, 1-sided p=0.80). Similar non-significant results were obtained when assessing absolute change (1-sided p=0.72). There were also no differences in cell proliferation or apoptosis in Barrett's epithelium as assayed by Ki-67 and caspase-3 immunohistochemistry when comparing metformin to placebo. Conclusions: In BE patients, short-term intervention with metformin appears to be safe but without a demonstrable effect on pS6K1 as compared to placebo. Metformin therapy also does not significantly alter proliferation or apoptosis in Barrett's epithelium. The findings of this short-term study do not
AGA Abstracts
Are All Patients With Histological Diagnosis of Atrophic Gastritis Really At Risk of Developing Gastric Cancer? Assessment of Gastric Acid Production by Correlation Between Maximal Acid Output and Pepsinogen I Francesco Di Mario, Hunor Pal Farkas, Francesco Ferrara, Nadia Dal Bo, Tiziana Slongo, Roberto Marcello, Stefania Liatopoulou, Alessandro Gnocchi, Vincenzo Corrente, Anna Bertele', Massimo Rugge, Carmelo Scarpignato Background: Gastric atrophy, which is believed to be a precursor for intestinal type gastric cancer, results in loss of parietal cell mass which manifests itself in reduced or absent gastric acid secretion. Increase in gastric pH may permits colonization of the stomach by bacteria which are capable of converting dietary nitrates to potent mutagenic N-nitroso compounds, consequently atrophic gastritis (AG) is associated with an increased risk of both cardia and non-cardia gastric adenocarcinomas. The gold standard for measuring gastric acid secretion remains the invasive method that involves aspiration of gastric content after pharmacological stimulation. In contrast serum pepsinogens are regarded as alternative, non-invasive, but reliable gastric secretory parameters, potential screening tools to detect patients at risk of developing gastric cancer. Aim: The aim of our study is to assess the usefulness of serum biomarkers in evaluating gastric cancer risk in patients with AG by correlation with the stomach's secretory function. Material and methods: A total of 42 subjects (18 male) were included in the study, aged between 41 and 71 years (mean: 53.7 years) and diagnosed with histologically confirmed AG (22 autoimmune). Fasting levels of pepsinogen I (sPGI), pepsinogen II and gastrin17 were measured as well as maximal acid output (MAO). Resulting data was statistically evaluated. Results: Patients were subdivided in groups with achlorhydria (64.3%) and normal gastric function according to MAO values. Statistically significant differences were found between these groups regarding both pepsinogen and gastrin 17 levels. Significant correlation was found between sPGI and MAO (Spearman r=0.782). A ROC curve identified the best sPGI cut-off point of 30 μg/L for the diagnosis of achlorhydria with a sensitivity of 100% (95% CI: 87.11-100), specificity of 93.33% (CI: 67.98-98.89) and negative predictive value of 100% (CI: 76.66-100). Conclusions: There is a correlation
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AGA Abstracts
Sa1860 Serum Pepsinogens for Detection of Fundic Gastric Atrophy in Subjects With Autoimmune Thyroid Disease Marino Venerito, Marcus Radünz, Kirsten Reschke, Peter R. Mertens, Francesco Di Mario, Peter Malfertheiner
Sa1858
Background: Autoimmune gastritis (AIG) leads to fundic gastric atrophy (FGA), a condition that increases the risk for gastric cancer. The prevalence of AIG is high among subjects with autoimmune thyroid disease (ATD). Aim: In this case-controlled study we evaluate the usefulness of serum pepsinogens for screening of FGA among subjects with ATD. Methods: Patients with known or newly diagnosed ATD (cases) and goitre (controls) presenting to the Department of Gastroenterology, Hepatology and Infectious Diseases and to the Department of Nephrology and Hypertension, Diabetes and Endocrinology of the Otto-von-Guericke University Hospital from October 2012 to October 2013 were enrolled in the study. Pepsinogen (PG)-I levels ≤ 25 μg/mL and PGI/II ratio ≤ 3 were indicative for FGA. Serum antiHelicobacter pylori (H. pylori) IgG antibody titers were also determined. Upper endoscopy was offered to subjects with serological FGA and histological FGA stage was assessed by OLGA. Results: 23 patients with ATD (17 with Hashimoto thyroiditis and 6 with Graves` disease), and 21 controls with goitre were enrolled. The majority of subjects were female, and subjects with ATD were younger than controls (mean age 56.6 ± 13.4 and 67.9 ± 12.8 years in cases and controls, respectively, p<0.05). Serological prevalence of H. pylori infection in cases and controls was 13.6% and 28.6%, respectively. Serological FGA was present only in cases with AITD (5/23, 21.8%). None of the patients with FGA had serological evidence of H. pylori Iinfection. One patient with serological FGA has not yet received endoscopy. In all other cases FGA was confirmed by histology. OLGA stage was II in 3 out of 4 cases and III in 1 case. Conclusions: Serum pepsinogens are useful for serological screening of FGA among patients with ATD and may have an impact on patient management.
High Prevalence of Barrett's Esophagus and Histological Inflammatory Changes in Patients With Esophageal Atresia Manon C. Spaander, Nicole W. van Beelen, Eleonore Dandrieu, Frédéric Gottrand, Laurent Michaud, Katharina Biermann, Marco J. Bruno, Rene M. Wijnen, Hanneke IJsselstijn Background After repair of esophageal atresia (EA) in newborns, gastroesophageal reflux (GER) is reported in 25-62% of cases during follow-up. The high incidence of GER and extended survival among individuals with repaired EA, raises concerns about the possibility of an increased risk of Barrett's esophagus and esophageal cancer. Incidence of Barrett's esophagus amongst adults in the general population is 2% and Barrett's is predominantly diagnosed in middle-aged males at an average of 55 years. In this multicenter follow-up study we assessed the prevalence of GER and Barrett's esophagus after EA repair. Methods EA can be classified according to the anatomic Gross classification: Type A: EA without tracheoesophageal fistula (TEF), type B: EA with proximal TEF, type C: EA with distal TEF (most common type) and type D: EA with proximal and distal TEF. Since 2011 all patients (age >16) that have a history of EA repair are invited for gastroscopy with random biopsies of the distal esophagus at the level of the gastro-esophageal junction (GEJ) and standard 4quadrant biopsies in case of Barrett's epithelium. All clinical, endoscopic and histological data are prospectively registered in a dedicated database. Results To date, a total of 74 patients (55% male) with a median age of 21 years (range 16-57 years) underwent a gastroscopy. Type of EA according to the Gross classification: type A was found in 6 (8%)patients, type C in 60 (81%) patients, type D in 4 (5%) and in 4 (5%) patients it was unknown. Twenty-four (32%) patients had a history of anti-reflux surgery, 8 patients (11%) used PPI and 24 patients (32%) had complaints of GER. Endoscopic findings were reflux esophagitis in 13 patients (18%), Barrett's esophagus in 14 patients (19%) with a maximal circumferential length of 4 cm, and inlet patch with gastric metaplasia in 6 patients (8%). In 42 patients (57%) no endoscopic abnormalities were found. Histology revealed Barrett's esophagus (BE) in 14 patients (19%), all without dysplasia, with a median age of 18 years (range 16- 51 years), 9 (64%) of whom were males. Chronic inflammation was seen in 36 (49%) patients and active esophagitis in 17 (23%). Inflammatory changes were absent in only 6 (8%) patients. One patient had developed squamous cell carcinoma (SCC) of the esophagus at the age of 44 years. Conclusion Almost all patients after EA repair have histological inflammatory abnormalities at the GEJ. The prevalence of Barrett' s esophagus is markedly increased after EA repair by almost a factor 10 and Barrett's is present at a much younger age compared to the general population. These observations may signify important and relevant clinical implications including the use of PPI after EA repair to mitigate development of (pre)neoplastic changes and life-long endoscopic follow-up to facilitate early diagnosis of clinically relevant lesions.
Sa1861 Antimicrobial Susceptibility and Virulence Factors in Two Populations in Contrast With Gastric Cancer Risk in Southwestern Colombia Alvaro J. Pazos, Luis E. Bravo, Mercedes . Figueroa BACKGROUND: The resistance of H. pylori to antibiotics used for its treatment focuses on the role of virulence and eradication of infection as a valid strategy for chemoprevention of gastric cancer (GC). It was reported that the infection for avirulent strains resistant to clarithromycin and amoxicillin are related to low rates of eradication. OBJECTIVE: To determine the association between the antibiotic susceptibility and virulence markers, depending on the type of gastritis in two Colombian populations with contrasting GC risk: Túquerres high risk and Tumaco: low risk. The hypothesis states that no virulent genotypes are associated with antibiotic resistance in patients with low risk of GC. METHODS: There were obtained gastric mucosal biopsies of 409 adult patients for histological evaluation, isolation of H. pylori antimicrobial susceptibility studies and determination of genotypes by PCR cagA and vacA virulence. The Fisher and χ2 allowed evaluating the relationship between sensitivity and virulence. RESULTS: The prevalence of resistance of H. pylori to amoxicillin and clarithromycin was significantly higher in Túquerres than Tumaco (22,8% and 20,5%) vs. (5,4% and 3,4%). The in vitro diagnosis of antimicrobial resistance does not predict the therapeutic failure of the H. pylori treatment (Kappa -0,037). CONCLUSIONS: There is a relationship between antibiotic resistance and virulence of the bacterium. The prevalence of resistance of H. pylori to clarithromycin and amoxicillin was significantly higher in nonvirulent isolates compared with virulent isolates.
Sa1859 Randomized Double Blind Placebo Controlled Phase II Trial of Barrett's Esophagus Chemoprevention With Metformin Amitabh Chak, Navtej Buttar, Nathan R. Foster, Drew K. Seisler, Norman E. Marcon, Robert E. Schoen, Marcia R. Cruz-Correa, Gary W. Falk, Prateek Sharma, Chin Hur, Anamay N. Sharma, Anushka Baruah, Sonia Chowdhury, Sarah Kossak, L. M. Rodriguez, Ellen Richmond, Sumithra Mandrekar, Paul J. Limburg
Sa1862
Background & Aims: Observational studies suggest that metformin is protective against obesity associated cancers. We conducted a randomized, double-blind, placebo-controlled, phase 2 trial to assess the effect of metformin (vs. placebo) in participants with Barrett's Esophagus (BE) with no dysplasia or low-grade dysplasia. Phosphorylated S6 kinase (pS6K1) was selected as a biomarker because this substrate of MTOR is a common molecular mediator of the insulin pathway as well as the AMPK pathway. The primary aim was to compare the percent change in the mean pS6K1 immunostaining from baseline to 12 weeks for metformin vs. placebo. Methods: Participants were recruited through the multicenter Cancer Prevention Network and randomly assigned to either metformin or placebo, where oral doses were given in an escalating fashion from 500 mg/day for week 1 up to 2000 mg/day by week 4 for a full 12 week intervention period. We collected esophageal biopsy specimens before and after the intervention period to determine the percent change in mean pS6K1 (the primary endpoint). Secondary endpoints compared baseline characteristics, agent adherence, adverse events (AEs), and changes in cell proliferation (Ki-67) and apoptosis (caspase-3) in the epithelium between intervention arms. The study yielded 84% power to detect at least a 35% decrease in the metformin arm as compared to placebo, using a 1-sided test with a significance level of 0.05. Results: Based on data from 74 participants, mean age = 58.7 years, 58 (78% ) men, 52 (70.3%) with circumferential BE > 5 cm, that were randomized and received study intervention (38-metformin, 36-placebo), baseline characteristics and agent adherence rates were similar between the 2 randomization arms. Treatment related AEs were similar for metformin vs. placebo (50% vs. 36%, p=0.25) and all but one AE were Grade 1 or 2. In the 69 participants that were evaluable for the primary endpoint, the percent change from baseline in tissue concentration of pS6K1 was similar for metformin vs. placebo (median = 1.4% vs. -14.7%, 1-sided p=0.80). Similar non-significant results were obtained when assessing absolute change (1-sided p=0.72). There were also no differences in cell proliferation or apoptosis in Barrett's epithelium as assayed by Ki-67 and caspase-3 immunohistochemistry when comparing metformin to placebo. Conclusions: In BE patients, short-term intervention with metformin appears to be safe but without a demonstrable effect on pS6K1 as compared to placebo. Metformin therapy also does not significantly alter proliferation or apoptosis in Barrett's epithelium. The findings of this short-term study do not
AGA Abstracts
Are All Patients With Histological Diagnosis of Atrophic Gastritis Really At Risk of Developing Gastric Cancer? Assessment of Gastric Acid Production by Correlation Between Maximal Acid Output and Pepsinogen I Francesco Di Mario, Hunor Pal Farkas, Francesco Ferrara, Nadia Dal Bo, Tiziana Slongo, Roberto Marcello, Stefania Liatopoulou, Alessandro Gnocchi, Vincenzo Corrente, Anna Bertele', Massimo Rugge, Carmelo Scarpignato Background: Gastric atrophy, which is believed to be a precursor for intestinal type gastric cancer, results in loss of parietal cell mass which manifests itself in reduced or absent gastric acid secretion. Increase in gastric pH may permits colonization of the stomach by bacteria which are capable of converting dietary nitrates to potent mutagenic N-nitroso compounds, consequently atrophic gastritis (AG) is associated with an increased risk of both cardia and non-cardia gastric adenocarcinomas. The gold standard for measuring gastric acid secretion remains the invasive method that involves aspiration of gastric content after pharmacological stimulation. In contrast serum pepsinogens are regarded as alternative, non-invasive, but reliable gastric secretory parameters, potential screening tools to detect patients at risk of developing gastric cancer. Aim: The aim of our study is to assess the usefulness of serum biomarkers in evaluating gastric cancer risk in patients with AG by correlation with the stomach's secretory function. Material and methods: A total of 42 subjects (18 male) were included in the study, aged between 41 and 71 years (mean: 53.7 years) and diagnosed with histologically confirmed AG (22 autoimmune). Fasting levels of pepsinogen I (sPGI), pepsinogen II and gastrin17 were measured as well as maximal acid output (MAO). Resulting data was statistically evaluated. Results: Patients were subdivided in groups with achlorhydria (64.3%) and normal gastric function according to MAO values. Statistically significant differences were found between these groups regarding both pepsinogen and gastrin 17 levels. Significant correlation was found between sPGI and MAO (Spearman r=0.782). A ROC curve identified the best sPGI cut-off point of 30 μg/L for the diagnosis of achlorhydria with a sensitivity of 100% (95% CI: 87.11-100), specificity of 93.33% (CI: 67.98-98.89) and negative predictive value of 100% (CI: 76.66-100). Conclusions: There is a correlation
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