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Tu1878 Correlation Between Hypersensitivity Induced by Esophageal Acid Infusion and Baseline Impedance Level in Patients With Suspected Gastroesophageal Reflux
AGA Abstracts
significant difference was observed for age (mean age 52 years in both groups, p=0.922), gender (50% men vs 34%, p=0.097) and body mass index (median 25 kg/m2 vs 24.7 kg/ m2, p=0.569). Patients with typical symptoms were non-responders in 86%, those with atypical symptoms alone in 74% and those with atypical symptoms dominant in 92%. The results of pH-impedance tests were not significantly different between PPI-responders and non-responders. The prevalence of PDS was significantly higher in PPI-non responders, while the prevalence of EPS and IBS almost reach statistical significance (Table). Conclusion This study confirms that pH-impedance monitoring does not help to predict clinical response or non-response to PPI treatment. Functional digestive disorders (EBS, PDS or IBS) appear more frequent in PPI-non responders. Visceral hypersensitivity may be a predictive factor of PPI-non-response in patients with typical or atypical GERD symptoms. References 1. Zerbib et al. Aliment Pharmacol Ther 2005 2. Zerbib et al. Clin Gastroenterol Hepatol 2013 prevalence of functional digestive disorders according to PPI response
Tu1879 The Relations Between Gastroesophageal Reflux Disease and Metabolic Syndrome-Related Diseases in Japanese: A Longitudinal Study Akio Moriya, Hiroyuki Terasawa, Yoshiaki Iwasaki, Akihiro Matsumi, Hiroyuki Sakae, Manabu Fujihara, Hisae Yasuhara, Hitomi Endo, Hideki Jinno, Atsushi Imagawa, Hidenori Hata, Morihito Nakatsu, Masaharu Ando Background and aims: Several cross-sectional studies have demonstrated associations between metabolic syndrome-related diseases and gastrointestinal diseases. Focusing on gastroesophageal reflux disease (GERD), we aimed to analyze those relations in a longitudinal study. Methods: We recruited participants who voluntarily underwent esophagogastroduodenoscopy (EGD) as a part of health checkups at Mitoyo General Hospital in both 2008 and 2011. Cases taking medication for esophagitis were excluded. We performed logistic regression analysis to estimate the relations between the development or remission of GERD observed by EGD and longitudinal change (normal/development/remission/sustainment) of the following factors: overweight or obesity (BMI ≥ 25 kg/m2), abdominal obesity (according to Japanese criteria, waist circumference ≥ 85 cm for men and ≥ 90 cm for women), hypertension (blood pressure at/above 130/85 or taking medication for hypertension), dyslipidemia (HDL < 40 mg/dL, triglycerides ≥ 150 mg/dL, or taking medication for dyslipidemia), and glucose intolerance (fasting plasma glucose ≥ 110 mg/dL or taking medication for diabetes). Results: At baseline, GERD was observed in 78 out of 686 cases (11.4%). In the individual analyses, abdominal obesity, hypertension, dyslipidemia, and the male sex were risk factors for having GERD; abdominal obesity (P = 0.002) and the male sex (P = 0.003) remained statistically significant in the multivariable analysis. In the follow-up study, 80 out of 608 cases (13.2%) had newly developed GERD. Development of hypertension (OR, 2.20; 95%CI, 1.19-3.98), remission of dyslipidemia (OR, 2.74; 95%CI, 1.34-5.37), and development of glucose intolerance (OR, 2.98; 95%CI, 1.19-6.88) were associated with the development of GERD. All of them were also significant in the multivariable analysis. On the other hand, 29 out of 78 cases (37.2%) had remitted GERD. The remission of GERD was associated with the remission of abdominal obesity (OR, 6.56; 95%CI, 1.16-52.89). Conclusions: In several metabolic syndrome-related diseases, their development and remission were associated with the development and remission of GERD, respectively. In dyslipidemia, however, the remission was associated with the development of GERD.
Tu1877 Different Contractile and Relaxant Effects of Trypsin in Phasic Smooth Muscles of the Esophageal Body and the Tonic Lower Esophageal Sphincter Xiaopeng Bai, Yoshimasa Tanaka, Eikichi Ihara, Katsuya Hirano, Mayumi Hirano, Kazuhiko Nakamura, Hirotada Akiho, Ryoichi Takayanagi Background and Aim: Duodenogastroesophageal reflux of duodenal juice with trypsin is related to the pathophysiology of gastroesophageal reflux disease (Kandulski A et. al., Am J Gastroenterol 2010). Furthermore, trypsin might play a role in esophageal motility. We have previously reported unique contractile and relaxant effects of trypsin on the lower esophageal sphincter (LES) (DDW2013, Orland). It has been reported that the contractile mechanisms of phasic smooth muscles are different from those of tonic smooth muscles. The aim of the present study was to investigate how trypsin affects phasic smooth muscle of the esophageal body compared with responses to trypsin in LES. Methods: Porcine esophagi were obtained from a local slaughterhouse. Circular smooth muscle (CSM) and longitudinal smooth muscle (LSM) strips were prepared from a 10 cm portion from the oral side of the esophagogastric junction. Changes in the force were then monitored in the strips. Results: Trypsin application had no contractile or relaxant effects on LSM strips. However, in CSM strips, trypsin (100 nM to 10 μM) induced contractions in a concentration-dependent manner. The maximal contraction obtained at 10 μM (0.091 ± 0.011 gf) in CSM was significantly larger than that (0.076 ± 0.0089 gf) obtained at 1 μM in LES. As was the case with LES, trypsin induced biphasic contractile and relaxant responses at concentrations of ≥1 μM in CSM. However, the maximal relaxation obtained at 10 μM (0.053 ± 0.0153 gf) in CSM was much smaller than that (0.071 ± 0.0109 gf) in LES. Similar to LES, pretreatment with 1 μM tetrodotoxin had no effects on these responses, suggesting a direct action of trypsin on CSM. In contrast, trypsin-induced responses were completely blocked by pretreatment with the serine protease inhibitor p-APMSF. Trypsin (10 μM)-induced contractions were partially inhibited by pretreatment with 10 μM Y-27632, but not with 10 μM PD98059 or 10 μM SB203580. Conclusion: Trypsin causes transient contractions in both LES and CSM of the esophageal body at low concentrations (100-300 nM). However, at a high concentration (10 μM), trypsin induces biphasic responses and the relaxant response is predominant in LES, while the contractile effects are predominant in CSM. Furthermore, trypsin has no contractile or relaxant effects on LSM. The different contractile and relaxant effects of trypsin on LES, CSM, and LSM might play a role in physiological and/or pathophysiological esophageal motility.
Tu1880 Gastro-Oesophageal Reflux Disease - A Decade Later: Rising Prevalence in a Chinese Population Victoria P. Tan, Benjamin C Y Wong, Daniel K. Tong, Ronnie Fass Background: The prevalence of gastro-esophageal reflux disease (GERD) prevalence is consistently lower in Chinese than in Caucasian populations. Population-based data tracking the prevalence of GERD over the last decade in Chinese subjects suggests that the prevalence of GERD is rising. The prevalence and risk factors associated with an epidemiological diagnosis of GERD were examined. Prevalence rates in 2002, 2006 and 2011 were compared. Method: 3360 Chinese subjects were polled in a telephone survey using a validated GERD questionnaire and the Hospital Anxiety and Depression Scale. Prevalence rates in 2011 were compared with prevalence rates in 2002 and 2006. A sensitivity analysis was undertaken to determine whether utilization of the Montreal definition of weekly GERD versus symptomatic weekly GERD, the original definition utilized in 2002, would alter the interpretation of weekly GERD prevalence rates in 2011. Multiple logistic regression was performed to determine the risk factors associated with weekly GERD. Results: A total of 2074 subjects (mean age, 48.1 ± 18.2 years, range 18-94; 63.1% female) completed the survey (response rate 61.7%). The prevalence of GERD as defined by the Montreal definition was 3.8%. The prevalence of moderate-to-severe GERD at least daily, weekly, monthly and yearly was 0.9%, 2.8%, 6.6% and 12.5% respectively. The prevalence of weekly GERD had increased by 1.3% between 2002 and 2011, which represents an at least 50% relative increase. A diagnosis of weekly GERD was associated with non-cardiac chest pain (Odd Ratio (OR) 1.7, 95% confidence interval (CI) 1.034-2.9, P=0.037), dyspepsia (OR 5.1, 95% CI 3.0-8.8, P<0.005), an acid feeling in the stomach (OR 3.0, 95% CI 1.8-5.1) and a need to raise the pillow to sleep (OR 1.8, 95% CI 1.017-3.1, P=0.044). Variables associated with a diagnosis of GERD are similar to a decade ago. Conclusion: GERD rates in the ethnic Chinese are consistently lower than in Western populations; however these rates have risen over the last decade. Despite this, variables associated with a survey diagnosis of GERD remain ostensibly unchanged.
Tu1878 Correlation Between Hypersensitivity Induced by Esophageal Acid Infusion and Baseline Impedance Level in Patients With Suspected Gastroesophageal Reflux A Young Seo, Cheol Min Shin, Nayoung Kim, Hyuk Yoon, Young Su Park, Jin-hyeok Hwang, Dong Ho Lee Objectives: To evaluate the relevance between pH parameters and the baseline impedance level or transition zone defect (TZD) length in patients with suspected gastroesophageal reflux in relation to acid sensitivity detected by Bernstein test. Method: The recordings of 50 patients recruited at gastroenterology clinic with symptoms of heartburn, acid regurgitation, globus, or non-cardiac chest pain were analyzed. Evaluation included 24-hr multichannel intraluminal impedance-pH test while off proton pump inhibitor therapy over 1 week, high resolution manometry and Bernstein test. Also, their baseline impedance level at the most distal part of the impedance channel was assessed manually. The TZD length was measured as the vertical distance between the skeletal and smooth muscle contraction segments on Clouse plots. Result: In the study subjects (n = 50), mean age was 58.5 ± 14.0 years and 28 (56.0 %) of them were females. Nine had a DeMeester score of more than 14.7 and 14 had a symptom index positive. Bernstein test was positive only in 10 patients. Baseline impedance level inversely correlated with acid exposure % (r = - 0.621, P < 0.001). Also, all reflux time % measured by impedance monitoring showed a weak correlation with TZD length (ρ = 0.332, P = 0.018). Although Bernstein test positive has no relevance to acid exposure % or acid-related symptoms represented by DeMeester score or symptom index, respectively (all P > 0.05), baseline impedance level was significantly lower in patients with positive Bernstein test compared to those with negative Bernstein test (2569.0 ± 859.0 V vs. 1818.5 ± 870.7 V, P = 0.017). Conclusion: Lower baseline impedance level is closely related to increased esophageal acid exposure. Hypersensitivity induced by esophageal acid infusion might be attributed to acid-induced mucosal changes of the esophagus.
AGA Abstracts
Tu1881 ERK1/2 Participates in Regulating the Expression and Distribution of Tight Junction Proteins in the Process of Reflux Esophagitis Jiacheng Tan, Lin Lin OBJECTIVE: To explore the mechanisms by which the esophageal epithelial barrier is altered during the process of reflux esophagitis. METHODS: Hematoxylin-eosin (HE) staining was used to evaluate the establishment of reflux esophagitis and the severity of esophagitis. Dilated intercellular spaces (DIS) in the esophageal epithelium was observed by Transmission electron microscopy (TEM). The cellular distribution of ZO-1, occludin and claudin-1 was assessed by immunohistochemical (IHC) staining. Western blotting (WB) examined the expression levels of these TJ proteins and the phosphorylation levels of extracellular signalregulated kinase 1/2 (ERK1/2), myosin light chain (MLC) and nonmuscular myosin light chain kinase (nmMLCK). RESULTS: The procedure was confirmed successfully by HE staining. TEM examination showed that DIS occurred gradually. IHC staining showed that ZO-1, occludin and claudin-1 were incompletely expressed in the experimental group, and in some cases, no expression was observed. These studied TJ proteins were expressed in the membrane instead of the cytoplasm in many epithelial cells. Using WB, we found that the expression levels of ZO-1, occludin and claudin-1 increased gradually in the RE group (p<0.05). The phosphorylation levels of nmMLCK, MLC and ERK1/2 also increased (p<0.05). There wasn't any marked change in the sham group. CONCLUSION: In conclusion, our
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significant difference was observed for age (mean age 52 years in both groups, p=0.922), gender (50% men vs 34%, p=0.097) and body mass index (median 25 kg/m2 vs 24.7 kg/ m2, p=0.569). Patients with typical symptoms were non-responders in 86%, those with atypical symptoms alone in 74% and those with atypical symptoms dominant in 92%. The results of pH-impedance tests were not significantly different between PPI-responders and non-responders. The prevalence of PDS was significantly higher in PPI-non responders, while the prevalence of EPS and IBS almost reach statistical significance (Table). Conclusion This study confirms that pH-impedance monitoring does not help to predict clinical response or non-response to PPI treatment. Functional digestive disorders (EBS, PDS or IBS) appear more frequent in PPI-non responders. Visceral hypersensitivity may be a predictive factor of PPI-non-response in patients with typical or atypical GERD symptoms. References 1. Zerbib et al. Aliment Pharmacol Ther 2005 2. Zerbib et al. Clin Gastroenterol Hepatol 2013 prevalence of functional digestive disorders according to PPI response
Tu1879 The Relations Between Gastroesophageal Reflux Disease and Metabolic Syndrome-Related Diseases in Japanese: A Longitudinal Study Akio Moriya, Hiroyuki Terasawa, Yoshiaki Iwasaki, Akihiro Matsumi, Hiroyuki Sakae, Manabu Fujihara, Hisae Yasuhara, Hitomi Endo, Hideki Jinno, Atsushi Imagawa, Hidenori Hata, Morihito Nakatsu, Masaharu Ando Background and aims: Several cross-sectional studies have demonstrated associations between metabolic syndrome-related diseases and gastrointestinal diseases. Focusing on gastroesophageal reflux disease (GERD), we aimed to analyze those relations in a longitudinal study. Methods: We recruited participants who voluntarily underwent esophagogastroduodenoscopy (EGD) as a part of health checkups at Mitoyo General Hospital in both 2008 and 2011. Cases taking medication for esophagitis were excluded. We performed logistic regression analysis to estimate the relations between the development or remission of GERD observed by EGD and longitudinal change (normal/development/remission/sustainment) of the following factors: overweight or obesity (BMI ≥ 25 kg/m2), abdominal obesity (according to Japanese criteria, waist circumference ≥ 85 cm for men and ≥ 90 cm for women), hypertension (blood pressure at/above 130/85 or taking medication for hypertension), dyslipidemia (HDL < 40 mg/dL, triglycerides ≥ 150 mg/dL, or taking medication for dyslipidemia), and glucose intolerance (fasting plasma glucose ≥ 110 mg/dL or taking medication for diabetes). Results: At baseline, GERD was observed in 78 out of 686 cases (11.4%). In the individual analyses, abdominal obesity, hypertension, dyslipidemia, and the male sex were risk factors for having GERD; abdominal obesity (P = 0.002) and the male sex (P = 0.003) remained statistically significant in the multivariable analysis. In the follow-up study, 80 out of 608 cases (13.2%) had newly developed GERD. Development of hypertension (OR, 2.20; 95%CI, 1.19-3.98), remission of dyslipidemia (OR, 2.74; 95%CI, 1.34-5.37), and development of glucose intolerance (OR, 2.98; 95%CI, 1.19-6.88) were associated with the development of GERD. All of them were also significant in the multivariable analysis. On the other hand, 29 out of 78 cases (37.2%) had remitted GERD. The remission of GERD was associated with the remission of abdominal obesity (OR, 6.56; 95%CI, 1.16-52.89). Conclusions: In several metabolic syndrome-related diseases, their development and remission were associated with the development and remission of GERD, respectively. In dyslipidemia, however, the remission was associated with the development of GERD.
Tu1877 Different Contractile and Relaxant Effects of Trypsin in Phasic Smooth Muscles of the Esophageal Body and the Tonic Lower Esophageal Sphincter Xiaopeng Bai, Yoshimasa Tanaka, Eikichi Ihara, Katsuya Hirano, Mayumi Hirano, Kazuhiko Nakamura, Hirotada Akiho, Ryoichi Takayanagi Background and Aim: Duodenogastroesophageal reflux of duodenal juice with trypsin is related to the pathophysiology of gastroesophageal reflux disease (Kandulski A et. al., Am J Gastroenterol 2010). Furthermore, trypsin might play a role in esophageal motility. We have previously reported unique contractile and relaxant effects of trypsin on the lower esophageal sphincter (LES) (DDW2013, Orland). It has been reported that the contractile mechanisms of phasic smooth muscles are different from those of tonic smooth muscles. The aim of the present study was to investigate how trypsin affects phasic smooth muscle of the esophageal body compared with responses to trypsin in LES. Methods: Porcine esophagi were obtained from a local slaughterhouse. Circular smooth muscle (CSM) and longitudinal smooth muscle (LSM) strips were prepared from a 10 cm portion from the oral side of the esophagogastric junction. Changes in the force were then monitored in the strips. Results: Trypsin application had no contractile or relaxant effects on LSM strips. However, in CSM strips, trypsin (100 nM to 10 μM) induced contractions in a concentration-dependent manner. The maximal contraction obtained at 10 μM (0.091 ± 0.011 gf) in CSM was significantly larger than that (0.076 ± 0.0089 gf) obtained at 1 μM in LES. As was the case with LES, trypsin induced biphasic contractile and relaxant responses at concentrations of ≥1 μM in CSM. However, the maximal relaxation obtained at 10 μM (0.053 ± 0.0153 gf) in CSM was much smaller than that (0.071 ± 0.0109 gf) in LES. Similar to LES, pretreatment with 1 μM tetrodotoxin had no effects on these responses, suggesting a direct action of trypsin on CSM. In contrast, trypsin-induced responses were completely blocked by pretreatment with the serine protease inhibitor p-APMSF. Trypsin (10 μM)-induced contractions were partially inhibited by pretreatment with 10 μM Y-27632, but not with 10 μM PD98059 or 10 μM SB203580. Conclusion: Trypsin causes transient contractions in both LES and CSM of the esophageal body at low concentrations (100-300 nM). However, at a high concentration (10 μM), trypsin induces biphasic responses and the relaxant response is predominant in LES, while the contractile effects are predominant in CSM. Furthermore, trypsin has no contractile or relaxant effects on LSM. The different contractile and relaxant effects of trypsin on LES, CSM, and LSM might play a role in physiological and/or pathophysiological esophageal motility.
Tu1880 Gastro-Oesophageal Reflux Disease - A Decade Later: Rising Prevalence in a Chinese Population Victoria P. Tan, Benjamin C Y Wong, Daniel K. Tong, Ronnie Fass Background: The prevalence of gastro-esophageal reflux disease (GERD) prevalence is consistently lower in Chinese than in Caucasian populations. Population-based data tracking the prevalence of GERD over the last decade in Chinese subjects suggests that the prevalence of GERD is rising. The prevalence and risk factors associated with an epidemiological diagnosis of GERD were examined. Prevalence rates in 2002, 2006 and 2011 were compared. Method: 3360 Chinese subjects were polled in a telephone survey using a validated GERD questionnaire and the Hospital Anxiety and Depression Scale. Prevalence rates in 2011 were compared with prevalence rates in 2002 and 2006. A sensitivity analysis was undertaken to determine whether utilization of the Montreal definition of weekly GERD versus symptomatic weekly GERD, the original definition utilized in 2002, would alter the interpretation of weekly GERD prevalence rates in 2011. Multiple logistic regression was performed to determine the risk factors associated with weekly GERD. Results: A total of 2074 subjects (mean age, 48.1 ± 18.2 years, range 18-94; 63.1% female) completed the survey (response rate 61.7%). The prevalence of GERD as defined by the Montreal definition was 3.8%. The prevalence of moderate-to-severe GERD at least daily, weekly, monthly and yearly was 0.9%, 2.8%, 6.6% and 12.5% respectively. The prevalence of weekly GERD had increased by 1.3% between 2002 and 2011, which represents an at least 50% relative increase. A diagnosis of weekly GERD was associated with non-cardiac chest pain (Odd Ratio (OR) 1.7, 95% confidence interval (CI) 1.034-2.9, P=0.037), dyspepsia (OR 5.1, 95% CI 3.0-8.8, P<0.005), an acid feeling in the stomach (OR 3.0, 95% CI 1.8-5.1) and a need to raise the pillow to sleep (OR 1.8, 95% CI 1.017-3.1, P=0.044). Variables associated with a diagnosis of GERD are similar to a decade ago. Conclusion: GERD rates in the ethnic Chinese are consistently lower than in Western populations; however these rates have risen over the last decade. Despite this, variables associated with a survey diagnosis of GERD remain ostensibly unchanged.
Tu1878 Correlation Between Hypersensitivity Induced by Esophageal Acid Infusion and Baseline Impedance Level in Patients With Suspected Gastroesophageal Reflux A Young Seo, Cheol Min Shin, Nayoung Kim, Hyuk Yoon, Young Su Park, Jin-hyeok Hwang, Dong Ho Lee Objectives: To evaluate the relevance between pH parameters and the baseline impedance level or transition zone defect (TZD) length in patients with suspected gastroesophageal reflux in relation to acid sensitivity detected by Bernstein test. Method: The recordings of 50 patients recruited at gastroenterology clinic with symptoms of heartburn, acid regurgitation, globus, or non-cardiac chest pain were analyzed. Evaluation included 24-hr multichannel intraluminal impedance-pH test while off proton pump inhibitor therapy over 1 week, high resolution manometry and Bernstein test. Also, their baseline impedance level at the most distal part of the impedance channel was assessed manually. The TZD length was measured as the vertical distance between the skeletal and smooth muscle contraction segments on Clouse plots. Result: In the study subjects (n = 50), mean age was 58.5 ± 14.0 years and 28 (56.0 %) of them were females. Nine had a DeMeester score of more than 14.7 and 14 had a symptom index positive. Bernstein test was positive only in 10 patients. Baseline impedance level inversely correlated with acid exposure % (r = - 0.621, P < 0.001). Also, all reflux time % measured by impedance monitoring showed a weak correlation with TZD length (ρ = 0.332, P = 0.018). Although Bernstein test positive has no relevance to acid exposure % or acid-related symptoms represented by DeMeester score or symptom index, respectively (all P > 0.05), baseline impedance level was significantly lower in patients with positive Bernstein test compared to those with negative Bernstein test (2569.0 ± 859.0 V vs. 1818.5 ± 870.7 V, P = 0.017). Conclusion: Lower baseline impedance level is closely related to increased esophageal acid exposure. Hypersensitivity induced by esophageal acid infusion might be attributed to acid-induced mucosal changes of the esophagus.
AGA Abstracts
Tu1881 ERK1/2 Participates in Regulating the Expression and Distribution of Tight Junction Proteins in the Process of Reflux Esophagitis Jiacheng Tan, Lin Lin OBJECTIVE: To explore the mechanisms by which the esophageal epithelial barrier is altered during the process of reflux esophagitis. METHODS: Hematoxylin-eosin (HE) staining was used to evaluate the establishment of reflux esophagitis and the severity of esophagitis. Dilated intercellular spaces (DIS) in the esophageal epithelium was observed by Transmission electron microscopy (TEM). The cellular distribution of ZO-1, occludin and claudin-1 was assessed by immunohistochemical (IHC) staining. Western blotting (WB) examined the expression levels of these TJ proteins and the phosphorylation levels of extracellular signalregulated kinase 1/2 (ERK1/2), myosin light chain (MLC) and nonmuscular myosin light chain kinase (nmMLCK). RESULTS: The procedure was confirmed successfully by HE staining. TEM examination showed that DIS occurred gradually. IHC staining showed that ZO-1, occludin and claudin-1 were incompletely expressed in the experimental group, and in some cases, no expression was observed. These studied TJ proteins were expressed in the membrane instead of the cytoplasm in many epithelial cells. Using WB, we found that the expression levels of ZO-1, occludin and claudin-1 increased gradually in the RE group (p<0.05). The phosphorylation levels of nmMLCK, MLC and ERK1/2 also increased (p<0.05). There wasn't any marked change in the sham group. CONCLUSION: In conclusion, our
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