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T1988 Short Segment Acid Reflux: Characterization with 24-Hour Esophageal Impedance-Double pH Monitoring
T1985
all three methods were negative, infection was considered negative. Erosive reflux disease (ERD) was defined as the presence of mucosal breaks in the esophagus. Subjects who had no mucosal breaks but complained of mild symptoms occurring two or more days a week, or moderate/severe symptoms occurring more than one day a week, were considered to have non-erosive reflux disease (NERD). RESULTS: Of the 678 subjects, 52 (7.7%) had ERD, 148 (21.8%) NERD, and 478 (70.5%) were normal. The prevalence of H. pylori infection was 17.6% in subjects with ERD, 18.2% with NERD, and 14.2% in normal ones, respectively; no significant differences were observed among the three groups (chi-square test). Of the 52 subjects with ERD, only 17 (32.7%) complained of typical symptoms, whereas 35 (67.3%) complained of fewer or no symptoms: The prevalence of H. pylori infection in these two subgroups was 17.6% and 20.0%, respectively, with no significant difference. CONCLUSION: H. pylori infection is not involved in the pathogenesis of both ERD and NERD in a young Japanese population in their 20s. It is postulated that in this population H. pylori-associated corpus gastritis and/or mucosal atrophy is not so extended, and so, gastric acid secretion, one of the most important aggressive factors in the esophageal mucosa, is not significantly decreased.
AGA Abstracts
Differential Gene Expression in the Duodenum May Contribute to Symptom Generation in GERD Durk Vries, de, Jose ter Linde, Margot A. van Herwaarden, Matthijs P. Schwartz, André Smout, Melvin Samsom Background: Signaling from the duodenum affects TLESR frequency, lower esophageal sphincter pressure and esophageal perception. Despite the putative role of the duodenum in the pathophysiology of gastroesophageal reflux disease (GERD), information regarding abnormalities in gene expression underlying altered sensorimotor function of the esophagus is lacking. Aim: Identify genes differentially expressed in duodenal biopsies from GERD patients as compared to healthy volunteers (HVs). Materials and methods: 20 symptomatic GERD patients (10 M/F, mean age 52) with a total 24-hour acid exposure of 6-12% and a SAP ≥95% were selected from recent pH-metry referrals. Patients with a history of organic disease and/or surgery affecting upper GI tract sensitivity and/or motility were excluded. Ten patients discontinued PPI treatment and ten patients took a maximum dose of PPI, both two weeks prior to sampling. In addition, ten age- and sex-matched HVs without gastrointestinal symptoms were recruited from the general population. During upper GI endoscopy mucosal biopsies were taken in the pars descendens of the duodenum and snapfrozen in liquid nitrogen. RNA was extracted and profiled on Affymetrix Human Genome U133 Plus 2.0 array. Genes exhibiting a fold change >1.4 (t-test p-value <1E-4) were considered differentially expressed. A subset of 21 differentially expressed genes was selected for confirmatory RT-PCR using TaqMan low density arrays. Results: Whole genome expression profiling revealed that 20 and 22 genes were higher respectively lower expressed in GERD patients off PPIs relative to HVs. In GERD patients on PPIs 34 upregulated and 5 downregulated genes were found, taking HVs as a reference. An overlap of 22 differentially expressed genes was observed between the two patient groups. The majority of the upregulated genes was associated with lipid absorption, particularly triglyceride resynthesis and intracellular vesicular transport, which are rate-limiting processes for chylomicron production and secretion. Differential expression of nine upregulated genes was confirmed by RT-PCR and three genes showed a trend towards significance. Conclusion: Our results suggest that in GERD patients chylomicron production and secretion is enhanced. Consequently, the release of apoA-IV, a signaling component derived from chylomicrons, may be higher. The subsequent potentially increased release of CCK may cause heightened activation of duodenal extrinsic primary afferents. Thus, the differences in gene expression identified may underlie a mechanism by which duodenal signaling intensifies the perception of symptoms induced by gastroesophageal reflux.
T1988 Short Segment Acid Reflux: Characterization with 24-Hour Esophageal Impedance-Double pH Monitoring Adriana Lazarescu, Raf Bisschops, Ingrid Demedts, Jan F. Tack, Guido N. Tytgat, Daniel Sifrim Background: Recent studies measuring esophageal pH at 1 cm proximal to the squamocolumnar junction (SCJ) have described the occurrence of a large number of short segment acid reflux episodes (pH drops below 4, observed at 1cm, but not at 5cm above SCJ). The aim of this study was to further characterize short segment acid reflux with impedance-double pH monitoring. Methods: Endoscopy and 24h impedance-double pH monitoring were performed “off” PPI in 18 patients (7 males, median age 43 (25-73)) to confirm the diagnosis of gastroesophageal reflux disease (GERD). During endoscopy, the distal tip of an impedancedouble pH catheter (Sandhill) was clipped to the esophageal mucosa with the distal pH sensor located at 1cm and the proximal pH sensor at 5 cm above the SCJ. Impedance was measured at 3, 5, 7, 9, 15 and 17 cm above the SCJ. Results: Based on endoscopy and conventional analysis of pHmetry, reflux disease was confirmed in 11/18 patients (6 with erosive esophagitis and 5 with NERD). Four hundred and twenty eight short acid reflux episodes were identified. One hundred and eighty four (43%) of these fulfilled the impedance diagnostic criteria of weakly acidic reflux (impedance retrograde drop in at least the two most distal channels with pH at 5 cm between 4-7). However, 244 (57%) short segment acid reflux episodes were not associated with typical impedance liquid reflux events. These included 115 (47.1%) episodes without any impedance change, 102 (41.8%) episodes with gas-only reflux (belches), and 27 (11.1%) with impedance changes (compatible with liquid) in only the most distal channel (3cm). Short segment acid reflux was rarely associated with typical symptoms. However, gas-only reflux (belches) was more often associated with regurgitation than heartburn, while short acid reflux with no impedance changes was associated only with heartburn. Conclusions: We confirmed the frequent occurrence of short acid reflux episodes. They are oligo-symptomatic. Half of them are associated with less acidic liquid retrograde flow in the esophageal body and the other half occurs with belching or small liquid volume restricted to the very distal esophagus.
T1986 Helicobacter Is An Independent Protective Factor for Erosive Esophagitis Su Youn Nam, Il Ju Choi, Kyung woo Park, Byung Chang Kim, Kum Hei Ryu BACKGROUND Although many case-control studies have suggested that Helicobacter pylori infection may decrease the risk for reflux esophagitis or Barrett's esophagus, any large scale population-based study adjusting many confounding factors has not been issued. METHODS A total of 11,800 healthy subjects who underwent routine check-up in the National Cancer Center from October 2003 to May 2007 were enrolled. The status of Helicobacter pylori infection was evaluated by rapid urease test. It has been adjusted for age, sex, body mass index, smoking status, alcohol intake, hiatal hernia, duodenal ulcer, dietary intake, current medication, and chronic disease. We used logistic regression models to evaluate the association between Helicobacter infection and erosive esophagitis. RESULTS The prevalence was 4.9% (576/11,800) in reflux esophagitis defined as LA classification. While the prevalence of reflux esophagitis was 6.5% (383/5854) in the subjects without Helicobacter infection, it was 3.2% (193/5946) in the subjects with Helicobacter infection (P < 0.001). Helicobacter pylori negative, male sex, current smoker, current drinker, symptoms of gastresophageal reflux disease, hiatal hernia, duodenal ulcer, and BMI > 25 were risk factors for reflux esophagitis in univariate analysis. In multivariate analysis, Helicobacter pylori infection (OR 0.36, 95% CI 0.28-0.45) is confirmatory protective factor for reflux esophagitis. Cofactors influencing the prevalence of reflux esophagits were male sex (OR 2.8, 95% CI 1.93-4.07), age older than 55 years (OR 1.40, 95% CI 1.04-1.77), BMI higher than 25 (OR 2.03, 95% CI 1.66-2.48), current drinker (OR 1.46, 95% CI 1.11-1.92), current smoker (OR 1.36, 95% CI 1.06-1.73), hiatal hernia (OR 9.22, 95% CI 4.91-17.3), and presence of duodenal ulcer or scar (OR 1.53, 95% CI 1.07-2.19). CONCLUSIONS Helicobacter pylori infection has a confirmatory protective role for reflux esophagitis in healthy subjects.
T1989 Weakly Acidic Gastroesophageal Reflux: Further Characterization with Impedance-Double pH Monitoring Adriana Lazarescu, Raf Bisschops, Ingrid Demedts, Jan F. Tack, Guido N. Tytgat, Daniel Sifrim Background: Impedance pH monitoring allows detection of weakly acidic reflux (WA), defined as a reflux episode detected by impedance with a pH drop between 4-7 at 5cm above the lower esophageal sphincter. Recent studies described short segment acid reflux episodes (pH drops below 4, observed at 1cm, but not at 5cm, above the squamocolumnar junction (SCJ)). The aim of this study was to further characterize weakly acidic reflux using impedance and double pH monitoring at 5cm and 1cm above the SCJ. Methods: Endoscopy and 24h impedance-double pH monitoring were performed “off” PPI in 18 patients (7 males, median age 43 (25-73)) to confirm diagnosis of GERD. During endoscopy, the distal tip of an impedance-double pH catheter (Sandhill) was clipped to the esophageal mucosa with the distal pH sensor located at 1cm and the proximal pH sensor at 5 cm above the SCJ. Impedance was measured at 3, 5, 7, 9, 15 and 17 cm above the SCJ. Results: Based on endoscopy and conventional analysis of pHmetry, reflux disease was confirmed in 11/18 patients (6 with erosive esophagitis and 5 with NERD). A total of 630 reflux episodes were identified with impedance. Of these, 304 (48.3%) were acidic at both 5cm and 1cm (A-A) and 323 (51.3%) events fulfilled diagnostic criteria of weakly acidic reflux (retrograde impedance drop in at least the two most distal channels with pH at 5 cm between 4-7). Weakly acidic reflux could be divided into those with pH>4 at both 5cm and 1cm above the SCJ (WA-WA) (n=139) and those that are weakly acidic at 5cm and acidic at 1cm (WAA) (n=184). The WA-WA episodes were equally likely to be mixed liquid-gas or pure liquid, occurred mainly in the first hour after a meal (54%) and were more likely to be associated with regurgitation than with heartburn. In contrast, WA-A episodes were more likely to be mixed liquid-gas (64.7%), occurred throughout the 24 hours and were equally likely to be associated with heartburn and regurgitation. Patients with GERD had more AA and less WA-A compared to patients without GERD (table). Conclusions: Half of weakly acidic reflux detected with impedance-pH monitoring in the lower and mid esophageal body is acidic at the very distal esophagus. This might be due to proximal pH measuring artifact, heterogeneous reflux material or rapid neutralization of very small volume of acid reflux.
T1987 H. pylori Infection Is Not Involved in the Pathogenesis of Erosive and NonErosive Reflux Disease in a Young Population: Studies from a Health CheckUp Program of 678 Consecutive Japanese Subjects in Their 20s Tomohiko Shimatani, Seiko Hirokawa, Kazuko Hamai, Yumiko Tawara, Mutsuko Matsumoto, Ayumi Furukawa, Susumu Tazuma, Masaki Inoue BACKGROUND: The relationship between H. pylori infection and gastroesophageal reflux disease (GERD) is controversial. In Japan, where the prevalence of H. pylori infection is relatively high, the prevalence of GERD is significantly lower than in developed Western countries, and there is significantly low prevalence of H. pylori infection in patients with GERD. Therefore, a negative relationship has been indicated between H. pylori infection and GERD in the elderly. However, such studies in a young population are rare, because few subjects within this age group consult their doctors if suffering from dyspeptic symptoms, or undergo endoscopy for mass screening of upper gastrointestinal diseases. AIMS: This study was undertaken to determine whether H. pylori infection was involved in the pathogenesis of GERD in a young population. METHODS: In a health check-up program from 1997 to 2005, a consecutive series of 678 young Japanese subjects aged between 20 and 29 years (416 men and 262 women) were interviewed, underwent endoscopy and tested for H. pylori. H. pylori infection was evaluated using serology, histology and rapid urease test. If the result of either method was positive, H. pylori infection was considered positive. If the results of
AGA Abstracts
A-594
all three methods were negative, infection was considered negative. Erosive reflux disease (ERD) was defined as the presence of mucosal breaks in the esophagus. Subjects who had no mucosal breaks but complained of mild symptoms occurring two or more days a week, or moderate/severe symptoms occurring more than one day a week, were considered to have non-erosive reflux disease (NERD). RESULTS: Of the 678 subjects, 52 (7.7%) had ERD, 148 (21.8%) NERD, and 478 (70.5%) were normal. The prevalence of H. pylori infection was 17.6% in subjects with ERD, 18.2% with NERD, and 14.2% in normal ones, respectively; no significant differences were observed among the three groups (chi-square test). Of the 52 subjects with ERD, only 17 (32.7%) complained of typical symptoms, whereas 35 (67.3%) complained of fewer or no symptoms: The prevalence of H. pylori infection in these two subgroups was 17.6% and 20.0%, respectively, with no significant difference. CONCLUSION: H. pylori infection is not involved in the pathogenesis of both ERD and NERD in a young Japanese population in their 20s. It is postulated that in this population H. pylori-associated corpus gastritis and/or mucosal atrophy is not so extended, and so, gastric acid secretion, one of the most important aggressive factors in the esophageal mucosa, is not significantly decreased.
AGA Abstracts
Differential Gene Expression in the Duodenum May Contribute to Symptom Generation in GERD Durk Vries, de, Jose ter Linde, Margot A. van Herwaarden, Matthijs P. Schwartz, André Smout, Melvin Samsom Background: Signaling from the duodenum affects TLESR frequency, lower esophageal sphincter pressure and esophageal perception. Despite the putative role of the duodenum in the pathophysiology of gastroesophageal reflux disease (GERD), information regarding abnormalities in gene expression underlying altered sensorimotor function of the esophagus is lacking. Aim: Identify genes differentially expressed in duodenal biopsies from GERD patients as compared to healthy volunteers (HVs). Materials and methods: 20 symptomatic GERD patients (10 M/F, mean age 52) with a total 24-hour acid exposure of 6-12% and a SAP ≥95% were selected from recent pH-metry referrals. Patients with a history of organic disease and/or surgery affecting upper GI tract sensitivity and/or motility were excluded. Ten patients discontinued PPI treatment and ten patients took a maximum dose of PPI, both two weeks prior to sampling. In addition, ten age- and sex-matched HVs without gastrointestinal symptoms were recruited from the general population. During upper GI endoscopy mucosal biopsies were taken in the pars descendens of the duodenum and snapfrozen in liquid nitrogen. RNA was extracted and profiled on Affymetrix Human Genome U133 Plus 2.0 array. Genes exhibiting a fold change >1.4 (t-test p-value <1E-4) were considered differentially expressed. A subset of 21 differentially expressed genes was selected for confirmatory RT-PCR using TaqMan low density arrays. Results: Whole genome expression profiling revealed that 20 and 22 genes were higher respectively lower expressed in GERD patients off PPIs relative to HVs. In GERD patients on PPIs 34 upregulated and 5 downregulated genes were found, taking HVs as a reference. An overlap of 22 differentially expressed genes was observed between the two patient groups. The majority of the upregulated genes was associated with lipid absorption, particularly triglyceride resynthesis and intracellular vesicular transport, which are rate-limiting processes for chylomicron production and secretion. Differential expression of nine upregulated genes was confirmed by RT-PCR and three genes showed a trend towards significance. Conclusion: Our results suggest that in GERD patients chylomicron production and secretion is enhanced. Consequently, the release of apoA-IV, a signaling component derived from chylomicrons, may be higher. The subsequent potentially increased release of CCK may cause heightened activation of duodenal extrinsic primary afferents. Thus, the differences in gene expression identified may underlie a mechanism by which duodenal signaling intensifies the perception of symptoms induced by gastroesophageal reflux.
T1988 Short Segment Acid Reflux: Characterization with 24-Hour Esophageal Impedance-Double pH Monitoring Adriana Lazarescu, Raf Bisschops, Ingrid Demedts, Jan F. Tack, Guido N. Tytgat, Daniel Sifrim Background: Recent studies measuring esophageal pH at 1 cm proximal to the squamocolumnar junction (SCJ) have described the occurrence of a large number of short segment acid reflux episodes (pH drops below 4, observed at 1cm, but not at 5cm above SCJ). The aim of this study was to further characterize short segment acid reflux with impedance-double pH monitoring. Methods: Endoscopy and 24h impedance-double pH monitoring were performed “off” PPI in 18 patients (7 males, median age 43 (25-73)) to confirm the diagnosis of gastroesophageal reflux disease (GERD). During endoscopy, the distal tip of an impedancedouble pH catheter (Sandhill) was clipped to the esophageal mucosa with the distal pH sensor located at 1cm and the proximal pH sensor at 5 cm above the SCJ. Impedance was measured at 3, 5, 7, 9, 15 and 17 cm above the SCJ. Results: Based on endoscopy and conventional analysis of pHmetry, reflux disease was confirmed in 11/18 patients (6 with erosive esophagitis and 5 with NERD). Four hundred and twenty eight short acid reflux episodes were identified. One hundred and eighty four (43%) of these fulfilled the impedance diagnostic criteria of weakly acidic reflux (impedance retrograde drop in at least the two most distal channels with pH at 5 cm between 4-7). However, 244 (57%) short segment acid reflux episodes were not associated with typical impedance liquid reflux events. These included 115 (47.1%) episodes without any impedance change, 102 (41.8%) episodes with gas-only reflux (belches), and 27 (11.1%) with impedance changes (compatible with liquid) in only the most distal channel (3cm). Short segment acid reflux was rarely associated with typical symptoms. However, gas-only reflux (belches) was more often associated with regurgitation than heartburn, while short acid reflux with no impedance changes was associated only with heartburn. Conclusions: We confirmed the frequent occurrence of short acid reflux episodes. They are oligo-symptomatic. Half of them are associated with less acidic liquid retrograde flow in the esophageal body and the other half occurs with belching or small liquid volume restricted to the very distal esophagus.
T1986 Helicobacter Is An Independent Protective Factor for Erosive Esophagitis Su Youn Nam, Il Ju Choi, Kyung woo Park, Byung Chang Kim, Kum Hei Ryu BACKGROUND Although many case-control studies have suggested that Helicobacter pylori infection may decrease the risk for reflux esophagitis or Barrett's esophagus, any large scale population-based study adjusting many confounding factors has not been issued. METHODS A total of 11,800 healthy subjects who underwent routine check-up in the National Cancer Center from October 2003 to May 2007 were enrolled. The status of Helicobacter pylori infection was evaluated by rapid urease test. It has been adjusted for age, sex, body mass index, smoking status, alcohol intake, hiatal hernia, duodenal ulcer, dietary intake, current medication, and chronic disease. We used logistic regression models to evaluate the association between Helicobacter infection and erosive esophagitis. RESULTS The prevalence was 4.9% (576/11,800) in reflux esophagitis defined as LA classification. While the prevalence of reflux esophagitis was 6.5% (383/5854) in the subjects without Helicobacter infection, it was 3.2% (193/5946) in the subjects with Helicobacter infection (P < 0.001). Helicobacter pylori negative, male sex, current smoker, current drinker, symptoms of gastresophageal reflux disease, hiatal hernia, duodenal ulcer, and BMI > 25 were risk factors for reflux esophagitis in univariate analysis. In multivariate analysis, Helicobacter pylori infection (OR 0.36, 95% CI 0.28-0.45) is confirmatory protective factor for reflux esophagitis. Cofactors influencing the prevalence of reflux esophagits were male sex (OR 2.8, 95% CI 1.93-4.07), age older than 55 years (OR 1.40, 95% CI 1.04-1.77), BMI higher than 25 (OR 2.03, 95% CI 1.66-2.48), current drinker (OR 1.46, 95% CI 1.11-1.92), current smoker (OR 1.36, 95% CI 1.06-1.73), hiatal hernia (OR 9.22, 95% CI 4.91-17.3), and presence of duodenal ulcer or scar (OR 1.53, 95% CI 1.07-2.19). CONCLUSIONS Helicobacter pylori infection has a confirmatory protective role for reflux esophagitis in healthy subjects.
T1989 Weakly Acidic Gastroesophageal Reflux: Further Characterization with Impedance-Double pH Monitoring Adriana Lazarescu, Raf Bisschops, Ingrid Demedts, Jan F. Tack, Guido N. Tytgat, Daniel Sifrim Background: Impedance pH monitoring allows detection of weakly acidic reflux (WA), defined as a reflux episode detected by impedance with a pH drop between 4-7 at 5cm above the lower esophageal sphincter. Recent studies described short segment acid reflux episodes (pH drops below 4, observed at 1cm, but not at 5cm, above the squamocolumnar junction (SCJ)). The aim of this study was to further characterize weakly acidic reflux using impedance and double pH monitoring at 5cm and 1cm above the SCJ. Methods: Endoscopy and 24h impedance-double pH monitoring were performed “off” PPI in 18 patients (7 males, median age 43 (25-73)) to confirm diagnosis of GERD. During endoscopy, the distal tip of an impedance-double pH catheter (Sandhill) was clipped to the esophageal mucosa with the distal pH sensor located at 1cm and the proximal pH sensor at 5 cm above the SCJ. Impedance was measured at 3, 5, 7, 9, 15 and 17 cm above the SCJ. Results: Based on endoscopy and conventional analysis of pHmetry, reflux disease was confirmed in 11/18 patients (6 with erosive esophagitis and 5 with NERD). A total of 630 reflux episodes were identified with impedance. Of these, 304 (48.3%) were acidic at both 5cm and 1cm (A-A) and 323 (51.3%) events fulfilled diagnostic criteria of weakly acidic reflux (retrograde impedance drop in at least the two most distal channels with pH at 5 cm between 4-7). Weakly acidic reflux could be divided into those with pH>4 at both 5cm and 1cm above the SCJ (WA-WA) (n=139) and those that are weakly acidic at 5cm and acidic at 1cm (WAA) (n=184). The WA-WA episodes were equally likely to be mixed liquid-gas or pure liquid, occurred mainly in the first hour after a meal (54%) and were more likely to be associated with regurgitation than with heartburn. In contrast, WA-A episodes were more likely to be mixed liquid-gas (64.7%), occurred throughout the 24 hours and were equally likely to be associated with heartburn and regurgitation. Patients with GERD had more AA and less WA-A compared to patients without GERD (table). Conclusions: Half of weakly acidic reflux detected with impedance-pH monitoring in the lower and mid esophageal body is acidic at the very distal esophagus. This might be due to proximal pH measuring artifact, heterogeneous reflux material or rapid neutralization of very small volume of acid reflux.
T1987 H. pylori Infection Is Not Involved in the Pathogenesis of Erosive and NonErosive Reflux Disease in a Young Population: Studies from a Health CheckUp Program of 678 Consecutive Japanese Subjects in Their 20s Tomohiko Shimatani, Seiko Hirokawa, Kazuko Hamai, Yumiko Tawara, Mutsuko Matsumoto, Ayumi Furukawa, Susumu Tazuma, Masaki Inoue BACKGROUND: The relationship between H. pylori infection and gastroesophageal reflux disease (GERD) is controversial. In Japan, where the prevalence of H. pylori infection is relatively high, the prevalence of GERD is significantly lower than in developed Western countries, and there is significantly low prevalence of H. pylori infection in patients with GERD. Therefore, a negative relationship has been indicated between H. pylori infection and GERD in the elderly. However, such studies in a young population are rare, because few subjects within this age group consult their doctors if suffering from dyspeptic symptoms, or undergo endoscopy for mass screening of upper gastrointestinal diseases. AIMS: This study was undertaken to determine whether H. pylori infection was involved in the pathogenesis of GERD in a young population. METHODS: In a health check-up program from 1997 to 2005, a consecutive series of 678 young Japanese subjects aged between 20 and 29 years (416 men and 262 women) were interviewed, underwent endoscopy and tested for H. pylori. H. pylori infection was evaluated using serology, histology and rapid urease test. If the result of either method was positive, H. pylori infection was considered positive. If the results of
AGA Abstracts
A-594