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50 cases with H. Pylori (Hp) associated atrophic body gastritis: Comparison of patients with eradication therapy versus untreated patients
A334 AGA ABSTRACTS
GASTROENTEROLOGY Vol. 114, No. 4
G1363 ARE DYSPEPTIC SYMPTOMS ASSOCIATED WITH TRANSDERMAL NICOTINE DELIVERY SYSTEMS CAUSED BY ESOPHAGEAL REFLUX OR DYSMOTILITY? R.A. Wright, V.Z. Ameen, *S.L. Kirby, S.R. Prakash, A. D'Angelo,* D.L. Huff, Div of GI/HE, Dpt of Med, Univ of Louisville, Louisville, KY. *McNeil CPC, Ft. Washington, PA. INTRO: Transdermal nicotine delivery systems are widely used in smoking cessation. The purpose of this study was to determine whether common symptoms of pyrosis and dyspepsia associated with these patches are related to GE reflux or esophageal dysmotility. METHODS: 27 paid volunteer cigarette smokers ( > 15 cigs/d) without symptomatic GERD participated in this single-blinded, placebocontrolled study. Twenty subjects completed the study. Subjects underwent three sequential 24 hour intraesophageal pH/motor studies (Synectics model P32342084, Shore View, MN). The pH/motility probe was positioned 5 cm above the manometrically determined LES. A placebo patch was applied for the first 24 hour study and a 15 mg nicotine patch (Nicotrol ®) was applied for the initial 16 hours (removed for remaining 8 hours) of the second 24 hour period. A 21 mg nicotine patch (Nicoderm®) was applied for another 24 hour study period. All subjects consumed an identical, defined diet documented by meal receipts, and refrained from smoking and tobacco use throughout the study periods (CO breath test confirmation). STATISTICS: Wilcoxon, paired t-test, exact MeNemar. RESULTS: There were no significant differences in reflux symptoms (pyrosis, chest pain, nausea, dysphagia), supine GE reflux (number of episodes, duration, or cumulative acid exposure) or the total number of reflux episodes between placebo and nicotine patch treatment periods. The number of postprandial upright acid reflux episodes (p=.04) and number of upright acid reflux episodes lasting more than 5 minutes (p=.007) were statistically higher with the placebo patch compared to the active nicotine patches. No differences in intraesophageal pH or motility indices were noted between the two transdermal nicotine patches (Nicotrol ®, Nicoderm®). CONCLUSIONS: Dyspeptic symptoms in subjects utilizing transdermal nicotine patches are not related to gastroesophageal reflux or to esophageal motor abnormalities. • G1364 PREVALENCE AND DISTRIBUTION OF H. PYLORI IN GASTROESOPHAGEAL REFLUX DISEASE: A STUDY IN CHINESE. JCY Wu, MYY Go, WB Chan, CL Choi*, FKL Cban, JY Sung. Depts of Medicine and Pathology*, The Chinese University of Hong Kong.
H. pylori infection has been implicated both in promoting and protecting against development of gastro-esopbageal reflux disease (GERD). Inflammation of the cardia has been proposed as a mechanism of LES dysfunction. In Asia H. pylori infection is highly prevalent, yet GERD is very uncommon. AIM. We tested the hypothesis that H. pylori is protective for the esophagus by studying 1. the prevalence of H. pylori infection in Chinese patients with GERD and 2. the distribution of this bacterium and inflammation in the stomach. METHOD. Diagnosis of GERD was based on persistent symptoms of heartburn and acid reflux plus either 1. symptomatic improvement with acidsuppressive therapy or 2. endoscopic evidence of esophagitis. Blood was taken for serology and biopsies taken from the antrum, corpus and cardia for assessment of H. pylori status (rapid urease test and histology with Giemsa stain). Density of bacterial colonization and activity of inflammation at these sites were graded according to Updated Sydney Classification. Asymptomatic, sex and age-matched subjects were recruited for case-control study. H. pylori status of these patients was determined by serology. RESULTS. 57 patients with GERD and I01 control subjects were recruited in this study. The rate of H. pylori infection was significantly lower in patients with GERD (31%) compared with control (61%) (P <0.001). Histological examination of GERD patients showed predominant colonization of H. pylori in the antrum and corpus. The activity of gastritis was found to be significantly higher in the antrum than in corpus or cardia. Scoring (Mean -+ SD) Antrum Corpus Density ofH. pylori* 1.33 +- .78 1.33 ± .65 Activity of Gastritis* 3.08 ± 1.38 1.58 ± 1.0 * P < 0.05 Kendall's coefficient of concordance
Cardia .41 ± .67 1.58 ± 1.62
CONCLUSION. H. pylori infection is less common in Chinese patients suffering from GERD. Colonization of the cardia is uncommon. O u r observations support the hypothesis that H. pylori PROTECTS, rather than PROMOTES, the esophagus from developing GERD. This research was not funded by any organization • G1365 CYCLOOXYGENASE (COX)-I AND -2 IN HUMAN GASTRIC MUCOSA: CONSTITUTIVE EXPRESSION BY PARIETAL CELLS AND INDUCTION OF COX-2 IN LAMINA PROPRIA CELLS PROXIMAL TO ULCERS. K C Wu, L Jackson, YR Mahida, D Jenkins* & CJ Hawkey. Divs of Gastroenterology & Pathology*, University Hospital, Nottingham, UK. Prostaglandins are important in the maintenance of gastric mucosal integrity. They are synthesized by two isoforms of the COX enzyme, COX-1 &-2.
Because of the development of drugs that are selective inhibitors, we have investigated the distribution of COX-1 and -2 in the normal and ulcerated human gastric mucosa. Methods. Mucosal samples were obtained from macroscopically normal mucosa and ulcer rim of 30 gastric operation resection specimens. Endoscopic biopsies were obtained from 15 normal stomachs. Light and electronic microscopic immunohistochemistry was performed using antibodies specific for COX-l, COX-2 or human milk fat globule-2 (HMFG2; specific for parietal cells). Gastric epithelial ceils enriched for parietal cells were recovered by sequential treatment of mucosal samples with EDTA (fraction 5). Expression of COX-1 & -2 by these ceils was studied by immunohistochemistry (cytospin preps.) and Western blot analysis. Prostaglandin E2 (PGE2) release in the presence or absence of specific COX1 & -2 inhibitors was studied by ELISA. Results, In all sections of normal gastric mucosa, there was strong COX-1 & -2 immunoreactivity in parietal cells (HMFG2+ve), This immunoreactivity was abolished by antigen absorption studies using purified COX-I & -2 enzymes (Cayman Chemicals). Immuno-EM suggested that both COX-1 & -2 were localized to the smooth endoplasmic reticulum in the parietal cells. Western blot analysis showed COX-1 & -2 expression by parietal cell-enriched gastric epithelial cells. These cells synthesized large quantities of PGE2 in culture [up to 4.7ng/2x106 ceils] and this could be inhibited by both a COX-1 (SC58560) and a COX-2 (NS398) inhibitor. In addition to parietal cells, COX-1 & -2 immunoreactivity was seen in lamina propria macrophages and subepithelial myofibroblasts in some (3/20 & 6•20 respectively) normal sections. Endothelial cell expression of COX-1 or -2 was not obvious (weak +ve in one sample). In sections of ulcerated gastric mucosa, COX-2 +ve endothelial cells (18130 samples; p<0.01 vs normal) and cells with morphological features of macrophages (27/30 samples; p < 0.01 vs normal) and myofibroblasts (28130 samples; p < 0.01 vs normal) were seen close to the ulcer. These changes appeared to be independent of NSAIDs exposure or H. pylori infection. COX-1 expression was not significantly different from normal gastric tissue. Conclusions. 1. COX-1 & -2 is expressed by normal human gastric parietal cells. 2. There is induction of COX-2 in macrophages, myofibroblasts and endothelial cells lying close to gastric ulcers. 3. Induction of COX-2 expression near ulcers appeared to be independent of NSAID usage and Hp status. G1366 50 CASES WITH H. PYLORI (Hp) ASSOCIATED ATROPHIC BODY GASTRITIS: COMPARISON OF PATIENTS WITH ERADICATION THERAPY VERSUS UNTREATED PATIENTS. Wiindisch T, Rappel S, Stolte M. Institute of Pathology, Klinikum Bayreuth, Germany. In a subgrop of patients Hp-infection is associated with atrophy and inflammation of the oxyntic mucosa. The aim of the presented study was to evaluate histologically the effect of eradication therapy in atrophic body gastritis. Biopsies of 50 patients from the routine daily workload with severe to mild glandular atrophy and severe inflammatory infiltration of the oxyntic mucosa were investigated. Hp-colonization, neutrophils, mononuclear cells, atrophy and intestinal metaplasia were graded according to the updated Sydney System. Lymphocytic infiltration of the oxyntic mucosa and existence of intraepithelial lymphocytes were also evaluated. Eradication therapy was performed in 30 cases. Histopathological evaluation of the gastric fundus was done at the earliest 6 weeks (up to 1 year) after eradication treatment. In 20 patients control biopsies without eradication treatment were available (6-24 months after the first biopsies were taken). The group with eradication therapy showed a highly significant reduction of bodyatrophy and chronic inflammatory cells. Neutrophil activity vanished after eradication. Pretreatment intraepithelial lymphocytes were also reduced. In contrast the second biopsies of the group without eradication treatment showed no change concerning active and chronic inflammation. Whereas atrophy of the oxyntic mucosa increased significantly. We conclude that in patients with atrophic body gastritis and infestion with Hp the oxyntic mucosa can recover after successful eradication treatment. G1367 CLINICAL EFFICACY AND SAFETY OF INTRAVENOUS PANTOPRAZOLE IN GASTROESOPHAGEAL REFLUX DISEASE (GERD). H. Wurzer (l), K. Schtitze (2), p. Kratochvil (3), Th. Stupnicki (4) & Austrian Intravenous Pantoprazole Study Group. (1) Medical Dpt. II, General Hospital, Graz; (2) Medical Dpt. I, Hanusch Hospital, Vienna; (3) Styrian Health Insurance Fund, Graz; (4) Medical Dpt., General Hospital, Deutschlandsberg Austria Background: Application of intravenous (i.v.) antisecretory drugs may be required in patients incapable of oral intake. Methods: We report on efficacy and tolerability of pantoprazole i.v. 40 mg o.m. over 5 to 7 days followed by oral intake (40 mg o.m.) for up to 7 weeks (i.v./p.o.) in GERD II/III (Savary/Miller). Endoscopies were done at 4 and 8 weeks to assess GERD healing. Symptoms were evaluated during each visit (days 1 to 5/7, 14, 28; if applicable 42 and 56). 110 (72 male, 38 female) patients were included in this open-labelled, multicenter trial.
GASTROENTEROLOGY Vol. 114, No. 4
G1363 ARE DYSPEPTIC SYMPTOMS ASSOCIATED WITH TRANSDERMAL NICOTINE DELIVERY SYSTEMS CAUSED BY ESOPHAGEAL REFLUX OR DYSMOTILITY? R.A. Wright, V.Z. Ameen, *S.L. Kirby, S.R. Prakash, A. D'Angelo,* D.L. Huff, Div of GI/HE, Dpt of Med, Univ of Louisville, Louisville, KY. *McNeil CPC, Ft. Washington, PA. INTRO: Transdermal nicotine delivery systems are widely used in smoking cessation. The purpose of this study was to determine whether common symptoms of pyrosis and dyspepsia associated with these patches are related to GE reflux or esophageal dysmotility. METHODS: 27 paid volunteer cigarette smokers ( > 15 cigs/d) without symptomatic GERD participated in this single-blinded, placebocontrolled study. Twenty subjects completed the study. Subjects underwent three sequential 24 hour intraesophageal pH/motor studies (Synectics model P32342084, Shore View, MN). The pH/motility probe was positioned 5 cm above the manometrically determined LES. A placebo patch was applied for the first 24 hour study and a 15 mg nicotine patch (Nicotrol ®) was applied for the initial 16 hours (removed for remaining 8 hours) of the second 24 hour period. A 21 mg nicotine patch (Nicoderm®) was applied for another 24 hour study period. All subjects consumed an identical, defined diet documented by meal receipts, and refrained from smoking and tobacco use throughout the study periods (CO breath test confirmation). STATISTICS: Wilcoxon, paired t-test, exact MeNemar. RESULTS: There were no significant differences in reflux symptoms (pyrosis, chest pain, nausea, dysphagia), supine GE reflux (number of episodes, duration, or cumulative acid exposure) or the total number of reflux episodes between placebo and nicotine patch treatment periods. The number of postprandial upright acid reflux episodes (p=.04) and number of upright acid reflux episodes lasting more than 5 minutes (p=.007) were statistically higher with the placebo patch compared to the active nicotine patches. No differences in intraesophageal pH or motility indices were noted between the two transdermal nicotine patches (Nicotrol ®, Nicoderm®). CONCLUSIONS: Dyspeptic symptoms in subjects utilizing transdermal nicotine patches are not related to gastroesophageal reflux or to esophageal motor abnormalities. • G1364 PREVALENCE AND DISTRIBUTION OF H. PYLORI IN GASTROESOPHAGEAL REFLUX DISEASE: A STUDY IN CHINESE. JCY Wu, MYY Go, WB Chan, CL Choi*, FKL Cban, JY Sung. Depts of Medicine and Pathology*, The Chinese University of Hong Kong.
H. pylori infection has been implicated both in promoting and protecting against development of gastro-esopbageal reflux disease (GERD). Inflammation of the cardia has been proposed as a mechanism of LES dysfunction. In Asia H. pylori infection is highly prevalent, yet GERD is very uncommon. AIM. We tested the hypothesis that H. pylori is protective for the esophagus by studying 1. the prevalence of H. pylori infection in Chinese patients with GERD and 2. the distribution of this bacterium and inflammation in the stomach. METHOD. Diagnosis of GERD was based on persistent symptoms of heartburn and acid reflux plus either 1. symptomatic improvement with acidsuppressive therapy or 2. endoscopic evidence of esophagitis. Blood was taken for serology and biopsies taken from the antrum, corpus and cardia for assessment of H. pylori status (rapid urease test and histology with Giemsa stain). Density of bacterial colonization and activity of inflammation at these sites were graded according to Updated Sydney Classification. Asymptomatic, sex and age-matched subjects were recruited for case-control study. H. pylori status of these patients was determined by serology. RESULTS. 57 patients with GERD and I01 control subjects were recruited in this study. The rate of H. pylori infection was significantly lower in patients with GERD (31%) compared with control (61%) (P <0.001). Histological examination of GERD patients showed predominant colonization of H. pylori in the antrum and corpus. The activity of gastritis was found to be significantly higher in the antrum than in corpus or cardia. Scoring (Mean -+ SD) Antrum Corpus Density ofH. pylori* 1.33 +- .78 1.33 ± .65 Activity of Gastritis* 3.08 ± 1.38 1.58 ± 1.0 * P < 0.05 Kendall's coefficient of concordance
Cardia .41 ± .67 1.58 ± 1.62
CONCLUSION. H. pylori infection is less common in Chinese patients suffering from GERD. Colonization of the cardia is uncommon. O u r observations support the hypothesis that H. pylori PROTECTS, rather than PROMOTES, the esophagus from developing GERD. This research was not funded by any organization • G1365 CYCLOOXYGENASE (COX)-I AND -2 IN HUMAN GASTRIC MUCOSA: CONSTITUTIVE EXPRESSION BY PARIETAL CELLS AND INDUCTION OF COX-2 IN LAMINA PROPRIA CELLS PROXIMAL TO ULCERS. K C Wu, L Jackson, YR Mahida, D Jenkins* & CJ Hawkey. Divs of Gastroenterology & Pathology*, University Hospital, Nottingham, UK. Prostaglandins are important in the maintenance of gastric mucosal integrity. They are synthesized by two isoforms of the COX enzyme, COX-1 &-2.
Because of the development of drugs that are selective inhibitors, we have investigated the distribution of COX-1 and -2 in the normal and ulcerated human gastric mucosa. Methods. Mucosal samples were obtained from macroscopically normal mucosa and ulcer rim of 30 gastric operation resection specimens. Endoscopic biopsies were obtained from 15 normal stomachs. Light and electronic microscopic immunohistochemistry was performed using antibodies specific for COX-l, COX-2 or human milk fat globule-2 (HMFG2; specific for parietal cells). Gastric epithelial ceils enriched for parietal cells were recovered by sequential treatment of mucosal samples with EDTA (fraction 5). Expression of COX-1 & -2 by these ceils was studied by immunohistochemistry (cytospin preps.) and Western blot analysis. Prostaglandin E2 (PGE2) release in the presence or absence of specific COX1 & -2 inhibitors was studied by ELISA. Results, In all sections of normal gastric mucosa, there was strong COX-1 & -2 immunoreactivity in parietal cells (HMFG2+ve), This immunoreactivity was abolished by antigen absorption studies using purified COX-I & -2 enzymes (Cayman Chemicals). Immuno-EM suggested that both COX-1 & -2 were localized to the smooth endoplasmic reticulum in the parietal cells. Western blot analysis showed COX-1 & -2 expression by parietal cell-enriched gastric epithelial cells. These cells synthesized large quantities of PGE2 in culture [up to 4.7ng/2x106 ceils] and this could be inhibited by both a COX-1 (SC58560) and a COX-2 (NS398) inhibitor. In addition to parietal cells, COX-1 & -2 immunoreactivity was seen in lamina propria macrophages and subepithelial myofibroblasts in some (3/20 & 6•20 respectively) normal sections. Endothelial cell expression of COX-1 or -2 was not obvious (weak +ve in one sample). In sections of ulcerated gastric mucosa, COX-2 +ve endothelial cells (18130 samples; p<0.01 vs normal) and cells with morphological features of macrophages (27/30 samples; p < 0.01 vs normal) and myofibroblasts (28130 samples; p < 0.01 vs normal) were seen close to the ulcer. These changes appeared to be independent of NSAIDs exposure or H. pylori infection. COX-1 expression was not significantly different from normal gastric tissue. Conclusions. 1. COX-1 & -2 is expressed by normal human gastric parietal cells. 2. There is induction of COX-2 in macrophages, myofibroblasts and endothelial cells lying close to gastric ulcers. 3. Induction of COX-2 expression near ulcers appeared to be independent of NSAID usage and Hp status. G1366 50 CASES WITH H. PYLORI (Hp) ASSOCIATED ATROPHIC BODY GASTRITIS: COMPARISON OF PATIENTS WITH ERADICATION THERAPY VERSUS UNTREATED PATIENTS. Wiindisch T, Rappel S, Stolte M. Institute of Pathology, Klinikum Bayreuth, Germany. In a subgrop of patients Hp-infection is associated with atrophy and inflammation of the oxyntic mucosa. The aim of the presented study was to evaluate histologically the effect of eradication therapy in atrophic body gastritis. Biopsies of 50 patients from the routine daily workload with severe to mild glandular atrophy and severe inflammatory infiltration of the oxyntic mucosa were investigated. Hp-colonization, neutrophils, mononuclear cells, atrophy and intestinal metaplasia were graded according to the updated Sydney System. Lymphocytic infiltration of the oxyntic mucosa and existence of intraepithelial lymphocytes were also evaluated. Eradication therapy was performed in 30 cases. Histopathological evaluation of the gastric fundus was done at the earliest 6 weeks (up to 1 year) after eradication treatment. In 20 patients control biopsies without eradication treatment were available (6-24 months after the first biopsies were taken). The group with eradication therapy showed a highly significant reduction of bodyatrophy and chronic inflammatory cells. Neutrophil activity vanished after eradication. Pretreatment intraepithelial lymphocytes were also reduced. In contrast the second biopsies of the group without eradication treatment showed no change concerning active and chronic inflammation. Whereas atrophy of the oxyntic mucosa increased significantly. We conclude that in patients with atrophic body gastritis and infestion with Hp the oxyntic mucosa can recover after successful eradication treatment. G1367 CLINICAL EFFICACY AND SAFETY OF INTRAVENOUS PANTOPRAZOLE IN GASTROESOPHAGEAL REFLUX DISEASE (GERD). H. Wurzer (l), K. Schtitze (2), p. Kratochvil (3), Th. Stupnicki (4) & Austrian Intravenous Pantoprazole Study Group. (1) Medical Dpt. II, General Hospital, Graz; (2) Medical Dpt. I, Hanusch Hospital, Vienna; (3) Styrian Health Insurance Fund, Graz; (4) Medical Dpt., General Hospital, Deutschlandsberg Austria Background: Application of intravenous (i.v.) antisecretory drugs may be required in patients incapable of oral intake. Methods: We report on efficacy and tolerability of pantoprazole i.v. 40 mg o.m. over 5 to 7 days followed by oral intake (40 mg o.m.) for up to 7 weeks (i.v./p.o.) in GERD II/III (Savary/Miller). Endoscopies were done at 4 and 8 weeks to assess GERD healing. Symptoms were evaluated during each visit (days 1 to 5/7, 14, 28; if applicable 42 and 56). 110 (72 male, 38 female) patients were included in this open-labelled, multicenter trial.