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Intestinal metaplasia of the gastric mucosa during long-term treatment with lansoprazole
GASTROENTEROLOGY Vol. 114, No. 4
All2 AGA ABSTRACTS G0459 HEALING
OF PEPTIC ULCERS AND ERADICATION OF HELICOBACTER PYLORI UNDER CONDITIONS OF A GASTROENTEROLOGICAL AMBULANCE. H. Eisold, internist and gastroenterologist in practice, M~Sssingen, Germany Objectives: To compare the efficacy and safety of a 7 day triple therapy including lansoprazole 30mg bid with lansoprazole 15mg bid combined with roxithromycin 300mg bid and metronidazole 400mg tid. Methods: 61 patients resp. 41 patients suffering from H. pylori-positive ulcer disease were treated with lansoprazole 30mg bid resp. 15mg bid. Additionally all patients received roxithromycin 300mg bid and metronidazole 400 mg tid for 7 days. Diagnose, healing and H. pylori were assessed by endoscopy, histology and rapid urease test. H. pylori eradication was investigated at least 4 weeks after the end of treatment. Results: Endoscopic healing was achieved in all patients of both groups. H. pylori eradication was obtained in 51 of 61 pateints (82%) in the 30mg bid lansoprazole group and in 36 of 41 patients (88%) in the 15mg bid lansoprazole group. The tolerance was good. Conclusion: The triple regime with lansoprazole 30mg bid resp. lansoprazole 15mg bid combinded with roxithromycin 300mg bid and metronidazole 400rag tid is an effective and cheap treatment for H. pylori eradication in peptic ulcer patients. G0460 INTESTINAL METAPLASIA OF THE GASTRIC MUCOSA DURING LONG-TERM TREATMENT WITH LANSOPRAZOLE. R. Eissele*, G. Brunner#, E. Solcia+, R. Arnold*. Depts. of Gastroenterology, Universities of Marburg* and Hannover#, Germany, and Dept. of Pathology, University of Pavia+, Italy. In the last years it has been demonstrated that long-term treatment with proton-pump inhibitors can worsen oxyntic mucosal gastritis in H. pylori infected patients. Thi s might result in an increased risk of gastric cancer. In a previous study we found in patients with reflux oesophagitis and/or ulcer disease a detoriation of the parameters of oxyntic mueosal gastritis, activity, chronic inflammation, and atrophy during 5 years treatment with lansoprazole in H. pylori positive patients, but not in H. pylori negative patients (Gastroenterology 1997;112:707). AIM: Intestinal metaplasia (IM) in the stomach, especially type lII of IM, is supposed to be a precursor lesion for mucosal dysplasia and neoplastic transformation. In the present study we investigated the extent and different types of IM in patients with reflux oesophagitis and/or ulcer disease during long-term treatment with lansoprazole. METHODS: 23 patients with reflux disease and 19 patients with peptic ulceration (4 with previous antrectomy), resistant to H2-blockers, were treated with lansoprazole 30-90 mg/day for up to 5 years. H. pylori infection was diagnosed in 19 of the 42 patients. Biopsies were taken prior to lansoprazole, after 3 months, and then every 6 months. In these biopsies intesinal metaplasia was evaluated in sections stained for alcian blue/PAS, high iron diamine, and Gomori's aldehyde fuchsin and classified into the 3 subtypes: complete IM (type I), incomplete IM (type II), and incomplete IM with secretion of sulphomucins (type III). The extent of IM was estimated in relation to the entire muCosa of the biopsy (in %). RESULTS: 1.) Antrum: In the antral stomach 9 of the 38 patients showed IM (type I and II) at the beginning of the study and during follow-up investigations. No patient newly developed IM during the 5 years. The extent of IM did not increase during the study in these 9 patients: 15% (median) prior to lansoprazole and 15% after 5 years. This correlated well with the time course of the scores of gastritis in these patients, which slightly decreased. 2. Oxyntic mucosa: Prior to lansoprazole in 2 patients IM of 5% was found, and 1 antrectomized patient showed pseudopyloric metaplasia. In addition, 1 patient newly developped mild IM of 5% during follow up. In the 2 patients with IM at the beginning, the extent of IM increased from 5% to 50% respective 60% after 5 years of treatment. In both patients no IM of type III could be diagnosed. Severe chronic inflammation and atrophy of the oxyntic mucosa, as well as H. pylori infection, was present in these patients. CONCLUSIONS: Intestinal metaplasia in the antra/stomach did not worsen in patients during long-term treatment with proton-pump inhibitors. In the oxytic stomach the extent of intestinal metaplasia markedly increased but no development of preneoplastic type III intestinal metaplasia could be found. It is questionable whether progression of IM in the oxytic mucosa is of any importance during long-term acid inhibition. Nevertheless, patients with 1M in the oxyntic mucosa should be followed up carefully and H. pylori should be treated in these patients. The study was funded in part by Takeda Pharma, Aachen, Germany.
G0461
H. PYLORI STRAINS IN HOUSEHOLD MEMBERS OF CHILDREN WITH H. PYLORI INFECTION. Y. Elitsur, D. Saeed, and C. Neace. Department of Pediatrics, Pediatric Gastroenterology Div., Marshall University, School of Medicine Huntington, WV. H. pylori infection has been associated with low socioeconomic status and crowding conditions. H. pylori strains, Cag-A/Vac-A, may be used to identify intra-familial contamination. Aims: To identify H. pylori strains, Cag-A/Vac:A, within household members of symptomatic children who were histologically identified with H. pylori infection. Methods: Serum samples of all household members of ten H. pylori seropositive children were prospectively collected. H. pylori seropositivity was identified by HM-CAP ELISA kit or FlexSure rapid test. H. pylori strains, Cag-A/Vac-A, were identified by Immuno-probing Western blot (Helico blot 2.0; GeneLabs Diagnostics, S.A). Results: Ten families with a total of 32 household non-patient members were identified. 20 (62%) had experienced non-specific abdominal symptoms in the past. 28 (88%) were seropositive for H. pylori infection. 12 (37%) were Cag-A positive, 9 (28%) were Vac-A positive, 8 (25%) were positive for both strains, and 14 (44%) were negative for both strains. Identical H. pylori strain between patient and all household members was found in 4 (40%) families. In 4 families (40%), H. pylori strains identity was found in more than 50% of household members, and complete dissociation was found in 2 (20%) families. Conclusion: (1) H. pylori infection is commonly found within household members. (2) The significant identity of H. pylori strains in family members, suggest an intra familiar contamination. (3) We recommend that similar to streptococcal infection, household members of children with H. pylori infection should be serologically screened to prevent future contamination. G0462
H. PYLORI STRAINS IN SYMPTOMATIC AND ASYMPTOMATIC CHILDREN FROM WV. Y. Elitsur, MC. Werthammer, and C. Neace. Department of Pediatrics, Pediatric Gastroenterology Div., Marshall University, School of Medicine Huntington, WV. H. pylori (HP) strains, Cag-A/Vac-A, determine the bacterial virulence and affect morbidity and mortality in adults. The distribution of these strains in the pediatric population in the United States is unknown. Aims: To identify the distribution of HP strains, Cag-A/Vac-A, in symptomatic and asymptomatic children from WV. Methods: Serum samples collected from symptomatic children diagnosed histologically with HP infection, and from children who visited the local pediatric clinic or hospitals for acute illness. HP-seropositivity was measured by commercial kits (HM-CAP, EIA). All positive samples were further evaluated for HP strains by Immunoprobing Western blot (Helico blot 2.0; GeneLabs Diagnostics, S.A). Results: HP-seropositive samples from 132 asymptomatic and 24 symptomatic children were included. Cag-A/Vac-A distribution is shown in Table. No. Patients M/F ratio Mean Age (Y) Cag-A pns. Vac-A pos. Cag-A/Vac-A pos. Cag-A/Vac-A neg.
Symptomatic 24 1:1 14 -+ 2.5 10 (41%) 10 (41%) 07 (29%) 11 (45%)
Asymptomatic 132 0.5:1 15 +_4.8 69 (52%) 72 (54%) 53 (40%) 44 (33%)
T-test NS NS NS NS NS NS
Regression analysis showed no significant difference between positive Cag-A or Vac-A results for age or gender in symptomatic or asymptomatic children. Conclusion: (1) The distribution of HP strains is similar in symptomatic and asymptomatic children from WV. (2) Significant number of HP-seropositive children harbor the virulent strains of the bacteria, indicating potentially higher morbidity for these children. • G0463 CALCIUM SIGNALING IN GASTRIC CELLS EXPOSED TO CagAPOSITIVE AND CagA-NEGATIVE H. PYLORI STRAINS. K. Elliget. M.W. Smith, Dept. of Pathology, University of Maryland, Baltimore, MD; H. Ashktorab, C.R. Allen, D.T. Smoot, G.I. Division, Dept. of Medicine, Howard University, Washington, D.C. Adherence of 1t. pylori to gastric epithelial cells is an important aspect of its pathogenesis. In vitro, 1-1.pylori adherence to gastric epithelial cells has been shown to stimulate signal transduction, resulting in tyrosine phosphorylation and actin polymerization. The following study was conducted to investigate the presence and timing of Ca2+ signaling in gastric ceils exposed to either cagA-positive or cagA-negative H. pylori strains. AGS cells were grown on glass cover slips in DMEM medium with 10% FBS. Cells were washed with PBS, placed in serum-free DMEM, and loaded with 5 IJM Fura-2/AM for 1 hour at room temperature. Three cagA-positive and 3 cagA-negative H. pylori strains were used separately in these experiments. H. pylori at a concentration of 100 bac/gastric cell was added to AGS ceils and [Ca2+]i was measured at 37°C using a Nikon Diaphot inverted microscope integrated to a Tracor
All2 AGA ABSTRACTS G0459 HEALING
OF PEPTIC ULCERS AND ERADICATION OF HELICOBACTER PYLORI UNDER CONDITIONS OF A GASTROENTEROLOGICAL AMBULANCE. H. Eisold, internist and gastroenterologist in practice, M~Sssingen, Germany Objectives: To compare the efficacy and safety of a 7 day triple therapy including lansoprazole 30mg bid with lansoprazole 15mg bid combined with roxithromycin 300mg bid and metronidazole 400mg tid. Methods: 61 patients resp. 41 patients suffering from H. pylori-positive ulcer disease were treated with lansoprazole 30mg bid resp. 15mg bid. Additionally all patients received roxithromycin 300mg bid and metronidazole 400 mg tid for 7 days. Diagnose, healing and H. pylori were assessed by endoscopy, histology and rapid urease test. H. pylori eradication was investigated at least 4 weeks after the end of treatment. Results: Endoscopic healing was achieved in all patients of both groups. H. pylori eradication was obtained in 51 of 61 pateints (82%) in the 30mg bid lansoprazole group and in 36 of 41 patients (88%) in the 15mg bid lansoprazole group. The tolerance was good. Conclusion: The triple regime with lansoprazole 30mg bid resp. lansoprazole 15mg bid combinded with roxithromycin 300mg bid and metronidazole 400rag tid is an effective and cheap treatment for H. pylori eradication in peptic ulcer patients. G0460 INTESTINAL METAPLASIA OF THE GASTRIC MUCOSA DURING LONG-TERM TREATMENT WITH LANSOPRAZOLE. R. Eissele*, G. Brunner#, E. Solcia+, R. Arnold*. Depts. of Gastroenterology, Universities of Marburg* and Hannover#, Germany, and Dept. of Pathology, University of Pavia+, Italy. In the last years it has been demonstrated that long-term treatment with proton-pump inhibitors can worsen oxyntic mucosal gastritis in H. pylori infected patients. Thi s might result in an increased risk of gastric cancer. In a previous study we found in patients with reflux oesophagitis and/or ulcer disease a detoriation of the parameters of oxyntic mueosal gastritis, activity, chronic inflammation, and atrophy during 5 years treatment with lansoprazole in H. pylori positive patients, but not in H. pylori negative patients (Gastroenterology 1997;112:707). AIM: Intestinal metaplasia (IM) in the stomach, especially type lII of IM, is supposed to be a precursor lesion for mucosal dysplasia and neoplastic transformation. In the present study we investigated the extent and different types of IM in patients with reflux oesophagitis and/or ulcer disease during long-term treatment with lansoprazole. METHODS: 23 patients with reflux disease and 19 patients with peptic ulceration (4 with previous antrectomy), resistant to H2-blockers, were treated with lansoprazole 30-90 mg/day for up to 5 years. H. pylori infection was diagnosed in 19 of the 42 patients. Biopsies were taken prior to lansoprazole, after 3 months, and then every 6 months. In these biopsies intesinal metaplasia was evaluated in sections stained for alcian blue/PAS, high iron diamine, and Gomori's aldehyde fuchsin and classified into the 3 subtypes: complete IM (type I), incomplete IM (type II), and incomplete IM with secretion of sulphomucins (type III). The extent of IM was estimated in relation to the entire muCosa of the biopsy (in %). RESULTS: 1.) Antrum: In the antral stomach 9 of the 38 patients showed IM (type I and II) at the beginning of the study and during follow-up investigations. No patient newly developed IM during the 5 years. The extent of IM did not increase during the study in these 9 patients: 15% (median) prior to lansoprazole and 15% after 5 years. This correlated well with the time course of the scores of gastritis in these patients, which slightly decreased. 2. Oxyntic mucosa: Prior to lansoprazole in 2 patients IM of 5% was found, and 1 antrectomized patient showed pseudopyloric metaplasia. In addition, 1 patient newly developped mild IM of 5% during follow up. In the 2 patients with IM at the beginning, the extent of IM increased from 5% to 50% respective 60% after 5 years of treatment. In both patients no IM of type III could be diagnosed. Severe chronic inflammation and atrophy of the oxyntic mucosa, as well as H. pylori infection, was present in these patients. CONCLUSIONS: Intestinal metaplasia in the antra/stomach did not worsen in patients during long-term treatment with proton-pump inhibitors. In the oxytic stomach the extent of intestinal metaplasia markedly increased but no development of preneoplastic type III intestinal metaplasia could be found. It is questionable whether progression of IM in the oxytic mucosa is of any importance during long-term acid inhibition. Nevertheless, patients with 1M in the oxyntic mucosa should be followed up carefully and H. pylori should be treated in these patients. The study was funded in part by Takeda Pharma, Aachen, Germany.
G0461
H. PYLORI STRAINS IN HOUSEHOLD MEMBERS OF CHILDREN WITH H. PYLORI INFECTION. Y. Elitsur, D. Saeed, and C. Neace. Department of Pediatrics, Pediatric Gastroenterology Div., Marshall University, School of Medicine Huntington, WV. H. pylori infection has been associated with low socioeconomic status and crowding conditions. H. pylori strains, Cag-A/Vac-A, may be used to identify intra-familial contamination. Aims: To identify H. pylori strains, Cag-A/Vac:A, within household members of symptomatic children who were histologically identified with H. pylori infection. Methods: Serum samples of all household members of ten H. pylori seropositive children were prospectively collected. H. pylori seropositivity was identified by HM-CAP ELISA kit or FlexSure rapid test. H. pylori strains, Cag-A/Vac-A, were identified by Immuno-probing Western blot (Helico blot 2.0; GeneLabs Diagnostics, S.A). Results: Ten families with a total of 32 household non-patient members were identified. 20 (62%) had experienced non-specific abdominal symptoms in the past. 28 (88%) were seropositive for H. pylori infection. 12 (37%) were Cag-A positive, 9 (28%) were Vac-A positive, 8 (25%) were positive for both strains, and 14 (44%) were negative for both strains. Identical H. pylori strain between patient and all household members was found in 4 (40%) families. In 4 families (40%), H. pylori strains identity was found in more than 50% of household members, and complete dissociation was found in 2 (20%) families. Conclusion: (1) H. pylori infection is commonly found within household members. (2) The significant identity of H. pylori strains in family members, suggest an intra familiar contamination. (3) We recommend that similar to streptococcal infection, household members of children with H. pylori infection should be serologically screened to prevent future contamination. G0462
H. PYLORI STRAINS IN SYMPTOMATIC AND ASYMPTOMATIC CHILDREN FROM WV. Y. Elitsur, MC. Werthammer, and C. Neace. Department of Pediatrics, Pediatric Gastroenterology Div., Marshall University, School of Medicine Huntington, WV. H. pylori (HP) strains, Cag-A/Vac-A, determine the bacterial virulence and affect morbidity and mortality in adults. The distribution of these strains in the pediatric population in the United States is unknown. Aims: To identify the distribution of HP strains, Cag-A/Vac-A, in symptomatic and asymptomatic children from WV. Methods: Serum samples collected from symptomatic children diagnosed histologically with HP infection, and from children who visited the local pediatric clinic or hospitals for acute illness. HP-seropositivity was measured by commercial kits (HM-CAP, EIA). All positive samples were further evaluated for HP strains by Immunoprobing Western blot (Helico blot 2.0; GeneLabs Diagnostics, S.A). Results: HP-seropositive samples from 132 asymptomatic and 24 symptomatic children were included. Cag-A/Vac-A distribution is shown in Table. No. Patients M/F ratio Mean Age (Y) Cag-A pns. Vac-A pos. Cag-A/Vac-A pos. Cag-A/Vac-A neg.
Symptomatic 24 1:1 14 -+ 2.5 10 (41%) 10 (41%) 07 (29%) 11 (45%)
Asymptomatic 132 0.5:1 15 +_4.8 69 (52%) 72 (54%) 53 (40%) 44 (33%)
T-test NS NS NS NS NS NS
Regression analysis showed no significant difference between positive Cag-A or Vac-A results for age or gender in symptomatic or asymptomatic children. Conclusion: (1) The distribution of HP strains is similar in symptomatic and asymptomatic children from WV. (2) Significant number of HP-seropositive children harbor the virulent strains of the bacteria, indicating potentially higher morbidity for these children. • G0463 CALCIUM SIGNALING IN GASTRIC CELLS EXPOSED TO CagAPOSITIVE AND CagA-NEGATIVE H. PYLORI STRAINS. K. Elliget. M.W. Smith, Dept. of Pathology, University of Maryland, Baltimore, MD; H. Ashktorab, C.R. Allen, D.T. Smoot, G.I. Division, Dept. of Medicine, Howard University, Washington, D.C. Adherence of 1t. pylori to gastric epithelial cells is an important aspect of its pathogenesis. In vitro, 1-1.pylori adherence to gastric epithelial cells has been shown to stimulate signal transduction, resulting in tyrosine phosphorylation and actin polymerization. The following study was conducted to investigate the presence and timing of Ca2+ signaling in gastric ceils exposed to either cagA-positive or cagA-negative H. pylori strains. AGS cells were grown on glass cover slips in DMEM medium with 10% FBS. Cells were washed with PBS, placed in serum-free DMEM, and loaded with 5 IJM Fura-2/AM for 1 hour at room temperature. Three cagA-positive and 3 cagA-negative H. pylori strains were used separately in these experiments. H. pylori at a concentration of 100 bac/gastric cell was added to AGS ceils and [Ca2+]i was measured at 37°C using a Nikon Diaphot inverted microscope integrated to a Tracor