April 1998

Results: Out of 98 per-protocol patients 85 (87%; 78%-93% [95% C1]) and 93 (95%; 88%-98% [95% CI]) were healed at 4 and 8 weeks, respectively. Intention to treat analysis revealed healing rates of 77% (68%-85%) after 4 and 85% (76%-91%) after 8 weeks. Key symptoms of GERD were markedly reduced after 3 days treatment with i.v. pantoprazole. At 2 weeks heartburn, acid eructation and pain on swallowing resolved in 97%, 98% and 100%, respectively of the i.v./p.o, per protocol collective. With the i.v./p.o, regimen 7 adverse events (AE) in 6 patients were recorded. The incidence of all AEs was 1. 6 AEs were considered as not related and 1 (pain in extremity) as unlikely related to pantoprazole. Conclusion: Treatment of reflux esophagitis grade 11/Ill with intravenous pantoprazole (40 mg o.m.) over 5 to 7 days followed by its oral application up to a maximum of 7 weeks represents a powerful regimen for endoscopic healing and symptom relief. The i.v./p.o, regimen is a very well tolerated and safe therapy. [ 1] M/Sssner Jet al. (1995) Aliment Pharmacol Ther 9, 321-326. [2] Koop H et al. (1995) J Clin Gastroentero120, 192-195. This study was funded by Byk Gulden Pharmaceuticals, Konstanz, Germany

G1368 ERADICATION OF HELICOBACTER PYLORI BY MEANS OF A LOW-DOSE ONE-WEEK TRIPLE THERAPY CONTAINING PANTOPRAZOLE, CLARITHROMYCIN AND METRONIDAZOLE. H. Wurzer (1), p. Kratochvil (2), Th. Stupnicki (3), & Austrian Pantoprazol Study Group. (1) Medical Dpt. II, General Hospital, Graz; (2) Styrian Health Insurance Fund, Graz; (3) Medical Dpt., General Hospital, Deutschlandsberg; Austria

Purpose: The aim of this study was to assess the efficacy and safety of a seven day triple therapy comprising pantoprazole, clarithromycin and metronidazole in the cure of H. pylori (Hp) infection. Methods: 61 patients were screened. During the first week, when culture was performed, symptoms were treated with 300 mg s.i.d, ranitidine. 9 patients with resistant strains were excluded from treatment, 3 had no Hpinfection. 49 patients (27 male, 22 female; median age 52 years) with Hppositive (rapid urease test, histology, culture) duodenal ulcer (35 pts) or non-ulcer dyspepsia (14 pts) were enrolled in this open-labeled, multicenter study. After culture had shown sensitivity to clarithromycin and metronidazole, patients received 40 mg o.m. pantoprazole, 250 mg b.i.d, clarithromycin and 500 mg b.i.d. metronidazole for 7 days (PCM). Control endoscopy was performed at least 4 weeks after the end of therapy (urease test, histology, culture). Results: 37 patients were evaluable according to the protocol. 12 patients were classed as protocol violators (8 major deviations to time schedule; 1 adverse event which was not related to study medication, 2 received PCM in spite of resistance to metronidazole and 2 received forbidden medication). 87% achieved cure of Hp-infection (71-96% [95% CI], 93% showed ulcer healing. After 1 week pretreatment with ranitidine 31% were free of epigastric pain, after 7 days triple therapy (PCM) and at study end 77% and 89%, respectively. Intention to treat analysis revealed 82% to be cured of Hp-infection (68-91% [95% CI]), ulcers were healed in 91%. 6 adverse events (AE) occurred in 4/49 patients. 1 AE showed up during the pretreatment period. The most frequent AE was taste disturbance. Conclusion: Low dose triple regimen of pantoprazole, clarithromycin and metronidazole is a highly effective and safe therapy for cure of H. pylori infection and ulcer healing. This study was funded by Byk Austria Pharmaceuticals, Vienna, Austria

• G1369

HELICOBACTER PYLORI-ASSOCIATED ANTRALIZATION OF PROXIMAL GASTRIC MUCOSA IS LINKED TO AN INCREASED RISK OF DEVELOPMENT OF INTESTINAL METAPLASIA. HH-X Xia, J Kalantar, J Ma Wyatt, S Adams, K Cheung and NJ Talley. Departments of Medicine and Pathology, University of Sydney, Nepean Hospital, Sydney, Australia

BACKGROUND: Gastric carcinogenesis is a multi-step process, progressing from chronic gastritis to intestinal metaplasia and dysplasia, but the "point of no return" has not been defined. We hypothesised that a change to antral type mucosa in the proximal stomach plays a role in this process. The aims of this study were to determine i) the distribution of mucosal types in biopsies taken from different gastric sites in H. pylori-infected and non-infected patients; and ii) whether the presence of antral mucosa (antralization) in the incisura, body and fundus was associated with the presence and severity of intestinal metaplasia (IM) at these sites. METHODS: 242 patients with dyspepsia were enrolled. Eight biopsies, ie. antrum (A) x3, body (B) x2, fundus (F) x2 and incisura (I) xl were obtained by a standard mapping protocol. One antral biopsy was used for the CLO-test. Three (one each from A, B and F) were cultured. The remaining biopsies were examined histologically according to the updated Sydney System after staining with H&E and Giemsa. Specific anti-//, pylori IgG antibodies were also detected using a validated ELISA test. RESULTS: Overall, 107 (44%) patients were infected with H. pylori (HP). Antral-type mucosa in the incisura was more prevalent in infected patients than in uninfected patients (89% (95/107) vs. 29% (39/135), OR=19.5, p < 0.0001, Z2-test). Antral type mucosa was also observed in the body and

Esophageal, Gastric, and Duodenal Disorders A335

fundus in five and three cases, respectively. The prevalence of IM was 23% and 12% in infected and uninfected groups, respectively (p < 0.05); the rates for the gastric antrum, incisura, body and fundus biopsies in infected and uninfected groups were 18% (19/107) and 8.1% (11/135) (p < 0.05), 12% (13/107) and 3.7% (5/135) (p < 0.02), 3.7% (4/107) and 2.2% (3/135), and 1.9% (2/107) and 0.7% (1/135), respectively. Moreover, IM was strongly associated with antralization in the incisura (13% vs. 0.9%, OR=15.5, p< 0.001), body (40% vs. 2.1%, OR=30.9, p<0.01) and fundus (33% vs. 0.8%, OR=59.3, p < 0.05) (Table).

Biopsy Prevalence (%) of intestinal metaplasia site Antralization Non-antralization

HP+ HP- Total HP+ HP- Total Incisura 14% (13D5) 10% (4/39) 13%(17/134)* 0(0/12) 1% (1/96) 0.9% (1/108) Body 33% (.1/3) 50% (1/2) 40% (2/5)* 2.9% (3/104) 1.5% (2/133) 2.1% (5/237) Fundus 100%(1/1) 0(0/2) 33%(1/3)** 0.9%(1/106) 0.8%(1/133) 0.8%(2/239) *, compared with non-antralization group, p < 0.00l ; ** p < 0.02.

The grade of IM increased from the distal to proximal stomach; the antrum 1.39 4- 0.72 (mean ± SD), incisura 1.78 _-. 0.94, body 2.3 ± 0.95 and fundus 2.33 ± 1.16 (F=3.16, p < 0.05). However, there was no significant difference in the grade of IM in the proximal stomach in those with and without antralisation (1.86 -+ 0.96 vs. 2.29 -+ 0.95). CONCLUSIONS: Antralization of the proximal stomach is common in H. pylori infected patients, and is associated with an increased risk of developing intestinal metaplasia. Antralization may represent a marker for gastric cancer risk.

• G1370

ANTI-SECRETORY DRUGS INCREASE CORPUS GASTRITIS BUT ONLY IN THE PRESENCE OF HELICOBACTER PYLORI INFECTION. HH-X Xia, J Kalantar, GD Eslick, I Ma Wyatt, S Adams, K Cheung and NJ Talley. Departments of Medicine and Pathology, University of Sydney, Nepean Hospital, Australia

BACKGROUND: It has been reported that proton pump inhibitors (PPIs) and H 2 blockers increase gastric inflammation in H. pylori infected individuals. Whether this effect is caused by acid suppression alone or by the interaction between antisecretory drugs and H. pylori is unknown. The aim of this study was to determine whether PPIs and H z blockers had the same effects in H. pylori positive and negative patients. METHODS: 242 patients with dyspepsia (120 males and 122 females; mean age of 52.4 years) were enrolled. Eight biopsies, ie. antrum (A) x3, body (B) x2, fundus (F) x2 and incisura (I) xl were taken from each patient during gastroscopy. One antral biopsy was used for the CLO-test. Three (one each from A, B and F) were cultured. The remaining biopsies were examined histologically according to the updated Sydney System after staining with H&E and Giemsa; severity and activity of chronic gastritis were graded. Administration of PPIs and H 2 blockers in the four week period prior to endoscopy was recorded. RESULTS: Overall, 95 patients were infected with H. pylori by CLO-test, histology and/or culture. Of these patients, 45 had taken H 2 blockers and seven PPIs. Among the 147 patients without H. pylori infection, 48 had taken H 2 blockers and 24 PPIs. The association of administration of these anti- secretory drugs with severity and activity of gastritis at different sites is shown in the Table.

Groups

H.pylori positive None H 2 blockers PPIs H.pylori negative None H 2 blockers PPIs

Score (mean) of gastritis a Antrum Incisura Body Fundus

Severity Activity Severity Activity Severity Activity Severity Activity

1.79 0.84 1.95 0.79 1.35 0.61 1.28 0.44 1.78 0.82 1.89 0.80 1.53 0.71" 1.42 0.58 1.67 0.50* 1.50 0 .50 2.0** 1.00"* 1.5 0.83**

0.44 0 .07 0 ,65 0 .09 0 .31 0 . 1 2 0 .32 0.11 0.10"* 0"* 0.34** 0.02** 0.02** 0.02** 0.08** 0"* 0.33 0 .04 0 .48 0.13 0.21 0"* 0.17" 0.08

a, severity of gastritis was graded as 0 (normal), 1 (mild), 2 (moderate) and 3 (marked) and activity of gastritis was graded as 0 (absent) and 1 (present). *, compared with group without anti-secondary therapy, p < 0.05; ** p < 0.01.

CONCLUSIONS: Proton pump inhibitors are associated with more severe body gastritis in the presence of H. pylori infection; this was not observed in the absence of the infection (scores were actually better). H 2 blockers did not significantly increase body gastritis (but in the absence of infection all scores were significantly better). These findings suggest that anti-secretory drugs do not worsen gastritis in the absence of H. pylori infection.