Helicobacter pylori gastritis and epithelial cell proliferation in patients with reflux oesophagitis after treatment with lansoprazole

Abstract

Background: Helicobacter pylori gastritis may spread proximally in the stomach during profound acid inhibition.

Aims: To examine histological gastric body changes and epithelial cell proliferation before and after treatment with lansoprazole.

Patients and methods: Patients diagnosed as having reflux oesophagitis grade 1 or 2 were enrolled and treated for 12 weeks with lansoprazole (30 mg every morning). After 12 weeks, 103 of the 118 patients appeared endoscopically healed and were asymptomatic; they then received maintenance treatment with 15 or 30 mg lansoprazole daily. Biopsy specimens obtained from similar sites before and after treatment, were available from 90 patients after a median of 64 weeks (range 15-73 weeks). Epithelial cell proliferation was determined by the number of Ki-67 antigen positive cells per gland.

Results: Of these 90 patients, 44 (49%) were found to be infected with H pylori. Their median inflammation score had increased from grade 1 before to grade 2 after treatment (p < 0.0001). Initially, the number of Ki-67 antigen positive cells per gland was significantly higher in the H pylori infected than in the uninfected group and increased further after treatment (p < 0.0001). In uninfected patients, no significant change in inflammation or proliferation occurred during treatment.

Conclusions: A marked increase in body gastritis was observed in H pylori infected individuals during long term treatment with the proton pump inhibitor lansoprazole. Epithelial cell proliferation and atrophy also increased in infected but not in uninfected patients.

Figure 1

: Scatter diagrams depicting (A) grade of corpus inflammation, (B) inflammatory activity, and (C) atrophy in H pylori infected and uninfected patients before and after treatment. Median scores indicated by horizontal lines.

Figure 2

: Effect of lansoprazole treatment on histology of gastric body mucosa (H&E staining) in H pylori infected patients. Few leucocytes are present within the lamina propria (grade 1 inflammation, grade 0 activity) in one patient before treatment (A); after 64 weeks of treatment, intensified inflammation (grade 2 inflammation, grade 1 activity) is evident (B). In another patient, neutrophils are absent before treatment (C); after 48 weeks of treatment, numerous neutrophils appear in the isthmus region and within the epithelium (D). In a third patient, moderate (grade 2) inflammation but no glandular atrophy is present before treatment (E); after 65 weeks of treatment, mild to moderate loss of glands (grade 1 atrophy) is evident together with persistent inflammation (F). Original magnifications: A and B, ×250; C and D, ×400; E and F, ×160.

Figure 3

: Immunostaining of Ki-67 nuclear antigen positive cells in the body isthmus zone of a patient without (A) or with (B) gastritis before lansoprazole treatment. Positive nuclei are stained brown. Immunoperoxidase counterstained with haematoxylin. Original magnifications: A, ×1000; B, ×400.

Figure 4

: Scatter diagram depicting gastric body epithelial cell proliferation in H pylori infected and uninfected patients before and after lansoprazole treatment. Data based on immunostaining for Ki-67 nuclear antigen. Median values indicated by horizontal lines.

Figure 5

: Scatter diagram depicting Ki-67 nuclear antigen positive cells per gastric gland in relation to grade of inflammation at the start of the study in H pylori infected and uninfected patients as indicated (Spearman's r=0.72, p<0.0001). Median values indicated by horizontal lines.