Usefulness of proton pump inhibitor (PPI) maintenance therapy for patients with H. pylori-negative recurrent peptic ulcer after eradication therapy for H. pylori: pathophysiological characteristics of H. pylori-negative recurrent ulcer scars and beyond acid suppression by PPI.

Abstract

BACKGROUND/AIMS:

Problems after Helicobacter pylori (Hp) eradication therapy include recurrence of Hp-negative peptic ulcers. We investigated the pathophysiological characteristics of Hp-negative recurrent ulcer scars, and performed proton pump inhibitor (PPI) maintenance therapy as a new therapy for prevention of recurrence in patients with Hp-negative recurrence after Hp eradication and investigated its usefulness.

METHODOLOGY:

The subjects were 21 patients with Hp-negative recurrent peptic ulcers after Hp eradication (gastric ulcer: 19, duodenal ulcer: 2) and 25 patients with non-recurrent ulcers (gastric ulcer: 20, duodenal ulcer: 5). The mucosa from the ulcer scar lesion was endoscopically obtained from patients, and HE staining, CD68 immunohistochemical staining, and investigation of the mucosal expression levels of TNF-alpha and IFN-gamma were performed by ELISA. Patients with recurrence after eradication were divided into two groups at the time of ulcer scar after the first treatment, and received maintenance therapy: the intermittent treatment group that received lansoprazole (LPZ), 30 mg/day, on two days on weekends (gastric ulcer: 9, duodenal ulcer: 1) and the ranitidine (RAN) 150 mg/day daily treatment group (gastric ulcer: 8, duodenal ulcer: 1).

RESULTS:

Infiltration of CD68-positive inflammatory cells was observed in the lamina propria mucosae over the epithelial layer in ulcer scars of the Hp-negative recurrent ulcer group compared with the non-recurrent ulcer group, and TNF-alpha and IFN-gamma significantly increased (27.22+/-6.23 pg/mg, 52.12+/-5.41 pg/mg vs. 4.23+/-2.14 pg/mg, 7.11+/-3.06 pg/mg, P<0.001). In the RAN maintenance therapy group, the ulcer recurred within 10 months in all patients, while the ulcer recurred in only one patient in the intermittent LPZ treatment group.

CONCLUSIONS:

These results suggested that the pathophysiological characteristic of Hp-negative recurrent ulcer scar lesions after eradication was infiltration of inflammatory cells, mainly monocytes/macrophages, in the lamina propria mucosae over the epithelial layer, and this may be a key factor in ulcer recurrence. Furthermore, intermittent PPI therapy using LPZ may be a useful maintenance therapy for prevention of recurrence in these cases.

• Authors: Tadashi Ohara, Tetsuo Morishita, Hidekazu Suzuki, Tatsuhiro Masaoka, Hiromasa Ishii
• Journal: Hepato-gastroenterology (Hepatogastroenterology) 2004 Mar-Apr Vol. 51 Issue 56 Pg. 338-42 ISSN: 0172-6390 [Print] Greece
• PMID: 15086153 (Publication Type: Comparative Study, Journal Article)

Chemical References

• 2-Pyridinylmethylsulfinylbenzimidazoles
• Anti-Ulcer Agents
• Proton Pump Inhibitors
• Tumor Necrosis Factor-alpha
• Lansoprazole
• Interferon-gamma
• Ranitidine
• Omeprazole

Topics

• 2-Pyridinylmethylsulfinylbenzimidazoles
• Anti-Ulcer Agents (therapeutic use)
• Gastric Mucosa (pathology)
• Helicobacter Infections (drug therapy)
• Helicobacter pylori
• Humans
• Interferon-gamma (metabolism)
• Lansoprazole
• Omeprazole (analogs & derivatives, therapeutic use)
• Peptic Ulcer (drug therapy, microbiology, physiopathology)
• Proton Pump Inhibitors
• Ranitidine (therapeutic use)
• Recurrence
• Tumor Necrosis Factor-alpha (metabolism)