title: 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: OBJECTIVE
  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.
  
  
  METHODS
  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.affiliation: Department of Internal Medicine, Tokyo Dental College, Chiba Hospital, Chiba, Japan. tohara@tdc.ac.jp
authors.forename: Tadashi
authors.initials: T
authors.lastname: Ohara
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Morishita
authors.forename: Hidekazu
authors.initials: H
authors.lastname: Suzuki
authors.forename: Tatsuhiro
authors.initials: T
authors.lastname: Masaoka
authors.forename: Hiromasa
authors.initials: H
authors.lastname: Ishii
mesh_terms: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000897:Anti-Ulcer Agents / Q000627:therapeutic use; D005753:Gastric Mucosa / Q000473:pathology; D016481:Helicobacter Infections / Q000188:drug therapy*; D016480:Helicobacter pylori; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D064747:Lansoprazole; D009853:Omeprazole / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D010437:Peptic Ulcer / Q000188:drug therapy* / Q000382:microbiology / Q000503:physiopathology; D054328:Proton Pump Inhibitors; D011899:Ranitidine / Q000627:therapeutic use; D012008:Recurrence; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000897:Anti-Ulcer Agents; D054328:Proton Pump Inhibitors; D014409:Tumor Necrosis Factor-alpha; D064747:Lansoprazole; D007371:Interferon-gamma; D011899:Ranitidine; D009853:Omeprazole