Skip to main content

Advertisement

SpringerLink
Log in

Clinical trial: rebamipide promotes gastric ulcer healing by proton pump inhibitor after endoscopic submucosal dissection—a randomized controlled study

  • Original Article—Alimentary Tract
  • Published:
Journal of Gastroenterology Aims and scope Submit manuscript

Abstract

Background

Endoscopic submucosal dissection (ESD) is useful for treating gastric tumors. Several trials have shown the efficacy of 4 or 8 weeks of proton pump inhibitor (PPI) administration for post-ESD ulcers. However, if the size of the post-ESD ulcer is larger than predicted, PPI administration alone might not be sufficient for the ulcer to heal within 4 weeks. We examined the efficacy of a combination therapy of PPI and rebamipide, a mucosal-protective antiulcer drug, on the acceleration of post-ESD ulcer healing.

Methods

Patients were randomly assigned to either the PPI and rebamipide therapy or the PPI alone. Sixty-two consecutive patients with gastric tumors gave informed consent for enrolling in the study. In all cases, the estimated size of the post-ESD ulcer was larger than 20 mm. Oral administration of the drug was started on the 2nd day post-ESD and continued to the 28th day.

Results

All patients received the assigned pharmaceuticals and adhered well to the treatment regimen for 28 days. The endpoint ulcers reached S1 (scar stage) in 11/31 (36%) patients in the PPI-only group and in 21/31 (68%) in the combination group (P = 0.010).

Conclusions

The combination of PPI plus rebamipide was more effective than the PPI alone for treating ulcers larger than 20 mm within 4 weeks after ESD.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Rembacken BJ, Gotoda T, Fujii T, Axon ATR. Endoscopic mucosal resection. Endoscopy. 2001;33:709–18.

    Article  CAS  PubMed  Google Scholar 

  2. Soetikno RM, Gotoda T, Nakanishi Y, Soehendra N. Endoscopic mucosal resection. Gastrointest Endosc. 2003;57:567–79.

    Article  PubMed  Google Scholar 

  3. Yanai H, Matsubara Y, Kawano T, Okamoto T, Hirano A, Nakamura Y, et al. Clinical impact of strip biopsy for early gastric cancer. Gastrointest Endosc. 2004;60:771–7.

    Article  PubMed  Google Scholar 

  4. Watanabe K, Ogata S, Kawazoe S, Watanabe K, Koyama T, Kajiwara T, et al. Clinical outcomes of EMR for gastric tumors: historical pilot evaluation between endoscopic submucosal dissection and conventional mucosal resection. Gastrointest Endosc. 2006;63:776–82.

    Article  PubMed  Google Scholar 

  5. Uedo N, Takeuchi Y, Yamada T, Ishihara R, Ogiyama H, Yamamoto S, et al. Effect of a proton pump inhibitor or an H2-receptor antagonist on prevention of bleeding from ulcer after endoscopic submucosal dissection of early gastric cancer: a prospective randomized controlled trial. Am J Gastroenterol. 2007;102:1610–6.

    Article  CAS  PubMed  Google Scholar 

  6. Oh TH, Jung HY, Choi KD, Lee GH, Song HJ, Choi KS, et al. Degree of healing and healing-associated factors of endoscopic submucosal dissection-induced ulcers after pantoprazole therapy for 4 weeks. Dig Dis Sci. 2009;54:1494–9.

    Article  CAS  PubMed  Google Scholar 

  7. Kakushima N, Fujishiro M, Yahagi N, Kodashima S, Nakamura M, Omata M. Helicobactor pylori status and the extent of gastric atrophy do not affect ulcer healing after endoscopic submucosal dissection. J Gastroenterol Hepatol. 2006;21:1586–9.

    Article  PubMed  Google Scholar 

  8. Furuta T, Sugimoto M, Kodaira C, Nishino M, Yamade M, Ikuma M, et al. CYP2C19 genotype is associated with symptomatic recurrence of GERD during maintenance therapy with low-dose lansoprazole. Eur J Clin Pharmacol. 2009;65:693–8.

    Article  CAS  PubMed  Google Scholar 

  9. Terano A, Arakawa T, Sugiyama T, Suzuki H, Joh T, Yoshikawa T, et al. Rebamipide, a gastro-protective and anti-inflammatory drug, promotes gastric ulcer healing following eradication therapy for Helicobactor pylori in Japanese population: a randomized, double-blind, placebo-controlled trial. J Gastroenterol. 2007;42:690–3.

    Article  CAS  PubMed  Google Scholar 

  10. Yamasaki K, Ishiyama H, Imaizumi T, Kanbe T, Yabuuchi Y, et al. Effect of OPC-12759, a novel antiulcer agent, on chronic and acute experimental gastric ulcer, and gastric secretion in rats. Jpn J Pharmacol. 1989;49:441–8.

    Article  CAS  PubMed  Google Scholar 

  11. Park SH, Cho CS, Lee OY, Jun JB, Lin SR, Zhou LY, et al. Comparison of prevention of NSAID-induced gastrointestinal complications by rebamipide and misoprostol: a randomized, multicenter, controlled trial—STORM STUDY. J Clin Biochem Nutr. 2007;40:148–55.

    Article  CAS  PubMed  Google Scholar 

  12. Du T, Li Z, Zhan X, Chen J, Gao J, Gong Y, et al. Anti-inflammatory effects of rebamipide according to Helicobacter pylori status in patients with chronic erosive gastritis: a randomized sucralfate-controlled multicenter trial in China—STARS study. Dig Dis Sci. 2008;53:2886–95.

    Article  CAS  PubMed  Google Scholar 

  13. Tarnawski A, Arakawa T, Kobayashi K. Rebamipide treatment activates epidermal growth factor and its receptor expression in normal and ulcerated gastric mucosa in rats: one mechanism for its ulcer healing action? Dig Dis Sci. 1998;43:90S–8S.

    Article  CAS  PubMed  Google Scholar 

  14. Tarnawski A, Chai J, Pai R, Chiou SK. Rebamipide activates genes encoding angiogenic growth factors and Cox2 and stimulates angiogenesis: a key to its ulcer healing action? Dig Dis Sci. 2004;49:202–9.

    Article  CAS  PubMed  Google Scholar 

  15. Lee SY, Kim JJ, Lee JH, Kim YH, Rhee PL, Paik SW, et al. Healing rate of EMR-induced ulcer in relation to the duration of treatment with omeprazole. Gastrointest Endosc. 2004;60:213–7.

    Article  PubMed  Google Scholar 

  16. Ye BD, Cheon JH, Choi KD, Kim SG, Kim JS, Jung HC, et al. Omeprazole may be superior to famotidine in the management of iatrogenic ulcer after endoscopic mucosal resection: a prospective randomized controlled trial. Aliment Pharmacol Ther. 2006;24:837–43.

    Article  CAS  PubMed  Google Scholar 

  17. Sakita T, Fukutomi H. Endoscopic diagnosis. In: Yoshitoshi Y, editor. Ulcer of the stomach and duodenum (in Japanese). Tokyo: Nankodo; 1971. p. 198–208.

    Google Scholar 

  18. Gotoda T. A large endoscopic resection by endoscopic submucosal dissection procedure for early gastric cancer. Clin Gastroenterol Hepatol. 2005;3:S71–3.

    Article  PubMed  Google Scholar 

  19. Ono H, Kondo H, Gotoda T, Shirao K, Yamaguchi H, Saito D, et al. Endoscopic mucosal resection for treatment of early gastric cancer. Gut. 2001;48:225–9.

    Article  CAS  PubMed  Google Scholar 

  20. Minami S, Gotoda T, Ono H, Oda I, Hamanaka H. Complete endoscopic closure of gastric perforation induced by endoscopic resection of early gastric cancer using endoclip can prevent surgery (with video). Gastrointest Endosc. 2006;63:596–601.

    Article  PubMed  Google Scholar 

  21. Oda I, Gotoda T, Hamanaka H, Eguchi T, Saito Y, Matsuda T, et al. Endoscopic submucosal dissection for early gastric cancer: technical feasibility, operation time and complications from a large series of consecutive cases. Dig Endosc. 2005;17:54–8.

    Article  Google Scholar 

  22. Yamaguchi Y, Katsumi N, Tauchi M, Toki K, Nakamura K, Aoki Y, et al. A prospective randomized trial of either famotidine or omeprazole for the prevention of bleeding after endoscopic mucosal resection and the healing of endoscopic mucosal resection-induced ulceration. Aliment Pharmacol Ther. 2005;21:111–5.

    Article  CAS  PubMed  Google Scholar 

  23. Kakushima N, Yahagi N, Fujishiro M, Iguchi M, Oka M, Kobayashi K, et al. The healing of gastric ulcers after endoscopic submucosal dissection. Dig Endosc. 2004;16:327–31.

    Article  Google Scholar 

Download references

Conflict of interest statement

None.

Author information

Authors and Affiliations

  1. Department of Gastroenterology, Gifu University Hospital, Gifu, Japan

    Tomohiro Kato, Hiroshi Araki, Fumito Onogi, Takashi Ibuka, Masahito Nagaki & Hisataka Moriwaki

  2. Department of Gastroenterology, Gifu Municipal Hospital, 7-1 Kashima-cho, Gifu, 500-8513, Japan

    Tomohiro Kato, Akihiko Sugiyama & Eiichi Tomita

Authors
  1. Tomohiro Kato
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hiroshi Araki
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Fumito Onogi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Takashi Ibuka
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Akihiko Sugiyama
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Eiichi Tomita
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Masahito Nagaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Hisataka Moriwaki
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Tomohiro Kato.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kato, T., Araki, H., Onogi, F. et al. Clinical trial: rebamipide promotes gastric ulcer healing by proton pump inhibitor after endoscopic submucosal dissection—a randomized controlled study. J Gastroenterol 45, 285–290 (2010). https://doi.org/10.1007/s00535-009-0157-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00535-009-0157-0

Keywords

Search

Navigation