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World J Gastroenterol. Sep 21, 2012; 18(35): 4811-4822
Published online Sep 21, 2012. doi: 10.3748/wjg.v18.i35.4811
Quality of ulcer healing in gastrointestinal tract: Its pathophysiology and clinical relevance
Tetsuo Arakawa, Toshio Watanabe, Tetsuya Tanigawa, Kazunari Tominaga, Yasuhiro Fujiwara, Ken’ichi Morimoto
Tetsuo Arakawa, Toshio Watanabe, Tetsuya Tanigawa, Kazunari Tominaga, Yasuhiro Fujiwara, Ken’ichi Morimoto, Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka 545-8585, Japan
Author contributions: Arakawa T performed all the managements and decision making to conduct animal experiments and clinical studies, and prepared this manuscript; Watanabe T and Tanigawa T performed most of the animal experiments; Tominaga K and Fujiwara Y performed most of the human study of peptic ulcer disease; Morimoto K performed the human study of Crohn’s disease.
Correspondence to: Tetsuo Arakawa, MD, PhD, Professor, Dean and Chairman, Department of Gastroenterology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585, Japan. arakawat@med.osaka-cu.ac.jp
Telephone: +81-6-66453810 Fax: +81-6-66463413
Received: July 20, 2012
Revised: August 2, 2012
Accepted: August 26, 2012
Published online: September 21, 2012
Processing time: 194 Days and 10.7 Hours
Abstract

In this paper, we review the concept of quality of ulcer healing (QOUH) in the gastrointestinal tract and its role in the ulcer recurrence. In the past, peptic ulcer disease (PUD) has been a chronic disease with a cycle of repeated healing/remission and recurrence. The main etiological factor of PUD is Helicobacter pylori (H. pylori), which is also the cause of ulcer recurrence. However, H. pylori-negative ulcers are present in 12%-20% of patients; they also recur and are on occasion intractable. QOUH focuses on the fact that mucosal and submucosal structures within ulcer scars are incompletely regenerated. Within the scars of healed ulcers, regenerated tissue is immature and with distorted architecture, suggesting poor QOUH. The abnormalities in mucosal regeneration can be the basis for ulcer recurrence. Our studies have shown that persistence of macrophages in the regenerated area plays a key role in ulcer recurrence. Our studies in a rat model of ulcer recurrence have indicated that proinflammatory cytokines trigger activation of macrophages, which in turn produce increased amounts of cytokines and chemokines, which attract neutrophils to the regenerated area. Neutrophils release proteolytic enzymes that destroy the tissue, resulting in ulcer recurrence. Another important factor in poor QOUH can be deficiency of endogenous prostaglandins and a deficiency and/or an imbalance of endogenous growth factors. Topically active mucosal protective and antiulcer drugs promote high QOUH and reduce inflammatory cell infiltration in the ulcer scar. In addition to PUD, the concept of QOUH is likely applicable to inflammatory bowel diseases including Crohn’s disease and ulcerative colitis.

Keywords: Quality of ulcer healing; Peptic ulcer disease; Recurrence; Prostaglandin; Cytokines; Growth factors