Proposal for an Organ-Specific Chronic Inflammation–Remodeling–Carcinoma Sequence

Abstract

An organ-specific chronic inflammation–remodeling–carcinoma sequence has been proposed, mainly for the alimentary tract. As representative diseases, gastroesophageal reflux disease, chronic gastritis and inflammatory bowel disease (ulcerative colitis and Crohn’s disease of the colitis type) were adopted for this discussion. Tissue remodeling is such an important part of tumorigenesis in this sequence that an organ-specific chronic inflammation–remodeling–carcinoma sequence has been proposed in detail. Chronic inflammation accelerates the cycle of tissue injury and regeneration; in other words, cell necrosis (or apoptosis) and proliferation result in tissue remodeling in long-standing cases of inflammation. Remodeling encompasses epithelial cell metaplasia and stromal fibrosis, and modifies epithelial–stromal cell interactions. Further, the accumulation of genetic, epigenetic and molecular changes—as well as morphologic disorganization—also occurs during tissue remodeling. The expression of mucosal tissue adapted to chronic inflammatory injury is thought to occur at an early stage. Subsequently, dysplasia and carcinoma develop on a background of remodeling due to continuous, active inflammation. Accordingly, organ-specific chronic inflammation should be ameliorated or well controlled with appropriate monitoring if complete healing is unachievable.