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

Isao Okayasu,Tsutomu Yoshida,Masaaki Ichinoe

doi:10.3390/gidisord1030028

Isao Okayasu, Tsutomu Yoshida + Show 1 more

Open Access

https://doi.org/10.3390/gidisord1030028

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Journal: Gastrointestinal Disorders	Publication Date: Aug 29, 2019
Citations: 2	License type: CC BY 4.0

Affiliation: Kiryu University, Kitasato University

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.

Highlights

It is believed that chronic inflammation induces carcinoma development in various organs.This has been predominantly shown at the epidemiological level
We propose a sequence of organ-specific chronic inflammation–remodeling leading to carcinoma
Focusing on tissue remodeling induced by chronic inflammation, we summarize and discuss tumorigenesis in organ-specific chronic inflammation (Figure 1)

Summary

Introduction

It is believed that chronic inflammation induces carcinoma development in various organs. This has been predominantly shown at the epidemiological level. The remodeling of target tissues by chronic or repeated inflammation has gone largely unnoticed and is important as a background for cancer development [1,2]. We propose a sequence of organ-specific chronic inflammation–remodeling leading to carcinoma. Typical examples include: gastroesophageal reflux disease (GERD)–Barrett’s esophagus–adenocarcinoma; chronic active gastritis–atrophic gastritis–gastric carcinoma; inflammatory bowel disease (IBD), ulcerative colitis (UC) and Crohn’s disease of colitis type–remodeled regenerative mucosa–dysplasia–colorectal carcinoma; chronic hepatitis–liver cirrhosis–hepatocellular carcinoma; and chronic cholecystitis–gall bladder carcinoma [3,4] in the alimentary tract. ** inflammatory bowel disease (IBD) includes ulcerative colitis and Crohn’s disease of colitis. **Chronic inflammatory bowel disease (IBD) includes ulcerativeSequence colitis and Crohn’s disease of Sequence in the alimentary tract. * This sequence shows no remodeling moving toward to carcinoma development. **Chronic inflammatory bowel disease (IBD) includes ulcerativeSequence colitis and Crohn’s disease of

Organ-Specific

Chronic

Findings

Conclusions