Inflammatory bowel disease-related colorectal cancer: Past, present and future perspectives

Abstract

Inflammatory bowel disease-related colorectal cancer (IBD-CRC) is one of the most serious complications of IBD contributing to significant mortality in this cohort of patients. IBD is often associated with diet and lifestyle-related gut microbial dysbiosis, the interaction of genetic and environmental factors, leading to chronic gut inflammation. According to the “common ground hypothesis”, microbial dysbiosis and intestinal barrier impairment are at the core of the chronic inflammatory process associated with IBD-CRC. Among the many underlying factors known to increase the risk of IBD-CRC, perhaps the most important factor is chronic persistent inflammation. The persistent inflammation in the colon results in increased proliferation of cells necessary for repair but this also increases the risk of dysplastic changes due to chromosomal and microsatellite instability. Multiple pathways have been identified, regulated by many positive and negative factors involved in the development of cancer, which in this case follows the ‘inflammation-dysplasia-carcinoma’ sequence. Strategies to lower this risk are extremely important to reduce morbidity and mortality due to IBD-CRC, among which colonoscopic surveillance is the most widely accepted and implemented modality, forming part of many national and international guidelines. However, the effectiveness of surveillance in IBD has been a topic of much debate in recent years for multiple reasons — cost-benefit to health systems, resource requirements, and also because of studies showing conflicting long-term data. Our review provides a comprehensive overview of past, present, and future perspectives of IBD-CRC. We explore and analyse evidence from studies over decades and current best practices followed globally. In the future directions section, we cover emerging novel endoscopic techniques and artificial intelligence that could play an important role in managing the risk of IBD-CRC.

Keywords: Inflammatory bowel disease, Colorectal cancer, Colitis-associated cancer, Surveillance in inflammatory bowel disease, Dye-spray colonoscopy, Adenomas, Dysplasia, Colectomy

Core Tip: The focus of the review is on the evolution of inflammatory bowel disease-related colorectal cancer (IBD-CRC) based on literature over the past decades to the present day. We provide a comprehensive overview of risk factors associated with IBD-CRC, molecular pathways identified and current strategies used to reduce incidence globally. We also touch upon the history of surveillance practice, its effectiveness, and the latest guidance on IBD surveillance by international societies. In a section on future directions, we discuss introduction of novel endoscopic technologies, artificial intelligence, and potential use of microbiota modulation, all of which could help reduce the risk of IBD-CRC.