The serrated neoplasia pathway to colorectal cancer: Molecular biology and clinical management

Colorectal cancer (CRC) is one of the most common types of cancer worldwide, and develops from colonic polyps. Traditionally, adenomatous polyps were considered the sole precursor lesion. We now know that 15-30% derives from serrated polyps instead. Serrated polyps are not well understood, and are frequently missed during colonoscopy due to their subtle appearance and (until recently) benign reputation. This seems to results in the development of preventable postcolonoscopy colorectal cancer. In part I of this thesis we therefore focus on improving serrated polyp detection among endoscopist. We demonstrate that education is a very effective intervention to accomplish this. We also describe several driver mutations that might be responsible for malignant conversion of serrated polyps. Part II of this thesis focuses on serrated polyposis syndrome, characterized by many serrated polyps and an increased CRC risk. We studied a new personalised protocol for the surveillance of these patients. This protocol was safe and effective, with a 40% reduction of surveillance colonoscopies without an increased CRC risk. Furthermore, we studied serrated polyposis syndrome patients with a history of extensive colonic surgery. We demonstrate that these patients have a low residual CRC risk, and propose that future studies should assess the safety of extending surveillance intervals for these patients up to five years. Finally, we have analysed over 10 years follow-up data of serrated polyposis syndrome patients in our centre. These data show that endoscopic surveillance is highly effective in CRC prevention, reducing CRC incidence to a near-normal with few colonoscopy related complications