Aspects of the Natural History of Sessile Serrated Adenomas/Polyps: Risk Indicators for Carcinogenesis in the Colorectal Mucosa?

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BACKGROUND:Sessile serrated adenomas/polyps are potentially premalignant colorectal lesions that are precursors to colorectal cancer arising via CpG island methylator phenotype. They are caused by the combination of a BRAF mutation and promoter hypermethylation. DNA methylation is an age-dependent phenomenon in the right colon, and we would expect the occurrence and severity of serrated neoplasia to reflect this.OBJECTIVE:The purpose of this study was to document the natural history of sessile serrated adenomas/polyps, including the ages at which they appear and the ranges of their number, size, and associated lesions.DESIGN:This was a retrospective cohort study.SETTINGS:The study was conducted at a tertiary referral center.PATIENTS:Consecutive patients with sessile serrated adenomas/polyps removed between 2006 and 2015 were included. Patients with IBD, familial adenomatous polyposis, Lynch syndrome, serrated polyposis, and hereditary nonpolyposis colorectal cancer were excluded.MAIN OUTCOME MEASURES:Age at which polyps were first diagnosed, location and size of polyps, demographics, and family history were measured.RESULTS:A total of 440 patients had 668 sessile serrated adenomas/polyps, 257 (58%) also had ≥1 adenoma, and 28 (6%) had a history of colorectal cancer. Mean age at diagnosis was 68 ± 11 years, and 45% were men. Two hundred had had ≥1 colonoscopy before the diagnosis of the first sessile serrated adenomas/polyps. A total of 136 patients (31%) had multiple sessile serrated adenomas/polyps, including 24% synchronous and 10% metachronous. The range of total cumulative sessile serrated adenomas/polyps was from 1 to 7. A total of 554 (83%) of 668 sessile serrated adenomas/polyps were right sided; 48% were ≥1 cm diameter and 22% were >2 cm. The size of the first sessile serrated adenomas/polyps in those diagnosed under age 50 years averaged 10 mm, those between 50 and 60 years averaged 12 mm, and those between 60 and 70 years averaged 12 mm.LIMITATIONS:No measurement of methylation or BRAF mutations in polyps or normal mucosa and a lack of subclassification of hyperplastic polyps limited this study.CONCLUSIONS:The age of onset of sessile serrated adenomas/polyps varies, but the pattern is consistent with increasing methylation in the mucosa. Early negative colonoscopies predict a low risk of methylator cancers. See Video Abstract at

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