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

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 https://ift.tt/2QqRNDX.

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