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Management of Serrated Polyps of Colorectum Eric YF Cheung Department of Surgery, NDH Three messages Serrated polyp-adenocarcinoma sequence Malignant risk of serrated polyps of colorectum Management and Surveillance: New guidelines needed Serrated polyps—An overview Colorectal polyps Adenoma Tubular adenoma Tubulovillous adenoma Villous adenoma Hyperplastic polyp/Serrated polyp Harmatoma Juvenile polyp Peutz-Jeghers polyps Inflammatory polyp Lymphoid aggregates Traditionally viewed as innocuous Serrated polyps (WHO) Hyperplastic polyp (HP): Small distal Microvesicular (MVHP) Globet-cell rich (GCHP) Mucin-poor Traditional serrated adenoma (TSA) Sessile serrated adenoma/polyp (SSA) Distal Proximal, large Sessile serrated adenoma/polyp with J Gastroenterol 2012; 107:1315–1329 dysplasia (SSAAmw/ dysplasia) Incidence of Colorectal Polyps Serrated polyp-Adenocarcinoma sequence Three pathways to CRC Adenoma Sessile Serrated Adenoma (SSA) Adenoma-carcinoma sequence: Chromosomal instability Serrated polyp-carcinoma sequence (20% CRC) Traditional Serrated Adenoma (TSA) Alternative/ fusion pathway Less well characterized Am J Gastroenterol 2012; 107:1315–1329 BJS 2011; 98: 1685-1694 Gastroenterol Clin N Am 2008; 37:25-46 Serrated polyp-Carcinoma sequence Initiation Hypermethylation of promotor silencing of DNA mismatch repair gene MLH-1 Microsatellite instability Am J Gastroenterol 2012; 107:1315–1329 Malignant Risk of Serrate Polyps Serrated Polyps and CRC Genetic and pathological study ~ 20% CRC from serrated pathway Large and proximal serrated polyps more synchronous advanced neoplasia/CRC Sessile serrated adenomas high metachronous CRC rate METHOD •3121 asymptomatic patients (aged 50–75 years) who had screening colonoscopies; 1371 had subsequent surveillance. RESULTS •Patient with proximal ND-SP were more likely to have advanced neoplasia (17.3% vs 10.0%; OR, 1.90; 95% CI, 1.33-2.70). •Patients with large ND-SP were also more likely to have synchronous advanced neoplasia (OR, 3.37; 95% CI, 1.7-6.65). During surveillance, •patients with baseline proximal ND-SP and no neoplasia were more likely to have neoplasia compared with subjects who did not have polyps (OR, 3.14; 95% CI,1.596.20). •Among patients with advanced neoplasia at baseline, those with proximal ND-SP were more likely to have advanced neoplasia during surveillance (OR, 2.17; 95% CI, 1.03-4.59). Serrated polyps and metachronous tumour Am J Surg Pathol 2010;34:927–934 •The incidence of subsequent CRCs was significantly higher in SSA patients than in control patients with HP (12.5% vs. 1.8%) and AP (12.5% vs. 1.8%). All of the subsequent CRCs or APs with HGD developed in the proximal colon. Four of the 5 CRCs demonstrated a high microsatellite instability phenotype. •We conclude that SSAs are high-risk lesions, with 15% of the SSA patients developing subsequent CRCs or APs with HGD. •support close endoscopic follow-up in patients harboring SSA Management and Surveillance Treatment Am J Gastroenterol 2012; 107:1315–1329 Complete removal of all serrated lesions Except diminutive sigmoid/rectal lesions Multiple diminutive (<5mm) serrated appear lesion should be randomly Bx Piecemeal resection/ possible incomplete removal surveillance colonoscopy 3-6 months Surgical resection: not endoscopically ressectable, numerous large serrated lesion of proximal colon, Serrated polyposis syndrome Current Surveillance strategies Guidelines based on observational studies that link baseline CLN findings to risk of advanced adenoma at FU For serrated lesions US After removal of HP 10 years interval No recommendation for SSA/TSA Europe HP: 10 years SSA/TSA consider as adenoma Why we need updated guidelines? Endoscopic detection is operator dependent and variable SSA is hard to detect and easy to miss Serrated adenoma are likely to grow faster then adenoma Serrated adenomas are responsible for a large portion of interval CRC Interval Colon Cancer RESULT MSI was found in 30.4% of interval cancers compared with 10.3% of noninterval cancers (P = .003). After adjusting for age, interval cancers were 3.7 times more likely to show MSI than noninterval cancers (95% CI, 1.5–9.1). Conceptual framework Am J Gastroenterol 2012; 107:1315–1329 Take home messages Some serrated polyps have malignant potential e.g. SSA/TSA Grows quicker then traditional adenomas All should be removed except diminutive HP in rectosigmoid region Current surveillance recommends treating SSA/TSA as adenoma Modify according to size, site and numbers The End Q&A References 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. Rex DK, Ahnen DJ, Baron JA et. al. Serrated lesions of the colorectum: Review and recommendations from an expert panel. Am J Gastroenterol 2012;107:1315-1329 Leonard DF, Dozois EJ, Smyrk TC, Suwanthanma W. et. al. Endoscopic and surical management of serrated colonic polyps. BJS 2011;98:1685-1694 East JE, Saunders BP, Jass JR. Sporadic and syndromic hyperplastic polyps and serrated adenoma of the colon: classification, molecular genetics, natural history and clinical management. Gastroenterol Clin N Am 2008;37:25-46 Bauer VP, Papaconstantinou HT. Management of serrated adenomas and hyperplastic polyps. Clin Colon Rectal Surg 2008;21L273-279 Groff RJ, Nash R, Ahnen DJ. Significance of serrated polyps of the colon. Current Gastroenterology Reports 2008;10:490-498 Liang JJ, Alrawi S, Tan D. Nomenclature, molecular genetics and clinic significance of the precursor lesions in the serrated polyp pathway of colorectal carcinoma. Int J Exp Pathol 2008;1:317-324 Snover DC, Jass JR, Fenoglio-Presiser CF, Batts KP. Serrated polyps of the large intestine. Am J Clin Pathol 2005;124:380-391 O’Brien MJ. Hyperplastic and serrated polyps of the colorectum. Gastroenterol Clin N Am 2007;36:947-968 O’Brien MJ, Yang S, Mack C et. al. Comparison of microsatellite instability, CpG island methylation phenotype, BRAF and KRAS status in serrated polyps and traditional adenomas indicates separate pathways to distint colorectal carcinoma endpoints. Am J Surg Pathol 2006;30:1491-1501 Lu F, Niekerk DW, Owen D et. al. Longitudinal outcome study of sessile serrated adenoma of the colorectum: An increased risk of subsequent right-sided colorectal carcinoma. Am J Surg Pathol 2010;34:927–934) 11. 12. 13. 14. 15. 16. 17. 18. Legget B, Whitehall V. Role of the serrated pathway in colorectal cancer pathogenesis. Gastroenterology 2010; 138:2088-2100 Farrar WD, Sawhney MS, Nelson DB et. al. Colorectal cancers found after a complete colonoscopy. Clin Gastroenterol Hepatol 2006; 4:1259-1264 Schrein WA, Weiss DG, Liberman DA. Proximal and large hyperplastic and nondysplastic serrated polyps detected by colonoscopy are associated with neoplasia. Gastroenterology 2010; 139:14971502 Lu F, Niekerk DW, Owen D et. al. Longitudinal outcome study of sessile serrated adenomas of the colorectum: an increased risk for subsequent right-sided colorectal carcinoma. Am J Pathol 2010;34:927-934 Sawhney MS, Farrar WD, Gudiseva S et. al. Microsatellite instability in interval colon cancers. Gastroenterology 2006;131:1700-1705 Spring KJ, Zhao ZZ, Karamatic R et. al. High prevalence of sessile serrated adenoma with BRAF mutations: a prospective study of patients undergoing colonoscopy. Gastroenterology 2006;131:1400-1407 Hetzel JT, Huang CS, Couko JA. Variation in the detection of serrated polyps in an average risk colorectal cancer screening cohort. Am J Gastroenterol 2010; 105: 2656-2664 Hiraoka S, KatoJ, Fujiki S et. al. The presence of large serrated polyps increases risk for colorectal cancer. Gastroenterology 2010; 139:1503-1510