Management of Serrated Polyps of Colorectum Eric YF Cheung Department of Surgery, NDH

Three messages Serrated polyp-adenocarcinoma sequence Serrated polyp-adenocarcinoma sequence Malignant risk of serrated polyps of colorectum Malignant risk of serrated polyps of colorectum Management and Surveillance: New guidelines needed Management and Surveillance: New guidelines needed

Serrated polyps—An overview

Colorectal polyps Adenoma Adenoma Tubular adenoma Tubular adenoma Tubulovillous adenoma Tubulovillous adenoma Villous adenoma Villous adenoma Hyperplastic polyp/Serrated polyp Hyperplastic polyp/Serrated polyp Harmatoma Harmatoma Juvenile polyp Juvenile polyp Peutz-Jeghers polyps Peutz-Jeghers polyps Inflammatory polyp Inflammatory polyp Lymphoid aggregates Lymphoid aggregates Traditionally viewed as innocuous

Serrated polyps (WHO) Hyperplastic polyp (HP): Small distal Hyperplastic polyp (HP): Small distal Microvesicular (MVHP) Microvesicular (MVHP) Globet-cell rich (GCHP) Globet-cell rich (GCHP) Mucin-poor Mucin-poor Traditional serrated adenoma (TSA) Traditional serrated adenoma (TSA) Distal Distal Sessile serrated adenoma/polyp (SSA) Sessile serrated adenoma/polyp (SSA) Proximal, large Proximal, large Sessile serrated adenoma/polyp with dysplasia (SSA w/ dysplasia) Sessile serrated adenoma/polyp with dysplasia (SSA w/ dysplasia) Am J Gastroenterol 2012; 107:1315–1329

Incidence of Colorectal Polyps

Serrated polyp-Adenocarcinoma sequence

Three pathways to CRC Adenoma Adenoma Adenoma-carcinoma sequence: Chromosomal instability Adenoma-carcinoma sequence: Chromosomal instability Sessile Serrated Adenoma (SSA) Sessile Serrated Adenoma (SSA) Serrated polyp-carcinoma sequence (20% CRC) Serrated polyp-carcinoma sequence (20% CRC) Traditional Serrated Adenoma (TSA) Traditional Serrated Adenoma (TSA) Alternative/ fusion pathway Alternative/ fusion pathway Less well characterized Less well characterized Am J Gastroenterol 2012; 107:1315–1329 BJS 2011; 98: Gastroenterol Clin N Am 2008; 37:25-46

Serrated polyp-Carcinoma sequence Am J Gastroenterol 2012; 107:1315 – 1329 Initiation Hypermethylation of promotor  silencing of DNA mismatch repair gene MLH-1  Microsatellite instability

Malignant Risk of Serrate Polyps

Serrated Polyps and CRC Genetic and pathological study  ~ 20% CRC from serrated pathway Genetic and pathological study  ~ 20% CRC from serrated pathway Large and proximal serrated polyps  more synchronous advanced neoplasia/CRC Large and proximal serrated polyps  more synchronous advanced neoplasia/CRC Sessile serrated adenomas  high metachronous CRC rate 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, ). Patients with large ND-SP were also more likely to have synchronous advanced neoplasia (OR, 3.37; 95% CI, ). 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, ). 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, ).

Serrated polyps and metachronous tumour 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 Am J Surg Pathol 2010;34:927 – 934

Management and Surveillance

Treatment Am J Gastroenterol 2012; 107:1315 – 1329 Complete removal of all serrated lesions Complete removal of all serrated lesions Except diminutive sigmoid/rectal lesions Except diminutive sigmoid/rectal lesions Multiple diminutive (<5mm) serrated appear lesion should be randomly Bx Multiple diminutive (<5mm) serrated appear lesion should be randomly Bx Piecemeal resection/ possible incomplete removal  surveillance colonoscopy 3-6 months 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 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 Guidelines based on observational studies that link baseline CLN findings to risk of advanced adenoma at FU For serrated lesions For serrated lesions US US After removal of HP  10 years interval After removal of HP  10 years interval No recommendation for SSA/TSA No recommendation for SSA/TSA Europe Europe HP: 10 years HP: 10 years SSA/TSA  consider as adenoma SSA/TSA  consider as adenoma

Why we need updated guidelines? Endoscopic detection is operator dependent and variable Endoscopic detection is operator dependent and variable SSA is hard to detect and easy to miss SSA is hard to detect and easy to miss Serrated adenoma are likely to grow faster then adenoma Serrated adenoma are likely to grow faster then adenoma Serrated adenomas are responsible for a large portion of interval CRC 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 Some serrated polyps have malignant potential e.g. SSA/TSA Grows quicker then traditional adenomas Grows quicker then traditional adenomas All should be removed except diminutive HP in rectosigmoid region All should be removed except diminutive HP in rectosigmoid region Current surveillance recommends treating SSA/TSA as adenoma Current surveillance recommends treating SSA/TSA as adenoma Modify according to size, site and numbers Modify according to size, site and numbers

The End Q&A

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