Management of Serrated Management of Serrated Polyps of ColorectumPolyps of Colorectum

Eric YF CheungEric YF Cheung

Department of Surgery, NDHDepartment of Surgery, NDH

Three messagesThree messages

Serrated polyp-adenocarcinoma Serrated polyp-adenocarcinoma sequencesequence

Malignant risk of serrated polyps of Malignant risk of serrated polyps of colorectumcolorectum

Management and Surveillance: New Management and Surveillance: New guidelines neededguidelines needed

Serrated polyps—An Serrated polyps—An overviewoverview

Colorectal polyps Colorectal polyps

AdenomaAdenoma Tubular adenomaTubular adenoma Tubulovillous adenomaTubulovillous adenoma Villous adenomaVillous adenoma

Hyperplastic polyp/Serrated polypHyperplastic polyp/Serrated polyp HarmatomaHarmatoma

Juvenile polypJuvenile polyp Peutz-Jeghers polypsPeutz-Jeghers polyps

Inflammatory polypInflammatory polyp Lymphoid aggregatesLymphoid aggregates

Traditionally viewed as innocuous

Serrated polyps (WHO)Serrated polyps (WHO)

Hyperplastic polyp (HP): Small distalHyperplastic 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) DistalDistal

Sessile serrated adenoma/polyp Sessile serrated adenoma/polyp (SSA)(SSA) Proximal, largeProximal, large

Sessile serrated adenoma/polyp with Sessile serrated adenoma/polyp with dysplasia (SSA w/ dysplasia)dysplasia (SSA w/ dysplasia)Am J Gastroenterol 2012; 107:1315–1329

Incidence of Colorectal Incidence of Colorectal PolypsPolyps

Serrated polyp-Serrated polyp-Adenocarcinoma sequenceAdenocarcinoma sequence

Three pathways to CRCThree pathways to CRC

AdenomaAdenoma Adenoma-carcinoma sequenceAdenoma-carcinoma sequence: :

Chromosomal instabilityChromosomal instability Sessile Serrated Adenoma (SSA)Sessile Serrated Adenoma (SSA)

Serrated polyp-carcinoma sequence Serrated polyp-carcinoma sequence (20% CRC)(20% CRC)

Traditional Serrated Adenoma (TSA)Traditional Serrated Adenoma (TSA) Alternative/ fusion pathwayAlternative/ fusion pathway Less well characterizedLess well characterized

Am J Gastroenterol 2012; 107:1315–1329BJS 2011; 98: 1685-1694Gastroenterol Clin N Am 2008; 37:25-46

Serrated polyp-Serrated polyp-Carcinoma sequenceCarcinoma 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 Malignant Risk of Serrate PolypsPolyps

Serrated Polyps and CRCSerrated Polyps and CRC

Genetic and pathological studyGenetic and pathological study ~ 20% CRC from serrated ~ 20% CRC from serrated pathwaypathway

Large and proximal serrated Large and proximal serrated polyps polyps more synchronous more synchronous advanced neoplasia/CRCadvanced neoplasia/CRC

Sessile serrated adenomas Sessile serrated adenomas high metachronous CRC ratehigh 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,1.59-6.20). •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 Serrated polyps and metachronous tumourmetachronous 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 Management and SurveillanceSurveillance

TreatmentTreatmentAm J Gastroenterol Am J Gastroenterol 2012; 107:13152012; 107:1315––13291329

Complete removal of all serrated lesions Complete removal of all serrated lesions Except diminutive sigmoid/rectal lesionsExcept diminutive sigmoid/rectal lesions

Multiple diminutive (<5mm) serrated appear lesion Multiple diminutive (<5mm) serrated appear lesion should be randomly Bxshould be randomly Bx

Piecemeal resection/ possible incomplete removal Piecemeal resection/ possible incomplete removal surveillance colonoscopy 3-6 months surveillance colonoscopy 3-6 months

Surgical resection: not endoscopically ressectable, Surgical resection: not endoscopically ressectable, numerous large serrated lesion of proximal colon, numerous large serrated lesion of proximal colon, Serrated polyposis syndromeSerrated polyposis syndrome

Current Surveillance Current Surveillance strategiesstrategies

Guidelines based on observational Guidelines based on observational studies that link baseline CLN studies that link baseline CLN findings to risk of advanced findings to risk of advanced adenoma at FUadenoma at FU

For serrated lesionsFor serrated lesions USUS

After removal of HP After removal of HP 10 years interval 10 years interval No recommendation for SSA/TSANo recommendation for SSA/TSA

EuropeEurope HP: 10 yearsHP: 10 years SSA/TSA SSA/TSA consider as adenoma consider as adenoma

Why we need updated Why we need updated guidelines?guidelines?

Endoscopic detection is operator Endoscopic detection is operator dependent and variabledependent 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 Serrated adenoma are likely to grow faster then adenomafaster then adenoma

Serrated adenomas are responsible Serrated adenomas are responsible for a large portion of interval CRCfor a large portion of interval CRC

Interval Colon CancerInterval Colon Cancer

RESULTRESULT

MSI was found in 30.4% of interval cancers MSI was found in 30.4% of interval cancers compared with 10.3% of noninterval compared with 10.3% of noninterval cancers (P = .003). After adjusting for age, cancers (P = .003). After adjusting for age, interval cancers were interval cancers were 3.7 times3.7 times more more likely to show MSI than noninterval likely to show MSI than noninterval cancers (95% CI, 1.5cancers (95% CI, 1.5––9.1).9.1).

Conceptual frameworkConceptual framework

Am J Gastroenterol 2012; 107:1315–1329

Take home messagesTake home messages

Some serrated polyps have Some serrated polyps have malignant potential e.g. SSA/TSAmalignant potential e.g. SSA/TSA

Grows quicker then traditional Grows quicker then traditional adenomasadenomas

All should be removed except All should be removed except diminutive HP in rectosigmoid diminutive HP in rectosigmoid regionregion

Current surveillance recommends Current surveillance recommends treating SSA/TSA as adenomatreating SSA/TSA as adenoma Modify according to size, site and Modify according to size, site and

numbersnumbers

The EndThe EndQ&AQ&A

ReferencesReferences1.1. Rex DK, Ahnen DJ, Baron JA et. al. Serrated lesions of the colorectum: Review and Rex DK, Ahnen DJ, Baron JA et. al. Serrated lesions of the colorectum: Review and

recommendations from an expert panel. recommendations from an expert panel. Am J Gastroenterol Am J Gastroenterol 2012;107:1315-13292012;107:1315-1329

2.2. Leonard DF, Dozois EJ, Smyrk TC, Suwanthanma W. et. al. Endoscopic and surical Leonard DF, Dozois EJ, Smyrk TC, Suwanthanma W. et. al. Endoscopic and surical management of serrated colonic polyps. management of serrated colonic polyps. BJS BJS 2011;98:1685-16942011;98:1685-1694

3.3. East JE, Saunders BP, Jass JR. Sporadic and syndromic hyperplastic polyps and serrated East JE, Saunders BP, Jass JR. Sporadic and syndromic hyperplastic polyps and serrated adenoma of the colon: classification, molecular genetics, natural history and clinical adenoma of the colon: classification, molecular genetics, natural history and clinical management. management. Gastroenterol Clin N AmGastroenterol Clin N Am 2008;37:25-46 2008;37:25-46

4.4. Bauer VP, Papaconstantinou HT. Management of serrated adenomas and hyperplastic Bauer VP, Papaconstantinou HT. Management of serrated adenomas and hyperplastic polyps. polyps. Clin Colon Rectal SurgClin Colon Rectal Surg 2008;21L273-279 2008;21L273-279

5.5. Groff RJ, Nash R, Ahnen DJ. Significance of serrated polyps of the colon. Groff RJ, Nash R, Ahnen DJ. Significance of serrated polyps of the colon. Current Current Gastroenterology Reports Gastroenterology Reports 2008;10:490-498 2008;10:490-498

6.6. Liang JJ, Alrawi S, Tan D. Nomenclature, molecular genetics and clinic significance of Liang JJ, Alrawi S, Tan D. Nomenclature, molecular genetics and clinic significance of the precursor lesions in the serrated polyp pathway of colorectal carcinoma. the precursor lesions in the serrated polyp pathway of colorectal carcinoma. Int J Exp Int J Exp Pathol Pathol 2008;1:317-324 2008;1:317-324

7.7. Snover DC, Jass JR, Fenoglio-Presiser CF, Batts KP. Serrated polyps of the large Snover DC, Jass JR, Fenoglio-Presiser CF, Batts KP. Serrated polyps of the large intestine. intestine. Am J Clin Pathol Am J Clin Pathol 2005;124:380-3912005;124:380-391

8.8. OO’’Brien MJ. Hyperplastic and serrated polyps of the colorectum.Brien MJ. Hyperplastic and serrated polyps of the colorectum. Gastroenterol Clin N Gastroenterol Clin N Am Am 2007;36:947-9682007;36:947-968

9.9. OO’’Brien MJ, Yang S, Mack C et. al. Comparison of microsatellite instability, CpG island 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 methylation phenotype, BRAF and KRAS status in serrated polyps and traditional adenomas indicates separate pathways to distint colorectal carcinoma endpoints. adenomas indicates separate pathways to distint colorectal carcinoma endpoints. Am J Am J Surg Pathol Surg Pathol 2006;30:1491-15012006;30:1491-1501

10.10. Lu F, Niekerk DW, Owen D et. al. Longitudinal outcome study of sessile serrated 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 adenoma of the colorectum: An increased risk of subsequent right-sided colorectal carcinoma. Am J Surg Pathol 2010;34:927carcinoma. Am J Surg Pathol 2010;34:927––934)934)

11.11. Legget B, Whitehall V. Role of the serrated pathway in colorectal cancer pathogenesis. Legget B, Whitehall V. Role of the serrated pathway in colorectal cancer pathogenesis. Gastroenterology Gastroenterology 2010; 138:2088-21002010; 138:2088-2100

12.12. Farrar WD, Sawhney MS, Nelson DB et. al. Colorectal cancers found after a complete Farrar WD, Sawhney MS, Nelson DB et. al. Colorectal cancers found after a complete colonoscopy. colonoscopy. Clin Gastroenterol Hepatol Clin Gastroenterol Hepatol 2006; 4:1259-12642006; 4:1259-1264

13.13. Schrein WA, Weiss DG, Liberman DA. Proximal and large hyperplastic and nondysplastic Schrein WA, Weiss DG, Liberman DA. Proximal and large hyperplastic and nondysplastic serrated polyps detected by colonoscopy are associated with neoplasia. serrated polyps detected by colonoscopy are associated with neoplasia. Gastroenterology Gastroenterology 2010; 139:1497-15022010; 139:1497-1502

14.14. Lu F, Niekerk DW, Owen D et. al. Longitudinal outcome study of sessile serrated 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 adenomas of the colorectum: an increased risk for subsequent right-sided colorectal carcinoma. carcinoma. Am J Pathol Am J Pathol 2010;34:927-9342010;34:927-934

15.15. Sawhney MS, Farrar WD, Gudiseva S et. al. Microsatellite instability in interval colon Sawhney MS, Farrar WD, Gudiseva S et. al. Microsatellite instability in interval colon cancers. cancers. Gastroenterology Gastroenterology 2006;131:1700-17052006;131:1700-1705

16.16. Spring KJ, Zhao ZZ, Karamatic R et. al. High prevalence of sessile serrated adenoma Spring KJ, Zhao ZZ, Karamatic R et. al. High prevalence of sessile serrated adenoma with BRAF mutations: a prospective study of patients undergoing colonoscopy. with BRAF mutations: a prospective study of patients undergoing colonoscopy. Gastroenterology Gastroenterology 2006;131:1400-14072006;131:1400-1407

17.17. Hetzel JT, Huang CS, Couko JA. Variation in the detection of serrated polyps in an Hetzel JT, Huang CS, Couko JA. Variation in the detection of serrated polyps in an average risk colorectal cancer screening cohort. average risk colorectal cancer screening cohort. Am J Gastroenterol Am J Gastroenterol 2010; 105: 2656-2010; 105: 2656-26642664

18.18. Hiraoka S, KatoJ, Fujiki S et. al. The presence of large serrated polyps increases risk for Hiraoka S, KatoJ, Fujiki S et. al. The presence of large serrated polyps increases risk for colorectal cancer. colorectal cancer. Gastroenterology Gastroenterology 2010; 139:1503-15102010; 139:1503-1510