Sessile Serrated Adenomas: An Evidence-Based Guide to Management Seth D. Crockett, Dale C. Snover, Dennis J. Ahnen, John A. Baron  Clinical Gastroenterology and Hepatology  Volume 13, Issue 1, Pages 11-26.e1 (January 2015) DOI: 10.1016/j.cgh.2013.10.035 Copyright © 2015 AGA Institute Terms and Conditions

Figure 1 Proposed serrated pathway to MSI CRC, with characteristic crypt alterations, histologic and endoscopic appearance, and epigenetic and genetic alterations. Dotted line between MVHP and SSA indicates a possible but unproven progression step. Regarding crypt alterations, the thickened line indicates a proliferative zone, which is expanded in HPs, and migrates upward in SSAs. Arrows indicate the direction of maturation. See text for details. MSI-H, high microsatellite instability. Modified with permission from Snover et al.17 Clinical Gastroenterology and Hepatology 2015 13, 11-26.e1DOI: (10.1016/j.cgh.2013.10.035) Copyright © 2015 AGA Institute Terms and Conditions

Figure 2 SSAs likely contribute to the problem of interval (or postcolonoscopy) cancers for 3 chief reasons: (1) SSAs can be difficult to detect during colonoscopy and are commonly missed; (2) it is thought that SSAs have the potential for rapid progression owing to the development of MSI, especially after dysplasia develops; and (3) incomplete polypectomy is common with SSAs. Hollow arrows represent potential targets for combating this problem. Clinical Gastroenterology and Hepatology 2015 13, 11-26.e1DOI: (10.1016/j.cgh.2013.10.035) Copyright © 2015 AGA Institute Terms and Conditions

Figure 3 Endoscopic images of SSA larger than 1 cm from 3 different patients featuring sessile or flat morphology and pale color (all), mucus/debris covering (all), resemblance to prominent folds (A and C), and indistinct borders (A and B). Some SSAs are located behind folds and are best visualized (and removed) from a retroflexed position (B). Clinical Gastroenterology and Hepatology 2015 13, 11-26.e1DOI: (10.1016/j.cgh.2013.10.035) Copyright © 2015 AGA Institute Terms and Conditions

Figure 4 The issue of serrated neoplasia magnifies many of the flaws of CRC screening programs, and colonoscopy screening specifically. (1) Risk factors for SSAs are poorly understood. Current risk-based screening recommendations (eg, screen between ages 50–75) may not optimize prevention of serrated pathway cancers. (2) SSAs are less likely to be detected by CT colonography (because of flat appearance) or flexible sigmoidoscopy (because of proximal location). Prevention of serrated pathway cancers may be more difficult in individuals who choose noncolonoscopy screening modalities. (3) SSAs have a subtle endoscopic appearance and can be missed during colonoscopy. There is significant variability in endoscopic detection of SSAs. Poor preparation quality (especially in the right colon) may further impair the detection of SSAs. (4) Because of flat/sessile morphology, size, and proximal location, removal of SSAs requires more polypectomy time and skill, and involves more risk. Incomplete resection is common with SSAs. (5) Pathologic understanding of serrated neoplasia is in evolution, with variability in interpretation and terminology used. SSAs may be read as HPs by some pathologists. (6) Surveillance recommendations are based largely on expert opinion and conjecture, not data. Some guidelines do not make specific management recommendations for serrated polyps. (7) Because of issues 3, 4, 5, and 6, individuals harboring SSAs may not undergo surveillance colonoscopy at appropriate intervals. f/u, follow up; prep, preparation. Clinical Gastroenterology and Hepatology 2015 13, 11-26.e1DOI: (10.1016/j.cgh.2013.10.035) Copyright © 2015 AGA Institute Terms and Conditions

Supplementary Figure 1 WHO taxonomy of serrated polyps. Clinical Gastroenterology and Hepatology 2015 13, 11-26.e1DOI: (10.1016/j.cgh.2013.10.035) Copyright © 2015 AGA Institute Terms and Conditions