A Canary in the ColonSurveillance of

Sessile Serrated Adenomas

Douglas Riegert-Johnson, MD

Mayo Clinic Florida

Gastroenterology and Genetics

Riegertjohnson.douglas@mayo.edu

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Topics

• Case of the sessile serrated adenoma Part 1.

• Guidelines.

• What are sessile serrated adenomas?

• Why are they important?

• Conclusion of the case of the sessile serrated adenoma.

• Serrated polyposis.

Sessile Serrated Adenoma Case – Part 1(from DRJ practice)

• 54 yo female presented for first time colorectal cancer prevention colonoscopy.

• No family history of colorectal cancer.

Reported Polyp Pathology

Sessile serrated adenoma

What follow up for this 10 mm SSA?

A. One year.

B. Three years.

C. Five years.

Consensus recommendations for sessile serrated adenomas are similar to that for adenomas (US 2012)

Histology Size Number Interval in years

SSA/P or TSA Large (≥10 mm) 1 3

SSA/P or TSA Small (<10 mm) 1 or 2 5

SSA/P or TSA <10 mm 3 or more 3

SSA/P ≥10 mm ≥21–3 Serrated

polyposis syndrome

SSA/P w/dysplasia Any Any 1–3

Serrated lesions: Recommendations from an expert panel 2012.

Piecemeal resection then follow up in 3-6 months. Serrated polyposis syndrome (SPS) discussed latter.Follow up for hyperplastic polyps included as addendum.

European and UK guidelines do not have as close follow up for SSAs as the US 2012

expert recommendations

• European Soc. Of GI Endoscopy Guidelines 2013

– Same as US: Large serrated polyps (≥10mm) or those with dysplasia should be classified as high risk [3 years] (weak recommendation, low quality evidence).

– Different than US: “The ESGE recommends that patients with serrated polyps <10mm in size with no dysplasia should be classified as low risk (weak recommendation, low quality evidence [10 years])

• United Kingdom Gut 2010

– No mention of serrated lesions.

There are three types of serrated polyps

• Hyperplastic

• Sessile serrated adenoma (1996)

SS adenoma/polyp = sessile serrated adenoma

• Traditional serrated adenoma (1990)

• Serrated polyposis syndrome to be discussed at end of talk (WHO criteria 2000)

Burt R, Jass JR. Hyperplastic polyposis. In: Hamilton SR, Aaltonen LA, eds. Pathology and Genetics of Tumours of the Digestive System. Vol 2. Lyon, France: IARC; 2000:35–136.

Incidence of Serrated Polyps

1 in 3 polyps is any type of serrated polyp

1 in 10 polyps is a sessile serrated adenoma

1 in 100 polyps is a traditional serrated adenoma

Hyperplastic polyp Sessile Serrated Adenoma

“The boot”Must have at least one

horizontally branched crypt

Traditional Serrated

Adenoma

Q: Why are sessile serrated adenomas important?A: Their association with interval colon cancers

Suspected causes of interval colon cancer

Systematic review and meta analysis of interval colorectal cancers: American J Gastro 2014.

Colorectal cancers soon after colonoscopy: a pooled multicohort analysis. Gut 2014

Interval cancers are uncommon (1 in 1075 colonoscopies® , 1/166 adenoma patients).

1. Not seen lesions 52%2. New lesions 24%3. Incomplete resection of an earlier, noninvasive lesions 19%

Scott HaldeneScottish physiologist 1860 - 1936

“Animal Sentinel”Last use in the UK in 1986

Sessile serrated adenoma =“Colonic sentinel”

Colon cancerDr. Emina Torlakovic and colleaugescoined the term SSA

Lifetime odds of colorectal

cancer diagnosis

Postulated lower limit (1/400 individuals have a hereditary syndrome

pre disposing to rapid polyp growth eg Lynch syndrome)

1/400

1/10-1/15

1/166

High water mark: Lifetime risk with no screening

Lifetime risk for patients in colonoscopy program

All odds are approximations

Why are SSAs important?Draining the colon cancer lake.

What is in the lake?Not seen lesionsOther lesionsIncompletely resection

Risk Stratification

Not seen (and not classified) lesions

2014 USA Septin 9 trial data on SAs per center

The proportion of colonoscopies where sessile serrated adenomas are found varies based on center (GI and

pathologist).Range 0-9.8% (Mean 2.8%)

Other lesionsMaybe SSAs themselves not so important,

but are markers for danger like canaries

• SSAs as markers for present and future neoplasia.

– 1 of 3 colonoscopies where a SSA is found, a conventional adenoma will also be found.

– Future neoplasia. Next slide.

• Not so important,

low CA risk for sessile serrated adenomas

– Norway: Twenty-three large serrated polyps (>10 mm) found at screening were left in situ for a median of 11.0 years. None developed into a malignant tumour.

Norway Gut 2014

2014 USA Septin 9 trial data on SAs per center

Risk Stratification for Future Neoplasia:SSAs associated with the highest risk of colorectal cancer

diagnosis, 3.7% at 10 years.

A population-based randomized

trial, 12 955 individuals aged

50-64 years were screened with

flexible sigmoidoscopy.

Norway Gut 2014

Norwegian Study Conclusion

“The excess risk of CRC in patients with large serrated polyps may not be due to malignant growth of the serrated polyp, but to a ‘field’-effect in the patient with these polyps.”

Norway Gut 2014Macaronesia, home of the canary

Lifetime odds of colorectal

cancer diagnosis

Postulated lower limit (1/400 individuals have a hereditary syndrome

pre disposing to rapid polyp growth eg Lynch syndrome)

1/400

1/10-1/15

1/166

High water mark: Lifetime risk with no screening

Lifetime risk for patients in colonoscopy program

All odds are approximations

Why are SSAs important?Draining the colon cancer lake

Not seen lesionsOther lesionsIncompletely resection

Risk Stratification

SSA contribution to Incomplete resection

During the Complete Adenoma Resection study (CARE Gastroenterology 2013, Vermont), what percentage of sessile serrated adenomas 10 mm – 20 mm were incompletely resected?

• A. 15%

• B. 30%

• C. 50%

Complete Adenoma Resection Study (CARE): Gastroenterology 2013

CARE study found SSA are often incompletely resected

After complete polypectomy by visible inspection, for small polyps 2 marginal biopsies were taken adjacent to polypectomy site, for large polyps 4 biopsies were taken.

Complete Adenoma Resection Study (CARE): Gastroenterology 2013

Polyp type Incompleteresection

n

Large SSA (10-20) mm 48% ?

All SSAs 30% (13/42)

Overall 10% ( of 346 by 11 GIs)

Sessile Serrated Adenoma Case – Part 2

• Marginal biopsies showed a fragment suggestive of sessile serrated adenoma.

• Interpretation of results of positive marginal biopsy: – Marginal biopsies found and treated microscopic disease.– Clinical significance of microscopic residual polyp unclear.

• Benefits of marginal biopsies include rapid and focused feedback to the endoscopist compared to ADR.

• Plan for patient: Follow up colonoscopy in 3 years.• I changed my polypectomy technique to grasp a larger

amount of tissue with the snare. Subsequent marginal biopsies have been negative.

What do you do when there are a lot of them?

Definition of a whole lot.WHO criteria for serrated polyposis syndrome

* Any type of serrated polyp.

WHO Criterion 1. At least 5 serrated polyps proximal to the sigmoid colon, of which 2 measure at least 10 mm in diameter). (Memory aid 5 × 2 = 10.)

WHO Criterion 2. Any number of serrated polyps occurring proximal to the sigmoid colon in an individual who has a first-degree relative with SPS.

*WHO Criterion 3. >20 serrated polyps spread throughout the colon. * About 80% of patients meet this criterion.

Serrated polyposis is uncommon, but not rare, and requires yearly follow up

• About 1 in 150 patients in FIT based colorectal cancer prevention program

• 1-year surveillance interval for these patients recommended by US Multi-Society Task Force on Colorectal Cancer and the European Society of Gastrointestinal Endoscopy.

Serrated lesions: Recommendations from an expert panel.

For serrated polyposis, colonoscopy of family members has high yield but genetic testing of

patients has a low yield• First degree relatives of SPS should have colonoscopy at

age 40 or 10 years prior to proband’s diagnosis of SPS

(4/10 significant polyp, 1/7 will have serrated polyposis Reference).

• Genetic evaluation recommended by the European guidelines.– Yield is low. DRJ “1, or less%”.

– Most common genetic dx MYH associated polyposis (MAP)• Others include Lynch syndrome (mutation in the DNA mismatch

repair genes and mutations in the RNAF4 gene.

• Patients can be referred to a genetic counselor using an online database (www.nsgc.org)

Summary• SSAs represent 1 in 10 colon polyps, and have a

“boot” histopathology.

• Surveillance similar to those for adenomas.

• Interval colon cancers are rare; SSAs may be a canary signal to the causative not seen lesions, new lesions, and incomplete polypectomies.

• Consider marginal biopsies.

• Serrated polyposis syndrome requires yearly follow up colonoscopy and colonoscopy is recommended for family members. Genetic testing is low yield.

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Addendum

Hyperplastic polyp follow up

Lesion Size Number Location Follow up

HP <10 mm Any numberb Rectosigmoid 10c

HP ≤5 mm ≤3Proximal to sigmoid

10

HP Any ≥4Proximal to sigmoid

5

HP >5 mm ≥1Proximal to sigmoid

5

The Good News:Sustained and notable downward trend in colon cancer and deaths from colon cancer

(per 100,000)

0

10

20

30

40

50

60

70

Number of new cases Number of deaths

Traditional serrated adenoma should be renamed as confused with SSA

• One in 100 polyps

• Much higher rate of high grade dysplasia or carcinoma compared to SSA. About 1 in 5 associated with advanced neoplasia (19%).

• Are rare, large (mean size 16 mm) mostly located in the sigmoid or rectum (71%) in older men and women (mean age 64 with equal male to female ratio).

A clinicopathological and molecular analysis of 200 traditional serrated adenomas.

292, 72%

112, 28%

Adenomas Serrated polyps

Complete Adenoma Resection Study (CARE): Gastroenterology 2013

64, 57%

6, 5%

42, 38%

Hyperplastic

Traditional serratedadenoma

Sessile serratedadenoma/polyp

About 3 in 10 polyps are serrated polyps, about 1 in 10 are sessile serrated

adenomas

Neoplastic polyps, n (%) 346 (82.8)

Adenomas 292 (69.9)

Tubular adenomas 260 (62.2)

Tubulovillous adenomas 21 (5.0)

Villous adenomas 5 (1.2)

Traditional serrated adenomas 6 (1.4)

Sessile serrated adenomas/polyps 42 (10.1)

Cancer 1 (0.2)

Hyperplastic polyps 64 (15.3)

Complete Adenoma Resection Study (CARE): Gastroenterology 2013

For the future…

• For the suspected SSA, – Recommendation of marginal biopsies? Compared to

ADR, quicker feedback for specific change in practice. Maybe better buy in, lacks negative connotations of ADR.

• For the “field defect”,– life long increased surveillance with colonoscopy every

? 7 years even when follow up colonoscopy negative.

APC following piecemeal polypectomy

Norway Gut 2014

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