Ashish Sharma

PGY4 GI fellow
Grand Rounds
2/19/15
Mentor- Milena Gould, MD

Case presentation
64 y/o Caucasian male with h/o heavy smoking,
COPD, CAD without CHF on Aspirin 81 mg, aflutter on
metoprolol, well compensated HCV/ETOH liver
cirrhosis (Child class A, MELD 9) on Harvoni was seen
in GI lab for colonoscopy in 10/2014 for being FOBT
positive
Family History Three siblings, all > 50 yrs of age and
with few colon polyps (type not known), but no colon
cancer. Two sons (38 and 41 y/o) with no previous
colonoscopies. No known h/o colonic polyposis or
colon cancer in other first degree relatives

Case presentation

olonoscopy exam and pathological findings

Polyp location
Cecum
Ascending colon

Polyp number, size and pathology

1 Tubular Adenoma (TA); < 1 cm
2 Sessile Serrated Polyp (SSP); 1/2 was > 1 cm

Transverse
colon

2 TA and 3 SSP; all < 1cm

Descending
colon

5 SSP; all < 1 cm

Sigmoid colon

1 TA and 8 SSP; all < 1cm

Rectosigmoid

2 TA and 1 SSP; all < 1cm

Rectum

3 TA and 2 Hyperplastic polyp (HP); all < 1cm

Total count 9 TA and 21 Serrated polyps

Diagnosis- Serrated Polyposis

Syndrome (SPS)
WHO diagnostic criteria
1.) At least 5 serrated polyps proximal to sigmoid colon
with
at least 2 or more of these greater than 1 cm size, or
2.) Any number of serrated polyps in an individual
proximal to sigmoid who has a 1st degree relative with
SPS, or
3.) Greater than 20 serrated polyps of any size
throughout the colon (cumulative count)
Snover DC et al. Serrated polyps of the colon and rectum
and serrated (hyperplastic) polyposis. WHO
Classification of tumours of the digestive system. Berlin:

Serrated Polyps,
with focus on
Sessile Serrated
Adenoma(SSA)

Clinical Questions
1. Background, types,
epidemiology, natural history,
genetics of serrated polyps
2. Interval/missed colorectal cancer and
serrated pathway
3. Sessile serrated adenoma current
detection rates, techniques for
improved detection, endoscopic
management

Background of Serrated
Polyps

Serrated polyps are characterized primarily by a sawtoothed appearance of colonic crypts, hence the name
Prior to 1990s Hyperplastic Polyps (HPs) were considered
benign. Term Serrated Adenoma was coined in 1990s
with findings of cytological atypia in HPs
With further advancement in knowledge about serrated
polyps terms Traditional Serrated Adenoma (TSA) and
Sessile Serrated Adenoma (SSA) were coined in 2003.
Best umbrella term to use today is serrated polyps, which
is further subdivided into HPs, SSA and TSA
1. Torlakovic et al. Morphologic reappraisal of serrated colorectal
polyps. Am J Surg Pathol 2003
2. Longacre et al. Mixed hyperplastic adenomatous polyps/serrated
adenomas. A d
distinct form of colorectal neoplasia. Am J

Types of Serrated Polyps

HPs - Microvesicular HP (MVHP), Mucin
poor HP, Goblet cell rich HP
SSA
TSA

Snover DC et al. Serrated polyps of the colon and rectum

and serrated (hyperplastic) polyposis. WHO
Classification of tumours of the digestive system. Berlin:

Epidemiology of Serrated
Polyps
At least 20-40% of average risk patients will have
at least 1 serrated polyp, including distal HPs on
colonoscopy
HPs represent 80-95%, SSA 3-22% and TSA <1%
of all serrated polyps
Proximal serrated polyp or large serrated polyp (> 1
cm) is used as a surrogate for SSA in epidemiological
studies
75-90% of SSA are right sided
Crockett et al. Sessile Serrated
Adenomas: An Evidence-Based Guide to

Epidemiology of Serrated
Polyps
SSA incidence shows equal gender distribution
Studies with regards to effect of race/ethnicity,
alcohol use, socio-economic factors, diet on
SSA incidence are limited
Smoking is associated with higher SSA
incidence
NSAIDs is associated with lower SSA incidence
Crockett et al. Sessile Serrated
Adenomas: An Evidence-Based Guide to

Natural history of SSA

Risk and rate of progression of SSA is not clear
In one large cross-sectional study of 2416 SSAs, 85%
were non-dysplastic, 14% had low- or high-grade
dysplasia, and 1% had adenocarcinoma. In addition,
there have been case reports of rapid
progression of SSAs to cancer in less than 1 year
SSA shows increased risk of synchronous and
metachronous SSA, advanced neoplasia and colorectal
cancer
1. Lash et al. Sessile serrated adenomas: prevalence of dysplasia and
carcinoma in 2139 patients. J Clin Pathol 2010
2. Oono et al.. Progression of a sessile serrated adenoma to an early invasive
cancer within 8 months. Dig Dis Sci 2009
3. Vu et al. Individuals with sessile serrated polyps express an aggressive
colorectal phenotype. Dis Colon Rectum 2011

Natural history of SSA

Crockett et al. Sessile Serrated

Adenomas: An Evidence-Based Guide to

Genetics of SSA - Serrated

Pathway

Rex et al. Serrated Lesions of the

Colorectum: Review and
Recommendations From an Expert

Clinical Questions
1. Background, types, epidemiology,
natural history, genetics of serrated
polyps
2. Interval/missed colorectal cancer
and serrated pathway
3. Sessile serrated adenoma current
detection rates, techniques for
improved detection, endoscopic
management

Interval CRC and Serrated Pathway

Crockett et al. Sessile Serrated

Adenomas: An Evidence-Based Guide to

Interval CRC and Serrated

Pathway

Interval CRC and Serrated

Pathway

Interval CRC and Serrated Pathway

Interval CRC and Serrated

Pathway

Clinical Questions
1. Background, types, epidemiology,
natural history, genetics of serrated
polyps
2. Interval/missed colorectal cancer and
serrated pathway
3. Sessile serrated adenoma
current detection rates, techniques
for improved detection, endoscopic
management

Detection of SSA- SSA

characteristics
Characteristic features of SSAs include
proximal
location (>75%), sessile or flat morphology
(>90%), a resemblance to prominent folds
(37%), pale color (75%), indistinct borders
(73%) and mucus capping (64%100%),
which makes detection difficult.

1. Tadepalli et al. A morphologic analysis of sessile serrated

polyps observed during routine colonoscopy. Gastrointest
Endosc 2011
2. Oka et al. Clinicopathologic and endoscopic features of
colorectal serrated adenoma: differences between

SSA - Current detection

rates
Hetzel et al. Sessile Serrated Adenoma Detection
Rate (SSADR) range from 0 to 2.2%
Kahi et al. Proximal Serrated Polyp(PSP) detection
rate ranged from 1 to 18%
Wijkerslooth et al. PSP detection rate ranged from
6 to 22%
Target PSP detection rate for average risk
1. Hetzel et al. Variation in the detection of serrated polyps
colonoscopies at least 5%
in an average risk colorectal cancer screening cohort. Am J
Gastroenterol 2010
2. Kahi et al. Prevalence and variable detection of proximal
colon serrated polyps during screening colonoscopy. Clin
Gastroenterol Hepatol 2011
3. Wijkerslooth et al. Differences in proximal serrated polyp

Risk score for detection of Large

Proximal or Dysplastic (LPD)
serrated polyp
Derived from a Dutch study, patients
were subdivided into an average
risk group (total score <5 points),
high risk group ( total score 5
points). Patients in the high risk
group had a 3.2 fold increased
odds of having 1 LPD SP than those
in the average risk group.
Bouwens et al. Simple clinical risk score
identifies patients with serrated polyps in
routine practice. Cancer Prev Res (Phila)
2013

>/= 1 LPD SP risk score

Risk factors

Score assignment

Age > 50 yrs or </= 50

yrs

H/o > /= 1 serrated polyp

Current smoker vs never

Non daily or no aspirin vs

daily aspirin

Bouwens et al. Simple clinical risk score

identifies patients with serrated polyps in
routine practice. Cancer Prev Res (Phila)

Techniques for improved detection

of SSA
-Bowel preparation split bowel prep
-Endoscopic technique 2nd look in right
colon, retroflexion in ascending colon,
chromoendoscopy and pit pattern,
NBI, cap fitted colonoscopy
-Withdrawal time - A prospective Dutch
study found that longer withdrawal time
(median 10 mins) was associated with
significantly better PSP detection
(OR,1.12; 95% CI, 1.101.16)
1. Crockett et al. Sessile Serrated Adenomas: An
Evidence-Based Guide to Management. CGH 2015
2. Wijkerslooth et al. Differences in proximal serrated
polyp detection among endoscopists are associated
with variability in withdrawal time. Gastrointest Endosc

Endoscopic resection/pathological
interpretation of SSA
CARE study found that 31 % of SSA
are incompletely resected vs 7%
of other polyps 50% of large SSA
(1-2 cm) are incompletely resected.
Canadian study with 2 GI pathologist
showed reclassification of 17% of
proximal HPs, and 20% of HPs > 5
mm as SSA, suggesting wide
variability in pathological
diagnosis of SSA

1. Pohl et al. Incomplete polyp resection during colonoscopy-results of

the complete adenoma resection (CARE) study. Gastroenterology
2013
2. Singh et al. Pathological reassessment of hyperplastic colon polyps
in a city-wide pathology practice: implications for polyp surveillance

Endoscopic resection of SSA

Resect carefully use of
submucosal injection, use of stiff
snare, target normal tissue
margin after resection, consider
tattooing site of > 1 cm PSP post
resection and repeat colonoscopy in
3-6 months, willingness to refer to
experts
Crockett et al. Sessile Serrated
Adenomas: An Evidence-Based Guide to
Management. CGH 2015

Colonoscopic surveillance of
SSA/SPS
Serrated pathway cancers comprise
about 20-35% of all sporadic colon
cancers
Upto 57% of all interval cancers
arise from CIMP pathway
With SPS lifetime risk of CRC is 3040%

Syngal et al. ACG Clinical Guideline:

Genetic Testing and Management of
Hereditary Gastrointestinal Cancer

Colonoscopic Surveillance of
SSA/SPS - Proband
US
Consensus
panel, 2012

Annual colonoscopy surveillance is recommended for SPS.

SPS patients should be referred to Genetics for initial evaluation.
No specific gene targets identified for SPS yet, however overlap
between SPS and MUTYH associated Polyposis (MAP) may occur in
1. Rex et al. Serrated Lesions of the Colorectum: Review and
few patients.
Recommendations From an Expert Panel. Am J Gastroenterol.
2012
2. Syngal et al. ACG Clinical Guideline: Genetic Testing and

Colonoscopic surveillance of 1st

degree relatives of SPS patient
NCCN guidelines
Recommended screening colonoscopy at the earliest of the
following -Age of 40 yrs
-Same age as the youngest diagnosis of SPS if uncomplicated
by cancer
-10 yrs earlier than diagnosis of cancer complicated by SPS
Following baseline exam, screen every 5yrs if no polyps
found. If proximal serrated polyps or multiple adenomas are
found, then consider colonoscopy every 1-3 yrs
NCCN Clinical Practice Guidelines in Oncology.
Genetic/Familial High Risk Assessment: Colorectal. Version

Back to our patient

Utilize above techniques for
detection and resection of SSA
during future colonoscopies
Yearly colonoscopic surveillance for
SPS
Risk factor modification stop
smoking, continue his daily ASA 81
mg for CVS disease
Referral to Genetics clinic to rule out
MAP

Take Home Points

Serrated pathway is an under-recognized but
dominant pathway for CRC development. No target
genes have been identified for SPS yet
Majority of interval CRCs occur via the serrated
pathway
Patient education, performing All eyes on the
screen colonoscopies, careful resection of PSP is
key to making colonoscopy protective in right colon
Consider to risk assess patient with SP score precolonoscopy, and target PSP detection rate of at
least 5% for average risk colonoscopies

Questions?