Grand Rounds 21915 Mentor Milena Gould MD Case presentation 64 yo Caucasian male with ho heavy smoking COPD CAD without CHF on A spirin 81 mg aflutter on metoprolol well compensated HCVETOH liver cirrhosis Child class A MELD 9 on Harvoni was seen in GI lab for colonosc ID: 798303
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Slide1
Ashish Sharma
PGY4 GI fellow
Grand Rounds
2/19/15
Mentor- Milena Gould, MD
Slide2Case presentation
64 y/o Caucasian male with h/o
heavy smoking
, COPD, CAD without CHF on
A
spirin 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
Slide3Case presentation
Polyp
location
Polyp number, size and pathology Cecum 1 Tubular Adenoma (TA); < 1 cm Ascending colon 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
Colonoscopy exam and pathological findings
Total count – 9 TA and
21 Serrated polyps
Slide4Diagnosis- 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, or3.) 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: Springer-Verlag, 2010
Slide5Serrated Polyps, with focus on Sessile Serrated Adenoma(SSA)
Clinical Questions
1. Background, types, epidemiology, natural history,
g
enetics of
serrated polyps2. Interval/missed colorectal cancer and serrated pathway3. Sessile serrated adenoma – current detection rates, techniques for improved detection, endoscopic management
Slide7Background of Serrated
P
olyps
Serrated polyps are characterized primarily
by a saw-toothed appearance of colonic crypts, hence the namePrior to 1990s “Hyperplastic Polyps” (HPs) were considered benign. Term “ Serrated Adenoma” was coined in 1990s with findings of cytological atypia in HPsWith 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 TSATorlakovic et al. Morphologic reappraisal of serrated colorectal polyps. Am J Surg Pathol 2003Longacre et al. Mixed hyperplastic adenomatous polyps/serrated adenomas. A d distinct form of colorectal neoplasia. Am J Surg Pathol 1990
Slide8Types of Serrated
P
olyps
HPs -
Microvesicular HP (MVHP), Mucin poor HP, Goblet cell rich HPSSATSASnover DC et al. Serrated polyps of the colon and rectum and serrated (“hyperplastic”) polyposis. WHO Classification of tumours of the digestive system. Berlin: Springer-Verlag, 2010
Slide9Epidemiology 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 polypsProximal serrated polyp or large serrated polyp (> 1 cm) is used as a surrogate for SSA in epidemiological studies75-90% of SSA are right sidedCrockett et al. Sessile Serrated Adenomas: An Evidence-Based Guide to Management. CGH 2015
Slide10Epidemiology 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
limitedSmoking is associated with higher SSA incidenceNSAIDs is associated with lower SSA incidenceCrockett et al. Sessile Serrated Adenomas: An Evidence-Based Guide to Management. CGH 2015
Slide11Natural 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 yearSSA shows increased risk of synchronous and metachronous SSA, advanced neoplasia and colorectal cancerLash et al. Sessile serrated adenomas: prevalence of dysplasia and carcinoma in 2139 patients. J Clin Pathol 2010Oono et al.. Progression of a sessile serrated adenoma to an early invasive cancer within 8 months. Dig Dis Sci 2009Vu et al. Individuals with sessile serrated polyps express an aggressive colorectal phenotype. Dis Colon Rectum 2011
Slide12Natural history of SSA
Crockett et al. Sessile
Serrated Adenomas: An
Evidence-Based Guide
to Management. CGH 2015
Slide13Genetics of SSA - Serrated Pathway
Rex et al.
Serrated Lesions of the Colorectum: Review
and Recommendations
From an Expert Panel. Am J Gastroenterol. 2012
Slide14Clinical Questions
1. Background, types, epidemiology, natural history,
g
enetics of
serrated polyps2. Interval/missed colorectal cancer and serrated pathway3. Sessile serrated adenoma – current detection rates, techniques for improved detection, endoscopic management
Slide15Interval CRC and Serrated Pathway
Crockett et al. Sessile
Serrated Adenomas: An
Evidence-Based Guide
to Management. CGH 2015
Slide16Interval CRC and Serrated Pathway
Slide17Interval CRC and Serrated Pathway
Slide18Interval CRC and Serrated Pathway
Slide19Interval CRC and Serrated Pathway
Slide20Clinical Questions
1. Background, types, epidemiology, natural history,
g
enetics of
serrated polyps2. Interval/missed colorectal cancer and serrated pathway3. Sessile serrated adenoma – current detection rates, techniques for improved detection, endoscopic management
Slide21Detection 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.Tadepalli et al. A morphologic analysis of sessile serrated polyps observed during routine colonoscopy. Gastrointest Endosc 2011Oka et al. Clinicopathologic and endoscopic features of colorectal serrated adenoma: differences between polypoid and superficial types. Gastrointest Endosc 2004
Slide22SSA - Current detection rates
Hetzel et al. Sessile Serrated
A
denoma
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 colonoscopies – at least 5%1. Hetzel et al. Variation in the detection of serrated polyps in an average risk colorectal cancer screening cohort. Am J Gastroenterol 20102. Kahi et al. Prevalence and variable detection of proximal colon serrated polyps during screening colonoscopy. Clin Gastroenterol Hepatol 20113. Wijkerslooth et al. Differences in proximal serrated polyp detection among endoscopists are associated with variability in withdrawal time. Gastrointest Endosc 2013
Slide23Risk score for detection of
L
arge
P
roximal 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
Slide24>/= 1 LPD SP risk score
Ris
k factors
Score assignment
Age > 50 yrs or </= 50 yrs 2H/o > /= 1 serrated polyp 3Current smoker vs never 2Non daily or no aspirin vs daily aspirin 2Bouwens et al. Simple clinical risk score identifies patients with serrated polyps in routine practice. Cancer Prev Res (Phila) 2013
Slide25Techniques for improved detection of SSA
-Bowel preparation – split bowel prep
-Endoscopic technique – 2
nd
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, 1.10–1.16)Crockett et al. Sessile Serrated Adenomas: An Evidence-Based Guide to Management. CGH 2015Wijkerslooth et al. Differences in proximal serrated polyp detection among endoscopists are associated with variability in withdrawal time. Gastrointest Endosc 2013
Slide26Endoscopic 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 SSAPohl et al. Incomplete polyp resection during colonoscopy-results of the complete adenoma resection (CARE) study. Gastroenterology 2013Singh et al. Pathological reassessment of hyperplastic colon polyps in a city-wide pathology practice: implications for polyp surveillance recommendations. Gastrointest Endos 2012
Slide27Endoscopic 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 expertsCrockett et al. Sessile Serrated Adenomas: An Evidence-Based Guide to Management. CGH 2015
Slide28Colonoscopic surveillance of SSA/SPS
S
errated 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 30-40%Syngal et al. ACG Clinical Guideline: Genetic Testing and Management of Hereditary Gastrointestinal Cancer Syndromes.. Am J Gastroenterol 2015
Slide29Colonoscopic 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 few patients.
1. Rex et al. Serrated Lesions of the Colorectum: Review and Recommendations From an Expert Panel. Am J Gastroenterol. 20122. Syngal et al. ACG Clinical Guideline: Genetic Testing and Management of Hereditary Gastrointestinal Cancer Syndromes.. Am J Gastroenterol 2015
Slide30Colonoscopic surveillance of 1
st
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 SPSFollowing baseline exam, screen every 5yrs if no polyps found. If proximal serrated polyps or multiple adenomas are found, then consider colonoscopy every 1-3 yrsNCCN Clinical Practice Guidelines in Oncology. Genetic/Familial High Risk Assessment: Colorectal. Version 2.2014
Slide31Back to our patient
Utilize above techniques for detection and resection of SSA during future colonoscopies
Yearly
c
olonoscopic surveillance for SPSRisk factor modification – stop smoking, continue his daily ASA 81 mg for CVS diseaseReferral to Genetics clinic to rule out MAPScreening colonoscopies for 1st degree relatives starting at 40 yrs
Slide32Take 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
i
nterval CRCs occur via the serrated pathwayPatient education, performing “All eyes on the screen” colonoscopies, careful resection of PSP is key to making colonoscopy protective in right colonConsider to risk assess patient with SP score pre-colonoscopy, and target PSP detection rate of at least 5% for average risk colonoscopies
Slide33Questions?