March - CRC Awareness Month

Colorectal Cancer Prevention & Early Detection

Vijay Arya M.D.,F.A.C.P.,F.A.C.G.,A.G.A.F. Clinical Asst. Prof. of Medicine at Northwell.

Director,Endoscopy Unit, WHMC.

March - CRC Awareness Month

• Third most common cancer in USA- 131,607 new cases/year (2012) 67,700

men, 63907 women• Second Leading cause of cancer

death in men and women- 51,690 deaths (2012)

• Average patient CRC death- Losses 13 years of life

• A person at age of 50 has about - 5 % lifetime risk- 2.5% CRC death rate

CRC Facts

CRC Etiology • Environmental

– Stress– Activity– Diet

• Genetic – Sporadic 85-90% Avg risk• - HCCS 5-10% High risk

Consumption of red meat and

Saturated fat

Refined carbohydrates

Alcohol

Lack of regular physical activity.

Low fruit and vegetable intake.

A low-fiber and high-fat diet.

Overweight and obesity.

Tobacco use.

INCREASED RISK

Dietary factors implicated in colorectal carcinogenesis

North America has highest rate of Obesity-related cancers

•Colon

•Rectum

•Pancreas

•Esophagus

•Others

Dietary fiber

Vegetables

Fruits

Antioxidant/ vitamins

Calcium

folate (B Vitamin)

DECREASED RISK

Dietary factors implicated in colorectal carcinogenesis

LIFESTYLE MODIFICATION

• 35% of all cancers are attributable to diet

• 50%-75% of CRC in the US may be preventable through dietary modifications

• You are what you EAT• When, what ,where, how, how much to

eat ?• You can,t change your genetic makeup

Chemo-Prevention

• Above age 50 ,Healthy ,without risk of GI Bleeding

• Aspirin 75 , 80 , 100 mg / day • Many years before benefit • High risk of bleeding- Hx of PUD, NSAID,S• Antiplatelet meds • Steroids • Age >65

Genetic Model of Colorectal Cancer

Bat-26(HNPCC)

APC

Mutation

NormalEpithelium

K-ras

Adenoma

Bat-26(Sporadic)

p53

LateAdenoma

Early LateCancer Cancer

Dwell Time: Many decades 2-5 years 2-5 years

Optimum phase forearly detection

Courtesy of Barry M. Berger. MD, FCAP EXACT Sciences

Janne and Mayer 2000

ADENOMA-CARCINOMA SEQUENCE (1993)

• AGE: 90% of cases occur at age 50 and above

Average Risk Factors for Colorectal CancerAverage Risk Factors for Colorectal Cancer

Average Risk Factors for Colorectal CancerAverage Risk Factors for Colorectal Cancer

• Male > Female

• Asymptomatic

Average Risk Factors for Colorectal CancerAverage Risk Factors for Colorectal Cancer

Age/ Gender/ Ethnicity• >80% of CRC diagnosed > 55 yrs• Life time risk 5.7% M v/s 5.1% F• Mortality for F lag behind by 10 yrs • Increased age, male sex, black race- Higher

incidence• African American screening start age 45 • USPSTF- recommends screening Age 50-75• >Age 76 , individual basis

COLONOSCOPY

• Excellent prep up to cecum/ withdrawal time at least 6 minutes/ No polyps- 10 yrs

• 1-3 Adenomas ( <1 cm) – 5 yrs• 3-10 Adenomas – 3 yrs• Poor prep ( unable to detect 5 mm polyp)- Rpt

colonoscopy with better prep • PCPs & Patients are requesting for rpt

colonoscopy sooner than required• New patients need to get screened

– First Degree Relative with colon cancer– Hx of ureterosigmoidostomy– Personal history of Adenomas– Inflammatory Bowel Disease / with PSC– Type 2 Diabetes– Acromegaly– Bacteremia – strep bovis, clos septicum,strep

agalactiae– Familail breast ca- BRCA 1 or 2 mutation pos

High Risk Factors for Colorectal Cancer?High Risk Factors for Colorectal Cancer?

Higher than Avg risk• Pt,s 53 yr old brother had an adenoma

• Start screening at age 40 or 10 yrs prior to diagnosis of affected relative,whichever comes first.

• Hx of CRC <55, Adenoma <60 – special efforts to screen first degree relatives

Higher than Avg Risk• Large adenoma >1 cm

• Multiple adenomas >2

• Villous adenoma or High grade dysplasia

• F hx of CRC

• RPT Colonoscopy should be done in 3 yrs

Malignant polyp

• Favorable criterion• Complete excision• Not poorly differentiated• No vascular/ lymphatic invasion• f/u colonoscopy in 3 months to check for

residual tissue at polypectomy site if neg rpt at 1 yr

Malignant plyp • Unfavorable signs• Incomplete excision• Less than 2 mm margin from polypectomy• Undifferentiated • Vascular/ lymphatic invasion• Hemicolectomy should be done

HCCS- CLUES• CRC/ Polyps Age < 50 • >10 Adenoma• Syn/ Meta cancers• Numerous relatives with cancers• Accurate personal /3 generation fhx• 3-2-1 rule• Age at diagnosis/ death• All- AD except MYH asso polyposis( MAP)

SHARE THE INFO

• 5-10% of CRC• Identify pts- counseling /genetic testing of at

risk • Risk reducing management • Syn specific surveillance• Not at risk- avg risk CRC

SAVE THE FAMILY

HCCS• A- non-polyposis-• HNPCC• LS• Lynch like syn• Familial crc type x

• B- polyposis syn-• FAP/ MAP/JPS/PJ/Hamartoma ts/ SPS

HCCS- 3 Q TOOL• Personal hx of polyp/ CRC < age 50• First degree relative < age 50 with CRC,

uterine, ovarian, gastric, small bowel, kidney, ureter, bladder, biliary, pancreas, or brain

• >2 FDR or SDR with CRC ,any age• One in Five ( 20%) LS Missed • Universal molecular testing of all

CRC/Adenoma

HCCS

• LS – germline mutation in MMR gene & MSI-H • MMR defi in Tumor can be detected by IHC• Histological clues to MSI-H• Poorly diff, mucinous & signet cell• Tumor infiltration by lymphocytes• Crohn’s like lymphocyte reaction

HCCS• Mutation in ¼ MMR gene• MLH1,MSH2,MSH6,PMS2• Large deletion in EPCAM /hyper MSH2• Microsatellites are areas of short DNA rpts• Cacacaca– prone to errors in replication

normally corrected by MMR gene• Can be studied in tumor/ nl tissue/blood• >2 MSI-H , 1 MSI-L ,0 MSS

HCCS – S/S Colonoscopy• Colonoscopy 1-2 yrs beginning age 20-25• Pelvic exam –annual• Transvaginal us/ endometrial sampling• EGD 2-3 yrs with HP testing -age 30-35 • Colectomy with ileo-anal anastomosis• Aspirin –chemoprevention• Hysterectomy/ bilat sal- age 40 / finished

child-bearing

HCCS- Case• 37 yr old pt,s 62 yr old mother with colon ca• Maternal uncle –colon ca• Maternal grand-mother- endometrial ca• Suspect HCCS• Genetic counselling• Mother,s tumor tissue for –MSI• If pos – blood test for germ line mutation in mmr

gene• Neg blood test does not exclude the dx

FAP/MAP• About 1% each with pheno overlap• <100 adenoma – attenuated FAP- late teenage• 100-1000- classic -preteenage• >1000 profuse -preteenage• 100% gastric/duod fundic gland polyps• 100% risk of CRC around age 40 • Bx nl papilla to r/o adenoma( 2 nd cancer)• Thyroid/ brain/hepatoblastoma• Cong hyp of retinal pigment

High Risk-Sporadic• 15% Sporadic CRC ,MSI-H • Pos MLH1 gene • Pos BRAF mutation

• Sporadic CRC ( 85-90%)- genetic alt in single cell- chromosomal instability with MSS

Symptoms associated with CRC

Weight loss

Loss of appetite

Night sweats

Fever

Rectal bleeding

Change in bowel habits

Obstruction

Abdominal pain & mass

Iron-deficiency anemia

• Offer Early Detection / Primarily Cancer• High-Sensitivity FOBT -Annual ( FIT ,Stool

DNA based Tests, (DCBE,CTC – every 5 yrs)

• Offer Detection of polyp/cancer &Prevention

• Flexible Sigmoidoscopy – Every 5 year• Colonoscopy- Every 10 year

Types of Screening

Benefits of Screening

Cancer Prevention• Removal of pre-cancerous polyps to prevent cancer(unique aspect of colon cancer screening)

Improved survival• Early detection markedly improves chancesof long-term survival

Largest reduction in mortality during the 10 yrs after screeningComes from detection and removal of early stage cancer

Annual FOBT reduces CRC mortality and incidence by 30%FS has also shown the same benefit

Colonoscopy reduces mortality by 60-70% ( RCTs Awaiting)

100% Adherence to same regimen is equally effective

Benefits of Screening

Survival Rates by Disease Stage*

5-yrSurvival

*1996 - 2003

100908070605040302010

0

89.8%

67.7%

10.3%

Local Regional Distant

Stage of Detection

Colorectal Screening Rates

Just 40% of colorectal cancers are detectedat the earliest stage.

A little more than half * of Americans overage 50 report having had a recent colorectalcancer screening testSlow but steady improvement in these numbersover the past decade (but all are not benefitingto the same degree)

*varies based on data source

Colorectal Screening Rates Low:Reasons (according to Patients)

Low awareness of CRC as a personal health threat

Lack of knowledge of screening benefits

Fear, embarrassment, discomfort

Time

Cost

Access

“My doctor never talked to me about it!”

22 million people not up-to-date with screening

CT Colonography (CTC)

CTC Image Optical Colonoscopy

*AKA “Virtual Colonoscopy”

Images courtesy of Beth McFarland, MD

CT Colonography

Rationale Allows detailed evaluation of the entire colon

A number of studies have demonstrated a highlevel of sensitivity for cancer and large polyps

Minimally invasive (rectal tube for air insufflation)

No sedation required

CT Colonography

Limitations

Requires full bowel prep (which most patients findto be the most distressing part of colonoscopy)

Colonoscopy is required if abnormalities are detected,sometimes necessitating a second bowel prep

Steep learning curve for radiologists

Limited availability to high quality exams in manyparts of the country

Most insurers do not currently cover CTC asa screening modality

CT Colonography

Limitations

Extra-colonic findings can lead to additional testing(may have both positive and negative connotations)

Questions regarding:

Significance of radiation exposure

Management of small polyps

Sigmoidoscopy is IncompleteEquivalent to“left breast mammogram”

Colonoscopy

Colonoscopy is considered the gold standard for colorectal cancer screening

Beth Israel Medical Center

1 Sivak et al., 2004, 2Winawer et al., 1993

Dr Hiromi Shinya1 and Dr William Wolf

1971 - First colonoscopic polypectomy

COLONOSCOPY

• Available best option:– Screening Colonoscopy/polypectomy

Polyp to Cancer Progression

CRC is Preventable / Curable

DISCOVERY OF THE CENTURY

Polypectomy snare

Quality Colonoscopy • An effort to make Colonoscopy less variable

through a process of measurement, education & performance enhancement

• Adenoma Detection Rate( ADR)• Withdrawal time• Cecal Intubation Rate ( CIR)• Adherence to screening / surveillance intervals• Prep quality to see polyp 6 mm & >

ADR• 1% increase in ADR = 3 % reduction in CRC

incidence / 5% reduction in mortality• Simple act of measurement improved ADR• ASGE-maintain passport• ADR= protection against CRC• Education• Withdrawal technique• Technical advances and devices

ADR • High ADR= Better cleared at first

colonoscopy=Shorter interval ( double protection)

• Low ADR= Not effectively cleared= Longer interval ( double lack of protection)

• 3 or > Adenoma( 1 cm/ >) ,f/u exam at 1 yr• Future--Incentive to achieve high ADR/ allow

longer interval = Improve cost-effectiveness

CIR• TI intubation is gold standard• IC valve, Appendiceal orifice, Taenia coli• Medial wall of cecum • Documentation with Photographs• Low CIR = Higher rate of interval CRC

Bowel Preparation

• Dreaded more than procedure itself • Patient perspective

High volume

Unpalatable

Dietary restriction

Complex instructions

Day before v/s split dose

Impact on work or daily activity

Tolerability (side effects)

Bowel Prep• Inadequate bowel prep -20-40%• Rpt procedures- Cost• Missed lesions-both small and large• Commonly used preps- PEG• 2 L V/S 4 L• Day of , Day before, Split • Adjuvant - Dietary restrictions/ NPO

TYPE OF PREPARATION

PREP COMPARISON

Bowel Prep Scale• Overall -Poor, Fair, Good , Excellent • Segmental scores• BBPS – R, T, L 0-1,2,3 Max 9 , Adequate 5• ABPS- C, A,T,D,S,R Max 24 , Adequate 13• Total score doesn’t guarantee adequate prep in

all segments

Complications

•Miss rate :

- 5% of Colorectal Cancer

- 2% - 12% Polyp 1cm or larger

- >20% Polyp 6mm or larger

•Bleeding (2 -6 per 1000 examination)

•Bowel Perforation ( approx 1 per 1000 examination)

•Infection (approx 4% )

•Mortality (0.03%)

•Abdominal Pain & discomfort (5% - 11%)

Source: National Endoscopy Database/Clinical Outcomes Research Initiative

COLONOSCOPY – ALL AGES

MortalityPerson years of life lost

COLORECTAL CANCER

Trends

Incidence and deaths rates have fallen steadily for the past20 yrs

U.S. Colorectal Cancer Mortality 1975-2005

40.0

35.0

30.0

25.0 Blalck Male

WhiteMale20.0

Black Female

15.0 White Female

10.0

5.0

0.0

Research suggests that these declines are due in large part to:

•Screening and polyp removal, preventing progression of polyps to invasive cancers

•Screening detecting cancers at earlier, more treatable Stages

•CRC treatment advances

CRC is third leading cause of death in USA

Early stages are detectable/ curable

Screening can prevent CRC

Katie Couric: http://www.nccra.com/about/videos.htm

SUMMARY

POLYPECTOMY

S

Endoscopic Removal of Large Colon Polyps

Endoscopic Mucosal Resection (EMR)

Endoscopic Submucosal dissection (ESD)

- ESD is a variant of EMR in which a specialized needle knife is used to dissect lesions from the submucosa. The advantage of ESD is that it often permits removal of large sessile polyps en bloc (eg. in one piece), whereas EMR often removes the polyp piecemeal.

Polypectomy Risks

Removal of large colon polyps during endoscopy is associated with various risk, including:

- Perforation- Bleeding- Post Polypectomy Syndrome- Inadequate Polypectomy

Non Invasive PolypLarge polyps may contain cancer that is completely contained within the polyp.In these cases, polypectomy is considered curative, provided:

- The cancer is completely contained within the resected tissue - No lymphovascular invasion- Resection margins are free of cancer

Invasive polyps features that suggest the presence of malignancy include:

- Friability- Induration- Ulceration- Smooth velvety surface (e.g. non-granular laterally spreading tumor in the Rt colon)- Non lifting sign

Invasive Polyp

Endoscopic Ultrasound Role (EUS)

EUS can be used to assess invasive polyps features, especially sessile lesions in the rectum, such as:

- Sub-mucosal invasion- Enlarged Lymph nodes

Conventional EUS vs High frequency Mini-probes through the biopsy channel of the colonoscope to visualize the entire colon

Polyp size and location- Unusually large polyps ( >10 cm or with circumferential growth ) are not a contraindication for endoscopic polypectomy.

- Such polyps may require multiple sessions for removal and subsequent surveillance is mandatory

- These considerations should be explained to the patient prior to embarking on a course of endoscopic resection

Patient Preparation

- The preparation for endoscopic removal of large colon polyps is the same as that for routine colonoscopy and includes dietary changes and consumption of a bowel preparation.

- Polypectomy is a high-risk procedure with regard to bleeding

- Patient taking antiplatelets and anticoagulants will need to stop the medication

- Antibiotic prophylaxis is not recommended for polypectomy

Equipment

 In addition to the standard endoscopic equipment, additional equipment that may be used for the removal of large colon polyps includes:

●Polypectomy snares●Electrosurgical generators●Injection needles●Saline or hyaluronic acid●Methylene blue or indigo carminedye for staining●India ink or other dye for tattooing●Retrieval nets●Hemoclips●Nylon loops●Argon plasma coagulation probes●Argon gas●Needle knivesAll of the devices used can pass through the working channel of a standard endoscope.

Submucosal Injecion-Injection of saline or an alternative substance into the submucosa below the polyp raises the polyp on a cushion of fluid, facilitating endoscopic resection and potentially decreasing the risk of perforation during subsequent snare excision

-A problem with saline injection is that it is rapidly absorbed. As a result, alternative agents that are not as rapidly absorbed have been studied (with and without epinephrine), including hyaluronic acid, dextrose solutions, succinylated gelatin, and hydroxyethyl starch

COLONOSCOPES

RETRO-VIEW COLONOSCOPE

HIGH DEF. COLONOSCOPE

Technique

There are two primary goals of colonic polypectomy:

- Complete remove of all neoplastic tissue.

- Retrieval of all tissue sample

Only complete excision of the polyp permits accurate histologic diagnosis

High Def. Colonoscopy vs Chromoscopic Colonoscopy

Chromoscopic Colonoscopy

Colonoscopy Report

Colonoscopy Report

Surgical RemovalHISTOLOGY (Invasive Polyp), SIZE, LOCATION

- Size: Polyp ≥2.0 cm in their greatest dimension, eg. large sessile polyp

- Difficult location, eg. Cecum

- Saddle polyp:

Figure: Supine double-contrast barium enema spot image shows a semiannular “saddle” carcinoma. This lesion in the transverse colon manifests as two convex, barium-etched lines (arrows) that represent the edges of the lesion, which straddles one-half of the circumference of the bowel.

Surgical RemovalSurgery may be a better option for patients with:

- Polyps that occupy more than 1/3 of the circumference of the colon wall- Presence of two cross haustral folds- Polyps involving the base of the appendix- Multiple large polyps in the right colon - Patients with uncontrollable bleeding disorders

HOW IS COLORECTAL CANCER PREVENTED

•SHORT TERM -Screening: A screening test is used to look for a

disease when a person is not experiencing any symptoms.

•LONG TERM -Life style modification

• Epidemiology • Who is at Risk – Avg risk $ High risk• How it can be prevented- short term/ long

term• Short term – screening methods• Long term – life style modification

Diagram of Colon and Rectum

TAKE THE QUIZ. GET THE TEST

Colorectal Cancer Screening

What is screening?A screening test is used to look for a disease when a person is not experiencing any symptoms.Why is screening Important?When Should I Begin to Get Screened?

Tests for Polyps andCancer

Anatomy and CRC Distribution

Transverse 15%

Ascending

25%

Cecum

Rectosigmoid10%

Descending 5%

Sigmoid25%

Rectum 20%

Colonoscopy

Colonoscopyallows doctorto directly seeinside entirebowel

• Do I need to get a screening test for colorectal cancer?

• What screening test(s) do you recommend for me?

• How do I prepare?

• Do I need to change my diet or my usual medication schedule?

• What's involved in the test?

• Will it be uncomfortable or painful?

• Is there any risk involved?

• When and from whom will I get results?

If you're having a colonoscopy or sigmoidoscopy, you will want to know—

• Who will do the exam?

• Will I need someone with me?

Ask Your Doctor

1. Can you use a brand new scope?2. I have no problems why do I need a colonoscopy?3. Can I use the pills for prep ? 4. Can I go for CTC instead of colonoscopy?5. I do not have any one to accompany me6. Can you schedule me in afternoon?7. Can I go back to work after the procedure?8. What is the age to stop screening ?9. Can I have a DVD of my colonoscopy?10.Is my risk lower if I am not born in USA?

FAQ

Prevention is better than CureScreening saves lives

Colon cancer is Curable if detected earlyIf you can’t do it for yourself, do it for your family

Health is Wealth

Thank you