Gastroenterologist Dr. Patricia Raymond takes medicine seriously, and herself lightly. As a female gastroenterologist, she is, in fact, a “Chick who checks cheeks”. Dr. Raymond’s mission is to decrease the fright and ‘ick’ that keep about 50% of Americans from getting their screening colonoscopy at age 50—using laughter and knowledge to combat the fear. You can enjoy some of that humor at her website ColonJoke.com. And you can watch her music parody videos on YouTube at www.ButtMeddler.com. Please give a warm welcome to Dr. Pat Raymond’s alter ego, the divine….Ms Butt Meddler!
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Butt Meddler and her Divine Colonoscopy Concert
1. The Diva of Doo…
The Divine Ms. Butt Meddler
aka Patricia L. Raymond MD FACG
2. Colon Cancer Awareness:
A Humorous View
Patricia L. Raymond MD FACG
Assistant Professor of Clinical Internal Medicine,
Eastern Virginia Medical School, Norfolk VA
3.
4.
5. The Bottom Line.
• If colorectal cancer is detected
at an early stage, the survival
rate is more than 90%.
x Represent only 37% of cases
• If colorectal cancer is detected
at a later stage, the survival
rate falls to 60% or less.
Iceberg/back door
6. “Looking Up My Back Door”
Just got home from pharmacy,
guzzled my GoLytely
Got to sit down, take a rest on the
commode
Colon prep it kicks in, pretty soon
I'm poopin'
Doo, doo, doo, poopin’ out
my back door
www.ButtMeddler.com
7. Now that I’m turnin’ 50, I need
colonoscopy
To look for all the scary polyps
rompin’ up my rear
If you don’t want the cancer,
scopin’ is the answer
Doo, doo, doo, lookin' up
my back door
8. Gastroenterologists want to frolic
in my bowels
Sayin’ “Take a ride on my flyin'
scope”-
Wond'rous apparitions from
narcotic medications
Doo, doo, doo, scopin' up
my back door
9. The nurses and the doctor pump
air between my cheeks
I’m takin’ a ride on their flyin'
scope!
The drugs pack quite a wallop,
but soon I’ll have no polyps
Doo, doo, doo, scopin’ up
my back door
10. Fraid of fartin’? Make a noise!
Release that back door, oh joy
Listen to that happy flatus echo
round the room.
{Slowly}
Repeat the fun in five years,
meantimes you’ll have no fears
Doo, doo, doo, scopin’ up my
back door
11.
12.
13.
14. Sing along with me!
It must have been dark there
in your colon
To never have sunlight in that
place
You were content to let me
shine
(a light up your bottom…)
You never let me too far
behind…you
15. Hum along with me!
Did you ever know you could be
my patient?
‘Cause you have a place I’d like
to be-
I can go further than a sigmoid…
I’ll put the wind between
your cheeks!
16. Sing along!
Your wife is wrong; your
heads not up here
At least so far as I can see!
I do your colon cancer
screening…
I put the wind between
your cheeks!
17. “Scope” of the Problem
• Second leading cause of cancer-related deaths
in U.S.
• 6% lifetime risk of developing colorectal cancer
(CRC), but 3% lifetime risk of dying from the
disease
• Mortality related with stage at diagnosis
• 5-year survival for early stage ca: >90%
• Only 37% of patients
• 5-year survival for metastatic ca: <10%
vacation American Cancer Society, 2007
18.
19. Colon Cancer Screening Lags
• Breast Cancer- 69%
mammography
• Cervical Cancer- 86%
Pap testing
• Prostate CA- 75% PSA
• Colon CA about 50%
• Includes FOBT, Flex
Sig or colonoscopy
Seef, Cancer 2002;95:2211-22
Butcher Sirovich, JAMA 2003:289:1414-20
20.
21. CRC Screening is a bargain
Incremental cost /
Medical Practice life year saved
(US$)
Colonoscopy every 10
years: $ 6,600
Breast cancer screening: $ 22,000
Heart transplantation: $ 160,000
Cervical cancer $ 250,000
screening:
Average CRC death = loss of 13 years of life
22.
23. Natural History of the Polyp
• ~90% of colon cancers start from an “adenomatous
polyp”
• Adenoma to carcinoma sequence: 8 to 12 yrs
• Polyp size correlates to cancer
probability
• Polyps < 1 cm -- 1% are cancerous
• Polyps > 2 cm -- 30% are cancerous
24. Development of Colorectal
Neoplasia
Genetically predisposed individual
Environmental Chromosomal changes
Factors
(Diet, smoking, Colonic cell proliferation
inactivity)
Adenoma
Dysplasia
Source: D. Lieberman, 1992.
Carcinoma
25. Surveillance Post-Polypectomy
• 1-2 adenomas <1cm- 5 yr
F/U exam
• >3 adenomas, >1cm, or
with villous component – 3
yr F/U exam
• Numerous adenomas – 1
year F/U exam
• Large sessile polyp- 2-6
month F/U exam
• Negative F/U exam – 5 year
F/U exam Winawer, Gastroenterology 2003; 124:544
39. Early Detection of Colorectal
Cancer: Menu of Options
• Annual FOBT
• Flexible Sigmoidoscopy
every 5 yrs
• Annual FOBT plus Flexible
Sigmoidoscopy every five
years
• Double-contrast Barium
enema every 5 years
• Colonoscopy every 10years
40. Digital Rectal Examination (DRE)
• Part of a comprehensive physical exam but not
effective as CRC screening test
• Sensitivity for CRC less than 10%
• Often used to obtain stool sample for FOBT
with chance for increased false positive
results
• DRE plus one-sample FOBT performed
in office most common approach to
screening in U.S.
41. Double-Contrast Barium Enema
Effectiveness as National Polyp Study:
screening test Sensitivity of 48% for
debated polyps > 1 cm
• Further evaluation
required if polyps
detected
• Less risk of
perforation than
endoscopic exams
• May be recommended with
flexible sigmoidoscopy for
CRC screening
42. Fecal Occult Blood Testing
(FOBT)
• Detects blood from cancers or large polyps
• Bleeding is intermittent and increases with polyp
size and stage of cancer
• Hemoccult II (guaiac-based) most widely used and
studied FOBT
• Inexpensive and easy to perform
• Diet and medications affect results
• False positives: oral iron, aspirin, NSAIDs,
anticoagualants
• False negatives: vitamin C
43. Evidence of FOBT Effectiveness
• 5 controlled trials with 320,000
subjects
• Minnesota’s Colon Cancer
Control Study
• 33% CRC mortality reduction
with annual screening
• 18 year follow up found a lower
incidence of colorectal cancer
(Mandel 2000)
• Trials in Denmark and United
Kingdom: 15% to 18% reductions
in CRC mortality with biennial
screening
44. Sigmoidoscopy
• No controlled trials show efficacy in reducing
mortality
• Case-control studies show a 60% to 85% reduction
in mortality
• Advantages
• Relatively accurate
• Quick procedure performed w/out sedation
• Inexpensive
45. Sigmoidoscopy
Disadvantages
• Misses 40% - 50%
of CRC and polyps
• Risk of colon
perforation is 1 to 2
per 10,000 exams
• Patient preparation
a significant barrier
to adherence
Evidence for most
effective screening
interval is
inconclusive
46. CTC screening in 3120 consecutive
adults
OC screening in 3163 consecutive
CT Colonography adults
CTC OC
Adv. neoplasms 123 121
Invasive Cancers 14 4
Polyps detected, not removed
( 6-9 mm) 193 0
Total polyps removed
561 2434
Referral rate for OC in the primary CTC
screening group was 7.9% (246 of 3120
patients)
Colon Perforations 0 7
N Engl J Med 2007; 357:1403-1412
48. Preferred Option Approach:
Colonscopy
• Polypectomy prevents cancer; 90%
of incidence reduction from index
colonoscopy
• Polyps detected in 26-42% of
colonoscopies compared to 10% of
sigmoidoscopies
• 40% of colon cancers are proximal
to splenic flexure
• Single session diagnosis and
treatment
Zauber A,Gastroenterology; 2000:118:A187
49. Colonoscopy
• 95% of CRC in reach of
colonoscope
• Estimated effect of population
screening: could eliminate 80%
to 90% of CRC mortality in
population over age 50 years
• Diagnostic use after positive
results on FOBT or FS
• Recommended as initial
screening test for high risk
individuals
50. Colonoscopy
• Disadvantages
• Expensive
• Negative impact on patient’s daily
life
• Trained endoscopists must
perform
• Bowel perforation most serious
complication--1 to 3 per 1000
procedures (Winawer et al. 1997)
• No evidence from controlled trials
that shows mortality reduction
51. CRC Screening Guidelines
(USPSTF)
• FOBT annually and
• Flexible sigmoidoscopy (FS) every 5 years
• Screening should be individualized according to
age and comorbidities
• Two screening options suggested
• Double-contrast barium enema (DCBE) plus
FS every 5 years
• Colonoscopy every 10 years
53. from BM does Broadway: My Fair
Colon
I have often scoped
Through this hole before.
But your rectum hasn’t ever felt this full
before.
Lots of sedative
means you will forgive (and forget)
When I scope through the hole in your
rear.
54. Polyps all around
They don’t bother me
Cause I’ll excise them with my
snare and electrocautery
Minor torment
Will Colon cancer prevent
So I “go fish” in the hole in your
rear.
55. And oh, the inflated feeling
as I fill your colon with gas
And you‘ll float up to the
ceiling
As I search all nooks and
crannies for a mass!
56. Splenic flexure seen
Transverse colon passed.
It’s amazing what we see when we
inflate with gas.
All at once see I
Dii- Verticuli!!!
When I scope through the hole in your
rear!
57. How much risk do YOU have
for Colon Cancer?
Average Risk
• Age >50 (6% lifetime risk)
• ~75% of colon cancers are in average risk
Moderate Risk
• 1st degree relative with CRC
diagnosed >60 (2 fold increase)
High Risk
• 1st degree relative with CRC <60 or
multiple 1st degree relatives (3-6 fold
increase)
Extreme High Risk
• FAP (>95%)
• HNPCC (>80%)
58. Risk for Colorectal Cancer
• GYN malignancy (ovary, uterine) before
age 50
• RR 3.5, colonoscopy q 5 years
• Breast cancer RR 1.1
• New concerns
• African Americans
• Obesity
• Smoking
59.
60. Who gets colon cancer?
Race Men Women
All 60.8 44.6
Black 72.6 55.0
White 60.4 44.0
Hispanic 47.5 32.9
Asian 49.7 35.3
American 42.1 39.6
Indian
NCI SEER CA Statistics 2000-2004
Age adjusted, cases per 100,000 population
www.ColonoscopyJoke.com
61. African-Americans and CRC
• Younger mean age at diagnosis
• Higher incidence
• Higher mortality
• More proximal distribution of cancer
and polyps
• Recommendation ACG 2009:
Begin screening at age 45
Ghafoor et al, Cancer J Clin,2002;52:326
Theuer et al, Gastroenterology, 2001;120:848
Ries et al, http//seer.cancer.gov/csr/1975-2000
63. “Start at 45”
If you don’t want it then you better
put a scope in it
If you don’t want it then you better
put a scope in it
Prevention’s better than just
prayin’ and a’hopin’ it
If you don’t want it then you better
put a scope in it
64. Epidemiology
• 30% - 50% of population will develop adenomatous
polyps over lifetime
• 1% - 3% of polyps become malignant
• Most remain asymptomatic & undetected
• Prevalence of polyps increases with age
• 50% of men, 40% of women by age 50
• > 90% of CRC diagnosed after 55 yrs
65. Colorectal Cancer:
Not all one flavor
Heterogenous group of diseases
• Sporadic (no family history)
• Familial
• At least one affected 1st degree
relative
• 15%-20% of those at high risk
• Recessive gene + environment/
dietary factors
• Hereditary
• Early age of diagnosis (< age 45)
• Multiple primary tumors
• Autosomal dominant
• FAP, HNPCC
67. FH Colon Cancer,
not necessary, but important
• 75% sporadic
• 15-20% FHCC
• 3-5% HNPCC
• 1% IBD
• <1% FAP
JNCI 1991;83:243-253
68. Screening Moderate Risk Patients
• Single first degree relative
diagnosed at age > 60 years with
cancer or adenoma
• Recommendation:
• Begin screening at age 40
Winawer et al, Gastroenterology2003;124:544
69.
70. Screening High Risk Patients
• Two or more first degree relatives with
cancer or adenomas
• First degree relative with cancer or
adenoma diagnosed at age < 60 years
• Recommendation:
• Begin screening at age 40 or 10
years younger than age at diagnosis
of youngest affected relative
• Colonoscopy every 3-5 years
Ahsan et al, Ann Intern Med 1998;128:900
72. HNPCC (Lynch Syndrome) –
Clinical Features
• Modified Amsterdam Criteria
• 3 relatives with HNPCC related cancer
(CRC, uterine, ovarian, small bowel, renal pelvis or
ureter)
• 2 generations affected
• 1 person diagnosed at age <50
• 1 person is a first degree relative of the
other two
Vasen et al, Gastroenterology 1999; 116:1453
73. Lynch Syndrome
• 3-2-1
• >25% colon cancer BY AGE 50
• 80% colon cancer by age 70
• Endometrial cancer 20% by 50, 60% by 70
• Ovary 12% by 70
• Stomach 13% by 70
• Urinary tract 4% by 70
• Small intestine <5% (100 fold relative risk)
• Biliary 2%
• Brain 4%
74. HNPCC
Screening Recommendations
• Colonoscopy beginning age 20-25 every
1-3 years
• Annual Endometrial aspirate and
transvaginal U/S
• CA-125 (controversial)
• Genetic Testing (microsatelite instability)
Burt, R. Gastroenterol Clin North Am. 1996 Dec;25(4):793-803.
75.
76. Effect of Smoking
2009 ACG CRC Guidelines
• 20 pack years smoking
• >2-3 times risk of
adenomas
• 30% increased risk
CRC
• Risk may remain
elevated as long as 20
years after cessation
Am J Gastro 2009;104: 739-750
77. Effect of Obesity
2009 ACG CRC Guidelines
• Overweight and obese
• Increase CRC by 1.5-2.8
fold
• Estimate 3% increase
CRC with each 1 unit
increase in BMI
• Doubles risk of adenomas
• More high risk
adenomas (> 1 cm,
tubulovilous)
Am J Gastro 2009;104: 739-750
79. Can you reduce your risks?
Risk factors Protective factors
Strong (RR > 4.0) Moderate (RR < 0.6)
Advanced age High physical activity
FAP / HNPCC Aspirin / NSAIDs use
Long-standing ulcerative colitis
Modest (RR 0.9 - 0.6)
Moderate (RR 2.1 - 4.0) High vegetable / fruit diet
High red meat diet High fiber diet
Previous adenoma or cancer High folate intake
Pelvic irradiation High calcium intake
Postmenopausal hormone
Modest (RR 1.1 - 2.0) therapy
High fat diet
Smoking and alcohol
consumption
Obesity
Cholecystectomy
Sandler, Gastroenterol Clin N Am
1996:27:717
81. Healthy Lifestyle Reduces Colon Cancer
• Exercise • Stop Smoking
• 40% reduction in polyps • 30% increased risk
• Greatest effect in cancer
vigorous exercisers (89 • 2-3 x number polyps
flights) • Low animal fat diet
• Maintain normal body • <2 servings red meat
weight (BMI 25) per week
• Overweight increases • Eat fresh fruits and
cancer by up to 2.8 vegetables
times
• Polyps 2x, bigger
• 4 and 3 per day
• Avoid excessive • Aspirin therapy
alcohol • Hormone replacement
therapy in women
www.ColonoscopyJoke.com
82.
83. Nurses Health Study:
Exercise
• Decreases
woman’s risk of
polyps and cancer
by half
• As little as 30
minutes per day
• Moderate level as
useful as intense
MedSciSports Exer 2003;35:1823-27.
Amer J Epid 2003;158:214-24
Inter J Cancer 2006;119:385-91
84. • Reduces colon (35%) but
not rectal cancer
• >4.5 servings vs <1.5
servings/day
• Swedish Mammogram Cohort, Br J
Cancer 2005;92:1803-7
• No significant association
between intake of fruits &
vegetables and CRC
incidence
• Nurses Health Study
85. Vitamin D
• Strong evidence to support anti CRC effect
• 15 minutes sunlight daily
• Fatty saltwater fish (tuna, halibut,
mackerel, herring, sardines), shitake
mushrooms, fortified milk or enriched
breakfast cereal
• Dosage
• 19-50yrs 200 IU
• 51-70 400 IU
• >70 600 IU
86. Vitamin D:
Prevention AND Survival?
• 51% decrease in CRC risk
with high Vitamin D levels
• High pre-diagnosis
levels of vitamin D
with significant
improvement in
overall survival
Am J Prev Med 2007, J Clin Onc 2008
87. Leafy greens
• Nurses Health Study
• 15 years MVI with folic acid
with 75% risk reduction in
CRC
• MVI with 400 mcg folic acid
• Spinach, kale, romaine,
asparagus, broccoli, Brussels
sprouts, cantaloupe, oranges,
oatmeal, peas
Baron et al. NEJM 1999
Giovannucci et al AnnInternMed 1998
88. Chemoprevention-ASA
• 19% reduction in adenoma
recurrence with low dose
ASA, 4% with high dose
• Relative risk of advanced
adenomas reduced 41% with
low dose ASA
• 25% decrease in adenoma
formation with ASA 2 or more
times/wk. 50% decrease with
>14 ASA/wk
• Need to weigh risk of stroke,
etc on case by case basis;
not enough information for
blanket recommendation
Sandler, et al, NEJM 2003
Chan, et al AnnInternMed 2004
89.
90. The BOTTOM line:
• Early diagnosis or prevention = cure
• Colon cancer screening IS cost
effective.
• If you, a friend, or loved one are in a
risk population, make sure you receive
screening.
93. Hum along with me!
As you approach your fifties,
Don’t put off this test too long-
‘Cause if you think that colon
screening’s
Just for SadoMasochistic
Idiots, then you’re wrong!
94. Just remember when you’re
fifty
Your risk of colon cancer
grows.
Suck it up, make your
appointment,
When you’re clean, here
comes…
The HOSE!
95.
96. If you’re BEHIND on
your screening
colonoscopy…
www.ColonoscopyJoke.com
To be a suitable target for population-based screening efforts, a disease should represent a significant public health burden. Colorectal carcinoma does have a significant impact in terms of incidence, treatment-related morbidity, and mortality. Colorectal is the third most commonly diagnosed cancer among men and women in the U.S. From American Cancer Society’s Cancer Facts and Figures 2002 : 135,400 new cases in 2001 (98,200 of colon cancer and 37,200 of rectal cancer) 56,700 deaths in 2001 (48,100 from colon cancer and 8,600 from rectal cancer) However, note that CRC incidence rates declined -1.6% per year during the period 1985-1997. Mortality rates likewise declined slightly over this same time period for white Americans. However, African Americans have higher incidence and mortality from colorectal cancer than any other group in the general US population except Alaska natives. When colorectal cancers are detected at an early, localized stage, the 5-year survival rate is near 90%. But, only 37% of CRC are discovered at this early stage. With metastases to regional lymph nodes or adjacent organs, 5-year survival falls to 65%. The 5-year survival for those with distant metastases is an even grimmer 8%.
A polyp is any “grossly visible protrusion from the mucosal surface” (Harrison’s Principles of Internal Medicine), p. 571. Polyps are histologically classified as juvenile, hyperplastic, or adenomatous. Only the adenomas are considered premalignant. In appearance, adenomatous polyps are either pedunculated (on a stalk) or sessile (flat). The evidence for the assumption that cancers of the colon develop from adenomas is indirect. Leaving polyps in place and observing the consequences to humans is obviously unethical. The adenoma to carcinoma sequence was first presented by Morson and colleagues in 1975 and includes: 1) cancers and adenomatous polyps have the same anatomic distribution; 2) cancers usually do not develop in the absence of adenomas; 3) average age of onset of adenomas precedes that of cancer by several years; 4) patients with one or more large (>1 cm) polyps have been found to be at increased risk of future cancer; 5) most of these cancers arise at the site of large polyps left in place; 6) patients with familial adenomatous polyposis have numerous adenomatous polyps and a greatly increased cancer risk. The adenoma-to-carcinoma sequence was further validated by the National Polyp Study (1980-1990), which determined optimal time interval for repeat colonoscopy after polypectomy. Colonoscopy at 3 years follow up was as effective as colonoscopies at 1 and 3 years in detecting colonic lesions. More importantly, Winawer and colleagues (1993) had compelling evidence that polypectomy and periodic colonoscopy reduced the incidence of CRC in the National Polyp Study population (by 76-90%) as compared to three groups of historical controls. Dukes was the first to chart the progression of polyp to carcinoma in 1925, and to note that polyps became more dysplastic with increases in size. Dukes developed the pathologic staging system for colorectal cancers based on tumor penetration in the bowel wall, spread to regional lymph nodes, and presence of metastatic disease (Dukes Stages A, B1, B2, C, D).
This figure was adapted from: Lieberman, D. 1992. Targeted Colon Cancer Screening: A concept whose time has almost come. Am J of Gastroenterology , 87(9): 1085-93. This figure represents the probable sequence of events in the development of colorectal cancer within individuals. The individual may become susceptible to CRC through an inherited gene or somatic cell mutation. The recognition of specific chromosomal alterations has given rise to the hypothesis that the inactivation of tumor suppressor genes leads to the mutation or activation of oncogenes. This sequence may be modified in different ways in different individuals. Using genetic markers for screening asymptomatic individuals is not possible at this time. Research has focused on the more indirect method of examining colon cancer incidence among first-degree relatives of cancer patients and of first degree relatives of those with adenomatous polyps. The greater incidence of polyps and colon cancers in first-degree relatives has led to the hypothesis that adenomatous polyps (and cancer) occur in those with inherited susceptibility. Thus, the parameter of risk remains—however imperfectly—family history.
Fewer than 10% of colorectal cancers can be palpated by examining finger; thus a negative DRE rarely conclusive as primary evidence in rejecting a cancer diagnosis. (Length of finger (7-8 cm) vs rectal mucosa (11 cm) In fact, “the digital rectal exam combined with a one-sample fecal occult blood test performed in the office is probably the most common approach to screening in the United States.” (Ransohoff and Sandler, NEJM , 2002, p. 42) The possibility of increased false positive results resulting from trauma induced by the rectal examination itself has led many professional groups to advise against using the DRE to obtain samples for the FOBT. However, Bini and colleagues (1999) reviewed records of patients referred to colonoscopy after positive results of FOBTs obtained by DRE or SPS (spontaneously passed stool) samples. During the five year study period, authors found no difference in number of false-positive test results or cost per cancer between the two patient groups The American Cancer Society guidelines for CRC screening (ACS 1997) recommends that DRE should be performed at the time of sigmoidoscopy or total colon examination, that is, every 5 to 10 years. The DRE may be performed more frequently for other purposes, such as prostate examination in men or as part of the bimanual pelvic examination in women. The digital rectal examination is not recommended by United States Preventive Services Task Force (USPSTF) for CRC screening.
Effectiveness of double contrast barium enema as a routine screening test for CRC has not been directly evaluated. Case studies have reported sensitivities of 80% to 95% and specificity of approximately 90% in identifying cancerous lesion. Limited data on screening populations results in difficulty in determining effective screening intervals using this procedure. Note that the double-contrast barium enema is incorporated into screening recommendations as an “optional” procedure. The DCBE study is relatively ineffectual at identifying polyps that are greater than 1 cm in diameter or are in an area of the colon where a single lumen cannot be seen, such as the hepatic and splenic flexures and the sigmoid colon. The DCBE has less risk for the patient than flexible sigmoidoscopy or colonoscopy (bowel perforation rate is 1 in 10,000). As the DCBE is a radiologic technique, it does not offer the ability to directly visualize, biopsy, or remove suspicious lesions. When polyps or other abnormalities are identified by DCBE, further evaluation by colonoscopy is required. Because many patients screened by DCBE also have a colonoscopy, many practitioners prefer to screen with colonoscopy and save patients the discomfort, inconvenience, and radiation exposure of the DCBE. Thus, the DCBE has become a less popular screening tool (Inger, 1999). Patients are exposed to 300-500 mrem of radiation during a DCBE. Compare this to the 300 mrem for a screening mammogram (Winawer et al., 1997) When used in conjunction with a flexible sigmoidoscopy, some groups consider the DCBE to be a reasonable alternative to colonoscopy for individuals of average risk for colorectal cancer.
All screening with FOBT is based on the concept that colonic neoplasms (e.g., early-state CRC) and large adenomatous polyps may bleed intermittently (about 30% of the time) and stool will contain a combination of hemoglobin, intact heme, and heme-derived porphyrins in amounts that depend on the site and amount of bleeding, and the transit time through the gut (Ransohoff and Lang 1997). Greegor (JAMA 1967) was the first to report the efficacy of occult blood testing in detecting asymptomatic CRC. Three types of FOBT tests are available: Chemical guaiac-based tests, such as Hemoccult II, are based on pseudoperoxidase activity of hemoglobin, which converts colorless guaiac to blue by phenolic oxidation. Heme-porphyrin testing (e.g., HemoQuant) increases the sensitivity of screening. Hemoglobin shed into GI tract undergoes bacterial degradation to heme-derived porphyrins, which are not detectable by the pseudoperoxidase reaction. This explains the relative insensitivity of guaiac-based tests to upper GI tract bleeding and to a lesser extent, to bleeding from the right side of the colon. Immunological testing (e.g., HemeSelect) detects intact hemoglobin or globin with a range of techniques. While these tests are relatively specific for colonic bleeding (with better accuracy for detecting colorectal tumors) and do not require dietary restrictions, they are more expensive than chemical tests and have a number of technical problems, such as cross-reactivity with animal hemoglobins and sample reproducibility (Simon 1998). Dietary restrictions are advisable for at least one to three days before sampling for FOBT begins. False positive results are caused by oral iron, aspirin, NSAIDs, anticoagualants. False negatives by foods or supplements containing vitamin C. Patients should abstain from red meat, poultry, fish, raw vegetables (radishes, broccoli, cauliflower, etc.) and citrus fruit for at least 24 hours before the first specimen is taken. Patients should not take any oral iron supplements or aspirin, anticoagulants, or NSAIDs (Motrin, Aleve, Advil). Taking these increases the test’s sensitivity but lowers its specificity, increasing the number of both “true” and “false” positives and therefore making it harder to determine who truly has a positive diagnosis.
The five prospective controlled trials were in the US and Europe, the most influential being the Minnesota Cancer Control Trial (Mandel 1993). The University of Minnesota study screened asymptomatic individuals aged 50 to 80 years with rehydrated Hemoccult II. Subjects were volunteers, often recruited from local ACS chapters. Sensitivity was 81% for unhydrated and 92% for hydrated samples. United Kingdom (Hardcastle 1996); Denmark (Kronborg 1996). Note that all of these trials differed in size, methodology, level of patient compliance, and length of follow up. Results from these five studies: screening detected colorectal cancers at earlier stages, and patients with screen-detected cancers had increased survival
Visualizes lower 2 feet of colon (left side), site of majority of CRC and polyps. Flexible sigmoidoscopy involves snaking a fiberoptic tube (60 cm) through the rectum and colon to view the intestinal lining. Polypectomy (removal and cauterization) possible in this procedure as well as in colonoscopy. Note that sensitivity and diagnostic yield of sigmoidoscopy varies with the instrument: length of the sigmoidoscope (usually 25, 30 or 60 cm.) has direct effect on CRC detection. Selby et al. (1992) published most convincing evidence for CRC mortality reduction. In a nested case-control study among members of Kaiser Permanente, use of proctosigmoidoscopy among those who died of CRC from 1971 to 1988 was compared to a group of matched controls. The authors concluded screening sigmoidoscopy reduced CRC mortality by about 60% within the screened region. Accuracy: few false positives or false negatives The procedure generally lasts from 10 to 15 minutes, and may be performed by trained general practitioners in an outpatient setting. Sigmoidoscopy cannot detect cancers in upper (right) bowel, which have increased over generations among the general population. About 72% of hereditary nonpolyposis CRC are also out of range of sigmoidoscope (Bond 2000).
Sigmoidoscopy is highly sensitive to those cancers within reach of the instrument, but misses the approximately 40-50% of lesions that are proximal or ‘right-sided.’ But, if the presence of any adenoma is used as the diagnostic threshold for colonoscopic workup, the sensitivity can be as high as 70% (Ransohoff and Sandler, NEJM, 2002) Patient preparation involves dietary restrictions and some bowel evacuative procedures (e.g., two enemas the morning of the exam) that have proven deterrents to patient adherence to screening recommendations. Selby et al. found protective effects of sigmoidoscopy lasted 9 to 10 years while Muller and Sonnenberg (1995) noted a six-year interval between procedures still protected against CRC.
Colonoscopy visualizes the entire colon (6 feet) and allows removal/cauterization of polyps (Winawer 1991; Eddy 1996). Sensitivity: 75% to 95% in various screening populations. Estimated effect when used as a screening procedure for average risk individuals >50 and combined with polypectomy (Winawer 1993). High costs from sedation and monitoring, which increases overhead costs. OR complication rate of 3 per 10,000 procedures (Winawer 1993). The use of colonoscopy for screening may possibly result in significant numbers of severe complications. Note that there are not enough trained endoscopists in the U.S. for use in full-scale CRC screening program Because of the limited sensitivities of FOBT and FS in detecting CRC, those who are at higher risk require a more accurate modality (e.g.,colonoscopy).
Costs usually dictate the test preferences of both patients and third-party payers. The costs associated with colonoscopy have decreased over the past decade, but charges (and reimbursement rates) vary regionally (or locally) depending on volume, market pressures, and contracts. Although it is the most expensive test, colonoscopy may ultimately cost less in that it prevents cancers and does not need to be performed frequently (once every 10 years). Insurers tend to be more worried about up-front costs, not ultimate cost savings from averting cancers 10 or 20 years in the future. Patient preparation generally requires dietary restrictions with a thorough bowel evacuation beginning the night before the exam. Because a sedative is administered, patients generally need assistance with transportation and to take a full day from work. The psychosocial aspects of patients’ experience with colonoscopy may include discomfort, embarrassment, anxiety, and other harms associated with testing. On a national level, the number of trained endoscopists may be inadequate to provide colonoscopy as a screening test for those over 50 years of age (Woolf, 2000). The rate of complications reported from six prospective studies of colonscopy indicate that about 1 in 1000 patients have perforation, 3 in 1000 have hemorrhage, and 1-3 in 10,000 die as a result of the procedure (Winawer et al. 1997)
The USPSTF guidelines are found in The Guide to Clinical Preventive Services, 2 nd ed . (1996) , which provides screening recommendations based on a review of evidence from over 100 interventions. The USPSTF guidelines offer recommendations on screening, counseling, and immunization practices that have proven efficacy and effectiveness and the least risk of harm to patients. These guidelines are for average risk, asymptomatic individuals over age 50. Why combine FS and FOBT in CRC screening guidelines? FOBT insensitive in detecting polyps, esp. small ones FOBT least effective in detecting rectosigmoid cancers FOBT can detect right-sided cancers that are out of sigmoidoscopic range USPSTF estimates that screening with both tests could reduce CRC mortality by 50% The American Cancer Society has also endorsed DCBE every 5-10 years as an alternative screening test. There are no prospective studies demonstrating efficacy of DCBE alone for reducing CRC mortality. FS should be done in conjunction because of poor visualization of rectosigmoid area by DCBE. Other disadvantages of DCBE include lower sensitivity (83%) for detecting CRC than colonoscopy (95%) and lack of therapeutic capability, e.g., polypectomy (Rex et al. 1997). Colonoscopy allows for full visualization of colon and therapeutic potential. There is no direct evidence that screening colonoscopy alone every 10 years reduces CRC mortality. Screening options are included although there is no supporting direct evidence for their efficacy in reducing CRC mortality.
Epidemiological studies in many different countries implicate environmental factors, particularly diet, in CRC incidence and mortality rates. Populations in countries with highest risk, including the U.S. and Canada, consume a diet that is high in red meat and total fat. Individuals moving from a low risk country to a high risk country assume the higher risk of the new country within a generation or two as they westernize their diets. Although genetic alterations are the underlying mechanisms of CRC carcinogenesis, genetic-environmental interactions seem to be key to the process. Biochemical basis for cancer-promoting action of fat has not been identified, but proposed mechanisms include: 1) High-fat diets increase concentration of biliary sterols that damage epithelial cells; 2) Lipid peroxidation releases free radicals that enhance carcinogenesis; and 3) Fat-induced prostaglandin synthesis promotes cellular proliferation Effects of fiber: 1) Inhibits carcinogenesis by diluting and decreasing intestinal transit time of luminal contents; 2) Reduces luminal pH, inhibiting harmful bacteria and reducing effects of bile acids; and 3) Binds and neutralizes potential carcinogenic substances. Case control studies have shown inconsistent results regarding the association between dietary fiber and colon cancer, although meta-analyses of these studies show an overall beneficial effect of fiber on CRC incidence (USPSTF 1996). It is not known how excessive calorie intake enhances carcinogenesis. The direct effect of calories, lack of exercise altering metabolic rates, and altered body weight and composition have all been postulated as primary factors enhancing CRC risk. Physical activity decreases colonic transit time, (like fiber ingestion), which may decrease exposure to luminal carcinogens (Bond 2000). Specific dietary guidelines for CRC prevention include limiting daily fat intake to less than 30% of total daily caloric intake and ingesting at least 20-23 g of fiber daily
The prevalence of polyps can only be estimated from data gathered in autopsy surveys or selected population-screening studies—the sources for this prevalence range.
The largest proportion of colorectal cancers are considered sporadic, which means there is no history of CRC in first degree relatives or a history of the hereditary forms of the disease among family members. No specific gene has been identified in patients with sporadic CRC. Familial colorectal cancers occur in persons who have at least one first degree relative with CRC. Researchers theorize that 1) the susceptibility to CRC may be linked to a recessive gene or genes that produce a heightened susceptibility to carcinogenic mutations in the intestinal mucosa; 2) dietary and environmental factors may play a key role in carcinogenesis rather than genetic inheritance; or 3) a combination of genetic predisposition and environmental triggers result in the development of CRC. Hereditary forms of CRC show a distinct autosomal-dominant pattern of transmission. Several types have been identified including: Familial Adenomatous Polyposis (FAP); carriers of the gene have a nearly 100% of developing CRC. In this rare condition, thousands of polyps invade the bowel of the affected individual, usually by age 25. If the polyposis is not treated surgically with total colectomy, cancer will develop in almost all patients by age 40. Hereditary Nonpolyposis Colon Cancer (Lynch Syndrome)—HNPCC is associated with a high frequency of adenocarcinomas arising in the proximal large bowel. HNPCC is often associated with other primary cancers; there is a strong association with ovarian or endometrial cancers in women.