10/9- Colorectal Cancer Syndromes and Screening Flashcards
Colorectal cancer is the __ most common cancer among men and women in the US
- __ leading COD of cancer
- Can largely be prevented with _____
Colorectal cancer is the 3rd most common cancer among men and women in the US
- 2nd leading COD of cancer
- Can largely be prevented with CRC screening
What is the lifetime risk of colorectal cancer?
5%
Death rates of colorectal cancer (male vs. female)?
Death rates per 100,000
Male: 32%
Female: 28%
What is the 5 yr survival rate if found at local stage?
Local stage: 90% 5 yr survival
- Only 40% diagnosed at early stage (low screening rates)
What are the stages of colon cancer?
Polyp
- Most colon cancers develop from these nancancerous growths
In situ
- Cancer has formed but is not yet growing inside the colon or rectum walls
Local
- Cancer is now growing int he colon or rectum walls; nearby tissue unaffected
Regional:
- Growth beyond the colon or rectum walls and into tissue or LNs
Distant:
- Cancer has spread to other parts of the body such as liver or lungs
The adenomatous polyp is precursor of __% of colorectal cancers
- Sequence?
The adenomatous polyp is precursor of 90% of colorectal cancers
- Adenoma to carcinoma sequence: 7-10 yrs
What are clinical features related to polyps and cancer risk?
Polyp size correlates to probability of containing cancer:
- Polyps < 1.5 cm: < 2%
- Polyps > 2.5 cm: 10%
Histology: villous > tubulovillous > tubular
Number of polyps
Appearance: sessile vs. pedunculated
___% of population will develop adenomatous polyps over lifetime
__% of polyps become malignant
__% of CRC diagnosed after __ yo
30-50% of population will develop adenomatous polyps over lifetime
1-3% of polyps become malignant
>90% of CRC diagnosed after 55yo
Is more colorectal cancer sporadic or familial?
Sporadic
What are risk factors for colorectal cancer?
Age: 90% of cases occur in people > 50yo
Gender: slight male predominance (but occur in both)
Race/ethnicity:
- African Americans have highest incidence and mortality rate of all groups in U.S. (it has been recommended to start screening at age 45)
- Increased rates also documented in Alaska natives, some American Indian tribes and Ashkenazi Jews
Increased risk also with:
- Personal history of inflammatory bowel disease, adenomatous and serrated polyps or colon cancer
- Family history of adenomatous polyps, colon cancer or other conditions (including hereditable gastrointestinal polyposis syndromes)
What are screening recommendations based on different degrees of family history/risk?
- Screening colonoscopy is recommended at age 40 or 10 years before the youngest relative’s diagnosis, to be repeated every 5 years:*
- If a single 1st degree relative was diagnosed before 60 years with CRC or advanced adenoma
- If ≥2 relatives had CRC or advanced adenomas at any age
- Advised to be screened as average-risk persons beginning at age 50*
- For individuals with some increased risk (1st degree relative with CRC or advanced adenoma diagnosed >60 years)
What are dietary factor risks for CRC?
- High fat diets correlate w/ high rates of CRC
- Protective effects of fiber are still unproven
- Excessive calorie intake may enhance risk
What are behavior factor risks for CRC?
- Physical activity may reduce risk
- Excessive alcohol use and smoking have been associated with increased risk
What is infectious risk for CRC?
Streptococcus Bovis Bacteremia
What are clinical features of CRC?
- Right sided- may be asymptomatic, or have symptoms of anemia
- Tumors more distal may have symptoms related to obstruction of the passage of stool
- Distal tumors may also present with bright red blood
- Unexplained Iron deficiency anemia warrants endoscopic evaluation
What is flexible sigmoidoscopy?
- Can identify what
- Sedation needed?
- Identifies lesions in the distal 60 cm of the bowel
- Requires minimal patient preparation
- Does not require sedation
- Performed by trained clinicians
- Abnormal findings require a full colonoscopy
What is colonoscopy?
- Requires what
- Miss rate
- Requires bowel preparation
- Conscious sedation
- Lesions can be removed during the procedure
- Risk of perforation (3/1000) and bleeding
- 5-10% miss rate
What is a Double Contrast Barium Enema
- Visualizes what
- Safety
- Miss rate
- Visualizes the entire large bowel
- Relatively safe
- Detects 50% of >1cm polyps
- Positive test requires colonoscopy
What is CT colonography?
- Requires what
- Risks
- Requires aggressive bowel preparation
- Does not require sedation
- Positive findings require colonoscopy
- Extracolonic findings
- Cumulative dose of radiation may increase cancer risk
- Most insurance companies do not currently cover CTC as a screening modality
Picture-
Left: colonoscopy
Right: CT?
What is patient preference for CRC screening tests?
- Colonoscopy was the preferred test
- Patients were least satisfied with DCBE
What is FOBT?
Fecal Occult Blood Test
- Low sensitivity for polyps
- Low specificity for significant disease therefore leading to workup on false positive testing
- Non-invasive
- Inexpensive
- Positive tests require a colonoscopy
Compare the sensitivity of take home vs. in office FOBT
What is FIT?
- How does it compare to FOBT?
Fecal immunochemical test (FIT)
- More expensive than guaiac-based tests
- Higher sensitivity for detecting advanced colorectal neoplasia than guaiac-based tests
- Does not require a restricted diet; only detects human globin
- Does not detect UGI bleeding
- Positive tests should be followed up with colonoscopy
- (No use in acute setting/acute GI bleeding)*
What does stool DNA (DNA) look for?
- Sensitivity?
Stool DNA tests look for abnormal DNA from cells that are passed into stool
- Sensitivity for cancer with one time testing 46-91%
- DNA testing detected more cancers than FIT, but had more false positives (leading to unnecessary testing)
When should you stop screening patients?
When a patient’s life expectancy is less than 10 years
Don’ts of Colon Cancer Screening
- Don’t perform stool testing after someone has had a colonoscopy
- Don’t check FIT testing on young patients or in the setting of acute GI bleed
What are surveillance guidelines for the following conditions?
What is CEA?
- Uses
Tumor marker: carcinoembryonic antigen
- Used for monitoring/recurrence but NOT for screening
Take home points:
- ______ should be the primary goal of colon cancer screening
- Screening of average-risk individuals can reduce CRC mortality by detecting cancer at an early, curable stage and by detecting and removing clinically significant adenomas
- All screening tests aside from colonoscopy require a colonoscopy if positive
- Colon cancer prevention should be the primary goal of colon cancer screening
- Screening of average-risk individuals can reduce CRC mortality by detecting cancer at an early, curable stage and by detecting and removing clinically significant adenomas
- All screening tests aside from colonoscopy require a colonoscopy if positive
What are some autosomal dominant inheritable GI syndromes?
- Familial Adenomatous Polyposis
- Lynch Syndrome
- Peutz-Jeghers Syndrome
- Juvenile Polyposis
Characteristics of Familial Adenomatous Polyposis (FAP):
- __% of CRC
- Genetic inheritance
- Gene
- Disease characteristics
- 1% of CRC
- Colorectal cancer in these pts is inevitable
- Autosomal Dominant
- Mutation of APC (Adenomatous Polyposis Coli) gene, located on chromosome 5
- Hundreds to thousands of adenomas in colon
What is the typical clinical course of CRC with FAP pts?
- 15 yo onset of polyps
- 33 yo symptoms appear
- 39 yo colorectal cancer
- 42 yo death
What is Gardner’s syndrome?
Variant of FAP
Extra-intestinal manifestations including:
- Soft tissue and bony tumors
- Congenital hypertrophy of the retinal pigment epithelium
- Mesenteric desmoid tumors
- Ampullary cancers
What are screening recommendations for FAP?
- Annual flexible sigmoidoscopy starting at age 12 OR
- DNA testing for mutation of APC gene
Treatment of FAP?
Colectomy- preferably with the removal of the rectum because of risk of rectal ca
What is Lynch Syndrome?
- Genetic inheritance
- Gene
- Location
- Age of onset
- Lifetime risk of CRC
- Previously known as HNPCC
- Autosomal Dominant
- Mismatch repair gene mutation with subsequent microsatellite instability
- Proximal location of colorectal cancer
- Early age of onset of colorectal cancer
- 70-80% lifetime risk of CRC
What is the Amsterdam Criteria?
For Lynch Syndrome: (3-2-1 rule)
- 3 or more relatives with CRC, 1 is a 1st degree of the other 2
- CRC involving 2 generations
- ≥ 1 CRC case diagnosed before the age of 50
What are the revised Bethesda guidelines regarding CRC tumors and testing for MSI?
Tumors from individuals should be tested for MSI in the following situations:
- Colorectal cancer diagnosed in a patient who is less than 50 years of age.
- Presence of synchronous, metachronous colorectal, or other HNPCC-associated tumors, regardless of age
- Colorectal cancer with the MSI-H histology diagnosed in a patient who is less than 60 years of age.
- Colorectal cancer diagnosed in one or more first-degree relatives with an HNPCC-related tumor, with one of the cancers being diagnosed under age 50 years.
- Colorectal cancer diagnosed in two or more first- or second-degree relatives with HNPCC-related tumors, regardless of age.
What is Lynch Syndrome prognosis?
- Better prognosis than sporadic CRC
- Multiple primary malignancies including:
- Endometrial
- Ovarian
Screening for Lynch Syndrome?
- Screen 1st degree relatives with genetic testing or
- Colonoscopy every 1-2 years starting between 20-30 and annually after age 40
- Endometrial cancer screening
What is Turcot syndrome?
Colorectal cancer or colorectal adenomas in addition to tumors of the central nervous system. (FAP or Lynch syndrome + CNS tumor)
What is Peutz-Jeghers Syndrome?
- Genetic inheritance
- Disease manifestations
- Transformation
- Histology
- Associated lesions
- Autosomal Dominant
- Polyps occur in small intestine, but can also be in colon and stomach
- Increased risk for GI cancer
- Neoplastic transformation of PJ polyp is infrequent
- Histology: Hamartoma Associated lesions
- Mucocutaneous pigmentation
- Tumors of the ovary, breast, pancreas, and endometrium
What is Juvenile Polyposis?
- Genetic inheritance
- Histology
- Disease manifestations
- Risk
- Autosomal Dominant
- Histology: hamartoma
- Polyps can be present in the large, small intestine and stomach
- Increased risk for development of colon cancer
