1. Colorectal Cancer

2. Epidemiology
Second leading cause of cancer death in US - approx 148,000 cases/yr and 58,000 deaths
Equal lifetime risk between men and women
93% of cases dx over age 50. Five-year survival of 60%
Treatment costs over $6.5 billion per year
Among malignancies, second only to breast cancer at $6.6 billion per year

3. Epidemiology Industrialized nations have the greatest risk
Geographic distribution of sporadic colon cancer

4. Pathogenesis
Adenoma to Carcinoma sequence:

5. Pathogenesis
Adenomatous polyps and adenocarcinoma are epithelial tumors of the large intestine
Risk factors for polyps/adenomas to develop into cancer:
Patient age (greatly increased after 50 yo, with prevalence doubling until age 80)
Adenomas greater than 1 cm
Extensive villous patterns

6. Pathogenesis
Polyp/Cancer locations

7. CRC Risk Factors
Age: CRC incidence increases rapidly after 50 years of age
Adenomatous Polyps:
30% at 50 years, 40-50% at 60 years, and up to 65% at 70 years
Most importantly, the risk of HGD in a polyp is 80% higher in an older person than younger person

8. CRC Risk Factors
Diet: Greatest association is between high fat diet/red meat and CRC
High cholesterol, obesity linked to CRC
A prospective study of more than 760,000 people showed diets rich in vegetables and high fiber grains demonstrated significant protection against fatal CRC

9. Diet and Colon Cancer Protective factors: Fiber:
decreases fecal transit time by increasing stool bulk
Dilutes the concentration of other colonic constituents which minimizes interactions btwn carcinogens and colon epithelium
Reduces colonic pH and generates short chain fatty acids

10. CRC Risk Factors Other risk factors: Hx of Ulcerative Colitis
Strep Bovis infection
Ureterosigmoidostomy
Dermatomyositis
Pelvic Irradiation
Smoking/ETOH consumption
Obesity

11. CRC Protective Factors
Other protective factors:
Exercise
NSAIDs/ASA
Folate
High calcium intake
Hormonal therapy
Selenium

12. CRC Risk Factors
Genetics:

13. CRC Risk Factors
Familial clustering present in 15% of all cases of CRC
Increased risk fold
Individuals with hx of adenomas are at three to sixfold increased risk of metachronous neoplasms

14. Genetic Sydromes
Familial adenomatous polyposis (FAP): an inherited condition caused by a germline mutation on chromosome 5 (APC gene)
Leads to hundreds to thousands of polyps throughout the GI tract
Other findings include:
- duodenal adenomas
- fundic gland hyperplasia
- mandibular osteomas
- supernumerary teeth

15. FAP

16. Genetic Sydromes
Attenuated FAP: (<100 adenomas) and later onset of CRC
Turcot’s Syndrome: familial predisposition for colonic polyposis and CNS tumors
Gardner’s Syndrome: variant of FAP
Osteomas of the skull and long bones
(CHRPE) Congenital Hypertrophy of the Retinal Pigmented Epithelium

17. Genetic Sydromes
Hereditary nonpolyposis colorectal cancer (HNPCC) syndrome: also called Lynch syndrome: characterized by proximal cancer in 3rd and 4th decade of life
Also associated with extracolonic cancers- (uterus, ovaries, stomach, small bowel and bile duct)
Mutations in DNA mismatch repair genes (MLH1, MSH2)

18. HNPCC Amsterdam Criteria for Dx of HNPCC
> 3 relatives with HNPCC related cancers
2. > 1 case is a first-degree relative of 2 other
cases
3. > 2 successive generations affected
4. > 1 case diagnosed before age 50 years

19. Genetic Sydromes Other Genetic Diseases linked to CRC:
Muir-Torre Syndrome
Peutz-Jeghers Syndrome
Tuberous Sclerosis
Juvenile Polyposis Sydrome
Cowden disease
Cronkhite-Canada Syndrome

20. Screening Annual Fecal Occult Blood Test (FOBT)
Flexible Sigmoidoscopy every 5 years
Annual FOBT + Flexible Sigmoidoscopy every 5 years
Colonoscopy every 10 years
Double Contrast Barium Enema (DCBE) every 5 years

21. FOBT
Uses the peroxidase activity of hemoglobin to cause a change in a reagent
Consume diets high in fiber, restrict red meat consumption, vitamin C, and NSAID drugs for several days prior to testing
The sensitivity of fecal occult blood testing ranges from 30–92% with a specificity of 98%

22. Barium Enema
-- The complication rate with the procedure is very low; the rate of perforation
is 1 in 25,000 examinations
-- The sensitivity of double contrast barium enema ranges from 39–90%

23. Flexible Sigmoidoscopy
Colonoscope inserted to the descending colon
60% of all neoplasms are within this distribution- therefore, flex sigmoidoscopy along with FOBT provides an effective screening tool
Minimal prep and no sedation required; office procedure performed by internists, fam med docs, NPs
Perforation risk: 1-2/10,000

24. Colonoscopy Gold standard for CRC screening
Risk of complications: 0.1–0.3% risk of hemorrhage and perforation
Allows for mucosal biopsy, polypectomy, tattooing, accurate localization and flushing/suctioning
Sensitivity of colonoscopy for the detection of polyps greater than or equal to 1 cm and tumors is greater than 95%

25. Colonoscopy

26. Chemoprevention
COX-II inhibitors
Estrogens
Ursodeoxycholic Acid

27. Adenocarcinoma
TNM and Dukes Staging for CRC

28. Treatment
Primary treatment for early colon cancer is surgery. For rectal cancer, total mesorectal excision
In tumors that are > T3 or > N1, preoperative chemo is recommended
Radiation is useful in rectal cancer, not colon cancer

29. CRC Treatment
Common chemotherapeutic regimen includes 5-fluorouracil, leucovorin, oxaliplatin (FOLFOX)
Other agents include bevacizumab, cetuximab,irinotecan, capecitabine

30. Question 1
A 32 yo male presents for annual health maintenance visit. His mother was dx with colon cancer at age 55. Patient should undergo screening at what age?
A. Now
40 yo
45 yo
50 yo

31. Question 1
Pt has a twofold increase in CRC compared to age matched controls due to first degree relative with cancer
Guideline- screen ten years before first-degree relative or at age 40 depending on which comes first

32. Question 2
Three months ago, a 62 yo BM underwent a flex sig and was found to have an obstructing mass. He underwent a sigmoid resection which was considered curative. Did not receive post-op chemo/radiation. Which is the most appropriate CRC surveillance procedure for this pt?
A. Colonoscopy Now
B. Colonoscopy In 1 year
C. Colonoscopy In 3 years
D. CT Abdomen now
E. CT Abdomen in 3 years

33. Question 2 Synchronous cancers occur in 3-5% of pts found to have CRC
Pt never had colonoscopy previously
Once resection performed- repeat colon in 1 year then 3 year intervals
Abdominal CT yearly for 3 years

34. Question 3
The test of choice for screening 1rst degree relatives of pts with FAP is:
Colonoscopy starting at age 12 every 5 years
Genetic testing at age 10 to 12 yo
Sigmoidoscopy starting at age 12 every year
Sigmoidoscopy starting at age 20 every year
No screening

35. Question 3
Genetic testing for a mutation in the APC gene if the first screening test.
If genetic testing is not available, then sigmoidoscopy starting at age 12