Colorectal Cancer

1
Colorectal Cancer

• Niraj Jani, MD
• Div of Gastroenterology
• Sinai Hospital

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 1.5-2.0 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 (lt100 adenomas) and later onset
  of CRC
• Turcots Syndrome familial predisposition for
  colonic polyposis and CNS tumors
• Gardners 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
• gt 3 relatives with HNPCC related cancers
• 2. gt 1 case is a first-degree relative of
  2 other
• cases
• 3. gt 2 successive generations affected
• 4. gt 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 3092 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 3990
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

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Colonoscopy

• Gold standard for CRC screening
• Risk of complications 0.10.3 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 gt T3 or gt 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

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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