Colorectal Cancer

  • Risk factors for colorectal cancer
    • Increasing age, family history of colon cancer, colon polyps (increased risk with larger & multiple polyps), inflammatory bowel disease (especially ulcerative colitis), genetic predisposition
      • Hereditary nonpolyposis colon cancer (HNPCC) aka Lynch syndrome is an autosomal dominant disorder that has an early onset in patients (40-45 years old), polyps aren’t really a manifestation
      • Familial adenomatosis polyposis (FAP) is an autosomal dominant disorder that results from a mutation of the APC gene
        • Cancer risk is 100%
        • Need to start screening early (start colonoscopies at age 12) & do a colectomy if polyps are found
    • Dietary risk factors:  high fat, red meat (cooking, carcinogens from grilled meat, processing), decreased Ca & vitamin D intake, decreased folate
    • Lifestyle risk factors:  NSAID, ASA use, hormone replacement therapy, physical inactivity, alcohol & tobacco use
  • Preventative and screening strategies for all types of patients
    • Prevention:  high fiber, low fat diet.  Adequate levels of Ca, folate, decrease COX-2 & NSAID use
    • Start colon cancer prevention screenings at age 50 (may be ale to prevent 50-60% of colon cancers)
    • Fecal occult blood test (FOBT) detects pseudoperoxidase activity.Should be done annually.
      • False positives caused by red meat, Fe
      • False negatives caused by vitamin C
    • Digital rectal exam:  annually after 50 if normal risk with FOBT (only detects 10% of cancers), not effective alone.
    • Endoscopy
      • Flexible sigmoidoscopy examines the lower 60% of the bowel & detects 50-60% of cancers.  Do every 5 years.
      • Colonoscopy looks at the whole bowel & can remove premalignant lesions.  Do every 10 years.
    • Tumor markers
      • CEA is a protein over-expressed in embryonic development that is increased in many GI tumors
    • Patients should get an annual CT scan for 3 years, a colonoscopy every 3 years, a CEA every 2-3 months for at least 2 years, H&P every 3-6 months for 3 years & then every year thereafter
    • Colon cancer is one of the most preventable cancers (screening, prevention, early prognosis)
  • Signs and symptoms for colorectal cancer
    • Early stage is usually asymptomatic
    • Common symptoms:  change in bowel habits, rectal bleeding, abdominal pain, weight loss
  • Staging system of colorectal cancer.
    • Duke’s criteria (stages A-D)
    • AJCC-TMN staging
      • Stage 1:  superficial tumor (no muscular involvement)
      • Stage 2A:  invasion through serosa
      • Stage 2B:  invasion through muscularis propria to subserosa or perforates visceral peritoneum
      • Stage 2C:  adherent to other organs
      • Stage 3:  invasion with regional lymph node involvement
      • Stage 4: metastasis
    • KRAS mutations are indicative of metastatic colon cancer
      • Testing for this will help predict whether or not the patient will respond
        • Don’t use EGFR inhibitors with mutant type K-ras
  • Treatment options for colorectal cancer based on patient specific factors, including stage
    • stages 1-3 are curable, not stage 4 (stage 4 only has an 8% survival rate)
    • Stage 1:  surgery (adjuvant therapy isn’t indicated)
    • Stage 2:  surgery (adjuvant chemo isn’t recommended but may benefit some high risk patients)
    • Stage 3:  surgery + 6 months of adjuvant FOLFOX (oxaliplatin + leucovorin + 5-FU) chemo
      • Alternatives:  5-FU/leucovorin or capecitabine or radiation
        • No role for irinotecan, cetuximab or bevacizumab in adjuvant therapy of colorectal cancer
    • Stage 4:  surgery then adjuvant FOLFOX-B (includes bevacizumab) chemo
      • Wait 6 weeks after surgery to initiate bevacizumab
      • Irinotecan, cetuximab, & bevacizumab are only used in stage 4 metastatic cancer
    • Rectal cancer has fairly similar treatments to colorectal cancer but you may not use leucovorin, radiation is standard
  • Adverse effects of the chemotherapy
    • Irinotecan = I run to the can (diarrhea)
      • Can test to see if the patient will respond to this
        • Shows decreased gene expression
    • N/V, anemia, diarrhea, mucositis, hand-foot syndrome (mainly w/ capecitabine), neuropathy, stroke/DVTs

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