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COLORECTAL CANCER
  • second leading cause of death in the USA
  • associated with the western dietary habits (increased dietary fat and low fiber diets)
  • risk factors include but not limited to
    • personal history of colorectal cancer in the past.
    • Family history of colorectal cancer and polyps.
    • Hereditary Syndromes e.g. Lynch Syndromes (types 1 and 2).These are not associated with polyps in the colon.
    • Inflammatory bowel disease e.g. chronic ulcerative colitis and Crohn's disease.
    • Polyposis syndromes: many associated conditions e.g. Gardner's, juvenile, Turcot's and Familial polyposis (adenomatous) syndromes.

  Genes Associated with colorectal cancers:

  • APC gene on chromosome 5 confers close to 100% chance of developing a colorectal malignancy.
  • HMSH2, HMLH1, HPMS1 and HPMS2
  • Mutations of tumor suppressor genes like p53 and DCC (deleted colorectal cancer) genes.


 SIGNS AND SYMPTOMS

  • There may be none and some cancers have been detected on routine physical examinations or during other unrelated surgical procedures.
  • Complaints may be due to the primary lesion or spread to other parts of the body.
  • Generalized weakness due to anemia from chronic blood loss.
  • Weight loss
  • Bloody stool
  • Abdominal pain and swelling
  • Change in bowel habits e.g. constipation and diarrhea for cancers on the left side of the colon.
  • Anemia for cancers in the right side of the colon (may be iron or vitamin B12 deficiency especially in terminal ileum involvement).
  • Jaundice especially in patients with liver involvement which portends a very poor prognosis.
  • Altered mental status with brain involvement.
  • Breathing difficulties in lung metastasis.


 DIAGNOSIS AND STAGING

  • a tissue biopsy is necessary to make a diagnosis
  • the commonest histology is adenocarcinoma
  • a colonoscopy is mandatory to obtain tissue
  • upper endoscopy (EGD) may also be necessary if there is a coexisting bleeding ulcer or malignancy.
  • CAT scan of the abdomen and pelvis with oral and intravenous contrasts may be necessary to detect sites of malignancy in tumors not seen on endoscopy and liver involvement .
  • Abdominal and rectal ultrasonography.
  • Blood tests include but not limited to CBC with differential, SMAC, PT/PTT, CEA level, Calcium, magnesium and phosphorus levels.
  • Chest X-ray, Bone scan, CAT scan or MRI scan of the brain to rule out metastasis (spread) to these sites.
  • The most important prognostic factor in colorectal cancer is the involvement and quantity of lymph nodes - less than 4 lymph node involvement is better than greater than 4 lymph node involvement.


 TREATMENT

  1. Surgery - cure is expected in about 50% of people .
    • surgery may also be necessary to prevent or treat obstruction or bleeding even when there is a documented evidence of spread or incurability.
    • no further therapy needed in patients with Duke's Stages A and B.
  2. Adjuvant treatment: includes the use of chemotherapy and / or radiation therapy after surgery.
    • The use of 5FU and oral levamisole for Duke's C colon cancer reduces the risk of death.
    • 5FU and Leucovorin for stage D , recurrent or metastatic diseases.
    • the intravenous drugs may be given as a bolus or continuous infusions with varying toxicities e.g. the bolus route bone marrow suppression with resulting anemia, less neutropenia (low white count) and low platelets and these side effects may be exaggerated in patients with an inherited enzymatic disorder. In patients who are refractory to 5FU based regimens, Irinotecan (CPT-11) , Gemcitabine, Uracil and Tegafur combination, Trimetrexate-5FU-Leucovorin combination, Edrecolomab (monoclonal antibody), Raltitrexed (thymidilate synthase inhibitor), Oxaliplatin may also be used . The use of radioimmunotherapy is gradually gaining grounds.
    • the liver is the commonest site of metastasis in colorectal cancer and the treatment alternatives include:
      • surgical resection if there is one or few contiguous lesions, but in unresectable lesions the following may be done:
      • ethanol injection
      • cryosurgery
      • regional chemotherapy via hepatic artery
  • Radiation therapy is added to 5FU and leucovorin in patients with rectal cancer to prevent local recurrence.
    1. Follow up requires regular physical examination, blood tests including CEA level , which if rising may signify a recurrence and appropriate actions taken to find the site and prompt resection is indicated. Monoclonal antibody may help in localizing the recurrent lesions. Annual colonoscopy is necessary.
    2. Terminally ill patients should be made comfortable with adequate analgesia using narcotics e.g. Duragesic patch, Morphine, Oxycontin, Percocet etc.
    3. Hospice care is necessary.
    4. Adequate communication with patient and family members .
    5. Living will to be discussed with patient on the need, or not, for resuscitation.
    6. Grieving period is also crucial to help the family members deal with the loss of their loved ones.
    7. Discuss burial arrangements with family etc.