Colon Cancer

Pathophyisology

1) solid tumors (usually adenocarcinoma) that develop from pre-existing adenomas 2) progression from adenomatous polyp to dysplastic lesion to microfoci of adenocarcinoma probably involves activation of an oncogene followed by loss of a tumor-suppressor gene 3) mets typically go to mesenteric nodes and liver

Signs and Symptoms

Right colon cancers – 1) fever 2) fatigue 3) palpitations 4) weight loss 5) angina Left colon cancers – 6) abdominal pain 7) abdominal cramping 8) bloating 9) perforation 10) hematochezia 11) tenesmus 12) small caliber stools

Characteristic Test Findings

Laboratory – 1) positive guaiac test on rectal exam 2) iron-deficient hypochromic microcytic anemia 3) increased CEA 4) mildly increased transaminases or GGT in liver mets Radiology – 5) “apple core” sign on barium enema

Histology/Gross Pathology

1) right colon tumors – typically large and exophytic but do not obstruct feces owing to semiliquid nature 2) left colon tumors – typically cause obstructive symptoms as bowel is formed 3) irregular colonic glands with pleomorphic nuclei

Associated Conditions

increased incidence with polyposis syndromes, Lynch’s syndrome, inflammatory bowel disease (especially ulcerative colitis), alcohol intake, tobacco intake, Streptococcus bovis bacteremia, low-calcium diet, ureterosigmoidoscopy

Biochemistry

associated with – 1) point mutations in k-ras 2) hypomethylation of DNA 3) DNA loss at the tumor-suppressor gene APC on chromosome 5q21 4) loss of DNA at tumor-suppressor gene DDC on chromosome 18 5) mutations in p53-suppressor gene on chromosome 17p

Inheritance/Epidemiology

130,000 new cases in USA each year

Treatment

1) surgical resection of the involved half of colon with adjacent mesentery and liver mets, if possible 2) if lymph nodes are involved, chemotherapy with 5-FU (inactivates thymidylate synthase) and leucovorin 3) evaluation of entire colon before surgery to insure no other lesions 4) screening colonoscopy now recommended every 10 years in normal patients and every 3-5 years if colon cancer has occurred 5) possible chemoprevention with NSAIDs/aspirin/Cox-2 inhibitors and folic acid is being tested

Tips for USMLE

1) in any patient with an unexplained iron deficiency anemia over the age of 50 years, consider colon cancer 2) right-sided tumors – rarely cause obstruction owing to liquid consistency of feces but do commonly ulcerate and cause chronic blood loss 3) typically, CEA levels are drawn every 3-6 months (if initially elevated, the level will fall to baseline after resection) to indicate possible recurrence

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