Colorectal Cancer
A. General characteristics
- Third most common cancer in the United States (in men and women)
- Virtually, all colorectal tumors arise from adenomas. Majority are endoluminal
adenocarcinomas arising from the mucosa. Rarely, carcinoid tumors, lymphomas, and Kaposi sarcoma may be present but majority are adenocarcinomas - Screening—refer to Chapter 12, Ambulatory Medicine
a. Fecal occult blood testing (FOBT) has poor sensitivity and specificity. Positive
predictive value is only about 20%, but all patients with positive FOBT need a
colonoscopy regardless
b. Digital rectal examination: Only about 10% of tumors are palpable by rectal
examination
c. Colonoscopy
• Most sensitive and specific test; the diagnostic study of choice for patients
with a positive FOBT
• Diagnostic and therapeutic (e.g., biopsy, polypectomy)
d. Flexible sigmoidoscopy
• Can be used to reach the area where approximately 50% to 70% of polyps
and cancers occur (with a 60-cm scope)
• Can be diagnostic in about two-thirds of all colorectal cancers (CRCs)
e. Barium enema
• Evaluates entire colon; complementary to flexible sigmoidoscopy
• Disadvantage is that any abnormal finding needs to be evaluated by colonoscopy
f. Carcinoembryonic antigen (CEA)—not useful for screening; useful for establishing baseline, monitoring treatment efficacy, and recurrence surveillance. CEA
does have prognostic significance: Patients with preoperative CEA >5 ng/mL
have a worse prognosis - Clinical staging done with CT scan of chest, abdomen, and pelvis and by physical
examination (ascites, hepatomegaly, lymphadenopathy) - Pattern of spread
a. Direct extension—circumferentially and then through the bowel wall to later
invade other abdominoperineal organs
b. Hematogenous
• Portal circulation to liver—liver is most common site of distant spread
• Lumbar/vertebral veins to lungs
c. Lymphatic—regionally
d. Transperitoneal and intraluminal
Risk factors
- Age—everyone over the age of 50 years is at increased risk
- Adenomatous polyps
a. These are premalignant lesions, but most do not develop into cancer.
b. Villous adenomas have higher malignant potential than tubular adenomas.
c. The larger the size, and the greater the number of polyps, the higher the risk of
cancer. - Personal history of prior CRC or adenomatous polyps
- Inflammatory bowel disease (IBD)
a. Both ulcerative colitis (UC) and Crohn disease pose an increased risk for CRC,
but UC poses
a greater risk than Crohn disease.
b. Incidence of CRC is
5
% to 10% at 20 years and 12% to 20% at 30 years with UC.
Begin surveillance colonoscopy for CRC
8 years following the diagnosis of IBD. - Family history
a. Multiple first-degree relatives with CRC.
b. Any first-degree relative diagnosed with CRC or adenoma under age 60. - Dietary factors—high-fat, low-fiber diets associated with
a higher risk of CRC - Major polyposis syndromes
a. Familial adenomatous polyposis (FAP)
• Autosomal dominant disease caused by hereditary mutations in the APC
tumor suppressor gene.
• Characterized by hundreds of adenomatous polyps in the colon. The colon is
always involved, and the duodenum is involved in 90% of cases. Polyps may
also form in the stomach, jejunum, and ileum.
• The risk of CRC is 100% by the third or fourth decade of life (in 100% of
FAP cases).
• Prophylactic colectomy is usually recommended.
b. Gardner syndrome
• Variant of FAP, autosomal dominant.
• Polyps plus osteomas, dental abnormalities, benign soft tissue tumors, des
moid tumors, sebaceous cysts.
• Risk of CRC is 100% by approximately age 40.
c. Turcot syndrome
• Can be inherited as autosomal dominant or recessive.
• Polyps plus cerebellar medulloblastoma or glioblastoma multiforme.
d. Peutz–Jeghers
• Autosomal dominant.
• Single or multiple hamartomas that may be scattered through entire GI tract:
in small bowel (78%), colon (60%), stomach (30%).
• Pigmented spots around lips, oral mucosa, face, genitalia, and palmar surfaces.
• Unlike adenomas, hamartomas have very low malignant potential.
• Slightly increased incidence in various carcinomas (e.g., stomach, ovary,
breast, cervix, testicle, lung).
• Intussusception or GI bleeding may occur.
e. Familial juvenile polyposis coli
• Rare; presents in childhood; only small risk of CRC.
• More than 10 and up to hundreds of juvenile colon polyps.
f. Hereditary nonpolyposis CRC—without adenomatous polyposis
• Lynch syndrome I (site-specific CRC)—early-onset CRC; absence of anteced
ent multiple polyposis.
• Lynch syndrome II (cancer family syndrome)—all features of Lynch
I plus
increased number and early occurrence of other cancers (e.g., female genital
tract, skin, stomach, pancreas, brain, breast, biliary tract)
C. Clinical features
1. The presence of symptoms is typically a manifestation of relatively advanced dis
ease. Most symptoms have melena or hematochezia, abdominal pain, change in
bowel habits, or unexplained iron deficiency anemia
Signs and symptoms potentially common to all locations
a. Abdominal pain is most common presenting symptom. Can be caused by partial obstruction or peritoneal dissemination. Remember that CRC is the most
common cause of large bowel obstruction in adults. Colonic perforation can
lead to peritonitis and is the most life-threatening complication
b. Weight loss
c. Blood in stool
d. May be asymptomatic
- Signs and symptoms based on specific location of tumor
a. Right-sided tumors
• Obstruction is unusual because of the larger luminal diameter (the cecum
has the largest luminal diameter of any part of the colon), allowing for large
tumor growth to go undetected.
• Common findings: occult blood in stool, iron deficiency anemia, and melena.
• Change in bowel habits is uncommon.
• Triad of anemia, weakness, RLQ mass (occasionally) is present.
b. Left-sided tumors
• Smaller luminal diameter—signs of obstruction more common
• Change in bowel habits more common—alternating constipation/diarrhea;
narrowing of stools (“pencil stools”)
• Hematochezia more common - Rectal cancer (20% to 30% of all CRCs)
a. Hematochezia—most common symptom
b. Tenesmus
c. Rectal mass; feeling of incomplete evacuation of stool (due to mass)
D. Treatment - Surgery is only curative treatment of CRC. Surgical resection of tumor-containing
bowel as well as resection of regional lymphatics - CEA level should be obtained before surgery (see below)
- Utility of adjuvant therapy (chemotherapy or radiation therapy) depends on stage
of tumor and is beyond scope of this book - Follow-up is important, and varies among physicians
a. Stool guaiac test
b. Annual CT scan of abdomen/pelvis and CXR for up to 5 years
c. Colonoscopy at 1 year and then every 3 years
d. CEA levels are checked periodically (every 3 to 6 months)
• A subsequent increase in CEA is a sensitive marker of recurrence
• Often, second-look operations are based on high CEA levels postresection
• Very high elevations of CEA suggest liver involvement - About 90% of recurrences occur within 3 years after surgery