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Chapter 168

Colorectal cancer

DEFINITION

Colorectal cancer is a neoplasm arising from the luminal surface of the large bowel: descending colon (40% to 42%), rectosigmoid and rectum (30% to 33%), cecum and ascending colon
(25% to 30%), transverse colon (10% to 13%).
PHYSICAL FINDINGS AND CLINICAL PRESENTATION

Physical examination may be completely unremarkable.

The clinical presentation of colorectal malignancies is initially vague and nonspecic (weight loss, anorexia, malaise). It is useful to divide colon cancer symptoms into
those usually associated with the right side of the colon and
those commonly associated with the left side of the colon,
because the clinical presentation varies with the location of
the carcinoma.
1. Right side of colon
a. Anemia (iron deciency secondary to chronic blood
loss).
b. Dull, vague, and uncharacteristic abdominal pain may
be present or patient may be completely asymptomatic.
c. Rectal bleeding is often missed because blood is mixed
with feces.
d. Obstruction and constipation are unusual because of
large lumen and more liquid stools.
2. Left side of colon
a. Change in bowel habits (constipation, diarrhea, tenesmus, pencil-thin stools).
b. Rectal bleeding (bright red blood coating the surface of
the stool).
c. Intestinal obstruction is frequent because of small
lumen.
Digital rectal examination can detect approximately 50% of
rectal cancers.
Palpable abdominal masses may indicate metastasis or
complications of colorectal carcinoma (abscess, intussusception, volvulus).
Abdominal distention and tenderness are suggestive of colonic obstruction.
Hepatomegaly may be indicative of hepatic metastasis.

Virtual colonoscopy (VC) uses helical (spiral) CT scan to

generate a two- or three-dimensional virtual colorectal image. VC does not require sedation, but like optical colonoscopy, it requires some bowel preparation (either bowel cathartics or ingestion of iodinated contrast medium with
meals during the 48 hours before CT) and air insufation. It
also involves substantial exposure to radiation. In addition,
patients with lesions detected by VC will require traditional
colonoscopy.
CT scan (Fig. 1682) of abdomen/pelvis/chest to assist in
preoperative staging. PET scan (Fig. 1682) is also used for
staging.

TREATMENT

Surgical resection (Fig. 1683): 70% of colorectal cancers

are resectable for cure at presentation; 45% of patients are
cured by primary resection.
Radiation therapy is a useful adjunct to chemotherapy with
uorouracil and levamisole therapy for stage II or III rectal
cancers.
The backbone of treatment of colorectal cancer is uorouracil (FL). Leucovorin (folinic acid) enhances the effect of
uorouracil and is given together with it. Adjuvant chemotherapy with a combination of 5-FU and levamisole substantially increases cure rates for patients with stage III colon cancer and should be considered standard treatment for
all such patients and select patients with high-risk stage II
colon cancer (adherence of tumor to an adjacent organ,
bowel perforation, or obstruction).

CAUSE

Colorectal cancer can arise through two mutational pathways:

microsatellite instability or chromosomal instability. Germline
genetic mutations are the basis of inherited colon cancer syndromes; an accumulation of somatic mutations in a cell is the
basis of sporadic colon cancer.
DIFFERENTIAL DIAGNOSIS

Diverticular disease (see Fig. 1643)

Strictures
IBD (see Fig. 1624, Fig. 1632)
Infectious or inammatory lesions (see Fig. 1892)
Adhesions
Arteriovenous malformations
Metastatic carcinoma (prostate, sarcoma)
Extrinsic masses (cysts, abscesses)

IMAGING STUDIES

600

Colonoscopy with biopsy (primary assessment tool) (Fig.

1681).

Fig 1681
Colonoscopic appearance of hemorrhagic carcinoma in ascending
colon.
(From Forbes A, Misiewicz J, Compton C, et al: Atlas of Clinical Gastroenterology, 3rd ed. Edinburgh, Elsevier Mosby, 2005.)

Chapter 168: Colorectal cancer

168

Fig 1682
Colon cancer. A, Positron emission tomography (PET) and computed tomography (CT) scans display of a patient with two 18uorodeoxyglucose
(FDG)-avid lesions in the liver. These are seen on the CT (upper left) scan, attenuation-corrected PET (upper right) scan, nonattenuation-corrected
PET (lower right) scan, and fused images (lower left). B, PET and CT scans of the pelvis, oriented as in (A), show increased FDG uptake in a left
external iliac lymph node metastasis.
(From Abeloff MD: Clinical Oncology, 3rd ed. Philadelphia, Elsevier, 2004.)

A
B

C
D
Fig 1683
Common gross appearances of colonic carcinoma. (A) Exophytic carcinoma of the cecum. (B) Circumferential, napkin ringlike pattern of carcinoma narrowing the lumen of descending colon. (C) Cross-section of (B) showing interruption of muscularis propria by carcinoma invading full
thickness of the bowel wall. (D) Ulcerating carcinoma in rectum, with raised edges and a necrotic center.
(From Silverberg SG: Principles and Practice of Surgical Pathology and Cytopathology, 4th ed. Philadelphia, Churchill Livingstone, 2006.)

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When given as adjuvant therapy after a complete resection

in stage III disease, FL increases overall 5-year survival from
51% to 64%. The use of adjuvant FL in stage II disease (no
involvement of regional nodes) is controversial because
5-year overall survival is 80% for treated or untreated patients, and the addition of FL only increases the probability
of 5-year disease-free interval from 72% to 76%. For patients with standard-risk stage III tumors (e.g., involvement
of one to three regional lymph nodes), both FL alone or FL
with oxaliplatin (an inhibitor of DNA synthesis) are reasonable choices. Generally, reversible peripheral neuropathy is
the main side effect of FL plus oxaliplatin. The oral uoropyrimidine capecitabine is a prodrug that undergoes enzymatic conversion to uorouracil. It is an effective alternative
to IV uorouracil as adjuvant treatment for stage III colon
cancer because it has a lower incidence of mouth sores and
bone marrow suppression. It does however have an increased incidence of palmar-plantar erythrodysesthesia
(hand-foot syndrome).
Irinotecan, a potent inhibitor of topoisomerase I, a nuclear
enzyme involved in the unwinding of DNA during replication, can be used to treat metastatic colorectal cancer refractory to other drugs, including 5-FU; it may offer a few
months of palliation but is expensive and associated with
signicant toxicity.
Oxaliplatin, a third-generation platinum derivative, can be
used in combination with uorouracil and leucovorin (FL)
for patients with metastatic colorectal cancer whose disease
has recurred or progressed despite treatment with uorouracil/leucovorin plus irinotecan. FL plus oxaliplatin should be
considered for high-risk patients with stage III cancers (e.g.,
3 involved regional nodes [N2] or tumor invasion beyond
the serosa [T4 lesion]).

Laboratory studies have identied molecular sites in tumor tissue that may serve as specic targets for treatment
by using epidermal growth factor receptor antagonists and
angiogenesis inhibitors. The monoclonal antibodies cetuximab and bevacizumab have been approved by the
FDA for advanced colorectal cancer. Bevacizumab is an
angiogenesis inhibitor that binds and inhibits the activity
of human vascular endothelial growth factor (VEGF). Cetuximab is an epidermal growth factor receptor [EGFR]
blocker that inhibits the growth and survival of tumor
cells that overexpress EGFR. Cetuximab has synergism
with irinotecan and its addition to irinotecan in patients
with advanced disease resistant to irinotecan increases the
response rate from 10% when cetuximab is used alone to
22% with a combination of cetuximab and irinotecan.
The addition of bevacizumab to FL in patients with advanced colorectal cancer has been reported to increase the
response rate from 17% to 40%.
In patients who undergo resection of liver metastases from
colorectal cancer, postoperative treatment with a combination of hepatic arterial infusion of oxuridine and IV uorouracil improves the outcome at 2 years.