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U N I T 8
Gastrointestinal and Hepatobiliary Function
thirds of the crypts, after which they mature, migrate to
the surface, and become senescent. They then become
apoptotic and are shed from the surface.
7
Adenomas
arise from a disruption in this sequence, such that the
epithelial cells retain their proliferative ability through-
out the entire length of the crypt. Aberrations in cell
differentiation can lead to dysplasia and progress to the
development of invasive adenocarcinoma.
Colorectal Cancer
Adenocarcinoma of the colon is the most common malig-
nancy of the gastrointestinal tract and is the major cause
of morbidity and mortality worldwide.
6,7,58–60
It affects
approximately 150,000 Americans annually, approxi-
mately one third of whom die.
58
It affects approximately
250,000 persons annually in Europe and approximately
1 million persons worldwide.
Epidemiology.
The incidence of colorectal cancer
peaks at 60 to 70 years of age, and fewer than 20%
of cases occur before age 50.
7
Its incidence is increased
among persons with a family history of cancer, persons
with Crohn disease or ulcerative colitis, and those with
familial adenomatous polyposis of the colon. Persons
with a familial risk—those who have two or more
first- or second-degree relatives (or both) with colorec-
tal cancer—make up approximately 20% of all persons
with colorectal cancer.
61
Familial adenomatous polyposis
is a rare autosomal dominant trait linked to a mutation
in the long arm of chromosome 5. Persons with the disor-
der develop multiple adenomatous polyps of the colon at
an early age.
7
Carcinoma of the colon is inevitable, often
by 40 years of age, unless a total colectomy is performed.
Diet also is thought to play a role.
7
Attention has
focused on dietary fat intake, refined sugar intake,
fiber intake, and the adequacy of such protective
micronutrients as vitamins A, C, and E in the diet. It
has been hypothesized that a high level of fat in the diet
increases the synthesis of bile acids in the liver, which
may be converted to potential carcinogens by the bacte-
rial flora in the colon. The proliferation of colonic bacte-
ria is enhanced by a high dietary level of refined sugars.
Dietary fiber is thought to increase stool bulk and thereby
dilute and remove potential carcinogens. Refined diets
often contain reduced amounts of vitamins A, C, and E,
which may act as oxygen free radical scavengers.
In addition to dietary modification, pharmacologic
chemoprevention has become an area of great interest.
Several studies indicate that aspirin or other NSAIDs
may protect against colorectal cancer.
62
An analysis of
the incidence of colorectal cancer in the Nurses’ Health
Study showed a decreased incidence of colorectal cancer
among women who took four to six aspirins per week.
Although the mechanism of aspirin’s action is unknown,
it may be related to its effect on the synthesis of pros-
taglandins, one or more of which may be involved in
signal systems that influence cell proliferation or tumor
growth. Aspirin inhibits cyclooxygenase, the enzyme
that catalyzes the conversion of arachidonic acid in cell
membranes to prostaglandins. One form of cyclooxy-
genase, COX-2, promotes inflammation and cell pro-
liferation, and colorectal cancers often overexpress this
enzyme.
Clinical Manifestations.
Cancer of the colon is usu-
ally present for a long period of time before it produces
symptoms.
58,59
Bleeding is a highly significant early
symptom and usually is the one that causes persons to
seek medical care. Other symptoms include a change in
bowel habits, diarrhea or constipation, and sometimes a
sense of urgency or incomplete emptying of the bowel.
Pain usually is a late symptom.
Normal
Initial
proliferative
abnormality
Progressive
proliferative
abnormality
Colonic crypt
Tubular adenoma
Invasive
adenocarcinoma
Invasive
adenocarcinoma
Villous adenoma
Benign colonic neoplasms
5%
40%
FIGURE 29-13.
The histogenesis of adenomatous polyps of the colon.The initial proliferative
abnormality of the colonic mucosa, the extension of the mitotic zone in the crypts, leads to
accumulation of mucosal cells.The formation of adenomas may reflect epithelial–mesenchymal
interactions. (From Rubin R.The gastrointestinal tract. In: Rubin R, Strayer DS, eds. Rubin’s Pathology:
Clinicopathologic Foundations of Medicine. 6th ed. Philadelphia, PA: Wolters Kluwer Health |
Lippincott Williams &Wilkins; 2012:663.)
