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1.d.i. Rationale for screening for colorectal
cancer
In common with other cancers such as breast and cervix,
colorectal cancer is suited to the institution of a screening programme:
ยท it is a major
health problem (1.b.i. Demographics)
ยท there is a
lengthy precancerous stage i.e. the adenomatous polyp.
ยท intervention at
an earlier stage affects morbidity and mortality.
ยท modalities are
available to detect polyps.
ยท the cost of
screening is not prohibitive
1.d.ii. Screening methods for colorectal
cancers and adenomas
At least 75% of colorectal cancers arise in persons who have
no known family history. As such the screening of high risk
families, while potentially valuable to the individuals, is unlikely to have a
major impact on the overall incidence or mortality. Therefore, population
based screening is recommended as the way forward.
There are several methods by which the population might be
screened:
ยท Symptom
questionnaire
ยท Faecal Occult
Blood Testing (FOBT)
ยท Barium enema
ยท Colonoscopy
ยท Flexible
sigmoidoscopy
ยท New advances e.g.
K-ras stool testing
Symptom Questionnaire
Bowel symptoms are very common and can be an indicator of
many general medical conditions (e.g. thyrotoxicosis), large bowel pathology
(e.g. colitis) or functional bowel disorders (e.g. irritable bowel
syndrome). As such, one cannot define a high risk group for further intervention
through symptomatology alone and the addition of a symptom questionnaire to
other screening modalities increases costs with little return.
Faecal Occult Blood Testing (FOBT)
FOBT is mainly aimed at the detection of early asymptomatic
cancers. The premise is that such cancers bleed and the detection of
these small amounts of blood define a high risk group who undergo further
intervention (colonoscopy). The main advantages of
FOBT screening is that it is non-invasive, easily performed without the need
for bowel preparation, can be performed on transported specimens and of low
cost. The main disadvantages, however, are low sensitivity, because 40%
of cancers and 80% of adenomas are missed by the test, and
the late stage in the disease at which lesions bleed, leading to a short
lead-time and a requirement for frequent testing.
Barium Enema
Traditionally before the advent of fibre-optic technology,
imaging of the colon was performed using a barium enema. It has been
shown however that the sensitivity for even quite large colonic lesions can be
quite low and the examination requires full bowel preparation and is poorly
accepted by patients.
Colonoscopy
Initially, colonoscopy may appear to be the best method for
screening for colorectal adenomas and cancers. The sensitivity for even
small polyps as small as 5mm is high so that neoplasia is detected at an early
stage. Also, lesions can be removed at the time of screening so
colonoscopy can be both diagnostic and therapeutic.
There are however disadvantages to colonoscopic screening:
ยท full bowel
preparation is required. This normally involves stimulant or osmotic
laxatives (e.g. Picolax or Klean prep). Recommendations include a low
fibre diet for several days prior to commencement of preparation which itself
starts the day before the examination.
ยท the majority of
colonoscopic examinations are carried out with sedation. This excludes
the subject from driving to and from the hospital, prevents the adequate
discussion of results on the day and can be distressing both from the anxiety
of not being fully conscious but also the hangover effects that are reported.
ยท complication
rates including perforation are reported as being approximately 1 in 2,000 and
a mortality of 1 in 5,000. Though this may be acceptable in
clinical practice in symptomatic patients, it would represent an obstacle to
the acceptance of the population to be screened.
ยท the overall
compliance is lower or comparable to flexible sigmoidoscopic screening.
ยท colonoscopy requires
considerable training, skill and experience. At present, as colonoscopy
becomes the investigation of choice for colonic disorders over barium enema,
there is a relative shortage of colonoscopists. A trend that seems set to
continue and would increase in magnitude should screening be introduced.
ยท colonoscopy is
the most expensive of the potential screening tools.
Flexible Sigmoidoscopy
Flexible sigmoidoscopy has advantages over colonoscopy in
that:
ยท bowel preparation
can be undertaken with a phosphate enema that gives good results, is quick and
easy to be self-administered at home and is acceptable.
ยท sedation is not
normally required
ยท there is a very
low complication rate including perforation
ยท it is associated
with 70% acceptance rate
ยท it can be
performed by non-medical personnel thus reducing the logistic problem of
requiring more endoscopists
ยท it is relatively
cheap
However, flexible sigmoidoscopy does not allow visualisation
of the proximal bowel. A 60cm sigmoidoscope, however, can be passed in
most cases to the junction of the sigmoid and descending colon below which 60%
of colorectal cancers are located.
New Advances
Screening for stool markers that are more accurate than
occult blood would substantially improve sensitivity. There is great
interest in looking for the DNA alterations that occur in the formation of
polyps and cancers in cells exfoliated from neoplasms. Early
investigations targeting single mutations, usually K-ras that is present in
less than half of all colorectal neoplasms, show that mutations in tumour can
be detected in stools from the same patients.
Colorectal neoplasms however are genetically heterogeneous and no one mutation
has been found to be universally expressed. It is likely that an approach
of investigating multiple mutations commonly expressed would improve diagnostic
yield. Ahlquist et al. demonstrated sensitivities of 91% for
colorectal cancer and 82% for adenomas >1cm using a multi-target assay that
assessed 15 mutations commonly seen in colorectal neoplasia.
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