Добавил:
Sekretar
kiopkiopkiop18@yandex.ru
t.me/Prokururor I Вовсе не секретарь, но почту проверяю
Опубликованный материал нарушает ваши авторские права? Сообщите нам.
Вуз:
Предмет:
Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_1520_Библиотеки_им_академика_М_И_Перельмана
.pdf
109
S.R. Brown et al. (eds.), Contemporary Coloproctology,
DOI 10.1007/978-0-85729-889-8_9, © Springer-Verlag London Limited 2012
9.1 Introduction
Worldwide, colorectal cancer causes approximately 600,000 deaths per year [ 1 ] .
About 16,000 of these occur in the UK, where it is the second commonest cause of
cancer death. Despite advances in surgery and adjuvant therapies, 5-year survival
remains around 50% [ 2 ] .
The natural history of colorectal cancer is now relatively well described. It is
clear that in the majority of cases there is a slow progression via the adenoma-
carcinoma sequence from a small to large adenoma and then to invasive cancer,
which takes the order of 7–10 years. Two-thirds are located in the rectum and sig-
moid colon. The molecular genetic changes underlying this pathway have been
broadly elucidated, although much still remains to be discovered. However, it is
clear that, in general, colorectal cancers develop slowly and that most adenomas
and early cancers are asymptomatic. This is one of the main reasons for the poor
outcome in colorectal cancer: patients tend not to present until they develop symp-
toms of bleeding or alteration in bowel habit, which in most cases does not occur
until the disease is advanced.
There is evidence that removing adenomatous polyps can prevent the develop-
ment of cancer altogether [ 3, 4 ] and also abundant data showing that the outcome of
treatment of early stage colorectal cancer is far better than that of more advanced
disease.
S. K. Clark , M.A., M.B.B.Chir., M.D., FRCS (Gen Surg.)
The Polyposis Registry, St Mark’s Hospital ,
Northwick Park, Watford Rd., Harrow ,
Middlesex, London ,
HA1 3UJ , UK
e-mail: rebecca.jones@nwlh.nhs.uk
Chapter 9
Colorectal Cancer Screening and Surveillance
Susan K. Clark
110
S.K. Clark
The refi nement of technologies allowing identifi cation of premalignant ade-
nomas and early asymptomatic cancers means that screening and surveillance
have enormous potential for improving outcomes or even preventing the disease
altogether.
9.2 Screening or Surveillance?
Screening involves assessing an asymptomatic population in order to identify indi-
viduals who are at high or low risk for the disease in question. Further investiga-
tion is then carried out in the “screen-positive” group. Screening does not
necessarily exclude the condition in the “screen-negative” group, but should pro-
vide a safe and cost-effective way of identifying individuals with substantially
increased risk.
In contrast, surveillance is the periodic assessment of individuals who have
already been identifi ed as being at high risk for development of a disease, for exam-
ple, individuals who suffer from a predisposing condition or have a genetic
susceptibility.
9.3 Population Screening for Colorectal Cancer
The World Health Organization has set out widely accepted principles on which
population screening programs should be based (Box 9.1 ).
Box 9.1: WHO Principles for Screening Programs
The condition being screened for should be an important health problem •
Its natural history should be adequately understood •
There should be a detectable early stage •
Treatment at an early stage should be of more benefi t than treatment later •
A suitable test should exist for the early stage, with good sensitivity and •
specifi city
The test should be acceptable •
The disease should have an insidious onset, and screening intervals will be •
determined by the natural history
Adequate health service provision should be made for the extra clinical •
workload (diagnosis and treatment) resulting from screening
The risk of physical and psychological harm should be less than the chance •
of benefi t
The cost should be balanced against the benefi ts (i.e., the screening program •
should represent value for money)
111
9 Colorectal Cancer Screening and Surveillance
It is clear that colorectal cancer satisfi es all of these criteria at least to some
extent, and as a result, population screening programs have been set up in many
countries. The debate now centers on the optimum method of delivering such
screening, rather than the merits of screening per se.
9.3.1 Screening Tests
There are several potential tools available for colorectal cancer screening, with dif-
fering acceptability, cost, risks, sensitivity, and specifi city (Table 9.1 ).
Table 9.1 Potential screening investigations for colorectal cancer
Test Pros Cons
Symptom questionnaire Cheap
Does not detect early
disease
Safe Poor sensitivity
Poor specifi city
Digital rectal examination Cheap Only detects low rectal tumors
(15%)
Safe
Serum CEA Reasonably cheap Poor sensitivity
Safe Poor specifi city
Fecal occult blood Cheap Sensitivity 50–60%
Safe
RCTs show reduction in
mortality
Rigid sigmoidoscopy Reasonably cheap Only detects rectal cancer (30%)
Low risk
Detects adenomas
Evidence of reduction in
rectal cancer death
Flexible sigmoidoscopy Detects 70% of cancers Does not detect proximal tumors
Detects adenomas More expensive
RCT shows reduction in
mortality
Colonoscopy High sensitivity Expensive
High specifi city Perforation rate
1:500–5,000
Examines entire colon Bowel preparation
required
Detects adenomas No trial data
Barium enema Reasonable sensitivity Expensive
Reasonable specifi city Radiation exposure
Images entire colon No trial data
Virtual colonoscopy Good sensitivity Expensive
Good specifi city Radiation exposure
Images entire colon No trial data
112
S.K. Clark
9.4 Fecal Occult Blood Testing
Fecal occult blood testing (FOBT) has found favor because it is relatively cheap,
safe, and generally more acceptable than invasive tests or radiological imaging.
Individuals can perform the test in the privacy of their home, using a kit to smear
feces onto the test strip, and the kit can be delivered and returned by post. There are
two forms available.
9.4.1 Guaiac FOBT
Heme (the iron-containing component of hemoglobin) has pseudoperoxidase activ-
ity, which releases oxygen from hydrogen peroxide. This reacts with stabilized gum
guaiac on a test strip to form a blue dye. The test strip can be rehydrated to increase
sensitivity, but at the cost of reduced specifi city.
9.4.2 Immunochemical FOBT
These are available using various different types of assays, but in all of them,
monoclonal or polyclonal antibodies raised against the globin moiety of human
hemoglobin detect intact human hemoglobin or very early degradation products.
This aims to enhance specifi city.
9.4.3 Comparison
The sensitivity of guaiac FOBT has a wide range between 25% and 80% for carci-
noma and between 5% and 20% for adenomas. There is a false-positive rate of
2–5% due to ingested meat, certain vegetables, or gastrointestinal bleeding from
other causes. Generally guaiac FOBT is more sensitive but less specifi c than the
more expensive immunological test. These fi gures all seem to vary widely between
studies, and a recent systematic review [ 5 ] has shown that there is no clear evidence
as to whether guaiac or immunohistochemical FOBTs perform better.
9.5 Flexible Sigmoidoscopy
This allows direct examination of the rectum and sigmoid colon together with
removal of polyps at the same time. An enema is required for preparation, but no
other medication is necessary.
113
9 Colorectal Cancer Screening and Surveillance
9.6 Colonoscopy
This requires full bowel preparation and, in most cases, sedation. Theoretically
colonoscopy is an attractive screening tool. However, it has not been subject to any
randomized controlled trial. Furthermore, it is expensive and carries signifi cant risk
of perforation ranging from 1 in 500 to 1 in 5,000 in various different series. While
there is some evidence that regular colonoscopy reduces the incidence of distal
colorectal cancers, it appears that it does not protect against proximal colon cancer
[
6, 7 ] . This may well be due to the biology of the disease in the right colon.
9.6.1 Randomized Trials of Population Screening
There have been four large randomized controlled trials of FOBT screening, in
Funen, Denmark [ 8 ] ; Goteborg, Sweden [ 9 ] ; Minnesota, USA [ 10 ] ; and Nottingham,
UK [ 11 ] . These included over 300,000 participants over the age of 50 years and
used annual or biannual screening.
All trials reported more early stage colorectal cancers in the screening groups
compared with the control groups and showed a relative reduction in mortality from
colorectal cancer of 15–33%.
Two of the trials (Funen and Nottingham) did not use rehydrated slides. This
resulted in a low test-positive rate (0.8–3.8%) and a higher positive predictive
value for colorectal cancer (5.0–18.7%). The Goteborg and Minnesota studies
used rehydrated slides, resulting in a positivity rate of 1.7–15.4% with a lower
positive predictive value (0.9–6.1%) for colorectal cancer. Overall, the sensitivity
ranged from 55% to 57% with the nonhydrated slides and 82–92% with the rehy-
drated slides.
The trial in Minnesota has been criticized because of the large number of positive
screening tests that resulted in colonoscopy. Overall, 38% of the group on annual
screening and 28% of the group on biannual screening underwent one or more
colonoscopies in this study (compared with 2.6–6.4% in the other studies).
A recent meta-analysis of these studies [ 12 ] and their longer term outcomes has
shown a relative reduction in colorectal cancer mortality of 16%, with a 23% reduc-
tion seen in those who actually attended for screening.
9.7 Flexible Sigmoidoscopy Screening
A recently published large randomized controlled trial of once only fl exible sigmoi-
doscopy screening between the ages of 55 and 64 showed an uptake of 71%, very
similar to that of FOBT screening [
13 ] .
Small polyps were removed at the screening investigation, and those with high-
risk features (polyp 1 cm or larger, three or more adenomas, tubulovillous or villous
114
S.K. Clark
histology, severe dysplasia, or more than 20 hyperplastic polyps above the rectum)
went on to colonoscopy. Overall, 5% of those screened underwent colonoscopy.
An intention to treat analysis showed a reduction in colorectal cancer incidence
of 23% in the intervention arm over a median follow-up of 11 years, with a reduc-
tion in mortality of 31%. In those who actually attended the screening, the incidence
of colorectal cancer was reduced by 33% and mortality by 43%. The number needed
to be screened to prevent one colorectal cancer diagnosis in the study period was
191 (95% CI 145–277) and to prevent one colorectal cancer death was 489 (95% CI
343–852).
Two further similar trials, one in Italy and one in the USA, are nearing publica-
tion, and the results are awaited.
9.7.1 The UK National Bowel Cancer Screening Programme
On the basis of the FOBT trial data, the NHS Bowel Cancer Screening Programme
was set up, announced in 2004, starting in 2006, with full rollout achieved by 2009.
The program consists of fecal occult blood testing every 2 years in individuals aged
60–69 years. Those over 70 can request a kit if they wish.
The program in England is coordinated through fi ve “hubs,” each covering a
population of approximately ten million people. These arrange the call and recall of
individuals and dispatch and process the FOBT kits. These hubs link with local
screening centers where those with a positive result go on to colonoscopy (or in
some cases, virtual colonoscopy or barium enema).
Prior to starting, the scheme pilots were undertaken in Warwickshire and
Scotland, which confi rmed that the research fi ndings could be replicated in an NHS
service setting [ 14 ] .
9.8 Future
The fi ndings of the recently published fl exible sigmoidoscopy screening study have
been suffi ciently dramatic that the UK government has undertaken to replace the
current FOBT screening with once only fl exible sigmoidoscopy. Economic analysis
suggests that such a program would be cost saving, largely because of the reduction
in incidence [ 15 ] , although there remain considerable workforce and resource issues
to be overcome.
Even though this test is more invasive than FOBT, uptake rates are very similar,
and it seems the main barriers to screening are lack of public awareness of the high
incidence of disease and value of screening [ 16 ] .
In the USA, current recommendations favor either colonoscopy or combination
of FOBT and fl exible sigmoidoscopy. It may well be that this latter approach, which
combines the cancer prevention advantages of fl exible sigmoidoscopy with the
detection of right-sided tumors by FOBT, is adopted in the UK.
115
9 Colorectal Cancer Screening and Surveillance
There are also considerable efforts being made to produce a more sensitive and
specifi c fecal screening tool, and current work using this approach to detect abnor-
mal DNA from adenomas and cancers is producing some promising results.
9.9 Surveillance in High-Risk Groups
There are a number of groups with a considerably higher risk of colorectal cancer
than the general population (Table 9.2 ). These require a different approach, in that
the technique of investigation used must be more sensitive, but a higher fi nancial
cost and more invasive test are acceptable in this context. In practice, this means the
use of colonoscopy (or fl exible sigmoidoscopy where anatomically appropriate).
Very comprehensive up-to-date evidence based guidelines encompassing most
of these groups have recently been published [ 17 ] .
9.10 Infl ammatory Bowel Disease
It is well known that extensive ulcerative colitis is associated with an increased risk
of colorectal cancer, which rises with time and becomes appreciable approximately
10 years from diagnosis. The risk associated with Crohn’s disease is thought to be
similar when the disease has a similar distribution. The estimate of risk is based on
historical data, and there is a strong suggestion that improved modern management
of ongoing infl ammation has resulted in a reduction in colorectal cancer incidence.
However, surveillance continues to be recommended.
It should commence approximately 10 years after the onset of symptoms of coli-
tis in patients with ulcerative colitis or Crohn’s colitis. The initial colonoscopy
should ideally be done with the patient in remission and with pancolonic dye spray.
Those with extensive colitis but no active infl ammation, either on endoscopy or on
Table 9.2 High-risk groups
Group at increased risk
Approximate relative risk
of colorectal cancer
Previous colorectal cancer
1.5–2
Previous colorectal adenomas 1.5–2
Infl ammatory bowel disease 2–5
Family history of colorectal
cancer
2–10
Hyperplastic polyposis 5 (in fi rst-degree relatives)
Peutz-Jeghers syndrome 5
Acromegaly 7
Juvenile polyposis 8
Lynch syndrome 20
Familial adenomatous polyposis 30
MYH-associated polyposis 30
Ureterosigmoidostomy 100
116
S.K. Clark
histological examination, can simply undergo 5 yearly colonoscopy. Biopsies should
be taken from any abnormal areas as well as two to four random biopsies from every
10 cm of normal-appearing colorectum.
If the initial colonoscopy shows extensive colitis with mild active infl ammation
or postinfl ammatory polyps, colonoscopy should be repeated at 3 years.
Extensive colitis with moderate or severe active infl ammation, dysplasia in the
last 5 years, and primary sclerosing cholangitis are associated with a higher risk of
malignancy; annual colonoscopy is required.
9.11 Acromegaly
A raised level of circulating growth hormone and its tissue mediator insulin-like
growth factor (IGF1) results in an increased risk of colorectal cancer. It is therefore
advised that those with acromegaly undergo regular colonoscopic screening from
the age of 40. This should be repeated every 5–10 years unless an adenoma is
detected, in which case, it should be done 3 yearly.
9.12 Ureterosigmoidostomy
Anastomosis of urinary and gastrointestinal tracts (most commonly ureterosigmoi-
dostomy and variants) results in a high risk of malignancy. It is recommended that
patients undergo annual fl exible sigmoidoscopy following such surgery.
9.13 Previous Colorectal Cancer
Overall, approximately 5% of patients overall develop metachronous colorectal
cancer. There is no evidence that ongoing colonoscopic surveillance improves sur-
vival after colorectal cancer resection, but a number of professional bodies have
produced guidelines suggesting that colonoscopy should be performed prior to or
soon after resection and then at 3–5 yearly intervals until it is felt that the risks out-
weigh the benefi ts because of a patient’s age and comorbidities.
9.14 Previous Colorectal Adenomas
Following polypectomy, the future risk of developing colorectal cancer or advanced
adenomas depends upon the number and size of those adenomas. This has resulted
in the suggestion that patients can be divided into low-, intermediate-, and high-risk
groups, guiding further management [ 18 ] .
117
9 Colorectal Cancer Screening and Surveillance
Those with no more than two small (<1 cm) adenomas need no follow-up or
colonoscopy at 5 years. Those with three or four small adenomas, or at least one
large adenoma, should be examined 3 yearly until two consecutive colonoscopies are
clear. Those with any of fi ve or more adenomas, or three or more adenomas of which
at least one is large, should have colonoscopy after 1 year, then at 3 years if clear.
9.15 Family History of Colorectal Cancer
There is clear evidence that the risk of developing colorectal cancer rises with
strength of family history and that this is not entirely explained by the existence of
the polyposis syndromes and Lynch syndrome.
Having a fi rst-degree relative with colorectal cancer diagnosed before the age of
45 confers an approximately sixfold relative risk, and having two fi rst-degree rela-
tives with the disease at any age results in a relative risk of about 10. However, when
this is coupled with the steep increase in background incidence with advancing age,
even such apparently dramatic relative risk does not result in particularly high abso-
lute risk in the 40s and 50s and below.
The chance of fi nding an abnormality in young or middle-aged individuals in this
category is low, and the approach to this group is controversial. Current British
Society of Gastroenterology guidelines [ 17 ] recommend a “one-off” colonoscopy at
age 55 for those with one affected fi rst-degree relative younger than 50 years or two
such relatives aged over 60. The remainder of this “intermediate-risk” group should
have 5 yearly colonoscopy from age 55 to 75 years.
9.16 Lynch Syndrome (Hereditary Nonpolyposis
Colorectal Cancer)
Lynch syndrome accounts for 3–5% of colorectal cancers and is therefore uncom-
mon, but those affected have an approximately 70% lifetime risk of developing
colorectal cancer.
Considerable confusion surrounds the terminology of these conditions. Lynch
syndrome is dominantly inherited and due to mutation in one of the six mismatch
repair genes, resulting in failure of the DNA mismatch repair mechanism. This
causes microsatellite instability within tumors, which can be detected by direct
examination of tumor DNA or by immunohistochemical staining for mismatch
repair proteins, which are found to be absent.
Family history criteria (the modifi ed Amsterdam criteria) have been described to
characterize families at high risk of dominantly inherited colorectal cancer predis-
position. It has however now become clear that approximately 50% of individuals
who have a genetic diagnosis of Lynch syndrome come from families in which
the family history is not strong enough to fulfi ll these criteria. Conversely, studies
of tumor DNA microsatellites or mismatch immunohistochemistry reveal that
118
S.K. Clark
approximately half of families who do fulfi ll the modifi ed Amsterdam criteria do
not have Lynch syndrome.
Families where the Amsterdam criteria are fulfi lled (high-risk family history
resembling an autosomal dominant inheritance pattern), but Lynch syndrome has
been excluded, are now said to have familial colorectal cancer (FCC).
This distinction is quite important because it is known that the colorectal cancer that
develops in Lynch syndrome patients is associated with few adenomas, rapid progres-
sion, and a higher propensity for the right colon. If colonoscopy is performed less than
biannually, there is a signifi cant rate of interval cancers. Therefore, it is recommended
that in individuals confi rmed by genetic testing to have Lynch syndrome, or who are at
risk of it and in whom it has not yet been excluded, colonoscopy should be performed
annually or biannually from the age of 25 years. In those from families fulfi lling the
Amsterdam criteria but with negative tumor analysis for microsatellite instability or
mismatch repair protein loss (i.e., FCC), 5 yearly colonoscopy is suffi cient.
9.17 Polyposis Syndromes
9.17.1 Familial Adenomatous Polyposis
This dominantly inherited syndrome has a penetrance of nearly 100% (i.e., every-
one with the syndrome is certain to develop colorectal cancer unless appropriately
managed) [ 19 ] .
In approximately 75% of affected families, the causative mutation in the APC gene
is known. At-risk relatives can therefore undergo predictive genetic testing. Once this
has been done, it is recommended that colonoscopy is performed to assess the polyp
burden and, in most cases, prophylactic surgery in the form of colectomy and ileorec-
tal anastomosis or restorative proctocolectomy is performed in adolescence.
Following colectomy and ileorectal anastomosis, the remaining rectum is at risk
of adenoma and carcinoma development and needs to be monitored regularly. It is
recommended that fl exible sigmoidoscopy and polypectomy are undertaken
6 monthly to annually.
Following restorative proctocolectomy, adenomatous polyps can occur both in
the body of the ileoanal pouch and in the rectal cuff, and annual pouchoscopy is
recommended.
In some families, the causative mutation is not identifi ed, and therefore clinical
surveillance is required for those at risk. Generally, fl exible sigmoidoscopy is ade-
quate until the age of 20 or so as the polyps are predominantly left sided. Addition
of dye spray can add to sensitivity. From the age of 20 or so, it is recommended that
colonoscopy be performed every 5 years with fl exible sigmoidoscopy in the inter-
vening years.
In addition, duodenal adenomas can be a signifi cant cause of morbidity. Surveillance
should begin at age 25 years, with frequency dictated by Spigelman stage.
Соседние файлы в папке Библиотека им академика М.И. Перельмана