Downloaded from gut.bmj.com on June 26, 2014 - Published by group.bmj.
com
1
Gastroenterology Division,
McMaster University, Health
Sciences Centre, Hamilton,
Ontario, Canada; 2 Division of
Gastroenterology, University of
Alberta, Edmonton, Alberta,
Canada; 3 Department of
Medicine, Dalhousie University,
Halifax, Nova Scotia, Canada;
4
Department of Medicine, Mayo
Clinic Jacksonville, Jacksonville,
Florida, USA; 5 Department of
Medicine, University of
Wisconsin School of Medicine
and Public Health, Madison,
Wisconsin, USA
Correspondence to:
Dr Alex Ford, Gastroenterology
Division, McMaster University,
Health Sciences Centre, 1200
Main Street West, Hamilton,
Ontario, Canada; alexf12399@
yahoo.com
Revised 16 July 2008
Accepted 22 July 2008
Published Online First
31 July 2008
Gut 2008;57:1545–1552. doi:10.1136/gut.2008.159723
Diagnostic utility of alarm features for colorectal
cancer: systematic review and meta-analysis
A C Ford,1 S J O Veldhuyzen van Zanten,2 C C Rodgers,3 N J Talley,4 N B Vakil,5
P Moayyedi1
ABSTRACT
Objective: Colorectal cancer is the second most common
cause of cancer death in Europe and North America.
Alarm features are used to prioritise access to urgent
investigation, but there is little information concerning
their utility in the diagnosis of colorectal cancer.
Methods: A systematic review and meta-analysis of the
published literature was carried out to assess the
diagnostic accuracy of alarm features in predicting
colorectal cancer. Primary or secondary care-based
studies in unselected cohorts of adult patients with lower
gastrointestinal symptoms were identified by searching
MEDLINE, EMBASE and CINAHL (up to October 2007).
The main outcome measures were accuracy of alarm
features or statistical models in predicting the presence of
colorectal cancer after investigation. Data were pooled to
estimate sensitivity, specificity, and positive and negative
likelihood ratios. The quality of the included studies was
assessed according to predefined criteria.
Results: Of 11 169 studies identified, 205 were retrieved
for evaluation. Fifteen studies were eligible for inclusion,
evaluating 19 443 patients, with a pooled prevalence of
colorectal carcinoma of 6% (95% CI 5% to 8%). Pooled
sensitivity of alarm features was poor (5% to 64%) but
specificity was .95% for dark red rectal bleeding and
abdominal mass, suggesting that the presence of either
rules the diagnosis of colorectal cancer in. Statistical
models had a sensitivity of 90%, but poor specificity.
Conclusions: Most alarm features had poor sensitivity
and specificity for the diagnosis of colorectal carcinoma,
whilst statistical models performed better in terms of
sensitivity. Future studies should examine the utility of
dark red rectal bleeding and abdominal mass, and
concentrate on maximising specificity when validating
statistical models.
Colorectal carcinoma is the second most common
cause of cancer death in the Western world.1 2
Traditionally, lower gastrointestinal (GI) symp-
toms are thought to be more common in those
with colorectal carcinoma.3 4 However, these
symptoms are also prevalent in healthy individuals
in the community,5–13 and in a health service with a
limited budget it is not economically feasible to
investigate every person who reports them. In the
UK, the National Institute for Health and Clinical
Excellence (NICE)14 15 has published guidelines to
assist general practitioners in identifying patients
with a high probability of colorectal carcinoma.
The presence of so-called ‘‘alarm’’ features, such as
rectal bleeding, a change of bowel habit to looser or
more frequent stools, iron deficiency anaemia, or a
palpable right-sided abdominal mass or rectal mass
have been proposed as the optimal method of
Colorectal cancer
identifying these individuals, who are required to
be seen by a specialist for further assessment and
investigation within 2 weeks of referral.
These symptoms and signs have been selected
because it is thought that they may predict a
diagnosis of colorectal cancer. However, colorectal
cancer can present with vague symptoms, or
patients may be completely asymptomatic, so
expecting clinical features to be highly sensitive is
unrealistic. Indeed, this is the rationale for screen-
ing of healthy asymptomatic individuals for color-
ectal cancer in many countries. In addition, as
lower GI symptoms are common, many individuals
will need to be investigated to detect one case of
cancer. Studies that have evaluated the accuracy of
clinical features in the diagnosis of colorectal
carcinoma have been conflicting, with some
suggesting that no single item can be used to
identify patients with colorectal cancer accurately,
and others reporting that certain individual symp-
toms or signs, or a combination of both in
statistical models, are accurate in this situation.16–19
All studies have focused on maximising sensitivity,
but this may not be appropriate when triaging
patients for urgent referral where the doctor wishes
to prioritise those with a high likelihood of having
malignancy. A better approach to this problem
would be to choose clinical features that have a
high specificity for the diagnosis of colorectal
carcinoma which, if present, would effectively rule
the disease in.20
There is currently little in the way of distillation
of published evidence to support the recommenda-
tions made by current guidelines. We have there-
fore conducted a systematic review of the literature
to identify studies that examine the accuracy of
alarm features to ascertain if it is possible, using
current available data, to identify subgroups of
patients who are likely to have colorectal carci-
noma, and therefore require rapid referral for
assessment and investigation to exclude this
diagnosis.
METHODS
Data sources and search strategy
The systematic review was performed according to
the Cochrane Methods Group on Screening and
Diagnostic Tests guidelines.21 Two authors per-
formed searches of the medical literature using
MEDLINE (1950 to October 2007), EMBASE (1988
to October 2007) and CINAHL (1982 to October
2007). Papers on lower GI neoplasia were identified
with the terms ‘‘colon neoplasms’’, ‘‘rectal neo-
plasms’’, ‘‘colorectal neoplasms’’ (both as Medical
Subject Heading and as free text terms), ‘‘colo$’’
1545
 Downloaded from gut.bmj.com on June 26, 2014 - Published by group.bmj.com
Colorectal cancer
adj5 ‘‘cancer’’, ‘‘colo$’’ adj5 ‘‘adenocarcinoma’’, ‘‘rectal’’ adj5
‘‘cancer’’ and ‘‘rectal’’ adj5 ‘‘adenocarcinoma’’ (all free text
terms). These were combined using the set operator AND with
papers evaluating clinical features using the terms ‘‘medical
history taking’’, ‘‘anaemia’’, ‘‘iron deficiency anaemia’’, ‘‘diar-
rhoea’’, ‘‘alarm’’, ‘‘weight’’ adj5 ‘‘loss’’, ‘‘altered’’ adj5 ‘‘bowel’’
and ‘‘rectal’’ adj5 ‘‘bleed$’’ (all free text terms). There were no
language restrictions, and papers published in abstract form
were eligible for inclusion in the review. Abstracts of the papers
identified by the initial search were evaluated for appropriate-
ness to the study question, and all potentially relevant papers
were obtained and evaluated in detail. The bibliographies of
identified studies were used to perform a recursive search of the
literature. Authors were contacted where study data or
methodology required further clarification.
Study selection
Studies were required to report prospectively on unselected
cohorts of adult patients attending for investigation of lower GI
symptoms, and had to record symptoms prior to investigation.
Those comparing accuracy of alarm features, a statistical model
or a combination of both with the results of lower GI
investigation were eligible for inclusion (Box 1). More than
90% of subjects were required to undergo lower GI investiga-
tion, defined as colonoscopy, barium enema or CT colography.
Studies that used flexible sigmoidoscopy alone to evaluate
patients were only eligible if patients were followed-up for at
least 1 year, or there was evidence that data on all potentially
missed colorectal cancers were collected at study end. Case–
control studies evaluating patients with cancer and comparing
them with patients without cancer were not included, as they
tend to bias results in favour of the diagnostic test being
studied.22 Articles were independently assessed by three
researchers according to the predefined eligibility criteria, with
disagreements resolved by consensus.
Data extraction and quality assessment
Data were extracted by three reviewers on to predesigned forms,
and discrepancies in data extraction were resolved by consensus.
The quality of included studies was assessed using a meta-
analysis, which identified factors that influenced the outcome
Box 1 Eligibility criteria
c Adult patients (aged.16 years) presenting with lower
gastrointestinal (GI) symptoms evaluated
c Cross-sectional design (not case–control)
c Patients not specially selected*
c Lower GI symptoms recorded{
c Symptoms and diagnosis recorded prospectively
c Patients undergo lower GI investigations with diagnosis
recorded{
c Symptoms and investigative diagnosis compared
c More than 100 patients included
c More than one colorectal cancer diagnosed
*Patients could be selected by age or by primary care doctor’s
referral, but not other criteria (eg, only patients without rectal
bleeding).
{This includes diagnostic criteria, scores generated from
symptom questionnaires and computer-aided diagnoses.
{Colonoscopy, barium enema, CT colography, flexible sigmoido-
scopy or any combination of the four.
1546
of diagnostic studies (Box 2).23 Studies were evaluated according
to whether assessors were blinded, cases were consecutive and
whether sample size was adequate.
Data synthesis and analysis
Diagnoses established according to individual alarm features
and statistical models were analysed separately. The primary
goal of the study was to describe the performance of the various
alarm features and statistical models in distinguishing colorectal
carcinoma from all other organic and functional lower GI
diseases. The sensitivity, specificity, positive likelihood ratio
(LR), negative LR and 95% CI were calculated for each alarm
feature using a Microsoft Excel spreadsheet (XP professional
edition; Microsoft Corp, Redmond, Washington, USA) and
checked using StatsDirect version 2.4.4 (StatsDirect, Sale,
Cheshire, UK). Data were pooled using a random effects
model,24 and StatsDirect was used to generate Forest plots of
pooled sensitivities, specificities, and positive and negative LRs.
Where sufficient studies reported the utility of an individual
alarm feature, the sensitivity and (1 – specificity) for each study
were plotted graphically and a pooled summary receiver
operating characteristics (ROC) curve constructed, and the area
under the curve calculated, using Meta-DiSc version 1.4
(Universidad Complutense, Madrid, Spain).
Heterogeneity between pooled studies for each alarm feature
was assessed using the I2 statistic and x2. Where statistically
significant heterogeneity between studies existed (I2.25% or
p,0.10)25 for a particular alarm feature and a sufficient number
of studies were available, potential reasons for this were
explored informally via subgroup analyses according to study
setting (primary care-based vs secondary care-based), number of
centres (single vs multicentre studies), type of lower GI
investigation used (colonoscopy vs other lower GI investiga-
tions), method of symptom data collection (questionnaire vs
clinical history vs method not reported) and study sample size
(,500 patients vs >500 patients). These are exploratory
analyses only, and the results should be interpreted with
caution. We compared LRs between these subgroups using the
Box 2 Method used for assigning quality of evidence
Level 1 (highest)
Independent blind comparisons of test with a valid criterion
standard in a large number (>200) of consecutive patients.
Level 2
Independent blind comparisons of test with a valid criterion
standard in a small number (,200) of consecutive patients.
Studies that had separate researchers performing test and
criterion standard but did not explicitly state that these were
masked included in this category.
Level 3
Independent blind comparison of test with a valid criterion
standard in patients who were not enrolled consecutively.
Level 4
Non-independent comparison of a test with a valid criterion
standard among a ‘‘convenience’’ sample of patients believed to
have the condition in question.
Level 5
Non-independent comparison of a test with a standard of
uncertain validity.
Gut 2008;57:1545–1552. doi:10.1136/gut.2008.159723
 Downloaded from gut.bmj.com on June 26, 2014 - Published by group.bmj.com
Cochrane Q statistic and, due to multiple analyses, a p value of
,0.01 was considered statistically significant.
RESULTS
The search strategy identified 11 169 studies of which 205 were
possibly relevant to the systematic review and retrieved (fig 1).
Of these, 15 studies were eligible for inclusion, evaluating a total
of 19 443 patients,16–19 26–36 with a pooled prevalence of colorectal
carcinoma in all studies of 6% (95% CI 5% to 8%). The
prevalence of colorectal carcinoma in individual studies varied
from 3% to 14.6%. Polyp detection rates in individual studies,
where reported, varied between 7% and 50%. Complete colonic
imaging rates for lower GI investigations varied between 56%
and 98%. None of the included studies reported on operator
experience, in terms of number of previous procedures
performed, or withdrawal times for colonoscopy. Only three
studies reported the method of bowel preparation,28 32 35 and
only one study reported the quality of bowel preparation
achieved,30 which was inadequate in 16% of patients. Other
study characteristics are provided in table 1.
Thirteen studies examined the accuracy of alarm features in
predicting colorectal carcinoma, one study reported on the
accuracy of a statistical model and one study reported on both.
Symptom data were collected using a questionnaire in seven
studies,17 18 26 27 29 31 34 via clinical history in three studies,16 32 33
and the method of collection was unclear in the remaining
studies. One study used barium enema alone as the lower GI
investigation of choice,29 and no study used CT colography
alone. Several studies included patients who required endo-
scopic visualisation of abnormalities detected at barium enema,
or who were asymptomatic but undergoing follow-up or
surveillance for previous colorectal carcinoma, polyps or
inflammatory bowel disease.16 27 28 31 33 35 36 These groups of
patients were always excluded from our analyses, as they were
not relevant to the clinical question we were addressing.
Rectal bleeding
We identified 14 studies evaluating 19 189 patients,16–19 27–36 with a
pooled prevalence of colorectal cancer of 7% (95% CI 5% to 8%).
The pooled prevalence of rectal bleeding in the studies was 49%
(95% CI 38% to 59%), the character of which was not specified in
Figure 1 Flow diagram of assessment of studies identified in the
systematic review.
Gut 2008;57:1545–1552. doi:10.1136/gut.2008.159723
Colorectal cancer
12 of the studies. The pooled positive and negative LRs for rectal
bleeding were poor, and there was statistically significant
heterogeneity between study results (table 2). The ROC curve
indicated that rectal bleeding had a limited accuracy for diagnosing
lower GI malignancy, with an area under the curve of 0.60 (fig 2).
Two studies collected more detailed information on the
character of rectal blood loss in 4440 patients,17 18 with a pooled
prevalence of colorectal cancer of 5% (95% CI 4% to 6%). The
pooled prevalence of dark blood loss per rectum was 5% (95% CI
2% to 9%), as distinct from bright red rectal bleeding. The
specificity of this symptom was high, which meant that the
pooled positive LR was greater than for rectal bleeding of
unspecified character (table 2).
Change in bowel habit
There were 11 studies evaluating a current change in bowel
habit in 17 581 patients,17–19 27–30 32 34–36 with a pooled prevalence
of colorectal cancer of 6% (95% CI% 5% to 8%). Only two
studies specified the duration of this symptom, and this was
between 3 and 12 months.17 34 The pooled prevalence of a
change in bowel habit in the studies was 32% (95% CI 22% to
43%). The pooled positive and negative LRs for a change in
bowel habit were poor, with statistically significant hetero-
geneity between studies (table 2).
Anaemia
We identified seven studies reporting on the presence or absence
of anaemia in 4404 patients,17 27 28 31 32 34 35 with a pooled
prevalence of colorectal cancer of 8% (95% CI 6% to 11%). The
pooled prevalence of anaemia was 11% (95% CI 8% to 15%).
Pooled positive and negative LRs were again disappointing for
anaemia in predicting underlying colorectal cancer (table 2).
Four studies specifically stated that they examined the utility
of iron deficiency anaemia in predicting a diagnosis of colorectal
carcinoma in 1571 patients,28 31 32 34 though only one study
defined this precisely,34 with a pooled prevalence of cancer in
these studies of 9% (95% CI 5% to 13%). The prevalence of iron
deficiency anaemia was 14% (95% CI% 9% to 22%). However,
the pooled LRs did not improve over those for anaemia of
unspecified type (table 2).
Weight loss
We identified five studies evaluating weight loss in 7418
patients,17 18 29 31 34 with a pooled prevalence of colorectal cancer
of 6% (95% CI% 4% to 8%). Overall, the pooled prevalence of
weight loss in the studies was 12% (95% CI% 6% to 20%).
Specificity of weight loss was generally high, meaning that the
pooled positive LR was almost 2, but the pooled negative LR
was poor (table 2).
Diarrhoea
There were five studies reporting on diarrhoea in 3904
patients,18 27 31 32 34 with a pooled prevalence of colorectal cancer
of 9% (95% CI 5% to 13%). The pooled prevalence of diarrhoea
in the studies was 20% (95% CI 6% to 38%). Both pooled
positive and negative LRs were poor, with a positive LR ,1,
suggesting that the presence of diarrhoea was actually a
negative predictor of colorectal cancer (table 2).
Abdominal mass
Two studies reported on the presence or absence of an
abdominal mass on physical examination in 2465 patients,17 35
with a pooled prevalence of cancer in the studies of 6% (95% CI
1547
 Downloaded from gut.bmj.com on June 26, 2014 - Published by group.bmj.com

Colorectal cancer

Table 1 Characteristics of included studies

No of
No of patients with Consecutive
Study Country patients CRC (%) Setting Investigation used patients Blinded? Quality level
32
Tate 1988 UK 130 14 (10.8) Secondary care Colonoscopy Unclear No 4
Bellentani 199026 Italy 254 10 (3.9) Primary and Colonoscopy or double- Yes Unclear 2*
secondary care contrast barium enema
Brenna 199033 Norway 311 24 (7.7) Secondary care Colonoscopy Yes No 4
Berkowitz 199328 South Africa 303 14 (4.6) Secondary care Colonoscopy Unclear Unclear 4
Neugut 199336 USA 936 74 (7.9) Secondary care Colonoscopy Unclear Unclear 4
Brewster 199430 UK 462 21 (4.5) Secondary care Double-contrast barium Unclear Unclear 4
enema and flexible
sigmoidoscopy
Steine 199429 Norway 1840 55 (3.0) Primary care Double-contrast barium Yes Yes 1
enema
Cheong 200035 Malaysia 293 20 (6.8) Secondary care Colonoscopy Unclear Unclear 4
Morini 200127 Italy 368 40 (10.9) Secondary care Colonoscopy Yes No 4
de Bosset 200231 Switzerland 858 51 (5.9) Secondary care Colonoscopy Yes No 4
Selvachandran 200218 UK 2268 95 (4.2) Secondary care Colonoscopy, double- Unclear Unclear 2*
contrast barium enema,
or flexible
sigmoidoscopy
Panzuto 200334 Italy 280 41 (14.6) Primary care Colonoscopy or double- Yes Unclear 2*
contrast barium enema
Ahmed 200516 UK 439 35 (8.0) Population-based Colonoscopy Yes Unclear 4
Bjerregaard 200717 Denmark 2172 122 (5.6) Secondary care Colonoscopy, double- Yes Unclear 4
contrast barium enema,
flexible sigmoidoscopy,
or CT colography
Thompson 200719 UK 8529 467(5.5) Secondary care Flexible sigmoidoscopy Yes Unclear 4
*Blinding in these studies was not stated explicitly, but they used separate researchers to collect symptom data from those who performed diagnostic tests, therefore their quality
level is assumed to be 2 (see box 2).
CRC, colorectal carcinoma.

5% to 7%). The pooled prevalence of a palpable abdominal mass
was 3% (95% CI 2% to 4%). Pooled specificity of an abdominal
mass was high, but pooled sensitivity was very low, resulting in
poor pooled positive and negative LRs (table 2).
Statistical models
We identified two studies reporting on statistical models in a
total of 2522 patients, with a pooled prevalence of colorectal
carcinoma of 4% (95% CI 3% to 5%).18 26 One of the models was
designed specifically to differentiate between colorectal carci-
noma and other organic diseases of the colon and rectum, and
was applied prospectively,18 and the other was designed to
differentiate between organic and functional lower GI disease,
and was applied retrospectively,26 but the reporting of data in
this study allowed us to examine the model’s accuracy in
predicting colorectal cancer compared with all other organic and
functional lower GI disease. The models predicted a pooled
prevalence of colorectal carcinoma of 44% (95% CI 36% to 51%).
Pooled sensitivity was high, meaning that the pooled positive
and negative LRs were better than for most of the individual
symptom items (table 2).
Subgroup analyses
There were sufficient studies available to perform subgroup
analyses for rectal bleeding, change in bowel habit and anaemia
of unspecified type (table 3). There were trends for a change in
bowel habit to perform better as a predictor of colorectal cancer
in secondary care studies compared with primary care studies,
and for anaemia of unspecified type to perform better in studies
that collected symptom data via a questionnaire, compared
with those that did not report the method of data collection,
and in multicentre studies. However, these did not achieve
statistical significance, and the positive and negative LRs
remained poor. The type of lower GI investigation used and
study sample size appeared to have little effect on the utility of
alarm features. Sensitivity was lower, and specificity higher, in
studies that used colonoscopy when change in bowel habit was
evaluated, but not for rectal bleeding or anaemia. The reason for
this is unclear, and is probably a chance finding.
DISCUSSION
To our knowledge this is the first systematic review and meta-
analysis of the accuracy of alarm features or statistical models in
predicting which individuals need urgent investigation to
exclude colorectal cancer. The current study suggests that
symptoms and signs traditionally thought to have high
sensitivity for the diagnosis of colorectal cancer, when taken
individually, perform little better than chance alone in
differentiating between cancer and other organic and functional
lower GI disease. Statistical models, validated in only two
studies, were also suboptimal. This is because these models were
heavily weighted towards detecting all colorectal cancers, and
therefore demonstrated high sensitivity, at the expense of
specificity. This aspect of their design means that many
individuals would need to be investigated to detect one case
of colon cancer, and they are therefore not suitable for triaging
patients for urgent referral.
However, the current data also provide additional novel, and
clinically more useful, information. The presence of a palpable
abdominal mass on examination and a report of dark red rectal
bleeding by the patient both had a specificity of .95% for the
diagnosis of colorectal carcinoma, because the vast majority of
individuals without cancer did not exhibit either of these
clinical features. This means that their presence in a patient
effectively rules in the diagnosis of colon cancer. These features

1548 Gut 2008;57:1545–1552. doi:10.1136/gut.2008.159723

 Downloaded from gut.bmj.com on June 26, 2014 - Published by group.bmj.com

Colorectal cancer

Table 2 Sensitivity, specificity, and positive and negative likelihood ratios of individual symptom items and
statistical models
Symptom item and studies Positive likelihood Negative likelihood ratio
reporting Sensitivity (95% CI) Specificity (95% CI) ratio (95% CI) (95% CI)

Rectal bleeding
Tate 198832 64% (35% to 87%) 65.5% (56% to 74%) 1.86 (1.07 to 2.77) 0.55 (0.25 to 0.96)
Brenna 199033 96% (79% to 100%) 40% (35% to 46%) 1.61 (1.32 to 1.80) 0.10 (0.02 to 0.50)
Berkowitz 199328 79% (49% to 95%) 61% (55% to 67%) 2.03 (1.33 to 2.57) 0.35 (0.12 to 0.78)
Neugut 199336 77% (66% to 86%) 34% (31% to 37%) 1.17 (1.0 to 1.31) 0.67 (0.43 to 1.0)
Brewster 199430 33% (15% to 57%) 65.5% (61% to 70%) 0.97 (0.49 to 1.62) 1.02 (0.69 to 1.28)
Steine 199429 31.5% (19.5% to 45.5%) 85% (83% to 86%) 2.06 (1.33 to 2.98) 0.81 (0.65 to 0.94)
Cheong 200035 55% (31.5% to 77%) 72% (66% to 77%) 1.95 (1.18 to 2.82) 0.63 (0.36 to 0.93)
Morini 200127 70% (53.5% to 83%) 37% (31% to 42%) 1.10 (0.85 to 1.33) 0.82 (0.49 to 1.28)
de Bosset 200231 49% (35% to 63%) 71% (68% to 74%) 1.71 (1.23 to 2.24) 0.71 (0.53 to 0.90)
Selvachandran 200218 86% (78% to 92.5%) 31% (29% to 33%) 1.25 (1.12 to 1.34) 0.45 (0.26 to 0.72)
Panzuto 200334 44% (28.5% to 60%) 60% (53% to 66%) 1.09 (0.72 to 1.54) 0.94 (0.68 to 1.21)
Ahmed 200516 63% (45% to 78.5%) 25% (21% to 29.5%) 0.84 (0.62 to 1.04) 1.49 (0.90 to 2.24)
Bjerregaard 200717 68% (59% to 76%) 47% (45% to 49%) 1.28 (1.11 to 1.44) 0.68 (0.52 to 0.87)
Thompson 200719 71% (67% to 75%) 37% (36% to 38%) 1.13 (1.06 to 1.20) 0.78 (0.67 to 0.89)
Summary measures 64% (55% to 73%) 52% (42% to 63%) 1.32 (1.19 to 1.47) 0.76 (0.66 to 0.87)
Change in bowel habit
Tate 198832 64% (35% to 87%) 78% (70% to 85.5%) 2.98 (1.64 to 4.79) 0.46 (0.21 to 0.79)
Berkowitz 199328 7% (0.2% to 34%) 73% (67.5% to 78%) 0.26 (0.05 to 1.19) 1.27 (0.93 to 1.42)
Neugut 199336 12% (6% to 22%) 83% (80.5% to 86%) 0.72 (0.38 to 1.31) 1.06 (0.94 to 1.13)
Brewster 199430 38% (18% to 62%) 82% (77% to 85%) 0.98 (0.53 to 1.55) 1.01 (0.67 to 1.32)
Steine 199429 45% (32% to 69%) 61% (56% to 66%) 1.00 (0.72 to 1.29) 1.00 (0.76 to 1.24)
Cheong 200035 25% (9% to 49%) 81% (76% to 86%) 1.34 (0.58 to 2.66) 0.92 (0.65 to 1.11)
Morini 200127 12.5% (4% to 27%) 94% (90% to 96%) 1.95 (0.78 to 4.57) 0.93 (0.79 to 1.02)
Selvachandran 200218 86% (78% to 92.5%) 28% (26% to 29.5%) 1.19 (1.07 to 1.28) 0.50 (0.29 to 0.80)
Panzuto 200334 19.5% (9% to 35%) 79.5% (74% to 84%) 0.95 (0.48 to 1.76) 1.01 (0.82 to 1.16)
Bjerregaard 200717 63% (54% to 72%) 55% (53% to 57%) 1.40 (1.20 to 1.60) 0.67 (0.52 to 0.83)
Thompson 200719 77% (73% to 81%) 56% (55% to 57%) 1.76 (1.66 to 1.85) 0.41 (0.35 to 0.48)
Summary measures 41% (23% to 60%) 69% (58% to 78%) 1.29 (1.05 to 1.59) 0.82 (0.66 to 1.01)
Anaemia
Tate 198832 7% (0.2% to 34%) 91% (85% to 96%) 0.83 (0.14 to 4.18) 1.02 (0.75 to 1.12)
Berkowitz 199328 7% (0.2% to 34%) 84% (80% to 88%) 0.46 (0.08 to 2.09) 1.10 (0.81 to 1.20)
Cheong 200035 2% (0% to 20%) 95% (92% to 98%) 0.52 (0.05 to 4.53) 1.02 (0.85 to 1.07)
Morini 200127 15% (6% to 30%) 93% (90% to 96%) 2.24 (0.96 to 4.89) 0.91 (0.76 to 1.00)
de Bosset 200231 12% (4% to 24%) 90% (87% to 92%) 1.14 (0.52 to 2.35) 0.98 (0.85 to 1.06)
Panzuto 200334 68% (52% to 82%) 83% (77% to 87%) 3.98 (2.77 to 5.59) 0.38 (0.24 to 0.57)
Bjerregaard 200717 11% (6% to 18.5%) 90% (89% to 92%) 1.19 (0.71 to 1.95) 0.98 (0.90 to 1.03)
Summary measures 17% (5.5% to 33%) 90% (87% to 92%) 1.43 (0.75 to 2.74) 0.96 (0.87 to 1.06)
Weight loss
Steine 199429 31% (19% to 45%) 81% (79% to 83%) 1.65 (1.07 to 2.38) 0.85 (0.69 to 0.98)
de Bosset 200231 8% (2% to 19%) 97% (96% to 98%) 3.01 (1.10 to 7.85) 0.95 (0.84 to 1.00)
Selvachandran 200218 18% (11% to 27%) 92% (91% to 94%) 2.39 (1.50 to 3.67) 0.89 (0.79 to 0.96)
Panzuto 200334 37% (22% to 53%) 89% (84% to 92%) 3.24 (1.86 to 5.41) 0.71 (0.54 to 0.87)
Bjerregaard 200717 21% (14% to 30%) 79% (77% to 81%) 1.03 (0.71 to 1.43) 0.99 (0.89 to 1.08)
Summary measures 22% (14% to 31%) 89% (81% to 95%) 1.96 (1.25 to 3.08) 0.91 (0.84 to 0.98)
Diarrhoea
Tate 198832 14% (2% to 42%) 78% (70% to 86%) 0.66 (0.18 to 2.0) 1.09 (0.76 to 1.29)
Morini 200127 1% (0% to 11%) 95% (92% to 97%) 0.26 (0.03 to 2.37) 1.04 (0.94 to 1.07)
de Bosset 200231 2% (0% to 10%) 89% (87% to 91%) 0.18 (0.03 to 0.94) 1.10 (1.01 to 1.14)
Selvachandran 200218 69.5% (59% to 78.5%) 61% (59% to 63%) 1.78 (1.52 to 2.02) 0.50 (0.36 to 0.66)
Panzuto 200334 24% (12% to 40%) 69% (62% to 74%) 0.78 (0.43 to 1.31) 1.10 (0.87 to 1.30)
Summary measures 19% (1% to 54%) 80% (63% to 93%) 0.74 (0.34 to 1.62) 0.98 (0.85 to 1.13)
Iron deficiency anaemia
Tate 198832 7% (0% to 34%) 91% (85% to 96%) 0.83 (0.14 to 4.18) 1.02 (0.75 to 1.12)
Berkowitz 199328 7% (0% to 34%) 84% (80% to 88%) 0.46 (0.08 to 2.09) 1.10 (0.81 to 1.20)
de Bosset 200231 12% (4% to 24%) 90% (87% to 92%) 1.14 (0.52 to 2.35) 0.98 (0.85 to 1.06)
Panzuto 200334 68% (52% to 82%) 83% (77% to 87%) 3.98 (2.77 to 5.59) 0.38 (0.24 to 0.57)
Summary measures 23% (2%% to 57%) 87% (83% to 91%) 1.38 (0.48 to 3.94) 0.88 (0.68 to 1.13)
Abdominal mass
Cheong 200035 5% (0% to 29%) 96% (93% to 98%) 1.37 (0.23 to 7.27) 0.99 (0.79 to 1.04)
Bjerregaard 200717 4% (1% to 9%) 97% (96% to 98%) 1.50 (0.62 to 3.51) 0.99 (0.93 to 1.01)
Continued

Gut 2008;57:1545–1552. doi:10.1136/gut.2008.159723 1549

 Downloaded from gut.bmj.com on June 26, 2014 - Published by group.bmj.com
Colorectal cancer
Table 2 Continued
Symptom item and studies
reporting Sensitivity (95% CI)
Summary measures 5% (2% to 9%)
Dark red rectal bleeding
Selvachandran 200218 7% (3% to 15%)
Bjerregaard 200717 24% (17% to 32%)
Summary measures 15% (3% to 34%)
Statistical models
Bellentani 199026 95% (65% to 100%)
Selvachandran 200218 91% (83% to 96%)
Summary measures 90% (84% to 95%)
could therefore have potential value to prioritise access to
urgent colonoscopy in the future. The caveat to this is that
these features were reported only in secondary care-based
studies, and both the spectrum of disease and the doctor making
the diagnosis will be different from those encountered in
primary care.
There may be ways to improve the utility of other individual
alarm features in predicting colorectal cancer. Examples include
specifying the amount of weight lost (and over what period of
time); the degree of anaemia (and whether there is definite
evidence that this is due to iron deficiency); and using more
precise definitions of diarrhoea and change in bowel habit based
on either stool frequency, form or a combination of the two. Of
the seven studies that reported on the presence of anaemia in
this meta-analysis, only four stated that this was iron deficiency
anaemia,28 31 32 34 and only one of these reported the threshold
used to define this.34 Excluding the three studies that did not
expand on the term anaemia from the meta-analysis,17 27 35 so
that only studies examining the utility of iron deficiency
anaemia were pooled, had little effect on the sensitivity,
specificity, or positive and negative LR of anaemia in predicting
colorectal carcinoma. However, from table 2 it can be seen that
the study providing a precise definition of what constituted iron
deficiency anaemia gave the best sensitivity, positive LR and
Figure 2 Receiver operating characteristics curve for accuracy of
rectal bleeding in predicting colorectal carcinoma. AUC, area under
the curve.
1550
Positive likelihood Negative likelihood ratio
Specificity (95% CI) ratio (95% CI) (95% CI)
97% (96% to 98%) 1.47 (0.68 to 3.19) 0.99 (0.95 to 1.02)
97% (97% to 98%) 2.71 (1.28 to 5.57) 0.95 (0.88 to 0.99)
94% (93% to 95%) 4.27 (2.94 to 6.07) 0.81 (0.72 to 0.88)
96% (93% to 98%) 3.83 (2.62 to 5.61) 0.88 (0.75 to 1.04)
54% (48% to 61%) 2.10 (1.47 to 2.46) 0.08 (0.01 to 0.59)
62% (60% to 64%) 2.38 (2.16 to 2.57) 0.15 (0.08 to 0.28)
59% (52% to 66%) 2.35 (2.16 to 2.55) 0.15 (0.08 to 0.26)
negative LR of these four studies.34 This suggests that definite
objective evidence of iron deficiency anaemia may provide
greater accuracy in predicting a diagnosis of colorectal carci-
noma, rather than anaemia of unspecified type. One study also
quantified the degree of weight loss,17 though the positive and
negative LRs derived from these data remain disappointing.
Another approach to improve the accuracy of alarm features
in predicting underlying colorectal carcinoma might be to
combine them. Two of the studies included in this meta-
analysis used this approach.19 36 However, the sensitivity and
positive and negative LRs remained poor. As data reporting was
inconsistent between the two studies that combined symp-
toms, in terms of the individual symptoms that were selected
for combination, it was not possible to pool the results for the
purpose of this meta-analysis in order to assess the value of this
approach further. Doctors often combine other items from the
clinical history, such as patient age and any relevant family
history, with the patient’s symptoms as part of the diagnostic
process,37 and this may improve overall accuracy. This is
essentially the approach taken by statistical models, but these
are currently suboptimal as they have focused on achieving a
high sensitivity, by predicting that between 40% and 50% of
patients presenting with lower GI symptoms will have color-
ectal cancer. A health service with a limited budget would be
unable to cope with the demands placed upon it if all these
patients were referred for urgent investigation. Future models
should concentrate on maximising specificity in order to rule in
a diagnosis of colorectal cancer and prioritise urgent referral
more effectively.
This systematic review is limited by the quality of the studies
included. The majority of the studies identified, while large in
several cases, were of poor quality in terms of reporting whether
either patient recruitment was consecutive or assessors were
blinded. As studies did not routinely report quality assurance
data such as quality of bowel preparation, operator experience,
withdrawal time for colonoscopy and completion rates, the
accuracy of colonoscopy or barium enema as a diagnostic test
cannot be assessed as part of the current study. However, even
if the quality of the examinations is suboptimal in some of these
studies, this is unlikely to account for the disappointing
accuracy of most alarm features.
Subgroup analyses conducted according to study setting, type
of lower GI investigation used, method of symptom data
collection, number of study centres and study sample size failed
to have any significant impact on the LRs of individual
symptom items, where sufficient studies reported them, and
did not reveal any obvious cause for the observed heterogeneity
between studies. The poor performance of alarm features in
predicting colorectal carcinoma may have been due, in part, to
Gut 2008;57:1545–1552. doi:10.1136/gut.2008.159723
 Downloaded from gut.bmj.com on June 26, 2014 - Published by group.bmj.com

Colorectal cancer

Table 3 Subgroup analyses for rectal bleeding, change in bowel habit and anaemia
Sensitivity Specificity Positive LR p Value for the Negative LR p Value for the
Symptom item and subgroup No of studies (95% CI) (95% CI) (95% CI) difference (95% CI) difference

Rectal bleeding
Study setting
Primary care-based
Secondary care-based
Lower GI investigation used
Colonoscopy
Other investigations
Symptom data collection
Via questionnaire
Not reported
Via clinical history
Number of centres
Single-centre studies
Multicentre studies
Study sample size
,500 patients
>500 patients
Change in bowel habit
Study setting
Primary care-based
Secondary care-based
Lower GI investigation used
Colonoscopy
Other investigations
Symptom data collection
Via questionnaire
Not reported
Number of centres
Single-centre studies
Multicentre studies
Study sample size
,500 patients
>500 patients
Anaemia
Lower GI investigation used
Colonoscopy
Other investigations
Symptom data collection
Via questionnaire
Not reported
Number of centres
Single-centre studies
Multicentre studies
Study sample size
,500 patients
>500 patients
LR, likelihood ratio.
2 37% (26% to 49%)
11 70% (61% to 77%)
8 69% (58% to 80%)
6 58% (43% to 78%)
6 59% (42% to 75%)
5 65% (53% to 76%)
3 76% (49% to 94%)
9 66% (52% to 78%)
5 62% (50% to 74%)
8 63% (49% to 77%)
6 65% (52% to 77%)
2 32% (11% to 59%)
9 43% (23% to 64%)
5 22% (9% to 38%)
6 57% (39% to 74%)
5 46% (20% to 73%)
5 32% (4% to 69%)
7 51% (32% to 70%)
4 26% (5% to 56%)
6 26% (14% to 41%)
5 57% (33% to 80%)
5 10% (5% to 17%)
2 37% (0% to 91%)
4 25% (6% to 50%)
2 4% (0% to 15%)
3 5% (1% to 13%)
4 25% (6% to 50%)
5 17% (1% to 47%)
2 12% (8% to 17%)
73% (46% to 93%) 1.49 (0.80 to 2.77) 0.84 (0.72 to 0.98)
51% (43% to 59%) 1.35 (1.21 to 1.50) 0.76 0.69 (0.59 to 0.81) 0.08
51% (37% to 65%) 1.42 (1.16 to 1.74) 0.69 (0.51 to 0.93)
55% (37% to 71%) 1.23 (1.11 to 1.36) 0.21 0.79 (0.68 to 0.91) 0.43
56% (35% to 75%) 1.31 (1.16 to 1.49) 0.75 (0.64 to 0.87)
54% (40% to 67%) 1.33 (1.10 to 1.62) 0.76 (0.61 to 0.93)
43% (23% to 64%) 1.34 (0.82 to 2.17) 0.99 0.56 (0.18 to 1.78) 0.88
54% (38% to 69%) 1.40 (1.19 to 1.64) 0.73 (0.58 to 0.92)
50% (36% to 63%) 1.24 (1.10 to 1.39) 0.23 0.76 (0.66 to 0.87) 0.77
53% (40% to 66%) 1.35 (1.07 to 1.72) 0.78 (0.57 to 1.05)
51% (34% to 68%) 1.27 (1.15 to 1.41) 0.64 0.76 (0.66 to 0.82) 0.88
67% (41% to 89%) 0.99 (0.76 to 1.29) 1.01 (0.88 to 1.16)
69% (56% to 80%) 1.38 (1.10 to 1.73) 0.06 0.77 (0.59 to 1.01) 0.08
83% (75% to 89%) 1.26 (0.62 to 2.57) 1.00 (0.86 to 1.16)
56% (45% to 66%) 1.26 (1.00 to 1.58) 0.99 0.73 (0.50 to 1.05) 0.12
64% (44% to 81%) 1.23 (1.07 to 1.41) 0.85 (0.71 to 1.02)
71% (57% to 84%) 1.05 (0.63 to 1.75) 0.56 0.87 (0.57 to 1.34) 0.92
62% (50% to 73%) 1.34 (1.02 to 1.76) 0.75 (0.50 to 1.12)
79% (59% to 94%) 1.18 (0.82 to 1.70) 0.58 0.93 (0.80 to 1.08) 0.33
79% (67% to 88%) 1.30 (0.77 to 2.20) 0.99 (0.85 to 1.14)
56% (42% to 69%) 1.26 (0.98 to 1.60) 0.92 0.69 (0.44 to 1.07) 0.13
91% (87% to 94%) 1.24 (0.74 to 2.08) 1.00 (0.96 to 1.06)
87% (79% to 94%) 2.21 (0.68 to 7.19) 0.38 0.63 (0.25 to 1.58) 0.33
90% (87% to 92%) 1.91 (0.94 to 3.91) 0.88 (0.75 to 1.03)
91% (77% to 98%) 0.48 (0.13 to 1.79) 0.07 1.06 (0.96 to 1.17) 0.05
91% (82% to 97%) 0.59 (0.21 to 1.67) 1.05 (0.96 to 1.15)
90% (87% to 92%) 1.91 (0.94 to 3.91) 0.07 0.88 (0.75 to 1.03) 0.08
90% (84% to 94%) 1.57 (0.67 to 3.72) 0.91 (0.75 to 1.10)
90% (89% to 91%) 1.18 (0.78 to 1.79) 0.56 0.98 (0.93 to 1.04) 0.47

the fact that the majority of included studies were based in
secondary care. This could have created a referral bias, whereby
primary care doctors preferentially referred only those indivi-
duals in whom it was not possible to reach a clear diagnosis,
after a comprehensive history and physical examination, to the
studies. However, this is unlikely to be a major explanation for
the findings of the current study, as the performance of these
individual symptoms was no better when only primary care-
based studies were included in the meta-analysis. The pre-
valence of colorectal cancer varied between studies, but in the
majority of cases was between 4% and 8%. Three studies
reported a prevalence in excess of 10%,27 32 34 higher than would
be expected in a Western population; two of these studies were
conducted in Italy.27 34 The reasons for this are speculative, but
may reflect a degree of selection bias. Eleven of the studies
stated that recruitment had been prospective, nine that they
had included consecutive patients, only one study specified that
investigators were blinded to patient data,29 and in four studies
clinical data were collected by the doctor performing the
investigative procedure,27 31–33 though the latter would be
expected to bias studies towards overestimating the accuracy
of alarm features in diagnosing colorectal cancer.
The findings of the current study demonstrate that there is
little evidence to support current NICE guidelines on rapid
referral for suspected colorectal cancer.14 15 The presence of a
palpable abdominal mass and dark red rectal bleeding appeared
to be the most useful individual clinical features to prioritise
access to urgent colonoscopy, due to their high specificity. The

Gut 2008;57:1545–1552. doi:10.1136/gut.2008.159723 1551

 Downloaded from gut.bmj.com on June 26, 2014 - Published by group.bmj.com
Colorectal cancer
latter item is not utilised in current guidelines, but this is an
important observation and needs further validation in future
studies. Finally, models assessing a combination of features
should be developed to focus on specificity rather than
sensitivity. These recommendations for research may enable
future referral criteria to better identify patients with high
likelihood of lower GI malignancy who warrant urgent
investigation.
Competing interests: None.
REFERENCES
1. American Cancer Society. Cancer facts & figures 2007. http://www.cancer.org/
downloads/STT/CAFF2007PWSecured.pdf (accessed 13 Aug 2008).
2. Ferlay J, Autier P, Boniol M, et al. Estimates of the cancer incidence and mortality in
Europe in 2006. Ann Oncol 2007;18:581–92.
3. Majumdar SR, Fletcher RH, Evans AT. How does colorectal cancer present?
Symptoms, duration, and clues to location. Am J Gastroenterol 1999;94:3039–45.
4. Keddie N, Hargreaves A. Symptoms of carcinoma of the colon and rectum. Lancet
1968;292:749–50.
5. Agreus L, Svardsudd K, Talley NJ, et al. Natural history of gastroesophageal
reflux disease and functional abdominal disorders. Am J Gastroenterol
2001;96:2905–14.
6. Boyce PM, Koloski NA, Talley NJ. Irritable bowel syndrome according to varying
diagnostic criteria: are the new Rome II criteria unnecessarily restrictive for research
and practice. Am J Gastroenterol 2000;95:3176–83.
7. Crosland A, Jones R. Rectal bleeding: prevalence and consultation behaviour. Br
Med J 1995;311:486–8.
8. Ford AC, Forman D, Bailey AG, et al. Irritable bowel syndrome: a 10-year natural
history of symptoms, and factors that influence consultation behavior.
Am J Gastroenterol 2008;103:1229–39.
9. Hillila MT, Farkkila MA. Prevalence of irritable bowel syndrome according to different
diagnostic criteria in a non-selected adult population. Aliment Pharmacol Ther
2004;20:339–45.
10. Hungin APS, Whorwell PJ, Tack J, et al. The prevalence, patterns and impact of
irritable bowel syndrome: an international survey of 40 000 subjects. Aliment
Pharmacol Ther 2003;17:643–50.
11. Jones R, Lydeard S. Irritable bowel syndrome in the general population. Br Med J
1992;304:87–90.
12. Talley NJ, Jones M. Self-reported rectal bleeding in a United States community:
prevalence, risk factors, and health care seeking. Am J Gastroenterol 1998;93:2179–83.
13. Wilson S, Roberts L, Roalfe A, et al. Prevalence of irritable bowel syndrome: a
community survey. Br J Gen Pract 2004;54:495–502.
14. NICE. Referral guidelines for suspected cancer in adults and children. www.nice.org.
uk/nicemedia/pdf/CG027fullguideline.pdf (accessed 14 Aug 2008).
15. NICE. Guidance on cancer services. Improving outcomes in colorectal cancers.
www.nice.org.uk/nicemedia/pdf/CSGCCfullguidance.pdf (accessed 14 Aug 2008).
1552
16. Ahmed S, Leslie A, Thaha MA, et al. Lower gastrointestinal symptoms are not
predictive of colorectal neoplasia in a faecal occult blood screen-positive population.
Br J Surg 2005;92:478–81.
17. Bjerregaard NC, Tottrup A, Sorensen HT, et al. Diagnostic value of self-reported
symptoms in Danish outpatients referred with symptoms consistent with colorectal
cancer. Colorectal Dis 2007;9:443–51.
18. Selvachandran SN, Hodder RJ, Ballal MS, et al. Prediction of colorectal cancer by a
patient consultation questionnaire and scoring system: a prospective study. Lancet
2002;360:278–83.
19. Thompson MR, Perera A, Senapati A, et al. Predictive value of common symptom
combinations in diagnosing colorectal cancer. Br J Surg 2007;94:1260–5.
20. Haynes RB, Sackett DL, Guyatt GH, et al. Evaluating diagnostic tests. In: Clinical
epidemiology: how to do clinical practice research. Philadelphia, PA: Lippincott,
Williams, and Wilkins, 2006:273–322.
21. The Cochrane Collaboration. The Cochrane Methods Group on systematic review
of screening and diagnostic tests: Recommended methods. Available at: http://www.
Cochrane.org/docs/sadtdoc1.2007 (accessed 13 Aug 2008).
22. Deeks JJ. Systematic reviews of evaluations of diagnostic and screening tests. Br
Med J 2001;323:157–62.
23. Scherer K, Bedlack RS, Simel DL. Does this patient have myasthenia gravis? JAMA
2005;293:1906–1914.
24. DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials
1986;7:177–88.
25. Higgins JPT, Thompson SG, Deeks JJ, et al. Measuring inconsistency in meta-
analyses. Br Med J 2003;327:557–60.
26. Bellentani S, Baldoni P, Petrella S, et al. A simple score for the identification of
patients at high risk of organic diseases of the colon in the family doctor consulting
room. Fam Pract 1990;7:307–12.
27. Morini S, Hassan C, Meucci G, et al. Diagnostic yield of open access colonoscopy
according to appropriateness. Gastrointest Endosc 2001;54:175–9.
28. Berkowitz A, Kaplan M. Indications for colonoscopy. An analysis based on
indications and diagnostic yield. S Afr Med J 1993;83:245–8.
29. Steine M, Stordahl A, Laerum F, et al. Referrals for double-contrast barium
examination. Factors influencing the probability of finding polyps or cancer.
Scand J Gastroenterol 1994;29:260–4.
30. Brewster NT, Grieve DC, Saunders JH. Double-contrast barium enema and flexible
sigmoidoscopy for routine colonic investigation. Br J Surg 1994;81:445–7.
31. de Bosset V, Froehlich F, Rey JP, et al. Do explicit appropriateness criteria enhance
the diagnostic yield of colonoscopy? Endoscopy 2002;34:360–8.
32. Tate JJT, Royle GT. Open access colonoscopy for suspected colonic neoplasia. Gut
1988;29:1322–5.
33. Brenna E, Skreden K, Waldum HL, et al. The benefit of colonoscopy.
Scand J Gastroenterol 1990;25:81–8.
34. Panzuto F, Chiriatti A, Bevilacqua S, et al. Symptom-based approach to colorectal
cancer: survey of primary care physicians in Italy. Dig Liver Dis 2003;35:869–75.
35. Cheong KL, Roohi S, Jarmin R, et al. The yield for colorectal cancer and adenoma by
indication at colonoscopy. Med J Malaysia 2000;55:464–6.
36. Neugut AI, Garbowski GC, Waye JD, et al. Diagnostic yield of colorectal neoplasia
with colonoscopy for abdominal pain, change in bowel habits, and rectal bleeding.
Am J Gastroenterol 1993;88:1179–83.
37. Thompson MR, Heath I, Ellis BG, et al. Identifying and managing patients at low risk
of bowel cancer in general practice. Br Med J 2003;327:263–5.
Gut 2008;57:1545–1552. doi:10.1136/gut.2008.159723
 Downloaded from gut.bmj.com on June 26, 2014 - Published by group.bmj.com

Diagnostic utility of alarm features for

colorectal cancer: systematic review and
meta-analysis
A C Ford, S J O Veldhuyzen van Zanten, C C Rodgers, et al.

Gut 2008 57: 1545-1553 originally published online August 1, 2008

doi: 10.1136/gut.2008.159723

Updated information and services can be found at:

http://gut.bmj.com/content/57/11/1545.full.html

These include:
References This article cites 32 articles, 9 of which can be accessed free at:
http://gut.bmj.com/content/57/11/1545.full.html#ref-list-1

Article cited in:

http://gut.bmj.com/content/57/11/1545.full.html#related-urls

Email alerting Receive free email alerts when new articles cite this article. Sign up in
service the box at the top right corner of the online article.

Topic Articles on similar topics can be found in the following collections

Collections
Colon cancer (1435 articles)

Notes

To request permissions go to:

http://group.bmj.com/group/rights-licensing/permissions

To order reprints go to:

http://journals.bmj.com/cgi/reprintform

To subscribe to BMJ go to:

http://group.bmj.com/subscribe/