t h e s u r g e o n 1 6 ( 2 0 1 8 ) 3 6 e3 9

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The Surgeon, Journal of the Royal Colleges
of Surgeons of Edinburgh and Ireland
www.thesurgeon.net

Are hemoglobin levels really lower in faecal

immunochemical test positive patients with
colorectal cancer?

Jing Yu Ng a, Ian Jse-Wei Tan a, Ker-Kan Tan a,b,*

a
Division of Colorectal Surgery, University Surgical Cluster, National University Health System, Singapore
b
Department of Surgery, Yong Yoo Lin School of Medicine, National University of Singapore, Singapore

article info abstract

Article history: Introduction: Faecal immunochemical test (FIT) is advocated in many colorectal cancer-
Received 3 October 2016 screening programs. A positive FIT translates to the need for a colonoscopy. However,
Received in revised form waiting times for diagnostic colonoscopy is long. The aim of our study is to determine the
5 December 2016 correlation of hemoglobin levels in patients with a positive FIT who were subsequently
Accepted 8 December 2016 diagnosed with colorectal cancer, and to compare them with patients with only colonic
Available online 17 January 2017 adenomas and those with normal colonoscopy with the intention of determining if he-
moglobin levels could be used to stratify the urgency of colonoscopy.
Keywords: Methodology: This is a matched caseecontrol study of patients who were FIT positive and
Anaemia subsequently underwent colonoscopy at the National University Hospital, Singapore.
Fecal occult blood test Newly diagnosed colorectal cancers formed the case group. The patients with colorectal
Colorectal cancer cancers were then matched for age, gender and ethnicity at a 1:1 ratio to patients with
Colon cancer colonic adenomas and then those in whom colonoscopy was normal.
Rectal cancer Results: Fifteen patients met the inclusion criteria and formed the case group. The differ-
Colonoscopy ences between the groups were not statistically significant in terms of age, gender and
Endoscopy ethnicity. The median hemoglobin level for the patients in the case group compared to the
control group was (12.4 vs 14.5, p ¼ 0.002) for the group with adenomas and (12.4 vs 14.4,
p ¼ 0.007) for the group with normal colonoscopy.
Conclusion: Colorectal cancer patients presenting with a positive FIT are more likely to be
anemic. A test to identify those patients who have a positive FIT that are anemic could
enable earlier colonoscopic evaluation.
© 2017 Royal College of Surgeons of Edinburgh (Scottish charity number SC005317) and
Royal College of Surgeons in Ireland. Published by Elsevier Ltd. All rights reserved.

benefits have been well documented by various randomized

Introduction studies.2e4 A positive FIT would naturally translate to the need
for a colonoscopy. However, the waiting time for diagnostic
Faecal immunochemical test (FIT) is advocated in many colonoscopy in these patients have been reported to be up to
colorectal cancer screening programs across the world.1 Its 18 weeks.5

* Corresponding author. Division of Colorectal Surgery, Department of Surgery, National University Health System, 1E Kent Ridge Road,
119228 Singapore. Fax: þ65 67778206.
E-mail addresses: jing_yu_ng@nuhs.edu.sg (J.Y. Ng), iantan.jse@gmail.com (I.J.-W. Tan), ker_kan_tan@nuhs.edu.sg (K.-K. Tan).
http://dx.doi.org/10.1016/j.surge.2016.12.001
1479-666X/© 2017 Royal College of Surgeons of Edinburgh (Scottish charity number SC005317) and Royal College of Surgeons in Ireland.
Published by Elsevier Ltd. All rights reserved.
 t h e s u r g e o n 1 6 ( 2 0 1 8 ) 3 6 e3 9 37

Anemia on the other hand, is one of the common signs
observed in patients with colorectal cancers. Although it does
not necessarily translate to a more advanced stage on diag-
nosis, it is nonetheless an independent predictor of an adverse
outcome post colonic surgery.6,7 It is however important to
note that a multitude of other causes could also present as
anemia, many of which are benign in nature.8
Whilst it is logical that patients with colorectal cancers that
present as a positive FIT should be more anemic on presen-
tation, this relationship has yet to be clearly demonstrated. In
light of this, we undertook this study to determine the corre-
lation of hemoglobin levels in patients with a positive FIT who
were subsequently diagnosed with colorectal cancer and
compared them with patients with only colonic adenomas
and those in whom colonoscopy were normal, with the ulti-
mate intention of determining if hemoglobin levels could be
used to stratify urgency of colonoscopy.
Following diagnosis, all of them underwent computed
tomographic scans of their Thorax, Abdomen and Pelvis to
complete the staging. Seven patients (46.7%) were Stage III or
IV on diagnosis. Table 2 depicts the distribution of cancer
stages and the tumour locations in the case group. Eleven
patients underwent eventual curative surgery and 2 patients
had surgery with a palliative intent. They all recovered well
with nil significant post-operative complications. One patient
was lost to follow-up post diagnosis of cancer and another had
extensive metastases on diagnosis, which precluded further
surgery.
When we compared the case group (colorectal cancer pa-
tients) to the group of patients with colonic adenomas (control
group), the median hemoglobin level was noted to be lower
(12.4 vs 14.5 g/dL). This relationship was again seen when we
compared the case group to the group of patients with normal
colonoscopy (12.4 vs 14.4 g/DL). Both differences were statis-
tically significant. Table 3 highlights the differences between
the case and control groups.

Methodology

A retrospective review of all patients who underwent a com-

Discussion
plete colonoscopy for a positive FIT between Jan 2008 and Dec
2012 was performed from a prospectively collected endoscopy
Anemia has long been associated with colorectal cancer
database at the National University Hospital (NUH),
particularly right-sided tumors.9 Our findings suggest that FIT
Singapore. FIT tests were administered in the outpatient
positive patients diagnosed with colorectal cancers are more
setting prior to referral to NUH, and any level of occult blood
likely to be anemic than FIT positive patients with adenomas
above 100 ng Hb/mL would be recorded as a positive test.
or normal colonoscopy. Whilst this may appear to be a logical
Experienced endoscopists performed all colonoscopy and we
assumption, its influence on the clinical algorithm could be
included all patients with newly diagnosed colorectal cancer
immense. The ability to perform a quick and easily replicable
on histology in our case group. This study was approved by the
tool incorporating the use of rapid hemoglobin tests to com-
institution ethics committee.
plement the current process of outpatient screening should be
Their colonoscopy results with relevant histology findings
considered. Rapid hemoglobin tests which may even be non-
were noted. Pre-endoscopy data collected included age,
invasive are accurate and increasingly used in emergency
gender, ethnicity and the respective indications for endos-
and elective settings.10 This would lead to eventual prioriti-
copy. Hemoglobin tests performed within 2 weeks of the
zation of patients with a positive FIT and concomitant anemia
procedure were also recorded. The patients with colorectal
to undergo an earlier diagnostic colonoscopy.
cancers and colonic adenomas were all confirmed on histo-
This can then translate to earlier detection and hence
logical examination. The patients with colorectal cancers
treatment of their cancer. Sey et al. demonstrated that 46% of
were then matched for age, gender and ethnicity at a 1:1 ratio
the patients with newly diagnosed colorectal cancer exceeded
to patients with colonic adenomas and then those in whom
the acceptable waiting time targets of 2 weeks for high-risk
colonoscopy was normal.
Data was analyzed using IBM SPSS Statistics Version 20
Statistical Software (IBM Corp, New York, USA). Categorical
Table 1 e Patient demographics (n ¼ 45).
variables were analyzed using chi square test and Mann
Whitney U test was used for analysis of continuous variables. Cancer Adenomas Normal
colonoscopy
A p value <0.05 was considered to be statistically significant.
Age (years)
Median age (range) 55 (23e79) 55 (22e79) 55 (28e81)
Below 40 years 2 2 1
Results 41e60 years 6 6 7
61e80 years 7 7 6
Above 80 years 0 0 1
A total of 526 patients underwent colonoscopy for FIT posi-
Gender (%)
tivity during the study period. Fifteen patients were diagnosed
Male 10 (66.7) 10 (66.7) 10 (66.7)
with colorectal cancers and formed the case group. The me- Female 5 (33.3) 5 (33.3) 5 (33.3)
dian age of the case group was 55 years (range, 23e79 years). Ethnicity (%)
The median timing from the clinic appointment to the colo- Chinese 14 (93.3) 15 (100) 15 (100)
noscopy was 5 weeks (range, 2e12). The median hemoglobin Malay 0 0 0
level was 12.4 (range, 8.4e16.3 g/dL). Table 1 illustrates the Indian 1 (0.7) 0 0
Others 0 0 0
demographic characteristics of the case group.
38 t h e s u r g e o n 1 6 ( 2 0 1 8 ) 3 6 e3 9
Table 2 e Breakdown of cancer patients (n ¼ 15).
Cancer stage (TNM)
I 3
II
III
IV
Unknown (lost to follow-up)
Location of cancer
Caecum
Ascending colon
Hepatic flexure
Transverse colon
Splenic flexure
Descending colon
Sigmoid
Rectum
Table 3 e Hemoglobin levels (n ¼ 45).
Cancer Adenomas Normal
colonoscopy
Hemoglobin levels (g/dl)
Median (95% CI) 12.4 14.5 14.4
(10.3e13.1) (13.6e14.9) (13.1e14.9)
Patients with anemia 7 1 3
(hemoglobin <12.0 g/dl)
cases and 2 months for their diagnostic colonoscopies.11
Young et al. further reported that a delay of more than 3
months was associated with lower likelihood of Stage 1 dis-
ease at surgery.12
It was also interesting to note that almost 50% (7 out of 15
patients) of the newly diagnosed colorectal cancers were
actually Stage III or IV on diagnosis. Whilst the exact reasons
for the late presentation in this otherwise asymptomatic group
of patients merits further work, the retrospective nature of this
study raised the possibility of information bias in this case.
These individuals may not have been forthcoming in
mentioning their symptoms to the medical practitioner. Be-
sides, a significant proportion of our patients had right-sided
tumors which could have accounted for their delayed presen-
tation. In addition, Sadahiro et al. demonstrated that anemia
was related to an advanced stage of colorectal cancer, which
was perhaps especially pertinent in our cancer patients.9
The issue of waiting time is not novel. Viiala et al reported
in 2007 that the waiting times in public tertiary hospitals in
Western Australia far exceed institutional recommendations
for provision of colonoscopy, with a median waiting time of up
to 37 weeks in routine cases.13 Our waiting time of 5 weeks
from the clinic to the colonoscopy was rather acceptable. But
with increasing focus on screening of colorectal cancer espe-
cially in developed countries and the adoption of colonoscopy,
the impact of higher demand for colonoscopy could lead to
further delays in the detection of newly diagnosed colorectal
cancers. Hence, the need for stratification patients who need
it more expediently than others has to be considered by cli-
nicians and administrators alike.
It is understandable that patients with colorectal cancers
who are not anemic on presentation would have their pro-
cedure delayed further as a consequence, with implications
on their resultant prognosis. This issue is real with only 23% of
colorectal cancers noted to have anemia on presentation.14 It
is however more likely that this group of patients should have
smaller cancers and should translate to an earlier stage dis-
4
ease.15 To add to that, FIT has a sensitivity of 88% and it is
4
3 reasonable to assume a proportion of colorectal cancer pa-
1 tients may test negative on FIT.16 The urgency of the colono-
scopic procedure should thus not be based on hemoglobin
3 level alone. Other factors such as chronicity of symptoms,
1 strong family history and of course positive physical signs of
2
masses on examination are equally important and would
2
0
render the need for earlier colonoscopy.
1 On the other hand, the authors do acknowledge the im-
4 plications of adopting this outpatient hemoglobin evaluation
2 in all patients with a positive FIT. The anxiety associated with
a positive test of anemia coupled with other possible unnec-
essary tests such as gastroscopy and even small bowel eval-
uation can be equally undesirable. Thus, a bigger scale
prospective study to evaluate the cost effectiveness of this
proposed test has to be performed before drawing any con-
crete conclusions.
Some of the limitations of our current study design include
its retrospective nature and its associated biases along with
the small number of patients. The highly selective process will
also likely limit the generalizability of our results to the other
communities. Our FIT positive patients were referred from
outpatient setting and it is likely that a significant proportion
of participants who tested positive refused further in-
vestigations and referrals. This forms the basis of our current
public health endeavor to determine the barriers precluding
further evaluation and thereby implementing interventions to
address them with the ultimate aim of improving earlier
detection and increase rates of primary prevention. However,
the authors do believe that further stratification of these pa-
tients could potentially lead to better utilization of existing
limited resources. Going ahead, further well-designed pro-
spective studies are necessary to validate the true efficacy of
hemoglobin tests in patients with positive FIT.
Conclusion
Colorectal cancer patients presenting with a positive FIT are
more likely to be anemic. There is a need to look into the
utilization of quick and easily administered tools in the
outpatient setting to identify the anemic patients and priori-
tize their colonoscopy appointments.
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