The American Journal of Surgery (2015) 210, 106-110

Clinical Science

The influence of mechanical bowel preparation

on long-term survival in patients surgically
treated for colorectal cancer
Hans Pieter vant Sant, M.D.a,*, Arnoud Kamman, M.D.a,
Wim C. J. Hop, Ph.D.b, Martijn van der Heijden, M.D.a,
Johan F. Lange, M.D., Ph.D.c, Caroline M. E. Contant, M.D., Ph.D.d
a

Department of Surgery, Ikazia Hospital, Montessoriweg 1, 3083 AN Rotterdam, The Netherlands;

Department of Biostatistics, cDepartment of Surgery, Erasmus University Medical Center, Rotterdam,
The Netherlands; dDepartment of Surgery, Maasstad Hospital, Rotterdam, The Netherlands

KEYWORDS:
Survival;
Colorectal cancer;
Surgery

Abstract
BACKGROUND: In this study, we evaluated long-term survival in patients treated with and without
mechanical bowel preparation (MBP) before colorectal surgery for cancer.
METHODS: Long-term outcome of patients of 2 main participating hospitals in a prior multicenter
randomized trial comparing clinical outcome of MBP versus no MBP was reviewed. Primary endpoint
was cancer-related mortality and secondary endpoint was all-cause mortality.
RESULTS: A total of 382 patients underwent potentially curative surgery for colorectal cancer. One
hundred seventy-seven (46%) patients were treated with MBP and 205 (54%) were not before surgery.
Median follow-up was 7.6 years (mean 6.6, range .01 to 12.73). There was no significant difference in
both cancer-related mortality and all-cause mortality in patients treated with MBP and without MBP (P
5 .76 and P 5 .36, respectively). Multivariate analysis, taking account of age, sex, AJCC cancer stage,
and ASA classification, also showed no survival difference.
CONCLUSIONS: Our results indicate that MBP does not seem to influence long-term survival in patients surgically treated for colorectal cancer.
2015 Elsevier Inc. All rights reserved.

There were no relevant financial relationships or any sources of support

in the form of grants, equipment, or drugs.
The authors declare no conflicts of interest.
Trial registration number for the randomized clinical trial this article
derived from was NCT00288496.
* Corresponding author. Tel.: 131-633332710; fax: 131-102975130.
E-mail address: hpieter44@hotmail.com
Manuscript received January 29, 2014; revised manuscript October 4,
2014
0002-9610/$ - see front matter 2015 Elsevier Inc. All rights reserved.
http://dx.doi.org/10.1016/j.amjsurg.2014.10.022

Traditionally, mechanical bowel preparation (MBP) was

believed to clean the colon and rectum from residual fecal
contents and lower the bacterial load to prevent anastomotic failure and reduce postoperative infectious complications.1 To date, however, there is significant evidence that
questions the beneficial effects of MBP. Recent systematic
reviews and meta-analyses of randomized controlled trials
have shown no evidence that MBP is associated with
reduced rates of anastomotic leakage or septic complications after elective colorectal surgery.24 Most studies

H.P. vant Sant et al.

MBP and survival for colorectal cancer

only evaluated the effects of MBP on short-term outcomes

and studies on the effects of long-term outcomes are scarce,
especially cancer related. At present, there is strong
evidence that postoperative complications influence the
long-term outcome and survival in patients with colorectal
cancer. Patients confronted with anastomotic leakage have
poorer long-term cancer-specific survival rates.57 In this
study, we tested the hypothesis that MBP has no positive influence on cancer-specific long-term survival (.6 years) after colorectal cancer surgery as MBP is not associated with
reduced anastomotic leakage rates in literature.

Methods
This study is a subgroup analysis of a prior large
multicenter randomized clinical trial published by Contant
et al.8 They enrolled 1,354 patients from 1998 to 2004 and
randomized between MBP and no MBP before elective
colorectal surgery and compared the incidence of anastomotic leakage and septic complications. Patients randomized for MBP received 2 to 4 l of polyethylene glycol
bowel lavage solution (***Klean Prep) in combination
with ***bisacodyl (11 hospitals) or sodium phosphate solution (2 hospitals). Exclusion criteria were an acute laparotomy, laparoscopic colorectal surgery, contraindications for
the use of MBP, an a priori diverting ileostomy, and age
less than 18 years old.
In the present subgroup analysis, 382 patients of 2 main
participating hospitals in the previously mentioned randomized trial were selected by the criteria of having
undergone potentially curative elective colorectal surgery
for cancer (Fig. 1). Clinical data were obtained through the
previous study by Contant et al8 with permission and linked
to death records to create a novel dataset. Death records up
to December 31, 2010 were obtained. The diagnosis of
colorectal cancer was confirmed by pathology reports. Cancer stage was determined through pathology reports, radiology reports, and clinical audit records. Our primary

Figure 1

107
endpoint was cancer-related mortality and secondary
endpoint was all-cause mortality.

Statistical analysis
KaplanMeier curves for overall and colon cancerspecific survival and log-rank tests were used to compare
the MBP arms. In the calculation of cancer-specific
survival, the survivals*** of patients who had died because
of other causes were considered censored*** survival
times. As the large majority of deaths were because of
cancer and there were only a few patients who had died
from an unknown cause, the latter patients were considered
to have died from cancer. Cox-regression analysis was used
to assess the independent effect of various putative
prognostic factors (age, sex, cancer stage, and ASA
classification) besides MBP. Analysis was by intention-totreat. Two-sided P value of less than .05 was considered
statistically significant.

Results
Data were collected from 382 patients retrospectively.
Patient selection is shown in Fig. 1. One hundred seventyseven (46%) patients were treated with MBP before surgery
and 205 (54%) were not. Baseline characteristics of patients are shown in Table 1 and were well balanced between
treatment groups. Overall median follow-up was 7.6 (mean
6.6, range .01 to 12.73) years. Median follow-up for MBP1
was 7.8 (mean 6.8, range .01 to 12.6) and for MBP2 was
7.4 (mean 6.4, range .01 to 12.7). One hundred ninetythree patients deceased during follow-up. Cancer-related
deaths occurred in 128 patients. Noncancer-related deaths
occurred in 48 patients. In 17 patients, the cause of death
could not be discovered. There was no significant difference in both overall mortality and cancer-related mortality
in patients treated with MBP and without MBP before elective colorectal surgery for cancer (log-rank test, P 5 .36

Organization chart for patient selection.9

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The American Journal of Surgery, Vol 210, No 1, July 2015

Table 1 Baseline characteristics of 382 patients undergoing

elective surgical treatment for colorectal cancer

Sex
Male
Female
Age (years)
%60
6170
.70
Cancer stage*
I
II
III
IV
ASA classification
I
II
III/IV
Adjuvant chemotherapy
Radiation therapy

MBP2
(n 5 205)

MBP1
(n 5 177)

98 (48%)
107 (52%)

91 (51%)
86 (49%)

50 (24%)
70 (34%)
85 (42%)

42 (24%)
56 (32%)
79 (44%)

34
98
55
18

(16%)
(48%)
(27%)
(9%)

35
77
51
14

(20%)
(43%)
(29%)
(8%)

57
113
35
47
12

(28%)
(55%)
(17%)
(23%)
(6%)

39
116
22
32
18

(22%)
(66%)
(12%)
(18%)
(10%)

ASA 5 American Society of Anesthesiologists; MBP 5 mechanical

bowel preparation.
*Colon and rectum cancer stage according to the American Joint
Committee on Cancer.

and P 5 .76, respectively; Fig. 2). Thirty-day mortality for

the groups with and without MBP was 4.0% (7/177) and
2.4% (5/205), respectively (P 5 .58).
Cancer-specific survival at 5- and 10 years in the MBP1
arm was 67% (64% standard error) and 59% (64%),

respectively. In the MBP2 arm, these figures were 68%

(63%) and 60% (64%), respectively (Fig. 2).
Overall survival at 5- and 10 years in the MBP1 arm
was 64% (64%) and 54% (64%), respectively. In the
MBP2 arm, these figures were 62% (63%) and 47%
(64%), respectively (Fig. 2).
Also within the separate cancer stages, there were no
significant differences in overall and cancer-specific survival between the MBP arms (all P . .31). Cox-regression
analysis, allowing for age, sex, cancer stage, and ASA classification, also showed no significant differences between
the 2 MBP arms (Table 2). Further extension of the Cox
models with interaction terms to investigate whether the
baseline characteristics influenced the difference between
the 2 MBP arms showed no significant effect of any of
the characteristics. Also, the treatment center did not affect
the survival outcomes.
Postoperative complication rates between patients
treated with and without MBP are shown in Table 3.

Comments
Sufficient evidence has shown that anastomotic leakage
is associated with a higher prevalence of local recurrence
and diminished long-term survival after elective colorectal
cancer surgery.57 Recent meta-analysis and systematic reviews show no difference in anastomotic leakage rates
comparing MBP versus no MBP. Only Slim et al9 published
a meta-analysis in 2004 and found significantly more anastomotic leakage after MBP (5.6% vs 3.2%, P 5 .032).
However, a more recent meta-analysis also by Slim et al
invalidate this outcome having added 2 large randomized

Figure 2 KaplanMeier survival curves for OS and CaS for patients treated with and without MBP before elective colorectal surgery for
cancer. CaS 5 cancer-specific survival; OS 5 overall survival.

H.P. vant Sant et al.

MBP and survival for colorectal cancer

109

Table 2 Multivariate analyses of various factors in relation to cancer-related and all-cause mortality after elective colorectal resection
for cancer
Cancer-related mortality
MBP
No
Yes
Sex
Female
Male
Age
%60
6170
.70
Cancer stage
I
II
III
IV
ASA classification
I
II
III/IV

All-cause mortality

Hazard ratio

95% CI

P value

Hazard ratio

95% CI

P value

1.00
.94

.671.32

.73

1.00
.81

.611.09

.16

1.00
1.14

.811.61

.46

1.00
1.23

.911.65

.17

1.00
1.10
2.77

.641.91
1.594.84

.73
,.001

1.00
1.28
2.56

.802.05
1.604.11

.30
,.001

1.00
2.67
6.91
41.01

1.205.91
3.1215.28
17.6095.58

.02
,.001
,.001

1.00
1.57
2.97
17.86

.952.61
1.765.00
9.7732.66

.08
,.001
,.001

1.00
1.11
2.36

.671.85
1.284.35

.68
.006

1.00
1.38
3.05

.892.14
1.815.13

.15
,.001

ASA 5 American Society of Anesthesiologists; CI 5 confidence interval; MBP 5 mechanical bowel preparation.

Contant et al8 showed that MBP was associated with fewer

intra-abdominal abscesses after anastomotic leakage
compared with no MBP in elective colorectal surgery.
However, both studies show no difference in anastomotic
leakage rates. In summary, this leaves us with controversial
effects of MBP on anastomotic leakage and postoperative
infection rates. As a result the influence of applying or
withholding MBP on survival in patients surgically treated
for colorectal cancer remains unpredictable and unclear.
When looking at literature regarding MBP and longterm survival, Nicholson et al retrospectively collected data
of 1,730 patients who underwent potentially curative
colorectal cancer surgery.15 One thousand four hundred
sixty patients were treated with MBP and 270 patients
were not. Median follow-up was 3.5 (range .1 to 6.7) years.
They found a 28% survival benefit in favor of patients
treated with MBP (HR*** .72, .57 to .91) (P 5 .005).

controlled trials to their data and find no difference in anastomotic leakage rate between MBP and no MBP.2,8,10 Other
effects of MBP on postoperative complications have been
thoroughly investigated presenting controversial results.
Bucher et al11,12 suggest that MBP is associated with structural alteration and inflammatory changes in the large
bowel wall and that MBP is associated with higher postoperative morbidity rates in elective left-sided colorectal surgery. This is supported by Bretagnol et al, who noted that
MBP was associated with a significantly higher rate of infectious extra-abdominal complications.7 Mean hospital
stay was significantly longer for patients treated with
MBP in both studies.11,13 In contrast, authors of the French
Greccar III trial demonstrated that rectal cancer surgery
without MBP was associated with higher risk of overall
and infectious morbidity rates and suggest continuing to
perform MBP before elective rectal resection for cancer.14

Table 3

Complication rate after elective surgery for patients with colorectal cancer with and without preoperative MBP

Complication

MBP1 (n 5 177)

MBP2 (n 5 205)

No. of patients with complications*

Anastomotic leakage
Wound infection
Urinary tract infection
Pneumonia
Intra-abdominal abscess
Fascia dehiscence

59
7
18
12
14
6
2

82
8
25
18
16
9
6

MBP 5 mechanical bowel preparation.

*Patients can have more than one complication at a time.

(33%)
(4%)
(10%)
(7%)
(8%)
(3%)
(1%)

(40%)
(4%)
(12%)
(3%)
(8%)
(4%)
(3%)

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The American Journal of Surgery, Vol 210, No 1, July 2015

However, this survival advantage was no longer significant

after adjustment for presentation for surgery (HR .85, .67 to
1.10) (P 5 .220). This can be clearly explained because of
the fact that patients undergoing emergency surgery are
usually not treated with MBP and that the emergency
setting is associated with poorer outcome.16,17 The authors
of this study conclude that neither postoperative complications nor long-term survival are improved by MBP in regards to colonic cancer. However, this retrospective
cohort study has several limitations. Their main conclusion
was based on all-cause mortality and not on cancer-related
mortality. In addition, patients were not randomized between MBP and no MBP and the decision for applying
MBP was solely made ad hoc by the medical staff before
surgery, creating a potential source of bias.
The results of the underlying study show that MBP has
no influence on all-cause and cancer-related long-term
survival in patients surgically treated for colorectal cancer
with a median follow-up of 6.7 years. Adverse events
relating to colorectal cancer survival would be expected
within this time frame. These findings were expected as we
found no difference in anastomotic leakage and other
postoperative morbidity rates between the MBP1 and
MBP2 groups in this study. One of the limitations of this
study is the selection procedure. We selected patients from
only 2 of the 13 hospitals who participated in a previous
randomized trial comparing the anastomotic leakage rate in
patients treated with and without MBP.8 By selecting patients only surgically treated for cancer, we created an
imbalance between MBP1 and MBP2 (177 vs 205,
respectively) and a possible selection bias cannot be
excluded. An additional limitation is that in 17 patients
the cause of death could not be recollected. For these 17 patients, cancer-related mortality was both calculated when
deaths were presumed cancer related and when left out.
There were no differences between both calculations.
Data are only shown when deaths were presumed cancer
related as this is most probable. As survival depends on
many factors, our study is underpowered. A large randomized trial would be preferable with long-term survival as
primary endpoint in a cancer-related patient group.
In conclusion, our results from a subgroup of a randomized trial suggest confirmation of our hypothesis that MBP
has no influence on long-term survival in patients surgically
treated for colorectal cancer. However, more research is
required to draw firm conclusions.

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