Cochrane Database of Systematic Reviews

Cholecystectomy for gallbladder polyp (Review)

Gurusamy KS, Abu-Amara M, Farouk M, Davidson BR

Gurusamy KS, Abu-Amara M, Farouk M, Davidson BR.

Cholecystectomy for gallbladder polyp.
Cochrane Database of Systematic Reviews 2009, Issue 1. Art. No.: CD007052.
DOI: 10.1002/14651858.CD007052.pub2.

www.cochranelibrary.com

Cholecystectomy for gallbladder polyp (Review)

Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 TABLE OF CONTENTS
HEADER . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
ABSTRACT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
PLAIN LANGUAGE SUMMARY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
BACKGROUND . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
OBJECTIVES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
METHODS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
RESULTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
DISCUSSION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
AUTHORS’ CONCLUSIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
ACKNOWLEDGEMENTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
DATA AND ANALYSES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
APPENDICES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
WHAT’S NEW . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
CONTRIBUTIONS OF AUTHORS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
DECLARATIONS OF INTEREST . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
SOURCES OF SUPPORT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
DIFFERENCES BETWEEN PROTOCOL AND REVIEW . . . . . . . . . . . . . . . . . . . . . 12
INDEX TERMS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12

Cholecystectomy for gallbladder polyp (Review) i

Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
[Intervention Review]

Cholecystectomy for gallbladder polyp

Kurinchi Selvan Gurusamy1 , Mahmoud Abu-Amara1 , Marwan Farouk2 , Brian R Davidson1

1 University
Department of Surgery, Royal Free Hospital and University College School of Medicine, London, UK. 2 Surgery, Bucking-
hamshire Hospitals NHS Trust, Aylesbury, UK

Contact address: Kurinchi Selvan Gurusamy, University Department of Surgery, Royal Free Hospital and University College School of
Medicine, 9th Floor, Royal Free Hospital, Pond Street, London, NW3 2QG, UK. kurinchi2k@hotmail.com.

Editorial group: Cochrane Hepato-Biliary Group.

Publication status and date: New, published in Issue 1, 2010.
Review content assessed as up-to-date: 9 July 2008.

Citation: Gurusamy KS, Abu-Amara M, Farouk M, Davidson BR. Cholecystectomy for gallbladder polyp. Cochrane Database of
Systematic Reviews 2009, Issue 1. Art. No.: CD007052. DOI: 10.1002/14651858.CD007052.pub2.

Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

ABSTRACT

Background

The management of gallbladder polyps is controversial. Cholecystectomy has been recommended for gallbladder polyps larger than 10
mm because of the association with gallbladder cancer. Cholecystectomy has also been suggested for gallbladder polyps smaller than
10 mm in patients with biliary type of symptoms.

Objectives

The aim of this review is to compare the benefits (relief of symptoms, decreased incidence of gallbladder cancer) and harms (surgical
morbidity) of cholecystectomy in patients with gallbladder polyp(s).

Search methods

We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL)
in The Cochrane Library, MEDLINE, EMBASE, and Science Citation Index Expanded until July 2008 to identify the randomised trials.

Selection criteria

Only randomised clinical trials (irrespective of language, blinding, or publication status) comparing cholecystectomy and no cholecys-
tectomy were considered for the review.

Data collection and analysis

We planned to collect the data on the characteristics, methodological quality, mortality, number of patients in whom symptoms were
improved or cured from the one identified trial. We planned to analyse the data using the fixed-effect and the random-effects models
using RevMan Analysis. For each outcome we planned to calculate the risk ratio (RR) with 95% confidence intervals based on intention-
to-treat analysis.

Main results

We were unable to identify any randomised clinical trials comparing cholecystectomy versus no cholecystectomy in patients with a
gallbladder polyp.
Cholecystectomy for gallbladder polyp (Review) 1
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Authors’ conclusions

There are no randomised trials comparing cholecystectomy versus no cholecystectomy in patients with gallbladder polyps. Randomised
clinical trials with low bias -risk are necessary to address the question of whether cholecystectomy is indicated in gallbladder polyps
smaller than10 mm.

PLAIN LANGUAGE SUMMARY

No evidence from randomised clinical trials for optimal treatment for gallbladder polyp

The management of gallbladder polyp is controversial. Removal of the gallbladder (cholecystectomy) for gallbladder polyps larger than
10 mm has been recommended because of the association between polyps larger than 10 mm and gallbladder cancer. Cholecystectomy
is often recommended for patients with biliary type pain and polyps smaller than 10 mm. There has been no randomised clinical trial
comparing cholecystectomy with observation for gallbladder polyps. Randomised clinical trials with low bias-risk (low likelihood of
systematic error) are necessary to evaluate the role of cholecystectomy in gallbladder polyps smaller than 10 mm.

BACKGROUND cholecystectomy has been currently been recommended in polyps

Gallbladder polypoid lesions are elevations in the gallbladder
mucosa (Chattopadhyay 2005). The prevalence of polypoid le-
sions in the gallbladders of healthy adults varies between 0.3%
to 12.3% (Hayashi 1996; Pandey 1996; Okamoto 1999; Lin
2008). Between 0.6% and 4% of the cholecystectomies are car-
ried out for gallbladder polyps (Jones-Monahan 2000; Yeh 2001;
Chattopadhyay 2005). These polypoidal lesions could be benign
or malignant (Mainprize 2000; Terzi 2000; Yeh 2001; Sun 2004;
Chattopadhyay 2005). The benign tumours could be neoplas-
tic (adenoma, leiomyoma) or non-neoplastic (cholesterol polyps,
adenomyosis) (Mainprize 2000). The management of gallbladder
polyp is controversial. Currently, it is recommended that polyps
larger than 10 mm in size on the transabdominal ultrasound are
removed by a cholecystectomy because of the association between
polyps larger than 10 mm and gallbladder cancer (Mainprize
2000; Terzi 2000; Huang 2001; Yeh 2001; Lee 2004; Sun 2004;
Chattopadhyay 2005). The incidence of polyps smaller than 10
mm was between 0% to 5% (Mainprize 2000; Terzi 2000; Csendes
2001; Huang 2001; Yeh 2001; Chattopadhyay 2005). Between
45% and 67% of polyps larger than 10 mm to 15 mm were ma-
lignant (Mainprize 2000; Terzi 2000; Yeh 2001; Chattopadhyay
2005). Apart from the size of the polyp, higher age of the patient
(Terzi 2000; Huang 2001; Yeh 2001; Sun 2004), solitary polyp
(Yeh 2001; Sun 2004), sessile polyp (Sugiyama 1999), concur-
rent gallstones (Lee 2004), and presence of symptoms (Lee 2004)
have all been implicated as factors associated with an increased
risk of malignancy in the polyp. Cholecystectomy has also been
recommended for smaller polyps, irrespective of size, because of
the relief of gallbladder symptoms (Huang 2001). Thus , currently
Cholecystectomy for gallbladder polyp (Review)
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
larger than 10 mm because of the high risk of malignancy and in
symptomatic polyps smaller than 10 mm .
Laparoscopic cholecystectomy (key hole removal of gallbladder) is
currently preferred over open cholecystectomy for elective chole-
cystectomy (NIH 1992; Fullarton 1994; Livingston 2004; Keus
2006). However, open cholecystectomy has been recommended
in gallbaldder polyps larger than 18 mm in size because of the risk
of invasion of surrounding structures by malignancy (Lee 2004).
Cholecystectomy is not without complications. The complica-
tions include mortality due to the various complications: injury
to vessels or bowel (Fletcher 1999) during port insertion for la-
paroscopic cholecystectomy, and bile duct injury. The reported
incidence of bile duct injury is between 0.3% (Richardson 1996;
Krahenbuhl 2001) and 1% (Buanes 1996; Gurusamy 2006). Ma-
jor bile duct injuries can be fatal due to sepsis (Sicklick 2005). Cor-
rective surgery for bile duct injury carries its own risks that include
mortality (Schmidt 2005; Sicklick 2005), bile leak (Schmidt 2005;
Sicklick 2005), cholangitis (Johnson 2000; Schmidt 2005; Sicklick
2005), biliary stricture (Johnson 2000; Huang 2003; Schmidt
2005), and biliary cirrhosis (Schmidt 2005). Bile leak may re-
quire endoscopic retrograde cholangio pancreatography (ERCP)
(Johansson 2003; Kimura 2005). ERCP has its own risks of mor-
tality, pancreatitis, haemorrhage, and perforation (Christensen
2004).
Csendes et al report that it is safe to follow-up gallbladder polyps
smaller than 10 mm based on their follow-up of 98 patients for
a mean period of six years when none of the patients developed
gallbladder cancer (Csendes 2001). Using endoscopic ultrasound,
2
it is possible to distinguish neoplastic and non-neoplastic polyps
reliably (Sugiyama 1999). This may raise the possibility of safe
follow-up of polyps even larger than 10 mm. More than half of the
polyps are non-neoplastic cholesterol polyps (Shinkai 1998; Terzi
2000; Huang 2001; Sun 2004), which are not associated with
an increased risk of malignancy. Lee et al, based on their review
of literature, suggest that gallbladder carcinomas arises de novo
rather than a polyp-carcinoma sequence (Lee 2004); ie, polyps
do not turn into cancer; cancers present as polyps. All the above
factors suggest the possibility of safe follow-up of selected polyps.
There have been no systematic reviews or meta-analyses comparing
cholecystectomy and no cholecystectomy for gallbladder polyps.
OBJECTIVES
To compare the benefits (relief of symptoms, decreased incidence
of gallbladder cancer) and harms (surgical morbidity) of cholecys-
tectomy in patients with gallbladder polyp(s).
METHODS
Criteria for considering studies for this review
Types of studies
We considered all randomised clinical trials, which compare chole-
cystectomy (open or laparoscopic) versus no cholecystectomy (ir-
respective of language, blinding, publication status, sample size, or
whether the trials were adequately powered) in patients with gall-
bladder polyp(s). We also included trials comparing laparoscopic
cholecystectomy with open cholecystectomy in patients with gall-
bladder polyp(s). We did not consider quasi-randomised studies
for inclusion.
Types of participants
Patients with gallbladder polyp(s) (irrespective of the size of the
polyp).
Types of interventions
1. Cholecystectomy (open or laparoscopic) versus no
cholecystectomy.
2. Laparoscopic cholecystectomy versus open cholecystectomy.
Cholecystectomy for gallbladder polyp (Review)
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Types of outcome measures
Primary outcomes
1. Mortality at maximal follow-up.
2. Procedure-related morbidity, such as injury to common bile
duct, cholangitis, bile leak, biliary peritonitis, wound infection.
3. Number of patients with gallbladder cancer (within six
months of diagnosis and after six months of diagnosis).
Secondary outcomes
1. Number of re-operations/completion surgeries required
because of diagnosis of malignancy in gallbladder polyps.
2. Number of outpatient visits to doctor for biliary symptoms
or anxiety (including planned reviews).
3. Number of hospital admissions for biliary symptoms.
4. Relief of biliary symptoms.
5. Total hospital stay.
6. Patient anxiety (however defined by authors).
7. Quality of life (however defined by authors).
Search methods for identification of studies
We searched The Cochrane Hepato-Biliary Group Controlled Tri-
als Register (Gluud 2008), the Cochrane Central Register of Con-
trolled Trials (CENTRAL) in The Cochrane Library, MEDLINE,
EMBASE, and Science Citation Index Expanded (Royle 2003). We
have given the search strategies in Appendix 1 with the time span
for the searches.
Data collection and analysis
Trial selection and extraction of data
The first two authors, KSG and MA, independently of each other,
identified the trials for inclusion and also planned to list the ex-
cluded studies with the reasons for the exclusion.
KSG and MA planned to extract the following data, independently
of each other.
1. Year and language of publication.
2. Country.
3. Year of conduct of the trial.
4. Inclusion and exclusion criteria.
5. Diagnostic tests performed.
6. Sample size.
7. Number of patients in each trial arm that crossed over to
the other trial arm.
8. Population characteristics such as age and sex ratio.
9. Cut-off value for operating on gallbladder polyp.
3
 10. Cut-off value for diagnosis of gallbladder polyp.
11. Open or laparoscopic cholecystectomy.
12. Outcomes (mentioned above).
13. Methodological quality (described below).
14. Sample size calculation.
KSG and MA planned to seek any unclear or missing information
by contacting the authors of the individual trials. If there was any
doubt whether the trials shared the same patients - completely or
partially (by identifying common authors and centres), KSG and
YK planned to contact the authors of the trials to clarify whether
the trial report had been duplicated.
We planned to resolve any differences in opinion through discus-
sion using BRD as adjudicator.
Assessment of methodological quality
Methodological quality was defined as the confidence that the de-
sign and the report of the randomised clinical trial would restrict
bias in the comparison of the intervention (Moher 1998). Accord-
ing to empirical evidence (Schulz 1995; Moher 1998; Kjaergard
2001; Wood 2008), we planned to assess the methodological qual-
ity of the trials based on sequence generation, allocation conceal-
ment, blinding of (participants, personnel, and outcome asses-
sors), incomplete outcome data, selective outcome reporting, and
other sources of bias. Quality components were classified as fol-
lows:
Sequence generation
• Low risk of bias (the methods used is either adequate (eg,
computer generated random numbers, table of random
numbers) or unlikely to introduce confounding).
• Uncertain risk of bias ( there is insufficient information to
assess whether the method used is likely to introduce
confounding).
• High risk of bias (the method used (eg, quasi-randomised
trials) is improper and likely to introduce confounding).
Allocation concealment
• Low risk of bias (the method used (eg, central allocation) is
unlikely to induce bias on the final observed effect).
• Uncertain risk of bias (there is insufficient information to
assess whether the method used is likely to induce bias on the
estimate of effect).
• High risk of bias (the method used (eg, open random
allocation schedule) is likely to induce bias on the final observed
effect).
Blinding of participants, personnel, and outcome assessors
Cholecystectomy for gallbladder polyp (Review)
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
It is difficult to blind surgeons to the groups. Thus only blinding
of patients and outcomes assessors were considered for assessing
the risk of bias.
• Low risk of bias (blinding was performed adequately, or the
outcome measurement is not likely to be influenced by lack of
blinding).
• Uncertain risk of bias (there is insufficient information to
assess whether the type of blinding used is likely to induce bias
on the estimate of effect).
• High risk of bias (no blinding or incomplete blinding, and
the outcome or the outcome measurement is likely to be
influenced by lack of blinding).
Incomplete outcome data
• Low risk of bias (the underlying reasons for missingness are
unlikely to make treatment effects departure from plausible
values, or proper methods have been employed to handle missing
data).
• Uncertain risk of bias (there is insufficient information to
assess whether the missing data mechanism in combination with
the method used to handle missing data is likely to induce bias
on the estimate of effect).
• High risk of bias (the crude estimate of effects (eg, complete
case estimate) will clearly be biased due to the underlying reasons
for missingness, and the methods used to handle missing data are
unsatisfactory).
Selective outcome reporting
• Low risk of bias (the trial protocol is available and all of the
trial’s pre-specified outcomes that are of interest in the review
have been reported or similar).
• Uncertain risk of bias (there is insufficient information to
assess whether the magnitude and direction of the observed
effect is related to selective outcome reporting).
• High risk of bias (not all of the trial’s pre-specified primary
outcomes have been reported or similar).
Other bias
Baseline imbalance
• Low risk of bias (there was no baseline imbalance in
important characteristics).
• Uncertain risk of bias (the baseline characteristics were not
reported).
• High risk of bias (there was an baseline imbalance due to
chance or due to imbalanced exclusion after randomisation).
4
Early stopping
• Low risk of bias (sample size calculation was reported and
the trial was not stopped or the trial was stopped early by a
formal stopping rule at a point where the likelihood of observing
an extreme intervention effect due to chance was low).
• Uncertain risk of bias (sample size calculations were not
reported and it is not clear whether the trial was stopped early or
not).
• High risk of bias (the trial was stopped early due to an
informal stopping rule or the trial was stopped early by a formal
stopping rule at a point where the likelihood of observing an
extreme intervention effect due to chance was high).
Academic bias
• Low risk of bias (the author of the trial has not conducted
previous trials addressing the same interventions).
• Uncertain risk of bias (It is not clear if the author has
conducted previous trials addressing the same interventions).
• High risk of bias (the author of the trial has conducted
previous trials addressing the same interventions).
Source of funding bias
• Low risk of bias (the trial’s source(s) of funding did not
come from any parties that might conflicting interest (eg,
instrument manufacturer).
• Uncertain risk of bias (the source of funding was not clear).
• High risk of bias (the trial was funded by an instrument
manufacturer).
We would have considered trials which were classified as low risk
of bias in sequence generation, allocation concealment, blinding,
incomplete data, and selective outcome reporting as low bias-risk
trials.
Statistical methods
We planned to perform the meta-analyses according to the recom-
mendations of The Cochrane Collaboration (Higgins 2008) and
the Cochrane Hepato-Biliary Group Module (Gluud 2008) using
the software package RevMan 5 (RevMan 2008). For dichoto-
mous variables, we planned to calculate the risk ratio (RR) with
95% confidence interval. For continuous variables, we planned
to calculate the mean difference (MD) for outcomes like hospital
stay and the standardised mean difference (SMD) for outcomes
like quality of life (where different scales might be used) with 95%
confidence interval. We planned to use a random-effects model
(DerSimonian 1986) and a fixed-effect model (DeMets 1987). In
case of discrepancy between the two models we planned to re-
port both results; otherwise we planned to report only the results
from one of the models based on the heterogeneity. We planned
to explore heterogeneity by chi-squared test with significance set
Cholecystectomy for gallbladder polyp (Review)
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
at P value 0.10, and measure the quantity of heterogeneity by I2
(Higgins 2002). An I2 of 30% or more was to be considered to
represent statistical heterogeneity.
We planned to adopt the ’intention-to-analysis’ whenever possible
(Newell 1992). Otherwise, we planned to adopt the ’available-case
analysis’. In case we found ’zero-event’ trials in statistically signif-
icant outcomes, we planned to perform a sensitivity analysis with
and without empirical continuity correction factors as suggested
by Sweeting et al (Sweeting 2004). We also planned to report the
results of risk difference.
Subgroup analysis
We planned to perform the following subgroup analyses.
• Trials with low bias-risk (see section ’assessment of
methodological quality’) compared to trials with high bias-risk.
• Different polyp sizes.
• Open and laparoscopic cholecystectomy.
Bias exploration
We planned to use a funnel plot to explore bias (Egger 1997;
Macaskill 2001). We planned to use asymmetry in funnel plot of
trial size against treatment effect to assess this bias. We also planned
to perform linear regression approach described by Egger et al to
determine the funnel plot asymmetry (Egger 1997).
RESULTS
Description of studies
We identified a total of 32 references through electronic searches
of The Cochrane Hepato-Biliary Group Controlled Trials Regis-
ter and the Cochrane Central Register of Controlled Trials (CEN-
TRAL) in The Cochrane Library (n = 2), MEDLINE (n = 24),
EMBASE (n = 3), and Science Citation Index Expanded (n = 3).
We excluded 5 duplicates. It was clear from reading titles and ab-
stracts that none of the remaining 27 references were randomised
clinical trials. Although we would have excluded quasi-randomised
trials, we searched for any quasi-randomised trial in order to cal-
culate the sample size and outcomes that can be used for any new
randomised clinical trial. We were not able to identify any quasi-
randomised trial also from the retrieved references.
Risk of bias in included studies
None of the studies identified through the search strategy qualified
for inclusion in this review. We were also unable to identify any
5
cohort studies or any case-control studies that could meaningfully
try to answer the questions posed in this systematic review.
Effects of interventions
None of the studies identified through the search strategy qualified
for this review.
DISCUSSION
None of the studies identified through the search strategy qualified
for this review. We were also unable to identify non-randomised
controlled studies, which could give information to facilitate the
design of a randomised clinical trial or answer the posed question.
Therefore, there seems to be an urgent need for trials on how to
treat patients with gallbladder polyps.
For patients with asymptomatic gallbladder polyps smaller than
10 mm, randomised clinical trial design is appropriate. There are
four problems expected in such a randomised clinical trial. The
first problem is with blinding. It is not possible to blind operating
health-care provider to the treatment group. However, it is possible
to perform observer blinding for most outcomes. Patients cannot
be easily blinded. Only a sham operation can blind the patients.
The sham operation is not difficult and does not endanger the
patient in any way as this involves a skin deep umbilical scar (1 cm),
a skin deep upper abdominal scar (1 cm), and 2 subcostal scars (5
mm each) under local anaesthetic. The patients have to be sedated
for this for about 30 to 45 minutes, but this carries a very small risk
of any mishap. The treatment group would also require to have
local anaesthetic wound infiltration so that it is not possible to
identify the group of the patients by finding out if there was a local
anaesthetic wound infiltration or not. Local anaesthetic wound
infiltration is safe in laparoscopic cholecystectomy (Gurusamy
2008). Thus, one has to balance between the risk of providing
(a large number of patients) a treatment based on biased trials or
subject a small number of patients to tiny incisions under sedation
to obtain a relatively unbiased effect estimate. While there are little
concerns about the safety of the ’sham operation’, the patients
may prefer to not have scars which do not result in a definitive
treatment of their symptoms.
The second problem is the way in which the people with increase
in size of the polyp or development of symptoms during ultra-
sound follow-up in the ’no cholecystectomy’ group are dealt with.
These patients would need to be operated upon. However, in or-
der to assess the interventions appropriately, an intention-to-treat
analysis has to be used. The third problem would be sample size
calculation. One of the main concerns about gallbladder polyp is
gallbladder cancer. However, the incidence of gallbladder cancer
in the gallbladder polyps is very low, with most studies reporting
Cholecystectomy for gallbladder polyp (Review)
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
that the size of gallbladder polyps with cancer being larger than
10 mm. The other possible outcome is biliary pain. The incidence
of this complication is also low in patients with asymptomatic
gallbladder polyps (Csendes 2001). In this study, none of the 98
patients developed symptoms after a mean follow-up of six years.
The fourth problem is the loss of patients to follow-up. Choos-
ing gallbladder cancer or biliary pain as the main outcome for
the trial, the number of patients included in the trial will be high
and the duration of follow-up will have to at least 10 years to get
meaningful results. Some patients are likely to be lost to follow-
up resulting in missing outcome bias in such a trial.
For patients with gallbladder polyps associated with pain symp-
toms, non-randomised studies have shown that cholecystec-
tomy offers good pain relief in more than 90% of the patients
(Jones-Monahan 2000). While there are no randomised clinical
trials to demonstrate the benefit of cholecystectomy in symp-
tomatic gallbladder polyps smaller than 10 mm, any such ran-
domised clinical trial will have relief of pain as the main outcome
measure and will be subject to bias because of lack of patient blind-
ing (which can only be achieved by a sham operation).
For patients with gallbladder polyps larger than 10 mm, obser-
vational studies evaluating the sensitivity and specificity of differ-
ent investigations such as ultrasound (transabdominal and endo-
scopic ultrasound), positron emission tomomography scan (PET
scan), computerised tomogram (CT scan), and magnetic reso-
nance imaging (MRI) are necessary to determine the safety of fol-
low-up. There is no Cochrane review evaluating the ability of the
different diagnostic methods in distinguishing benign and malig-
nant gallbladder polyps. In the absence of such data, one has to
balance the risk of malignancy between 45% and 67% in polyps
larger than 10 mm to 15 mm in size (Mainprize 2000; Terzi 2000;
Yeh 2001; Chattopadhyay 2005) and the ris ks associated with
cholecystectomy . If the accuracy of the diagnostic test is high,
then it may be possible to perform a randomised clinical trial of
cholecystectomy versus follow-up using the ’accurate’ diagnostic
test.
AUTHORS’ CONCLUSIONS
Implications for practice
There is no evidence from randomised clinical trials to either
recommend or refute surgery to patients with gallbladder polyp
smaller than 10 mm.
Implications for research
• Randomised clinical trials are necessary to address the
question of whether cholecystectomy is indicated in
asymptomatic gallbladder polyps < 10 mm.
• Such randomised clinical trials should include blinded
assessment of outcomes, whenever possible. Blinding the patients
6
using sham operation should also be considered to decrease bias-
risk.
• Trials need to be conducted and reported according to the
CONSORT Statement (www.consort-statement.org).
• Further studies are needed to evaluate the role of different
diagnostic modalities in the follow-up of gallbladder polyps.
ACKNOWLEDGEMENTS
REFERENCES
Additional references
Buanes 1996
Buanes T, Waage A, Mjaland O, Solheim K. Bile leak
after cholecystectomy significance and treatment: results
from the National Norwegian Cholecystectomy Registry.
International Surgery 1996;81(3):276–9.
Chattopadhyay 2005
Chattopadhyay D, Lochan R, Balupuri S, Gopinath BR,
Wynne KS. Outcome of gall bladder polypoidal lesions
detected by transabdominal ultrasound scanning: a nine
year experience. World Journal of Gastroenterology 2005;11
(14):2171–3.
Christensen 2004
Christensen M, Matzen P, Schulze S, Rosenberg
J. Complications of ERCP: a prospective study.
Gastrointestinal Endoscopy 2004;60(5):721–31.
Csendes 2001
Csendes A, Burgos AM, Csendes P, Smok G, Rojas J. Late
follow-up of polypoid lesions of the gallbladder smaller than
10 mm. Annals of Surgery 2001;234(5):657–60.
DeMets 1987
DeMets DL. Methods for combining randomized clinical
trials: strengths and limitations. Statistics in Medicine 1987;
6(3):341–50.
DerSimonian 1986
DerSimonian R, Laird N. Meta-analysis in clinical trials.
Controlled Clinical Trials 1986;7(3):177–88.
Egger 1997
Egger M, Davey SG, Schneider M, Minder C. Bias in meta-
analysis detected by a simple, graphical test. BMJ (Clinical
Research Ed.) 1997;315(7109):629–34.
Fletcher 1999
Fletcher DR, Hobbs MS, Tan P, Valinsky LJ, Hockey RL,
Pikora TJ, et al. Complications of cholecystectomy: risks of
the laparoscopic approach and protective effects of operative
cholangiography: a population-based study. Annals of
Surgery 1999;229(4):449–57.
Cholecystectomy for gallbladder polyp (Review)
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
To TC Mahendran, Chennai, India, the first author’s first surgical
teacher.
To Martyn Parker, author of more than 15 Cochrane reviews, who
inspired the first author to write Cochrane reviews.
To The Cochrane Hepato-Biliary Group for the support that they
have provided.
Peer Reviewers: T Awad, Denamrk.
Contact Editor: C Gluud, Denmark.
Fullarton 1994
Fullarton GM, Bell G. Prospective audit of the introduction
of laparoscopic cholecystectomy in the west of Scotland.
West of Scotland Laparoscopic Cholecystectomy Audit
Group. Gut 1994;35(8):1121–6.
Gluud 2008
Gluud C, Nikolova D, Klingenberg SL, Whitfield K,
Alexakis N, Als-Nielsen B, et al. Cochrane Hepato-Biliary
Group. About The Cochrane Collaboration (Cochrane
Review Groups (CRGs)) 2008, Issue 1. Art. No.: LIVER.
Gurusamy 2006
Gurusamy KS, Samraj K. Early versus delayed laparoscopic
cholecystectomy for acute cholecystitis. Cochrane Database
of Systematic Reviews 2006, Issue 4. Art. No.: CD005440.
DOI: 10.1002/14651858.CD005440.pub2.
Gurusamy 2008
Gurusamy KS, Kumar Y, Davidson BR. Wound
infiltration with local anaesthetic agents for laparoscopic
cholecystectomy. Cochrane Database of Systematic Reviews
2008, Issue 2. [DOI: 10.1002/14651858.CD007049]
Hayashi 1996
Hayashi Y, Liu JH, Moriguchi H, Takenawa H, Tazawa J,
Nakayama E, et al. Prevalence of polypoid lesions of the
gallbladder in urban and rural areas of Japan: comparison
between 1988 and 1993. Journal of Clinical Gastroenterology
1996;23(2):158–9.
Higgins 2002
Higgins JPT, Thompson SG. Quantifying heterogeneity in a
meta-analysis. Statistics in Medicine 2002;21(11):1539–58.
Higgins 2008
Higgins JPT, Green S (editors). Cochrane Handbook for
Systematic Reviews of Intervention 5.0.0 [updated February
2008]. The Cochrane Colloboration, 2008. Available from
www.cochrane–handbook.org.
Huang 2001
Huang CS, Lien HH, Jeng JY, Huang SH. Role of
laparoscopic cholecystectomy in the management of
polypoid lesions of the gallbladder. Surgical Laparoscopy,
Endoscopy & Percutaneous Techniques 2001;11(4):242–7.
7
Huang 2003
Huang CS, Lein HH, Tai FC, Wu CH. Long-term results
of major bile duct injury associated with laparoscopic
cholecystectomy. Surgical Endoscopy 2003;17(9):1362–7.
Johansson 2003
Johansson M, Thune A, Blomqvist A, Nelvin L, Lundell L.
Management of acute cholecystitis in the laparoscopic era:
results of a prospective, randomized clinical trial. Journal of
Gastrointestinal Surgery 2003;7(5):642–5.
Johnson 2000
Johnson SR, Koehler A, Pennington LK, Hanto DW.
Long-term results of surgical repair of bile duct injuries
following laparoscopic cholecystectomy. Surgery 2000;128
(4):668–77.
Jones-Monahan 2000
Jones-Monahan KS, Gruenberg JC, Finger JE, Tong
GK. Isolated small gallbladder polyps: an indication for
cholecystectomy in symptomatic patients. The American
Surgeon 2000;66(8):716–9.
Keus 2006
Keus F, de Jong JAF, Gooszen HG, van Laarhoven CJHM.
Laparoscopic versus open cholecystectomy for patients with
symptomatic cholecystolithiasis. Cochrane Database of
Systematic Reviews 2006, Issue 4. Art. No.: CD006231.
DOI: 10.1002/14651858.CD006231.
Kimura 2005
Kimura T, Suzuki K, Umehara Y, Kawabe A, Wada H.
Features and management of bile leaks after laparoscopic
cholecystectomy. Journal of Hepato-Biliary-Pancreatic
Surgery 2005;12(1):61–4.
Kjaergard 2001
Kjaergard LL, Villumsen J, Gluud C. Reported
methodologic quality and discrepancies between large and
small randomized trials in meta-analyses. Annals of Internal
Medicine 2001;135(11):982–9.
Krahenbuhl 2001
Krahenbuhl L, Sclabas G, Wente MN, Schafer M, Schlumpf
R, Buchler MW. Incidence, risk factors, and prevention of
biliary tract injuries during laparoscopic cholecystectomy
in Switzerland. World Journal of Surgery 2001;25(10):
1325–30.
Lee 2004
Lee KF, Wong J, Li JC, Lai PB. Polypoid lesions of the
gallbladder. American Journal of Surgery 2004;188(2):
186–90.
Lin 2008
Lin WR, Lin DY, Tai DI, Hsieh SY, Lin CY, Sheen IS, et al.
Prevalence of and risk factors for gallbladder polyps detected
by ultrasonography among healthy Chinese: analysis of 34
669 cases. Journal of Gastroenterology and Hepatology 2008;
23(6):965–9.
Livingston 2004
Livingston EH, Rege RV. A nationwide study of conversion
from laparoscopic to open cholecystectomy. American
Journal of Surgery 2004;188(3):205–11.
Cholecystectomy for gallbladder polyp (Review)
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Macaskill 2001
Macaskill P, Walter SD, Irwig L. A comparison of methods
to detect publication bias in meta-analysis. Statistics in
Medicine 2001;20(4):641–54.
Mainprize 2000
Mainprize KS, Gould SW, Gilbert JM. Surgical management
of polypoid lesions of the gallbladder. The British Journal of
Surgery 2000;87(4):414–7.
Moher 1998
Moher D, Pham B, Jones A, Cook DJ, Jadad AR, Moher
M, et al. Does quality of reports of randomised trials affect
estimates of intervention efficacy reported in meta-analyses?
. Lancet 1998;352(9128):609–13.
Newell 1992
Newell DJ. Intention-to-treat analysis: implications for
quantitative and qualitative research. International Journal
of Epidemiology 1992;21(5):837–41.
NIH 1992
NIH. NIH consensus statement on gallstones and
laparoscopic cholecystectomy. http://consensus.nih.gov/
1992/1992GallstonesLaparoscopy090html.htm 1992
(accessed 26 September 2008).
Okamoto 1999
Okamoto M, Okamoto H, Kitahara F, Kobayashi K,
Karikome K, Miura K, et al. Ultrasonographic evidence of
association of polyps and stones with gallbladder cancer.
American Journal of Gastroenterology 1999;94(2):446–50.
Pandey 1996
Pandey M, Khatri AK, Sood BP, Shukla RC, Shukla VK.
Cholecystosonographic evaluation of the prevalence of
gallbladder diseases. A university hospital experience.
Clinical Imaging 1996;20(4):269–72.
RevMan 2008 [Computer program]
The Nordic Cochrane Centre, The Cochrane Collaboration.
Review Manager (RevMan). Copenhagen: The Nordic
Cochrane Centre, The Cochrane Collaboration, 2008.
Richardson 1996
Richardson MC, Bell G, Fullarton GM. Incidence
and nature of bile duct injuries following laparoscopic
cholecystectomy: an audit of 5913 cases. West of Scotland
Laparoscopic Cholecystectomy Audit Group. The British
Journal of Surgery 1996;83(10):1356–60.
Royle 2003
Royle P, Milne R. Literature searching for randomized
controlled trials used in Cochrane reviews: rapid versus
exhaustive searches. International Journal of Technology
Assessment in Health Care 2003;19(4):591–603.
Schmidt 2005
Schmidt SC, Langrehr JM, Hintze RE, Neuhaus P. Long-
term results and risk factors influencing outcome of major
bile duct injuries following cholecystectomy. The British
Journal of Surgery 2005;92(1):76–82.
Schulz 1995
Schulz KF, Chalmers I, Hayes RJ, Altman DG. Empirical
evidence of bias. Dimensions of methodological quality
8
 associated with estimates of treatment effects in controlled
trials. JAMA 1995;273(5):408–12.
Shinkai 1998
Shinkai H, Kimura W, Muto T. Surgical indications for
small polypoid lesions of the gallbladder. American Journal
of Surgery 1998;175(2):114–7.
Sicklick 2005
Sicklick JK, Camp MS, Lillemoe KD, Melton GB, Yeo CJ,
Campbell KA, et al. Surgical management of bile duct
injuries sustained during laparoscopic cholecystectomy:
perioperative results in 200 patients. Annals of Surgery 2005;
241(5):786–92.
Sugiyama 1999
Sugiyama M, Xie XY, Atomi Y, Saito M. Differential
diagnosis of small polypoid lesions of the gallbladder: the
value of endoscopic ultrasonography. Annals of Surgery
1999;229(4):498–504.
Sun 2004
Sun XJ, Shi JS, Han Y, Wang JS, Ren H. Diagnosis and
treatment of polypoid lesions of the gallbladder: report of
194 cases. Hepatobiliary Pancreatic Diseases International
2004;3(4):591–4.
Cholecystectomy for gallbladder polyp (Review)
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Sweeting 2004
Sweeting MJ, Sutton AJ, Lambert PC. What to add to
nothing? Use and avoidance of continuity corrections in
meta-analysis of sparse data. Statistics in Medicine 2004;23
(9):1351–75.
Terzi 2000
Terzi C, Sokmen S, Seckin S, Albayrak L, Ugurlu M.
Polypoid lesions of the gallbladder: report of 100 cases with
special reference to operative indications. Surgery 2000;127
(6):622–7.
Wood 2008
Wood L, Egger M, Gluud LL, Schulz KF, Juni P, Altman
DG, et al. Empirical evidence of bias in treatment effect
estimates in controlled trials with different interventions
and outcomes: meta-epidemiological study. BMJ (Clinical
research ed.) 2008;336(7644):601–5. [PUBMED:
18316340]
Yeh 2001
Yeh CN, Jan YY, Chao TC, Chen MF. Laparoscopic
cholecystectomy for polypoid lesions of the gallbladder: a
clinicopathologic study. Surgical Laparoscopy, Endoscopy &
Percutaneous Techniques 2001;11(3):176–81.
∗
Indicates the major publication for the study
9
DATA AND ANALYSES
This review has no analyses.

APPENDICES

Appendix 1. Search Strategies

Database Period of search Search strategy

The Cochrane Hepato-Biliary Group Con- July 2008 (adenoma OR adenomas OR polyp OR polyps) AND (gallblad-
trolled Trials Register der OR gall-bladder OR ”gall bladder“) AND (cholecystecto* OR
colecystecto* )

Cochrane Central Register of Controlled Issue 2, 2008
Trials (CENTRAL) in The Cochrane Li-
brary
#1 MeSH descriptor Polyps explode all trees
#2 MeSH descriptor Adenoma explode all trees
#3 MeSH descriptor Adenomatous Polyps explode all trees
#4 adenoma OR adenomas OR polyp OR polyps
#5 (#1 OR #2 OR #3 OR #4)
#6 MeSH descriptor Gallbladder explode all trees
#7 MeSH descriptor Gallbladder Neoplasms explode all trees
#8 MeSH descriptor Gallbladder Diseases explode all trees
#9 gallbladder OR gall-bladder OR ”gall bladder“
#10 (#6 OR #7 OR #8 OR #9)
#11 MeSH descriptor Cholecystectomy explode all trees
#12 cholecystecto* OR colecystecto*
#13 (#11 OR #12)
#14 (#5 AND #10 AND #13)

MEDLINE (PubMed) 1951 to July 2008 (”Polyps“[MeSH] OR ”Adenoma“[MeSH] OR ”Adenomatous

Polyps“[MeSH] OR adenoma OR adenomas OR polyp OR
polyps) AND (gallbladder OR gall-bladder OR “gall bladder” OR
”Gallbladder“[MeSH] OR ”Gallbladder Neoplasms“[MeSH] OR
”Gallbladder Diseases“[MeSH]) AND (cholecystecto* OR colecys-
tecto* OR “cholecystectomy”[MeSH]) AND ((randomized con-
trolled trial [pt] OR controlled clinical trial [pt] OR randomized
[tiab] OR placebo [tiab] OR drug therapy [sh] OR randomly [tiab]
OR trial [tiab] OR groups [tiab]) AND humans [mh])

EMBASE (Dialog Datastar) 1974 to July 2008 1 ADENOMA#.W..DE. OR POLYP#.W..DE. OR adenoma OR

adenomas OR polyp OR polyps
2 gallbladder OR gall-bladder OR gall ADJ bladder OR GALL-
BLADDER-DISEASE#.DE. OR GALLBLADDER-TUMOR#.
DE. OR GALLBLADDER#.W..DE.
3 CHOLECYSTECTOMY#.W..DE. OR cholecystecto$ OR cole-

Cholecystectomy for gallbladder polyp (Review) 10

Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
(Continued)

cystecto$
4 1 AND 2 AND 3
5 RANDOM$ OR FACTORIAL$ OR CROSSOVER$ OR
CROSS ADJ OVER$ OR PLACEBO$ OR DOUBL$ ADJ
BLIND$ OR SINGL$ ADJ BLIND$ OR ASSIGN$ OR AL-
LOCAT$ OR VOLUNTEER$ OR CROSSOVER-PROCE-
DURE#.MJ. OR DOUBLE-BLIND-PROCEDURE#.DE. OR
SINGLE-BLIND-PROCEDURE#.DE. OR RANDOMIZED-
CONTROLLED-TRIAL#.DE.
6 4 AND 5

Science Citation Index Expanded (http:// 1987 to July 2008
portal.isiknowledge.com/portal.cgi?
DestApp=WOS&Func=Frame)
#1 TS=(adenoma OR adenomas OR polyp OR polyps)
#2 TS=(gallbladder OR gall-bladder OR “gall bladder”)
#3 TS=(cholecystecto* OR colecystecto*)
#4 TS=(random* OR blind* OR placebo* OR meta-analysis)
#5 #1 AND #2 AND #3 AND #4

WHAT’S NEW
Last assessed as up-to-date: 9 July 2008.

Date Event Description

10 July 2008 Amended Converted to new review format.

CONTRIBUTIONS OF AUTHORS
KS Gurusamy wrote the review and assessed the trials for inclusion and extracted data on included trials. M Abu-amara is the co-author
for the review and independently assessed the trials for inclusion and extracted data on included trials. M Farouk and BR Davidson
critically commented on the review and provided advice for improving the review.

DECLARATIONS OF INTEREST
None known.

Cholecystectomy for gallbladder polyp (Review) 11

Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
SOURCES OF SUPPORT

Internal sources
• none, Not specified.

External sources
• none, Not specified.

DIFFERENCES BETWEEN PROTOCOL AND REVIEW

The outcomes have been divided into primary and secondary outcomes. The assessment of methodological quality of studies has been
revised in line with the recommendations of the Cochrane Handbook (Higgins 2008).

INDEX TERMS

Medical Subject Headings (MeSH)

∗ Cholecystectomy; Gallbladder Neoplasms [∗ surgery]; Polyps [∗ surgery]

MeSH check words

Humans

Cholecystectomy for gallbladder polyp (Review) 12

Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.