Cochrane Revision. Menos de 4 Puertos VS 4 Puertos en Colelap. 2014

Cochrane
Library
Cochrane Database of Systematic Reviews

Fewer-than-four ports versus four ports for laparoscopic
cholecystectomy (Review)
Gurusamy KS, Vaughan J, Rossi M, Davidson BR
Gurusamy KS, Vaughan J, Rossi M, Davidson BR.

Fewer-than-four ports versus four ports for laparoscopic cholecystectomy.
Cochrane Database of Systematic Reviews 2014, Issue 2. Art. No.: CD007109.
DOI: 10.1002/14651858.CD007109.pub2.
www.cochranelibrary.com

Fewer-than-four ports versus four ports for laparoscopic cholecystectomy (Review)
Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Cochrane Trusted evidence.
Informed decisions.

Library Better health. Cochrane Database of Systematic Reviews
TABLE OF CONTENTS
HEADER......................................................................................................................................................................................................... 1
ABSTRACT..................................................................................................................................................................................................... 1
PLAIN LANGUAGE SUMMARY....................................................................................................................................................................... 2
SUMMARY OF FINDINGS.............................................................................................................................................................................. 4
BACKGROUND.............................................................................................................................................................................................. 6
OBJECTIVES.................................................................................................................................................................................................. 6
METHODS..................................................................................................................................................................................................... 6
RESULTS........................................................................................................................................................................................................ 9
Figure 1.................................................................................................................................................................................................. 10
Figure 2.................................................................................................................................................................................................. 12
Figure 3.................................................................................................................................................................................................. 13
Figure 4.................................................................................................................................................................................................. 14
Figure 5.................................................................................................................................................................................................. 15
Figure 6.................................................................................................................................................................................................. 16
Figure 7.................................................................................................................................................................................................. 17
Figure 8.................................................................................................................................................................................................. 18
Figure 9.................................................................................................................................................................................................. 19
Figure 10................................................................................................................................................................................................ 20
Figure 11................................................................................................................................................................................................ 21
DISCUSSION.................................................................................................................................................................................................. 22
AUTHORS' CONCLUSIONS........................................................................................................................................................................... 23
ACKNOWLEDGEMENTS................................................................................................................................................................................ 23
REFERENCES................................................................................................................................................................................................ 24
CHARACTERISTICS OF STUDIES.................................................................................................................................................................. 30
DATA AND ANALYSES.................................................................................................................................................................................... 44
Analysis 1.1. Comparison 1 Fewer-than-four ports versus four ports, Outcome 1 Serious adverse events..................................... 45
Analysis 1.2. Comparison 1 Fewer-than-four ports versus four ports, Outcome 2 Quality of life..................................................... 46
Analysis 1.3. Comparison 1 Fewer-than-four ports versus four ports, Outcome 3 Conversion to open cholecystectomy.............. 46
Analysis 1.4. Comparison 1 Fewer-than-four ports versus four ports, Outcome 4 Operating time.................................................. 47
Analysis 1.5. Comparison 1 Fewer-than-four ports versus four ports, Outcome 5 Hospital stay...................................................... 48
Analysis 1.6. Comparison 1 Fewer-than-four ports versus four ports, Outcome 6 Proportion discharged as day-surgery............. 48
Analysis 1.7. Comparison 1 Fewer-than-four ports versus four ports, Outcome 7 Return to normal activity.................................. 49
Analysis 1.8. Comparison 1 Fewer-than-four ports versus four ports, Outcome 8 Return to work.................................................. 49
Analysis 1.9. Comparison 1 Fewer-than-four ports versus four ports, Outcome 9 Cosmetic score.................................................. 49
Analysis 2.1. Comparison 2 Fewer-than-four ports versus four ports (sensitivity analysis), Outcome 1 Quality of life................... 50
Analysis 2.2. Comparison 2 Fewer-than-four ports versus four ports (sensitivity analysis), Outcome 2 Operating time................ 51
Analysis 2.3. Comparison 2 Fewer-than-four ports versus four ports (sensitivity analysis), Outcome 3 Hospital stay.................... 51
Analysis 2.4. Comparison 2 Fewer-than-four ports versus four ports (sensitivity analysis), Outcome 4 Return to normal activity.... 52
APPENDICES................................................................................................................................................................................................. 52
CONTRIBUTIONS OF AUTHORS................................................................................................................................................................... 53
DECLARATIONS OF INTEREST..................................................................................................................................................................... 53
SOURCES OF SUPPORT............................................................................................................................................................................... 53
DIFFERENCES BETWEEN PROTOCOL AND REVIEW.................................................................................................................................... 53
NOTES........................................................................................................................................................................................................... 53
INDEX TERMS............................................................................................................................................................................................... 54
Fewer-than-four ports versus four ports for laparoscopic cholecystectomy (Review) i

Informed decisions.

[Intervention Review]
Fewer-than-four ports versus four ports for laparoscopic

cholecystectomy
Kurinchi Selvan Gurusamy1, Jessica Vaughan1, Michele Rossi2, Brian R Davidson1
1Department of Surgery, Royal Free Campus, UCL Medical School, London, UK. 2Endoscopia Chirurgica, Azienda Ospedaliero-
Universitaria Careggi, Firenze, Italy
Contact address: Kurinchi Selvan Gurusamy, Department of Surgery, Royal Free Campus, UCL Medical School, Royal Free Hospital,
Rowland Hill Street, London, NW3 2PF, UK. k.gurusamy@ucl.ac.uk.
Editorial group: Cochrane Hepato-Biliary Group

Publication status and date: New, published in Issue 2, 2014.
Citation: Gurusamy KS, Vaughan J, Rossi M, Davidson BR. Fewer-than-four ports versus four ports for laparoscopic cholecystectomy.
Cochrane Database of Systematic Reviews 2014, Issue 2. Art. No.: CD007109. DOI: 10.1002/14651858.CD007109.pub2.
ABSTRACT
Background
Traditionally, laparoscopic cholecystectomy is performed using two 10-mm ports and two 5-mm ports. Recently, a reduction in the number
of ports has been suggested as a modification of the standard technique with a view to decreasing pain and improving cosmesis. The safety
and effectiveness of using fewer-than-four ports has not yet been established.
Objectives
To assess the benefits (such as improvement in cosmesis and earlier return to activity) and harms (such as increased complications) of
using fewer-than-four ports (fewer-than-four-ports laparoscopic cholecystectomy) versus four ports in people undergoing laparoscopic
cholecystectomy for any reason (symptomatic gallstones, acalculous cholecystitis, gallbladder polyp, or any other condition).
Search methods
We searched the Cochrane Central Register of Controlled Trials (CENTRAL; Issue 8, 2013), MEDLINE, EMBASE, Science Citation Index
Expanded, and the World Health Organization International Clinical Trials Registry Platform portal to September 2013.
Selection criteria
We included all randomised clinical trials comparing fewer-than-four ports versus four ports, that is, with standard laparoscopic
cholecystectomy that is performed with two ports of at least 10-mm incision and two ports of at least 5-mm incision.
Data collection and analysis

Two review authors independently identified the trials and extracted the data. We analysed the data using both the fixed-effect and the
random-effects models. For each outcome, we calculated the risk ratio (RR) or mean difference (MD) with 95% confidence intervals (CI)
based on intention-to-treat analysis, whenever possible.
Main results
We found nine trials with 855 participants that randomised participants to fewer-than-four-ports laparoscopic cholecystectomy (n =
427) versus four-port laparoscopic cholecystectomy (n = 428). Most trials included low anaesthetic risk participants undergoing elective
laparoscopic cholecystectomy. Seven of the nine trials used a single port laparoscopic cholecystectomy and the remaining two trials used
three-port laparoscopic cholecystectomy as the experimental intervention. Only one trial including 70 participants had low risk of bias.
Fewer-than-four-ports laparoscopic cholecystectomy could be completed successfully in more than 90% of participants in most trials.
Fewer-than-four ports versus four ports for laparoscopic cholecystectomy (Review) 1

Informed decisions.

The remaining participants were mostly converted to four-port laparoscopic cholecystectomy but some participants had to undergo open
cholecystectomy.
There was no mortality in either group in the seven trials that reported mortality (318 participants in fewer-than-four-ports laparoscopic
cholecystectomy group and 316 participants in four-port laparoscopic cholecystectomy group). The proportion of participants with serious
adverse events was low in both treatment groups and the estimated RR was compatible with a reduction and substantial increased risk
with the fewer-than-four-ports group (6/318 (1.9%)) and four-port laparoscopic cholecystectomy group (0/316 (0%)) (RR 3.93; 95% CI 0.86
to 18.04; 7 trials; 634 participants; very low quality evidence). The estimated difference in the quality of life (measured between 10 and 30
days) was imprecise (standardised mean difference (SMD) 0.18; 95% CI -0.05 to 0.42; 4 trials; 510 participants; very low quality evidence),
as was the proportion of participants in whom the laparoscopic cholecystectomy had to be converted to open cholecystectomy between
the groups (fewer-than-four ports 3/289 (adjusted proportion 1.2%) versus four port: 5/292 (1.7%); RR 0.68; 95% CI 0.19 to 2.35; 5 trials;
581 participants; very low quality evidence). The fewer-than-four-ports laparoscopic cholecystectomy took 14 minutes longer to complete
(MD 14.44 minutes; 95% CI 5.95 to 22.93; 9 trials; 855 participants; very low quality evidence). There was no clear difference in hospital
stay between the groups (MD -0.01 days; 95% CI -0.28 to 0.26; 6 trials; 731 participants) or in the proportion of participants discharged
as day surgery (RR 0.92; 95% CI 0.70 to 1.22; 1 trial; 50 participants; very low quality evidence) between the two groups. The times taken
to return to normal activity and work were shorter by two days in the fewer-than-four-ports group compared with four-port laparoscopic
cholecystectomy (return to normal activity: MD -1.20 days; 95% CI -1.58 to -0.81; 2 trials; 325 participants; very low quality evidence; return
to work: MD -2.00 days; 95% CI -3.31 to -0.69; 1 trial; 150 participants; very low quality evidence). There was no significant difference in
cosmesis scores at 6 to 12 months between the two groups (SMD 0.37; 95% CI -0.10 to 0.84; 2 trials; 317 participants; very low quality
evidence).
Authors' conclusions
There is very low quality evidence that is insufficient to determine whether there is any significant clinical benefit in using fewer-than-four-
ports laparoscopic cholecystectomy compared with four-port laparoscopic cholecystectomy. The safety profile of using fewer-than-four
ports is yet to be established and fewer-than-four-ports laparoscopic cholecystectomy should be reserved for well-designed randomised
clinical trials.
PLAIN LANGUAGE SUMMARY
Fewer-than-four ports versus four ports for laparoscopic cholecystectomy
Background
About 10% to 15% of the adult Western population have gallstones. Between 1% and 4% become symptomatic each year. Removal of
the gallbladder (cholecystectomy) is the main stay treatment for symptomatic gallstones. More than half a million cholecystectomies
are performed per year in the United States alone. Laparoscopic cholecystectomy (removal of gallbladder through a key-hole-sized
incision, also known as port) is now the preferred method of cholecystectomy. In conventional or standard laparoscopic cholecystectomy
(key hole removal of gallbladder), four ports (two of 10-mm diameter and two of 5-mm diameter) are usually used. The use of fewer
ports has been reported (fewer-than-four-ports laparoscopic cholecystectomy). However, the safety of fewer-than-four-ports laparoscopic
cholecystectomy and whether it offers any advantages over four-port laparoscopic cholecystectomy is not known. We sought to answer
this question by reviewing the medical literature and obtaining information from randomised clinical trials commonly called randomised
controlled trials. When conducted well, such studies provide the most accurate information. Two review authors searched the literature
to September 2013 and obtained information from the trials, thereby minimising errors.
Study characteristics
We identified nine trials that compared fewer-than-four-ports laparoscopic cholecystectomy with four-port laparoscopic cholecystectomy.
In these nine studies, 855 participants were included. Four hundred and twenty seven participants underwent fewer-than-four-ports
laparoscopic cholecystectomy while the remaining 428 participants underwent four-port laparoscopic cholecystectomy. The choice of the
treatment that the participants received was determined by a method similar to toss of a coin so that the two treatments were given to
participants with similar characteristics. Most of these studies included low anaesthetic risk patients undergoing planned laparoscopic
cholecystectomy.
Key results
Fewer-than-four-ports laparoscopic cholecystectomy could be completed successfully in more than 90% of participants in most of the
trials. The remaining participants were mostly converted to four-port laparoscopic cholecystectomy but some participants had to undergo
open cholecystectomy (through a large incision in the abdomen). There was no mortality in either group in the seven trials that reported
mortality (634 participants in the two groups). There was no significant difference in the proportion of participants who developed serious
complications, quality of life between 10 and 30 days after operation, proportion of participants in whom the laparoscopic operation
had to be converted to open cholecystectomy, or in the length of hospital stay between the groups. Fewer-than-four-ports laparoscopic
cholecystectomy took about 15 minutes longer to complete than four-port laparoscopic cholecystectomy. The time taken to return to
normal activity was one day shorter and time taken to return to work two days shorter in the fewer-than-four-ports group compared with

Informed decisions.

four-port laparoscopic cholecystectomy. There was no significant difference in the cosmetic appearance between the two groups at 6 to
12 months after surgery. There appears to be no advantage of fewer-than-four-ports laparoscopic cholecystectomy in terms of decreasing
surgical complications, hospital stay, or in improving quality of life and cosmetic appearance. In contrast, the safety of fewer-than-four
port laparoscopic cholecystectomy is yet to be established. Fewer-than-four-ports laparoscopic cholecystectomy cannot be recommended
routinely outside well-designed clinical trials.
Quality of evidence
Most of the trials were of high risk of bias, that is, there is possibility of arriving at wrong conclusions because of the way that the trial was
conducted. The overall quality of evidence was very low.
Future research
Further well-designed randomised clinical trials (which have low probability to arrive at wrong conclusions because of chance and because
of participant or researcher prejudice) are necessary to determine whether fewer-than-four-ports laparoscopic cholecystectomy is safe
and whether there is any advantage of fewer-than-four-ports laparoscopic cholecystectomy over four-port laparoscopic cholecystectomy.

SUMMARY OF FINDINGS

Summary of findings for the main comparison. Fewer-than-four ports compared with four ports for laparoscopic cholecystectomy
Library
Cochrane
Fewer-than-four ports compared with four ports for laparoscopic cholecystectomy
Patient or population: people undergoing laparoscopic cholecystectomy.

Settings: secondary.
Intervention: fewer-than-four ports.
Better health.
Informed decisions.
Trusted evidence.
Comparison: four ports.
Outcomes Illustrative comparative risks* (95% CI) Relative ef- No of partici- Quality of the
fect pants evidence
Assumed risk Corresponding risk (95% CI) (studies) (GRADE)
Four ports Fewer-than-four ports
Mortality There was no mortality in either group Not estimable 634 ⊕⊝⊝⊝
very low1,2,3
(7 studies)
Serious ad- Low RR 3.93 634 ⊕⊝⊝⊝

verse events (0.86 to 18.04) (7 studies) very low1,2,3
10 per 1000 39 per 1000
(9 to 180)
Moderate
30 per 1000 118 per 1000

(26 to 541)
Quality of life - The mean quality of life in the intervention groups was - 510 ⊕⊝⊝⊝

0.18 standard deviations higher (4 studies) very low1,3,4
(0.05 lower to 0.42 higher)
Conversion to 17 per 1000 12 per 1000 RR 0.68 581 ⊕⊝⊝⊝

open cholecys- (3 to 40) (0.19 to 2.35) (5 studies) very low1,2,3
tectomy
Operating time The mean operating time in the The mean operating time in the intervention groups was - 855 ⊕⊝⊝⊝
control groups was 14.44 higher (9 studies) very low1,5
56 minutes (5.95 to 22.93 higher)
4

Hospital stay The mean hospital stay in the The mean hospital stay in the intervention groups was - 731 ⊕⊝⊝⊝
control groups was 0.01 lower (6 studies) very low1,3,5
2 days (0.28 lower to 0.26 higher)
Library
Cochrane
Proportion dis- 833 per 1000 767 per 1000 RR 0.92 50 ⊕⊝⊝⊝
charged as day (583 to 1000) (0.7 to 1.22) (1 study) very low1,2,3
surgery
Return to nor- The mean return to normal ac- The mean return to normal activity in the intervention groups - 325 ⊕⊝⊝⊝
Better health.
Informed decisions.
Trusted evidence.
mal activity tivity in the control groups was was (2 studies) very low1,3,4
6.1 days 1.2 lower
(1.58 lower to 0.81 lower)
Return to work The mean return to work in the The mean return to work in the intervention groups was - 150 ⊕⊝⊝⊝
control groups was 2 lower (1 study) very low1,3
12 days (3.31 to 0.69 lower)
Cosmetic score - The mean cosmetic score in the intervention groups was - 317 ⊕⊝⊝⊝
0.37 standard deviations higher (2 studies) very low3,4
(0.1 lower to 0.84 higher)
*The basis for the assumed risk was the control group risk across studies in all outcomes other serious adverse events. There were no serious adverse events in the control
group and so the information is presented for different control group risks.
The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: confidence interval; RR: risk ratio.
GRADE Working Group grades of evidence

High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

1 The trial(s) was (were) of high risk of bias.
2 The confidence intervals overlapped 1 and either 0.75 or 1.25, or both. The number of events in the intervention and control group was fewer than 300.
3 It was not possible to explore reporting bias because of the few trials included.
4 The confidence intervals overlapped 0 and minimal clinically important difference (one day for hospital stay, return to activity, and return to work; 15 minutes for operating
time; and 0.25 standard deviations for quality of life and cosmesis). The total number of participants in the intervention and control group was fewer than 400.
5 There was severe heterogeneity as noted by the I2 statistic and the lack of overlap of confidence intervals.

5

Informed decisions.

BACKGROUND METHODS
Description of the condition Criteria for considering studies for this review
About 10% to 15% of the adult western population have gallstones Types of studies
(Jørgensen 1987; NIH 1992; Muhrbeck 1995; Halldestam 2004).
We included only randomised clinical trials irrespective of
Between 1% and 4% become symptomatic in one year (NIH 1992;
language, blinding, sample size, or publication status.
Halldestam 2004). More than half a million cholecystectomies
(removal of gallbladder) are performed per year in the United States We excluded quasi-randomised studies (where the method of
alone (NIH 1992). Regional differences exist in the cholecystectomy allocating participants to a treatment were not strictly random (eg,
rates (Mjäland 1998). Laparoscopic ('key-hole') cholecystectomy, date of birth, hospital record number, alternation), cohort studies,
which was introduced in 1987, is now the preferred method and case-control studies because of the selection bias in such
of cholecystectomy (NIH 1992; Fullarton 1994; Bakken 2004; studies. People who were generally considered easy to operate
Livingston 2004; Keus 2006; David 2008). would have undergone laparoscopic cholecystectomy by fewer
ports while those who were considered to be difficult to operate
Description of the intervention would have undergone four-port laparoscopic cholecystectomy.
Traditionally four ports are used to perform laparoscopic Besides, people in whom the surgery was started as fewer-than-
cholecystectomy. These include one port for the camera; one four-ports laparoscopic cholecystectomy and converted to four-
port for instruments used to carry out the dissection, diathermy, port laparoscopic cholecystectomy might have been excluded
and clip application; and two ports for manipulation of the (as we found was the case even in randomised clinical trials
gallbladder for adequate exposure of the field of surgery. Two using a similar intervention, ie, smaller size ports or miniport
ports are usually 10 mm in size and two ports are usually laparoscopic cholecystectomy (Gurusamy 2013)), or would have
5 mm in size (Alponat 2002; Bisgaard 2002). Laparoscopic been included in four-port laparoscopic cholecystectomy making
cholecystectomy has been performed using one, two, or three any such comparisons in non-randomised studies meaningless or
ports (Poon 2003; Gupta 2005). The technique in performing misleading. However, we recorded any rare harms attributed to
laparoscopic cholecystectomy with fewer ports, in particular, fewer-than-four-ports laparoscopic cholecystectomy in such non-
single-port laparoscopic cholecystectomy varies from conventional randomised studies.
four-port method laparoscopic cholecystectomy with regards to
the dissection of the gallbladder and the use of roticulating Types of participants
instruments that have articulations with the ability to rotate the tip People undergoing laparoscopic cholecystectomy (elective or
at the articulation (Roberts 2010). emergency) for any reason (symptomatic gallstones, acalculous
cholecystitis, gallbladder polyp, or any other condition).
How the intervention might work
Types of interventions
The use of fewer ports may decrease the pain (and analgesic
requirements) (Gupta 2005). Because of the fewer scars, it may Fewer-than-four ports (one, two, or three) versus four ports
result in better cosmesis (Gupta 2005). (two ports of at least 10 mm and two ports of at least
5 mm) in people undergoing laparoscopic cholecystectomy.
Why it is important to do this review We considered laparoscopic cholecystectomy using four-port
Any new technique has to be evaluated with regards to safety and laparoscopic cholecystectomy with two 10-mm ports and two 5-
effectiveness before it can be adopted in routine practice. There mm ports as standard laparoscopic cholecystectomy. We excluded
are concerns about the safety of using fewer-than-four ports (Hall trials that did not use the above definition of four-port laparoscopic
2012). The concern about using fewer-than-four ports is about cholecystectomy. The reason for excluding trials in which smaller
damage to the bile duct or other important structures such as blood ports were used in the control group was because of the lack of
vessels supplying the liver because of the fewer ports not allowing information on safety in miniport laparoscopic cholecystectomy
adequate vision and sufficient traction on the structures because (Gurusamy 2013).
of the angle at the which the instruments work and because of
Types of outcome measures
the fewer instruments that can be used within the body at any
given time. The potential advantages include decreased pain and Primary outcomes
improved cosmesis because of fewer ports being used. There has
1. Mortality.
been no Cochrane systematic review on this topic.
2. Serious adverse events defined as any event that would increase
OBJECTIVES mortality, was life-threatening, required hospitalisation,
resulted in a persistent or significant disability, or any
To assess the benefits (such as improvement in cosmesis and earlier important medical event that might have jeopardised the
return to activity) and harms (such as increased complications) person or required intervention to prevent it (ICH-GCP 1997). We
of using fewer-than-four ports (fewer-than-four-ports laparoscopic classified complications such as bile duct injury, re-operations,
cholecystectomy) versus four ports in people undergoing intra-abdominal collections requiring drainage (radiological
laparoscopic cholecystectomy for any reason (symptomatic or surgical), infected intra-abdominal collections, bile leaks
gallstones, acalculous cholecystitis, gallbladder polyp, or any other requiring drainage, stent, or surgery as serious adverse events.
condition). We did not consider complications such as wound infections,
bile leaks, or abdominal collections that did not require any

Informed decisions.

treatment and settled spontaneously to be serious adverse We sought any unclear or missing information by contacting the
events. authors of the individual trials. If there was any doubt whether
3. Patient quality of life (however defined by authors). the trials shared the same participants - completely or partially (by
identifying common authors and centres) - we planned to contact
Secondary outcomes the authors of the trials to clarify whether the trial report had
been duplicated. We resolved any differences in opinion through
1. Conversion to open cholecystectomy.
discussion.
2. Operating time.
3. Hospital stay (length of hospital stay, proportion discharged as Assessment of risk of bias in included studies
day-case laparoscopic cholecystectomy).
We followed the instructions given in the Cochrane Handbook for
4. Return to activity. Systematic Reviews of Intervention (Higgins 2011), and the Cochrane
5. Return to work. Hepato-Biliary Group Module (Gluud 2013). According to empirical
6. Cosmesis (however defined by authors but at least six months evidence (Schulz 1995; Moher 1998; Kjaergard 2001; Wood 2008;
after surgery). Lundh 2012; Savovic 2012; Savovic 2012a), the risk of bias of the
trials were assessed based on the following domains.
Search methods for identification of studies
Sequence generation
Electronic searches
• Low risk of bias (the methods used was either adequate
We searched the Cochrane Central Register of Controlled Trials (eg, computer-generated random numbers, table of random
(CENTRAL) (Issue 8, 2013), MEDLINE, EMBASE, Science Citation numbers) or unlikely to introduce confounding).
Index Expanded (Royle 2003), and the World Health Organization
• Uncertain risk of bias (there was insufficient information to
International Clinical Trials Registry Platform (WHO ICTRP) portal
assess whether the method used was likely to introduce
(apps.who.int/trialsearch). The WHO ICTRP portal allows search of
confounding).
various trial registers including clinicaltrials.gov and International
Standard Randomised Controlled Trial Number (ISRCTN) among • High risk of bias (the method used (eg, quasi-randomised
other registers to September 2013. We have given the search studies) was improper and likely to introduce confounding).
strategies in Appendix 1 with the time spans for the searches. Allocation concealment
Searching other resources • Low risk of bias (the method used (eg, central allocation) was
We handsearched the references of the identified trials to identify unlikely to induce bias on the final observed effect).
further relevant trials. • Uncertain risk of bias (there was insufficient information to
assess whether the method used was likely to induce bias on the
Data collection and analysis estimate of effect).
• High risk of bias (the method used (eg, open random allocation
We performed the systematic review according to the
schedule) was likely to induce bias on the final observed effect).
recommendations of The Cochrane Collaboration (Higgins 2011),
and the Cochrane Hepato-Biliary Group Module (Gluud 2013). Blinding of participants, personnel, and outcome assessors
Selection of studies It is impossible to blind the surgeons who performed the
surgery. However, by the use of a second surgical team, it is
KG and JV or MR independently identified the trials for inclusion.
possible to determine whether a patient needs conversion to open
KG and JV or MR listed the excluded trials with the reasons for
cholecystectomy or whether the patient can be discharged from
the exclusion. We resolved any differences in opinion through
hospital (ie, the performance bias can be reduced by using a second
discussion.
surgical team to determine patient care).
Data extraction and management
• Low risk of bias (blinding was performed adequately, or the
KG and JV or MR independently extracted the following data. outcome measurement was not likely to be influenced by lack of
blinding).
1. Year and language of publication.
• Uncertain risk of bias (there was insufficient information to
2. Country. assess whether the type of blinding used was likely to induce
3. Year of conduct of the trial. bias on the estimate of effect).
4. Inclusion and exclusion criteria. • High risk of bias (no blinding or incomplete blinding, and
5. Sample size. the outcome or the outcome measurement was likely to be
6. Population characteristics such as age and sex ratio. influenced by lack of blinding).
7. Proportion of people who underwent successful fewer-than- Incomplete outcome data
four-ports laparoscopic cholecystectomy.
8. Intra-operative cholangiogram. • Low risk of bias (the underlying reasons for missingness are
unlikely to make treatment effects departure from plausible
9. Outcomes (see Primary outcomes; Secondary outcomes).
values, or proper methods have been employed to handle
10.Risk of bias (see Assessment of risk of bias in included studies). missing data).

Informed decisions.

• Uncertain risk of bias (there was insufficient information to Dealing with missing data
assess whether the missing data mechanism in combination
We sought any unclear or missing information by contacting the
with the method used to handle missing data was likely to
authors of the individual trials. We performed an intention-to-treat
induce bias on the estimate of effect).
analysis (Newell 1992), whenever possible. We planned to impute
• High risk of bias (the crude estimate of effects (eg, complete case data for binary outcomes using various scenarios such as best-best
estimate) was clearly biased due to the underlying reasons for scenario, worst-worst scenario, best-worst scenario, and worst-best
missingness, and the methods used to handle missing data are scenario (Gurusamy 2009; Gluud 2013).
unsatisfactory).
For continuous outcomes, we used available-case analysis. We
Selective outcome reporting imputed the standard deviation from P values according to the
• Low risk of bias (the trial protocol was available and all of instructions given in the Cochrane Handbook for Systematic Reviews
the trial's pre-specified outcomes that are of interest in the of Intervention (Higgins 2011), and used the median for the meta-
review had been reported or similar; if the trial protocol was not analysis when the mean was not available. If it was not possible
available, mortality and morbidity were reported). to calculate the standard deviation from the P value or the CIs, we
• Uncertain risk of bias (there was insufficient information to imputed the standard deviation as the highest standard deviation
assess whether the magnitude and direction of the observed in the other trials included under that outcome, fully recognising
effect was related to selective outcome reporting). that this form of imputation will decrease the weight of the study
for calculation of mean differences and bias the effect estimate to
• High risk of bias (not all of the trial's pre-specified primary
no effect in case of SMD (Higgins 2011).
outcomes had been reported or similar).
Assessment of heterogeneity
For this purpose, the trial should have been registered either on the
www.clinicaltrials.gov website or a similar register, or there should We explored heterogeneity using the Chi2 test with significance set
be a protocol (eg, published in a paper journal). In the case when at P value 0.10 and measured the quantity of heterogeneity using
the trial was run and published in the years when trial registration the I2 statistic (Higgins 2002). We also used overlapping of CIs on
was not required, we scrutinised all publications reporting on the the forest plot to determine heterogeneity.
trial carefully to identify the trial objectives and outcomes and
determine whether usable data were provided in the publication's Assessment of reporting biases
results section on all outcomes specified in the trial objectives.
We planned to use visual asymmetry on a funnel plot to explore
Vested interest bias reporting bias if 10 or more trials were identified (Egger 1997;
Macaskill 2001). We also planned to perform linear regression
• Low risk of bias (the trial was not performed or supported by approach described by Egger 1997 to determine the funnel plot
any parties that might have conflicting interest, eg, instrument asymmetry.
manufacturer).
• Uncertain risk of bias (any conflicts of interest of the trialist or Data synthesis
trial funder was not clear). Meta-analysis
• High risk of bias (the trial was performed or supported by
any parties that might have conflicting interest, eg, instrument We performed the meta-analyses using the software package
manufacturer). Review Manager 5 (RevMan 2012), and following the
recommendations of The Cochrane Collaboration (Higgins 2011),
We classified trials with high risk of bias or uncertain risk of bias in and the Cochrane Hepato-Biliary Group Module (Gluud 2013). We
any of the domains as trials with high risk of bias. The trials judged used both random-effects model (DerSimonian 1986) and fixed-
with low risk of bias in all domains were classified as trials with low effect model (DeMets 1987) meta-analyses. In case of discrepancy
risk of bias. between the two models resulting in change of conclusions,
we have reported both results in the full text and the more
Measures of treatment effect conservative model in the abstract, Summary of findings for the
main comparison, and the plain language summary; otherwise, we
For binary outcomes, we calculated the risk ratio (RR) with 95%
have reported the results of the fixed-effect model.
confidence interval (CI). RR calculations do not include trials in
which no events occurred in either group, whereas risk difference Trial sequential analysis
calculations do. We planned to report the risk difference if the
conclusions using this association measure were different from RR. We used trial sequential analysis to control for random errors due
For continuous outcomes, we calculated the mean difference (MD) to sparse data and repetitive testing of the accumulating data for
with 95% CI for outcomes such as operating time and hospital stay the primary outcomes (CTU 2011; Thorlund 2011). We added the
and the standardised mean difference (SMD) with 95% CI for quality trials according to the year of publication. If more than one trial
of life (where different scales might be used). was published in a year, we added the trials in alphabetical order
according to the last name of the first author. We constructed the
Unit of analysis issues trial sequential monitoring boundaries on the basis of the diversity-
adjusted required information size (Wetterslev 2008; Wetterslev
The unit of analysis were individual participants undergoing
2009).
fewer-than-four-ports laparoscopic cholecystectomy or four-port
laparoscopic cholecystectomy. We applied trial sequential analysis (CTU 2011; Thorlund 2011)
using a required sample size calculated from an alpha error of 0.05,
Informed decisions.

a beta error of 0.20, a control group proportion obtained from the Sensitivity analysis
results, and a relative risk reduction of 20% for primary binary
We planned to perform a sensitivity analysis by imputing data
outcomes with two or more trials to determine whether more
for binary outcomes using various scenarios such as best-best
trials are necessary on this topic (if the trial sequential monitoring
scenario, worst-worst scenario, best-worst scenario, and worst-best
boundary and the required information size is reached or the
scenario in the presence of missing outcome data (Gurusamy 2009;
futility zone is crossed, then more trials may be unnecessary) (Brok
Gluud 2013). We performed a sensitivity analysis by excluding the
2008; Wetterslev 2008; Brok 2009; Thorlund 2009; Wetterslev 2009;
trials in which the mean and the standard deviation were imputed.
Thorlund 2010). For quality of life, the required sample size was
calculated from an alpha error of 0.05, a beta error of 0.20, the Summary of findings table
variance estimated from the meta-analysis results of low risk of bias
trials if possible, and a minimal clinically relevant difference of 0.25. We have reported all the outcomes with at least one trial in
In trial sequential analyses in which the accrued information size Summary of findings for the main comparison. This table provides
surpassed the diversity-adjusted required information size (DARIS) a summary of the number of participants, number of trials,
(ie, days of hospital stay and days of return to normal activity), intervention effect estimates, and the quality of evidence for each
we post-hoc challenged the accrued information size with trial outcome.
sequential analyses based on a minimal relevant difference equal
to the smallest of the 95% CIs of the meta-analysis. RESULTS
Subgroup analysis and investigation of heterogeneity Description of studies

We planned to perform the following subgroup analyses. Results of the search
We identified 4780 references through electronic searches of
• Trials with high risk of bias compared to trials with low risk of
bias. CENTRAL (N = 761), MEDLINE (N = 1240), EMBASE (N = 1086), Science
Citation Index Expanded (N = 1663), and WHO ICTRP (N = 30). We
• Elective cholecystectomy compared to trials with emergency identified one further reference on handsearching of reference lists
cholecystectomy. of identified trials. We excluded 1563 duplicates and 3147 clearly
• Number of ports (one or two or three). irrelevant references through reading abstracts. We retrieved 71
references in full text for further assessment. Three trials were
Of these, we performed only the last subgroup analysis because of
ongoing trials with no interim reports available (Characteristics
the reasons stated in the results section. We used the Chi2 test for of ongoing studies). We excluded 58 references of 54 studies or
subgroup differences to identify subgroup differences. reports. The reasons for exclusion are stated in the Characteristics
of excluded studies. In total, we included 10 references of nine
completed trials in this review. The reference flow is shown in Figure
1.


Informed decisions.

Figure 1. Study flow diagram.


Informed decisions.

Figure 1. (Continued)

Included studies five trials that provided this information (Bucher 2011; Lirici 2011;
Herrero 2012; Sinan 2012; Saad 2013). The length of the incision was
Nine trials randomised 855 participants to fewer-than-four-ports
not reported in the two other trials in which a single port was used
laparoscopic cholecystectomy (n = 427) and four-port laparoscopic
(Abd Ellatif 2013; Luna 2013). Two trials included three ports, where
cholecystectomy (n = 428). Four trials included low anaesthetic risk
one of the subcostal incisions was left out in the intervention group
participants undergoing elective laparoscopic cholecystectomy
(Cerci 2007; Kumar 2007).
(Kumar 2007; Lirici 2011; Abd Ellatif 2013; Saad 2013). The
anaesthetic risk status was not available in the remaining five Excluded studies
trials (Cerci 2007; Bucher 2011; Herrero 2012; Sinan 2012; Luna
2013). Seven trials stated that they included people undergoing We excluded some studies because they were not
elective laparoscopic cholecystectomy (Kumar 2007; Bucher 2011; randomised trials. We excluded othertrials because the
Lirici 2011; Herrero 2012; Sinan 2012; Abd Ellatif 2013; Saad control group was not standard laparoscopic cholecystectomy
2013). The information on the inclusion of emergency laparoscopic although the authors stated that the control group was
cholecystectomies was not available in two trials (Cerci 2007; Luna standard laparoscopic cholecystectomy. We considered standard
2013). The mean age ranged between 39 and 50 years in the laparoscopic cholecystectomy as that performed with two ports of
eight trials that provided this information (Kumar 2007; Cerci 2007; at least 10 mm in size and two ports of at least 5 mm in size. A
Bucher 2011; Lirici 2011; Herrero 2012; Sinan 2012; Abd Ellatif 2013; few trials were ongoing trials and it is difficult to judge whether
Saad 2013). The proportion of females ranged between 23% and these trials will meet the inclusion criteria in future because of the
83% in the seven trials that reported this information (Cerci 2007; limited information available from interim reports or trial registers.
Kumar 2007; Lirici 2011; Herrero 2012; Sinan 2012; Abd Ellatif 2013; The reasons for exclusion in the individual trials are stated in the
Saad 2013). In seven trials, a single umbilical port was used (Bucher 'Characteristics of excluded studies' table.
2011; Lirici 2011; Herrero 2012; Sinan 2012; Abd Ellatif 2013; Luna
2013; Saad 2013). There were two channels (Abd Ellatif 2013), three Risk of bias in included studies
channels (Bucher 2011; Lirici 2011; Herrero 2012; Saad 2013), or The risk of bias is summarised in Figure 2. The risk of bias in
four channels (Luna 2013) in the single port through which the individual trials is stated in Figure 3. Only one trial had low risk of
instruments could be introduced. The number of channels in the bias (Saad 2013). The remaining trials had high risk of bias (Cerci
single port was not available in one trial (Sinan 2012). The length 2007; Kumar 2007; Bucher 2011; Lirici 2011; Herrero 2012; Sinan
of the umbilical incision ranged between 15 and 25 mm in the 2012; Abd Ellatif 2013; Luna 2013).


Informed decisions.

Figure 2. Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages
across all included studies.


Informed decisions.

Figure 3. Risk of bias summary: review authors' judgements about each risk of bias item for each included study.

Effects of interventions seven trials in which it was possible to calculate this (Kumar 2007;
Bucher 2011; Lirici 2011; Herrero 2012; Abd Ellatif 2013; Luna 2013;
See: Summary of findings for the main comparison Fewer- Saad 2013). The remaining participants were mostly converted
than-four ports compared with four ports for laparoscopic to four-port laparoscopic cholecystectomy, but some were also
cholecystectomy converted to open cholecystectomy. The findings are summarised
in Summary of findings for the main comparison.
Fewer-than-four-ports laparoscopic cholecystectomy was
successful in between 90% and 100% of the participants in the

Informed decisions.

Primary outcomes mortality in either group, we were unable to use the control
group proportion for the calculation of the required information
Mortality
size of the trial sequential analysis as before. Instead, we used
Mortality data were available from seven trials (Bucher 2011; a proportion of 0.2% in the control group based on data from
Lirici 2011; Herrero 2012; Sinan 2012; Abd Ellatif 2013; Luna approximately 30,000 people included in a database in Switzerland
2013; Saad 2013). There was no mortality in either group (Giger 2011). The proportion of information accrued was only 0.18%
in these seven trials (318 participants in fewer-than-four-ports of the DARIS and so the trial sequential monitoring boundaries
laparoscopic cholecystectomy group and 316 participants in four- were not drawn (Figure 4). The cumulative Z-curve did not cross the
port laparoscopic cholecystectomy group). Since there was no conventional statistical boundaries.

Figure 4. Trial sequential analysis of mortality The diversity-adjusted required information size (DARIS) was
calculated to 352,564 participants, based on the proportion of participants in the control group with the outcome
of 0.2%, a relative risk reduction of 20%, an alpha of 5%, a beta of 20%, and a diversity of 0%. To account for zero
event groups, a continuity correction of 0.01 was used in the calculation of the cumulative Z-curve (blue line). After
accruing 634 participants in seven trials, only 0.18% of the DARIS has been reached. Accordingly, the trial sequential
analysis does not show the required information size and the trial sequential monitoring boundaries. As shown, the
conventional boundaries (dotted red line) have also not been crossed by the cumulative Z-curve.

Surgical morbidity (serious adverse events) or by using risk difference as the effect measure. Since there were
no serious adverse events in the control group, we were unable
Seven trials reported the proportion of participants with serious
to use the control group proportion for the calculation of the
adverse events (Bucher 2011; Lirici 2011; Herrero 2012; Sinan 2012;
required information size of the trial sequential analysis as before.
Abd Ellatif 2013; Luna 2013; Saad 2013). There were no serious
Instead, we used a proportion of 0.3% in the control group based on
adverse events in the four-port group. There was no significant
data from approximately 30,000 people included in a database in
difference in the proportion of participants with serious adverse
Switzerland as before (Giger 2011). The proportion of information
events between the fewer-than-four-ports group and four-port
accrued was only 0.27% of the DARIS and so the trial sequential
laparoscopic cholecystectomy group using the fixed-effect model
monitoring boundaries were not drawn (Figure 5). The cumulative
(RR 3.93; 95% CI 0.86 to 18.04) (Analysis 1.1). There were no changes
Z-curve does not cross the conventional statistical boundaries.
in the results with the random-effects model for the meta-analysis
Informed decisions.


Figure 5. Trial sequential analysis of serious adverse events The diversity-adjusted required information size
(DARIS) was calculated to 234,831 participants, based on the proportion of participants in the control group with the
outcome of 0.3%, a relative risk reduction of 20%, an alpha of 5%, a beta of 20%, and a diversity of 0%. To account
for zero event groups, a continuity correction of 0.01 was used in the calculation of the cumulative Z-curve (blue
line). After accruing 634 participants in seven trials, only 0.27% of the DARIS has been reached. Accordingly, the trial
sequential analysis does not show the required information size and the trial sequential monitoring boundaries. As
shown, the conventional boundaries (dotted red line) have also not been crossed by the cumulative Z-curve.

Quality of life Secondary outcomes
Four trials reported this outcome (Bucher 2011; Lirici 2011; Abd Conversion to open cholecystectomy
Ellatif 2013; Saad 2013). The quality of life was measured between
Five trials reported the proportion of participants in whom
10 days and one month after surgery in these trials (Bucher
the laparoscopic cholecystectomy had to be converted to open
2011; Lirici 2011; Abd Ellatif 2013; Saad 2013). The scales used
cholecystectomy (Cerci 2007; Kumar 2007; Bucher 2011; Lirici
included EQ-5D (Abd Ellatif 2013), Gastrointestinal Quality of Life
2011; Abd Ellatif 2013). There was no significant difference
Index (GIQLI) (Saad 2013), Short Form - 12 (SF-12) (Bucher 2011),
in the proportion of participants in whom the laparoscopic
and Short Form - 36 (Lirici 2011). Quality of life was significantly
cholecystectomy had to be converted to open cholecystectomy
better with fewer-than-four-ports than four-port laparoscopic
between the two groups using the fixed-effect model (RR 0.68;
cholecystectomy with the fixed-effect model (SMD 0.21; 95% CI
95% CI 0.19 to 2.35) (Analysis 1.3). Using the random-effects model
0.03 to 0.38). There was no significant difference between the two
or risk difference did not alter the conclusions. Trial sequential
treatments with the random-effects model (SMD 0.18; 95% CI -0.05
analysis revealed that the proportion of information accrued was
to 0.42) (Analysis 1.2). Trial sequential analysis was not performed
only 1.42% of the DARIS and so the trial sequential monitoring
since the software does not allow calculation of SMD.
boundaries were not drawn (Figure 6). The cumulative Z-curve did
not cross the conventional statistical boundaries.


Informed decisions.

Figure 6. Trial sequential analysis of conversion to open cholecystectomy The diversity-adjusted required
information size (DARIS) was calculated to 40,918 participants, based on the proportion of patients in the control
group with the outcome of 1.7%, a relative risk reduction of 20%, an alpha of 5%, a beta of 20%, and a diversity of
0%. To account for zero event groups, a continuity correction of 0.01 was used in the calculation of the cumulative
Z-curve (blue line). After accruing 581 participants in five trials, only 1.42% of the DARIS has been reached.
Accordingly, the trial sequential analysis does not show the required information size and the trial sequential
monitoring boundaries. As shown, the conventional boundaries (dotted red line) have also not been crossed by the
cumulative Z-curve.

Operating time (Analysis 1.4). There was no change in the results by using the
random-effects model. Trial sequential analysis revealed that the
All the trials reported operating time. The fewer-than-four-ports
trial sequential boundaries were crossed suggesting that the
laparoscopic cholecystectomy took seven minutes longer to
operating time was likely to be longer in the fewer-than-four-ports
complete than the four-ports laparoscopic cholecystectomy using
group than four-ports group with low risk of random errors (Figure
the fixed-effect model (MD 14.44 minutes; 95% CI 5.95 to 22.93)
7).


Informed decisions.

Figure 7. Trial sequential analysis of operating time The diversity-adjusted required information size (DARIS)
was 1124 participants based on a minimal relevant difference (MIRD) of 15 minutes, a variance (VAR) of 385.03,
an alpha (a) of 5%, a beta (b) of 20%, and a diversity (D2) of 95.2%.The cumulative Z-curve (blue line) crosses the
conventional boundary (dotted red line) and the trial sequential monitoring boundaries (continuous red line) after
the seventh trial. Although the DARIS has not been reached after accrual of 855 participants in nine trials, the results
suggest that operating time is longer with fewer-than-four-ports laparoscopic cholecystectomy as compared with
four-ports laparoscopic cholecystectomy with low risk of random errors.

Hospital stay underwent day-surgery laparoscopic cholecystectomy between
the groups (RR 0.92; 95% CI 0.70 to 1.22) (Analysis 1.6). Trial
Six trials reported the length of hospital stay (Cerci 2007; Kumar
sequential analysis revealed that the DARIS has been reached and
2007; Bucher 2011; Lirici 2011; Abd Ellatif 2013; Saad 2013). Hospital
the conventional boundaries were not crossed (Figure 8). This
stay was significantly longer in the fewer-than-four-ports group
suggests that there is unlikely to be a difference in the length
than four-ports group using the fixed-effect model (MD 0.14 days;
of hospital stay between the groups with low risk of random
95% CI 0.02 to 0.26). There was no significant difference in the
errors. Trial sequential analysis after changing the minimal relevant
hospital stay between the groups by using the random-effects
difference (MIRD) to the smallest limit of the 95% CI of the meta-
model (MD -0.01 days; 95% CI -0.28 to 0.26) (Analysis 1.5). One
analysis showed that the proportion of information accrued was
trial reported the proportion of participants discharged as day-
only 26.09% of the DARIS and that neither the trial sequential
surgery laparoscopic cholecystectomy (Herrero 2012). There was
monitoring boundaries nor the conventional boundaries were
no significant difference in the proportion of participants who
crossed (Figure 9).


Informed decisions.

Figure 8. Trial sequential analysis of hospital stay

The diversity-adjusted required information size (DARIS) was 222 participants based on a minimal relevant
difference (MIRD) of 1 day, a variance (VAR) of 1.29, an alpha (a) of 5%, a beta (b) of 20%, and a diversity (D2) of
81.55%. Seven hundred and thirty-one participants were accrued in six trials. The cumulative Z-curve (blue line)
crosses the DARIS after the third trial (vertical red line). However, it does not cross the conventional boundaries
(dotted red line). This suggests that there is no significant difference in the length of hospital stay between fewer-
than-four-ports laparoscopic cholecystectomy versus four-ports laparoscopic cholecystectomy with low risk of
random errors.


Informed decisions.

Figure 9. Trial sequential analysis of hospital stay with smallest confidence interval used as minimal relevant
difference
difference (MIRD) of 0.28 days, a variance (VAR) of 1.29, an alpha (a) of 5%, a beta (b) of 20%, and a diversity (D2) of
81.55%. After accruing 731 participants in six trials, only 26.09% of the DARIS has been reached. Accordingly, the
trial sequential analysis does not show the futility area. As shown, the cumulative Z-curve (blue line) does not cross
the trial sequential boundaries (red line). Conventional boundaries (dotted red line) have also not been crossed by
the cumulative Z-curve.

Return to activity and work between the two groups using the random-effects model. Trial
sequential analysis revealed that the trial sequential boundaries
Two trials reported the time taken to return to activity (Kumar 2007;
were crossed suggesting that the time taken to return to activity
Abd Ellatif 2013). The time taken to return to normal activity was
was likely to be shorter in the fewer-than-four-ports group than
significantly shorter in the fewer-than-four-ports group than the
four-ports group with low risk of random errors (Figure 10). The trial
four-ports group using the fixed-effect model (MD -1.20 days; 95%
sequential analysis results did not change by changing the MIRD to
CI -1.58 to -0.81) (Analysis 1.7). There was no change in the results
the smallest of the 95% CI of the meta-analysis (Figure 11).


Informed decisions.

Figure 10. Trial sequential analysis of return to normal activity
difference (MIRD) of 1 day, a variance (VAR) of 6.35, an alpha (a) of 5%, a beta (b) of 20%, and a diversity (D2) of 0%.
Three hundred and twenty-five participants were accrued in two trials. The cumulative Z-curve crosses the trial
sequential monitoring boundaries (continuous red lines) and the conventional boundaries (dotted red line) after the
second trial. The results are compatible with significantly fewer days to return to normal activity in the fewer-than-
four-ports group with four-ports group with low risk of random errors.


Informed decisions.

Figure 11. Trial sequential analysis of return to normal activity with smallest confidence interval used as minimal
relevant difference The diversity-adjusted required information size (DARIS) was 304 participants based on a
minimal relevant difference (MIRD) of 0.81 day, a variance (VAR) of 6.35, an alpha (a) of 5%, a beta (b) of 20%, and a
diversity (D2) of 0%. Three hundred and twenty-five participants were accrued in two trials. The cumulative Z-curve
crosses the trial sequential monitoring boundaries (continuous red lines) and the conventional boundaries (dotted
red line) after the second trial. The results are compatible with significantly fewer days to return to normal activity
in the fewer-than-four-ports group with four-ports group with low risk of random errors.

One trial reported the time taken to return to work (Bucher 2011). We performed a subgroup analysis based on the number of ports.
The time taken to return to work was shorter by two days in the We compared whether the results were different between the trials
fewer-than-four-ports group compared with four-port laparoscopic that used a single port versus those that used three ports. The Chi2
cholecystectomy (MD -2.00 days; 95% CI -3.31 to -0.69) (Analysis test for subgroup differences was not statistically significant for
1.8). Since this was the only trial, the issue of fixed-effect versus any of the outcomes in which the two subgroups were represented
random-effects meta-analysis does not arise and trial sequential (conversion to open cholecystectomy (Analysis 1.3; P value = 0.62),
analysis was not performed. hospital stay (Analysis 1.5; P value = 0.67), return to normal activity
(Analysis 1.7; P value = 0.89) except operating time (Analysis 1.4; P
Cosmesis value = 0.001). For operating time, the operating time was longer
Two trials reported cosmesis at multiple time points (Abd Ellatif for one-port than four-ports group (MD 21.04 minutes; 95% CI 10.45
2013; Saad 2013). We obtained the values at six months and one to 31.62) while there was no significant difference in the operating
year since wound remodelling can take place even one year after time between three-port and four-port groups (MD -5.32 minutes;
surgery (Gurtner 2008). The cosmesis scores were significantly 95% CI -17.38 to 6.73) (Analysis 1.4).
better in the fewer-than-four-ports group than four-ports group
Sensitivity analysis
using the fixed-effect model (SMD 0.46; 95% CI 0.24 to 0.69). There
was no significant difference in the cosmesis scores between the We did not perform the planned sensitivity analysis by imputing
groups using the random-effects model (SMD 0.37; 95% CI -0.10 to data for binary outcomes using various scenarios such as best-best
0.84) (Analysis 1.9). Trial sequential analysis cannot be performed scenario, worst-worst scenario, best-worst scenario, and worst-best
when SMD is calculated. scenario in the presence of missing outcome data (Gurusamy 2009;
Gluud 2013). This was because there were no post-randomisation
Subgroup analysis drop-outs in six of the nine included trials (Cerci 2007; Kumar
Two planned subgroup analyses (trials with high risk of bias 2007; Bucher 2011; Lirici 2011; Abd Ellatif 2013; Saad 2013). In the
versus low risk of bias and elective cholecystectomy versus remaining three trials, it was not clear whether there were any post-
emergency cholecystectomy) were not performed because one of randomisation drop-outs (Herrero 2012; Sinan 2012; Luna 2013).
the subgroups had only one trial (only one trial was of low risk
We performed a sensitivity analysis by excluding the trials in
of bias (Saad 2013) and only one trial had a possible inclusion
which either the mean or the standard deviation or both were
of emergency laparoscopic cholecystectomy (Cerci 2007)). Such a
imputed. This was only possible for quality of life (Analysis 2.1),
subgroup analysis is prone to error.

Informed decisions.

operating time (Analysis 2.2), hospital stay (Analysis 2.3), and return analogue scale is unknown for laparoscopic cholecystectomy.
to normal activity (Analysis 2.4). There was no change in the Future trials assessing fewer-than-four ports could use the length
conclusions by performing this sensitivity analysis for operating of hospital stay or the proportion of people discharged as day-
time, hospital stay, and return to normal activity. However, there surgery laparoscopic cholecystectomy as the outcome based on
was no significant difference in the quality of life between the which sample size calculations are performed to decrease type I
groups when the trials in which either the mean or the standard and type II errors. This has significant cost benefits to the healthcare
deviation or both were imputed (SMD 0.14; 95% CI -0.08 to 0.36). funder. Any cost savings can be used to fund other treatments
or other socially beneficial projects in a state-sponsored health
Of the remaining continuous outcomes, there was no imputation scheme.
of mean or standard deviation of cosmetic score in the two trials
that reported this outcome (Abd Ellatif 2013; Saad 2013). Although It is important that the participants and outcome assessors
the mean and the standard deviation were imputed for return to are blinded to the groups if discharge following day-procedure
work, we did not perform a sensitivity analysis since only one trial laparoscopic cholecystectomy is used as primary outcome in such
reported this outcome (Analysis 1.8). trials, as the decision to discharge a participant following day
procedure is subjective. Quality of life is another outcome that
Funnel plot should be measured in such trials as they have implications in
We did not explore reporting bias using funnel plot because this cost-effectiveness analysis. Cosmesis is only one aspect of quality
review included nine trials only. of life and cannot be used in any economic health evaluation.
However, it is an important patient outcome. Wound remodelling
DISCUSSION occurs even at one year after surgery (Gurtner 2008). Trials should
follow participants for at least one year if cosmesis is assessed. It is
Summary of main results important to perform intention-to-treat analyses so that the mean
clinical efficacy and cost-effectiveness of the intervention (fewer-
In this review, we did not find any difference in than-four ports) can be easily determined and used in economic
mortality or morbidity between fewer-than-four-ports laparoscopic evaluation.
cholecystectomy versus four-port laparoscopic cholecystectomy.
There were no deaths in the seven trials that reported Overall completeness and applicability of evidence
this outcome (Bucher 2011; Lirici 2011; Herrero 2012; Sinan
2012; Abd Ellatif 2013; Luna 2013; Saad 2013). Mortality after This review is applicable only to elective laparoscopic
laparoscopic cholecystectomy is approximately 0.2% (Giger 2011). cholecystectomy performed in low anaesthetic risk participants as
Most of the trials included in this review randomised people most trials included such participants. Most of the trials excluded
with low anaesthetic risk and undergoing elective laparoscopic moderately obese (Herrero 2012; Abd Ellatif 2013; Luna 2013),
cholecystectomy. Therefore, it is not surprising that there was no severely obese (Lirici 2011; Saad 2013), or very severely obese
mortality in either group. There was no significant difference in participants undergoing laparoscopic cholecystectomy (Sinan
the proportion of people who developed serious adverse events. 2012). Therefore, the findings of the review are applicable only in
However, it is unsure if this was because there was no difference non-obese people undergoing laparoscopic cholecystectomy.
in the proportion of people who develop serious adverse events
between fewer-than-four-ports laparoscopic cholecystectomy and Quality of the evidence
four-port laparoscopic cholecystectomy or whether this is because Only one trial was of low risk of bias (Saad 2013). There was
of lack of evidence of a difference between the groups. This is moderate to severe inconsistency in some of the outcomes, such as
because of wide CI values that overlapped no effect (RR of 1) and hospital stay and operating time. Overall, the evidence is of very low
a 25% relative risk reduction or increase (0.75 or 1.25). It should be quality as shown in Summary of findings for the main comparison.
noted that the proportion of people with serious adverse events However, it must be noted that this is the best level of evidence
was higher in the fewer-than-four-ports group (6/318 (1.9%)) versus available.
four-port laparoscopic cholecystectomy (0/318 (0%)). This could
have happened by chance, but there is also a possibility that this Potential biases in the review process
was a true difference. Until further trials demonstrate the safety
of fewer-than-four-ports laparoscopic cholecystectomy, it cannot We imputed the mean from median and standard deviation based
be recommended routinely particularly because it does not seem on guidance from the Cochrane Handbook for Systematic Reviews of
to offer any significant benefits in terms of improved quality of Interventions (Higgins 2011). This might have introduced bias in the
life or decreased length of hospital stay. Although the fewer-than- review process.
four-ports group returned to normal activity and work significantly
Agreements and disagreements with other studies or
earlier compared to the four-port laparoscopic cholecystectomy
group, it must be noted that the trials appeared to lack blinding, reviews
which may have a significant influence on these outcomes. Several reviews exist on fewer-than-four ports (mostly
single-port laparoscopic cholecystectomy) versus conventional
Given the low incidence of complications in four-port laparoscopic laparoscopic cholecystectomy in people undergoing laparoscopic
cholecystectomy, it is unlikely that the trials assessing the cholecystectomy for various indications such as symptomatic
fewer ports can be powered to measure a reduction in the gallstones and gallbladder polyps. Some reviews suggested
complications after laparoscopic cholecystectomy. Use of pain that single-port laparoscopic cholecystectomy was safe (Markar
as one of the primary outcomes can also be misleading, as the 2012; Song 2012) and effective (Garg 2012a; Pisanu 2012), and
clinical significance of reduction in pain scores measured by visual can be offered as alternatives to conventional laparoscopic

Informed decisions.

cholecystectomy while other reviews suggested that there was Implications for research
no benefit with single-port laparoscopic cholecystectomy or that
there was a balance between benefits and harms and suggested Further well-designed randomised clinical trial with low risk
a more cautious approach (Sun 2009; Hall 2012; Wang 2012). We of random and systematic errors are necessary. Such trials
have recommended that using fewer-than-four ports should be should be designed according to the SPIRIT (Standard Protocol
reserved to well-designed randomised clinical trials. Some of the Items: Recommendations for Interventional Trials) statement and
reasons for our disagreements with other researchers are that the reported according to the CONSORT (CONsolidated Standards Of
other researchers included trials in which the control group was not Reporting Trials) statement (Moher 2010; Chan 2013).
necessarily four ports with at least two 10-mm ports and two 5-mm
ACKNOWLEDGEMENTS
ports, misinterpretation between lack of evidence of harm and lack
of harm, and use of very early cosmesis scores that are ultimately To the Cochrane Hepato-Biliary Group for the support that they
of no clinical significance. have provided.
AUTHORS' CONCLUSIONS Peer reviewers: Stefano Trastulli, Italy; Giorgakis Emmanouil, UK.
Contact editor: Christian Gluud, Denmark.
Implications for practice
This project was funded by the National Institute for Health
The safety profile of using fewer-than-four ports is yet
Research.
to be established and fewer-than-four-ports laparoscopic
cholecystectomy should be reserved to well-designed randomised Disclaimer of the Department of Health: "The views and
clinical trials. We found very low quality evidence on clinical opinions expressed in the review are those of the authors and
outcomes to support the use of fewer-than-four-ports laparoscopic do not necessarily reflect those of the National Institute for
cholecystectomy. The shorter time taken to return to normal Health Research (NIHR), National Health Services (NHS), or the
activity and time taken to return to work associated with using Department of Health".
fewer-than-four ports comes from evidence of very low quality.

Informed decisions.

REFERENCES

References to studies included in this review Sinan 2012 {published data only}
Abd Ellatif 2013 {published data only} Sinan H, Demirbas S, Ozer MT, Sucullu I, Akyol M. Single-
incision laparoscopic cholecystectomy versus laparoscopic
Abd Ellatif ME, Askar WA, Abbas AE, Noaman N, Negm A,
cholecystectomy: a prospective randomized study. Surgical
El-Morsy G, et al. Quality-of-life measures after single-
Laparoscopy, Endoscopy and Percutaneous Techniques
access versus conventional laparoscopic cholecystectomy:
2012;22(1):12-6.
a prospective randomized study. Surgical Endoscopy
2013;27(6):1896-906.
References to studies excluded from this review
Bucher 2011 {published data only}
Bucher P, Pugin F, Buchs NC, Ostermann S, Morel P. Randomized Allemann 2012 {published data only}
clinical trial of laparoendoscopic single-site versus conventional Allemann P. Safety and cost-effectiveness study of single
laparoscopic cholecystectomy. British Journal of Surgery port laparoscopic cholecystectomies (SPoCOT), 2012.
2011;98(12):1695-702. clinicaltrials.gov/show/NCT00974194 (accessed 13 February
2014).
Cerci 2007 {published data only}
Cerci C, Tarhan OR, Barut I, Bulbul M. Three-port versus four- Asakuma 2011 {published data only}
port laparoscopic cholecystectomy. Hepato-Gastroenterology Asakuma M. Randomized controlled trial to evaluate the
2007;54(73):15-6. superiority of the Single Port Cholecystectomy (SPC)
on reduction of postoperative pain, compared with the
Herrero 2012 {published data only} conventional laparoscopic cholecystectomy at the single
Herrero E, Cugat E, García-Domingo MI, Camps J, Porta R, institution, 2011. www.umin.ac.jp/ctr/index.htm (accessed 13
Carvajal F, et al. A randomised prospective comparative February 2014).
study between laparoscopic cholecystectomy and single port
cholecystectomy in a major outpatient surgery unit. Cirugia Bansal 2012 {published data only}
Espanola 2012;90(10):641-6. Bansal VK. A prospective randomized control trial comparing
the outcome of the two modalities of treatment of gall stone
Kumar 2007 {published data only} disease viz. single incision laparoscopic cholecystectomy
Kumar M, Agrawal CS, Gupta RK. Three-port versus standard with standard 4 port laparoscopic cholecystectomy, 2012.
four-port laparoscopic cholecystectomy: A randomized www.ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=5253
controlled clinical trial in a community-based teaching hospital (accessed 13 February 2014).
in eastern Nepal. Journal of the Society of Laparoendoscopic
Surgeons 2007;11(3):358-62. Barugola 2011 {published data only}
Barugola G. Single port laparoscopic cholecystectomy
Lirici 2011 {published data only} versus four port laparoscopic cholecystectomy: impact on
Lirici MM, Califano AD, Angelini P, Corcione F. Laparo- postoperative pain, 2011. clinicaltrials.gov/show/NCT01348620
endoscopic single site cholecystectomy versus standard (accessed 13 February 2014).
laparoscopic cholecystectomy: results of a pilot randomized
trial. American Journal of Surgery 2011;202(1):45-52. Bingener-Casey 2012 {published data only}
Bingener-Casey J. Comparative effectiveness of novel minimally
Luna 2013 {published data only} invasive procedures, 2012. clinicaltrials.gov/show/NCT01489436
Luna RA, Nogueira DB, Varela PS, De ORNE, Norton MJR, Do (accessed 13 February 2014).
Carmo BRL, et al. A prospective, randomized comparison
of pain, inflammatory response, and short-term outcomes Bresadola 1999 {published data only}
between single port and laparoscopic cholecystectomy. Bresadola F, Pasqualucci A, Donini A, Chiarandini P, Anania G,
Surgical Endoscopy 2013;27(4):1254-9. Terrosu G, et al. Elective transumbilical compared with standard
laparoscopic cholecystectomy. European Journal of Surgery
Saad 2013 {published data only} 1999;165(1):29-34.
Saad S, Strassel V, Martin C, Sauerland S. Single port-versus
mini-versus conventional laparoscopic cholecystectomy- Broeders 2010 {published data only}
a blinded randomized controlled trial. Surgical Endoscopy Broeders IAMJ. Randomized clinical trial of single-incision
2013;27(Suppl 1):S14. laparoscopic cholecystectomy versus minilaparoscopic
cholecystectomy. British Journal of Surgery 2010;97(7):1012.
* Saad S, Strassel V, Sauerland S. Randomized clinical trial of
single-port, minilaparoscopic and conventional laparoscopic Brown 2013 {published data only}
cholecystectomy. British Journal of Surgery 2013;100(3):339-49. Brown KM, Moore BT, Sorensen GB, Boettger CH, Tang F,
Jones PG, et al. Patient-reported outcomes after single-incision
versus traditional laparoscopic cholecystectomy: a randomized
prospective trial. Surgical Endoscopy 2013;27(9):3108-15.

Informed decisions.

Cao 2011 {published data only} conventional laparoscopic cholecystectomy: a prospective trial
Cao ZG, Cai W, Qin MF, Zhao HZ, Yue P, Li Y. Randomized clinical of the Club Coelio. Surgical Endoscopy 2013;27(5):1689-94.
trial of single-incision versus conventional laparoscopic
Hu 2005 {published data only}
cholecystectomy: short-term operative outcomes. Surgical
Laparoscopy, Endoscopy and Percutaneous Techniques Hu H. Clinical application and study on three-port-looping
2011;21(5):311-3. laparoscopic cholecystectomy. China Journal of Endoscopy
2005;11:552.
Chang 2013 {published data only}
Hu 2010 {published data only}
Chang SK, Wang YL, Shen L, Iyer SG, Shaik AB, Lomanto D.
Interim report: A randomized controlled trial comparing Hu H, Zhu J, Wang W, Huang A. Optimized transumbilical
postoperative pain in single-incision laparoscopic endoscopic cholecystectomy: a randomized comparison of two
cholecystectomy and conventional laparoscopic procedures. Surgical Endoscopy 2010;24(5):1080-4.
cholecystectomy. Asian Journal of Endoscopic Surgery
Jorgensen 2010 {published data only}
2013;6(1):14-20.
Jorgensen LN. Efficacy of transumbilical versus standard
Chen 2002 {published data only} laparoscopic cholecystectomy on postoperative pain, 2010.
Chen TW, Hsieh CB, Huang SH, Yu JC, Liu YC, Monduzzi clinicaltrials.gov/show/NCT01268748 (accessed 13 February
Editore MEME. Learning curves of an inexperienced surgeon for 2014).
three-port microlaparoscopic cholecystectomy and four-port
Khorgami 2011 {published data only}
laparoscopic cholecystectomy. XXXIII World Congress of the
International College of Surgeons - ICS 2002. 2002:99-103. Khorgami Z. Comparison of perioperative outcomes following
four port, three port and single incision laparoscopic
Cockbain 2013 {published data only} cholecystectomy in patients of Shariati hospital in 2011.
Cockbain AJ. Randomized clinical trial of single-port, www.irct.ir/searchresult.php?id=2982&number=4 (accessed 13
minilaparoscopic and conventional laparoscopic February 2014).
cholecystectomy. British Journal of Surgery 2013;100(3):349-50.
Kim 2009 {published data only}
Dam 2011 {published data only} Kim SS, Kim SH, Mun SP. Should subcostal and lateral trocars
Dam DAV. Single Incision, MiniPort or convEntional be used in laparoscopic cholecystectomy? A randomized,
Laparoscopic surgery for uncomplicated sympthomatic prospective study. Journal of Laparoendoscopic and Advanced
cholecystolithiasis (SIMPEL-trial), 2011. www.trialregister.nl/ Surgical Techniques. Part A 2009;19(6):749-53.
trialreg/admin/rctview.asp?TC=3100 (accessed 13 February
Lai 2011 {published data only}
2014).
Lai EC, Yang GP, Tang CN, Yih PC, Chan OC, Li MK.
de Carvalho 2013 {published data only} Prospective randomized comparative study of single incision
de Carvalho LFA, Fierens K, Kint M. Mini-laparoscopic versus laparoscopic cholecystectomy versus conventional four-port
conventional laparoscopic cholecystectomy: a randomized laparoscopic cholecystectomy. American Journal of Surgery
controlled trial. Journal of Laparoendoscopic & Advanced 2011;202(3):254-8.
Surgical Techniques 2013;23(2):109-16.
Lee 2010 {published data only}
Garg 2012 {published data only} Lee PC, Lo C, Lai PS, Chang JJ, Huang SJ, Lin MT, et al.
Garg P, Thakur JD, Singh I, Nain N, Mittal G, Gupta V. A Randomized clinical trial of single-incision laparoscopic
prospective controlled trial comparing single-incision and cholecystectomy versus minilaparoscopic cholecystectomy.
conventional laparoscopic cholecystectomy: caution before British Journal of Surgery 2010;97(7):1007-12.
damage control. Surgical Laparoscopy, Endoscopy and
Leung 2011 {published data only}
Percutaneous Techniques 2012;22(3):220-5.
Leung D, Denham W, Salabat M, Butt Z, Barrera E, Ujiki M.
Gupta 2005 {published data only} Single-incision laparoscopic cholecystectomy results in similar
Gupta A, Shrivastava UK, Kumar P, Burman D. Minilaparoscopic short-term post-operative pain and quality of life scores when
versus laparoscopic cholecystectomy: a randomised controlled compared to multi-incision: A prospective randomized blinded
trial. Tropical Gastroenterology 2005;26(3):149-51. comparison. Surgical Endoscopy and Other Interventional
Techniques 2011;25(1 Suppl):S239.
Hansen 2011 {published data only}
Limberger 2005 {published data only}
Hansen P. A randomized trial of single port laparoscopic
cholecystectomy versus four port laparoscopic Limberger A, Pluszcyk T, Schilling M. [Laparoscopic
cholecystectomy, 2011. clinicaltrials.gov/show/NCT00892879 cholecystectomy. Preliminary results of a comparison of
(accessed 13 February 2014). 2 and 3 trocar operation techniques]. Chirurgische Praxis
2005;64(1):35-40.
Hauters 2013 {published data only}
Hauters P, Auvray S, Cardin JL, Papillon M, Delaby J,
Dabrowski A, et al. Comparison between single-incision and

Informed decisions.

Ma 2011 {published data only} Ng 1999 {published data only}

Ma J, Cassera MA, Spaun GO, Hammill CW, Hansen PD, Aliabadi- Ng WT. Three-port laparoscopic cholecystectomy: a plea for
Wahle S. Randomized controlled trial comparing single-port scientific evidence. Surgical Laparoscopy, Endoscopy and
laparoscopic cholecystectomy and four-port laparoscopic Percutaneous Techniques 1999;9(4):314-5.
cholecystectomy. Annals of Surgery 2011;254(1):22-7.
Noguera 2012 {published data only}
Madureira 2013 {published data only} Noguera JF, Cuadrado A, Dolz C, Olea JM, Garcia JC.
Madureira FA, Manso JE, Madureira Filho D, Iglesias AC. Prospective randomized clinical trial comparing laparoscopic
Inflammation in laparoendoscopic single-site surgery versus cholecystectomy and hybrid Natural Orifice Transluminal
laparoscopic cholecystectomy. Surgical Innovation 2013; Vol. Endoscopic Surgery (NOTES) (NCT00835250). Surgical
Epub ahead of print. Endoscopy 2012;26(12):3435-41.
* Madureira FAV, Manso JEF, Fo DM, Iglesias ACG. Randomized Ospanov 2013 {published data only}
clinical study for assessment of incision characteristics and pain Ospanov OB, Khassenov RE. Length of the wound and
associated with LESS versus laparoscopic cholecystectomy. postoperative scar after using single port laparoscopic
Surgical Endoscopy 2013;27(3):1009-15. cholecystectomy. Surgical Endoscopy 2013;27(Suppl 1):S74.
Madureira FAV, Manso JEF, Madureira D, Iglesias ACG. Ostlie 2013 {published data only}
Inflammation in less versus laparoscopic cholecystectomy.
Ostlie DJ, Adibe David Juang OO, Iqbal CW, Sharp SW,
Surgical Endoscopy 2013;27:S444.
Snyder CL, Andrews WS, et al. Single incision versus standard 4-
Marks 2011 {published data only} port laparoscopic cholecystectomy: a prospective randomized
trial. Journal of Pediatric Surgery 2013;48(1):209-14.
Marks J, Tacchino R, Roberts K, Onders R, Denoto G,
Paraskeva P, et al. Prospective randomized controlled trial of * Ostlie DJ, Sharp NE, Thomas P, Sharp SW, Holcomb GW,
traditional laparoscopic cholecystectomy versus single-incision Peter SD. Patient scar assessment after single-incision
laparoscopic cholecystectomy: report of preliminary data. versus four-port laparoscopic cholecystectomy: long-term
American Journal of Surgery 2011;201(3):369-72. follow-up from a prospective randomized trial. Journal of
Laparoendoscopic and Advanced Surgical Techniques. Part A
Marks 2012 {published data only}
2013;23(6):553-5.
Marks J. Prospective randomized controlled trial of traditional
laparoscopic cholecystectomy versus SILS™ port laparoscopic Pappas-Gogos 2010 {published data only}
cholecystectomy, 2012. clinicaltrials.gov/show/NCT00832767 Pappas-Gogos G. Study of oxidative stress in standard
(accessed 13 February 2014). laparoscopic vs single port cholecystectomy for uncomplicated
cholelithiasis (LAP vs SILS), 2010. clinicaltrials.gov/show/
Marks 2013 {published data only}
NCT01211743 (accessed 13 February 2014).
Marks JM, Phillips MS, Tacchino R, Roberts K, Onders R,
DeNoto G, et al. Single-incision laparoscopic cholecystectomy Pathania 2013 {published data only}
is associated with improved cosmesis scoring at the cost of Pathania BS. A comparative clinical evaluation of single incision
significantly higher hernia rates: 1-year results of a prospective laparoscopic cholecystectomy with single and multiport access
randomized, multicenter, single-blinded trial of traditional versus conventional mufti -port laparoscopic cholecystectomy.
multiport laparoscopic cholecystectomy vs single-incision European Surgical Research 2013;50:13-4.
laparoscopic cholecystectomy. Journal of the American College
of Surgeons 2013;216(6):1037-47. Patricia 2010 {published data only}
Patricia YCL. Prospective randomized trial of single port
McGregor 2011 {published data only}
laparoscopic cholecystectomy versus four ports laparoscopic
McGregor CG, Sodergren MH, Aslanyan A, Wright VJ, cholecystectomy in patients with gallbladder stones, 2010.
Purkayastha S, Darzi A, et al. Evaluating systemic stress www.anzctr.org.au/Trial/Registration/TrialReview.aspx?
response in single port vs. multi-port laparoscopic ACTRN=12610000006044 (accessed 13 February 2014).
cholecystectomy. Journal of Gastrointestinal Surgery
2011;15(4):614-22. Phillips 2012 {published data only}
* Phillips MS, Marks JM, Roberts K, Tacchino R, Onders R,
Moran 2011 {published data only}
DeNoto G, et al. Intermediate results of a prospective
Moran M, Gundogdu E, Dizen H, Akgun AE, Ozmen MM. Single randomized controlled trial of traditional four-port laparoscopic
vs two vs three vs four incision laparoscopic cholecystectomy: cholecystectomy versus single-incision laparoscopic
a randomized controlled clinical trial. Surgical Endoscopy and cholecystectomy. Surgical Endoscopy 2012;26(5):1296-303.
Other Interventional Techniques 2011;25(1 Suppl):S34.
Phillips MS, Marks JM, Tacchino R, Roberts K, Onders R,
Mosca 2012 {published data only} De Noto G, et al. Prospective randomized controlled trial of
Mosca F, Cuschieri A. EndoCone single port versus conventional traditional four port laparoscopic cholecystectomy versus
multi-port laparoscopic approach, 2012. clinicaltrials.gov/show/ single incision laparoscopic cholecystectomy. Surgical
NCT01709877 (accessed 13 February 2014). Endoscopy 2011;25:S217.

Informed decisions.

Poon 2003 {published data only} Vilallonga 2012 {published data only}
Poon CM, Chan KW, Lee DW, Chan KC, Ko CW, Cheung HY, et Vilallonga R, Barbaros U, Sumer A, Demirel T, Fort J, Gonzalez O,
al. Two-port versus four-port laparoscopic cholecystectomy. et al. Single-port transumbilical laparoscopic cholecystectomy:
Surgical Endoscopy 2003;17(10):1624-7. a prospective randomised comparison of clinical results of 140
cases. Journal of Minimal Access Surgery 2012;8(3):74-8.
Sasaki 2012 {published data only}
Sasaki A, Ogawa M, Tono C, Obara S, Hosoi N, Wakabayashi G.
Single-port versus multiport laparoscopic cholecystectomy: References to ongoing studies
a prospective randomized clinical trial. Surgical Laparoscopy, Mosca 2013 {published data only}
Endoscopy and Percutaneous Techniques 2012;22(5):396-9.
Mosca F. EndoCone single port versus conventional multi-
Soroush 2011 {published data only} port laparoscopic approach, 2013. clinicaltrials.gov/show/
NCT01709877 (accessed 13 February 2014).
Soroush M. The comparison between result of single port
laparoscopic cholecystectomy with 4 ports cholecystectomy, Soroush 2013 {published data only}
2011. www.irct.ir/searchresult.php?id=6359&number=1
Soroush M. The comparison between result of single port
(accessed 13 February 2014).
laparoscopic cholecystectomy with 4 ports cholecystectomy,
Steinemann 2011 {published data only} 2013. www.irct.ir/searchresult.php?id=6359&number=1
(accessed 13 February 2014).
Steinemann DC, Raptis DA, Lurje G, Oberkofler CE, Wyss R,
Zehnder A, et al. Cosmesis and body image after single-port Takada 2013 {published data only}
laparoscopic or conventional laparoscopic cholecystectomy:
Takada Y. Randomized study comparing quality of life
a multicenter double blinded randomised controlled trial
after single-port versus conventional 4-port laparoscopic
(SPOCC-trial). BMC Surgery 2011;11:24.
cholecystectomy, 2013. www.umin.ac.jp/ctr/index.htm
Tacchino 2011 {published data only} (accessed 13 February 2014).
Tacchino R, Marks J, Onders R, DeNoto G, Paraskeva B, Rivas H,
et al. Conventional 4-port laparoscopic cholecystectomy versus Additional references
SILS port laparoscopic cholecystectomy. The first prospective
randomized sham controlled trial. Surgical Endoscopy and Other Alponat 2002
Interventional Techniques 2011;25(1 Suppl):S35. Alponat A, Cubukcu A, Gonullu N, Canturk Z, Ozbay O. Is
minisite cholecystectomy less traumatic? Prospective
Trichak 2003 {published data only} randomized study comparing minisite and conventional
Trichak S. Three-port vs standard four-port laparoscopic laparoscopic cholecystectomies. World Journal of Surgery
cholecystectomy - a prospective randomized study. Surgical 2002;26(12):1437-40.
Endoscopy 2003;17(9):1434-6.
Bakken 2004
Tsimogiannis 2010 {published data only} Bakken IJ, Skjeldestad FE, Mjåland O, Johnson E.
Tsimogiannis K. Study of the inflammatory reaction in standard Cholecystectomy in Norway 1990-2002 [Kolecystektomi i
vs single port cholecystectomy for uncomplicated cholelithiasis, Norge i 1990-2002]. Tidsskrift for den Norske Laegeforening
2010. clinicaltrials.gov/show/NCT01116492 (accessed 13 2004;124(18):2376-8.
February 2014).
Bisgaard 2002
Tsimoyiannis 2010 {published data only} Bisgaard T, Klarskov B, Trap R, Kehlet H, Rosenberg J.
Tsimoyiannis EC, Tsimogiannis KE, Pappas-Gogos G, Farantos C, Microlaparoscopic vs conventional laparoscopic
Benetatos N, Mavridou P, et al. Different pain scores in single cholecystectomy: a prospective randomized double-blind trial.
transumbilical incision laparoscopic cholecystectomy versus Surgical Endoscopy 2002;16(3):458-64.
classic laparoscopic cholecystectomy: a randomized controlled
trial. Surgical Endoscopy 2010;24(8):1842-8. Brok 2008
Brok J, Thorlund K, Gluud C, Wetterslev J. Trial sequential
Umit Ugurlu 2013 {published data only} analysis reveals insufficient information size and potentially
Umit Ugurlu M, Tahir Oruc M. Comparison of single-incision false positive results in many meta-analyses. Journal of Clinical
laparoscopic cholecystectomy with standard laparoscopic Epidemiology 2008;61:763-9.
approach. Surgical Endoscopy 2013;27(Suppl S1):S457.
Brok 2009
Vezakis 2010 {published data only} Brok J, Thorlund K, Wetterslev J, Gluud C. Apparently conclusive
Vezakis A, Polymeneas G. A randomised comparison between meta-analyses may be inconclusive - trial sequential analysis
single incision laparoscopic cholecystectomy and standard adjustment of random error risk due to repetitive testing
laparoscopic cholecystectomy, 2010. clinicaltrials.gov/show/ of accumulating data in apparently conclusive neonatal
NCT01094379 (accessed 13 February 2014). meta-analyses. International Journal of Epidemiology
2009;38(1):287-98.

Informed decisions.

Chan 2013 Gurusamy 2013

Chan AW, Tetzlaff JM, Altman DG, Laupacis A, Gotzsche PC, Gurusamy KS, Vaughan J, Ramamoorthy R, Fusai G,
Krleza-Jeric K, et al. SPIRIT 2013 statement: defining standard Davidson BR. Miniports versus standard ports for laparoscopic
protocol items for clinical trials. Annals of Internal Medicine cholecystectomy. Cochrane Database of Systematic Reviews
2013;158(3):200-7. 2013, Issue 8. [DOI: 10.1002/14651858.CD006804.pub3]
CTU 2011 Hall 2012

Copenhagen Trial Unit. TSA - Trial Sequential Analysis. ctu.dk/ Hall TC, Dennison AR, Bilku DK, Metcalfe MS, Garcea G. Single-
tsa/ 2011 (accessed 13 February 2014). incision laparoscopic cholecystectomy: a systematic review.
Archives of Surgery 2012;147(7):657-66.
David 2008
David GG, Al-Sarira AA, Willmott S, Deakin M, Corless DJ, Halldestam 2004
Slavin JP. Management of acute gallbladder disease in England. Halldestam I, Enell EL, Kullman E, Borch K. Development of
British Journal of Surgery 2008;95(4):472-6. symptoms and complications in individuals with asymptomatic
gallstones. British Journal of Surgery 2004;91(6):734-8.
DeMets 1987
DeMets DL. Methods for combining randomized clinical Higgins 2002
trials: strengths and limitations. Statistics in Medicine Higgins JPT, Thompson SG. Quantifying heterogeneity in a
1987;6(3):341-50. meta-analysis. Statistics in Medicine 2002;21(11):1539-58.
DerSimonian 1986 Higgins 2011

DerSimonian R, Laird N. Meta-analysis in clinical trials. Higgins JPT, Green S (editors). Cochrane Handbook for
Controlled Clinical Trials 1986;7(3):177-88. Systematic Reviews of Interventions Version 5.1.0 [updated
March 2011]. The Cochrane Collaboration, 2011. Available from
Egger 1997 www.cochrane-handbook.org.
Egger M, Davey SG, Schneider M, Minder C. Bias in meta-analysis
detected by a simple, graphical test. BMJ (Clinical Research Ed.) ICH-GCP 1997
1997;315(7109):629-34. International Conference on Harmonisation Expert Working
Group. International conference on harmonisation of technical
Fullarton 1994 requirements for registration of pharmaceuticals for human
Fullarton GM, Bell G. Prospective audit of the introduction of use. ICH harmonised tripartite guideline. Guideline for good
laparoscopic cholecystectomy in the west of Scotland. West clinical practice CFR & ICH Guidelines. Vol. 1, PA 19063-2043,
of Scotland Laparoscopic Cholecystectomy Audit Group. Gut USA: Barnett International/PAREXEL, 1997.
1994;35(8):1121-6.
Jørgensen 1987
Garg 2012a Jørgensen T. Prevalence of gallstones in a Danish population.
Garg P, Thakur JD, Garg M, Menon GR. Single-incision American Journal of Epidemiology 1987;126(5):912-21.
laparoscopic cholecystectomy vs. conventional laparoscopic
cholecystectomy: a meta-analysis of randomized controlled Keus 2006
trials. Journal of Gastrointestinal Surgery 2012;16(8):1618-28. Keus F, de Jong JAF, Gooszen HG, van Laarhoven CJHM.
Laparoscopic versus open cholecystectomy for patients
Giger 2011 with symptomatic cholecystolithiasis. Cochrane
Giger U, Ouaissi M, Schmitz SF, Krahenbuhl S, Krahenbuhl L. Database of Systematic Reviews 2006, Issue 4. [DOI:
Bile duct injury and use of cholangiography during laparoscopic 10.1002/14651858.CD006231]
cholecystectomy. British Journal of Surgery 2011;98(3):391-6.
Kjaergard 2001
Gluud 2013 Kjaergard LL, Villumsen J, Gluud C. Reported methodologic
Gluud C, Nikolova D, Klingenberg SL, Alexakis N, Als-Nielsen B, quality and discrepancies between large and small
Colli A, et al. Cochrane Hepato-Biliary Group. About The randomized trials in meta-analyses. Annals of Internal Medicine
Cochrane Collaboration (Cochrane Review Groups (CRGs)). 2001;135(11):982-9.
2013, Issue 5. Art. No.: LIVER.
Livingston 2004
Gurtner 2008 Livingston EH, Rege RV. A nationwide study of conversion from
Gurtner GC, Werner S, Barrandon Y, Longaker MT. Wound repair laparoscopic to open cholecystectomy. American Journal of
and regeneration. Nature 2008;453(7193):314-21. [PUBMED: Surgery 2004;188(3):205-11. [PUBMED: 15450821]
18480812]
Lundh 2012
Gurusamy 2009 Lundh A, Sismondo S, Lexchin J, Busuioc OA, Bero L.
Gurusamy KS, Gluud C, Nikolova D, Davidson BR. Assessment Industry sponsorship and research outcome. Cochrane
of risk of bias in randomized clinical trials in surgery. British Database of Systematic Reviews 2012, Issue 12. [DOI:
Journal of Surgery 2009;96(4):342-9. 10.1002/14651858.MR000033.pub2]
Informed decisions.

Macaskill 2001 Roberts 2010

Macaskill P, Walter SD, Irwig L. A comparison of methods to Roberts KE, Solomon D, Duffy AJ, Bell RL. Single-incision
detect publication bias in meta-analysis. Statistics in Medicine laparoscopic cholecystectomy: a surgeon's initial experience
2001;20(4):641-54. with 56 consecutive cases and a review of the literature. Journal
of Gastrointestinal Surgery 2010;14(3):506-10.
Markar 2012
Markar SR, Karthikesalingam A, Thrumurthy S, Muirhead L, Royle 2003
Kinross J, Paraskeva P. Single-incision laparoscopic Royle P, Milne R. Literature searching for randomized controlled
surgery (SILS) vs. conventional multiport cholecystectomy: trials used in Cochrane reviews: rapid versus exhaustive
systematic review and meta-analysis. Surgical Endoscopy searches. International Journal of Technology Assessment in
2012;26(5):1205-13. Health Care 2003;19(4):591-603.
Mjäland 1998 Savovic 2012

Mjäland O, Adamsen S, Hjelmquist B, Ovaska J, Buanes T. Savovic J, Jones HE, Altman DG, Harris RJ, Jüni P, Pildal J,
Cholecystectomy rates, gallstone prevalence, and handling of et al. Influence of reported study design characteristics on
bile duct injuries in Scandinavia. A comparative audit. Surgical intervention effect estimates from randomized, controlled
Endoscopy 1998;12(12):1386-9. trials. Health Technology Assessment 2012;16(35):1-82.
Moher 1998 Savovic 2012a

Moher D, Pham B, Jones A, Cook DJ, Jadad AR, Moher M, et al. Savovic J, Jones HE, Altman DG, Harris RJ, Jüni P, Pildal J,
Does quality of reports of randomised trials affect estimates et al. Influence of reported study design characteristics on
of intervention efficacy reported in meta-analyses?. Lancet intervention effect estimates from randomized, controlled
1998;352(9128):609-13. trials. Annals of Internal Medicine 2012;157(6):429-38.
Moher 2010 Schulz 1995

Moher D, Hopewell S, Schulz KF, Montori V, Gotzsche PC, Schulz KF, Chalmers I, Hayes RJ, Altman DG. Empirical evidence
Devereaux PJ, et al. CONSORT 2010 Explanation and of bias. Dimensions of methodological quality associated
Elaboration: Updated guidelines for reporting parallel with estimates of treatment effects in controlled trials. JAMA
group randomised trials. Journal of Clinical Epidemiology 1995;273(5):408-12.
2010;63(8):e1-37.
Song 2012
Muhrbeck 1995 Song T, Liao B, Liu J, Yin Y, Luo Q, Cheng N. Single-incision
Muhrbeck O, Ahlberg J. Prevalence of gallstone disease in a versus conventional laparoscopic cholecystectomy: a
Swedish population. Scandinavian Journal of Gastroenterology systematic review of available data. Surgical Laparoscopy,
1995;30(11):1125-8. Endoscopy & Percutaneous Techniques 2012;22(4):e190-6.
Newell 1992 Sun 2009

Newell DJ. Intention-to-treat analysis: implications for Sun S, Yang K, Gao M, He X, Tian J, Ma B. Three-port versus
quantitative and qualitative research. International Journal of four-port laparoscopic cholecystectomy: Meta-analysis
Epidemiology 1992;21(5):837-41. of randomized clinical trials. World Journal of Surgery
2009;33(9):1904-8. [19597878]
NIH 1992
NIH. NIH consensus statement on gallstones Thorlund 2009
and laparoscopic cholecystectomy, 1992. Thorlund K, Devereaux PJ, Wetterslev J, Guyatt G, Ioannidis JP,
consensus.nih.gov/1992/1992GallstonesLaparoscopy090html.htm Thabane L, et al. Can trial sequential monitoring boundaries
(accessed 13 February 2014). reduce spurious inferences from meta-analyses. International
Journal of Epidemiology 2009;38(1):276-86.
Pisanu 2012
Pisanu A, Reccia I, Porceddu G, Uccheddu A. Meta-analysis of Thorlund 2010
prospective randomized studies comparing single-incision Thorlund K, Anema A, Mills E. Interpreting meta-analysis
laparoscopic cholecystectomy (SILC) and conventional according to the adequacy of sample size. An example using
multiport laparoscopic cholecystectomy (CMLC). Journal of isoniazid chemoprophylaxis for tuberculosis in purified
Gastrointestinal Surgery 2012;16(9):1790-801. protein derivative negative HIV-infected individuals. Clinical
Epidemiology 2010;2:57-66.
RevMan 2012 [Computer program]
The Nordic Cochrane Centre, The Cochrane Collaboration. Thorlund 2011
Review Manager (RevMan). Version 5.2. Copenhagen: The Thorlund K, Engstrøm J, Wetterslev J, Brok J, Imberger G,
Nordic Cochrane Centre, The Cochrane Collaboration, 2012. Gluud C. User manual for Trial Sequential Analysis (TSA). ctu.dk/
tsa/files/tsa_manual.pdf 2011 (accessed 13 February 2014).

Informed decisions.

Wang 2012 Wetterslev 2009

Wang D, Wang Y, Ji ZL. Laparoendoscopic single-site Wetterslev J, Thorlund K, Brok J, Gluud C. Estimating required
cholecystectomy versus conventional laparoscopic information size by quantifying diversity in random-effects
cholecystectomy: a systematic review of randomized model meta-analyses. BMC Medical Research Methodology
controlled trials. Australian and New Zealand Journal of Surgery 2009;9:86.
2012;82(5):303-10.
Wood 2008
Wetterslev 2008 Wood L, Egger M, Gluud LL, Schulz KF, Jüni P, Altman GD, et
Wetterslev J, Thorlund K, Brok J, Gluud C. Trial sequential al. Empirical evidence of bias in treatment effect estimates in
analysis may establish when firm evidence is reached in controlled trials with different interventions and outcomes:
cumulative meta-analysis. Journal of Clinical Epidemiology meta-epidemiological study. BMJ (Clinical Research Ed.)
2008;61(1):64-75. 2008;336:601-5.

* Indicates the major publication for the study

CHARACTERISTICS OF STUDIES
Characteristics of included studies [ordered by study ID]

Abd Ellatif 2013
Methods Randomised clinical trial.
Participants Country: Egypt.
Number randomised: 250.
Post-randomisation drop-outs: 0 (0%).
Revised sample size: 250.
Mean age: 47 years.
Females: 183 (73.2%).
Inclusion criteria
1. People with symptomatic cholelithiasis, verified by abdominal ultrasonography.

2. Scheduled for elective cholecystectomy.
3. ASA classification 1 or 2.
Exclusion criteria
1. Pregnancy.
2. Acute cholecystitis (clinical or radiological).
3. A preoperative indication for a cholangiogram.
4. BMI > 35 kg/m2.
5. Previous upper laparotomy.
6. Previous umbilical hernia repair.
7. History of peptic ulcer or bronchial asthma.
8. Allergy to non-steroidal anti-inflammatory drugs.
9. Long-term use of analgesia.
Interventions Participants were randomly assigned to 1 of 2 groups.

Group 1: fewer-than-four-ports laparoscopic cholecystectomy (n = 125).
Further details: single port: 2 cannulas were inserted (1 × 10 mm and 1 × 5 mm).
Successful completion of less-port laparoscopic cholecystectomy: 121/125 (96.8%).
Group 2: four-port laparoscopic cholecystectomy (n = 125).
Further details: size of port in mm: 10 + 10 + 5 + 5.

Informed decisions.

Abd Ellatif 2013 (Continued)

Other details:
intra-operative cholangiogram: no.
Outcomes Mortality, morbidity, quality of life, conversion to open cholecystectomy, operating time, hospital stay,
and return to normal activity.
Notes Authors contacted in September 2013. Authors provided replies.
Risk of bias
Bias Authors' judgement Support for judgement
Random sequence genera- Low risk Quote: "Randomization was achieved using a computer-generated schedule,
tion (selection bias) and the results were sealed into envelopes (either SALC [single-access laparo-
scopic cholecystectomy] or CLC groups)".
Allocation concealment Low risk Quote: "An envelope was fetched and opened in the operating room by an op-
(selection bias) erating room nurse not otherwise engaged in the study".
Blinding (performance Unclear risk Comment: this information was not available.
bias and detection bias)
All outcomes
Incomplete outcome data Low risk Comment: there were no post-randomisation drop-outs.
(attrition bias)
All outcomes
Selective reporting (re- Low risk Comment: mortality and morbidity were reported.
porting bias)
Free from vested interest Low risk Quote: "Our hospital is a governmental university hospital, there was no
bias? fund" (author replies).

Bucher 2011
Participants Country: Switzerland.
Mean age: 43 years.
Females: not stated.
Inclusion criteria
1. Elective patients with symptomatic gallbladder stones (history of cholecystitis, history of common
bile duct stone migration, biliary pancreatitis, or a combination of these).
2. Aged > 18 years.
Exclusion criteria
1. People presenting as an emergency with acute gallbladder disease.

Informed decisions.

Bucher 2011 (Continued)
2. Contraindications to pneumoperitoneum.
3. Cirrhosis or mental impairment.

Further details: single port: 1.5-cm umbilical TriPort (multiport trocar).
Successful completion of fewer-than-four-ports laparoscopic cholecystectomy: 73/75 (97.3%).
Other details: intra-operative cholangiogram: attempted in all participants and successful in 57/75 in
single-port group and 62/75 operations in four-port group.
Outcomes Mortality, morbidity, quality of life, operating time, hospital stay, and return to work.
Notes Authors contacted in February 2013. No replies were received.
Risk of bias
Random sequence genera- Low risk Quote: "Patients were allocated to LESS or CL cholecystectomy using a ran-
tion (selection bias) domization table after their preoperative visit by the surgeon".
Allocation concealment Unclear risk Comment: this information was not available.
(selection bias)
All outcomes
(attrition bias)
All outcomes
porting bias)
Free from vested interest Unclear risk Comment: this information was not available.
bias?

Cerci 2007
Participants Country: Turkey.
Sample size: 146.
Post-randomisation drop-out(s): 0 (0%).
Mean age: 50 years.
Females: 109 (74.7%).
Inclusion criteria:

Informed decisions.

Cerci 2007 (Continued)
1. People undergoing laparoscopic cholecystectomy for gallstones.
Exclusion criteria:
1. People with upper abdominal scars.

Further details: size of port in mm: 10 + 10 + 5.
Successful completion of fewer-than-four-ports laparoscopic cholecystectomy: not stated.
Other details: intra-operative cholangiogram: not stated.
Outcomes Operating time and hospital stay.
Notes Authors contacted in September 2010. No replies were received.
Risk of bias
Random sequence genera- Unclear risk Comment: this information was not available.
tion (selection bias)
(selection bias)
All outcomes
(attrition bias)
All outcomes
Selective reporting (re- High risk Comment: mortality and morbidity were not reported.
porting bias)
bias?

Herrero 2012
Participants Country: Spain.
Post-randomisation drop-outs: not stated.
Mean age: 47 years.
Females: 34 (68%).

Informed decisions.

Herrero 2012 (Continued)
Inclusion criteria
1. People undergoing day-surgery laparoscopic cholecystectomy for symptomatic cholelithiasis.
Exclusion criteria
1. Obesity with BMI > 35 kg/m2.

2. Hepatitis.
3. Alcoholism.
4. Pregnancy.
5. Previous acute pancreatitis.
6. Cholecystitis.
7. Choledocholithiasis.
8. Previous upper abdominal surgery.

Further details: single port: 2-cm umbilical SILSTM Port (Covidien) with 3 openings (allowing the use of
3 × 5-mm trocars).
Outcomes Mortality, morbidity, operating time, and proportion discharged as day surgery.
Notes Authors contacted in February 2013. Authors replied in February 2013.
Risk of bias
Random sequence genera- Low risk Quote: "Patients were randomized to SILS in LC or surgery on the same day of
tion (selection bias) the procedure using a random table generated by a computer program".
Allocation concealment Unclear risk Quote: "The random allocation of patients to the single port or group of con-
(selection bias) ventional laparoscopic cholecystectomy was performed in the operating room
minutes before starting the intervention by the surgical team" (author replies).
Comment: further details about how the allocation concealment was per-
formed were not available.
Blinding (performance High risk Quote: "Neither the patients nor the health professionals were blinded. The
bias and detection bias) outcome assessors were blinded. The results in terms of pain and analgesic re-
All outcomes quirements were made through telephone calls by nurses who did not know
the method used in each case" (author replies).
Incomplete outcome data Low risk Quote: "There were no post-randomisation drop-outs" (author replies).
(attrition bias)
All outcomes
porting bias)
Free from vested interest Low risk Quote: "The study did not receive any funding" (author replies).
bias?

Informed decisions.


Kumar 2007
Participants Country: Nepal.
Sample size: 75.
Post-randomisation drop-out(s): 0 (0%).
Mean age: 39 years.
Females: 62 (82.7%).
Inclusion criteria:
1. Elective laparoscopic cholecystectomy.

2. Aged 18 to 75 years.
3. Fit for cholecystectomy on anaesthetic grounds.

Further details: size of port in mm: 11 + 10 + 5.
Successful completion of fewer-than-four-ports laparoscopic cholecystectomy: 36/36 (100%).
Outcomes Conversion to open cholecystectomy, hospital stay, and operating time.
Risk of bias
(selection bias)
Blinding (performance High risk Quote: "All patient dressings were kept for one week. Thus, all patients were
bias and detection bias) blinded to the type of operation they underwent".
All outcomes Comment: blinding of observers was not reported.
(attrition bias)
All outcomes
Selective reporting (re- High risk Comment: mortality and morbidity were not reported.
porting bias)
Free from vested interest Low risk Quote: "This study was supported by the research grant issued to the Depart-
bias? ment of Surgery by BP Koirala Institute of Health Sciences, Nepal".

Informed decisions.


Lirici 2011
Participants Country: Italy.
Mean age: 48 years.
Females: 28 (70%).
Inclusion criteria
2. BMI < 30 kg/m2.
3. Presence of Gallstones.
4. ASA classification I to III.
5. Nassar grade I to III.
Exclusion criteria
1. Previous upper abdominal or right colonic surgery.

2. Acute cholecystitis, bile duct stones, pancreatitis.

Further details: single port: 2-cm umbilical TriPort with 3 legs (allowing the use of 1 × 12 mm and 2 × 5-
mm instruments).
Successful completion of fewer-than-four-ports laparoscopic cholecystectomy: 18/20 (90%).
Outcomes Mortality, morbidity, conversion to open cholecystectomy, operating time, hospital stay, and quality of
life.
Notes Authors contacted in February 2013. No replies were received.
Risk of bias
Allocation concealment Low risk Quote: "Randomization was performed preparing 2 sets of 20 numbered,
(selection bias) opaque, sealed envelopes, with the envelopes of each set containing indica-
tions for 10 LESS cholecystectomy procedures and 10 standard LC procedures.
One set of envelopes was kept at Bianchi Melacrino Morelli Hospital and the
other at Monaldi Hospital. The envelopes were opened in numeric order for
each patient by an assistant not involved in the surgical operations, right be-
fore surgery".

Informed decisions.

Lirici 2011 (Continued)
Blinding (performance Unclear risk Quote: "Patients did not know the treatment received until their discharge. A
bias and detection bias) large drape was used to cover the abdomen after surgery, thus hiding the sur-
All outcomes gical wounds".
Comment: it is not clear whether the healthcare providers involved in the care
of the participants were blinded.
(attrition bias)
All outcomes
Selective reporting (re- Low risk Comment: mortality and morbidity were reported
porting bias)
bias?

Luna 2013
Participants Country: Brazil.
Mean age: not stated.
Females: not stated.
Inclusion criteria
1. People with symptomatic cholelithiasis, diagnosed based on clinical symptoms and confirmed with
abdominal ultrasound scan.
2. BMI ≤ 35 kg/m2.

Further details: single port: four channels (SITRACC device; 1 × 10 mm and 3 × 5 mm).
Successful completion of less-port laparoscopic cholecystectomy: 18/20 (90%).

Other details: intra-operative cholangiogram: no.
Outcomes Mortality, morbidity, and operating time.
Risk of bias

Informed decisions.

Luna 2013 (Continued)
(selection bias)
All outcomes
Incomplete outcome data Unclear risk Comment: this information was not available.
(attrition bias)
All outcomes
porting bias)
Free from vested interest High risk Quote: "Funding: All single-port devices were provided without cost by EDLO
bias? S/A Produtos Medicos".

Saad 2013
Participants Country: Germany.
Mean age: 47 years.
Females: 16 (22.9%).
Inclusion criteria
1. Aged ≥ 18 years.
2. Indication for elective cholecystectomy.
3. Uncomplicated, symptomatic cholecystolithiasis.
Exclusion criteria
1. Aged > 80 years.

2. BMI > 30 kg/m2.
3. Acute cholecystitis.
4. Gallbladder empyema.
5. Pancreatitis or other complications.
6. ASA grade IV or V.
7. Previous upper abdominal laparotomy with suspicion of peritoneal adhesions.
8. Allergy to paracetamol or piritramide.
9. History of pain medication or alcohol abuse.
10.Neuromuscular disease.
11.Pregnancy or lactation.

Informed decisions.

Saad 2013 (Continued)
Further details: single port: 2-cm umbilical SILS Port (Covidien, Norwalk, Connecticut, USA) with 3
openings (allowing the use of 3 × 5-mm trocars or 2 × 5-mm and 1 × 10-mm trocar).
Outcomes Mortality, morbidity, quality of life, conversion to open cholecystectomy, operating time, hospital stay,
and cosmetic scores.
Notes Reasons for post-randomisation drop-outs: 1 participant was lost to follow-up on day 7 and 2 partici-
pants by 1 year in the single-port group. These participants were included for operative outcomes but
not for quality of life (1 participant) and cosmesis (3 participants).
Risk of bias
Random sequence genera- Low risk Quote: "A sequence with block sizes of three and six in random order was gen-
tion (selection bias) erated by computer (http://www.randomization. com)".
Allocation concealment Low risk Quote: "Patients were randomized to CL, ML [mini-laparoscopic] or SP [single
(selection bias) port] cholecystectomy by drawing sequentially numbered, opaque, sealed en-
velopes that had been prepared earlier by a third party".
Blinding (performance Low risk Quote: "After completion of cholecystectomy, all patients received non-trans-
bias and detection bias) parent waterproof dressings at four sites on the abdomen, reflecting the inci-
All outcomes sions necessary for CL cholecystectomy. This ensured that patients, ward doc-
tors and nurses responsible for the postoperative evaluation and care of pa-
tients were unaware of which procedure had actually been performed. The op-
erating surgeons and operating room staff were excluded from postoperative
treatment and evaluation".
Incomplete outcome data Low risk Comment: all participants were included for operative outcomes. 2 partici-
(attrition bias) pants were lost to follow-up and so the quality of life and cosmetic scores may
All outcomes be at high risk of bias. However, mortality and morbidity are at low risk of bias.
porting bias)
Free from vested interest Low risk Quote: "This study was funded partly by the German Federal Ministry of Educa-
bias? tion and Research: grant numbers 01GH0605 and 01GH1001E (CHIR-Net)".

Sinan 2012
Participants Country: Turkey.

Informed decisions.

Sinan 2012 (Continued)
Mean age: 49 years.
Females: 22 (64.7%).
Inclusion criteria
1. Symptomatic or asymptomatic gallbladder pathology such as gallstones, mud, or polyps.

2. No previous history of upper gastrointestinal surgery.
3. BMI < 40 kg/m2.
Exclusion criteria
1. Patient's refusal to participate.

2. Acute cholecystitis or pancreatitis.
3. Umbilical hernia.

Further details: single port: 2.5-cm Singleport (allowing the use of 5-mm instruments).
Successful completion of less-port laparoscopic cholecystectomy: not stated.

Other details: intra-operative cholangiogram: no.
Outcomes Mortality, morbidity, and operating time.
Risk of bias
(selection bias)
Blinding (performance Unclear risk Quote: "Postoperative abdominal pain and shoulder pain were assessed and
bias and detection bias) noted by nurses who were blinded to the study".
All outcomes Comment: unclear whether the participants and surgeons involved in manage-
ment of participants were blinded.
Incomplete outcome data Unclear risk Quote: "Postoperative abdominal pain and shoulder pain were assessed and
(attrition bias) noted by nurses who were blinded to the study".
All outcomes Comment: unclear whether the complications were assessed by a blinded ob-
server.
porting bias)
bias?
ASA: American Society of Anesthesiologists classification; BMI: body mass index; CL or CLC: conventional laparoscopic cholecystectomy; LC:
laparoscopic cholecystectomy; LESS: laparoendoscopic single-site surgery; SILS: single umbilical incision laparoscopic surgery; SITRACC:
single trocar access.

Informed decisions.


Characteristics of excluded studies [ordered by study ID]

Study Reason for exclusion
Allemann 2012 In this ongoing trial, the control group was not standard laparoscopic cholecystectomy as defined
in this review.
Asakuma 2011 It is not clear whether the control group was standard laparoscopic cholecystectomy as defined in
this review.
Bansal 2012 In this ongoing trial, it is not clear whether the control group was standard laparoscopic cholecys-
tectomy as defined in this review.
Barugola 2011 In this ongoing trial, it is not clear whether the control group was standard laparoscopic cholecys-
Bingener-Casey 2012 In this ongoing trial, it is not clear whether the control group was standard laparoscopic cholecys-
Bresadola 1999 It is not clear whether the control group was standard laparoscopic cholecystectomy as defined in
this review.
Broeders 2010 The control group was not standard laparoscopic cholecystectomy as defined in this review.
Brown 2013 The control group was not standard laparoscopic cholecystectomy as defined in this review.
Cao 2011 The control group was not standard laparoscopic cholecystectomy as defined in this review.
Chang 2013 The control group was not standard laparoscopic cholecystectomy as defined in this review.
Chen 2002 There is no information as whether the difference between the groups was only in the number of
ports or in the size of the ports also.
Cockbain 2013 Comment on an included trial (Saad 2013).
Dam 2011 In this ongoing trial, it is not clear whether the control group was standard laparoscopic cholecys-
de Carvalho 2013 The intervention group also had four ports.
Garg 2012 Not a randomised clinical trial.
Gupta 2005 The intervention involves a combination of smaller ports and fewer ports.
Hansen 2011 In this ongoing trial, it is not clear whether the control group was standard laparoscopic cholecys-
Hauters 2013 Not a randomised clinical trial
Hu 2005 The control group was not standard laparoscopic cholecystectomy as defined in this review.
Hu 2010 The control group was not standard laparoscopic cholecystectomy as defined in this review.
Jorgensen 2010 In this ongoing trial, it is not clear whether the control group was standard laparoscopic cholecys-

Informed decisions.

Khorgami 2011 The control group was not standard laparoscopic cholecystectomy as defined in this review.
Kim 2009 The control group was not standard laparoscopic cholecystectomy as defined in this review.
Lai 2011 The control group was not standard laparoscopic cholecystectomy as defined in this review.
Lee 2010 The control group was not standard laparoscopic cholecystectomy as defined in this review.
Leung 2011 It is not clear whether the control group was standard laparoscopic cholecystectomy as defined in
this review.
Limberger 2005 The control group was not standard laparoscopic cholecystectomy as defined in this review.
Ma 2011 The control group was not standard laparoscopic cholecystectomy as defined in this review.
Madureira 2013 It is not clear whether the control group was standard laparoscopic cholecystectomy as defined in
this review.
Marks 2011 The control group was not standard laparoscopic cholecystectomy as defined in this review.
Marks 2012 It is not clear whether the participants are being randomly allocated. It is also not clear whether the
control group is standard laparoscopic cholecystectomy as defined in this review.
Marks 2013 The control group was not standard laparoscopic cholecystectomy as defined in this review.
McGregor 2011 The control group was not standard laparoscopic cholecystectomy as defined in this review.
Moran 2011 It is not clear whether the control group was standard laparoscopic cholecystectomy as defined in
this review.
Mosca 2012 In this ongoing trial, it is not clear whether the control group was standard laparoscopic cholecys-
Ng 1999 Letter to editor not involving a randomised clinical trial.
Noguera 2012 The control group was not standard laparoscopic cholecystectomy as defined in this review.
Ospanov 2013 It is not clear whether the control group was standard laparoscopic cholecystectomy as defined in
this review.
Ostlie 2013 The control group was not standard laparoscopic cholecystectomy as defined in this review.
Pappas-Gogos 2010 It is not clear whether the control group is standard laparoscopic cholecystectomy as defined in
this review.
Pathania 2013 It is not clear whether the control group was standard laparoscopic cholecystectomy as defined in
this review.
Patricia 2010 In this ongoing trial, the control group was not standard laparoscopic cholecystectomy as defined
in this review.
Phillips 2012 The control group was not standard laparoscopic cholecystectomy as defined in this review.
Poon 2003 The control group was not standard laparoscopic cholecystectomy as defined in this review.

Informed decisions.

Sasaki 2012 The control group was not standard laparoscopic cholecystectomy as defined in this review.
Soroush 2011 In this ongoing study, it is not clear whether the participants are being randomly allocated. It is also
not clear whether the control group is standard laparoscopic cholecystectomy as defined in this re-
view.
Steinemann 2011 Protocol of an ongoing trial. This trial will meet the inclusion criteria once completed.
Tacchino 2011 It is not clear whether the control group is standard laparoscopic cholecystectomy as defined in
this review.
Trichak 2003 The intervention involves a combination of smaller ports and fewer ports.
Tsimogiannis 2010 It is not clear whether the control group was standard laparoscopic cholecystectomy as defined in
this review.
Tsimoyiannis 2010 The control group was not standard laparoscopic cholecystectomy as defined in this review.
Umit Ugurlu 2013 It is not clear whether the control group was standard laparoscopic cholecystectomy as defined in
this review.
Vezakis 2010 In this ongoing trial, it is not clear whether the control group was standard laparoscopic cholecys-
Vilallonga 2012 It is not clear whether the control group is standard laparoscopic cholecystectomy as defined in
this review.

Characteristics of ongoing studies [ordered by study ID]

Mosca 2013
Trial name or title EndoCone Single Port Versus Conventional Multi-port Laparoscopic Approach.
Participants People undergoing laparoscopic cholecystectomy.
Interventions Single-port versus conventional multi-port laparoscopic cholecystectomy.
Outcomes Mortality, morbidity, conversion to open cholecystectomy, and hospital stay.
Starting date April 2013.
Contact information Franco Mosca (email: f.mosca@med.unipi.it).
Notes

Soroush 2013
Trial name or title The Comparison Between Result of Single Port Laparoscopic Cholecystectomy with 4 Ports Chole-
cystectomy.

Informed decisions.

Soroush 2013 (Continued)
Participants 1. People with symptomatic cholelithiasis without complications.

3. Body mass index < 35 kg/m2.
4. No history of other diseases.
5. No history of previous abdominal surgery.
Interventions Single-port versus four-ports.
Outcomes Morbidity.
Starting date August 2011.
Contact information Mohammad Soroush (email: soroushm@tbzmed.ac.ir).
Notes

Takada 2013
Trial name or title Randomized Study Comparing Quality of Life after Single-Port Versus Conventional 4-Port Laparo-
scopic Cholecystectomy.
Participants 1. Symptomatic cholelithiasis.

2. Gallbladder polyp.
3. Adenomyomatosis.
Interventions Single-port versus four-port laparoscopic cholecystectomy.
Outcomes Morbidity, quality of life, operating time, and hospital stay.
Starting date 26 April 2013 (anticipated).
Contact information Y Takada (telephone: +81899605327).
Notes

DATA AND ANALYSES

Comparison 1. Fewer-than-four ports versus four ports
Outcome or subgroup title No. of No. of Statistical method Effect size

studies partici-
pants
1 Serious adverse events 7 634 Risk Ratio (M-H, Fixed, 95% CI) 3.93 [0.86, 18.04]

Informed decisions.

Outcome or subgroup title No. of No. of Statistical method Effect size

studies partici-
pants
1.1 One port 7 634 Risk Ratio (M-H, Fixed, 95% CI) 3.93 [0.86, 18.04]
2 Quality of life 4 510 Std. Mean Difference (IV, Random, 95% CI) 0.18 [-0.05, 0.42]
2.1 One port 4 510 Std. Mean Difference (IV, Random, 95% CI) 0.18 [-0.05, 0.42]
3 Conversion to open chole- 5 581 Risk Ratio (M-H, Fixed, 95% CI) 0.68 [0.19, 2.35]
cystectomy
3.2 Three ports 2 221 Risk Ratio (M-H, Fixed, 95% CI) 0.79 [0.20, 3.14]
4 Operating time 9 855 Mean Difference (IV, Random, 95% CI) 14.44 [5.95, 22.93]
4.1 One port 7 634 Mean Difference (IV, Random, 95% CI) 21.04 [10.45, 31.62]
4.2 Three ports 2 221 Mean Difference (IV, Random, 95% CI) -5.32 [-17.38, 6.73]
5 Hospital stay 6 731 Mean Difference (IV, Random, 95% CI) -0.01 [-0.28, 0.26]
5.1 One port 4 510 Mean Difference (IV, Random, 95% CI) 0.02 [-0.32, 0.37]
5.2 Three ports 2 221 Mean Difference (IV, Random, 95% CI) -0.09 [-0.47, 0.30]
6 Proportion discharged as 1 50 Risk Ratio (M-H, Fixed, 95% CI) 0.92 [0.70, 1.22]
day-surgery
7 Return to normal activity 2 325 Mean Difference (IV, Fixed, 95% CI) -1.20 [-1.58, -0.81]
7.1 One port 1 250 Mean Difference (IV, Fixed, 95% CI) -1.20 [-1.59, -0.81]
7.2 Three ports 1 75 Mean Difference (IV, Fixed, 95% CI) -0.90 [-5.08, 3.28]
8 Return to work 1 150 Mean Difference (IV, Random, 95% CI) -2.0 [-3.31, -0.69]
8.1 One port 1 150 Mean Difference (IV, Random, 95% CI) -2.0 [-3.31, -0.69]
9 Cosmetic score 2 317 Std. Mean Difference (IV, Random, 95% CI) 0.37 [-0.10, 0.84]
9.1 One port 2 317 Std. Mean Difference (IV, Random, 95% CI) 0.37 [-0.10, 0.84]

Analysis 1.1. Comparison 1 Fewer-than-four ports versus four ports, Outcome 1 Serious adverse events.
Study or subgroup Fewer ports LC Standard Risk Ratio Weight Risk Ratio
ports LC
n/N n/N M-H, Fixed, 95% CI M-H, Fixed, 95% CI
1.1.1 One port
Favours fewer ports 0.01 0.1 1 10 100 Favours standard ports

Informed decisions.

ports LC
Abd Ellatif 2013 0/125 0/125 Not estimable
Bucher 2011 0/75 0/75 Not estimable
Herrero 2012 1/26 0/24 25.71% 2.78[0.12,65.08]
Lirici 2011 1/20 0/20 24.76% 3[0.13,69.52]
Luna 2013 0/20 0/20 Not estimable
Saad 2013 3/35 0/35 24.76% 7[0.37,130.69]
Sinan 2012 1/17 0/17 24.76% 3[0.13,68.84]
Subtotal (95% CI) 318 316 100% 3.93[0.86,18.04]
Total events: 6 (Fewer ports LC), 0 (Standard ports LC)
Heterogeneity: Tau2=0; Chi2=0.25, df=3(P=0.97); I2=0%
Test for overall effect: Z=1.76(P=0.08)

Total (95% CI) 318 316 100% 3.93[0.86,18.04]

Analysis 1.2. Comparison 1 Fewer-than-four ports versus four ports, Outcome 2 Quality of life.
Study or subgroup Fewer ports LC Standard ports LC Std. Mean Difference Weight Std. Mean Difference
N Mean(SD) N Mean(SD) Random, 95% CI Random, 95% CI
1.2.1 One port
Abd Ellatif 2013 125 94 (27) 125 87.5 (25) 39.39% 0.25[0,0.5]
Bucher 2011 75 40 (13.8) 75 35 (13.8) 30.28% 0.36[0.04,0.68]
Lirici 2011 20 84.3 (27) 20 79.2 (25) 11.9% 0.19[-0.43,0.81]
Saad 2013 35 101.6 (19.1) 35 105.9 (14) 18.44% -0.25[-0.72,0.22]
Subtotal *** 255 255 100% 0.18[-0.05,0.42]
Heterogeneity: Tau2=0.02; Chi2=4.67, df=3(P=0.2); I2=35.72%

Total *** 255 255 100% 0.18[-0.05,0.42]
Favours standard ports -1 -0.5 0 0.5 1 Favours fewer ports

Analysis 1.3. Comparison 1 Fewer-than-four ports versus
four ports, Outcome 3 Conversion to open cholecystectomy.
ports LC
1.3.1 One port
Abd Ellatif 2013 0/125 0/125 Not estimable
Lirici 2011 0/20 1/20 25.25% 0.33[0.01,7.72]
Saad 2013 0/35 0/35 Not estimable

Informed decisions.

ports LC
Subtotal (95% CI) 180 180 25.25% 0.33[0.01,7.72]
Heterogeneity: Not applicable

1.3.2 Three ports
Cerci 2007 3/73 3/73 50.49% 1[0.21,4.79]
Kumar 2007 0/36 1/39 24.26% 0.36[0.02,8.57]
Subtotal (95% CI) 109 112 74.75% 0.79[0.2,3.14]

Total (95% CI) 289 292 100% 0.68[0.19,2.35]
Test for subgroup differences: Chi2=0.24, df=1 (P=0.62), I2=0%

Analysis 1.4. Comparison 1 Fewer-than-four ports versus four ports, Outcome 4 Operating time.
Study or subgroup Fewer ports LC Standard ports LC Mean Difference Weight Mean Difference
1.4.1 One port
Abd Ellatif 2013 125 62.7 (10.2) 125 55.3 (8.9) 13.5% 7.4[5.03,9.77]
Bucher 2011 75 66 (29.7) 75 64 (26.1) 11.85% 2[-6.95,10.95]
Herrero 2012 26 54 (21) 24 48.5 (17) 11.27% 5.5[-5.06,16.06]
Lirici 2011 20 76.8 (25.3) 20 48.3 (25.3) 9.31% 28.5[12.82,44.18]
Luna 2013 20 92 (27.7) 20 41.9 (14) 10.1% 50.1[36.5,63.7]
Saad 2013 35 45.7 (10.9) 35 35 (14) 12.8% 10.7[4.82,16.58]
Sinan 2012 17 124.4 (29.7) 17 64.1 (26.1) 8.17% 60.3[41.5,79.1]
Subtotal *** 318 316 77% 21.04[10.45,31.62]
Heterogeneity: Tau2=170.46; Chi2=74.33, df=6(P<0.0001); I2=91.93%
Test for overall effect: Z=3.9(P<0.0001)

1.4.2 Three ports
Cerci 2007 73 59.6 (15) 73 60.3 (14.5) 13.07% -0.7[-5.48,4.08]
Kumar 2007 36 47.3 (29.8) 39 60.8 (32.3) 9.93% -13.5[-27.55,0.55]
Subtotal *** 109 112 23% -5.32[-17.38,6.73]

Total *** 427 428 100% 14.44[5.95,22.93]
Heterogeneity: Tau2=137.55; Chi2=97.48, df=8(P<0.0001); I2=91.79%
Test for overall effect: Z=3.33(P=0)
Test for subgroup differences: Chi2=10.38, df=1 (P=0), I2=90.36%
Favours fewer ports -100 -50 0 50 100 Favours standard ports

Informed decisions.


Analysis 1.5. Comparison 1 Fewer-than-four ports versus four ports, Outcome 5 Hospital stay.
1.5.1 One port
Abd Ellatif 2013 125 2.7 (0.5) 125 2.4 (0.8) 27.47% 0.3[0.13,0.47]
Bucher 2011 75 0 (2.5) 75 1 (2.5) 8.37% -1[-1.8,-0.2]
Lirici 2011 20 2.5 (2.5) 20 2.7 (2.5) 2.79% -0.15[-1.7,1.4]
Saad 2013 35 3.1 (0.6) 35 3 (0.2) 25.87% 0.1[-0.11,0.31]
Subtotal *** 255 255 64.5% 0.02[-0.32,0.37]

1.5.2 Three ports
Cerci 2007 73 2 (1.7) 73 1.8 (1.3) 15.34% 0.15[-0.34,0.64]
Kumar 2007 36 1.2 (0.4) 39 1.4 (1.1) 20.17% -0.25[-0.6,0.1]
Subtotal *** 109 112 35.5% -0.09[-0.47,0.3]

Total *** 364 367 100% -0.01[-0.28,0.26]

four ports, Outcome 6 Proportion discharged as day-surgery.
ports LC
1.6.1 One port
Herrero 2012 20/26 20/24 100% 0.92[0.7,1.22]
Subtotal (95% CI) 26 24 100% 0.92[0.7,1.22]

Total (95% CI) 26 24 100% 0.92[0.7,1.22]
Favours fewer ports 0.5 0.7 1 1.5 2 Favours standard ports


Informed decisions.

Analysis 1.7. Comparison 1 Fewer-than-four ports versus four ports, Outcome 7 Return to normal activity.
N Mean(SD) N Mean(SD) Fixed, 95% CI Fixed, 95% CI
1.7.1 One port
Abd Ellatif 2013 125 5 (1.3) 125 6.2 (1.8) 99.14% -1.2[-1.59,-0.81]
Subtotal *** 125 125 99.14% -1.2[-1.59,-0.81]

1.7.2 Three ports
Kumar 2007 36 4.9 (5.1) 39 5.8 (12.2) 0.86% -0.9[-5.08,3.28]
Subtotal *** 36 39 0.86% -0.9[-5.08,3.28]

Total *** 161 164 100% -1.2[-1.58,-0.81]

Analysis 1.8. Comparison 1 Fewer-than-four ports versus four ports, Outcome 8 Return to work.
1.8.1 One port
Bucher 2011 75 10 (4.1) 75 12 (4.1) 100% -2[-3.31,-0.69]
Subtotal *** 75 75 100% -2[-3.31,-0.69]

Total *** 75 75 100% -2[-3.31,-0.69]
Favours fewer ports -5 -2.5 0 2.5 5 Favours standard ports

Analysis 1.9. Comparison 1 Fewer-than-four ports versus four ports, Outcome 9 Cosmetic score.
1.9.1 One port
Abd Ellatif 2013 125 9.7 (2.5) 125 8.5 (1.6) 59.07% 0.57[0.32,0.82]
Saad 2013 32 -1.1 (0.3) 35 -1.1 (0.4) 40.93% 0.08[-0.4,0.56]
Subtotal *** 157 160 100% 0.37[-0.1,0.84]

Total *** 157 160 100% 0.37[-0.1,0.84]

Informed decisions.


Comparison 2. Fewer-than-four ports versus four ports (sensitivity analysis)
Outcome or subgroup ti- No. of No. of Statistical method Effect size

tle studies partici-
pants
1 Quality of life 2 320 Std. Mean Difference (IV, Fixed, 95% CI) 0.14 [-0.08, 0.36]
1.1 One port 2 320 Std. Mean Difference (IV, Fixed, 95% CI) 0.14 [-0.08, 0.36]
2 Operating time 7 665 Mean Difference (IV, Fixed, 95% CI) 7.40 [5.48, 9.31]
2.1 One port 5 444 Mean Difference (IV, Fixed, 95% CI) 9.45 [7.34, 11.57]
2.2 Three ports 2 221 Mean Difference (IV, Fixed, 95% CI) -2.03 [-6.56, 2.50]
3 Hospital stay 3 466 Mean Difference (IV, Random, 95% CI) 0.21 [0.08, 0.35]
3.1 One port 2 320 Mean Difference (IV, Random, 95% CI) 0.21 [0.02, 0.41]
3.2 Three ports 1 146 Mean Difference (IV, Random, 95% CI) 0.15 [-0.34, 0.64]
4 Return to normal activity 1 250 Mean Difference (IV, Fixed, 95% CI) -1.20 [-1.59, -0.81]
4.1 One port 1 250 Mean Difference (IV, Fixed, 95% CI) -1.20 [-1.59, -0.81]

Analysis 2.1. Comparison 2 Fewer-than-four ports versus four ports (sensitivity analysis), Outcome 1 Quality of life.
2.1.1 One port
Abd Ellatif 2013 125 94 (27) 125 87.5 (25) 78.14% 0.25[0,0.5]
Saad 2013 35 101.6 (19.1) 35 105.9 (14) 21.86% -0.25[-0.72,0.22]
Subtotal *** 160 160 100% 0.14[-0.08,0.36]
Heterogeneity: Tau2=0; Chi2=3.43, df=1(P=0.06); I2=70.85%

Total *** 160 160 100% 0.14[-0.08,0.36]


Informed decisions.


four ports (sensitivity analysis), Outcome 2 Operating time.
2.2.1 One port
Abd Ellatif 2013 125 62.7 (10.2) 125 55.3 (8.9) 65.17% 7.4[5.03,9.77]
Herrero 2012 26 54 (21) 24 48.5 (17) 3.29% 5.5[-5.06,16.06]
Luna 2013 20 92 (27.7) 20 41.9 (14) 1.98% 50.1[36.5,63.7]
Saad 2013 35 45.7 (10.9) 35 35 (14) 10.62% 10.7[4.82,16.58]
Sinan 2012 17 124.4 (29.7) 17 64.1 (26.1) 1.04% 60.3[41.5,79.1]
Subtotal *** 223 221 82.11% 9.45[7.34,11.57]
Heterogeneity: Tau2=0; Chi2=66, df=4(P<0.0001); I2=93.94%

2.2.2 Three ports
Cerci 2007 73 59.6 (15) 73 60.3 (14.5) 16.04% -0.7[-5.48,4.08]
Kumar 2007 36 47.3 (29.8) 39 60.8 (32.3) 1.86% -13.5[-27.55,0.55]
Subtotal *** 109 112 17.89% -2.03[-6.56,2.5]

Total *** 332 333 100% 7.4[5.48,9.31]
Heterogeneity: Tau2=0; Chi2=89.13, df=6(P<0.0001); I2=93.27%
Test for subgroup differences: Chi2=20.27, df=1 (P<0.0001), I2=95.07%

Analysis 2.3. Comparison 2 Fewer-than-four ports versus four ports (sensitivity analysis), Outcome 3 Hospital stay.
2.3.1 One port
Abd Ellatif 2013 125 2.7 (0.5) 125 2.4 (0.8) 55.14% 0.3[0.13,0.47]
Saad 2013 35 3.1 (0.6) 35 3 (0.2) 37.19% 0.1[-0.11,0.31]
Subtotal *** 160 160 92.33% 0.21[0.02,0.41]

2.3.2 Three ports
Cerci 2007 73 2 (1.7) 73 1.8 (1.3) 7.67% 0.15[-0.34,0.64]
Subtotal *** 73 73 7.67% 0.15[-0.34,0.64]

Total *** 233 233 100% 0.21[0.08,0.35]
Favours fewer ports -1 -0.5 0 0.5 1 Favours standard ports

Informed decisions.

Analysis 2.4. Comparison 2 Fewer-than-four ports versus four

ports (sensitivity analysis), Outcome 4 Return to normal activity.
2.4.1 One port
Abd Ellatif 2013 125 5 (1.3) 125 6.2 (1.8) 100% -1.2[-1.59,-0.81]
Subtotal *** 125 125 100% -1.2[-1.59,-0.81]

Total *** 125 125 100% -1.2[-1.59,-0.81]

APPENDICES
Appendix 1. Search strategies

Database Period of search Search strategy
Cochrane Cen- Issue 8, 2013 #1 minilaparoscopic OR mini-laparoscopic OR minisite OR mini-site OR miniport OR mi-
tral Register of ni-port OR one OR two OR three OR transumbilical OR trans-umbilical
Controlled Trials #2 MeSH descriptor Miniaturization explode all trees
(CENTRAL) in The #3 MeSH descriptor Microsurgery explode all trees
Cochrane Library #4 (#1 OR #2 OR #3)
#5 (laparoscop* OR celioscop* OR coelioscop* OR abdominoscop* OR peritoneoscop*)
AND (cholecystecto* OR colecystecto*)
#6 MeSH descriptor Cholecystectomy, Laparoscopic explode all trees
#7 (#5 OR #6)
#8 (#4 AND #7)
MEDLINE 1987 to Septem- (minilaparoscopic OR mini-laparoscopic OR minisite OR mini-site OR miniport OR mi-

(PubMed) ber 2013 ni-port OR one OR two OR three OR transumbilical OR trans-umbilical OR "Miniaturiza-
tion"[MeSH] OR "Microsurgery"[MeSH]) AND (((laparoscop* OR celioscop* OR coelio-
scop* OR abdominoscop* OR peritoneoscop*) AND (cholecystecto* OR colecystecto*)) OR
"cholecystectomy, laparoscopic"[MeSH]) AND (((randomized controlled trial [pt] OR con-
trolled clinical trial [pt] OR randomized controlled trials [mh] OR random allocation [mh]
OR double-blind method [mh] OR single-blind method [mh] OR clinical trial [pt] OR clin-
ical trials [mh] OR ("clinical trial" [tw]) OR ((singl* [tw] OR doubl* [tw] OR trebl* [tw] OR
tripl* [tw]) AND (mask* [tw] OR blind* [tw])) OR (placebos [mh] OR placebo* [tw] OR ran-
dom* [tw] OR research design [mh:noexp]) NOT (animals [mh] NOT human [mh]))))
EMBASE (Ovid SP) 1987 to Septem- 1 exp CROSSOVER PROCEDURE/

ber 2013 2 exp DOUBLE BLIND PROCEDURE/
3 exp SINGLE BLIND PROCEDURE/
4 exp RANDOMIZED CONTROLLED TRIAL/
5 (((RANDOM* or FACTORIAL* or CROSSOVER* or CROSS) and OVER*) or PLACEBO*
or (DOUBL* and BLIND*) or (SINGL* and BLIND*) or ASSIGN* or ALLOCAT* or VOLUN-
TEER*).af.
6 1 or 2 or 3 or 4 or 5
7 (minilaparoscopic or mini-laparoscopic or minisite or mini-site or miniport or mini-port
or one or two or three or transumbilical OR trans-umbilical).af.

Informed decisions.

(Continued)
8 exp microsurgery/
9 7 or 8
10 (laparoscop* or celioscop* or coelioscop* or abdominoscop* or peritoneoscop*).af.
11 exp laparoscopic surgery/ or exp laparoscopy/
12 10 or 11
13 (cholecystect* or colecystect*).af.
14 exp cholecystectomy/
15 13 or 14
16 6 and 9 and 12 and 15
Science Citation 1987 to Septem- #1 TS=( minilaparoscopic OR mini-laparoscopic OR minisite OR mini-site OR miniport OR
Index Expanded ber 2013 mini-port OR one OR two OR three OR transumbilical OR trans-umbilical)
(apps.isiknowl- #2 TS=(laparoscop* OR celioscop* OR coelioscop* OR abdominoscop* OR peritoneo-
edge.com) scop*)
#3 TS=(cholecystecto* OR colecystecto*)
#4 TS=(random* OR rct* OR crossover OR masked OR blind* OR placebo* OR meta-analy-
sis OR systematic review* OR meta-analys*)
#5 #4 AND #3 AND #2 AND #1
World Health Or- September 2013 port AND laparoscopic cholecystectomy

ganization Inter-
national Clinical
Trials Registry
Platform Portal
(apps.who.int/tri-
alsearch/)

CONTRIBUTIONS OF AUTHORS
KSG selected trials, extracted data, and wrote the review.
JV or MR independently assessed the trials for inclusion and extracted the data.
BRD critically commented on the review and provided advice for improving the review.
DECLARATIONS OF INTEREST
None known.
SOURCES OF SUPPORT
Internal sources
• None, Not specified.
External sources
• None, Not specified.
DIFFERENCES BETWEEN PROTOCOL AND REVIEW
1. The control group has been defined very clearly now.
2. The outcomes have been divided into primary and secondary. Important patient outcomes have been used. The assessment of the risk
of bias has been revised in line with the recommendations of the Cochrane Handbook for Systematic Reviews of Interventions (Higgins
2011).
3. S Junnarkar was unable to perform the data extraction as per the protocol. J Vaughan or M Rossi performed the data extraction instead.
NOTES
There are changes in the review authors' team; the review has been prepared by KS Gurusamy, J Vaughan, M Rossi, and BR Davidson. The
protocol was prepared by KS Gurusamy, S Junnarkar, and BR Davidson.

Informed decisions.

INDEX TERMS
Medical Subject Headings (MeSH)

Cholecystectomy, Laparoscopic [adverse effects] [*methods]; Elective Surgical Procedures [adverse effects] [methods]; Operative
Time; Randomized Controlled Trials as Topic
MeSH check words

Humans


Cochrane Revision. Menos de 4 Puertos VS 4 Puertos en Colelap. 2014

Uploaded by

Document Information

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Cochrane Revision. Menos de 4 Puertos VS 4 Puertos en Colelap. 2014

Uploaded by

Copyright:

Available Formats

Gurusamy KS, Vaughan J, Rossi M, Davidson BR

Gurusamy KS, Vaughan J, Rossi M, Davidson BR.

Fewer-than-four ports versus four ports for laparoscopic cholecystectomy (Review) i

Fewer-than-four ports versus four ports for laparoscopic

Kurinchi Selvan Gurusamy1, Jessica Vaughan1, Michele Rossi2, Brian R Davidson1

Editorial group: Cochrane Hepato-Biliary Group

Data collection and analysis

Fewer-than-four ports versus four ports for laparoscopic cholecystectomy (Review) 1

Fewer-than-four ports versus four ports for laparoscopic cholecystectomy

Fewer-than-four ports versus four ports for laparoscopic cholecystectomy (Review) 2

Fewer-than-four ports versus four ports for laparoscopic cholecystectomy (Review) 3

Patient or population: people undergoing laparoscopic cholecystectomy.

Four ports Fewer-than-four ports

Serious ad- Low RR 3.93 634 ⊕⊝⊝⊝

30 per 1000 118 per 1000

Cochrane Database of Systematic Reviews

Conversion to 17 per 1000 12 per 1000 RR 0.68 581 ⊕⊝⊝⊝

GRADE Working Group grades of evidence

Cochrane Database of Systematic Reviews

Fewer-than-four ports versus four ports for laparoscopic cholecystectomy (Review) 6

Fewer-than-four ports versus four ports for laparoscopic cholecystectomy (Review) 7

Subgroup analysis and investigation of heterogeneity Description of studies

Fewer-than-four ports versus four ports for laparoscopic cholecystectomy (Review) 9

Figure 1. Study flow diagram.

Fewer-than-four ports versus four ports for laparoscopic cholecystectomy (Review) 10

Fewer-than-four ports versus four ports for laparoscopic cholecystectomy (Review) 11

Fewer-than-four ports versus four ports for laparoscopic cholecystectomy (Review) 12

Fewer-than-four ports versus four ports for laparoscopic cholecystectomy (Review) 13

Fewer-than-four ports versus four ports for laparoscopic cholecystectomy (Review) 15

Fewer-than-four ports versus four ports for laparoscopic cholecystectomy (Review) 16

Fewer-than-four ports versus four ports for laparoscopic cholecystectomy (Review) 17

Figure 8. Trial sequential analysis of hospital stay

Fewer-than-four ports versus four ports for laparoscopic cholecystectomy (Review) 18

Fewer-than-four ports versus four ports for laparoscopic cholecystectomy (Review) 19

Figure 10. Trial sequential analysis of return to normal activity

Fewer-than-four ports versus four ports for laparoscopic cholecystectomy (Review) 20

Fewer-than-four ports versus four ports for laparoscopic cholecystectomy (Review) 21

Fewer-than-four ports versus four ports for laparoscopic cholecystectomy (Review) 22

Fewer-than-four ports versus four ports for laparoscopic cholecystectomy (Review) 23

Fewer-than-four ports versus four ports for laparoscopic cholecystectomy (Review) 24

Fewer-than-four ports versus four ports for laparoscopic cholecystectomy (Review) 25

Ma 2011 {published data only} Ng 1999 {published data only}

Fewer-than-four ports versus four ports for laparoscopic cholecystectomy (Review) 26

Fewer-than-four ports versus four ports for laparoscopic cholecystectomy (Review) 27

Chan 2013 Gurusamy 2013

CTU 2011 Hall 2012

DerSimonian 1986 Higgins 2011

Macaskill 2001 Roberts 2010

Mjäland 1998 Savovic 2012

Moher 1998 Savovic 2012a

Moher 2010 Schulz 1995

Newell 1992 Sun 2009

Fewer-than-four ports versus four ports for laparoscopic cholecystectomy (Review) 29

Wang 2012 Wetterslev 2009

Characteristics of included studies [ordered by study ID]

Participants Country: Egypt.

Number randomised: 250.

Post-randomisation drop-outs: 0 (0%).

Revised sample size: 250.

Mean age: 47 years.

Females: 183 (73.2%).

1. People with symptomatic cholelithiasis, verified by abdominal ultrasonography.

Interventions Participants were randomly assigned to 1 of 2 groups.