Laparoscopic Versus Open Cholecystectomy For Patients With

Cochrane Database of Systematic Reviews
Laparoscopic versus open cholecystectomy for patients with

symptomatic cholecystolithiasis (Review)
Keus F, de Jong J, Gooszen HG, Laarhoven CJHM
Keus F, de Jong J, Gooszen HG, Laarhoven CJHM.

Laparoscopic versus open cholecystectomy for patients with symptomatic cholecystolithiasis.
Cochrane Database of Systematic Reviews 2006, Issue 4. Art. No.: CD006231.
DOI: 10.1002/14651858.CD006231.
www.cochranelibrary.com
Laparoscopic versus open cholecystectomy for patients with symptomatic cholecystolithiasis (Review)
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
TABLE OF CONTENTS
HEADER . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
ABSTRACT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
PLAIN LANGUAGE SUMMARY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
BACKGROUND . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
OBJECTIVES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
METHODS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
RESULTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
Figure 1. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
Figure 2. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
Figure 3. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
DISCUSSION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
AUTHORS’ CONCLUSIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12
ACKNOWLEDGEMENTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12
REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13
CHARACTERISTICS OF STUDIES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21
DATA AND ANALYSES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 62
Analysis 1.1. Comparison 1 LC versus OC - high-quality and low-quality trials regarding generation of the allocation
sequence, Outcome 1 Mortality. . . . . . . . . . . . . . . . . . . . . . . . . . . . 66
sequence, Outcome 2 Intra-operative complications. . . . . . . . . . . . . . . . . . . . . 67
sequence, Outcome 3 Minor complications. . . . . . . . . . . . . . . . . . . . . . . . 69
sequence, Outcome 4 Severe complications (without bile duct injuries). . . . . . . . . . . . . . . 71
sequence, Outcome 5 Bile duct injuries. . . . . . . . . . . . . . . . . . . . . . . . . . 73
sequence, Outcome 6 Total complications. . . . . . . . . . . . . . . . . . . . . . . . . 75
sequence, Outcome 7 Operative time (minutes). . . . . . . . . . . . . . . . . . . . . . . 77
sequence, Outcome 8 Hospital stay (days). . . . . . . . . . . . . . . . . . . . . . . . . 79
sequence, Outcome 9 Convalescence: work leave (days). . . . . . . . . . . . . . . . . . . . 80
Analysis 2.1. Comparison 2 LC versus OC - high-quality and low-quality trials regarding concealment of allocation,
Outcome 1 Mortality. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 81
Outcome 2 Intra-operative complications. . . . . . . . . . . . . . . . . . . . . . . . . 82
Outcome 3 Minor complications. . . . . . . . . . . . . . . . . . . . . . . . . . . . 84
Outcome 4 Severe complications (without bile duct injuries). . . . . . . . . . . . . . . . . . 86
Outcome 5 Bile duct injuries. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 88
Outcome 6 Total complications. . . . . . . . . . . . . . . . . . . . . . . . . . . . 90
Outcome 7 Operative time (minutes). . . . . . . . . . . . . . . . . . . . . . . . . . 92
Outcome 8 Hospital stay (days). . . . . . . . . . . . . . . . . . . . . . . . . . . . 94
Laparoscopic versus open cholecystectomy for patients with symptomatic cholecystolithiasis (Review) i
Outcome 9 Convalescence: work leave (days). . . . . . . . . . . . . . . . . . . . . . . . 95
Analysis 3.1. Comparison 3 LC versus OC - high-quality and low-quality trials regarding blinding, Outcome 1 Mortality. 96
Analysis 3.2. Comparison 3 LC versus OC - high-quality and low-quality trials regarding blinding, Outcome 2 Intra-
operative complications. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 97
Analysis 3.3. Comparison 3 LC versus OC - high-quality and low-quality trials regarding blinding, Outcome 3 Minor
complications. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 99
Analysis 3.4. Comparison 3 LC versus OC - high-quality and low-quality trials regarding blinding, Outcome 4 Severe
complications (without bile duct injuries). . . . . . . . . . . . . . . . . . . . . . . . . 101
Analysis 3.5. Comparison 3 LC versus OC - high-quality and low-quality trials regarding blinding, Outcome 5 Bile duct
injuries. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 103
Analysis 3.6. Comparison 3 LC versus OC - high-quality and low-quality trials regarding blinding, Outcome 6 Total
complications. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 105
Analysis 3.7. Comparison 3 LC versus OC - high-quality and low-quality trials regarding blinding, Outcome 7 Operative
time (minutes). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 107
Analysis 3.8. Comparison 3 LC versus OC - high-quality and low-quality trials regarding blinding, Outcome 8 Hospital
stay (days). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 109
Analysis 3.9. Comparison 3 LC versus OC - high-quality and low-quality trials regarding blinding, Outcome 9
Convalescence: work leave (days). . . . . . . . . . . . . . . . . . . . . . . . . . . . 110
Analysis 4.1. Comparison 4 LC versus OC - high-quality and low-quality trials regarding follow-up, Outcome 1
Mortality. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 111
Analysis 4.2. Comparison 4 LC versus OC - high-quality and low-quality trials regarding follow-up, Outcome 2 Intra-
operative complications. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 112
Analysis 4.3. Comparison 4 LC versus OC - high-quality and low-quality trials regarding follow-up, Outcome 3 Minor
complications. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 114
Analysis 4.4. Comparison 4 LC versus OC - high-quality and low-quality trials regarding follow-up, Outcome 4 Severe
complications (without bile duct injuries). . . . . . . . . . . . . . . . . . . . . . . . . 116
Analysis 4.5. Comparison 4 LC versus OC - high-quality and low-quality trials regarding follow-up, Outcome 5 Bile duct
injuries. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 118
Analysis 4.6. Comparison 4 LC versus OC - high-quality and low-quality trials regarding follow-up, Outcome 6 Total
complications. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 120
Analysis 4.7. Comparison 4 LC versus OC - high-quality and low-quality trials regarding follow-up, Outcome 7 Operative
time (minutes). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 122
Analysis 4.8. Comparison 4 LC versus OC - high-quality and low-quality trials regarding follow-up, Outcome 8 Hospital
stay (days). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 124
Analysis 4.9. Comparison 4 LC versus OC - high-quality and low-quality trials regarding follow-up, Outcome 9
Convalescence: work leave (days). . . . . . . . . . . . . . . . . . . . . . . . . . . . 125
Analysis 5.1. Comparison 5 LC versus OC - sensitivity and subgroup analyses, Outcome 1 Sensitivity analysis 1: Assuming
zero mortality in non-reporting trials. . . . . . . . . . . . . . . . . . . . . . . . . . 126
Analysis 5.2. Comparison 5 LC versus OC - sensitivity and subgroup analyses, Outcome 2 Sensitivity analysis 2: Imputing
medians and standard deviations for missing data in operative time (minutes). . . . . . . . . . . . 128
Analysis 5.3. Comparison 5 LC versus OC - sensitivity and subgroup analyses, Outcome 3 Sensitivity analysis 3: Imputing
medians and standard deviations for missing data in hospital stay (days). . . . . . . . . . . . . . 130
Analysis 5.4. Comparison 5 LC versus OC - sensitivity and subgroup analyses, Outcome 4 Subgroup analysis 1: Influence
antibiotic prophylaxis on total complications. . . . . . . . . . . . . . . . . . . . . . . . 131
cholangiography on operative time (minutes). . . . . . . . . . . . . . . . . . . . . . . . 133
antibiotic prophylaxis on hospital stay (days). . . . . . . . . . . . . . . . . . . . . . . . 135
ADDITIONAL TABLES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 136
APPENDICES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 150
WHAT’S NEW . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 152
CONTRIBUTIONS OF AUTHORS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 152
Laparoscopic versus open cholecystectomy for patients with symptomatic cholecystolithiasis (Review) ii
DECLARATIONS OF INTEREST . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 152
SOURCES OF SUPPORT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 153
NOTES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 153
INDEX TERMS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 153
Laparoscopic versus open cholecystectomy for patients with symptomatic cholecystolithiasis (Review) iii
[Intervention Review]
Laparoscopic versus open cholecystectomy for patients with

symptomatic cholecystolithiasis
Frederik Keus1 , Jeroen de Jong2 , H G Gooszen3 , C JHM Laarhoven4

1 Surgery,
Diakonessenhuis, Utrecht, Netherlands. 2 University Medical Center, Utrecht, Netherlands. 3 Surgery, University Medical
Center, Utrecht, Netherlands. 4 Surgery, St. Elisabeth Hospital, Tilburg, Netherlands
Contact address: Frederik Keus, Surgery, Diakonessenhuis, Bosboomstraat 1, Utrecht, Utrecht, 3582 KE, Netherlands.
erickeus@hotmail.com.
Editorial group: Cochrane Hepato-Biliary Group.

Publication status and date: Edited (no change to conclusions), published in Issue 1, 2010.
Review content assessed as up-to-date: 7 August 2006.
Citation: Keus F, de Jong J, Gooszen HG, Laarhoven CJHM. Laparoscopic versus open cholecystectomy for patients with symptomatic
cholecystolithiasis. Cochrane Database of Systematic Reviews 2006, Issue 4. Art. No.: CD006231. DOI: 10.1002/14651858.CD006231.
ABSTRACT
Background
Cholecystectomy is one of the most frequently performed operations. Open cholecystectomy has been the gold standard for over 100
years. Laparoscopic cholecystectomy was introduced in the 1980s.
Objectives
To compare the beneficial and harmful effects of laparoscopic versus open cholecystectomy for patients with symptomatic cholecys-
tolithiasis.
Search methods
We searched The Cochrane Hepato-Biliary Group Controlled Trials Register (April 2004), The Cochrane Library (Issue 1, 2004), MEDLINE
(1966 to January 2004), EMBASE (1980 to January 2004), Web of Science (1988 to January 2004), and CINAHL (1982 to January
2004) for randomised trials.
Selection criteria
All published and unpublished randomised trials in patients with symptomatic cholecystolithiasis comparing any kind of laparoscopic
cholecystectomy versus any kind of open cholecystectomy. No language limitations were applied.
Data collection and analysis
Two authors independently performed selection of trials and data extraction. The methodological quality of the generation of the
allocation sequence, allocation concealment, blinding, and follow-up was evaluated to assess bias risk. Analyses were based on the
intention-to-treat principle. Authors were requested additional information in case of missing data. Sensitivity and subgroup analyses
were performed when appropriate.
Main results
Thirty-eight trials randomised 2338 patients. Most of the trials had high bias risk. There was no significant difference regarding
mortality (risk difference 0,00, 95% confidence interval (CI) -0.01 to 0.01). Meta-analysis of all trials suggests less overall complications
in the laparoscopic group, but the high-quality trials show no significant difference (’allocation concealment’ high-quality trials risk
Laparoscopic versus open cholecystectomy for patients with symptomatic cholecystolithiasis (Review) 1
difference, random effects -0.01, 95% CI -0.05 to 0.02). Laparoscopic cholecystectomy patients have a shorter hospital stay (weighted
mean difference (WMD), random effects -3 days, 95% CI -3.9 to -2.3) and convalescence (WMD, random effects -22.5 days, 95%
CI -36.9 to -8.1) compared to open cholecystectomy.
Authors’ conclusions
No significant differences were observed in mortality, complications and operative time between laparoscopic and open cholecystectomy.
Laparoscopic cholecystectomy is associated with a significantly shorter hospital stay and a quicker convalescence compared with
the classical open cholecystectomy. These results confirm the existing preference for the laparoscopic cholecystectomy over open
cholecystectomy.
PLAIN LANGUAGE SUMMARY
Laparoscopic and open cholecystectomy seem equivalent considering complications and operative time, but laparoscopic
cholecystectomy is associated with quicker recovery
The classical open cholecystectomy and the minimally invasive laparoscopic cholecystectomy are two alternative operations for removal
of the gallbladder. There are no significant differences in mortality and complications between the laparoscopic and the open techniques.
The laparoscopic operation has advantages over the open operation regarding duration of hospital stay and convalescence.
BACKGROUND like non-severe complications, pulmonary outcomes, differences

in health status related quality-of-life, hospital stay, and differences
Gallstones are one of the major causes of morbidity in western in cost-effectiveness analysis should help decide which technique
society. It is estimated that the incidence of symptomatic chole- is superior.
cystolithiasis is up to 2.17 per thousand inhabitants (Legorreta
1993; Steiner 1994) with an annual performance rate of chole- Up to now, despite the availability of numerous randomised trials
cystectomies of more than 500,000 in USA (Olsen 1991; NIH on this topic, no systematic review or meta-analysis of randomised
Consensus 1993; Roslyn 1993). Until the end of the 1980s, open trials has been conducted in order to compare laparoscopic and
cholecystectomy was the gold standard for treatment of stones in open cholecystectomy. This lack of evidence was the main reason
the gallbladder. This operative procedure was effective with low for writing this systematic review. The objective is to evaluate the
mortality and complication proportions. assumed superiority of the laparoscopic over the open cholecys-
Laparoscopic cholecystectomy was introduced in 1985 (Mühe tectomy.
1986) and rapidly became the method of choice for surgical re-
moval of the gallbladder (NIH Consensus 1993) although the
evidence of superiority was absent. This rising popularity was
based on many arguments, including assumed lower morbidity
OBJECTIVES
and complication proportions, and a quicker postoperative recov-
ery compared to open cholecystectomy, despite an apparent in-
To evaluate the beneficial and harmful effects of laparoscopic and
crease in bile duct lesions. In non-randomised studies, the laparo-
open cholecystectomy for patients with symptomatic cholecys-
scopic cholecystectomy seemed superior to open cholecystectomy
tolithiasis. To assess whether laparoscopic and open cholecystec-
(Deziel 1993; Downs 1996; Shea 1996), but due to non-randomi-
tomy are different in terms of primary (mortality, complications,
sation adequate assessment of intervention effects may be missing.
and relief of symptoms) and secondary outcomes (conversions to
Differences in primary outcomes like mortality and complication open cholecystectomy, operative time, hospital stay, and conva-
proportions (particularly bile duct injuries) are important reasons lescence). When data were present, differences in other secondary
to choose one of the two operative techniques. When these primary outcomes like analgesic use, postoperative pain, pulmonary func-
outcomes show no significant difference, then secondary outcomes tion, and costs were compared as well.
METHODS Types of outcome measures
The primary outcome measures are mortality, complication pro-

portions (intra-operative, severe, bile duct injuries and total com-
plications; except minor complications), and relief of symptoms
Criteria for considering studies for this review
(pain relief ). Although relief of symptoms is the aim of cholecys-
tectomy, some patients continue to suffer from their complaints
and have persistent pain. Most important in obtaining a high pro-
portion of patients with relief of symptoms is adequate decision
Types of studies
making in setting the indication to operate or not. However, it
All randomised clinical trials comparing laparoscopic cholecystec- cannot be ruled out that some of this persistent pain should be
tomy to classical open cholecystectomy. Trials were included irre- attributed to the way of incision for cholecystectomy. Therefore,
spectively of blinding, number of patients randomised, and lan- it is of interest to include pain relief as a primary outcome.
guage of the article. Quasi-randomised studies were excluded. Secondary outcome measures are all other outcomes assessed in
comparing the two operative techniques. We assessed the follow-
ing secondary outcomes: operative time, hospital stay, convales-
cence, analgesic use, postoperative pain (visual analogue scale),
Types of participants
pulmonary outcome (pulmonary function tests by flow-volume
Patients with one or more stones in the gallbladder confirmed by curves), and cost-effectiveness if data were available.
ultrasonography or other imaging technique and symptoms at-
tributable to them, scheduled for cholecystectomy. Acute chole-
cystitis is a disease with different operative results including the
number of complications and conversions. Cholecystectomy in
patients suffering from acute cholecystitis should be distinguished
from cholecystectomy in patients suffering from symptomatic
Search methods for identification of studies
cholecystolithiasis. Therefore, randomised trials only including We searched the following databases: The Cochrane Hepato-Bil-
patients with acute cholecystitis were excluded from this review. iary Group Controlled Trials Register (6 April 2004), the Cochrane
Randomised trials including both symptomatic cholecystolithiasis Database of Systematic Reviews, Database of Abstracts of Reviews of
and acute cholecystitis were included in the review only if the large Effects (DARE), the Cochrane Central Register of Controlled Trials
majority (more than half ) of the included patients were operated (CENTRAL), Health Technology Assessment (HTA) Database, NHS
on because of symptomatic cholecystolithiasis. Economic Evaluation Database, all in The Cochrane Library (Issue
1, 2004), The National Library of Medicine (MEDLINE) (1966
to January 2004), The Intelligent Gateway to Biomedical & Phar-
macological Information (EMBASE) (1980 to January 2004), ISI
Types of interventions
Web of Knowledge (Web of Science) (1988 to January 2004), and
Any kind of laparoscopic cholecystectomy was assessed versus any CINAHL (1982 to January 2004). The search strategies used are
kind of open cholecystectomy. The group of open cholecystectomy provided in Appendix 1.
does not include small-incision cholecystectomy. Our aim was to perform a maximal sensitive search in order to
The following classifications of the surgical procedures (based on conduct a more complete review. As describing an operation of the
intention-to-treat) were used: gallbladder in medical terms without the word ’cholecystectomy’
Laparoscopic cholecystectomy includes those procedures started is impossible, a maximal sensitive search with the term cholecys-
as a laparoscopic procedure. Any kind of laparoscopic cholecystec- tectomy was used. For our MEDLINE search, a more sophisti-
tomy with creation of a pneumoperitoneum (by Veress needle or cated strategy, advised by the Dutch Cochrane Centre and listed
open introduction) or mechanical abdominal wall lift, irrespective in Table 1 was used (with help from Geert van der Heijden, Julius
of the number of trocars used. Center, Utrecht).
In all other cases the surgical intervention was classified as ’open Additional relevant trials were looked for by cross reference check-
cholecystectomy’; this traditional procedure can be carried out ing of identified randomised trials. Finally all authors of included
through a larger subcostal incision or median laparotomy. The trials were requested by letter for additional information on any
length of incision of 8 cm was used as cut-off point between small- published, unpublished, or ongoing trials.
incision and open cholecystectomy. This incision length was cho- Furthermore, during data extraction it turned out that in a large
sen arbitrary as in literature most authors used this length as a cut- number of trials essential data and information on methods were
off point between small-incision and (conversion to) open chole- missing. To improve the quality of the analysis, individual trialists
cystectomy. were contacted and asked for missing data.
Data collection and analysis • Unclear, if the report gave the impression that there had
been no dropouts or withdrawals, but this was not specifically
The review was conducted according to the present protocol (Keus
stated.
2004) and the recommendations by the Cochrane Handbook for
• Inadequate, if the number or reasons for dropouts and
Systematic Reviews of Interventions (Higgins 2005). All identified
withdrawals were not described.
trials were listed in the characteristics of included studies table and
an evaluation whether the trials fulfilled the inclusion criteria was Extraction of data
made. Excluded trials and the reasons for exclusion were listed as Inclusion and exclusion criteria used in each trial.
well (characteristics of excluded studies). The following data on the randomisation procedure have been
Assessment of methodological quality extracted:
Inadequate methodological quality in randomised clinical trials (1) Number of randomised patients.
carries the risk of overestimating intervention effects (Schulz 1995; (2) Number of patients not randomised and reasons for non-ran-
Moher 1998; Kjaergard 2001). Methodological quality, study de- domisation.
sign, and reporting quality have been recognised as criteria that (3) Exclusion after randomisation.
can restrict bias in the comparisons of interventions (Moher 1998; (4) Drop-outs.
Kjaergard 2001). Therefore the methodological quality of ran- (5) ’Intention-to-treat’ analysis.
domised clinical trials was assessed using the following compo- Also information on sample size, single- or multicentre study de-
nents. sign, assessment of primary and secondary outcome measures, use
Generation of the allocation sequence of antibiotic prophylaxis, surgical experience, and intra-operative
• Adequate, if the allocation sequence was generated by a cholangiography was registered (Table 1).
computer or random number table. Drawing of lots, tossing of a General descriptive data (like sex, age, body mass index (BMI),
coin, shuffling of cards, or throwing dice was considered as and American Society of Anaesthesiology (ASA) classification) are
adequate if a person who was not otherwise involved in the supposed to be equally divided due to randomisation (Assmann
recruitment of participants performed the procedure. 2000). These data are presented in Table 2 as far as available.
• Unclear, if the trial was described as randomised, but the Outcome data on mortality, complications, health-related quality-
method used for the allocation sequence generation was not of-life, pulmonary function, pain, duration of operation, hospital
described. stay, and convalescence were extracted according to availability.
• Inadequate, if a system involving dates, names, or Statistical analysis
admittance numbers were used for the allocation of patients. With adequate binary data available, a priori presentation in odds
These studies are known as quasi-randomised and were excluded ratios was preferred, based on clinical considerations and statistical
from the present review. robustness of the odds ratio. From this, results could be presented
in relative risk (ratio) (RR(R)) or numbers needed to treat (NNT)
Allocation concealment
by recalculation. However, exploring the data showed that for
• Adequate, if the allocation of patients involved a central
many binary data the outcome was rare or zero in both arms. Odds
independent unit, on-site locked computer, or sealed envelopes.
ratios (OR) and risk ratios (RR) are not estimable in trials with
• Unclear, if the trial was described as randomised, but the
zero events in both arms (Sweeting 2004). Binary outcomes with
method used to conceal the allocation was not described.
zero events in both arms can merely be presented in risk differences
• Inadequate, if the allocation sequence was known to the
(RD). Although risk differences are statistically less robust and
investigators who assigned participants or if the study was quasi-
result in conservative estimates, they are simple measures, easy to
randomised.
understand, and useful for public communication.
Blinding For continuous data, authors generally present their results in me-
• Adequate, if the trial was described (at least) as blind to dians with ranges due to suspicion of skewed data. However, for the
participants or assessors and the method of blinding was analysis of data in a meta-analysis, means with their corresponding
described. We are well aware that it is very difficult to properly standard deviations (SD) are needed to calculate mean differences
blind trials comparing surgical treatments. (MD) or weighted mean differences (WMD) with 95% confi-
• Unclear, if the trial was described as (double) blind, but the dence intervals (CI). Using means from all trials would ignore a
method of blinding was not described. non-Gaussian distribution. Therefore, skewness ratios (mean di-
• Not performed, if the trial was not blinded. vided by the standard deviation) were calculated first (Higgins
2005, page 96). With a ratio larger than two, skewness is ruled out,
Follow-up whereas skewness is suggested when the ratio is between one and
• Adequate, if the numbers and reasons for dropouts and two and a ratio less than one indicates strong evidence of skewness.
withdrawals in all intervention groups were described or if it was In situations where skewness could be ruled out, assumptions on
specified that there were no dropouts or withdrawals. equality of median to mean was made and used in the sensitivity
analyses. For trials presenting confidence intervals or standard er- large trials conducted with unclear or inadequate methods
ror of means, we performed a recalculation to a standard deviation (Kjaergard 2001).
(SD) (Higgins 2005, page 90-91). In case no data on standard de- • In situations of excessive heterogeneity we refrained from
viation were available, we calculated an average standard deviation reporting a pooled estimate when inappropriate.
from those observed in other studies and imputed this value for
The main focus of looking at heterogeneity in meta-analysis is
the standard deviation in the sensitivity analysis (Higgins 2005,
to discriminate true effect modifiers from other sources of het-
page 92).
erogeneity. Heterogeneity was calculated by the Cochrane Q test
Results were considered according to the four different criteria of
and quantified by measuring I2 (Higgins 2002). If excessive het-
quality. The existence of an overall difference in outcome was clear
erogeneity occurred, data were re-checked first and then adjusted.
when all four criteria showed significance. However, when the dif-
Extreme outliers were excluded (and tested in sensitivity analyses)
ferent quality criteria showed contradicting results, then an overall
when adequate reasons were available. If excessive heterogeneity
conclusion considering one outcome was not obvious and had to
still remained, depending on the specific research question, alter-
be made individually. In each individual component, results from
native methods were considered: subgroup analysis and meta-re-
high-quality trials subgroups were given more weight compared to
gression if appropriate.
analyses including all trials or low-quality trials subgroups. Results
with confidence intervals that touched, but did not cross, the line
Subgroup analysis
of equivalence were considered not significant.
Subgroup analyses were performed to compare the effects of the
Apart from comparisons in the four individual quality criteria,
interventions according to the methodological quality of the trials
we also performed a comparison with trials divided into low-bias
(adequate compared to unclear/inadequate). Furthermore, causes
risk trials (high methodological quality) and high-bias risk trials
of heterogeneity (defined as the presence of statistical heterogeneity
(low methodological quality). Trials that were assessed as adequate
by chi-squared test with significance set at P-value < 0.10 and
regarding all the four methodological criteria were considered low-
measured by the quantities of heterogeneity by I2 (Higgins 2002))
bias risk trials. All trials that were not assessed adequate with regard
were explored by comparing different groups of trials stratified
to all the four methodological criteria were considered high-bias
to level of experience of the surgeon and other factors that may
risk trials.
explain heterogeneity.
Bias detection
We have used funnel plots to provide a visual assessment of whether
Sensitivity analyses were performed assuming zero mortality for
treatment estimates were associated with study size. The presence
missing data. Sensitivity analyses were performed imputing medi-
of publication bias and other biases (Begg 1994; Egger 1997;
ans and using average standard deviations for missing data. In case
Macaskill 2001) varies with the magnitude of the treatment effect,
of outliers and borderline trials sensitivity analyses were performed
the distribution of study size, and whether a one- or two-tailed
as well. Subgroup analyses were performed testing the influence
test is used (Macaskill 2001).
of antibiotic prophylaxis, surgical experience and intra-operative
Both the random-effects model (DerSimonian 1986) and the
cholangiography on operative time, complications and hospital
fixed-effect model (DeMets 1987) for pooling effect estimates were
stay. These subgroup and sensitivity analyses were performed as
explored.
far as data were available.
• In case of no discrepancy (and no heterogeneity) the fixed-
The statistical package (RevMan Analyses) provided by The
effect models were presented.
Cochrane Collaboration was used (RevMan 2003). The statistical
• In case of discrepancy between the two models (ie, one
analyses were performed by FK and CL.
giving a significant intervention effect and the other no
significant intervention effect) both results were reported.
Discrepancy will only occur when substantial heterogeneity is
present.
• Most weight was put on the results of the fixed-effect model RESULTS
if the meta-analysis included one or more large trials, provided
that they had adequate methodology. (By large trials we refer to
those that outnumber the rest of the included trials in terms of Description of studies
numbers of outcomes and participants (ie, more than half of all
Searches and trial identification
included events and participants)).
For the search strategies used and the number of hits we refer to
• Otherwise, most weight was put on the results of the
additional Table 1.
random-effects model as it incorporated heterogeneity. The
The search was conducted in The Cochrane Hepato-Biliary Group
reason for this is that the random-effects model increases the
Controlled Trials Register (840 hits, 65 selected) and The Cochrane
weight of small trials. Small trials, however, are more often than
Library, Issue 1, 2004 with the following results: the Cochrane
Database of Systematic Reviews (33 hits, none were selected), the Trial designs
Database of Abstracts of Reviews on Effects (DARE) (17 hits, 5 se- One trial used a three-arm design (Coelho 1993). Another trial
lected), the Cochrane Central Register of Controlled Trials (CEN- used a five-arm design with in the first until the fourth arm open
TRAL) (1343 hits, 146 selected), the Health Technology Assessment cholecystectomy in combination with variable applications (in-
(HTA) Database (11 hits, 4 selected), and the NHS Economic Eval- tra-operative injection of bupivacaine for sympathetic blockade,
uation Database (43 hits, 6 selected). and propranolol combined with neostigmine treatment in or-
The search further comprised the following databases: The Na- der to evaluate postoperative paralytic ileus). We summarized all
tional Library of Medicine (MEDLINE) (8354 hits, 347 selected), open cholecystectomy patients in one group, resulting in a ratio
The Intelligent Gateway to Biomedical & Pharmacological Infor- of one to four of included patients in both groups in this trial
mation (EMBASE) (685 hits, 131 selected), ISI Web of Knowledge (GarciaCaballero 1993).
(Web of Science) (1163 hits, 148 selected), and CINAHL (740 hits, The trial by Lausten included two groups: patients with post-
9 selected). necrotic liver cirrhosis and patients with chronic hepatitis (both
Altogether, the search resulted in 13229 hits. The first selection groups classified ASA classification III-IV). Both groups were ran-
process was performed based on the title of the publications. In domised separately resulting in four groups. For data management
each step of selection, we included the publication in case of any reasons we listed both groups as separate trials (Lausten 1999 (1);
doubt. The total number of selections by title from this group of Lausten 1999 (2)).
13229 publications was 911 hits. After correction for duplicates, All other trials used a two-arm parallel-group design.
586 remained. Surgical interventions
The abstracts of these 586 publications were reviewed indepen- Usually laparoscopic cholecystectomy was not further specified.
dently by two reviewers (FK and JJ) in order to evaluate whether Some trials stated that a four trocar technique was used, creating
the study should be included in or excluded from the review. Dif- a pneumoperitoneum by using carbon dioxide insufflation with a
ferences between FK and JJ were discussed with CL. A total of 428 maximum intraperitoneal pressure of 12 to 15 millimetres mer-
publications could be rejected based on their abstract. Initially, tri- cury.
als which did not clearly mention whether they were randomised Open cholecystectomy was normally performed by a subcostal in-
clinical trials or not, were given the benefit of the doubt. If appro- cision, sometimes by midline laparotomy. As noted before, an in-
priate, they were excluded later on. Eventually, 158 publications cision length of 8 centimetres was taken as the cut-off point be-
were selected for further evaluation and these are all listed in the tween small-incision and open cholecystectomy. Trials with small-
review with reasons for in- or exclusion. incision cholecystectomy were excluded from this review.
A total of 112 publications were excluded (see table with ’Charac- Antibiotic prophylaxis administered at induction of anaesthesia
teristics of excluded studies’). A total of 46 publications describing was explicitly mentioned in some trials. In others the explicit omis-
38 trials including 2338 patients were included (see table with sion of antibiotic prophylaxis was mentioned, but most trials did
’Characteristics of included studies’ and Table 1). Critical appraisal not report on its use. Information on surgical experience (one or
and data extraction of these 38 trials were done by FK, JJ, and a few highly experienced surgeons performing all operations or
CL separately. Any disagreements were solved in several consensus also involving registrars) and intra-operative cholangiography (at-
meetings. tempted in all or only in selected patients) was recorded as well.
Of the 38 included trials, one trial was only described in short Outcome measures
(abstract: Zulfikaroglu 2002). Therefore only limited information A problem considering relief of symptoms and pain is how this
was obtained from this trial. As no language restrictions were used, outcome is defined and measured. Apart from differences in mea-
two publications (Jan 1993; Charlo 1995) were translated. Dou- surement, very few trials reported on this outcome. Therefore, we
ble publications of the trial results by the same research group are were unable to report results considering relief of symptoms and
listed in the references of included studies and are considered one pain. Nearly all trials reported on complications, operative time,
trial (eg, Agnifili 1993; Karayiannakis 1997). After contacting in- and hospital stay. Duration of sick leave was another commonly
dividual trialists additional data and information were obtained examined outcome. Not all trials clearly mentioned mortality. In
from 7 out of 38 included trials (see ’Acknowledgements’). trials in which mortality remained unclear, only in a sensitivity
All included trials used similar inclusion criteria, ie, patients with analysis the assumption that no patient had died was made when
symptomatic cholecystolithiasis who were scheduled for elective mortality was not mentioned (mean and most probable outcome
cholecystectomy. The extensiveness in which exclusion criteria of a trial). Some trials included mortality in their complications;
were described varied among the trials, but nearly all trials ex- we considered them separately. Because of the wide range of the
cluded acute cholecystitis. Trials with exclusively acute cholecysti- types of complications described, we classified (subcategorised) all
tis as inclusion criterion for cholecystectomy were excluded. Trials complications into four subcategories (intra-operative, minor, se-
that included minorities of patients with acute cholecystitis next vere, or bile duct injury) in addition to a total complication pro-
to patients with symptomatic cholecystolithiasis were included. portion (Table 3). Each complication was classified twice: once in
one of the four subcategories (intra-operative, minor, severe, or Our intention was to cover costs (an important secondary out-
bile duct injury) and once again in the total complication pro- come) as well, but although costs were described in several trials,
portion. Consequently, all bile duct complications were registered it was reported in a lot of different ways. Moreover, as different
separately from all other complications (and not counted in the points of view were taken in those analyses, and regarding the cul-
severe and minor subcategories). Likewise, all intra-operative com- tural differences (Vitale 1991) as well as differences in local costs,
plications (except from the bile duct injuries) were categorised sep- we decided that reporting this outcome would not be meaningful.
arately from other minor and severe complications.
The following outcomes were reported in one trial only or in dif-
ferent ways: bowel function, haemostatic markers (thrombin and Risk of bias in included studies
fibrinolysis markers), Swann-Ganz haemodynamic monitoring of
operation, endocrinological parameters, immunological parame- We evaluated the internal validity of the trials by considering the
ters and cytokines, acute phase proteins, and acute phase hor- four quality components, resulting in the following number of
mones. Pain scores and analgesic use as well as health-related qual- high-quality (ie, adequate) trials. Information that was not men-
ity-of-life were frequently examined outcomes. Due to the great tioned in a trial, was scored ’unclear’. When necessary information
variation in the way these were measured and reported, it appeared about randomisation, blinding procedure, or follow-up was un-
impossible to pool results. clear or missing, the authors were contacted to obtain specific ad-
Considering pulmonary function there is some limited data avail- ditional information on these issues. Trials, of which no response
able from randomised trials. However, considering the inconsis- was received, remained classified as ’unclear’ trials.
tency in the type of effect measure reported, as well as the dif- We assessed the quality of the 38 included trials as follows: gen-
ference in moments in time the outcome was measured, and the eration of allocation sequence was adequate in five trials (13.2%),
statistical problems that arise in pooling these results, we decided allocation concealment in nine trials (23.7%), blinding in three
to refrain from reporting these results. trials (7.9%), and follow-up in six trials (15.8%) (Table 4; Figure
1; Figure 2).
Figure 1. Methodological quality graph: review authors’ judgements about each methodological quality
item presented as percentages across all included studies.
Figure 2. Methodological quality summary: review authors’ judgements about each methodological quality
item for each included study.
The comparison dividing trials into low-bias risk trials (adequate
methodological quality in all four criteria) versus high-bias risk Demirer 2000; Hendolin 2000; Hasukic 2002; Zulfikaroglu 2002;
trials could not be performed as there was no low-bias risk trial Luo 2003; Bukan 2004). No significant differences were identified
present. in analysis stratifying trials for all four quality components. There
was no heterogeneity, therefore the fixed-effect model has been
Effects of interventions
applied (risk difference 0.00, 95% CI -0.02 to 0.01). Sensitivity
We conducted five analyses: four comparisons based on the analysis (10-1) assuming zero mortality in the trials that did not
four methodological quality components including the subgroups report mortality led to the same result (risk difference, fixed-effect
high- and low-quality trials, and a fifth comparison containing 0.00, 95% CI -0.01 to 0.01). The mortality proportions were 0%
sensitivity and subgroup analyses. Background data of all trials on and 0.09% in the laparoscopic and open groups, respectively.
age, sex, body mass index (BMI), and American Society of Anaes- Intra-operative complications
thesiology (ASA) classification are shown in Table 2. Complications were explicitly reported in 29 trials. Intra-operative
We identified a total of 38 randomised trials comparing laparo- complication proportions were 0.9% and 0.1% in the laparoscopic
scopic versus open cholecystectomy (one trial was split up into two and open group, respectively. Applying the fixed-effect model, no
trials for data management reasons (Lausten 1999 (1); Lausten significant differences in all four quality components were iden-
1999 (2)). Some authors excluded patients with complications or tified (risk difference, fixed-effect, all trials 0.01, 95% CI 0.00 to
converted laparoscopic procedures for reasons of influencing anal- 0.02).
yses (eg, Chaudhary 1999). As we are interested in complication Minor complications
proportions and intention-to-treat, we included these patients in The minor complication proportions were 2.1% and 3.1% in the
our analyses. A total of 1165 and 1173 patients were included in laparoscopic and open group respectively. There was no significant
the laparoscopic and open groups, respectively. Data are presented difference present in analysis of all trials. As heterogeneity was not
in Table 1 together with data on antibiotic prophylaxis, perfor- present, the fixed-effect model has been applied (risk difference
mance of cholangiography, and experience of the surgeon. -0.01, 95% CI -0.03 to 0.00). No significant differences were
In the analyses, there were no significant differences in mortality, present in any of the subgroups.
intra-operative complications, minor complications, and bile duct Severe complications
injuries considering all trials, neither in the subgroups high-qual- The severe complication proportions were 2.2% and 6.8% in the
ity and low-quality trials, nor between the fixed-effect model and laparoscopic and open group respectively. As heterogeneity was
the random-effects model. As ’concealment of allocation’ is con- present (up to 69%), the random-effects model has been applied
sidered the most important component of methodological quality, and no significant differences were present. There were no discrep-
all subgroup results considering this aspect (except for the fore- ancies between the four quality components.
mentioned results that were not significantly different) were pre- Bile duct injury
sented in additional Table 5. The bile duct injury proportions were 0.2% in both groups. No
Sensitivity analyses were performed assuming zero mortality and significant differences were present and there were no discrepancies
imputing medians and standard deviations for missing data (oper- between the four quality components in the subgroups. As no
ative time and hospital stay). No outliers and no borderline trials heterogeneity was present, the fixed-effect model has been applied
were identified. Subgroup analyses were performed testing the in- (risk difference 0.00, 95% CI -0.01 to 0.01).
fluence of cholangiography on operative time and the influence of Total complications
antibiotic prophylaxis on hospital stay. Other sensitivity and sub- Complications were not reported in nine trials (Blanc-Louvry
group analyses were not performed as necessary data were missing 2000; Bukan 2004; GarciaCaballero 1993; Kjaersgaard 1994;
or analyses were considered inappropriate. Koprulu 1996; Luo 2003; Putensen-Himmer 1992; Rovina 1996;
Mortality Zulfikaroglu 2002). All complications (and frequencies) were
Mortality was explicitly reported in 14 trials. Mortality was not listed (Table 3). There were three re-operations reported in each
reported in 24 trials (Putensen-Himmer 1992; Coelho 1993; group. We defined a complication as something the author called
GarciaCaballero 1993; Trondsen 1993; Dionigi 1994; Kjaersgaard a complication and refrained from interpretation by ourselves. In
1994; Dauleh 1995; Essen 1995; Huang 1996; Koprulu 1996; a funnel plot using total complication proportions we did not find
Ortega 1996; Rovina 1996; Karayiannakis 1997; Volpino 1998; indications of publication bias (Figure 3).
Zajac 1998; Chaudhary 1999; Blanc-Louvry 2000; Coskun 2000;
Figure 3. Funnel plot on laparoscopic versus open cholecystectomy regarding concealment of allocation
considering total complications, including 95% confidence interval lines. No arguments for bias.
The total complication proportions were 5.4% and 10.1% in the

laparoscopic and open group respectively (Table 3). Reoperation has been used and no significant differences were present in all
proportions were 0.3% in both groups. methodological quality components (the high-quality subgroup
Heterogeneity was present, therefore the random-effects model in the ’blinding’ quality component did show a significant dif-
has been applied resulting in significant differences in analysis of ference, but was calculated from one trial only) (WMD all trials,
all trials and in the low-quality trials subgroups (risk difference all random effects 3.79 minutes, 95% CI -4.88 to 12.46). All avail-
trials -0.04, 95% CI -0.07 to -0.01). Meta-analysis of all trials sug- able data were presented in Table 6. In a sensitivity analysis (10-
gested fewer overall complications in the laparoscopic group, but 2) including the assumptions on standard deviations and medians
not in the high-quality trials subgroups (’allocation concealment’ considering skewness, there was no significant difference present
high-quality trials risk difference, random effects -0.01, 95% CI - (WMD, random effects 6.42 minutes, 95% CI -1.21 to 14.04).
0.05 to 0.02). Regarding the high-quality trials subgroup analyses Comparing in a subgroup analysis (10-5) the operative time from
as most reliable, we conclude that there is no significant difference trials that explicitly mentioned they did attempt intra-operative
in total complication proportions (allocation concealment, high- cholangiography in all patients versus the operative time from tri-
quality trials: laparoscopic: 2.5% versus open: 4.3%). als that explicitly mentioned they did not attempt routine intra-
Comparing in subgroup analysis (10-4) total complication pro- operative cholangiography in all patients (but only in selected or
portions from trials that explicitly mentioned that they did use no patients) (and also including the assumptions on standard de-
antibiotic prophylaxis versus the total complication proportions viations and medians) did not show an influence of cholangiogra-
from trials that explicitly mentioned that they did not use antibi- phy on operative time.
otic prophylaxis, showed no clear influence of antibiotic prophy-
laxis on total complication proportions. Hospital stay
There was a significant shorter hospital stay in the laparoscopic
Operative time group. There was severe heterogeneity present, therefore the ran-
Heterogeneity was present, therefore the random-effects method dom-effects model was applied. This model resulted in a signifi-
cant difference in all four methodological comparisons (WMD all niques considering total complication proportions. Regarding in-
trials, random effects -3.07 days, 95% CI -3.89 to -2.26). Only tra-operative, minor, and bile duct injury complication propor-
two high-quality trials subgroups did not show this significant dif- tions there are no significant differences (fixed-effect and random-
ference. effects models) between laparoscopic and open cholecystectomy.
All available data were presented in Table 7. In a sensitivity analysis Regarding severe complications, the low-quality group and all tri-
(10-3) including the assumptions on standard deviations and me- als group suggest a lower complication proportion in the laparo-
dians considering skewness, there was a significant shorter hospital scopic treatment group applying the fixed-effect model. However,
stay in the laparoscopic group (WMD, random effects -3.15 days, after incorporating the high degree of heterogeneity (up to 69%)
95% CI -3.94 to -2.35). Comparing in a subgroup analysis (10- in the random-effects model, no significant difference in severe
6) hospital stay from trials that explicitly mentioned that they did complications could be observed.
use antibiotic prophylaxis versus the hospital stay from trials that
Comparing high-quality trials with low-quality and all trials for to-
explicitly mentioned that they did not use antibiotic prophylaxis
tal complication proportions, a significant difference is suggested
(and also including the assumptions on standard deviations and
using the fixed-effect model. However, incorporating the high de-
medians) did not show an influence of antibiotic prophylaxis on
gree of heterogeneity (up to 68%) in the random-effects model,
hospital stay.
the high-quality trials subgroup that is the most reliable, shows
Convalescence
no significant difference for total complications. In the subgroup
Unfortunately convalescence involving normal activity was not re-
analysis evaluating the influence of antibiotic prophylaxis on total
ported, therefore only convalescence considering work leave could
complications no evidence of effect was found. There were no sig-
be analysed. Applying the random effects model, there was a sig-
nificant differences in the subgroup analyses of the four method-
nificant difference favouring the laparoscopic technique, equal in
ology quality aspects.
all methodological comparisons (WMD, random effects -22.51
days, 95% CI -36.89 to -8.13). However, only three trials de- We found no significant difference in operative time. Incorporat-
scribed return to work. ing the high degree of heterogeneity (98%) in the random-effects
models in all four methodological subgroup analyses, the signifi-
cant differences in operative time (in the fixed-effect models) dis-
appear. The significant result of one high-quality trial (subgroup
DISCUSSION analysis in the ’blinding’ comparison) is considered an outlier and
ignored in our conclusion.
The present systematic review contains four major findings. First,
the comparison of the clinical outcome of laparoscopic to open In sensitivity analysis assumptions were made on medians for
cholecystectomy has been well tested in randomised clinical trials means and imputing values for standard deviations. Skewness was
(over 2300 patients have been randomised in 38 trials), but the ruled out and reported in additional Table 6. Incorporating exces-
methodological quality has been disappointingly low. Not even sive heterogeneity (97%) in the random-effects model reduces the
one trial could be graded as low-bias risk trial (adequate method- suggested shorter operative time of the open group to no signifi-
ological quality in all four components). Secondly, laparoscopic cant difference in operative time between laparoscopic and open
cholecystectomy did not carry more bile duct injuries than open cholecystectomy. This is in line with the previous results in the
cholecystectomy. Thirdly, hospital stay was significantly shorter four methodological subgroups. In subgroup analysis of the effect
for laparoscopic cholecystectomy compared with open cholecys- of intra-operative cholangiography on operative time, no effect
tectomy. Fourthly, convalescence after laparoscopic cholecystec- was found.
tomy, measured by return to work, was significantly shorter com-
Hospital stay was shorter in the laparoscopic group. After incor-
pared with open cholecystectomy.
poration of severe heterogeneity in the random-effects model, and
We identified a total of 38 trials comparing laparoscopic and open also in sensitivity analysis assuming values for missing standard
cholecystectomy with different focuses on outcome measures. In deviations and means, both in the fixed-effect as in the random-
these comparisons mortality was near 0% which is in concordance effects model a significant difference persists. Subgroup analysis
with data from the non-randomised literature (Downs 1996). on antibiotic prophylaxis as a potential factor influencing hospi-
With 1165 and 1173 patients included in the trials of this com- tal stay (through complications) demonstrated that we still have
parison, only one death was reported. insufficient data.
Meta-analysis of all trials showed a significant difference in total Convalescence regarding work leave is quicker after laparoscopic
complications in favour of the laparoscopic technique, however, cholecystectomy. Distinction was made in convalescence concern-
high-quality trials subgroups showed no significant difference. As ing work leave and return to normal activity. Unfortunately, only
most value must be given to the high-quality trials, it must be con- three trials reported on convalescence considering work leave and
cluded that there is no significant difference between both tech- none reported on return to normal activity. The results of all four
methodological subgroup analyses agree on their findings: both in ciated with a significantly shorter hospital stay and faster return
the fixed-effect and random-effects model there were significant to work. These seem the reasons for laparoscopic cholecystectomy
differences in favour of laparoscopic cholecystectomy considering being the preferred method of choice above open cholecystectomy.
convalescence.
Implications for research
Considering methodological quality there were five, nine, three,
and six trials classified as being high-quality considering ’genera- Cost-minimisation analyses could probably play a decisive role.
tion of allocation sequence’, ’concealment of allocation’, ’blinding’
Future research on implementation issues of laparoscopic tech-
and ’follow-up’, respectively. In a total of 38 trials we thought this
niques in general, with the cholecystectomy as a model, should
rather disappointing. As many trials did not report on items like
focus not only on clinical outcome measures, but also, or more
mortality and complication proportions, the number of trials left
importantly, on differences in costs.
for analysis in some outcomes (and subgroups) were rather low,
sometimes even only one or two. In accordance with research in general, the overall quality of
the randomised trials included in this systematic review varied
Another aspect of trial quality is that a lot of trials focus on
enormously, with the majority of trials having several method-
haemodynamics, acute phase reactants, oxidative stress factors,
ological deficiencies. In line with conclusions from other sys-
or endocrine functioning etcetera, making comparison of these
tematic reviews, the quality of trials needs to improve in order
items impossible because authors used different outcome mea-
to limit bias. Reports can be improved importantly by adopting
sures. Moreover, these outcomes are short-term results, implying
the CONSORT Statement while conducting and reporting trials
a limited follow-up in all patients in these randomised trials. For
(www.consort-statement.org).
the sake of equal comparisons, some authors even excluded com-
plicated and/or converted patients, thereby ignoring the inten- More trials ought to become multi-centre trials with larger number
tion-to-treat principle. As we performed all our analyses accord- of participants.
ing to intention-to-treat, we included these patients again in our
analyses. As authors describing these ’immunological’ and other
comparable outcome measures are not focused on complications
(not looking for them, making registration of complications prob-
ACKNOWLEDGEMENTS
ably less accurate) and especially taking into account that they
only perform very short-term follow-up (hospital stay of a few The Cochrane Hepato-Biliary Review Group, Copenhagen, for
days), we are afraid that some underreporting of complications excellent support;
must exist. As high-quality trials are more likely to estimate the
The Dutch Cochrane Centre, Amsterdam, for advice;
’true’ effects of the interventions (Schulz 1995; Moher 1998; Jüni
2001; Kjaergard 2001; Egger 2003), the relatively low percentage The Library of the University Medical Center, Utrecht, for coop-
of high-quality trials in this review is probably the most important eration in the search for full text articles;
factor of possible underestimation of complication proportions.
Geert van der Heijden (Julius Center for Health Sciences and
All 38 trials were conducted as single-centre trials. With the risks of Primary Care, University Medical Center, Utrecht) for advice in
false-positive and false-negative findings in small trials this single- systematic searches;
centre culture ought to be replaced by large trials conducted as
multi-centre trials. Although many trials in this systematic review Ingeborg van der Tweel (Julius Center for Health Sciences and
were small trials, no clear indications of publication bias were Primary Care, University Medical Center, Utrecht) for statistical
found analysing total complication proportions (Figure 3). advice;
Laura Breuning, Jan Willem Elshof, and Yan Gong (Cochrane
Hepato-Biliary Review Group, Copenhagen) for translations.
AUTHORS’ CONCLUSIONS We wish to thank all authors for their willingness to help in im-
Implications for practice proving the review by responding to our request for additional
Laparoscopic cholecystectomy did not differ significantly from information. Unfortunately, not all information we asked for was
open cholecystectomy regarding mortality, complications, bile always useful for pooling into overall effect measures. The authors
duct injuries, and operative time. However, laparoscopic cholecys- are: U Berggren, MS Chumillas, A Engin, A Thorell (Essen 1995),
tectomy leads to shorter incisional wounds and seems to be asso- G Galizia, Z Mimica, and D Prisco.
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Blanc-Louvry 2000 {published data only} Cuffari S, Bordone N, et al. Effects of surgical trauma
Blanc-Louvry I, Coquerel A, Koning E, Maillot C, Ducrotte of laparoscopic vs open cholecystectomy. Hepato-
P. Operative stress response is reduced after laparoscopic Gastroenterology 1994;41(5):471–6.
compared to open cholecystectomy - The relationship with Dominioni L, Benevento A, Carcano G, Chiappa A,
postoperative pain and ileus. Digestive Diseases and Sciences Dionigi R. Acute-phase response after laparoscopic and
2000;45(9):1703–13. open cholecystectomy [abstract]. British Journal of Surgery
Bukan 2004 {published data only} 1993;80:S44.
Bukan MH, Bukan N, Kaymakcioglu N, Tufan T. Effects of Engin 1998 {published data only}
open vs. laparoscopic cholecystectomy on oxidative stress. Engin A, Bozkurt S, Ersoy E, Oguz M, Gokcora N. Stress
Tohoku Journal of Experimental Medicine 2004;202(1):51–6. hyperglycemia in minimally invasive surgery. Surgical
Laparoscopy & Endoscopy 1998;8(6):435–7.
Charlo 1995 {published data only}
Charlo DT, Fernandez MM, Tejido SC. A cost analysis Essen 1995 {published data only}
of laparoscopic cholecystectomy compared with the Essen P, Thorell A, McNurlan MA, Anderson S, Ljungqvist
open technic [Analisis de costes de la colecistectomia O, Wernerman J, et al. Laparoscopic cholecystectomy does
not prevent the postoperative protein catabolic response in Koprulu 1996 {published data only}
muscle. Annals of Surgery 1995;222:36–42. Koprulu G, Esen F, Pembeci K, Denkel T. Pulmonary
Gal 1997 {published data only} mechanics during laparoscopic surgery. Advances in
Gal I, Roth E, Lantos J, Varga G, Jaberansari MT. Experimental Medicine and Biolology 1996;388:643–6.
Inflammatory mediators and surgical trauma regarding Lausten 1999 (1) {published data only}
laparoscopic access: free radical mediated reactions. Acta Lausten SB, El Sefi T, Marwan I, Ibrahim TM, Jensen
Chirurgica Hungarica 1997;36:97–9. LS, Grofte T, et al. Postoperative hepatic catabolic stress
Galizia 2001 {published data only} response in patients with cirrhosis and chronic hepatitis.
Galizia G, Prizio G, Lieto E, Castellano P, Pelosio L, World Journal of Surgery 2000;24(3):365–71.
Imperatore V, et al. Hemodynamic and pulmonary changes
∗
Lausten SB, Ibrahim TM, El Sefi T, Jensen LS, Gesser
during open, carbon dioxide pneumoperitoneum, and B, Larsen CG, et al. Systemic and cell-mediated immune
abdominal wall-lifting cholecystectomy - A prospective, response after laparoscopic and open cholecystectomy
randomized study. Surgical Endoscopy 2001;15(5):477–83. in patients with chronic liver disease - A randomized,
prospective study. Digestive Surgery 1999;16(6):471–7.
GarciaCaballero 1993 {published data only}
Garcia-Caballero M, Vara-Thorbeck C. The evolution of Lausten 1999 (2) {published data only}
postoperative ileus after laparoscopic cholecystectomy - a Lausten SB, El Sefi T, Marwan I, Ibrahim TM, Jensen
comparative study with conventional cholecystectomy and LS, Grofte T, et al. Postoperative hepatic catabolic stress
sympathetic blockade treatment. Surgical Endoscopy 1993;7 response in patients with cirrhosis and chronic hepatitis.
(5):416–9. World Journal of Surgery 2000;24(3):365–71.
Hasukic 2002 {published data only}
∗
Lausten SB, Ibrahim TM, El Sefi T, Jensen LS, Gesser
Hasukic S, Mesic D, Dizdarevic E, Keser D, Hadziselimovic B, Larsen CG, et al. Systemic and cell-mediated immune
S, Bazardzanovic M. Pulmonary function after laparoscopic response after laparoscopic and open cholecystectomy
and open cholecystectomy. Surgical Endoscopy 2002;16(1): in patients with chronic liver disease - A randomized,
163–5. prospective study. Digestive Surgery 1999;16(6):471–7.
Hendolin 2000 {published data only} Lujan 1998 {published data only}
Hendolin HI, Paakkonen ME, Alhava EM, Tarvainen Lujan JA, Sanchez-Bueno F, Parrilla P, Robles R, Torralba JA,
R, Kemppinen T, Lahtinen P. Laparoscopic or open Gonzalez-Costea R. Laparoscopic vs. open cholecystectomy
cholecystectomy: a prospective randomised trial to compare in patients aged 65 and older. Surgical Laparoscopy &
postoperative pain, pulmonary function, and stress response. Endoscopy 1998;8(3):208–10.
European Journal of Surgery 2000;166(5):394–9.
Luo 2003 {published data only}
Huang 1996 {published data only} Luo K, Li J, Li L, Wang G, Sun J, Wu S. Operative
Huang SM, Wu CW, Lui WY, Peng FK. A prospective stress response and energy metabolism after laparoscopic
randomised study of laparoscopic v. open cholecystectomy cholecystectomy and open cholecystectomy. Zhonghua Wai
in aged patients with cholecystolithiasis. South African Ke Za Zhi [Chinese Journal of Surgery] 2002;40(12):923–6.
Journal of Surgery 1996;34(4):177–9. ∗
Luo K, Li JS, Li LT, Wang KH, Shun JM. Operative
Jan 1993 {published data only} stress response and energy metabolism after laparoscopic
Jan YY, Chen MF. Laparoscopic versus open cholecystectomy compared to open surgery. World Journal
cholecystectomy: a prospective randomized study. Journal of Gastroenterology 2003;9(4):847–50.
of the Formosan Medical Association 1993;92(Suppl 4):
Milheiro 1994 {published data only}
S243–S249.
Milheiro A, Sousa FC, Manso EC, Leitao F. Metabolic
Karayiannakis 1997 {published data only} responses to cholecystectomy - open vs laparoscopic
Karayiannakis AJ, Makri GG, Mantzioka A, Karousos approach. Journal of Laparoendoscopic Surgery 1994;4(5):
D, Karatzas G. Postoperative pulmonary function after 311–7.
laparoscopic and open cholecystectomy. British Journal of
Anaesthesia 1996;77(4):448–52. Mimica 2000 {published data only}
∗
Karayiannakis AJ, Makri GG, Mantzioka A, Karousos D, Mimica Z, Biocic M, Bacic A, Banovic I, Tocilj J, Radonic
Karatzas G. Systemic stress response after laparoscopic or V, et al. Laparoscopic and laparotomic cholecystectomy:
open cholecystectomy: a randomized trial. British Journal of a randomized trial comparing postoperative respiratory
Surgery 1997;84(4):467–1. function. Respiration 2000;67(2):153–8.
Kjaersgaard 1994 {published data only} Ortega 1996 {published data only}
Kjaersgaard P, Reiertsen O, Trondsen E, Rosseland AR, Ortega AE, Peters JH, Incarbone R, Estrada L, Ehsan A,
Larsen S. Comparison of sequential and fixed-sample Kwan Y, et al. A prospective randomized comparison of the
designs in a controlled clinical trial with laparoscopic versus metabolic and stress hormonal responses of laparoscopic
conventional cholecystectomy. Scandinavian Journal of and open cholecystectomy. Journal of the American College
Gastroenterology 1994;29(9):854–8. of Surgeons 1996;183(3):249–56.
Prisco 2000 {published data only} Assalia 1993 {published data only}
Prisco D, De Gaudio AR, Carla R, Gori AM, Fedi S, Cella Assalia A, Schein M, Kopelman D, Hashmonai M.
AP, et al. Videolaparoscopic cholecystectomy induces a Minicholecystectomy vs conventional cholecystectomy
hemostasis activation of lower grade than does open surgery. - a prospective randomized trial - implications in the
Surgical Endoscopy 2000;14(2):170–4. laparoscopic era. World Journal of Surgery 1993;17(6):
Putensen-Himmer 1992 {published data only} 755–9.
Putensen-Himmer G, Putensen C, Lammer H, Lingnau Assalia 1997 {published data only}
W, Aigner F, Benzer H. Comparison of postoperative Assalia A, Kopelman D, Hashmonai M. Emergency
respiratory function after laparoscopy or open laparotomy minilaparotomy cholecystectomy for acute cholecystitis:
for cholecystectomy. Anesthesiology 1992;77(4):675–80. prospective randomized trial - implications for the
laparoscopic era. World Journal of Surgery 1997;21(5):
Rovina 1996 {published data only}
534–9.
Rovina N, Bouros D, Tzanakis N, Velegrakis M, Kandilakis
S, Vlasserou F, et al. Effects of laparoscopic cholecystectomy Bablekos 2003 {published data only}
on global respiratory muscle strength. American Journal of Bablekos GD, Roussou T, Rasmussen T, Vassiliou MP,
Respiratory and Critical Care Medicine 1996;153(1):458–61. Behrakis PK. Postoperative changes on pulmonary function
after laparoscopic and open cholecystectomy. Hepato-
Trondsen 1993 {published data only}
Gastroenterology 2003;50(53):1193–200.
Trondsen E, Reiertsen O, Andersen OK, Kjaersgaard P.
Laparoscopic and open cholecystectomy - a prospective, Barkun 1992 {published data only}
randomized study. European Journal of Surgery 1993;159
∗
Barkun JS, Barkun AN, Sampalis JS, Fried G, Taylor
(4):217–21. B, Wexler MJ, et al. Randomized controlled trial of
laparoscopic versus mini cholecystectomy. Lancet 1992;340
Volpino 1998 {published data only}
(7):1116–9.
Volpino P, Cangemi V, D’Andrea N, Cangemi B, Piat
Barkun JS, Caro JJ, Barkun AN, Trindade E. Cost-
G. Hemodynamic and pulmonary changes during and
effectiveness of laparoscopic and mini-cholecystectomy in
after laparoscopic cholecystectomy. A comparison with
a prospective randomized trial. Surgical Endoscopy 1995;9
traditional surgery. Surgical Endoscopy 1998;12(2):119–23.
(11):1221–4.
Zajac 1998 {published data only}
Barkun 1993 {published data only}
Zajac M, Zajac K, Engel Z. Laparoscopy vs laparotomy
Barkun JS, Barkun AN, Meakins JL, Bailar J, Battista RN,
for cholecystectomy in elderly patients [abstract]. British
Brassard R, et al. Laparoscopic versus open cholecystectomy
Journal of Anaesthesia 1998;80(Suppl 1):2.
- the Canadian experience. American Journal of Surgery
Zulfikaroglu 2002 {published data only} 1993;165(4):455–8.
Zulfikaroglu B, Koc M, Soran A, Isman FK, Cinel
Baxter 1992 {published data only}
I. Evaluation of oxidative stress in laparoscopic
Baxter JN, O’Dwyer PJ. Laparoscopic or minilaparotomy
cholecystectomy. Surgery Today 2002;32(10):869–74.
cholecystectomy?. BMJ (Clinical Research Ed.) 1992;304
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Bernard 1994 {published data only}
Al Tameem 1995 {published data only} Bernard A, Aho S, Charvet-Protat S, Durieux P. Evaluation
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Alponat 2002 {published data only} 707–17.
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∗
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Gough DB, et al. Minimal access surgery for cholelithiasis Delogu 1999 {published data only}
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open versus laparoscopic cholecystectomy [Veranderungen
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Frazee 1991 {published data only}
Champault 2002 {published data only}
Frazee RC, Roberts JW, Okeson GC, Symmonds RE,
Champault A, Vons C, Dagher I, Amerlinck S, Franco D.
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Clezy 1996 {published data only}
Glaser 1995 {published data only}
Clezy JKA. Randomized trial of laparoscopic
Glaser F, Kuntz C, Klee F, Buhr HJ, Sannwald G, Herfarth
cholecystectomy and mini-cholecystectomy [letter]. British
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cholecystectomy. Langenbecks Archiv fur Chirurgie 1993;
Coelho 1992 {published data only} Suppl 1 Forumband:45–8.
Coelho JC, Marchesini JB, Campos AC, Camargo CA, ∗
Glaser F, Sannwald GA, Buhr HJ, Kuntz C, Mayer H,
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laparotomy [Colecistectomia por mini–laparotomia]. laparoscopic cholecystectomy. Annals of Surgery 1995;221
Revista Brasileira de Cirurgia 1992;19:213–5. (4):372–80.
Coelho 1992a {published data only} Go 1995 {published data only}
Coelho JC, Campos GM, Matias JE. Cholecystectomy Go PMNYH, Stolk MFJ, Obertop H, Dirksen C, van
through mini-incision and through classic subcostal der Elst DH, Ament A, et al. Symptomatic gallbladder
incision: a prospective randomized study [Colecistectomia stones: cost-effectiveness of treatment with extracorporeal
por mini–incisao subcostal classica: estudo prospectivo shock-wave lithotripsy, conventional and laparoscopic
randomizado]. Revista Brasileira de Cirurgia 1992;82:67–9. cholecystectomy. Surgical Endoscopy 1995;9(1):37–41.
Da Costa 1995 {published data only} Grande 2002 {published data only}
Da Costa ML, Qureshi MA, Brindley NM, Burke PE, Grace Grande M, Tucci GF, Adorisio O, Barini A, Rulli F, Neri
PA, Bouchier-Hayes D. Normal inspiratory muscle strength A, et al. Systemic acute-phase response after laparoscopic
is restored more rapidly after laparoscopic cholecystectomy. and open cholecystectomy. Surgical Endoscopy 2002;16(2):
Annals of the Royal College of Surgeons of England 1995;77: 313–6.
252–5. Hagmuller 1997 {published data only}
Decker 1993 {published data only} Hagmuller E, Lorenz D, Gunther HJ, Rumstadt B,
Decker D, Schondorf M, Decker P, Bidlingmaier F, Jentschura D. Comparison of catabolic response in
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chlecystectomy using a 13C-leucine tracer model Keus 2006 {unpublished data only}
[Untersuchungen zum Ausmass der postoperativen Keus E, van Laarhoven CJHM. Small-incision versus
Katabolie nach laparoskopischer und konventioneller laparoscopic cholecystectomy: blind RCT. Unpublished
Cholecystektomie unter Anwendung eines 13C–leuzin– data.
tracermodells]. Langenbecks Archiv fur Chirurgie 1997;I
Forumband:241–5. Kiviluoto 1997 {published data only}
Kiviluoto T, Siren J, Luukkonen P, Kivilaakso E.
Hauer-Jensen 1986 {published data only}
Laparoscopic vs. open cholecystectomy for acute
Hauer-Jensen M, Karesen R, Nygaard K, Solheim K, Amlie
cholecystitis. A prospective randomized study.
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cholangiography during cholecystectomy for gallstone
disease: a prospective, randomized study. World Journal of Krasinski 1998 {published data only}
Surgery 1986;10(6):996–1002. Krasinski Z, Gabriel M, Oszkinis G, Dzieciuchowicz
Hobbs 1995 {published data only} L, Begier-Krasinska B. Thrombophlebitis profunda
Hobbs KEF. Laparoscopic cholecystectomy. Gut 1995;36 in patients after conventional and laparoscopic
(2):161–4. cholecystectomy [Trombophlebitis profunda bei Patienten
Huguier 1997 {published data only} nach der konventionellen und laparoskopischen
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Gastroenterology 1997;44(13):2–3. 1998;115(Supp lI Kongressbericht):1105–6.
Hunter 2001 {published data only} Krawczyk 1993 {published data only}
Hunter JG. Clinical trials and the development of Krawczyk M, Zieniewicz K, Najnigier B, Patkowski W,
laparoscopic surgery. Surgical Endoscopy 2001;15(1):1–3. Nyckowski P. Laparoscopic versus open cholecystectomy
Iwase 1992 {published data only} [abstract]. British Journal of Surgery 1993;80(Suppl):S46.
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- compared with mini-laparotomy cholecystectomy: Results of a prospective randomized study [Cholezystektomie
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663. Ergebnisse einer prospektiv randomisierten Studie].
Langenbecks Archiv fur Chirurgie 1993;Suppl
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Kongressbericht:84–8.
∗
Johnson A. Laparoscopic surgery. Lancet 1997;349(9052):
Kunz R, Berger R, Beger HG. Laparoscopic versus
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conventional cholecystectomy [Laparoskopische versus
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konventionelle Cholezystektomie]. Minimal Invasive
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Surgery. Lancet (349) 636-41). British Journal of Theatre ∗
Kunz R, Orth K, Vogel J, Steinacker JM, Meitinger
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and training. Australian and New Zealand Journal of Surgery versus mini–lap–Cholecystektomie – Ergebnisse einer
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conventional cholecystectomy versus minicholecystectomy Peri- and postoperative mediator release: laparoscopic
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mini or laparoscopic cholecystectomy? [Behandling Lam 1996 {published data only}
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Lukichev 1983 {published data only} laparoscopic cholecystectomy and minicholecystectomy
Lukichev OD, Filimonov MI, Zybin IM. A method of [abstract]. British Journal of Surgery 1992;79(11):1224.
laparoscopic cholecystostomy [Metodika laparoskopicheskoi McMahon AJ, Baxter JN, Anderson JR, Ramsay G,
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and perceived health after laparoscopic and small incision Ventilatory changes during laparoscopic and open
cholecystectomy. Surgery 1998;123(5):485–95. cholecystectomy: a randomized trial [abstract]. British
Makinen 1995 {published data only} Journal of Surgery 1993;80(5):647.
Makinen AMH, Nordback IH. Cholecystectomy McMahon AJ, O’Dwyer PJ, Cruikshank A, McMillan
- comparison of minilaparotomy and laparoscopy. D, Lowe G, Rumley A, et al. Metabolic changes after
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Matsunaga 1996 {published data only} McMahon AJ, Ross S, Russell IT, Baxter JN, Anderson JR,
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JR, Ramsay G, et al. Return to normal activity after
McGinn 1995 {published data only} laparoscopic and mini-cholecystectomy - a randomized trial
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Indicates the major publication for the study
CHARACTERISTICS OF STUDIES
Characteristics of included studies [ordered by study ID]
Agnifili 1993
Methods Single-centre randomised trial.

Generation of allocation: unclear.
Allocation concealment: unclear.
Blinding: not performed.
Follow-up: unclear. Drop-outs: none mentioned.
Intention-to-treat: not mentioned.
Sample size calculations: no.
Participants Elective cholecystectomy.

In- and exclusion criteria: not mentioned.
Comparability groups: similar.
Interventions LC versus OC.

Laparoscopic cholecystectomy and open cholecystectomy: not specified
Antibiotic prophylaxis: not mentioned.
Intra-operative cholangiography: yes.
Outcomes Primary and secondary outcome (endpoints): not mentioned.

Outcomes: pulmonary function, postoperative pain, endocrine-metabolic parameters
Duration of follow-up: hospital stay (maximum 5 days).
Notes
Risk of bias
Bias Authors’ judgement Support for judgement
Allocation concealment? Unclear risk B - Unclear
Blinding? High risk

All outcomes
Free of selective reporting? High risk
Free of other bias? High risk short FU
Bellon 1998

Generation of allocation: unclear (method not explained).
Follow-up: unclear (suggestion of no drop-outs, but not specified). Drop-outs: none mentioned
Participants Having cholelithiasis without previous complications.

In- and exclusion criteria: not well described.

Laparoscopic cholecystectomy by 4 trocars (two 10 mm ports and two 5 mm ports)
Open cholecystectomy: right sided transversal 12 cm subcostal incision
Intra-operative cholangiography: no (LC no, OC yes).

Outcome: endocrine and immune response measured.
Duration of follow-up: 7 days.
Notes
Risk of bias
Blinding? High risk

All outcomes
Berggren 1994

Generation of allocation: unclear (method not described).
Allocation concealment: adequate (sealed envelopes)*.
A prospective randomised study.
Participants Patients with proven stones in the gallbladder, fit for elective cholecystectomy
In- and exclusion criteria: well described.

Laparoscopic cholecystectomy: preoperative intravenous cholangiography. LC carried out as reported
by Dubois
Open cholecystectomy: with intraoperative cholangiography, through a right subcostal incision tran-
secting at least the lateral half of the ipsilateral rectus abdominis muscle
Antibiotic prophylaxis: no.
Intra-operative cholangiography: no.
Outcomes Primary and secondary outcome (endpoints): not defined.

Outcome measures: duration of hospital stay and sick leave, postoperative pain (measured by pethidine
consumption), and the response of trauma markers in blood and urine
Duration of follow-up: one week and weekly afterwards until return to work
Notes * Correspondence with U Berggren on 6 December 2004: allocation concealment by cards in envelopes.
Also additional data considering outcome
Risk of bias
Allocation concealment? Low risk A - Adequate
Blinding? High risk

All outcomes
Free of other bias? Low risk adequate FU
Blanc-Louvry 2000

Generation of allocation: adequate. Patients were randomly assigned by hazard tables.
Sample size calculations: no; sizes were determined with the ratio N1 = 1.5 x N2, because of better
acceptance of LC by patients
Participants Painful cholelithiasis.


LC: as described by Dubois.
OC: by subcostal incision.
Intra-operative cholangiography: performed in all patients.
Outcomes Primary and secondary outcome (endpoints): not described.

Outcome measures: postoperative functional recovery of patients and the stress neurohormonal
transmitter concentrations, postoperative pain level, duration of ileus
Duration of follow-up: hospital stay.
Notes
Risk of bias
Adequate sequence generation? Low risk
Blinding? High risk

All outcomes
Bukan 2004
Methods Single-centre trial.

Participants Elective cholecystectomy for symptomatic cholelithiasis.

In- and exclusion criteria: not described.
Comparability groups: well matched.

LC and OC: not specified.
Intra-operative cholangiography: not mentioned.

Outcome measures: oxidative stress: malondialdehyde and nitrite and nitrate
Notes
Risk of bias
Blinding? High risk

All outcomes
Charlo 1995

Generation of allocation: adequate (aleatorriamente = randomisation with dice).
Participants Elective cholecystectomy for symptomatic cholelithiasis.

Comparability groups: yes.
Charlo 1995 (Continued)

LC and OC: not specified.

Outcome measures: cost analysis (direct and indirect), mortality, morbidity
Duration of follow-up: untill return to work.
Notes
Risk of bias
Blinding? High risk

All outcomes
Free of other bias? Low risk adequate FU
Chaudhary 1999

Generation of allocation: adequate, Tippett’s random number table.
Blinding: adequate, follow-up by blinded observer.
Follow-up: adequate. Drop-outs: no drop-outs.
Sample size calculations: no, “...restricted to 40 patients so as to complete the study in
time...”
Participants Ultrasound-proven cholecystolithiasis.


LC: with standard four-port technique.
OC: via a subcostal muscle-cutting incision of 8-10 cm.
Antibiotic prophylaxis: yes.
Chaudhary 1999 (Continued)

Outcome measures: alterations in inflammatory mediators.
Duration of follow-up: 10 days after surgery.
Notes
Risk of bias
Blinding? Low risk

All outcomes
Incomplete outcome data addressed? Low risk

All outcomes
Chumillas 1998

Generation of allocation: unclear (method not mentioned).
Allocation concealment: adequate (sealed envelopes).
Participants Elective cholecystectomy for uncomplicated cholelithiasis.


LC: not specified.
OC: through a supra umbilical midline laparotomy.

Outcome measures: impairment of pulmonary function and arterial blood gas
Chumillas 1998 (Continued)
Notes Correspondence with MS Chumillas on 24 November 2004: additional data considering outcome
Risk of bias
Blinding? High risk

All outcomes
Coelho 1993

Generation of allocation: unclear. Patients randomly and prospectively divided into three groups.
Participants Chronic calculous cholecystitis admitted for elective cholecystectomy

Interventions LC versus SIC versus OC.

LC: four-trocar technique, carbon dioxide insufflated.
SIC: right upper quadrant transverse incision of 5 to 8 cm.
OC: right upper quadrant subcostal incision of 15 to 20 cm.

Outcome measures: comparison of reduction in pulmonary function
Duration of follow-up: not mentioned.
Notes
Risk of bias
Coelho 1993 (Continued)
Blinding? High risk

All outcomes
Coskun 2000

Generation of allocation: unclear. Patients randomly divided into two groups.
Follow-up: unclear (impression of no drop-outs). Drop-outs: none mentioned
Participants Patients for cholecystectomy.

In- and exclusion criteria: non-smoking patients aged 40-55 years with no respiratory, circulatory or
any other major system problems

LC and OC techniques not specified.

Outcome measures: changes in pulmonary function tests.
Notes
Risk of bias
Blinding? High risk

All outcomes
Dauleh 1995

Generation of allocation: unclear. Patients randomly allocated into two groups.
Participants Patients undergoing cholecystectomy.

In- and exclusion criteria: not very well described.

LC: standard four abdominal ports.
OC: using an upper midline incision.

Outcome measures: postoperative fever, analgesic requirement, anaesthesia time, hospital stay
Notes
Risk of bias
Blinding? High risk

All outcomes
Demirer 2000

Follow-up: adequate (complete description of follow-up group). Drop-outs: 2 converted
LC patients were excluded from analysis
Participants Chronic cholecystitis secondary to cholelithiasis.

Demirer 2000 (Continued)

LC: a four trocar technique with CO2 insufflation.
OC: right subcostal incision.
Intra-operative cholangiography: no intraoperative cholangiogram was needed

Outcome measures: postoperative changes in acute phase reactants
Notes
Risk of bias
Blinding? High risk

All outcomes

All outcomes
Dionigi 1994

Follow-up: unclear. Drop-outs: not mentioned.
Participants Symptomatic uncomplicated cholelithiasis.


LC: four portal technique, two 10 mm and two 5 mm trocars.
OC: not specified.
Intra-operative cholangiography: no intraoperative cholangiography needed
Dionigi 1994 (Continued)

Outcome measures: acute phase proteins, acute phase hormones and lymphocyte subpopulations
Duration of follow-up: not mentioned (hospital stay).
Notes
Risk of bias
Blinding? High risk

All outcomes
Engin 1998

Allocation concealment: adequate, by closed envelopes.
Participants Symptomatic gallstone disease.


LC: four-trocar technique.
OC: through a right subcostal incision.

Outcome measures: plasma cortisol, glucagon and insulin levels
Notes Correspondence with A Engin on 17 October 2004: additional data considering outcome
Risk of bias
Engin 1998 (Continued)
Blinding? High risk

All outcomes
Essen 1995

Generation of allocation: unclear: randomisation.
Allocation concealment: adequate (sealed envelopes)*.
RCT: patients were randomised to undergo LC or OC.
Participants Patients who were to undergo cholecystectomy.


LC: four-trocar technique, two 5 mm and two 10 mm trocars.
Intra-operative cholangiography: normal perioperative cholangiography in all patients

Outcome measures: protein synthesis in skeletal muscle.
Notes * Correspondence with A Thorell in January 2005: allocation concealment by sealed envelopes. Also
additional data considering outcome
Risk of bias
Blinding? High risk

All outcomes
Essen 1995 (Continued)
Gal 1997

Participants Patients for elective cholecystectomy.

Comparability groups: “similar characteristics”.

LC: four-trocar technique.
OC: standard subcostal incision.

Outcome measures: free radical mediated mechanism and activation of leucocytes
Duration of follow-up: not mentioned (5 days hospital stay).
Notes
Risk of bias
Blinding? High risk

All outcomes
Galizia 2001

Allocation concealment: adequate (sealed envelope, opened in the operation room).
Blinding: not performed (only preoperatively).
Participants Patients with symptomatic gallstones eligible for cholecystectomy

Interventions Two types of LC versus OC.

LC-PP group: four-trocar technique, two 5 mm and two 10 mm trocars, patients in pneumoperitoneum
(PP) group had a 12 mmHg pneumoperitoneum by Veress needle, which was maintained by an automatic
gas insufflator.
LC-AWL group: after placement of subcutaneous needles, 10 mm optical trocar inserted and the retractor
system was raised to obtain a good exposure by abdominal wall lifting (AWL)

Outcome measures: haemodynamic en pulmonary monitoring.
Notes Correspondence with G Galizia on 30 September 2004: additional data considering outcome
Risk of bias
Blinding? High risk

All outcomes
GarciaCaballero 1993

Blinding: adequate (postoperative observation in a blind fashion).
Follow-up: adequate (table 2 and 3). Drop-outs: in 4 patients (OC) treatment was
suspended and were excluded from analysis
Participants Patients undergoing a cholecystectomy for simple cholelithiasis

Comparability groups: homogeneous.
Interventions 5 groups: 4 types of OC versus LC.

I: conventional open cholecystectomy (OC).
II: OC with intraoperative injection of bupivacaine.
III: OC with postoperative instilling of propranolol plus neostigmine.
IV: OC with treatment of group II and III.
V: laparoscopic cholecystectomy without additional treatment

Outcome measures: postoperative ileus.
Notes
Risk of bias
Blinding? Low risk

All outcomes

All outcomes
Hasukic 2002

Generation of allocation: unclear (method not described).
RCT: prospective study; randomly assigned to surgical teams performing either LC or OC.
Participants Patients presenting for LC and OC.


LC: using a three trocar technique with patients in anti-Trendelenburg, insufflating with CO2 to a
maximum pressure of 12 mmHg
OC: subcostal incision.

Outcome measures: physiologic effect of LC and OC on postoperative pulmonary function
Notes
Risk of bias
Blinding? High risk

All outcomes
Hendolin 2000

Follow-up: unclear (table 2). Drop-outs: none mentioned.
Intention-to-treat: not mentioned, but LC conversions in LC group analysed.
Participants Patients who required elective cholecystectomy for symptomatic cholelithiasis confirmed by ultrasonog-
raphy

LC: four trocar technique with electrocautery dissection, pneumoperitoneum with CO2 insufflation,
pressure at 12 to 15 mmHg
OC: not further described.
Intra-operative cholangiography: no routine cholangiography.
Outcomes Primary and secondary outcome (endpoints): not specified.

Outcome measures: pain, pulmonary function, and the endocrine stress response
Duration of follow-up: 4-6 weeks after discharge.
Notes
Risk of bias
Blinding? High risk

All outcomes
Huang 1996

(Remark: although for ethical reasons the study was terminated preliminary, randomisation and follow-
up were correct. Reason for termination was believe of superiority, but outcome measures were analysed
correctly. No reason to exclude the study)
Study was terminated for ethical reasons (it became more difficult for patients to accept randomisation).
Participants Patients (age >70 years) with symptomatic cholelithiasis.


LC and OC: not further described.

Outcome measures: peri-operative morbidity and mortality rates in patients aged 70 years or older
Notes
Risk of bias
Blinding? High risk

All outcomes
Free of other bias? High risk short FU, trial terminated preliminary
Jan 1993

Generation of allocation: adequate, coin flipping (translation by member of CRG Copen-
hagen).
Allocation concealment: not used.
Follow-up: adequate, none lost to follow-up before hospital discharge. Drop-outs: none
mentioned
Sample size calculations: not mentioned.
Participants Patients undergoing elective cholecystectomy for symptomatic cholecystolithiasis


LC: four trocar technique with electrocautery dissection, pneumoperitoneum with CO2
insufflation, pressure at 14 mmHg
OC: using an upper midline or right subcostal incision.
Outcomes Primary and secondary outcome (or endpoints): not mentioned.

Outcome measures: mortality, morbidity, re-operations, complications, operation time,
wound pain, hospitalisation time and cost, postoperative bowel function recovery time,
and postoperative symptoms or stone retaining
Duration of follow-up: range 6 to 13 months.
Notes
Risk of bias
Blinding? High risk

All outcomes

All outcomes
Free of selective reporting? Low risk
Free of other bias? Low risk
Karayiannakis 1997

Allocation concealment: adequate (closed envelopes).
Follow-up: adequate. Drop-outs: 13. Eight patients (LC:3; SIC:5) declined after ran-
domisation; 4 patients required conversion; 1 patient (OC) underwent common bile
duct exploration. All patients were excluded from analyses. No corrections in analysis
were performed
Participants Patients undergoing elective cholecystectomy for symptomatic cholelithiasis


Laparoscopic cholecystectomy: by a four-trocar technique, carbon dioxide insufflation
at 14 mmHg pressure
Open cholecystectomy: by a right subcostal incision with partial transection of the
ipsilateral rectus abdominis muscle
Outcomes Primary and secondary outcome (or endpoints): not defined.

Outcome measures: systemic stress response, postoperative pain (VAS), analgesic usage,
pulmonary function
Notes
Risk of bias
Blinding? High risk

All outcomes

All outcomes
Kjaersgaard 1994

Follow-up: adequate. Drop-outs: complete registrations for all patients were obtained
RCT: “by randomisation, the patients were divided in two groups”.
intention-to-treat: not mentioned.
sample size calculations: yes, comparison of sequential and fixed-sample designs
Participants Patients undergoing elective cholecystectomy for symptomatic cholecystolithiasis


OC: performed with an 8 cm to 15 cm incision in the right hypochondrium
LC: in accordance with the Anglo-American method.

Outcome measures: efficacy, hospital costs and complications
Notes
Risk of bias
Blinding? High risk

All outcomes

All outcomes
Koprulu 1996

Participants Patients scheduled for elective cholecystectomy.

In- and exclusion criteria: adult patients ASA I or II; not further described
Comparability groups: not described.

Operative techniques not described.

Outcome measures: pulmonary function; no further information
Notes
Risk of bias
Blinding? High risk

All outcomes
Lausten 1999 (1)

Generation of allocation: unclear. Patients from each group randomly allocated to the two interventions.
Participants Patients with symptomatic gallstone disease in association with chronic liver disease (with or without
cirrhosis) admitted for elective cholecystectomy
Patients categorized in two groups: chronic viral hepatitis without cirrhosis (14) and the other associated
liver cirrhosis (16).
Lausten 1999 (1) (Continued)
Lausten 1999 (1): postnecrotic liver cirrhosis.

Interventions LC versus OC (2 x 7).

OC: right-sided subcostal skin incision was employed.
LC: performed according to the American method: 4 trocar technique

Outcome measures: hormonal and functional hepatic nitrogen clearance response to stress
Duration of follow-up: hospital stay, further not specified.
Notes
Risk of bias
Blinding? High risk

All outcomes
Lausten 1999 (2)

Generation of allocation: unclear. Patients from each group randomly allocated to either LC or OC.
Participants Patients with symptomatic gallstone disease in association with chronic liver disease (with or without
cirrhosis) admitted for elective cholecystectomy
Patients categorized in two groups: chronic viral hepatitis without cirrhosis (14) and the other associated
liver cirrhosis (16).
Lausten 1999 (2): chronic hepatitis.
In- and exclusion criteria: well described
Comparability groups: well matched
Lausten 1999 (2) (Continued)
Interventions LC versus OC (2 x 7).

OC: right-sided subcostal skin incision was employed.
LC: performed according to the American method: 4 trocar technique
Intra-operative cholangiography: no

Outcome measures: hormonal and functional hepatic nitrogen clearance response to stress
Duration of follow-up: hospital stay, further not specified.
Notes
Risk of bias
Blinding? High risk

All outcomes
Lujan 1998
Methods Single-centre trial. Prospective comparative study with simple randomisation

Intention-to-treat: not mentioned
Sample size calculations: no
Participants Patients aged >65 years undergoing surgery for symptomatic cholelithiasis

OC: subcostal incision cholecystectomy and transcystic cholangiography
LC: performed according to the French technique.
Intra-operative cholangiography: yes.

Outcome measures: surgical time, rate of conversion in the LC group, postoperative complications
Lujan 1998 (Continued)
(divided into four groups according to severity), hospital stay

Notes
Risk of bias
Blinding? High risk

All outcomes
Luo 2003

Participants Patients with uncomplicated gallstones.


OC: subcostal incision cholecystectomy.
LC: standard 4-trochar approach with electrocautery dissection, pneumoperitoneum with carbon diox-
ide insufflation

Outcome measures: body oxygen supply, metabolic hormones and response-reactive protein (CRP)
levels, body energy metabolism, and acid-base balance
Notes
Risk of bias
Luo 2003 (Continued)
Blinding? High risk

All outcomes
Milheiro 1994

Participants Patients with chronic cholecystitis undergoing elective cholecystectomy

Comparability groups: there was a significant difference in age between the two groups

LC: using the technique described by others (Olsen and Zucker)
No routine preoperative cholangiography.

Outcome measures: complications, operative time, metabolic response
Notes
Risk of bias
Blinding? High risk

All outcomes
Milheiro 1994 (Continued)
Mimica 2000

Allocation concealment: adequate (by closed envelopes)*.
RCT: prospective randomised trial.
Participants Patients submitted for elective cholecystectomy.


LC: four trocar technique with the surgeon standing to the left of the patient
OC: 15 cm right oblique subcostal (Kocher’s) incision.
Routine perioperative cholangiography: not mentioned.

Outcome measures: respiratory function.
Duration of follow-up: hospital stay (6 days).
Notes * Correspondence with Z Mimica on 15 December 2004: allocation concealment by closed envelopes.
Also additional data considering outcome
Risk of bias
Blinding? High risk

All outcomes
Ortega 1996

Generation of allocation: adequate (computer generated list).
Blinding: adequate (widely covered dressings).
Participants Patients with symptomatic cholelithiasis confirmed by ultrasonography


LC: standard four trocar technique with the patient in a reverse Trendelenburg position, pneu-
moperitoneum with CO2 maintained at 15 mmHg
OC: through an 8 to 9 cm rectus-cutting right subcostal incision, and otherwise performed in a
conventional manner
Intra-operative cholangiography: not standard.

Outcome measures: stress hormonal and metabolic responses.
Duration of follow-up: not specified (for hospital stay duration)
Notes
Risk of bias
Blinding? Low risk

All outcomes
Free of other bias? Unclear risk short FU
Prisco 2000

Follow-up: unclear. Drop-outs: 5 conversions (from LC to OC) were excluded from analysis
RCT: patients were randomly assigned to two groups.
Intention-to-treat: no, not performed (conversions not included in the analysis).
Participants Patients scheduled for cholecystectomy operations.


Surgical techniques not further described.
Intra-operative cholangiography routinely: yes.

Outcome measures: behaviour of thrombin generation and fibrinolysis markers after anaesthesia and
differences in haemostatic alterations induced by the two surgical techniques
Duration of follow-up: not specified (hospital stay).
Notes Correspondence with D Prisco on 9 December 2004: additional data considering outcome
Risk of bias
Blinding? High risk

All outcomes
Putensen-Himmer 1992

RCT: randomly assigned to surgical teams performing either LC or OC.
Sample size calculations: yes.
Participants Patients scheduled for elective cholecystectomy.


LC: as described by Dubois with the patient in reverse Trendelenburg, insufflating the abdomen with
CO2 to a maximum pressure of 12 mmHg
OC: subcostal incision.
Intra-operative cholangiography: not mentioned

Outcome measures: changes in lung volumes and gas exchange.
Duration of follow-up: not specified (hospital stay).
Notes
Risk of bias
Blinding? High risk

All outcomes
Rovina 1996
Methods Single-centre trial. RCT: 26 patients underwent LC and the other 25 underwent OC in random order
Participants Patients who underwent cholecystectomy were studied.


LC: not specified.
OC: with a right paramedian incision.
Intra-operative cholangiography: yes; should be attempted by protocol

Outcome measures: pulmonary function.
Notes
Risk of bias
Blinding? High risk

All outcomes
Trondsen 1993

Follow-up: unclear. Drop-outs: one patient (OC) lost for evaluation
RCT: randomisation in groups of eight.
Participants Patients who were to undergo elective cholecystectomy.

Comparability groups: difference in age in favour of LC.
Trondsen 1993 (Continued)

LC: by the Anglo-American method, dissection with a laser or electrocautery
OC: through a 8 to 15 cm incision in the right hypochondrium, with transection of the rectus abdominis
muscle

Outcome measures: duration of operation, hospital stay, amount of postoperative pain, complications,
duration of postoperative convalescence, sick leave
Duration of follow-up: 30 days postoperative.
Notes
Risk of bias
Blinding? High risk

All outcomes
Free of selective reporting? Low risk
Free of other bias? Low risk
Volpino 1998
Methods Single-centre randomised clinical trial.

Follow-up: unclear. Drop-outs: none mentioned; 2 converted patients (from LC to OC) were excluded
from analysis
Intention-to-treat: no, conversions were excluded.
Participants Patients with symptomatic cholelithiasis referred for elective cholecystectomy


LC: pneumoperitoneum by carbon dioxide insufflation, pressures at 1.6-2.0 kPa, in reverse Trendelen-
burg
OC: not specified.
Volpino 1998 (Continued)
Intra-operative cholangiography: not mentioned

Outcome measures: effects of LC and OC on intra- and postoperative haemodynamic and respiratory
function, complications
Duration of follow-up: unclear (hospital stay).
Notes
Risk of bias
Blinding? High risk

All outcomes
Zajac 1998

Randomised clinical trial, blinded randomisation (abstract).
Participants Patients aged 70 or over, scheduled for cholecystectomy.

Comparability groups: difference in ASA 3 classification in favour of OC

Operative procedures not specified.

Outcome measures: complications, operative time, hospital stay
Duration of follow-up: 7 days observation.
Notes
Zajac 1998 (Continued)
Risk of bias
Blinding? High risk

All outcomes
Zulfikaroglu 2002

Follow-up: unclear. Drop-outs: none mentioned, but patients were excluded when analysis could not
be completed or when conversion was needed
Intention-to-treat: no, conversions would be excluded. Patients were excluded when the analysis could
not be completed due to technical reasons, or when surgical findings necessitated conversion to OC.
Participants Patients with chronic uncomplicated cholelithiasis.


LC: through four ports, by Veress needle introduction and carbon dioxide pneumoperitoneum, maxi-
mum pressure at 12 mmHg
OC: through a 10 cm subcostal incision.

Outcome measures: oxidative stress.
Duration of follow-up: unclear (hospital stay).
Notes
Risk of bias
Zulfikaroglu 2002 (Continued)
Blinding? High risk

All outcomes
LC - laparoscopic cholecystectomy,
SIC - small-incision cholecystectomy,
OC - open cholecystectomy.
Characteristics of excluded studies [ordered by study ID]
Study Reason for exclusion
Al Tameem 1995 Prospective study on three different types of small-incision cholecystectomy, not randomised
Alexander 1997 Review on pain after laparoscopy; not a randomised trial.
Allen 2002 Comparison of costs of LC between ten surgeons; no comparison of operative procedures
Alponat 2002 Randomised clinical trial on conventional LC (two 10 mm and two 5 mm ports) and LC by small instruments
(one 10 mm and three 2 mm ports); thus comparison of two types of LC
Anonymous 1995 Editorial: discussion of other article.
Assalia 1993 Randomised clinical trial evaluating small-incision and open cholecystectomy
Assalia 1997 Randomised clinical trial only including patients with acute cholecystitis
Bablekos 2003 Correspondence with GD Bablekos on 11 October 2004: separating patients in triads with allocation
according to registration sequence at the emergency ward: quasi-randomised study
Barkun 1992 Randomised clinical trial evaluating laparoscopic and small-incision cholecystectomy
Barkun 1993 Comparison of three different time periods; not a randomised trial
Baxter 1992 Debate, consideration.
Bernard 1994 Economic evaluation.
Bigard 1995 Review on indications and methods of cholecystectomy in treatment of gallstones
(Continued)
Blomstedt 1972 Study on the frequency of incisional hernias after different types of conventional cholecystectomy; not a
randomised trial
Bolke 2000 Quasi-randomised study: “... patients were randomised by alternate number to LC or OC ...”
Bruce 1999 Randomised clinical trial evaluating laparoscopic and small-incision cholecystectomy
Byrne 1994 Prospective, not a randomised trial: “ ... equipment was only made available on an intermittent basis ...”
Calland 2001 Prospective study on outpatient LC, comparing with historical (inpatient) LC; not a randomised trial
Caplan 1999 Study on costs and patient satisfaction before and after re-engineering of a surgical service in LC patients
and elective herniorrhaphy; no comparison of different types of cholecystectomy
Champault 2002 One-arm prospective study on costs; not a randomised trial (not two arms)
Clezy 1996 Letter.
Coelho 1992 Not a randomised trial; prospective study of small-incision cholecystectomy
Coelho 1992a Randomised clinical trial evaluating small-incision and open cholecystectomy
Da Costa 1995 Prospective study, not randomised: “... patients were not randomised as it was felt that it was unethical to
do so ...”
Decker 1993 Not a randomised trial; prospective study.
Delogu 1999 Stress response in LC and OC patients, not randomised: “... 22 patients underwent OC and the other 24
had LC according to the availability of laparoscopic equipment ...”
Dohrmann 1993 Not randomised; randomisation was not possible as most patients opted for the laparoscopic technique
Eickhoff 1997 No randomised trial: patients who were operated by LC or OC were analysed
Frazee 1991 No correct randomisation between two operative techniques: “... patients were randomly assigned to indi-
vidual staff surgeons, as is our customary practice ...”
Glaser 1995 Prospective study with control group, not randomised: “... because of the ethical problems associated with
randomisation of LC and OC, we decided to conduct a prospective trial without randomisation, but with a
control group ...”
Go 1995 Retrospective study on cost-effectiveness between extracorporeal shock-wave lithotripsy, conventional chole-
cystectomy, and laparoscopic cholecystectomy
Grande 2002 Randomised clinical trial evaluating laparoscopic and small-incision cholecystectomy
Hagmuller 1997 Not randomised: the authors felt that randomisation was not possible on ethical grounds
(Continued)
Hauer-Jensen 1986 Randomised clinical trial comparing performing cholecystectomy with or without a routine cholangiography
Hobbs 1995 Considerations on laparoscopic cholecystectomy, not a randomised trial
Huguier 1997 Considerations on laparoscopic digestive surgery, not a randomised trial
Hunter 2001 Editorial.
Iwase 1992 Not a randomised trial.
Johnson 1997 Considerations on laparoscopic surgery.
Johnson 1998 Personal view: consideration on efficacy, safety and training; not a randomised trial
Johnson 1998a Letter.
Karayiannakis 2002 Prospective study in patients having LC and OC, but no randomisation: “... twelve patients who had OC
were recruited and served as the control group ...”
Kehlet 1993 Consideration of gallstone treatment modalities.
Keus 2006 Randomised clinical trial evaluating laparoscopic and small-incision cholecystectomy
Kiviluoto 1997 Randomised clinical trial between LC and OC on acute cholecystitis
Krasinski 1998 Prospective study on patients who underwent LC: patients with uncomplicated LC were compared to patients
who had conversion from LC to OC
Krawczyk 1993 Not a randomised trial: “the groups were not randomised”.
Kunz 1992 Randomised clinical trial evaluating laparoscopic and small-incision cholecystectomy
Kurzawinski 1992 Prospective study, but not randomised: “... patients were randomly allocated to either LC or OC, based on
the availability of laparoscopic equipment ...”
Lam 1996 Survey in Scotland on cholecystectomy rate; not a randomised trial
Lukichev 1983 Cohort of patients treated by one technique; not a randomised trial
Majeed 1996 Randomised clinical trial evaluating laparoscopic and small-incision cholecystectomy
Makinen 1995 Only pilot phase of the trial; in pilot phase no randomisation: SIC was performed when LC instruments
were not available
Malaysian HTA 2005 Systematic review on different types of minimal access surgery; not a randomised trial
Maruszynski 1995 Patients with acute cholecystitis only.
(Continued)
Matsunaga 1996 Comparison of two different types of anaesthesia in cholecystectomy
McGinn 1995 Randomised clinical trial evaluating laparoscopic and small-incision cholecystectomy
McKellar 1995 Comparison of historical cohorts.
McMahon 1994 Randomised clinical trial evaluating laparoscopic and small-incision cholecystectomy
McMahon 1996 Letter, not a randomised trial.
Mealy 1992 An unselected group of patients undergoing LC in one hospital was compared with a group undergoing OC
in another hospital
Mrksic 2001 No randomisation.
Novitsky 2002 Randomised clinical trial on two types of laparoscopic cholecystectomy (mini-port LC (2 mm) versus
conventional LC)
O’Dwyer 1992 Randomised trial evaluating small-incision and open cholecystectomy
Ogawa 2001 Retrospective study on LC versus OC in patients with cardiac valve replacement
Olsen 1993 Review of literature from 1970 to 1992 on mini-lap cholecystectomy: only articles in English were included
and data on conventional and laparoscopic cholecystectomy were obtained from large series reported in
literature
Plaisier 1995 Prospective not randomised study: “... allocation to either laparoscopic or conventional cholecystectomy
depended on the availability of a laparoscopic set ...”
Rademaker 1992 Patients underwent conventional subcostal cholecystectomy whenever the instrumentation for laparoscopic
surgery was not available; the laparoscopic group had on alternating basis general anaesthesia combined with
epidural analgesia or general anaesthesia alone; not randomised
Redmond 1994 Study evaluating laparoscopic and small-incision cholecystectomy
Rhodes 1996 No randomised trial; comment on other article.
Romana 2000 Not randomised: “patients were divided into two groups”.
Ros 2001 Randomised clinical trial evaluating laparoscopic and small-incision cholecystectomy
Schauer 1993 No correct randomisation of surgical techniques: “.. patients were randomly assigned to one of four general
surgical services; two of these used only the open cholecystectomy technique, and the other two used the
laparoscopic approach ..”
Schauer 1995 Not randomised; “.. procedure was determined by the attending physician ..”
(Continued)
Schaupp 1988 Randomised clinical trial on two types of conventional cholecystectomy (with nasogastric tube, iv infusion
and subhepatic drain versus no tube, no infusion and no drain)
Schmitz 1997 Randomised clinical trial evaluating small-incision and open cholecystectomy
Secco 2002 Randomised clinical trial evaluating laparoscopic and small-incision cholecystectomy
Seenu 1994 Randomised clinical trial evaluating small-incision and open cholecystectomy
Srivastava 2001 Randomised clinical trial evaluating laparoscopic and small-incision cholecystectomy
Tate 1993 Randomised clinical trial evaluating laparoscopic and small-incision cholecystectomy
Thaler 1995 Trial on LC and OC patients, but no randomisation as the authors found that laparoscopic cholecystectomy
was the method of first choice
Toouli 1998 Review on gallstones; not a randomised trial.
Ueo 1994 Prospective comparison between IL-6 levels in LC and OC patients, but not randomised: “ ... patients who
underwent cholecystectomy, 12 each for OC and LC, were chosen as subjects in this study ...”
Wani 2002 Randomised trial evaluating small-incision and open cholecystectomy
Williams 1993 Prospective study on LC and OC pulmonary function, but not randomised: “... selection for OC or LC
depended upon surgeon ...”
Yerdel 1997 Prospective study in cirrhotic patients on laparoscopic versus open cholecystectomy; not randomised ( “...
all cirrhotic patients were offered LC ...” )
LC: laparoscopic cholecystectomy;

OC: open cholecystectomy.
DATA AND ANALYSES
Comparison 1. LC versus OC - high-quality and low-quality trials regarding generation of the allocation sequence
No. of No. of
Outcome or subgroup title studies participants Statistical method Effect size
1 Mortality 15 987 Risk Difference (M-H, Fixed, 95% CI) -0.00 [-0.02, 0.01]
1.1 High-quality trial 2 301 Risk Difference (M-H, Fixed, 95% CI) 0.0 [-0.02, 0.02]
1.2 Low-quality trial 13 686 Risk Difference (M-H, Fixed, 95% CI) -0.00 [-0.02, 0.02]
2 Intra-operative complications 30 1914 Risk Difference (M-H, Fixed, 95% CI) 0.01 [-0.00, 0.02]
2.2 Low-quality trial 26 1550 Risk Difference (M-H, Fixed, 95% CI) 0.01 [-0.01, 0.02]
3 Minor complications 30 1914 Risk Difference (M-H, Fixed, 95% CI) -0.01 [-0.03, 0.00]
3.1 High-quality trial 4 364 Risk Difference (M-H, Fixed, 95% CI) -0.01 [-0.04, 0.03]
4 Severe complications (without 30 1914 Risk Difference (M-H, Random, 95% CI) -0.03 [-0.06, 0.00]
bile duct injuries)
4.1 High-quality trial 4 364 Risk Difference (M-H, Random, 95% CI) -0.00 [-0.06, 0.05]
4.2 Low-quality trial 26 1550 Risk Difference (M-H, Random, 95% CI) -0.03 [-0.07, 0.00]
5 Bile duct injuries 30 1914 Risk Difference (M-H, Fixed, 95% CI) -.00 [-0.01, 0.01]
6 Total complications 30 1914 Risk Difference (M-H, Random, 95% CI) -0.04 [-0.07, -0.01]
6.1 High-quality trial 4 364 Risk Difference (M-H, Random, 95% CI) -.00 [-0.08, 0.08]
6.2 Low-quality trial 26 1550 Risk Difference (M-H, Random, 95% CI) -0.05 [-0.09, -0.01]
7 Operative time (minutes) 24 1134 Mean Difference (IV, Random, 95% CI) 3.79 [-4.88, 12.46]
7.1 High-quality trial 3 162 Mean Difference (IV, Random, 95% CI) 6.04 [-25.72, 37.81]
7.2 Low-quality trial 21 972 Mean Difference (IV, Random, 95% CI) 3.37 [-6.29, 13.04]
8 Hospital stay (days) 21 1111 Mean Difference (IV, Random, 95% CI) -3.07 [-3.89, -2.26]
8.1 High-quality trial 4 362 Mean Difference (IV, Random, 95% CI) -1.76 [-3.70, 0.17]
8.2 Low-quality trial 17 749 Mean Difference (IV, Random, 95% CI) -3.34 [-3.97, -2.71]
9 Convalescence: work leave (days) 3 328 Mean Difference (IV, Random, 95% CI) -22.51 [-36.89, -8.
13]
9.1 High-quality trial 2 301 Mean Difference (IV, Random, 95% CI) -28.10 [-36.75, -19.
44]
9.2 Low-quality trial 1 27 Mean Difference (IV, Random, 95% CI) -12.3 [-15.54, -9.06]
Comparison 2. LC versus OC - high-quality and low-quality trials regarding concealment of allocation
No. of No. of
1.1 High-quality trials 6 254 Risk Difference (M-H, Fixed, 95% CI) 0.0 [-0.04, 0.04]
1.2 Low-quality trials 9 733 Risk Difference (M-H, Fixed, 95% CI) -0.00 [-0.02, 0.01]
2.2 Low-quality trials 22 1526 Risk Difference (M-H, Fixed, 95% CI) 0.01 [-0.01, 0.02]
3.1 High-quality trials 8 388 Risk Difference (M-H, Fixed, 95% CI) -0.02 [-0.06, 0.02]
bile duct injuries)
4.1 High-quality trials 8 388 Risk Difference (M-H, Random, 95% CI) -.00 [-0.03, 0.02]
4.2 Low-quality trials 22 1526 Risk Difference (M-H, Random, 95% CI) -0.04 [-0.08, -.00]
5.2 Low-quality trials 22 1526 Risk Difference (M-H, Fixed, 95% CI) -.00 [-0.01, 0.01]
6.1 High-quality trials 8 388 Risk Difference (M-H, Random, 95% CI) -0.01 [-0.05, 0.02]
6.2 Low-quality trials 22 1526 Risk Difference (M-H, Random, 95% CI) -0.05 [-0.10, -0.01]
7.1 High-quality trials 7 341 Mean Difference (IV, Random, 95% CI) -1.14 [-12.80, 10.
52]
7.2 Low-quality trials 17 793 Mean Difference (IV, Random, 95% CI) 5.72 [-5.34, 16.77]
8.1 High-quality trials 5 201 Mean Difference (IV, Random, 95% CI) -3.23 [-4.75, -1.71]
8.2 Low-quality trials 16 910 Mean Difference (IV, Random, 95% CI) -3.01 [-3.97, -2.06]
13]
9.2 Low-quality trials 2 301 Mean Difference (IV, Random, 95% CI) -28.10 [-36.75, -19.
44]
Comparison 3. LC versus OC - high-quality and low-quality trials regarding blinding
No. of No. of
1.1 High-quality trials 0 0 Risk Difference (M-H, Fixed, 95% CI) 0.0 [0.0, 0.0]
bile duct injuries)
4.2 Low-quality trials 28 1851 Risk Difference (M-H, Random, 95% CI) -0.03 [-0.06, 0.00]
8.1 High-quality trials 1 20 Mean Difference (IV, Random, 95% CI) 0.10 [-0.04, 0.24]
13]
9.1 High-quality trials 0 0 Mean Difference (IV, Random, 95% CI) 0.0 [0.0, 0.0]
13]
Comparison 4. LC versus OC - high-quality and low-quality trials regarding follow-up
No. of No. of
bile duct injuries)
4.1 High-quality trials 4 331 Risk Difference (M-H, Random, 95% CI) 0.00 [-0.02, 0.03]
6.1 High-quality trials 4 331 Risk Difference (M-H, Random, 95% CI) 0.01 [-0.03, 0.05]
7.1 High-quality trials 2 188 Mean Difference (IV, Random, 95% CI) 22.42 [-7.67, 52.50]
13]
9.1 High-quality trials 1 101 Mean Difference (IV, Random, 95% CI) -23.10 [-29.26, -16.
94]
91]
Comparison 5. LC versus OC - sensitivity and subgroup analyses
No. of No. of
1 Sensitivity analysis 1: Assuming 39 2338 Risk Difference (M-H, Fixed, 95% CI) -.00 [-0.01, 0.01]
zero mortality in non-reporting
trials
2 Sensitivity analysis 2: Imputing 33 1889 Mean Difference (IV, Random, 95% CI) 6.42 [-1.21, 14.04]
medians and standard
deviations for missing data in
operative time (minutes)
3 Sensitivity analysis 3: Imputing 28 1728 Mean Difference (IV, Random, 95% CI) -3.15 [-3.94, -2.35]
medians and standard
deviations for missing data in
hospital stay (days)
4 Subgroup analysis 1: Influence 30 1914 Risk Difference (M-H, Random, 95% CI) -0.04 [-0.08, -0.01]
antibiotic prophylaxis on total
complications
4.1 Antibiotic: yes 3 349 Risk Difference (M-H, Random, 95% CI) -0.06 [-0.14, 0.03]
4.2 Antibiotic: no / unknown 27 1565 Risk Difference (M-H, Random, 95% CI) -0.04 [-0.08, -0.01]
5 Subgroup analysis 2: Influence 14 746 Mean Difference (IV, Random, 95% CI) -2.02 [-9.36, 5.33]
cholangiography on operative
time (minutes)
5.1 Cholangiography: yes 5 387 Mean Difference (IV, Random, 95% CI) -1.95 [-11.40, 7.51]
5.2 Cholangiography: no 9 359 Mean Difference (IV, Random, 95% CI) -2.16 [-12.89, 8.58]
6 Subgroup analysis 3: Influence 28 1728 Mean Difference (IV, Random, 95% CI) -3.15 [-3.94, -2.35]
antibiotic prophylaxis on
hospital stay (days)
6.1 Antibiotic prophylaxis: yes 1 264 Mean Difference (IV, Random, 95% CI) -6.19 [-6.49, -5.89]
6.2 Antibiotic prophylaxis: no 27 1464 Mean Difference (IV, Random, 95% CI) -3.02 [-3.73, -2.31]
/ unknown
Analysis 1.1. Comparison 1 LC versus OC - high-quality and low-quality trials regarding generation of the
allocation sequence, Outcome 1 Mortality.
Review: Laparoscopic versus open cholecystectomy for patients with symptomatic cholecystolithiasis
Comparison: 1 LC versus OC - high-quality and low-quality trials regarding generation of the allocation sequence
Outcome: 1 Mortality
Risk Risk
Study or subgroup laparoscopic (LC) open (OC) Difference Weight Difference
n/N n/N M-H,Fixed,95% CI M-H,Fixed,95% CI
1 High-quality trial
Charlo 1995 0/100 0/100 20.3 % 0.0 [ -0.02, 0.02 ]
Jan 1993 0/50 0/51 10.3 % 0.0 [ -0.04, 0.04 ]
Subtotal (95% CI) 150 151 30.6 % 0.0 [ -0.02, 0.02 ]

Total events: 0 (laparoscopic (LC)), 0 (open (OC))
Heterogeneity: Chi2 = 0.0, df = 1 (P = 1.00); I2 =0.0%
Test for overall effect: Z = 0.0 (P = 1.0)
2 Low-quality trial
Agnifili 1993 0/29 0/21 5.0 % 0.0 [ -0.08, 0.08 ]
Bellon 1998 0/14 0/14 2.8 % 0.0 [ -0.13, 0.13 ]
Berggren 1994 0/15 0/12 2.7 % 0.0 [ -0.13, 0.13 ]
Chumillas 1998 0/20 0/20 4.1 % 0.0 [ -0.09, 0.09 ]
Engin 1998 0/16 0/16 3.3 % 0.0 [ -0.11, 0.11 ]
Gal 1997 0/21 0/21 4.3 % 0.0 [ -0.09, 0.09 ]
Galizia 2001 0/10 0/5 1.4 % 0.0 [ -0.25, 0.25 ]
Lausten 1999 (1) 0/7 0/7 1.4 % 0.0 [ -0.24, 0.24 ]
Lausten 1999 (2) 0/7 0/7 1.4 % 0.0 [ -0.24, 0.24 ]
Lujan 1998 0/133 1/131 26.8 % -0.01 [ -0.03, 0.01 ]
Milheiro 1994 0/20 0/20 4.1 % 0.0 [ -0.09, 0.09 ]
Mimica 2000 0/50 0/50 10.2 % 0.0 [ -0.04, 0.04 ]
Prisco 2000 0/10 0/10 2.0 % 0.0 [ -0.17, 0.17 ]
Subtotal (95% CI) 352 334 69.4 % 0.00 [ -0.02, 0.02 ]

Total (95% CI) 502 485 100.0 % 0.00 [ -0.02, 0.01 ]
-0.5 -0.25 0 0.25 0.5

Favours LC Favours OC
allocation sequence, Outcome 2 Intra-operative complications.
Outcome: 2 Intra-operative complications
Risk Risk
Charlo 1995 0/100 0/100 10.5 % 0.0 [ -0.02, 0.02 ]
Chaudhary 1999 0/21 0/22 2.3 % 0.0 [ -0.09, 0.09 ]
Jan 1993 1/50 0/51 5.3 % 0.02 [ -0.03, 0.07 ]
Ortega 1996 0/10 0/10 1.0 % 0.0 [ -0.17, 0.17 ]
Subtotal (95% CI) 181 183 19.1 % 0.01 [ -0.02, 0.03 ]

2 Low-quality trial
Agnifili 1993 0/29 0/21 2.6 % 0.0 [ -0.08, 0.08 ]
Bellon 1998 0/14 0/14 1.5 % 0.0 [ -0.13, 0.13 ]
Berggren 1994 0/15 0/12 1.4 % 0.0 [ -0.13, 0.13 ]
Chumillas 1998 0/20 0/20 2.1 % 0.0 [ -0.09, 0.09 ]
Coelho 1993 0/15 0/15 1.6 % 0.0 [ -0.12, 0.12 ]
Coskun 2000 0/35 0/35 3.7 % 0.0 [ -0.05, 0.05 ]
Dauleh 1995 0/40 0/38 4.1 % 0.0 [ -0.05, 0.05 ]
Demirer 2000 0/50 0/50 5.2 % 0.0 [ -0.04, 0.04 ]
Dionigi 1994 0/30 0/27 3.0 % 0.0 [ -0.07, 0.07 ]
Engin 1998 0/16 0/16 1.7 % 0.0 [ -0.11, 0.11 ]
Essen 1995 0/6 0/6 0.6 % 0.0 [ -0.27, 0.27 ]
Gal 1997 0/21 0/21 2.2 % 0.0 [ -0.09, 0.09 ]
Galizia 2001 2/10 0/5 0.7 % 0.20 [ -0.13, 0.53 ]
-0.5 -0.25 0 0.25 0.5

(Continued . . . )
(. . . Continued)
Risk Risk
Hasukic 2002 0/30 0/28 3.0 % 0.0 [ -0.06, 0.06 ]
Hendolin 2000 0/25 0/22 2.5 % 0.0 [ -0.08, 0.08 ]
Huang 1996 0/15 0/12 1.4 % 0.0 [ -0.13, 0.13 ]
Karayiannakis 1997 0/45 0/42 4.6 % 0.0 [ -0.04, 0.04 ]
Lausten 1999 (1) 0/7 0/7 0.7 % 0.0 [ -0.24, 0.24 ]
Lausten 1999 (2) 0/7 0/7 0.7 % 0.0 [ -0.24, 0.24 ]
Lujan 1998 0/133 0/131 13.8 % 0.0 [ -0.01, 0.01 ]
Milheiro 1994 0/20 0/20 2.1 % 0.0 [ -0.09, 0.09 ]
Mimica 2000 0/50 0/50 5.2 % 0.0 [ -0.04, 0.04 ]
Prisco 2000 0/10 0/10 1.0 % 0.0 [ -0.17, 0.17 ]
Trondsen 1993 6/35 1/35 3.7 % 0.14 [ 0.01, 0.28 ]
Volpino 1998 0/58 0/60 6.2 % 0.0 [ -0.03, 0.03 ]
Zajac 1998 0/58 0/52 5.7 % 0.0 [ -0.03, 0.03 ]
Subtotal (95% CI) 794 756 80.9 % 0.01 [ -0.01, 0.02 ]

Total (95% CI) 975 939 100.0 % 0.01 [ 0.00, 0.02 ]
-0.5 -0.25 0 0.25 0.5

allocation sequence, Outcome 3 Minor complications.
Outcome: 3 Minor complications
Risk Risk
Charlo 1995 4/100 4/100 10.5 % 0.0 [ -0.05, 0.05 ]
Chaudhary 1999 0/21 1/22 2.3 % -0.05 [ -0.16, 0.07 ]
Jan 1993 0/50 0/51 5.3 % 0.0 [ -0.04, 0.04 ]
Ortega 1996 0/10 0/10 1.0 % 0.0 [ -0.17, 0.17 ]
Subtotal (95% CI) 181 183 19.1 % -0.01 [ -0.04, 0.03 ]

2 Low-quality trial
Agnifili 1993 0/29 0/21 2.6 % 0.0 [ -0.08, 0.08 ]
Bellon 1998 0/14 0/14 1.5 % 0.0 [ -0.13, 0.13 ]
Berggren 1994 1/15 0/12 1.4 % 0.07 [ -0.11, 0.24 ]
Chumillas 1998 0/20 0/20 2.1 % 0.0 [ -0.09, 0.09 ]
Coelho 1993 0/15 1/15 1.6 % -0.07 [ -0.23, 0.10 ]
Coskun 2000 0/35 0/35 3.7 % 0.0 [ -0.05, 0.05 ]
Dauleh 1995 0/40 0/38 4.1 % 0.0 [ -0.05, 0.05 ]
Demirer 2000 0/50 0/50 5.2 % 0.0 [ -0.04, 0.04 ]
Dionigi 1994 0/30 1/27 3.0 % -0.04 [ -0.13, 0.06 ]
Engin 1998 0/16 0/16 1.7 % 0.0 [ -0.11, 0.11 ]
Essen 1995 0/6 0/6 0.6 % 0.0 [ -0.27, 0.27 ]
Gal 1997 0/21 0/21 2.2 % 0.0 [ -0.09, 0.09 ]
Galizia 2001 0/10 0/5 0.7 % 0.0 [ -0.25, 0.25 ]
Hasukic 2002 0/30 0/28 3.0 % 0.0 [ -0.06, 0.06 ]
Hendolin 2000 0/25 2/22 2.5 % -0.09 [ -0.23, 0.05 ]
Huang 1996 0/15 2/12 1.4 % -0.17 [ -0.40, 0.06 ]
-0.5 -0.25 0 0.25 0.5

(Continued . . . )
(. . . Continued)
Risk Risk
Karayiannakis 1997 0/45 0/42 4.6 % 0.0 [ -0.04, 0.04 ]
Lausten 1999 (1) 0/7 0/7 0.7 % 0.0 [ -0.24, 0.24 ]
Lausten 1999 (2) 0/7 0/7 0.7 % 0.0 [ -0.24, 0.24 ]
Lujan 1998 13/133 15/131 13.8 % -0.02 [ -0.09, 0.06 ]
Milheiro 1994 1/20 2/20 2.1 % -0.05 [ -0.21, 0.11 ]
Mimica 2000 0/50 2/50 5.2 % -0.04 [ -0.11, 0.03 ]
Prisco 2000 0/10 0/10 1.0 % 0.0 [ -0.17, 0.17 ]
Trondsen 1993 4/35 5/35 3.7 % -0.03 [ -0.19, 0.13 ]
Volpino 1998 0/58 0/60 6.2 % 0.0 [ -0.03, 0.03 ]
Zajac 1998 0/58 0/52 5.7 % 0.0 [ -0.03, 0.03 ]
Subtotal (95% CI) 794 756 80.9 % -0.02 [ -0.04, 0.01 ]

Total (95% CI) 975 939 100.0 % -0.01 [ -0.03, 0.00 ]
-0.5 -0.25 0 0.25 0.5

allocation sequence, Outcome 4 Severe complications (without bile duct injuries).
Outcome: 4 Severe complications (without bile duct injuries)
Risk Risk
M- M-
H,Random,95% H,Random,95%
n/N n/N CI CI
Charlo 1995 8/100 12/100 4.4 % -0.04 [ -0.12, 0.04 ]
Chaudhary 1999 0/21 1/22 3.2 % -0.05 [ -0.16, 0.07 ]
Jan 1993 4/50 1/51 4.3 % 0.06 [ -0.02, 0.14 ]
Ortega 1996 0/10 0/10 1.9 % 0.0 [ -0.17, 0.17 ]
Subtotal (95% CI) 181 183 13.8 % 0.00 [ -0.06, 0.05 ]

Heterogeneity: Tau2 = 0.00; Chi2 = 3.55, df = 3 (P = 0.31); I2 =16%
2 Low-quality trial
Agnifili 1993 1/29 4/21 1.8 % -0.16 [ -0.34, 0.02 ]
Bellon 1998 0/14 0/14 2.9 % 0.0 [ -0.13, 0.13 ]
Berggren 1994 0/15 0/12 2.7 % 0.0 [ -0.13, 0.13 ]
Chumillas 1998 0/20 1/20 2.9 % -0.05 [ -0.18, 0.08 ]
Coelho 1993 0/15 0/15 3.1 % 0.0 [ -0.12, 0.12 ]
Coskun 2000 0/35 10/35 2.3 % -0.29 [ -0.44, -0.13 ]
Dauleh 1995 0/40 0/38 5.8 % 0.0 [ -0.05, 0.05 ]
Demirer 2000 0/50 0/50 6.2 % 0.0 [ -0.04, 0.04 ]
Dionigi 1994 0/30 0/27 5.1 % 0.0 [ -0.07, 0.07 ]
Engin 1998 0/16 0/16 3.3 % 0.0 [ -0.11, 0.11 ]
Essen 1995 0/6 0/6 1.0 % 0.0 [ -0.27, 0.27 ]
Gal 1997 0/21 0/21 4.2 % 0.0 [ -0.09, 0.09 ]
Galizia 2001 0/10 1/5 0.6 % -0.20 [ -0.57, 0.17 ]
Hasukic 2002 0/30 6/28 2.2 % -0.21 [ -0.37, -0.06 ]
Hendolin 2000 1/25 0/22 3.5 % 0.04 [ -0.07, 0.15 ]
-0.5 -0.25 0 0.25 0.5

(Continued . . . )
(. . . Continued)
Risk Risk
M- M-
n/N n/N CI CI
Huang 1996 0/15 0/12 2.7 % 0.0 [ -0.13, 0.13 ]
Karayiannakis 1997 0/45 0/42 6.0 % 0.0 [ -0.04, 0.04 ]
Lausten 1999 (1) 1/7 0/7 0.7 % 0.14 [ -0.18, 0.46 ]
Lausten 1999 (2) 0/7 0/7 1.2 % 0.0 [ -0.24, 0.24 ]
Lujan 1998 5/133 16/131 5.1 % -0.08 [ -0.15, -0.02 ]
Milheiro 1994 0/20 0/20 4.0 % 0.0 [ -0.09, 0.09 ]
Mimica 2000 0/50 0/50 6.2 % 0.0 [ -0.04, 0.04 ]
Prisco 2000 0/10 0/10 1.9 % 0.0 [ -0.17, 0.17 ]
Trondsen 1993 3/35 1/35 3.5 % 0.06 [ -0.05, 0.17 ]
Volpino 1998 2/58 5/60 4.3 % -0.05 [ -0.13, 0.04 ]
Zajac 1998 0/58 14/52 3.1 % -0.27 [ -0.39, -0.15 ]
Subtotal (95% CI) 794 756 86.2 % -0.03 [ -0.07, 0.00 ]

Heterogeneity: Tau2 = 0.00; Chi2 = 80.16, df = 25 (P<0.00001); I2 =69%
Total (95% CI) 975 939 100.0 % -0.03 [ -0.06, 0.00 ]
-0.5 -0.25 0 0.25 0.5

allocation sequence, Outcome 5 Bile duct injuries.
Outcome: 5 Bile duct injuries
Risk Risk
Charlo 1995 1/100 0/100 10.5 % 0.01 [ -0.02, 0.04 ]
Chaudhary 1999 0/21 0/22 2.3 % 0.0 [ -0.09, 0.09 ]
Jan 1993 0/50 0/51 5.3 % 0.0 [ -0.04, 0.04 ]
Ortega 1996 0/10 0/10 1.0 % 0.0 [ -0.17, 0.17 ]
Subtotal (95% CI) 181 183 19.1 % 0.01 [ -0.02, 0.03 ]

2 Low-quality trial
Agnifili 1993 0/29 0/21 2.6 % 0.0 [ -0.08, 0.08 ]
Bellon 1998 0/14 0/14 1.5 % 0.0 [ -0.13, 0.13 ]
Berggren 1994 0/15 0/12 1.4 % 0.0 [ -0.13, 0.13 ]
Chumillas 1998 0/20 0/20 2.1 % 0.0 [ -0.09, 0.09 ]
Coelho 1993 0/15 0/15 1.6 % 0.0 [ -0.12, 0.12 ]
Coskun 2000 0/35 0/35 3.7 % 0.0 [ -0.05, 0.05 ]
Dauleh 1995 0/40 0/38 4.1 % 0.0 [ -0.05, 0.05 ]
Demirer 2000 0/50 0/50 5.2 % 0.0 [ -0.04, 0.04 ]
Dionigi 1994 0/30 0/27 3.0 % 0.0 [ -0.07, 0.07 ]
Engin 1998 0/16 0/16 1.7 % 0.0 [ -0.11, 0.11 ]
Essen 1995 0/6 0/6 0.6 % 0.0 [ -0.27, 0.27 ]
Gal 1997 0/21 0/21 2.2 % 0.0 [ -0.09, 0.09 ]
Galizia 2001 0/10 0/5 0.7 % 0.0 [ -0.25, 0.25 ]
Hasukic 2002 0/30 0/28 3.0 % 0.0 [ -0.06, 0.06 ]
Hendolin 2000 0/25 0/22 2.5 % 0.0 [ -0.08, 0.08 ]
Huang 1996 0/15 1/12 1.4 % -0.08 [ -0.28, 0.11 ]
-0.5 -0.25 0 0.25 0.5

(Continued . . . )
(. . . Continued)
Risk Risk
Karayiannakis 1997 0/45 0/42 4.6 % 0.0 [ -0.04, 0.04 ]
Lausten 1999 (1) 0/7 0/7 0.7 % 0.0 [ -0.24, 0.24 ]
Lausten 1999 (2) 0/7 0/7 0.7 % 0.0 [ -0.24, 0.24 ]
Lujan 1998 0/133 0/131 13.8 % 0.0 [ -0.01, 0.01 ]
Milheiro 1994 0/20 0/20 2.1 % 0.0 [ -0.09, 0.09 ]
Mimica 2000 0/50 0/50 5.2 % 0.0 [ -0.04, 0.04 ]
Prisco 2000 0/10 0/10 1.0 % 0.0 [ -0.17, 0.17 ]
Trondsen 1993 1/35 1/35 3.7 % 0.0 [ -0.08, 0.08 ]
Volpino 1998 0/58 0/60 6.2 % 0.0 [ -0.03, 0.03 ]
Zajac 1998 0/58 0/52 5.7 % 0.0 [ -0.03, 0.03 ]
Subtotal (95% CI) 794 756 80.9 % 0.00 [ -0.01, 0.01 ]

Total (95% CI) 975 939 100.0 % 0.00 [ -0.01, 0.01 ]
-0.5 -0.25 0 0.25 0.5

allocation sequence, Outcome 6 Total complications.
Outcome: 6 Total complications
Risk Risk
M- M-
n/N n/N CI CI
Charlo 1995 13/100 16/100 4.4 % -0.03 [ -0.13, 0.07 ]
Chaudhary 1999 0/21 2/22 3.0 % -0.09 [ -0.23, 0.05 ]
Jan 1993 5/50 1/51 4.6 % 0.08 [ -0.01, 0.17 ]
Ortega 1996 0/10 0/10 2.3 % 0.0 [ -0.17, 0.17 ]
Subtotal (95% CI) 181 183 14.4 % 0.00 [ -0.08, 0.08 ]

2 Low-quality trial
Agnifili 1993 1/29 4/21 2.2 % -0.16 [ -0.34, 0.02 ]
Bellon 1998 0/14 0/14 3.4 % 0.0 [ -0.13, 0.13 ]
Berggren 1994 1/15 0/12 2.3 % 0.07 [ -0.11, 0.24 ]
Chumillas 1998 0/20 1/20 3.4 % -0.05 [ -0.18, 0.08 ]
Coelho 1993 0/15 1/15 2.5 % -0.07 [ -0.23, 0.10 ]
Coskun 2000 0/35 10/35 2.8 % -0.29 [ -0.44, -0.13 ]
Dauleh 1995 0/40 0/38 6.3 % 0.0 [ -0.05, 0.05 ]
Demirer 2000 0/50 0/50 6.7 % 0.0 [ -0.04, 0.04 ]
Dionigi 1994 0/30 1/27 4.5 % -0.04 [ -0.13, 0.06 ]
Engin 1998 0/16 0/16 3.8 % 0.0 [ -0.11, 0.11 ]
Essen 1995 0/6 0/6 1.2 % 0.0 [ -0.27, 0.27 ]
Gal 1997 0/21 0/21 4.8 % 0.0 [ -0.09, 0.09 ]
Galizia 2001 2/10 1/5 0.5 % 0.0 [ -0.43, 0.43 ]
Hasukic 2002 0/30 6/28 2.7 % -0.21 [ -0.37, -0.06 ]
Hendolin 2000 1/25 2/22 3.0 % -0.05 [ -0.19, 0.09 ]
-0.5 -0.25 0 0.25 0.5

(Continued . . . )
(. . . Continued)
Risk Risk
M- M-
n/N n/N CI CI
Huang 1996 0/15 3/12 1.3 % -0.25 [ -0.51, 0.01 ]
Karayiannakis 1997 0/45 0/42 6.5 % 0.0 [ -0.04, 0.04 ]
Lausten 1999 (1) 1/7 0/7 0.9 % 0.14 [ -0.18, 0.46 ]
Lausten 1999 (2) 0/7 0/7 1.5 % 0.0 [ -0.24, 0.24 ]
Lujan 1998 18/133 31/131 4.6 % -0.10 [ -0.19, -0.01 ]
Milheiro 1994 1/20 2/20 2.6 % -0.05 [ -0.21, 0.11 ]
Mimica 2000 0/50 2/50 5.7 % -0.04 [ -0.11, 0.03 ]
Prisco 2000 0/10 0/10 2.3 % 0.0 [ -0.17, 0.17 ]
Trondsen 1993 14/35 8/35 1.7 % 0.17 [ -0.04, 0.39 ]
Volpino 1998 2/58 5/60 4.9 % -0.05 [ -0.13, 0.04 ]
Zajac 1998 0/58 14/52 3.6 % -0.27 [ -0.39, -0.15 ]
Subtotal (95% CI) 794 756 85.6 % -0.05 [ -0.09, -0.01 ]

Total (95% CI) 975 939 100.0 % -0.04 [ -0.07, -0.01 ]
-0.5 -0.25 0 0.25 0.5

allocation sequence, Outcome 7 Operative time (minutes).
Outcome: 7 Operative time (minutes)
Mean Mean
Study or subgroup Laparoscopic (LC) Open (OC) Difference Weight Difference
N Mean(SD) N Mean(SD) IV,Random,95% CI IV,Random,95% CI
Blanc-Louvry 2000 25 61 (20) 16 74 (20) 4.3 % -13.00 [ -25.55, -0.45 ]
Jan 1993 50 85.7 (25.2) 51 48 (13.9) 4.5 % 37.70 [ 29.74, 45.66 ]
Ortega 1996 10 70 (6) 10 77 (6.3) 4.6 % -7.00 [ -12.39, -1.61 ]
Subtotal (95% CI) 85 77 13.4 % 6.04 [ -25.72, 37.81 ]

2 Low-quality trial
Agnifili 1993 29 43.2 (16) 21 53.3 (19.1) 4.4 % -10.10 [ -20.13, -0.07 ]
Berggren 1994 15 87 (24.33) 12 69.17 (11.25) 4.2 % 17.83 [ 3.97, 31.69 ]
Bukan 2004 15 55 (15.4) 15 73 (24.3) 4.1 % -18.00 [ -32.56, -3.44 ]
Chumillas 1998 20 104 (34.39) 20 111.75 (30.57) 3.7 % -7.75 [ -27.92, 12.42 ]
Dionigi 1994 30 89 (29) 27 78 (20) 4.3 % 11.00 [ -1.83, 23.83 ]
Engin 1998 16 82.4 (26.64) 16 79.5 (31.23) 3.8 % 2.90 [ -17.21, 23.01 ]
Essen 1995 6 87 (36) 6 79 (22) 2.7 % 8.00 [ -25.76, 41.76 ]
Galizia 2001 10 68 (14.7) 5 60 (3.6) 4.4 % 8.00 [ -1.64, 17.64 ]
Hasukic 2002 30 77.83 (12.01) 28 71.48 (8.26) 4.6 % 6.35 [ 1.07, 11.63 ]
Huang 1996 15 93.3 (25.3) 12 176.3 (26.1) 3.8 % -83.00 [ -102.54, -63.46 ]
Karayiannakis 1997 45 105 (25) 42 98 (17) 4.5 % 7.00 [ -1.93, 15.93 ]
Lausten 1999 (1) 7 121 (14) 7 129 (23) 3.8 % -8.00 [ -27.95, 11.95 ]
Lausten 1999 (2) 7 122 (12) 7 90 (7) 4.4 % 32.00 [ 21.71, 42.29 ]
Milheiro 1994 20 60 (21) 20 88 (15) 4.4 % -28.00 [ -39.31, -16.69 ]
Mimica 2000 50 102 (20) 50 110 (32) 4.4 % -8.00 [ -18.46, 2.46 ]
Prisco 2000 10 115 (22) 10 105 (19) 3.9 % 10.00 [ -8.02, 28.02 ]
Putensen-Himmer 1992 10 104 (25) 10 112 (37) 3.2 % -8.00 [ -35.68, 19.68 ]
Rovina 1996 26 155 (27) 25 46 (13) 4.3 % 109.00 [ 97.44, 120.56 ]
-100 -50 0 50 100

(Continued . . . )
(. . . Continued)
Mean Mean
Volpino 1998 58 86.6 (22) 60 81 (24.79) 4.5 % 5.60 [ -2.85, 14.05 ]
Zajac 1998 58 54 (5) 52 47 (4) 4.7 % 7.00 [ 5.32, 8.68 ]
Zulfikaroglu 2002 25 69.2 (17.2) 25 66.8 (16.8) 4.5 % 2.40 [ -7.02, 11.82 ]
Subtotal (95% CI) 502 470 86.6 % 3.37 [ -6.29, 13.04 ]

Total (95% CI) 587 547 100.0 % 3.79 [ -4.88, 12.46 ]
-100 -50 0 50 100

allocation sequence, Outcome 8 Hospital stay (days).
Outcome: 8 Hospital stay (days)
Mean Mean
Blanc-Louvry 2000 25 2.5 (1) 16 4.6 (1.2) 4.9 % -2.10 [ -2.81, -1.39 ]
Charlo 1995 100 3 (1.01) 100 7 (2.63) 4.9 % -4.00 [ -4.55, -3.45 ]
Jan 1993 50 4.5 (1.4) 51 5.6 (1.3) 4.9 % -1.10 [ -1.63, -0.57 ]
Ortega 1996 10 1.2 (0.2) 10 1.1 (0.1) 5.0 % 0.10 [ -0.04, 0.24 ]
Subtotal (95% CI) 185 177 19.8 % -1.76 [ -3.70, 0.17 ]

2 Low-quality trial
Agnifili 1993 29 3.2 (1.2) 21 7.3 (3.2) 4.4 % -4.10 [ -5.54, -2.66 ]
Berggren 1994 15 1.8 (0.56) 12 2.83 (0.84) 4.9 % -1.03 [ -1.58, -0.48 ]
Bukan 2004 15 2 (0.2) 15 5 (0.4) 5.0 % -3.00 [ -3.23, -2.77 ]
Chumillas 1998 20 3.25 (0.71) 20 10.57 (4.67) 3.8 % -7.32 [ -9.39, -5.25 ]
Dionigi 1994 30 3.1 (0.5) 27 7.1 (1.6) 4.9 % -4.00 [ -4.63, -3.37 ]
Engin 1998 16 1.68 (0.6) 16 3.06 (0.77) 5.0 % -1.38 [ -1.86, -0.90 ]
Essen 1995 6 1.3 (0.5) 6 2.5 (0.6) 4.9 % -1.20 [ -1.82, -0.58 ]
Galizia 2001 10 1 (0.01) 5 5.2 (2.2) 3.9 % -4.20 [ -6.13, -2.27 ]
Huang 1996 15 3.93 (1.71) 12 7.92 (0.79) 4.7 % -3.99 [ -4.96, -3.02 ]
Karayiannakis 1997 45 2 (0.6) 42 5.6 (1.1) 5.0 % -3.60 [ -3.98, -3.22 ]
Kjaersgaard 1994 35 2.5 (1.61) 35 4.9 (4.25) 4.3 % -2.40 [ -3.91, -0.89 ]
Lausten 1999 (1) 7 2.9 (0.3) 7 5.3 (0.3) 5.0 % -2.40 [ -2.71, -2.09 ]
Lausten 1999 (2) 7 2.7 (0.3) 7 4.6 (0.2) 5.0 % -1.90 [ -2.17, -1.63 ]
Luo 2003 14 3.2 (1.12) 12 6.7 (0.69) 4.9 % -3.50 [ -4.20, -2.80 ]
Prisco 2000 10 2 (0.01) 10 5.6 (0.52) 5.0 % -3.60 [ -3.92, -3.28 ]
Volpino 1998 58 4.6 (2.9) 60 7.77 (3.1) 4.6 % -3.17 [ -4.25, -2.09 ]
Zajac 1998 58 1 (0.01) 52 9.1 (2.8) 4.8 % -8.10 [ -8.86, -7.34 ]
-10 -5 0 5 10
(Continued . . . )
(. . . Continued)
Mean Mean
Subtotal (95% CI) 390 359 80.2 % -3.34 [ -3.97, -2.71 ]
Test for overall effect: Z = 10.38 (P < 0.00001)
Total (95% CI) 575 536 100.0 % -3.07 [ -3.89, -2.26 ]
-10 -5 0 5 10
allocation sequence, Outcome 9 Convalescence: work leave (days).
Outcome: 9 Convalescence: work leave (days)
Mean Mean
Charlo 1995 100 10 (1.57) 100 42 (3.23) 34.2 % -32.00 [ -32.70, -31.30 ]
Jan 1993 50 12.8 (8.8) 51 35.9 (20.6) 32.2 % -23.10 [ -29.26, -16.94 ]
Subtotal (95% CI) 150 151 66.4 % -28.10 [ -36.75, -19.44 ]

2 Low-quality trial
Berggren 1994 15 11.7 (4.1) 12 24 (4.4) 33.6 % -12.30 [ -15.54, -9.06 ]
Subtotal (95% CI) 15 12 33.6 % -12.30 [ -15.54, -9.06 ]

Heterogeneity: not applicable
Total (95% CI) 165 163 100.0 % -22.51 [ -36.89, -8.13 ]
-100 -50 0 50 100

Analysis 2.1. Comparison 2 LC versus OC - high-quality and low-quality trials regarding concealment of
allocation, Outcome 1 Mortality.
Comparison: 2 LC versus OC - high-quality and low-quality trials regarding concealment of allocation
Risk Risk
1 High-quality trials
Berggren 1994 0/15 0/12 2.7 % 0.0 [ -0.13, 0.13 ]
Chumillas 1998 0/20 0/20 4.1 % 0.0 [ -0.09, 0.09 ]
Engin 1998 0/16 0/16 3.3 % 0.0 [ -0.11, 0.11 ]
Galizia 2001 0/10 0/5 1.4 % 0.0 [ -0.25, 0.25 ]
Milheiro 1994 0/20 0/20 4.1 % 0.0 [ -0.09, 0.09 ]
Mimica 2000 0/50 0/50 10.2 % 0.0 [ -0.04, 0.04 ]
Subtotal (95% CI) 131 123 25.6 % 0.0 [ -0.04, 0.04 ]

2 Low-quality trials
Agnifili 1993 0/29 0/21 5.0 % 0.0 [ -0.08, 0.08 ]
Bellon 1998 0/14 0/14 2.8 % 0.0 [ -0.13, 0.13 ]
Charlo 1995 0/100 0/100 20.3 % 0.0 [ -0.02, 0.02 ]
Gal 1997 0/21 0/21 4.3 % 0.0 [ -0.09, 0.09 ]
Jan 1993 0/50 0/51 10.3 % 0.0 [ -0.04, 0.04 ]
Lausten 1999 (1) 0/7 0/7 1.4 % 0.0 [ -0.24, 0.24 ]
Lausten 1999 (2) 0/7 0/7 1.4 % 0.0 [ -0.24, 0.24 ]
Lujan 1998 0/133 1/131 26.8 % -0.01 [ -0.03, 0.01 ]
Prisco 2000 0/10 0/10 2.0 % 0.0 [ -0.17, 0.17 ]
Subtotal (95% CI) 371 362 74.4 % 0.00 [ -0.02, 0.01 ]
-0.5 -0.25 0 0.25 0.5

(Continued . . . )
(. . . Continued)
Risk Risk
Total (95% CI) 502 485 100.0 % 0.00 [ -0.02, 0.01 ]
-0.5 -0.25 0 0.25 0.5

allocation, Outcome 2 Intra-operative complications.
Risk Risk
Berggren 1994 0/15 0/12 1.4 % 0.0 [ -0.13, 0.13 ]
Chumillas 1998 0/20 0/20 2.1 % 0.0 [ -0.09, 0.09 ]
Engin 1998 0/16 0/16 1.7 % 0.0 [ -0.11, 0.11 ]
Galizia 2001 2/10 0/5 0.7 % 0.20 [ -0.13, 0.53 ]
Hendolin 2000 0/25 0/22 2.5 % 0.0 [ -0.08, 0.08 ]
Karayiannakis 1997 0/45 0/42 4.6 % 0.0 [ -0.04, 0.04 ]
Milheiro 1994 0/20 0/20 2.1 % 0.0 [ -0.09, 0.09 ]
Mimica 2000 0/50 0/50 5.2 % 0.0 [ -0.04, 0.04 ]
Subtotal (95% CI) 201 187 20.2 % 0.01 [ -0.02, 0.04 ]
-0.5 -0.25 0 0.25 0.5

(Continued . . . )
(. . . Continued)
Risk Risk
Agnifili 1993 0/29 0/21 2.6 % 0.0 [ -0.08, 0.08 ]
Bellon 1998 0/14 0/14 1.5 % 0.0 [ -0.13, 0.13 ]
Charlo 1995 0/100 0/100 10.5 % 0.0 [ -0.02, 0.02 ]
Chaudhary 1999 0/21 0/22 2.3 % 0.0 [ -0.09, 0.09 ]
Coelho 1993 0/15 0/15 1.6 % 0.0 [ -0.12, 0.12 ]
Coskun 2000 0/35 0/35 3.7 % 0.0 [ -0.05, 0.05 ]
Dauleh 1995 0/40 0/38 4.1 % 0.0 [ -0.05, 0.05 ]
Demirer 2000 0/50 0/50 5.2 % 0.0 [ -0.04, 0.04 ]
Dionigi 1994 0/30 0/27 3.0 % 0.0 [ -0.07, 0.07 ]
Essen 1995 0/6 0/6 0.6 % 0.0 [ -0.27, 0.27 ]
Gal 1997 0/21 0/21 2.2 % 0.0 [ -0.09, 0.09 ]
Hasukic 2002 0/30 0/28 3.0 % 0.0 [ -0.06, 0.06 ]
Huang 1996 0/15 0/12 1.4 % 0.0 [ -0.13, 0.13 ]
Jan 1993 1/50 0/51 5.3 % 0.02 [ -0.03, 0.07 ]
Lausten 1999 (1) 0/7 0/7 0.7 % 0.0 [ -0.24, 0.24 ]
Lausten 1999 (2) 0/7 0/7 0.7 % 0.0 [ -0.24, 0.24 ]
Lujan 1998 0/133 0/131 13.8 % 0.0 [ -0.01, 0.01 ]
Ortega 1996 0/10 0/10 1.0 % 0.0 [ -0.17, 0.17 ]
Prisco 2000 0/10 0/10 1.0 % 0.0 [ -0.17, 0.17 ]
Trondsen 1993 6/35 1/35 3.7 % 0.14 [ 0.01, 0.28 ]
Volpino 1998 0/58 0/60 6.2 % 0.0 [ -0.03, 0.03 ]
Zajac 1998 0/58 0/52 5.7 % 0.0 [ -0.03, 0.03 ]
Subtotal (95% CI) 774 752 79.8 % 0.01 [ -0.01, 0.02 ]

Total (95% CI) 975 939 100.0 % 0.01 [ 0.00, 0.02 ]
-0.5 -0.25 0 0.25 0.5

allocation, Outcome 3 Minor complications.
Risk Risk
Berggren 1994 1/15 0/12 1.4 % 0.07 [ -0.11, 0.24 ]
Chumillas 1998 0/20 0/20 2.1 % 0.0 [ -0.09, 0.09 ]
Engin 1998 0/16 0/16 1.7 % 0.0 [ -0.11, 0.11 ]
Galizia 2001 0/10 0/5 0.7 % 0.0 [ -0.25, 0.25 ]
Hendolin 2000 0/25 2/22 2.5 % -0.09 [ -0.23, 0.05 ]
Karayiannakis 1997 0/45 0/42 4.6 % 0.0 [ -0.04, 0.04 ]
Milheiro 1994 1/20 2/20 2.1 % -0.05 [ -0.21, 0.11 ]
Mimica 2000 0/50 2/50 5.2 % -0.04 [ -0.11, 0.03 ]
Subtotal (95% CI) 201 187 20.2 % -0.02 [ -0.06, 0.02 ]

Agnifili 1993 0/29 0/21 2.6 % 0.0 [ -0.08, 0.08 ]
Bellon 1998 0/14 0/14 1.5 % 0.0 [ -0.13, 0.13 ]
Charlo 1995 4/100 4/100 10.5 % 0.0 [ -0.05, 0.05 ]
Chaudhary 1999 0/21 1/22 2.3 % -0.05 [ -0.16, 0.07 ]
Coelho 1993 0/15 1/15 1.6 % -0.07 [ -0.23, 0.10 ]
Coskun 2000 0/35 0/35 3.7 % 0.0 [ -0.05, 0.05 ]
Dauleh 1995 0/40 0/38 4.1 % 0.0 [ -0.05, 0.05 ]
Demirer 2000 0/50 0/50 5.2 % 0.0 [ -0.04, 0.04 ]
Dionigi 1994 0/30 1/27 3.0 % -0.04 [ -0.13, 0.06 ]
-0.5 -0.25 0 0.25 0.5

(Continued . . . )
(. . . Continued)
Risk Risk
Essen 1995 0/6 0/6 0.6 % 0.0 [ -0.27, 0.27 ]
Gal 1997 0/21 0/21 2.2 % 0.0 [ -0.09, 0.09 ]
Hasukic 2002 0/30 0/28 3.0 % 0.0 [ -0.06, 0.06 ]
Huang 1996 0/15 2/12 1.4 % -0.17 [ -0.40, 0.06 ]
Jan 1993 0/50 0/51 5.3 % 0.0 [ -0.04, 0.04 ]
Lausten 1999 (1) 0/7 0/7 0.7 % 0.0 [ -0.24, 0.24 ]
Lausten 1999 (2) 0/7 0/7 0.7 % 0.0 [ -0.24, 0.24 ]
Lujan 1998 13/133 15/131 13.8 % -0.02 [ -0.09, 0.06 ]
Ortega 1996 0/10 0/10 1.0 % 0.0 [ -0.17, 0.17 ]
Prisco 2000 0/10 0/10 1.0 % 0.0 [ -0.17, 0.17 ]
Trondsen 1993 4/35 5/35 3.7 % -0.03 [ -0.19, 0.13 ]
Volpino 1998 0/58 0/60 6.2 % 0.0 [ -0.03, 0.03 ]
Zajac 1998 0/58 0/52 5.7 % 0.0 [ -0.03, 0.03 ]
Subtotal (95% CI) 774 752 79.8 % -0.01 [ -0.03, 0.01 ]

Total (95% CI) 975 939 100.0 % -0.01 [ -0.03, 0.00 ]
-0.5 -0.25 0 0.25 0.5

allocation, Outcome 4 Severe complications (without bile duct injuries).
Risk Risk
M- M-
n/N n/N CI CI
Berggren 1994 0/15 0/12 2.7 % 0.0 [ -0.13, 0.13 ]
Chumillas 1998 0/20 1/20 2.9 % -0.05 [ -0.18, 0.08 ]
Engin 1998 0/16 0/16 3.3 % 0.0 [ -0.11, 0.11 ]
Galizia 2001 0/10 1/5 0.6 % -0.20 [ -0.57, 0.17 ]
Hendolin 2000 1/25 0/22 3.5 % 0.04 [ -0.07, 0.15 ]
Karayiannakis 1997 0/45 0/42 6.0 % 0.0 [ -0.04, 0.04 ]
Milheiro 1994 0/20 0/20 4.0 % 0.0 [ -0.09, 0.09 ]
Mimica 2000 0/50 0/50 6.2 % 0.0 [ -0.04, 0.04 ]
Subtotal (95% CI) 201 187 29.1 % 0.00 [ -0.03, 0.02 ]

Heterogeneity: Tau2 = 0.0; Chi2 = 2.52, df = 7 (P = 0.93); I2 =0.0%
Agnifili 1993 1/29 4/21 1.8 % -0.16 [ -0.34, 0.02 ]
Bellon 1998 0/14 0/14 2.9 % 0.0 [ -0.13, 0.13 ]
Charlo 1995 8/100 12/100 4.4 % -0.04 [ -0.12, 0.04 ]
Chaudhary 1999 0/21 1/22 3.2 % -0.05 [ -0.16, 0.07 ]
Coelho 1993 0/15 0/15 3.1 % 0.0 [ -0.12, 0.12 ]
Coskun 2000 0/35 10/35 2.3 % -0.29 [ -0.44, -0.13 ]
Dauleh 1995 0/40 0/38 5.8 % 0.0 [ -0.05, 0.05 ]
Demirer 2000 0/50 0/50 6.2 % 0.0 [ -0.04, 0.04 ]
Dionigi 1994 0/30 0/27 5.1 % 0.0 [ -0.07, 0.07 ]
Essen 1995 0/6 0/6 1.0 % 0.0 [ -0.27, 0.27 ]
Gal 1997 0/21 0/21 4.2 % 0.0 [ -0.09, 0.09 ]
-0.5 -0.25 0 0.25 0.5

(Continued . . . )
(. . . Continued)
Risk Risk
M- M-
n/N n/N CI CI
Hasukic 2002 0/30 6/28 2.2 % -0.21 [ -0.37, -0.06 ]
Huang 1996 0/15 0/12 2.7 % 0.0 [ -0.13, 0.13 ]
Jan 1993 4/50 1/51 4.3 % 0.06 [ -0.02, 0.14 ]
Lausten 1999 (1) 1/7 0/7 0.7 % 0.14 [ -0.18, 0.46 ]
Lausten 1999 (2) 0/7 0/7 1.2 % 0.0 [ -0.24, 0.24 ]
Lujan 1998 5/133 16/131 5.1 % -0.08 [ -0.15, -0.02 ]
Ortega 1996 0/10 0/10 1.9 % 0.0 [ -0.17, 0.17 ]
Prisco 2000 0/10 0/10 1.9 % 0.0 [ -0.17, 0.17 ]
Trondsen 1993 3/35 1/35 3.5 % 0.06 [ -0.05, 0.17 ]
Volpino 1998 2/58 5/60 4.3 % -0.05 [ -0.13, 0.04 ]
Zajac 1998 0/58 14/52 3.1 % -0.27 [ -0.39, -0.15 ]
Subtotal (95% CI) 774 752 70.9 % -0.04 [ -0.08, 0.00 ]

Total (95% CI) 975 939 100.0 % -0.03 [ -0.06, 0.00 ]
-0.5 -0.25 0 0.25 0.5

allocation, Outcome 5 Bile duct injuries.
Risk Risk
Berggren 1994 0/15 0/12 1.4 % 0.0 [ -0.13, 0.13 ]
Chumillas 1998 0/20 0/20 2.1 % 0.0 [ -0.09, 0.09 ]
Engin 1998 0/16 0/16 1.7 % 0.0 [ -0.11, 0.11 ]
Galizia 2001 0/10 0/5 0.7 % 0.0 [ -0.25, 0.25 ]
Hendolin 2000 0/25 0/22 2.5 % 0.0 [ -0.08, 0.08 ]
Karayiannakis 1997 0/45 0/42 4.6 % 0.0 [ -0.04, 0.04 ]
Milheiro 1994 0/20 0/20 2.1 % 0.0 [ -0.09, 0.09 ]
Mimica 2000 0/50 0/50 5.2 % 0.0 [ -0.04, 0.04 ]
Subtotal (95% CI) 201 187 20.2 % 0.0 [ -0.03, 0.03 ]

Agnifili 1993 0/29 0/21 2.6 % 0.0 [ -0.08, 0.08 ]
Bellon 1998 0/14 0/14 1.5 % 0.0 [ -0.13, 0.13 ]
Charlo 1995 1/100 0/100 10.5 % 0.01 [ -0.02, 0.04 ]
Chaudhary 1999 0/21 0/22 2.3 % 0.0 [ -0.09, 0.09 ]
Coelho 1993 0/15 0/15 1.6 % 0.0 [ -0.12, 0.12 ]
Coskun 2000 0/35 0/35 3.7 % 0.0 [ -0.05, 0.05 ]
Dauleh 1995 0/40 0/38 4.1 % 0.0 [ -0.05, 0.05 ]
Demirer 2000 0/50 0/50 5.2 % 0.0 [ -0.04, 0.04 ]
Dionigi 1994 0/30 0/27 3.0 % 0.0 [ -0.07, 0.07 ]
Essen 1995 0/6 0/6 0.6 % 0.0 [ -0.27, 0.27 ]
Gal 1997 0/21 0/21 2.2 % 0.0 [ -0.09, 0.09 ]
Hasukic 2002 0/30 0/28 3.0 % 0.0 [ -0.06, 0.06 ]
-0.5 -0.25 0 0.25 0.5

(Continued . . . )
(. . . Continued)
Risk Risk
Huang 1996 0/15 1/12 1.4 % -0.08 [ -0.28, 0.11 ]
Jan 1993 0/50 0/51 5.3 % 0.0 [ -0.04, 0.04 ]
Lausten 1999 (1) 0/7 0/7 0.7 % 0.0 [ -0.24, 0.24 ]
Lausten 1999 (2) 0/7 0/7 0.7 % 0.0 [ -0.24, 0.24 ]
Lujan 1998 0/133 0/131 13.8 % 0.0 [ -0.01, 0.01 ]
Ortega 1996 0/10 0/10 1.0 % 0.0 [ -0.17, 0.17 ]
Prisco 2000 0/10 0/10 1.0 % 0.0 [ -0.17, 0.17 ]
Trondsen 1993 1/35 1/35 3.7 % 0.0 [ -0.08, 0.08 ]
Volpino 1998 0/58 0/60 6.2 % 0.0 [ -0.03, 0.03 ]
Zajac 1998 0/58 0/52 5.7 % 0.0 [ -0.03, 0.03 ]
Subtotal (95% CI) 774 752 79.8 % 0.00 [ -0.01, 0.01 ]

Total (95% CI) 975 939 100.0 % 0.00 [ -0.01, 0.01 ]
-0.5 -0.25 0 0.25 0.5

allocation, Outcome 6 Total complications.
Risk Risk
M- M-
n/N n/N CI CI
Berggren 1994 1/15 0/12 2.3 % 0.07 [ -0.11, 0.24 ]
Chumillas 1998 0/20 1/20 3.4 % -0.05 [ -0.18, 0.08 ]
Engin 1998 0/16 0/16 3.8 % 0.0 [ -0.11, 0.11 ]
Galizia 2001 2/10 1/5 0.5 % 0.0 [ -0.43, 0.43 ]
Hendolin 2000 1/25 2/22 3.0 % -0.05 [ -0.19, 0.09 ]
Karayiannakis 1997 0/45 0/42 6.5 % 0.0 [ -0.04, 0.04 ]
Milheiro 1994 1/20 2/20 2.6 % -0.05 [ -0.21, 0.11 ]
Mimica 2000 0/50 2/50 5.7 % -0.04 [ -0.11, 0.03 ]
Subtotal (95% CI) 201 187 27.8 % -0.01 [ -0.05, 0.02 ]

Agnifili 1993 1/29 4/21 2.2 % -0.16 [ -0.34, 0.02 ]
Bellon 1998 0/14 0/14 3.4 % 0.0 [ -0.13, 0.13 ]
Charlo 1995 13/100 16/100 4.4 % -0.03 [ -0.13, 0.07 ]
Chaudhary 1999 0/21 2/22 3.0 % -0.09 [ -0.23, 0.05 ]
Coelho 1993 0/15 1/15 2.5 % -0.07 [ -0.23, 0.10 ]
Coskun 2000 0/35 10/35 2.8 % -0.29 [ -0.44, -0.13 ]
Dauleh 1995 0/40 0/38 6.3 % 0.0 [ -0.05, 0.05 ]
Demirer 2000 0/50 0/50 6.7 % 0.0 [ -0.04, 0.04 ]
Dionigi 1994 0/30 1/27 4.5 % -0.04 [ -0.13, 0.06 ]
Essen 1995 0/6 0/6 1.2 % 0.0 [ -0.27, 0.27 ]
Gal 1997 0/21 0/21 4.8 % 0.0 [ -0.09, 0.09 ]
-0.5 -0.25 0 0.25 0.5

(Continued . . . )
(. . . Continued)
Risk Risk
M- M-
n/N n/N CI CI
Hasukic 2002 0/30 6/28 2.7 % -0.21 [ -0.37, -0.06 ]
Huang 1996 0/15 3/12 1.3 % -0.25 [ -0.51, 0.01 ]
Jan 1993 5/50 1/51 4.6 % 0.08 [ -0.01, 0.17 ]
Lausten 1999 (1) 1/7 0/7 0.9 % 0.14 [ -0.18, 0.46 ]
Lausten 1999 (2) 0/7 0/7 1.5 % 0.0 [ -0.24, 0.24 ]
Lujan 1998 18/133 31/131 4.6 % -0.10 [ -0.19, -0.01 ]
Ortega 1996 0/10 0/10 2.3 % 0.0 [ -0.17, 0.17 ]
Prisco 2000 0/10 0/10 2.3 % 0.0 [ -0.17, 0.17 ]
Trondsen 1993 14/35 8/35 1.7 % 0.17 [ -0.04, 0.39 ]
Volpino 1998 2/58 5/60 4.9 % -0.05 [ -0.13, 0.04 ]
Zajac 1998 0/58 14/52 3.6 % -0.27 [ -0.39, -0.15 ]
Subtotal (95% CI) 774 752 72.2 % -0.05 [ -0.10, -0.01 ]

Total (95% CI) 975 939 100.0 % -0.04 [ -0.07, -0.01 ]
-0.5 -0.25 0 0.25 0.5

allocation, Outcome 7 Operative time (minutes).
Mean Mean
Berggren 1994 15 87 (24.33) 12 69.17 (11.25) 4.2 % 17.83 [ 3.97, 31.69 ]
Chumillas 1998 20 104 (34.39) 20 111.75 (30.57) 3.7 % -7.75 [ -27.92, 12.42 ]
Engin 1998 16 82.4 (26.64) 16 79.5 (31.23) 3.8 % 2.90 [ -17.21, 23.01 ]
Galizia 2001 10 68 (14.7) 5 60 (3.6) 4.4 % 8.00 [ -1.64, 17.64 ]
Karayiannakis 1997 45 105 (25) 42 98 (17) 4.5 % 7.00 [ -1.93, 15.93 ]
Milheiro 1994 20 60 (21) 20 88 (15) 4.4 % -28.00 [ -39.31, -16.69 ]
Mimica 2000 50 102 (20) 50 110 (32) 4.4 % -8.00 [ -18.46, 2.46 ]
Subtotal (95% CI) 176 165 29.4 % -1.14 [ -12.80, 10.52 ]

Agnifili 1993 29 43.2 (16) 21 53.3 (19.1) 4.4 % -10.10 [ -20.13, -0.07 ]
Blanc-Louvry 2000 25 61 (20) 16 74 (20) 4.3 % -13.00 [ -25.55, -0.45 ]
Bukan 2004 15 55 (15.4) 15 73 (24.3) 4.1 % -18.00 [ -32.56, -3.44 ]
Dionigi 1994 30 89 (29) 27 78 (20) 4.3 % 11.00 [ -1.83, 23.83 ]
Essen 1995 6 87 (36) 6 79 (22) 2.7 % 8.00 [ -25.76, 41.76 ]
Hasukic 2002 30 77.83 (12.01) 28 71.48 (8.26) 4.6 % 6.35 [ 1.07, 11.63 ]
Huang 1996 15 93.3 (25.3) 12 176.3 (26.1) 3.8 % -83.00 [ -102.54, -63.46 ]
Jan 1993 50 85.7 (25.2) 51 48 (13.9) 4.5 % 37.70 [ 29.74, 45.66 ]
Lausten 1999 (1) 7 121 (14) 7 129 (23) 3.8 % -8.00 [ -27.95, 11.95 ]
Lausten 1999 (2) 7 122 (12) 7 90 (7) 4.4 % 32.00 [ 21.71, 42.29 ]
Ortega 1996 10 70 (6) 10 77 (6.3) 4.6 % -7.00 [ -12.39, -1.61 ]
Prisco 2000 10 115 (22) 10 105 (19) 3.9 % 10.00 [ -8.02, 28.02 ]
Putensen-Himmer 1992 10 104 (25) 10 112 (37) 3.2 % -8.00 [ -35.68, 19.68 ]
Rovina 1996 26 155 (27) 25 46 (13) 4.3 % 109.00 [ 97.44, 120.56 ]
-100 -50 0 50 100

(Continued . . . )
(. . . Continued)
Mean Mean
Volpino 1998 58 86.6 (22) 60 81 (24.79) 4.5 % 5.60 [ -2.85, 14.05 ]
Zajac 1998 58 54 (5) 52 47 (4) 4.7 % 7.00 [ 5.32, 8.68 ]
Zulfikaroglu 2002 25 69.2 (17.2) 25 66.8 (16.8) 4.5 % 2.40 [ -7.02, 11.82 ]
Subtotal (95% CI) 411 382 70.6 % 5.72 [ -5.34, 16.77 ]

Total (95% CI) 587 547 100.0 % 3.79 [ -4.88, 12.46 ]
-100 -50 0 50 100

allocation, Outcome 8 Hospital stay (days).
Mean Mean
Berggren 1994 15 1.8 (0.56) 12 2.83 (0.84) 4.9 % -1.03 [ -1.58, -0.48 ]
Chumillas 1998 20 3.25 (0.71) 20 10.57 (4.67) 3.8 % -7.32 [ -9.39, -5.25 ]
Engin 1998 16 1.68 (0.6) 16 3.06 (0.77) 5.0 % -1.38 [ -1.86, -0.90 ]
Galizia 2001 10 1 (0.01) 5 5.2 (2.2) 3.9 % -4.20 [ -6.13, -2.27 ]
Karayiannakis 1997 45 2 (0.6) 42 5.6 (1.1) 5.0 % -3.60 [ -3.98, -3.22 ]
Subtotal (95% CI) 106 95 22.6 % -3.23 [ -4.75, -1.71 ]

Agnifili 1993 29 3.2 (1.2) 21 7.3 (3.2) 4.4 % -4.10 [ -5.54, -2.66 ]
Blanc-Louvry 2000 25 2.5 (1) 16 4.6 (1.2) 4.9 % -2.10 [ -2.81, -1.39 ]
Bukan 2004 15 2 (0.2) 15 5 (0.4) 5.0 % -3.00 [ -3.23, -2.77 ]
Charlo 1995 100 3 (1.01) 100 7 (2.63) 4.9 % -4.00 [ -4.55, -3.45 ]
Dionigi 1994 30 3.1 (0.5) 27 7.1 (1.6) 4.9 % -4.00 [ -4.63, -3.37 ]
Essen 1995 6 1.3 (0.5) 6 2.5 (0.6) 4.9 % -1.20 [ -1.82, -0.58 ]
Huang 1996 15 3.93 (1.71) 12 7.92 (0.79) 4.7 % -3.99 [ -4.96, -3.02 ]
Jan 1993 50 4.5 (1.4) 51 5.6 (1.3) 4.9 % -1.10 [ -1.63, -0.57 ]
Kjaersgaard 1994 35 2.5 (1.61) 35 4.9 (4.25) 4.3 % -2.40 [ -3.91, -0.89 ]
Lausten 1999 (1) 7 2.9 (0.3) 7 5.3 (0.3) 5.0 % -2.40 [ -2.71, -2.09 ]
Lausten 1999 (2) 7 2.7 (0.3) 7 4.6 (0.2) 5.0 % -1.90 [ -2.17, -1.63 ]
Luo 2003 14 3.2 (1.12) 12 6.7 (0.69) 4.9 % -3.50 [ -4.20, -2.80 ]
Ortega 1996 10 1.2 (0.2) 10 1.1 (0.1) 5.0 % 0.10 [ -0.04, 0.24 ]
Prisco 2000 10 2 (0.01) 10 5.6 (0.52) 5.0 % -3.60 [ -3.92, -3.28 ]
Volpino 1998 58 4.6 (2.9) 60 7.77 (3.1) 4.6 % -3.17 [ -4.25, -2.09 ]
Zajac 1998 58 1 (0.01) 52 9.1 (2.8) 4.8 % -8.10 [ -8.86, -7.34 ]
-10 -5 0 5 10
(Continued . . . )
(. . . Continued)
Mean Mean
Subtotal (95% CI) 469 441 77.4 % -3.01 [ -3.97, -2.06 ]
Total (95% CI) 575 536 100.0 % -3.07 [ -3.89, -2.26 ]
-10 -5 0 5 10
allocation, Outcome 9 Convalescence: work leave (days).
Mean Mean
Berggren 1994 15 11.7 (4.1) 12 24 (4.4) 33.6 % -12.30 [ -15.54, -9.06 ]
Subtotal (95% CI) 15 12 33.6 % -12.30 [ -15.54, -9.06 ]

Charlo 1995 100 10 (1.57) 100 42 (3.23) 34.2 % -32.00 [ -32.70, -31.30 ]
Jan 1993 50 12.8 (8.8) 51 35.9 (20.6) 32.2 % -23.10 [ -29.26, -16.94 ]
Subtotal (95% CI) 150 151 66.4 % -28.10 [ -36.75, -19.44 ]

Total (95% CI) 165 163 100.0 % -22.51 [ -36.89, -8.13 ]
-100 -50 0 50 100

Analysis 3.1. Comparison 3 LC versus OC - high-quality and low-quality trials regarding blinding, Outcome
1 Mortality.
Comparison: 3 LC versus OC - high-quality and low-quality trials regarding blinding
Risk Risk
Subtotal (95% CI) 0 0 Not estimable
Test for overall effect: not applicable
Agnifili 1993 0/29 0/21 5.0 % 0.0 [ -0.08, 0.08 ]
Bellon 1998 0/14 0/14 2.8 % 0.0 [ -0.13, 0.13 ]
Berggren 1994 0/15 0/12 2.7 % 0.0 [ -0.13, 0.13 ]
Charlo 1995 0/100 0/100 20.3 % 0.0 [ -0.02, 0.02 ]
Chumillas 1998 0/20 0/20 4.1 % 0.0 [ -0.09, 0.09 ]
Engin 1998 0/16 0/16 3.3 % 0.0 [ -0.11, 0.11 ]
Gal 1997 0/21 0/21 4.3 % 0.0 [ -0.09, 0.09 ]
Galizia 2001 0/10 0/5 1.4 % 0.0 [ -0.25, 0.25 ]
Jan 1993 0/50 0/51 10.3 % 0.0 [ -0.04, 0.04 ]
Lausten 1999 (1) 0/7 0/7 1.4 % 0.0 [ -0.24, 0.24 ]
Lausten 1999 (2) 0/7 0/7 1.4 % 0.0 [ -0.24, 0.24 ]
Lujan 1998 0/133 1/131 26.8 % -0.01 [ -0.03, 0.01 ]
Milheiro 1994 0/20 0/20 4.1 % 0.0 [ -0.09, 0.09 ]
Mimica 2000 0/50 0/50 10.2 % 0.0 [ -0.04, 0.04 ]
Prisco 2000 0/10 0/10 2.0 % 0.0 [ -0.17, 0.17 ]
Subtotal (95% CI) 502 485 100.0 % 0.00 [ -0.02, 0.01 ]
-0.5 -0.25 0 0.25 0.5

(Continued . . . )
(. . . Continued)
Risk Risk
Total (95% CI) 502 485 100.0 % 0.00 [ -0.02, 0.01 ]
-0.5 -0.25 0 0.25 0.5

2 Intra-operative complications.
Risk Risk
Chaudhary 1999 0/21 0/22 2.3 % 0.0 [ -0.09, 0.09 ]
Ortega 1996 0/10 0/10 1.0 % 0.0 [ -0.17, 0.17 ]
Subtotal (95% CI) 31 32 3.3 % 0.0 [ -0.09, 0.09 ]

Agnifili 1993 0/29 0/21 2.6 % 0.0 [ -0.08, 0.08 ]
Bellon 1998 0/14 0/14 1.5 % 0.0 [ -0.13, 0.13 ]
Berggren 1994 0/15 0/12 1.4 % 0.0 [ -0.13, 0.13 ]
-0.5 -0.25 0 0.25 0.5

(Continued . . . )
(. . . Continued)
Risk Risk
Charlo 1995 0/100 0/100 10.5 % 0.0 [ -0.02, 0.02 ]
Chumillas 1998 0/20 0/20 2.1 % 0.0 [ -0.09, 0.09 ]
Coelho 1993 0/15 0/15 1.6 % 0.0 [ -0.12, 0.12 ]
Coskun 2000 0/35 0/35 3.7 % 0.0 [ -0.05, 0.05 ]
Dauleh 1995 0/40 0/38 4.1 % 0.0 [ -0.05, 0.05 ]
Demirer 2000 0/50 0/50 5.2 % 0.0 [ -0.04, 0.04 ]
Dionigi 1994 0/30 0/27 3.0 % 0.0 [ -0.07, 0.07 ]
Engin 1998 0/16 0/16 1.7 % 0.0 [ -0.11, 0.11 ]
Essen 1995 0/6 0/6 0.6 % 0.0 [ -0.27, 0.27 ]
Gal 1997 0/21 0/21 2.2 % 0.0 [ -0.09, 0.09 ]
Galizia 2001 2/10 0/5 0.7 % 0.20 [ -0.13, 0.53 ]
Hasukic 2002 0/30 0/28 3.0 % 0.0 [ -0.06, 0.06 ]
Hendolin 2000 0/25 0/22 2.5 % 0.0 [ -0.08, 0.08 ]
Huang 1996 0/15 0/12 1.4 % 0.0 [ -0.13, 0.13 ]
Jan 1993 1/50 0/51 5.3 % 0.02 [ -0.03, 0.07 ]
Karayiannakis 1997 0/45 0/42 4.6 % 0.0 [ -0.04, 0.04 ]
Lausten 1999 (1) 0/7 0/7 0.7 % 0.0 [ -0.24, 0.24 ]
Lausten 1999 (2) 0/7 0/7 0.7 % 0.0 [ -0.24, 0.24 ]
Lujan 1998 0/133 0/131 13.8 % 0.0 [ -0.01, 0.01 ]
Milheiro 1994 0/20 0/20 2.1 % 0.0 [ -0.09, 0.09 ]
Mimica 2000 0/50 0/50 5.2 % 0.0 [ -0.04, 0.04 ]
Prisco 2000 0/10 0/10 1.0 % 0.0 [ -0.17, 0.17 ]
Trondsen 1993 6/35 1/35 3.7 % 0.14 [ 0.01, 0.28 ]
Volpino 1998 0/58 0/60 6.2 % 0.0 [ -0.03, 0.03 ]
Zajac 1998 0/58 0/52 5.7 % 0.0 [ -0.03, 0.03 ]
Subtotal (95% CI) 944 907 96.7 % 0.01 [ 0.00, 0.02 ]

Total (95% CI) 975 939 100.0 % 0.01 [ 0.00, 0.02 ]
-0.5 -0.25 0 0.25 0.5

3 Minor complications.
Risk Risk
Chaudhary 1999 0/21 1/22 2.3 % -0.05 [ -0.16, 0.07 ]
Ortega 1996 0/10 0/10 1.0 % 0.0 [ -0.17, 0.17 ]
Subtotal (95% CI) 31 32 3.3 % -0.03 [ -0.14, 0.07 ]

Agnifili 1993 0/29 0/21 2.6 % 0.0 [ -0.08, 0.08 ]
Bellon 1998 0/14 0/14 1.5 % 0.0 [ -0.13, 0.13 ]
Berggren 1994 1/15 0/12 1.4 % 0.07 [ -0.11, 0.24 ]
Charlo 1995 4/100 4/100 10.5 % 0.0 [ -0.05, 0.05 ]
Chumillas 1998 0/20 0/20 2.1 % 0.0 [ -0.09, 0.09 ]
Coelho 1993 0/15 1/15 1.6 % -0.07 [ -0.23, 0.10 ]
Coskun 2000 0/35 0/35 3.7 % 0.0 [ -0.05, 0.05 ]
Dauleh 1995 0/40 0/38 4.1 % 0.0 [ -0.05, 0.05 ]
Demirer 2000 0/50 0/50 5.2 % 0.0 [ -0.04, 0.04 ]
Dionigi 1994 0/30 1/27 3.0 % -0.04 [ -0.13, 0.06 ]
Engin 1998 0/16 0/16 1.7 % 0.0 [ -0.11, 0.11 ]
Essen 1995 0/6 0/6 0.6 % 0.0 [ -0.27, 0.27 ]
Gal 1997 0/21 0/21 2.2 % 0.0 [ -0.09, 0.09 ]
Galizia 2001 0/10 0/5 0.7 % 0.0 [ -0.25, 0.25 ]
Hasukic 2002 0/30 0/28 3.0 % 0.0 [ -0.06, 0.06 ]
-0.5 -0.25 0 0.25 0.5

(Continued . . . )
(. . . Continued)
Risk Risk
Hendolin 2000 0/25 2/22 2.5 % -0.09 [ -0.23, 0.05 ]
Huang 1996 0/15 2/12 1.4 % -0.17 [ -0.40, 0.06 ]
Jan 1993 0/50 0/51 5.3 % 0.0 [ -0.04, 0.04 ]
Karayiannakis 1997 0/45 0/42 4.6 % 0.0 [ -0.04, 0.04 ]
Lausten 1999 (1) 0/7 0/7 0.7 % 0.0 [ -0.24, 0.24 ]
Lausten 1999 (2) 0/7 0/7 0.7 % 0.0 [ -0.24, 0.24 ]
Lujan 1998 13/133 15/131 13.8 % -0.02 [ -0.09, 0.06 ]
Milheiro 1994 1/20 2/20 2.1 % -0.05 [ -0.21, 0.11 ]
Mimica 2000 0/50 2/50 5.2 % -0.04 [ -0.11, 0.03 ]
Prisco 2000 0/10 0/10 1.0 % 0.0 [ -0.17, 0.17 ]
Trondsen 1993 4/35 5/35 3.7 % -0.03 [ -0.19, 0.13 ]
Volpino 1998 0/58 0/60 6.2 % 0.0 [ -0.03, 0.03 ]
Zajac 1998 0/58 0/52 5.7 % 0.0 [ -0.03, 0.03 ]
Subtotal (95% CI) 944 907 96.7 % -0.01 [ -0.03, 0.01 ]

Total (95% CI) 975 939 100.0 % -0.01 [ -0.03, 0.00 ]
-0.5 -0.25 0 0.25 0.5

4 Severe complications (without bile duct injuries).
Risk Risk
M- M-
n/N n/N CI CI
Chaudhary 1999 0/21 1/22 3.2 % -0.05 [ -0.16, 0.07 ]
Ortega 1996 0/10 0/10 1.9 % 0.0 [ -0.17, 0.17 ]
Subtotal (95% CI) 31 32 5.1 % -0.03 [ -0.13, 0.07 ]

Agnifili 1993 1/29 4/21 1.8 % -0.16 [ -0.34, 0.02 ]
Bellon 1998 0/14 0/14 2.9 % 0.0 [ -0.13, 0.13 ]
Berggren 1994 0/15 0/12 2.7 % 0.0 [ -0.13, 0.13 ]
Charlo 1995 8/100 12/100 4.4 % -0.04 [ -0.12, 0.04 ]
Chumillas 1998 0/20 1/20 2.9 % -0.05 [ -0.18, 0.08 ]
Coelho 1993 0/15 0/15 3.1 % 0.0 [ -0.12, 0.12 ]
Coskun 2000 0/35 10/35 2.3 % -0.29 [ -0.44, -0.13 ]
Dauleh 1995 0/40 0/38 5.8 % 0.0 [ -0.05, 0.05 ]
Demirer 2000 0/50 0/50 6.2 % 0.0 [ -0.04, 0.04 ]
Dionigi 1994 0/30 0/27 5.1 % 0.0 [ -0.07, 0.07 ]
Engin 1998 0/16 0/16 3.3 % 0.0 [ -0.11, 0.11 ]
Essen 1995 0/6 0/6 1.0 % 0.0 [ -0.27, 0.27 ]
Gal 1997 0/21 0/21 4.2 % 0.0 [ -0.09, 0.09 ]
Galizia 2001 0/10 1/5 0.6 % -0.20 [ -0.57, 0.17 ]
Hasukic 2002 0/30 6/28 2.2 % -0.21 [ -0.37, -0.06 ]
Hendolin 2000 1/25 0/22 3.5 % 0.04 [ -0.07, 0.15 ]
Huang 1996 0/15 0/12 2.7 % 0.0 [ -0.13, 0.13 ]
-0.5 -0.25 0 0.25 0.5

(Continued . . . )
(. . . Continued)
Risk Risk
M- M-
n/N n/N CI CI
Jan 1993 4/50 1/51 4.3 % 0.06 [ -0.02, 0.14 ]
Karayiannakis 1997 0/45 0/42 6.0 % 0.0 [ -0.04, 0.04 ]
Lausten 1999 (1) 1/7 0/7 0.7 % 0.14 [ -0.18, 0.46 ]
Lausten 1999 (2) 0/7 0/7 1.2 % 0.0 [ -0.24, 0.24 ]
Lujan 1998 5/133 16/131 5.1 % -0.08 [ -0.15, -0.02 ]
Milheiro 1994 0/20 0/20 4.0 % 0.0 [ -0.09, 0.09 ]
Mimica 2000 0/50 0/50 6.2 % 0.0 [ -0.04, 0.04 ]
Prisco 2000 0/10 0/10 1.9 % 0.0 [ -0.17, 0.17 ]
Trondsen 1993 3/35 1/35 3.5 % 0.06 [ -0.05, 0.17 ]
Volpino 1998 2/58 5/60 4.3 % -0.05 [ -0.13, 0.04 ]
Zajac 1998 0/58 14/52 3.1 % -0.27 [ -0.39, -0.15 ]
Subtotal (95% CI) 944 907 94.9 % -0.03 [ -0.06, 0.00 ]

Total (95% CI) 975 939 100.0 % -0.03 [ -0.06, 0.00 ]
-0.5 -0.25 0 0.25 0.5

5 Bile duct injuries.
Risk Risk
Chaudhary 1999 0/21 0/22 2.3 % 0.0 [ -0.09, 0.09 ]
Ortega 1996 0/10 0/10 1.0 % 0.0 [ -0.17, 0.17 ]
Subtotal (95% CI) 31 32 3.3 % 0.0 [ -0.09, 0.09 ]

Agnifili 1993 0/29 0/21 2.6 % 0.0 [ -0.08, 0.08 ]
Bellon 1998 0/14 0/14 1.5 % 0.0 [ -0.13, 0.13 ]
Berggren 1994 0/15 0/12 1.4 % 0.0 [ -0.13, 0.13 ]
Charlo 1995 1/100 0/100 10.5 % 0.01 [ -0.02, 0.04 ]
Chumillas 1998 0/20 0/20 2.1 % 0.0 [ -0.09, 0.09 ]
Coelho 1993 0/15 0/15 1.6 % 0.0 [ -0.12, 0.12 ]
Coskun 2000 0/35 0/35 3.7 % 0.0 [ -0.05, 0.05 ]
Dauleh 1995 0/40 0/38 4.1 % 0.0 [ -0.05, 0.05 ]
Demirer 2000 0/50 0/50 5.2 % 0.0 [ -0.04, 0.04 ]
Dionigi 1994 0/30 0/27 3.0 % 0.0 [ -0.07, 0.07 ]
Engin 1998 0/16 0/16 1.7 % 0.0 [ -0.11, 0.11 ]
Essen 1995 0/6 0/6 0.6 % 0.0 [ -0.27, 0.27 ]
Gal 1997 0/21 0/21 2.2 % 0.0 [ -0.09, 0.09 ]
Galizia 2001 0/10 0/5 0.7 % 0.0 [ -0.25, 0.25 ]
Hasukic 2002 0/30 0/28 3.0 % 0.0 [ -0.06, 0.06 ]
Hendolin 2000 0/25 0/22 2.5 % 0.0 [ -0.08, 0.08 ]
Huang 1996 0/15 1/12 1.4 % -0.08 [ -0.28, 0.11 ]
Jan 1993 0/50 0/51 5.3 % 0.0 [ -0.04, 0.04 ]
-0.5 -0.25 0 0.25 0.5

(Continued . . . )
(. . . Continued)
Risk Risk
Karayiannakis 1997 0/45 0/42 4.6 % 0.0 [ -0.04, 0.04 ]
Lausten 1999 (1) 0/7 0/7 0.7 % 0.0 [ -0.24, 0.24 ]
Lausten 1999 (2) 0/7 0/7 0.7 % 0.0 [ -0.24, 0.24 ]
Lujan 1998 0/133 0/131 13.8 % 0.0 [ -0.01, 0.01 ]
Milheiro 1994 0/20 0/20 2.1 % 0.0 [ -0.09, 0.09 ]
Mimica 2000 0/50 0/50 5.2 % 0.0 [ -0.04, 0.04 ]
Prisco 2000 0/10 0/10 1.0 % 0.0 [ -0.17, 0.17 ]
Trondsen 1993 1/35 1/35 3.7 % 0.0 [ -0.08, 0.08 ]
Volpino 1998 0/58 0/60 6.2 % 0.0 [ -0.03, 0.03 ]
Zajac 1998 0/58 0/52 5.7 % 0.0 [ -0.03, 0.03 ]
Subtotal (95% CI) 944 907 96.7 % 0.00 [ -0.01, 0.01 ]

Total (95% CI) 975 939 100.0 % 0.00 [ -0.01, 0.01 ]
-0.5 -0.25 0 0.25 0.5

6 Total complications.
Risk Risk
M- M-
n/N n/N CI CI
Chaudhary 1999 0/21 2/22 3.0 % -0.09 [ -0.23, 0.05 ]
Ortega 1996 0/10 0/10 2.3 % 0.0 [ -0.17, 0.17 ]
Subtotal (95% CI) 31 32 5.4 % -0.05 [ -0.16, 0.06 ]

Agnifili 1993 1/29 4/21 2.2 % -0.16 [ -0.34, 0.02 ]
Bellon 1998 0/14 0/14 3.4 % 0.0 [ -0.13, 0.13 ]
Berggren 1994 1/15 0/12 2.3 % 0.07 [ -0.11, 0.24 ]
Charlo 1995 13/100 16/100 4.4 % -0.03 [ -0.13, 0.07 ]
Chumillas 1998 0/20 1/20 3.4 % -0.05 [ -0.18, 0.08 ]
Coelho 1993 0/15 1/15 2.5 % -0.07 [ -0.23, 0.10 ]
Coskun 2000 0/35 10/35 2.8 % -0.29 [ -0.44, -0.13 ]
Dauleh 1995 0/40 0/38 6.3 % 0.0 [ -0.05, 0.05 ]
Demirer 2000 0/50 0/50 6.7 % 0.0 [ -0.04, 0.04 ]
Dionigi 1994 0/30 1/27 4.5 % -0.04 [ -0.13, 0.06 ]
Engin 1998 0/16 0/16 3.8 % 0.0 [ -0.11, 0.11 ]
Essen 1995 0/6 0/6 1.2 % 0.0 [ -0.27, 0.27 ]
Gal 1997 0/21 0/21 4.8 % 0.0 [ -0.09, 0.09 ]
Galizia 2001 2/10 1/5 0.5 % 0.0 [ -0.43, 0.43 ]
Hasukic 2002 0/30 6/28 2.7 % -0.21 [ -0.37, -0.06 ]
Hendolin 2000 1/25 2/22 3.0 % -0.05 [ -0.19, 0.09 ]
Huang 1996 0/15 3/12 1.3 % -0.25 [ -0.51, 0.01 ]
-0.5 -0.25 0 0.25 0.5

(Continued . . . )
(. . . Continued)
Risk Risk
M- M-
n/N n/N CI CI
Jan 1993 5/50 1/51 4.6 % 0.08 [ -0.01, 0.17 ]
Karayiannakis 1997 0/45 0/42 6.5 % 0.0 [ -0.04, 0.04 ]
Lausten 1999 (1) 1/7 0/7 0.9 % 0.14 [ -0.18, 0.46 ]
Lausten 1999 (2) 0/7 0/7 1.5 % 0.0 [ -0.24, 0.24 ]
Lujan 1998 18/133 31/131 4.6 % -0.10 [ -0.19, -0.01 ]
Milheiro 1994 1/20 2/20 2.6 % -0.05 [ -0.21, 0.11 ]
Mimica 2000 0/50 2/50 5.7 % -0.04 [ -0.11, 0.03 ]
Prisco 2000 0/10 0/10 2.3 % 0.0 [ -0.17, 0.17 ]
Trondsen 1993 14/35 8/35 1.7 % 0.17 [ -0.04, 0.39 ]
Volpino 1998 2/58 5/60 4.9 % -0.05 [ -0.13, 0.04 ]
Zajac 1998 0/58 14/52 3.6 % -0.27 [ -0.39, -0.15 ]
Subtotal (95% CI) 944 907 94.6 % -0.04 [ -0.07, -0.01 ]

Total (95% CI) 975 939 100.0 % -0.04 [ -0.07, -0.01 ]
-0.5 -0.25 0 0.25 0.5

7 Operative time (minutes).
Mean Mean
Ortega 1996 10 70 (6) 10 77 (6.3) 4.6 % -7.00 [ -12.39, -1.61 ]
Subtotal (95% CI) 10 10 4.6 % -7.00 [ -12.39, -1.61 ]

Agnifili 1993 29 43.2 (16) 21 53.3 (19.1) 4.4 % -10.10 [ -20.13, -0.07 ]
Berggren 1994 15 87 (24.33) 12 69.17 (11.25) 4.2 % 17.83 [ 3.97, 31.69 ]
Blanc-Louvry 2000 25 61 (20) 16 74 (20) 4.3 % -13.00 [ -25.55, -0.45 ]
Bukan 2004 15 55 (15.4) 15 73 (24.3) 4.1 % -18.00 [ -32.56, -3.44 ]
Chumillas 1998 20 104 (34.39) 20 111.75 (30.57) 3.7 % -7.75 [ -27.92, 12.42 ]
Dionigi 1994 30 89 (29) 27 78 (20) 4.3 % 11.00 [ -1.83, 23.83 ]
Engin 1998 16 82.4 (26.64) 16 79.5 (31.23) 3.8 % 2.90 [ -17.21, 23.01 ]
Essen 1995 6 87 (36) 6 79 (22) 2.7 % 8.00 [ -25.76, 41.76 ]
Galizia 2001 10 68 (14.7) 5 60 (3.6) 4.4 % 8.00 [ -1.64, 17.64 ]
Hasukic 2002 30 77.83 (12.01) 28 71.48 (8.26) 4.6 % 6.35 [ 1.07, 11.63 ]
Huang 1996 15 93.3 (25.3) 12 176.3 (26.1) 3.8 % -83.00 [ -102.54, -63.46 ]
Jan 1993 50 85.7 (25.2) 51 48 (13.9) 4.5 % 37.70 [ 29.74, 45.66 ]
Karayiannakis 1997 45 105 (25) 42 98 (17) 4.5 % 7.00 [ -1.93, 15.93 ]
Lausten 1999 (1) 7 121 (14) 7 129 (23) 3.8 % -8.00 [ -27.95, 11.95 ]
Lausten 1999 (2) 7 122 (12) 7 90 (7) 4.4 % 32.00 [ 21.71, 42.29 ]
Milheiro 1994 20 60 (21) 20 88 (15) 4.4 % -28.00 [ -39.31, -16.69 ]
Mimica 2000 50 102 (20) 50 110 (32) 4.4 % -8.00 [ -18.46, 2.46 ]
Prisco 2000 10 115 (22) 10 105 (19) 3.9 % 10.00 [ -8.02, 28.02 ]
Putensen-Himmer 1992 10 104 (25) 10 112 (37) 3.2 % -8.00 [ -35.68, 19.68 ]
Rovina 1996 26 155 (27) 25 46 (13) 4.3 % 109.00 [ 97.44, 120.56 ]
-100 -50 0 50 100

(Continued . . . )
(. . . Continued)
Mean Mean
Volpino 1998 58 86.6 (22) 60 81 (24.79) 4.5 % 5.60 [ -2.85, 14.05 ]
Zajac 1998 58 54 (5) 52 47 (4) 4.7 % 7.00 [ 5.32, 8.68 ]
Zulfikaroglu 2002 25 69.2 (17.2) 25 66.8 (16.8) 4.5 % 2.40 [ -7.02, 11.82 ]
Subtotal (95% CI) 577 537 95.4 % 4.25 [ -5.03, 13.53 ]

Total (95% CI) 587 547 100.0 % 3.79 [ -4.88, 12.46 ]
-100 -50 0 50 100

8 Hospital stay (days).
Mean Mean
Ortega 1996 10 1.2 (0.2) 10 1.1 (0.1) 5.0 % 0.10 [ -0.04, 0.24 ]
Subtotal (95% CI) 10 10 5.0 % 0.10 [ -0.04, 0.24 ]

Agnifili 1993 29 3.2 (1.2) 21 7.3 (3.2) 4.4 % -4.10 [ -5.54, -2.66 ]
Berggren 1994 15 1.8 (0.56) 12 2.83 (0.84) 4.9 % -1.03 [ -1.58, -0.48 ]
Blanc-Louvry 2000 25 2.5 (1) 16 4.6 (1.2) 4.9 % -2.10 [ -2.81, -1.39 ]
Bukan 2004 15 2 (0.2) 15 5 (0.4) 5.0 % -3.00 [ -3.23, -2.77 ]
Charlo 1995 100 3 (1.01) 100 7 (2.63) 4.9 % -4.00 [ -4.55, -3.45 ]
Chumillas 1998 20 3.25 (0.71) 20 10.57 (4.67) 3.8 % -7.32 [ -9.39, -5.25 ]
Dionigi 1994 30 3.1 (0.5) 27 7.1 (1.6) 4.9 % -4.00 [ -4.63, -3.37 ]
Engin 1998 16 1.68 (0.6) 16 3.06 (0.77) 5.0 % -1.38 [ -1.86, -0.90 ]
Essen 1995 6 1.3 (0.5) 6 2.5 (0.6) 4.9 % -1.20 [ -1.82, -0.58 ]
Galizia 2001 10 1 (0.01) 5 5.2 (2.2) 3.9 % -4.20 [ -6.13, -2.27 ]
Huang 1996 15 3.93 (1.71) 12 7.92 (0.79) 4.7 % -3.99 [ -4.96, -3.02 ]
Jan 1993 50 4.5 (1.4) 51 5.6 (1.3) 4.9 % -1.10 [ -1.63, -0.57 ]
Karayiannakis 1997 45 2 (0.6) 42 5.6 (1.1) 5.0 % -3.60 [ -3.98, -3.22 ]
Kjaersgaard 1994 35 2.5 (1.61) 35 4.9 (4.25) 4.3 % -2.40 [ -3.91, -0.89 ]
Lausten 1999 (1) 7 2.9 (0.3) 7 5.3 (0.3) 5.0 % -2.40 [ -2.71, -2.09 ]
Lausten 1999 (2) 7 2.7 (0.3) 7 4.6 (0.2) 5.0 % -1.90 [ -2.17, -1.63 ]
Luo 2003 14 3.2 (1.12) 12 6.7 (0.69) 4.9 % -3.50 [ -4.20, -2.80 ]
Prisco 2000 10 2 (0.01) 10 5.6 (0.52) 5.0 % -3.60 [ -3.92, -3.28 ]
Volpino 1998 58 4.6 (2.9) 60 7.77 (3.1) 4.6 % -3.17 [ -4.25, -2.09 ]
Zajac 1998 58 1 (0.01) 52 9.1 (2.8) 4.8 % -8.10 [ -8.86, -7.34 ]
-10 -5 0 5 10
(Continued . . . )
(. . . Continued)
Mean Mean
Subtotal (95% CI) 565 526 95.0 % -3.19 [ -3.77, -2.61 ]
Total (95% CI) 575 536 100.0 % -3.07 [ -3.89, -2.26 ]
-10 -5 0 5 10
9 Convalescence: work leave (days).
Mean Mean
Subtotal (95% CI) 0 0 Not estimable
Test for overall effect: not applicable
Berggren 1994 15 11.7 (4.1) 12 24 (4.4) 33.6 % -12.30 [ -15.54, -9.06 ]
Charlo 1995 100 10 (1.57) 100 42 (3.23) 34.2 % -32.00 [ -32.70, -31.30 ]
Jan 1993 50 12.8 (8.8) 51 35.9 (20.6) 32.2 % -23.10 [ -29.26, -16.94 ]
Subtotal (95% CI) 165 163 100.0 % -22.51 [ -36.89, -8.13 ]

Total (95% CI) 165 163 100.0 % -22.51 [ -36.89, -8.13 ]
-100 -50 0 50 100

Favours LC Favours SIC
Analysis 4.1. Comparison 4 LC versus OC - high-quality and low-quality trials regarding follow-up, Outcome
1 Mortality.
Comparison: 4 LC versus OC - high-quality and low-quality trials regarding follow-up
Risk Risk
Jan 1993 0/50 0/51 10.7 % 0.0 [ -0.04, 0.04 ]
Subtotal (95% CI) 50 51 10.7 % 0.0 [ -0.04, 0.04 ]

Agnifili 1993 0/29 0/21 5.2 % 0.0 [ -0.08, 0.08 ]
Bellon 1998 0/14 0/14 3.0 % 0.0 [ -0.13, 0.13 ]
Berggren 1994 0/15 0/12 2.8 % 0.0 [ -0.13, 0.13 ]
Charlo 1995 0/100 0/100 21.2 % 0.0 [ -0.02, 0.02 ]
Chumillas 1998 0/20 0/20 4.2 % 0.0 [ -0.09, 0.09 ]
Engin 1998 0/16 0/16 3.4 % 0.0 [ -0.11, 0.11 ]
Gal 1997 0/1 0/1 0.2 % 0.0 [ -0.85, 0.85 ]
Galizia 2001 0/10 0/5 1.4 % 0.0 [ -0.25, 0.25 ]
Lausten 1999 (1) 0/7 0/7 1.5 % 0.0 [ -0.24, 0.24 ]
Lausten 1999 (2) 0/7 0/7 1.5 % 0.0 [ -0.24, 0.24 ]
Lujan 1998 0/133 1/131 28.0 % -0.01 [ -0.03, 0.01 ]
Milheiro 1994 0/20 0/20 4.2 % 0.0 [ -0.09, 0.09 ]
Mimica 2000 0/50 0/50 10.6 % 0.0 [ -0.04, 0.04 ]
Prisco 2000 0/10 0/10 2.1 % 0.0 [ -0.17, 0.17 ]
Subtotal (95% CI) 432 414 89.3 % 0.00 [ -0.02, 0.02 ]
-0.5 -0.25 0 0.25 0.5

(Continued . . . )
(. . . Continued)
Risk Risk
Total (95% CI) 482 465 100.0 % 0.00 [ -0.02, 0.01 ]
-0.5 -0.25 0 0.25 0.5

2 Intra-operative complications.
Risk Risk
Chaudhary 1999 0/21 0/22 2.3 % 0.0 [ -0.09, 0.09 ]
Demirer 2000 0/50 0/50 5.2 % 0.0 [ -0.04, 0.04 ]
Jan 1993 1/50 0/51 5.3 % 0.02 [ -0.03, 0.07 ]
Karayiannakis 1997 0/45 0/42 4.6 % 0.0 [ -0.04, 0.04 ]
Subtotal (95% CI) 166 165 17.3 % 0.01 [ -0.02, 0.03 ]

Agnifili 1993 0/29 0/21 2.6 % 0.0 [ -0.08, 0.08 ]
-0.5 -0.25 0 0.25 0.5

(Continued . . . )
(. . . Continued)
Risk Risk
Bellon 1998 0/14 0/14 1.5 % 0.0 [ -0.13, 0.13 ]
Berggren 1994 0/15 0/12 1.4 % 0.0 [ -0.13, 0.13 ]
Charlo 1995 0/100 0/100 10.5 % 0.0 [ -0.02, 0.02 ]
Chumillas 1998 0/20 0/20 2.1 % 0.0 [ -0.09, 0.09 ]
Coelho 1993 0/15 0/15 1.6 % 0.0 [ -0.12, 0.12 ]
Coskun 2000 0/35 0/35 3.7 % 0.0 [ -0.05, 0.05 ]
Dauleh 1995 0/40 0/38 4.1 % 0.0 [ -0.05, 0.05 ]
Dionigi 1994 0/30 0/27 3.0 % 0.0 [ -0.07, 0.07 ]
Engin 1998 0/16 0/16 1.7 % 0.0 [ -0.11, 0.11 ]
Essen 1995 0/6 0/6 0.6 % 0.0 [ -0.27, 0.27 ]
Gal 1997 0/21 0/21 2.2 % 0.0 [ -0.09, 0.09 ]
Galizia 2001 2/10 0/5 0.7 % 0.20 [ -0.13, 0.53 ]
Hasukic 2002 0/30 0/28 3.0 % 0.0 [ -0.06, 0.06 ]
Hendolin 2000 0/25 0/22 2.5 % 0.0 [ -0.08, 0.08 ]
Huang 1996 0/15 0/12 1.4 % 0.0 [ -0.13, 0.13 ]
Lausten 1999 (1) 0/7 0/7 0.7 % 0.0 [ -0.24, 0.24 ]
Lausten 1999 (2) 0/7 0/7 0.7 % 0.0 [ -0.24, 0.24 ]
Lujan 1998 0/133 0/131 13.8 % 0.0 [ -0.01, 0.01 ]
Milheiro 1994 0/20 0/20 2.1 % 0.0 [ -0.09, 0.09 ]
Mimica 2000 0/50 0/50 5.2 % 0.0 [ -0.04, 0.04 ]
Ortega 1996 0/10 0/10 1.0 % 0.0 [ -0.17, 0.17 ]
Prisco 2000 0/10 0/10 1.0 % 0.0 [ -0.17, 0.17 ]
Trondsen 1993 6/35 1/35 3.7 % 0.14 [ 0.01, 0.28 ]
Volpino 1998 0/58 0/60 6.2 % 0.0 [ -0.03, 0.03 ]
Zajac 1998 0/58 0/52 5.7 % 0.0 [ -0.03, 0.03 ]
Subtotal (95% CI) 809 774 82.7 % 0.01 [ -0.01, 0.02 ]

Total (95% CI) 975 939 100.0 % 0.01 [ 0.00, 0.02 ]
-0.5 -0.25 0 0.25 0.5

3 Minor complications.
Risk Risk
Chaudhary 1999 0/21 1/22 2.3 % -0.05 [ -0.16, 0.07 ]
Demirer 2000 0/50 0/50 5.2 % 0.0 [ -0.04, 0.04 ]
Jan 1993 0/50 0/51 5.3 % 0.0 [ -0.04, 0.04 ]
Karayiannakis 1997 0/45 0/42 4.6 % 0.0 [ -0.04, 0.04 ]
Subtotal (95% CI) 166 165 17.3 % -0.01 [ -0.03, 0.02 ]

Agnifili 1993 0/29 0/21 2.6 % 0.0 [ -0.08, 0.08 ]
Bellon 1998 0/14 0/14 1.5 % 0.0 [ -0.13, 0.13 ]
Berggren 1994 1/15 0/12 1.4 % 0.07 [ -0.11, 0.24 ]
Charlo 1995 4/100 4/100 10.5 % 0.0 [ -0.05, 0.05 ]
Chumillas 1998 0/20 0/20 2.1 % 0.0 [ -0.09, 0.09 ]
Coelho 1993 0/15 1/15 1.6 % -0.07 [ -0.23, 0.10 ]
Coskun 2000 0/35 0/35 3.7 % 0.0 [ -0.05, 0.05 ]
Dauleh 1995 0/40 0/38 4.1 % 0.0 [ -0.05, 0.05 ]
Dionigi 1994 0/30 1/27 3.0 % -0.04 [ -0.13, 0.06 ]
Engin 1998 0/16 0/16 1.7 % 0.0 [ -0.11, 0.11 ]
Essen 1995 0/6 0/6 0.6 % 0.0 [ -0.27, 0.27 ]
Gal 1997 0/21 0/21 2.2 % 0.0 [ -0.09, 0.09 ]
Galizia 2001 0/10 0/5 0.7 % 0.0 [ -0.25, 0.25 ]
-0.5 -0.25 0 0.25 0.5

(Continued . . . )
(. . . Continued)
Risk Risk
Hasukic 2002 0/30 0/28 3.0 % 0.0 [ -0.06, 0.06 ]
Hendolin 2000 0/25 2/22 2.5 % -0.09 [ -0.23, 0.05 ]
Huang 1996 0/15 2/12 1.4 % -0.17 [ -0.40, 0.06 ]
Lausten 1999 (1) 0/7 0/7 0.7 % 0.0 [ -0.24, 0.24 ]
Lausten 1999 (2) 0/7 0/7 0.7 % 0.0 [ -0.24, 0.24 ]
Lujan 1998 13/133 15/131 13.8 % -0.02 [ -0.09, 0.06 ]
Milheiro 1994 1/20 2/20 2.1 % -0.05 [ -0.21, 0.11 ]
Mimica 2000 0/50 2/50 5.2 % -0.04 [ -0.11, 0.03 ]
Ortega 1996 0/10 0/10 1.0 % 0.0 [ -0.17, 0.17 ]
Prisco 2000 0/10 0/10 1.0 % 0.0 [ -0.17, 0.17 ]
Trondsen 1993 4/35 5/35 3.7 % -0.03 [ -0.19, 0.13 ]
Volpino 1998 0/58 0/60 6.2 % 0.0 [ -0.03, 0.03 ]
Zajac 1998 0/58 0/52 5.7 % 0.0 [ -0.03, 0.03 ]
Subtotal (95% CI) 809 774 82.7 % -0.01 [ -0.04, 0.01 ]

Total (95% CI) 975 939 100.0 % -0.01 [ -0.03, 0.00 ]
-0.5 -0.25 0 0.25 0.5

4 Severe complications (without bile duct injuries).
Risk Risk
M- M-
n/N n/N CI CI
Chaudhary 1999 0/21 1/22 3.2 % -0.05 [ -0.16, 0.07 ]
Demirer 2000 0/50 0/50 6.2 % 0.0 [ -0.04, 0.04 ]
Jan 1993 4/50 1/51 4.3 % 0.06 [ -0.02, 0.14 ]
Karayiannakis 1997 0/45 0/42 6.0 % 0.0 [ -0.04, 0.04 ]
Subtotal (95% CI) 166 165 19.6 % 0.00 [ -0.02, 0.03 ]

Agnifili 1993 1/29 4/21 1.8 % -0.16 [ -0.34, 0.02 ]
Bellon 1998 0/14 0/14 2.9 % 0.0 [ -0.13, 0.13 ]
Berggren 1994 0/15 0/12 2.7 % 0.0 [ -0.13, 0.13 ]
Charlo 1995 8/100 12/100 4.4 % -0.04 [ -0.12, 0.04 ]
Chumillas 1998 0/20 1/20 2.9 % -0.05 [ -0.18, 0.08 ]
Coelho 1993 0/15 0/15 3.1 % 0.0 [ -0.12, 0.12 ]
Coskun 2000 0/35 10/35 2.3 % -0.29 [ -0.44, -0.13 ]
Dauleh 1995 0/40 0/38 5.8 % 0.0 [ -0.05, 0.05 ]
Dionigi 1994 0/30 0/27 5.1 % 0.0 [ -0.07, 0.07 ]
Engin 1998 0/16 0/16 3.3 % 0.0 [ -0.11, 0.11 ]
Essen 1995 0/6 0/6 1.0 % 0.0 [ -0.27, 0.27 ]
Gal 1997 0/21 0/21 4.2 % 0.0 [ -0.09, 0.09 ]
Galizia 2001 0/10 1/5 0.6 % -0.20 [ -0.57, 0.17 ]
Hasukic 2002 0/30 6/28 2.2 % -0.21 [ -0.37, -0.06 ]
Hendolin 2000 1/25 0/22 3.5 % 0.04 [ -0.07, 0.15 ]
-0.5 -0.25 0 0.25 0.5

(Continued . . . )
(. . . Continued)
Risk Risk
M- M-
n/N n/N CI CI
Huang 1996 0/15 0/12 2.7 % 0.0 [ -0.13, 0.13 ]
Lausten 1999 (1) 1/7 0/7 0.7 % 0.14 [ -0.18, 0.46 ]
Lausten 1999 (2) 0/7 0/7 1.2 % 0.0 [ -0.24, 0.24 ]
Lujan 1998 5/133 16/131 5.1 % -0.08 [ -0.15, -0.02 ]
Milheiro 1994 0/20 0/20 4.0 % 0.0 [ -0.09, 0.09 ]
Mimica 2000 0/50 0/50 6.2 % 0.0 [ -0.04, 0.04 ]
Ortega 1996 0/10 0/10 1.9 % 0.0 [ -0.17, 0.17 ]
Prisco 2000 0/10 0/10 1.9 % 0.0 [ -0.17, 0.17 ]
Trondsen 1993 3/35 1/35 3.5 % 0.06 [ -0.05, 0.17 ]
Volpino 1998 2/58 5/60 4.3 % -0.05 [ -0.13, 0.04 ]
Zajac 1998 0/58 14/52 3.1 % -0.27 [ -0.39, -0.15 ]
Subtotal (95% CI) 809 774 80.4 % -0.04 [ -0.07, 0.00 ]

Total (95% CI) 975 939 100.0 % -0.03 [ -0.06, 0.00 ]
-0.5 -0.25 0 0.25 0.5

5 Bile duct injuries.
Risk Risk
Chaudhary 1999 0/21 0/22 2.3 % 0.0 [ -0.09, 0.09 ]
Demirer 2000 0/50 0/50 5.2 % 0.0 [ -0.04, 0.04 ]
Jan 1993 0/50 0/51 5.3 % 0.0 [ -0.04, 0.04 ]
Karayiannakis 1997 0/45 0/42 4.6 % 0.0 [ -0.04, 0.04 ]
Subtotal (95% CI) 166 165 17.3 % 0.0 [ -0.02, 0.02 ]

Agnifili 1993 0/29 0/21 2.6 % 0.0 [ -0.08, 0.08 ]
Bellon 1998 0/14 0/14 1.5 % 0.0 [ -0.13, 0.13 ]
Berggren 1994 0/15 0/12 1.4 % 0.0 [ -0.13, 0.13 ]
Charlo 1995 1/100 0/100 10.5 % 0.01 [ -0.02, 0.04 ]
Chumillas 1998 0/20 0/20 2.1 % 0.0 [ -0.09, 0.09 ]
Coelho 1993 0/15 0/15 1.6 % 0.0 [ -0.12, 0.12 ]
Coskun 2000 0/35 0/35 3.7 % 0.0 [ -0.05, 0.05 ]
Dauleh 1995 0/40 0/38 4.1 % 0.0 [ -0.05, 0.05 ]
Dionigi 1994 0/30 0/27 3.0 % 0.0 [ -0.07, 0.07 ]
Engin 1998 0/16 0/16 1.7 % 0.0 [ -0.11, 0.11 ]
Essen 1995 0/6 0/6 0.6 % 0.0 [ -0.27, 0.27 ]
Gal 1997 0/21 0/21 2.2 % 0.0 [ -0.09, 0.09 ]
Galizia 2001 0/10 0/5 0.7 % 0.0 [ -0.25, 0.25 ]
Hasukic 2002 0/30 0/28 3.0 % 0.0 [ -0.06, 0.06 ]
Hendolin 2000 0/25 0/22 2.5 % 0.0 [ -0.08, 0.08 ]
Huang 1996 0/15 1/12 1.4 % -0.08 [ -0.28, 0.11 ]
-0.5 -0.25 0 0.25 0.5

(Continued . . . )
(. . . Continued)
Risk Risk
Lausten 1999 (1) 0/7 0/7 0.7 % 0.0 [ -0.24, 0.24 ]
Lausten 1999 (2) 0/7 0/7 0.7 % 0.0 [ -0.24, 0.24 ]
Lujan 1998 0/133 0/131 13.8 % 0.0 [ -0.01, 0.01 ]
Milheiro 1994 0/20 0/20 2.1 % 0.0 [ -0.09, 0.09 ]
Mimica 2000 0/50 0/50 5.2 % 0.0 [ -0.04, 0.04 ]
Ortega 1996 0/10 0/10 1.0 % 0.0 [ -0.17, 0.17 ]
Prisco 2000 0/10 0/10 1.0 % 0.0 [ -0.17, 0.17 ]
Trondsen 1993 1/35 1/35 3.7 % 0.0 [ -0.08, 0.08 ]
Volpino 1998 0/58 0/60 6.2 % 0.0 [ -0.03, 0.03 ]
Zajac 1998 0/58 0/52 5.7 % 0.0 [ -0.03, 0.03 ]
Subtotal (95% CI) 809 774 82.7 % 0.00 [ -0.01, 0.01 ]

Total (95% CI) 975 939 100.0 % 0.00 [ -0.01, 0.01 ]
-0.5 -0.25 0 0.25 0.5

6 Total complications.
Risk Risk
M- M-
n/N n/N CI CI
Chaudhary 1999 0/21 2/22 3.0 % -0.09 [ -0.23, 0.05 ]
Demirer 2000 0/50 0/50 6.7 % 0.0 [ -0.04, 0.04 ]
Jan 1993 5/50 1/51 4.6 % 0.08 [ -0.01, 0.17 ]
Karayiannakis 1997 0/45 0/42 6.5 % 0.0 [ -0.04, 0.04 ]
Subtotal (95% CI) 166 165 20.9 % 0.01 [ -0.03, 0.05 ]

Agnifili 1993 1/29 4/21 2.2 % -0.16 [ -0.34, 0.02 ]
Bellon 1998 0/14 0/14 3.4 % 0.0 [ -0.13, 0.13 ]
Berggren 1994 1/15 0/12 2.3 % 0.07 [ -0.11, 0.24 ]
Charlo 1995 13/100 16/100 4.4 % -0.03 [ -0.13, 0.07 ]
Chumillas 1998 0/20 1/20 3.4 % -0.05 [ -0.18, 0.08 ]
Coelho 1993 0/15 1/15 2.5 % -0.07 [ -0.23, 0.10 ]
Coskun 2000 0/35 10/35 2.8 % -0.29 [ -0.44, -0.13 ]
Dauleh 1995 0/40 0/38 6.3 % 0.0 [ -0.05, 0.05 ]
Dionigi 1994 0/30 1/27 4.5 % -0.04 [ -0.13, 0.06 ]
Engin 1998 0/16 0/16 3.8 % 0.0 [ -0.11, 0.11 ]
Essen 1995 0/6 0/6 1.2 % 0.0 [ -0.27, 0.27 ]
Gal 1997 0/21 0/21 4.8 % 0.0 [ -0.09, 0.09 ]
Galizia 2001 2/10 1/5 0.5 % 0.0 [ -0.43, 0.43 ]
Hasukic 2002 0/30 6/28 2.7 % -0.21 [ -0.37, -0.06 ]
Hendolin 2000 1/25 2/22 3.0 % -0.05 [ -0.19, 0.09 ]
-0.5 -0.25 0 0.25 0.5

(Continued . . . )
(. . . Continued)
Risk Risk
M- M-
n/N n/N CI CI
Huang 1996 0/15 3/12 1.3 % -0.25 [ -0.51, 0.01 ]
Lausten 1999 (1) 1/7 0/7 0.9 % 0.14 [ -0.18, 0.46 ]
Lausten 1999 (2) 0/7 0/7 1.5 % 0.0 [ -0.24, 0.24 ]
Lujan 1998 18/133 31/131 4.6 % -0.10 [ -0.19, -0.01 ]
Milheiro 1994 1/20 2/20 2.6 % -0.05 [ -0.21, 0.11 ]
Mimica 2000 0/50 2/50 5.7 % -0.04 [ -0.11, 0.03 ]
Ortega 1996 0/10 0/10 2.3 % 0.0 [ -0.17, 0.17 ]
Prisco 2000 0/10 0/10 2.3 % 0.0 [ -0.17, 0.17 ]
Trondsen 1993 14/35 8/35 1.7 % 0.17 [ -0.04, 0.39 ]
Volpino 1998 2/58 5/60 4.9 % -0.05 [ -0.13, 0.04 ]
Zajac 1998 0/58 14/52 3.6 % -0.27 [ -0.39, -0.15 ]
Subtotal (95% CI) 809 774 79.1 % -0.05 [ -0.09, -0.02 ]

Total (95% CI) 975 939 100.0 % -0.04 [ -0.07, -0.01 ]
-0.5 -0.25 0 0.25 0.5

7 Operative time (minutes).
Mean Mean
Jan 1993 50 85.7 (25.2) 51 48 (13.9) 4.5 % 37.70 [ 29.74, 45.66 ]
Karayiannakis 1997 45 105 (25) 42 98 (17) 4.5 % 7.00 [ -1.93, 15.93 ]
Subtotal (95% CI) 95 93 9.0 % 22.42 [ -7.67, 52.50 ]

Agnifili 1993 29 43.2 (16) 21 53.3 (19.1) 4.4 % -10.10 [ -20.13, -0.07 ]
Berggren 1994 15 87 (24.33) 12 69.17 (11.25) 4.2 % 17.83 [ 3.97, 31.69 ]
Blanc-Louvry 2000 25 61 (20) 16 74 (20) 4.3 % -13.00 [ -25.55, -0.45 ]
Bukan 2004 15 55 (15.4) 15 73 (24.3) 4.1 % -18.00 [ -32.56, -3.44 ]
Chumillas 1998 20 104 (34.39) 20 111.75 (30.57) 3.7 % -7.75 [ -27.92, 12.42 ]
Dionigi 1994 30 89 (29) 27 78 (20) 4.3 % 11.00 [ -1.83, 23.83 ]
Engin 1998 16 82.4 (26.64) 16 79.5 (31.23) 3.8 % 2.90 [ -17.21, 23.01 ]
Essen 1995 6 87 (36) 6 79 (22) 2.7 % 8.00 [ -25.76, 41.76 ]
Galizia 2001 10 68 (14.7) 5 60 (3.6) 4.4 % 8.00 [ -1.64, 17.64 ]
Hasukic 2002 30 77.83 (12.01) 28 71.48 (8.26) 4.6 % 6.35 [ 1.07, 11.63 ]
Huang 1996 15 93.3 (25.3) 12 176.3 (26.1) 3.8 % -83.00 [ -102.54, -63.46 ]
Lausten 1999 (1) 7 121 (14) 7 129 (23) 3.8 % -8.00 [ -27.95, 11.95 ]
Lausten 1999 (2) 7 122 (12) 7 90 (7) 4.4 % 32.00 [ 21.71, 42.29 ]
Milheiro 1994 20 60 (21) 20 88 (15) 4.4 % -28.00 [ -39.31, -16.69 ]
Mimica 2000 50 102 (20) 50 110 (32) 4.4 % -8.00 [ -18.46, 2.46 ]
Ortega 1996 10 70 (6) 10 77 (6.3) 4.6 % -7.00 [ -12.39, -1.61 ]
Prisco 2000 10 115 (22) 10 105 (19) 3.9 % 10.00 [ -8.02, 28.02 ]
Putensen-Himmer 1992 10 104 (25) 10 112 (37) 3.2 % -8.00 [ -35.68, 19.68 ]
Rovina 1996 26 155 (27) 25 46 (13) 4.3 % 109.00 [ 97.44, 120.56 ]
-100 -50 0 50 100

(Continued . . . )
(. . . Continued)
Mean Mean
Volpino 1998 58 86.6 (22) 60 81 (24.79) 4.5 % 5.60 [ -2.85, 14.05 ]
Zajac 1998 58 54 (5) 52 47 (4) 4.7 % 7.00 [ 5.32, 8.68 ]
Zulfikaroglu 2002 25 69.2 (17.2) 25 66.8 (16.8) 4.5 % 2.40 [ -7.02, 11.82 ]
Subtotal (95% CI) 492 454 91.0 % 1.94 [ -7.19, 11.07 ]

Total (95% CI) 587 547 100.0 % 3.79 [ -4.88, 12.46 ]
-100 -50 0 50 100

8 Hospital stay (days).
Mean Mean
Jan 1993 50 4.5 (1.4) 51 5.6 (1.3) 4.9 % -1.10 [ -1.63, -0.57 ]
Karayiannakis 1997 45 2 (0.6) 42 5.6 (1.1) 5.0 % -3.60 [ -3.98, -3.22 ]
Kjaersgaard 1994 35 2.5 (1.61) 35 4.9 (4.25) 4.3 % -2.40 [ -3.91, -0.89 ]
Subtotal (95% CI) 130 128 14.2 % -2.37 [ -4.29, -0.45 ]

Agnifili 1993 29 3.2 (1.2) 21 7.3 (3.2) 4.4 % -4.10 [ -5.54, -2.66 ]
Berggren 1994 15 1.8 (0.56) 12 2.83 (0.84) 4.9 % -1.03 [ -1.58, -0.48 ]
Blanc-Louvry 2000 25 2.5 (1) 16 4.6 (1.2) 4.9 % -2.10 [ -2.81, -1.39 ]
Bukan 2004 15 2 (0.2) 15 5 (0.4) 5.0 % -3.00 [ -3.23, -2.77 ]
Charlo 1995 100 3 (1.01) 100 7 (2.63) 4.9 % -4.00 [ -4.55, -3.45 ]
Chumillas 1998 20 3.25 (0.71) 20 10.57 (4.67) 3.8 % -7.32 [ -9.39, -5.25 ]
Dionigi 1994 30 3.1 (0.5) 27 7.1 (1.6) 4.9 % -4.00 [ -4.63, -3.37 ]
Engin 1998 16 1.68 (0.6) 16 3.06 (0.77) 5.0 % -1.38 [ -1.86, -0.90 ]
Essen 1995 6 1.3 (0.5) 6 2.5 (0.6) 4.9 % -1.20 [ -1.82, -0.58 ]
Galizia 2001 10 1 (0.01) 5 5.2 (2.2) 3.9 % -4.20 [ -6.13, -2.27 ]
Huang 1996 15 3.93 (1.71) 12 7.92 (0.79) 4.7 % -3.99 [ -4.96, -3.02 ]
Lausten 1999 (1) 7 2.9 (0.3) 7 5.3 (0.3) 5.0 % -2.40 [ -2.71, -2.09 ]
Lausten 1999 (2) 7 2.7 (0.3) 7 4.6 (0.2) 5.0 % -1.90 [ -2.17, -1.63 ]
Luo 2003 14 3.2 (1.12) 12 6.7 (0.69) 4.9 % -3.50 [ -4.20, -2.80 ]
Ortega 1996 10 1.2 (0.2) 10 1.1 (0.1) 5.0 % 0.10 [ -0.04, 0.24 ]
Prisco 2000 10 2 (0.01) 10 5.6 (0.52) 5.0 % -3.60 [ -3.92, -3.28 ]
Volpino 1998 58 4.6 (2.9) 60 7.77 (3.1) 4.6 % -3.17 [ -4.25, -2.09 ]
Zajac 1998 58 1 (0.01) 52 9.1 (2.8) 4.8 % -8.10 [ -8.86, -7.34 ]
-10 -5 0 5 10
(Continued . . . )
(. . . Continued)
Mean Mean
Subtotal (95% CI) 445 408 85.8 % -3.19 [ -4.09, -2.29 ]
Total (95% CI) 575 536 100.0 % -3.07 [ -3.89, -2.26 ]
-10 -5 0 5 10
9 Convalescence: work leave (days).
Mean Mean
Jan 1993 50 12.8 (8.8) 51 35.9 (20.6) 32.2 % -23.10 [ -29.26, -16.94 ]
Subtotal (95% CI) 50 51 32.2 % -23.10 [ -29.26, -16.94 ]

Berggren 1994 15 11.7 (4.1) 12 24 (4.4) 33.6 % -12.30 [ -15.54, -9.06 ]
Charlo 1995 100 10 (1.57) 100 42 (3.23) 34.2 % -32.00 [ -32.70, -31.30 ]
Subtotal (95% CI) 115 112 67.8 % -22.22 [ -41.52, -2.91 ]

Total (95% CI) 165 163 100.0 % -22.51 [ -36.89, -8.13 ]
-100 -50 0 50 100

Analysis 5.1. Comparison 5 LC versus OC - sensitivity and subgroup analyses, Outcome 1 Sensitivity
analysis 1: Assuming zero mortality in non-reporting trials.
Comparison: 5 LC versus OC - sensitivity and subgroup analyses
Outcome: 1 Sensitivity analysis 1: Assuming zero mortality in non-reporting trials
Risk Risk
Agnifili 1993 0/29 0/21 2.1 % 0.0 [ -0.08, 0.08 ]
Bellon 1998 0/14 0/14 1.2 % 0.0 [ -0.13, 0.13 ]
Berggren 1994 0/15 0/12 1.2 % 0.0 [ -0.13, 0.13 ]
Blanc-Louvry 2000 0/25 0/16 1.7 % 0.0 [ -0.10, 0.10 ]
Bukan 2004 0/15 0/15 1.3 % 0.0 [ -0.12, 0.12 ]
Charlo 1995 0/100 0/100 8.7 % 0.0 [ -0.02, 0.02 ]
Chaudhary 1999 0/21 0/22 1.9 % 0.0 [ -0.09, 0.09 ]
Chumillas 1998 0/20 0/20 1.7 % 0.0 [ -0.09, 0.09 ]
Coelho 1993 0/15 0/15 1.3 % 0.0 [ -0.12, 0.12 ]
Coskun 2000 0/35 0/35 3.0 % 0.0 [ -0.05, 0.05 ]
Dauleh 1995 0/40 0/38 3.4 % 0.0 [ -0.05, 0.05 ]
Demirer 2000 0/50 0/50 4.4 % 0.0 [ -0.04, 0.04 ]
Dionigi 1994 0/30 0/27 2.5 % 0.0 [ -0.07, 0.07 ]
Engin 1998 0/16 0/16 1.4 % 0.0 [ -0.11, 0.11 ]
Essen 1995 0/6 0/6 0.5 % 0.0 [ -0.27, 0.27 ]
Gal 1997 0/21 0/21 1.8 % 0.0 [ -0.09, 0.09 ]
Galizia 2001 0/10 0/5 0.6 % 0.0 [ -0.25, 0.25 ]
GarciaCaballero 1993 0/20 0/76 2.8 % 0.0 [ -0.07, 0.07 ]
Hasukic 2002 0/30 0/28 2.5 % 0.0 [ -0.06, 0.06 ]
Hendolin 2000 0/25 0/22 2.0 % 0.0 [ -0.08, 0.08 ]
-0.5 -0.25 0 0.25 0.5

(Continued . . . )
(. . . Continued)
Risk Risk
Huang 1996 0/15 0/12 1.2 % 0.0 [ -0.13, 0.13 ]
Jan 1993 0/50 0/51 4.4 % 0.0 [ -0.04, 0.04 ]
Karayiannakis 1997 0/45 0/42 3.8 % 0.0 [ -0.04, 0.04 ]
Kjaersgaard 1994 0/35 0/35 3.0 % 0.0 [ -0.05, 0.05 ]
Koprulu 1996 0/20 0/20 1.7 % 0.0 [ -0.09, 0.09 ]
Lausten 1999 (1) 0/7 0/7 0.6 % 0.0 [ -0.24, 0.24 ]
Lausten 1999 (2) 0/7 0/7 0.6 % 0.0 [ -0.24, 0.24 ]
Lujan 1998 0/133 1/131 11.5 % -0.01 [ -0.03, 0.01 ]
Luo 2003 0/14 0/12 1.1 % 0.0 [ -0.14, 0.14 ]
Milheiro 1994 0/20 0/20 1.7 % 0.0 [ -0.09, 0.09 ]
Mimica 2000 0/50 0/50 4.4 % 0.0 [ -0.04, 0.04 ]
Ortega 1996 0/10 0/10 0.9 % 0.0 [ -0.17, 0.17 ]
Prisco 2000 0/10 0/10 0.9 % 0.0 [ -0.17, 0.17 ]
Putensen-Himmer 1992 0/10 0/10 0.9 % 0.0 [ -0.17, 0.17 ]
Rovina 1996 0/26 0/25 2.2 % 0.0 [ -0.07, 0.07 ]
Trondsen 1993 0/35 0/35 3.0 % 0.0 [ -0.05, 0.05 ]
Volpino 1998 0/58 0/60 5.1 % 0.0 [ -0.03, 0.03 ]
Zajac 1998 0/58 0/52 4.8 % 0.0 [ -0.03, 0.03 ]
Zulfikaroglu 2002 0/25 0/25 2.2 % 0.0 [ -0.07, 0.07 ]
Total (95% CI) 1165 1173 100.0 % 0.00 [ -0.01, 0.01 ]

-0.5 -0.25 0 0.25 0.5

analysis 2: Imputing medians and standard deviations for missing data in operative time (minutes).
Outcome: 2 Sensitivity analysis 2: Imputing medians and standard deviations for missing data in operative time (minutes)
Mean Mean
Agnifili 1993 29 43.2 (16) 21 53.3 (19.1) 3.2 % -10.10 [ -20.13, -0.07 ]
Berggren 1994 15 87 (24.33) 12 69.17 (11.25) 3.0 % 17.83 [ 3.97, 31.69 ]
Blanc-Louvry 2000 25 61 (20) 16 74 (20) 3.1 % -13.00 [ -25.55, -0.45 ]
Bukan 2004 15 55 (15.4) 15 73 (24.3) 3.0 % -18.00 [ -32.56, -3.44 ]
Chumillas 1998 20 104 (34.39) 20 111.75 (30.57) 2.7 % -7.75 [ -27.92, 12.42 ]
Coelho 1993 15 107 (19.5) 15 86 (18.46) 3.0 % 21.00 [ 7.41, 34.59 ]
Coskun 2000 35 78.2 (19.5) 35 99.7 (18.46) 3.2 % -21.50 [ -30.40, -12.60 ]
Dauleh 1995 40 97.3 (19.5) 38 48.2 (18.46) 3.2 % 49.10 [ 40.68, 57.52 ]
Demirer 2000 50 40 (19.5) 50 59 (18.46) 3.2 % -19.00 [ -26.44, -11.56 ]
Dionigi 1994 30 89 (29) 27 78 (20) 3.1 % 11.00 [ -1.83, 23.83 ]
Engin 1998 16 82.4 (26.64) 16 79.5 (31.23) 2.7 % 2.90 [ -17.21, 23.01 ]
Essen 1995 6 87 (36) 6 79 (22) 2.0 % 8.00 [ -25.76, 41.76 ]
Galizia 2001 10 68 (14.7) 5 60 (3.6) 3.2 % 8.00 [ -1.64, 17.64 ]
Hasukic 2002 30 77.83 (12.01) 28 71.48 (8.26) 3.3 % 6.35 [ 1.07, 11.63 ]
Hendolin 2000 25 90 (19.5) 22 90 (18.46) 3.1 % 0.0 [ -10.86, 10.86 ]
Huang 1996 15 93.3 (25.3) 12 176.3 (26.1) 2.7 % -83.00 [ -102.54, -63.46 ]
Jan 1993 50 85.7 (25.2) 51 48 (13.9) 3.2 % 37.70 [ 29.74, 45.66 ]
Karayiannakis 1997 45 105 (25) 42 98 (17) 3.2 % 7.00 [ -1.93, 15.93 ]
Kjaersgaard 1994 35 103 (19.5) 35 53 (18.46) 3.2 % 50.00 [ 41.10, 58.90 ]
Lausten 1999 (1) 7 121 (14) 7 129 (23) 2.7 % -8.00 [ -27.95, 11.95 ]
Lausten 1999 (2) 7 112 (12) 7 90 (7) 3.2 % 22.00 [ 11.71, 32.29 ]
Lujan 1998 133 75 (19.5) 131 70.9 (18.46) 3.3 % 4.10 [ -0.48, 8.68 ]
Luo 2003 14 50.9 (33.3) 12 58.5 (21.8) 2.7 % -7.60 [ -28.96, 13.76 ]
Milheiro 1994 20 60 (21) 20 88 (15) 3.1 % -28.00 [ -39.31, -16.69 ]
-100 -50 0 50 100

(Continued . . . )
(. . . Continued)
Mean Mean
Mimica 2000 50 102 (20) 50 110 (32) 3.1 % -8.00 [ -18.46, 2.46 ]
Ortega 1996 10 70 (6) 10 77 (6.3) 3.3 % -7.00 [ -12.39, -1.61 ]
Prisco 2000 10 115 (22) 10 105 (19) 2.8 % 10.00 [ -8.02, 28.02 ]
Putensen-Himmer 1992 10 104 (25) 10 112 (37) 2.3 % -8.00 [ -35.68, 19.68 ]
Rovina 1996 26 155 (27) 25 46 (13) 3.1 % 109.00 [ 97.44, 120.56 ]
Trondsen 1993 35 100 (19.5) 35 50 (18.46) 3.2 % 50.00 [ 41.10, 58.90 ]
Volpino 1998 58 86.6 (22) 60 81 (24.79) 3.2 % 5.60 [ -2.85, 14.05 ]
Zajac 1998 58 54 (5) 52 47 (4) 3.3 % 7.00 [ 5.32, 8.68 ]
Zulfikaroglu 2002 25 69.2 (17.2) 25 66.8 (16.8) 3.2 % 2.40 [ -7.02, 11.82 ]
Total (95% CI) 969 920 100.0 % 6.42 [ -1.21, 14.04 ]

-100 -50 0 50 100

analysis 3: Imputing medians and standard deviations for missing data in hospital stay (days).
Outcome: 3 Sensitivity analysis 3: Imputing medians and standard deviations for missing data in hospital stay (days)
Mean Mean
Agnifili 1993 29 3.2 (1.2) 21 7.3 (3.2) 3.3 % -4.10 [ -5.54, -2.66 ]
Bellon 1998 14 2.3 (0.78) 14 6.2 (1.58) 3.5 % -3.90 [ -4.82, -2.98 ]
Berggren 1994 15 1.8 (0.56) 12 2.83 (0.84) 3.7 % -1.03 [ -1.58, -0.48 ]
Blanc-Louvry 2000 25 2.5 (1) 16 4.6 (1.2) 3.6 % -2.10 [ -2.81, -1.39 ]
Bukan 2004 15 2 (0.2) 15 5 (0.4) 3.7 % -3.00 [ -3.23, -2.77 ]
Charlo 1995 100 3 (1.01) 100 7 (2.63) 3.7 % -4.00 [ -4.55, -3.45 ]
Chumillas 1998 20 3.25 (0.71) 20 10.57 (4.67) 3.0 % -7.32 [ -9.39, -5.25 ]
Coelho 1993 15 1 (0.78) 15 2 (1.58) 3.6 % -1.00 [ -1.89, -0.11 ]
Dauleh 1995 40 3.4 (0.78) 38 6.5 (1.58) 3.7 % -3.10 [ -3.66, -2.54 ]
Demirer 2000 50 2 (0.78) 50 7 (1.58) 3.7 % -5.00 [ -5.49, -4.51 ]
Dionigi 1994 30 3.1 (0.5) 27 7.1 (1.6) 3.6 % -4.00 [ -4.63, -3.37 ]
Engin 1998 16 1.68 (0.6) 16 3.06 (0.77) 3.7 % -1.38 [ -1.86, -0.90 ]
Essen 1995 6 1.3 (0.5) 6 2.5 (0.6) 3.6 % -1.20 [ -1.82, -0.58 ]
Galizia 2001 10 1 (0.01) 5 5.2 (2.2) 3.1 % -4.20 [ -6.13, -2.27 ]
Hendolin 2000 25 2 (0.78) 22 4 (1.58) 3.6 % -2.00 [ -2.73, -1.27 ]
Huang 1996 15 3.93 (1.71) 12 7.92 (0.79) 3.5 % -3.99 [ -4.96, -3.02 ]
Jan 1993 50 4.5 (1.4) 51 5.6 (1.3) 3.7 % -1.10 [ -1.63, -0.57 ]
Karayiannakis 1997 45 2 (0.6) 42 5.6 (1.1) 3.7 % -3.60 [ -3.98, -3.22 ]
Kjaersgaard 1994 35 2.5 (1.61) 35 4.9 (4.25) 3.3 % -2.40 [ -3.91, -0.89 ]
Lausten 1999 (1) 7 2.9 (0.3) 7 5.3 (0.3) 3.7 % -2.40 [ -2.71, -2.09 ]
Lausten 1999 (2) 7 2.7 (0.3) 7 4.6 (0.2) 3.7 % -1.90 [ -2.17, -1.63 ]
Lujan 1998 133 3.71 (0.78) 131 9.9 (1.58) 3.7 % -6.19 [ -6.49, -5.89 ]
Luo 2003 14 3.2 (1.12) 12 6.7 (0.69) 3.6 % -3.50 [ -4.20, -2.80 ]
Ortega 1996 10 1.2 (0.2) 10 1.1 (0.1) 3.7 % 0.10 [ -0.04, 0.24 ]
-10 -5 0 5 10
(Continued . . . )
(. . . Continued)
Mean Mean
Prisco 2000 10 2 (0.01) 10 5.6 (0.52) 3.7 % -3.60 [ -3.92, -3.28 ]
Trondsen 1993 35 2 (0.78) 35 4 (1.58) 3.6 % -2.00 [ -2.58, -1.42 ]
Volpino 1998 58 4.6 (2.9) 60 7.77 (3.1) 3.5 % -3.17 [ -4.25, -2.09 ]
Zajac 1998 58 1 (0.01) 52 9.1 (2.8) 3.6 % -8.10 [ -8.86, -7.34 ]
Total (95% CI) 887 841 100.0 % -3.15 [ -3.94, -2.35 ]

-10 -5 0 5 10
Analysis 5.4. Comparison 5 LC versus OC - sensitivity and subgroup analyses, Outcome 4 Subgroup analysis
1: Influence antibiotic prophylaxis on total complications.
Outcome: 4 Subgroup analysis 1: Influence antibiotic prophylaxis on total complications
Risk Risk
M- M-
n/N n/N CI CI
1 Antibiotic: yes
Chaudhary 1999 0/21 2/22 3.0 % -0.09 [ -0.23, 0.05 ]
Gal 1997 0/21 0/21 4.7 % 0.0 [ -0.09, 0.09 ]
Lujan 1998 18/133 31/131 4.5 % -0.10 [ -0.19, -0.01 ]
Subtotal (95% CI) 175 174 12.3 % -0.06 [ -0.14, 0.03 ]

2 Antibiotic: no / unknown
-0.5 -0.25 0 0.25 0.5

(Continued . . . )
(. . . Continued)
Risk Risk
M- M-
n/N n/N CI CI
Agnifili 1993 1/29 4/21 2.2 % -0.16 [ -0.34, 0.02 ]
Bellon 1998 0/14 0/14 3.4 % 0.0 [ -0.13, 0.13 ]
Berggren 1994 1/15 0/12 2.3 % 0.07 [ -0.11, 0.24 ]
Charlo 1995 13/100 16/100 4.4 % -0.03 [ -0.13, 0.07 ]
Chumillas 1998 0/20 1/20 3.4 % -0.05 [ -0.18, 0.08 ]
Coelho 1993 0/15 1/15 2.5 % -0.07 [ -0.23, 0.10 ]
Coskun 2000 0/35 10/35 2.8 % -0.29 [ -0.44, -0.13 ]
Dauleh 1995 0/40 0/38 6.2 % 0.0 [ -0.05, 0.05 ]
Demirer 2000 0/50 0/50 6.6 % 0.0 [ -0.04, 0.04 ]
Dionigi 1994 0/30 1/27 4.5 % -0.04 [ -0.13, 0.06 ]
Engin 1998 0/16 0/16 3.8 % 0.0 [ -0.11, 0.11 ]
Essen 1995 0/6 0/6 1.2 % 0.0 [ -0.27, 0.27 ]
Galizia 2001 2/10 1/5 0.5 % 0.0 [ -0.43, 0.43 ]
Hasukic 2002 0/30 6/28 2.7 % -0.21 [ -0.37, -0.06 ]
Hendolin 2000 1/25 2/22 3.0 % -0.05 [ -0.19, 0.09 ]
Huang 1996 0/15 3/12 1.3 % -0.25 [ -0.51, 0.01 ]
Jan 1993 5/50 1/51 4.6 % 0.08 [ -0.01, 0.17 ]
Karayiannakis 1997 0/45 0/42 6.4 % 0.0 [ -0.04, 0.04 ]
Lausten 1999 (1) 1/7 0/7 0.9 % 0.14 [ -0.18, 0.46 ]
Lausten 1999 (2) 0/7 0/7 1.5 % 0.0 [ -0.24, 0.24 ]
Milheiro 1994 1/20 2/20 2.6 % -0.05 [ -0.21, 0.11 ]
Mimica 2000 0/50 2/50 5.6 % -0.04 [ -0.11, 0.03 ]
Ortega 1996 0/10 0/10 2.3 % 0.0 [ -0.17, 0.17 ]
Prisco 2000 0/10 0/10 2.3 % 0.0 [ -0.17, 0.17 ]
Trondsen 1993 14/35 8/35 1.7 % 0.17 [ -0.04, 0.39 ]
Volpino 1998 0/58 5/60 5.2 % -0.08 [ -0.16, -0.01 ]
Zajac 1998 0/58 14/52 3.6 % -0.27 [ -0.39, -0.15 ]
Subtotal (95% CI) 800 765 87.7 % -0.04 [ -0.08, -0.01 ]

Total (95% CI) 975 939 100.0 % -0.04 [ -0.08, -0.01 ]
-0.5 -0.25 0 0.25 0.5

(Continued . . . )
(. . . Continued)
Risk Risk
M- M-
n/N n/N CI CI
-0.5 -0.25 0 0.25 0.5

2: Influence cholangiography on operative time (minutes).
Outcome: 5 Subgroup analysis 2: Influence cholangiography on operative time (minutes)
Mean Mean
1 Cholangiography: yes
Agnifili 1993 29 43.2 (16) 21 53.3 (19.1) 8.0 % -10.10 [ -20.13, -0.07 ]
Blanc-Louvry 2000 25 61 (20) 16 74 (20) 7.4 % -13.00 [ -25.55, -0.45 ]
Essen 1995 6 87 (36) 6 79 (22) 3.2 % 8.00 [ -25.76, 41.76 ]
Lujan 1998 133 75 (19.5) 131 70.9 (18.46) 9.1 % 4.10 [ -0.48, 8.68 ]
Prisco 2000 10 115 (22) 10 105 (19) 6.0 % 10.00 [ -8.02, 28.02 ]
Subtotal (95% CI) 203 184 33.6 % -1.95 [ -11.40, 7.51 ]

2 Cholangiography: no
Berggren 1994 15 87 (24.33) 12 69.17 (11.25) 7.0 % 17.83 [ 3.97, 31.69 ]
Chumillas 1998 20 104 (34.39) 20 111.75 (30.57) 5.5 % -7.75 [ -27.92, 12.42 ]
Demirer 2000 50 40 (19.5) 50 59 (18.46) 8.6 % -19.00 [ -26.44, -11.56 ]
-100 -50 0 50 100

(Continued . . . )
(. . . Continued)
Mean Mean
Dionigi 1994 30 89 (29) 27 78 (20) 7.3 % 11.00 [ -1.83, 23.83 ]
Hendolin 2000 25 90 (19.5) 22 90 (18.46) 7.8 % 0.0 [ -10.86, 10.86 ]
Lausten 1999 (1) 7 121 (14) 7 129 (23) 5.6 % -8.00 [ -27.95, 11.95 ]
Lausten 1999 (2) 7 112 (12) 7 90 (7) 7.9 % 22.00 [ 11.71, 32.29 ]
Milheiro 1994 20 60 (21) 20 88 (15) 7.7 % -28.00 [ -39.31, -16.69 ]
Ortega 1996 10 70 (6) 10 77 (6.3) 9.0 % -7.00 [ -12.39, -1.61 ]
Subtotal (95% CI) 184 175 66.4 % -2.16 [ -12.89, 8.58 ]

Total (95% CI) 387 359 100.0 % -2.02 [ -9.36, 5.33 ]
-100 -50 0 50 100

3: Influence antibiotic prophylaxis on hospital stay (days).
Outcome: 6 Subgroup analysis 3: Influence antibiotic prophylaxis on hospital stay (days)
Mean Mean
1 Antibiotic prophylaxis: yes

Lujan 1998 133 3.71 (0.78) 131 9.9 (1.58) 3.7 % -6.19 [ -6.49, -5.89 ]
Subtotal (95% CI) 133 131 3.7 % -6.19 [ -6.49, -5.89 ]

2 Antibiotic prophylaxis: no / unknown
Agnifili 1993 29 3.2 (1.2) 21 7.3 (3.2) 3.3 % -4.10 [ -5.54, -2.66 ]
Bellon 1998 14 2.3 (0.78) 14 6.2 (1.58) 3.5 % -3.90 [ -4.82, -2.98 ]
Berggren 1994 15 1.8 (0.56) 12 2.83 (0.84) 3.7 % -1.03 [ -1.58, -0.48 ]
Blanc-Louvry 2000 25 2.5 (1) 16 4.6 (1.2) 3.6 % -2.10 [ -2.81, -1.39 ]
Bukan 2004 15 2 (0.2) 15 5 (0.4) 3.7 % -3.00 [ -3.23, -2.77 ]
Charlo 1995 100 3 (1.01) 100 7 (2.63) 3.7 % -4.00 [ -4.55, -3.45 ]
Chumillas 1998 20 3.25 (0.71) 20 10.57 (4.67) 3.0 % -7.32 [ -9.39, -5.25 ]
Coelho 1993 15 1 (0.78) 15 2 (1.58) 3.6 % -1.00 [ -1.89, -0.11 ]
Dauleh 1995 40 3.4 (0.78) 38 6.5 (1.58) 3.7 % -3.10 [ -3.66, -2.54 ]
Demirer 2000 50 2 (0.78) 50 7 (1.58) 3.7 % -5.00 [ -5.49, -4.51 ]
Dionigi 1994 30 3.1 (0.5) 27 7.1 (1.6) 3.6 % -4.00 [ -4.63, -3.37 ]
Engin 1998 16 1.68 (0.6) 16 3.06 (0.77) 3.7 % -1.38 [ -1.86, -0.90 ]
Essen 1995 6 1.3 (0.5) 6 2.5 (0.6) 3.6 % -1.20 [ -1.82, -0.58 ]
Galizia 2001 10 1 (0.01) 5 5.2 (2.2) 3.1 % -4.20 [ -6.13, -2.27 ]
Hendolin 2000 25 2 (0.78) 22 4 (1.58) 3.6 % -2.00 [ -2.73, -1.27 ]
Huang 1996 15 3.93 (1.71) 12 7.92 (0.79) 3.5 % -3.99 [ -4.96, -3.02 ]
Jan 1993 50 4.5 (1.4) 51 5.6 (1.3) 3.7 % -1.10 [ -1.63, -0.57 ]
Karayiannakis 1997 45 2 (0.6) 42 5.6 (1.1) 3.7 % -3.60 [ -3.98, -3.22 ]
Kjaersgaard 1994 35 2.5 (1.61) 35 4.9 (4.25) 3.3 % -2.40 [ -3.91, -0.89 ]
Lausten 1999 (1) 7 2.9 (0.3) 7 5.3 (0.3) 3.7 % -2.40 [ -2.71, -2.09 ]
-10 -5 0 5 10
(Continued . . . )
(. . . Continued)
Mean Mean
Lausten 1999 (2) 7 2.7 (0.3) 7 4.6 (0.2) 3.7 % -1.90 [ -2.17, -1.63 ]
Luo 2003 14 3.2 (1.12) 12 6.7 (0.69) 3.6 % -3.50 [ -4.20, -2.80 ]
Ortega 1996 10 1.2 (0.2) 10 1.1 (0.1) 3.7 % 0.10 [ -0.04, 0.24 ]
Prisco 2000 10 2 (0.01) 10 5.6 (0.52) 3.7 % -3.60 [ -3.92, -3.28 ]
Trondsen 1993 35 2 (0.78) 35 4 (1.58) 3.6 % -2.00 [ -2.58, -1.42 ]
Volpino 1998 58 4.6 (2.9) 60 7.77 (3.1) 3.5 % -3.17 [ -4.25, -2.09 ]
Zajac 1998 58 1 (0.01) 52 9.1 (2.8) 3.6 % -8.10 [ -8.86, -7.34 ]
Subtotal (95% CI) 754 710 96.3 % -3.02 [ -3.73, -2.31 ]

Total (95% CI) 887 841 100.0 % -3.15 [ -3.94, -2.35 ]
-10 -5 0 5 10
ADDITIONAL TABLES
Table 1. Randomised, excluded, and included in LC versus OC
Trial Randomised Excluded Included LC Included OC cholangiogra- antibiotics surgical exper-

phy tise
Agnifili 1993 50 0 29 21 Y U U
Bellon 1998 28 0 14 14 N U U
Berggren 30 3 15 12 N N SS
1994
Blanc-Louvry 41 0 25 16 Y U S
2000
Bukan 2004 30 0 15 15 U U U
Charlo 1995 200 0 100 100 U U U
Table 1. Randomised, excluded, and included in LC versus OC (Continued)
Chaudhary 43 0 21 22 U Y U
1999
Chumillas 40 0 20 20 N U U
1998
Coelho 1993 45* 0 15 15 U U U
Coskun 2000 70 0 35 35 U U U
Dauleh 1995 78 0 40 38 U N S
Demirer 2000 100 0 50 50 N N SS
Dionigi 1994 57 0 30 27 N U SS
Engin 1998 32 0 16 16 U U SS
Essen 1995 12 0 6 6 Y U U
Gal 1997 42 0 21 21 U Y U
Galizia 2001 33 18 10 5 U U U
Garcia-Ca- 100 4 20 76 U U S
ballero 1993
Hasukic 2002 60 2 30 28 U U SS
Hendolin 49 2 25 22 N U S
2000
Huang 1996 29 2 15 12 U U U
Jan 1993 101 0 50 51 U U U
Karayiannakis 96 9 45 42 U U SS
1997
Kjaersgaard 72 2 35 35 U U U
1994
Koprulu 1996 40 0 20 20 U U U
Lausten 16 2 7 7 N U SS
1999 - 1 (post-
necrotic cirro-
sis)
Table 1. Randomised, excluded, and included in LC versus OC (Continued)
Lausten 1999 14 0 7 7 N U SS
- 2 (chronic
hepatitis)
Lujan 1998 285 21 133 131 Y Y U
Luo 2003 26 0 14 12 U U U
Milheiro 1994 40 0 20 20 N U U
Mimica 2000 100 0 50 50 U U U
Ortega 1996 20 0 10 10 N U U
Prisco 2000 25 5 10 10 Y U U
Putensen- 20 0 10 10 U U U
Himmer 1992
Rovina 1996 51 0 26 25 U U SS
Trondsen 72 2 35 35 U U U
1993
Volpino 1998 120 2 58 60 U U U
Zajac 1998 110 0 58 52 U U U
Zulfikaroglu 50 0 25 25 U U U
2002
total 2427 74 1165 1173
* three- N = no Y = yes U = unknown S = one surgeon SS = a few sur- R = also regis-

arm trial, pa- geons trars
tients in the
SIC group not
listed in this
table
Table 2. Description of background data (age, gender, BMI and ASA)
Trial N Age Age Sex (m/f ) Sex (m/f ) BMI BMI ASA (I-II- ASA (I-II-
III-IV) III-IV)
LC vs OC ran- LC OC LC OC LC OC LC OC
domised
Table 2. Description of background data (age, gender, BMI and ASA) (Continued)
Agnifili 29 / 21 46.7 (4.5) 48.2 (3.4) 12 / 19 9 / 10 - - 21 - 7 - 3 - 15 - 3 - 1 -

1993 0 0
Bablekos 18 / 10 52.6 (12. 54.8 (9.2) - - - - -

2003 2)
Bellon 14 / 14 42 ( - ) 47 ( - ) 7/7 6/8 - - -

1998
Berggren 15 / 12 41.4 (12. 42.8 (13. 5 / 10 4/8 - - - -

1994 9) 7)
Blanc- 25 / 16 63 (5)# 55 (4)# 12 / 13 7/9 - - 13 - 12 - 0 - 9 - 7 - 0 - 0

Louvry 0
2000
Bukan 15 / 15 50 (38-65) 48 (41-62) 6 / 9 5 / 10 - - - -

2004
Charlo 100 / 100 49 (16) 49 (16) 22 / 78 25 / 75 - - - -

1995
Chaud- 21 / 22 36.1 (8.7) 37.6 (9.7) 1 / 19 1 / 19 22.4 (1.4) 23.0 (1.1) 20 - 0 - 0 - 20 - 0 - 0 -

hary 1999 0 0
Chumillas 20 / 20 60.7 (12. 63.3 (10) 4 / 16 5 / 15 26.5 (4.5) 27.1 (4.9) - -

1998 6)
Coelho 15 / 15 42.7 (25- 45.4 (18- 3 / 12 3 / 12 - - - -

1993 70) 73)
Coskun 35 / 35 46.7 (40- 46.4 (40- 5 / 30 6 / 29 - - - -

2000 54) 55)
Dauleh 40 / 38 47.7 (18- 50.8 (20- 8 / 30 10 / 28 - - - -

1995 75) 88)
Demirer 50 / 50 46* (31- 48* (20- 14 / 36 18 / 32 - - 50 - 0 - 0 - 50 - 0 - 0 -

2000 70) 66) 0 0
Dionigi 30 / 27 39 (11) 46 (14) 7 / 23 9 / 18 - - - -

1994
Engin 16 / 16 - - - - - - - -
1998
Essen 6/6 38 (3)# 38 (6)# 2/4 2/4 - - - -

1995
Gal 1997 21 / 21 - - - - - - - -
Galizia 10 / 5 37.4 (2.2) 36.8 (2.7) 8 / 2 3/2 24.8 (1.0) 25.5 (0.5) 10 - 0 - 0 - 5 - 0 - 0 - 0
2001 # # 0
Garcia- 20 / 76 - - - - - - - -
Caballero
1993
Hasukic 30 / 28 46.9 (2.3) 49.2 (12. 7 / 23 5 / 23 - - - -

2002 9)
Hendolin 25 / 22 49 (12) 53 (12) 7 / 18 7 / 15 27 (8) 28 (8) 16 - 8 - 1 - 7 - 11 - 2 -

2000 0 0
Huang 15 / 12 nd nd nd nd - - - -
1996
Jan 1993 50 / 51 49.5 (11. 50.3 (13. 18 / 32 20 / 31 - - - -

3) 1)
Karayian- 45 / 42 57 (12) 58 (10) 18 / 23 18 / 24 - - - -

nakis 1997
Kjaers- 35 / 35 43 (19-80) 53 (19-79) 5 / 30 5 / 30 - - - -

gaard 1994
Koprulu 20 / 20 47 (6) 42 (9) 6 / 14 8 / 12 - - - -

1996
Lausten 7/7 48 (3) 48.6 (4) 4/3 3/4 - - - -

1999 (1)
Lausten 7/7 40.7 (2.8) 46.1 (5.8) 2/5 4/3 - - - -

1999 (2)
Lujan 133 / 131 71 (65-87) 72 (65-87) 42 / 91 38 / 93 - - - -

1998
Luo 2003 14 / 12 46.6* (15. 45.5* (12. 6 / 8 3/9 - - - -

8)# 6)#
Milheiro 20 / 20 51 (16) 62 (18) 5 / 15 7 / 13 - - 13 - 5 - 2 - 13 - 5 - 2 -

1994 0 0
Mimica 50 / 50 nd nd - - - - 50 - 0 - 0 - 50 - 0 - 0 -
2000 0 0
Ortega 10 / 10 34 (2) 33 (3) 0 / 10 0 / 10 - - 10 - 0 - 0 - 10 - 0 - 0 -

1996 0 0
Prisco 10 / 10 55 (12.5) 58.3 (9.3) 4/6 6/4 27.3 (5.2) 28.9 (4.5) - -
2000
Putensen- 10 / 10 41.2 (10. 41.5 (13. 3 / 7 2/8 - - 10 - 0 - 0 - 10 - 0 - 0 -

Himmer 7) 5) 0 0
1992
Rovina 26 / 25 49 (12) 50 (15) 4 / 22 6 / 19 - - - -

1996
Schauer 20 / 20 37.2 (17- 38.5 (13- 2 / 18 4 / 16 32.2 30.3 - -

1993 63) 64)
Trondsen 35 / 35 43* (19- 55* (19- 30 / 5 30 / 5 - - - -

1993 80) 78)
Volpino 58 / 60 47.7 (17. 53.5 (16. 16 / 42 20 / 40 - - 44 - 14 - 0 45 - 15 - 0

1998 1) 0)
Zajac 1998 58 / 52 76.7 (2.2) 75.9 (2.1) nd nd - - 0 - 19 - 39 - 0 - 28 - 24 -

0 0
Zul- 25 / 25 45.8 (11) 52.9 (12. 2 / 23 3 / 22 - - 25 - 0 - 0 25 - 0 - 0

fikaroglu 1)
2002
* median # standard nd: ’no dif-

error of ference’ re-
mean ported
Table 3. Complications specified per operative technique: LC versus OC
Complications LC OC
INTRA-OPERATIVE (10 / 0.9%) (1 / 0.1%)
gallbladder perforation 7 1
bleeding 2 0
other (not specified) 1 0
Table 3. Complications specified per operative technique: LC versus OC (Continued)
POSTOPERATIVE - MINOR (25 / 2.1%) (36 / 3.1%)
retained bile duct stone (ERCP) 1 2
wound infection 3 17
wound hematoma 3 0
urinary tract infection 7 7
flebitis 3 4
readmission (abdominal pain) 2 0
other (unspecified) 6 6
POSTOPERATIVE - SEVERE (26 / 2.2%) (80 / 6.8%)
bleeding: drainage/blood transfusion 4 1
bleeding: re-operation 2 0
ileus: conservative 4 9
platzbauch 0 3
abscess (drainage / unspecified) 1 2
biliary fistula (unspecified / conservative) 1 1
pneumonia 6 18
respiratory insufficiency / atelectasis 6 35
septic shock (multi organ failure) 0 1
cardiovascular 0 5
Cerebrovascular accident 0 1
upper GI bleeding (endoscopy / conserva- 0 3

tive)
other (unspecified) 2 1
Table 3. Complications specified per operative technique: LC versus OC (Continued)
BILE DUCT INJURY (2 / 0.2%) (2 / 0.2%)
cystic duct leakage: drainage/ERCP 0 1
bile leakage (origin unknown): conserva- 2 1

tive
TOTAL COMPLICATIONS 63 (5.4%) 119 (10.1%)
RE-OPERATIONS (all complications) 3 (0.3%) 3 (0.3%)
TOTAL NUMBER OF PATIENTS IN- 1165 1173

CLUDED (all trials)
Table 4. Internal validity assessment of included trials: LC vs OC
Trial Generation of alloca- Concealment of alloca- Blinding Follow-up

tion sequence tion
Agnifili 1993 U U N U
Bellon 1998 U U N U
Berggren 1994 U A N U
Blanc-Louvry 2000 A U N U
Bukan 2004 U U N U
Charlo 1995 A U N U
Chaudhary 1999 A U A A
Chumillas1998 U A N U
Coelho 1993 U U N U
Coskun 2000 U U N U
Dauleh 1995 U U N U
Demirer 2000 U U N A
Dionigi 1994 U U N U
Table 4. Internal validity assessment of included trials: LC vs OC (Continued)
Engin 1998 U A N U
Essen 1995 U A N U
Gal 1997 U U N U
Galizia 2001 U A N U
Garcia-Caballero 1993 U U A A
Hasukic 2002 U U N U
Hendolin 2000 U A N U
Huang 1996 U U N U
Jan 1993 A N N A
Karayiannakis1997 U A N A
Kjaersgaard 1994 U U N A
Koprulu 1996 U U N U
Lausten 1999 U U N U
Lujan 1998 U U N U
Luo 2003 U U N U
Milheiro 1994 U A N U
Mimica 2000 U A N U
Ortega 1996 A U A U
Prisco 2000 U U N U
Putensen-Himmer 1992 U U N U
Rovina 1996 U U N U
Trondsen 1993 U U N U
Volpino 1998 U U N U
Zajac 1998 U U N U
Zulfikaroglu 2002 U U N U
Table 4. Internal validity assessment of included trials: LC vs OC (Continued)
A: Adequate U: Unclear I: Inadequate N: Not performed
Table 5. Results of LC versus OC: allocation concealment (comparison 2)
Outcome RD/WMD HQ/LQ/AT Fixed Random Discrep- Emphasize HQ-LQ Significant

ancy difference
severe com- RD HQ -0.01 (-0. 0.00 (-0.03, no

plications 04, 0.03) 0.02)
LQ -0.06 (-0. -0.04 (-0. yes

09, -0.04) * 08, 0.00)
AT -0.05 (-0. -0.03 (-0. yes random no no

07, -0.03) * 06, 0.00)
total com- RD HQ -0.02 (-0. -0.01 (-0. no

plications 06, 0.02) 05, 0.02)
LQ -0.07 (-0. -0.05 (-0. no

10, -0.04) * 10, -0.01) *
AT -0.06 (-0. -0.04 (-0. no random yes no

08, -0.03) * 07, -0.01) *
operative WMD HQ -0.74 (-5. -1.14 (-12. no

time 20, 3.71) 80, 10.52)
LQ 7.45 (6.06, 5.72 (-5.34, yes

8.84) * 16.77)
AT 6.73 (5.40, 3.79 (-4.88, yes random no no

8.05) * 12.46)
hospital stay WMD HQ -2.48 (-2. -3.23 (-4. no

73, -2.22) * 75, -1.71) *
LQ -1.62 (-1. -3.01 (-3. no

71, -1.53) * 97, -2.06) *
AT -1.72 (-1. -3.07 (-3. no random no yes

80, -1.63) * 89, -2.26) *
convales- WMD HQ -12.30 (-15. -12.30 (-15. no

cence work 54, -9.06) * 54, -9.06) *
leave
Table 5. Results of LC versus OC: allocation concealment (comparison 2) (Continued)
LQ -31.89 (-32. -28.10 (-36. no

58, -31.19) * 75, -19.44) *
AT -31.01 (-31. -22.51 (-36. no random no yes

70, -30.33) * 89, -8.13) *
* significant HQ: high LQ: low AT: all trials RD: risk dif- WMD: random:
result quality trials quality trials ference weighted random-
mean differ- effects
ence method
Table 6. Operative time LC versus OC: all available data
Trial Type of data LC - mean/ LC - SD/ OC - mean/ OC - SD/ Skewness LC Skewness OC

median range median range
Agnifili 1993 A - SD 43.2 16 53.3 19.1 2.7 2.79
Bellon 1998 - - 60 - 80 - 60 - 80 - -
Berggren A - SD 87.00 24.33 69.17 11.25 3.58 6.18

1994
Blanc-Louvry A - SEM 61 4 (20*) 74 5 (20*) 3.05 3.7

2000
Bukan 2004 A - SD 55 15.4 73 24.3 3.57 3.00
Charlo 1995 - - - - - - -
Chaudhary - - - - - - -
1999
Chumillas A - SD 104 34.39 111.75 30.57 3.02 3.66

1998
Coelho 1993 A - range 107 55 - 150 86 40 - 140 - -
Coskun 2000 A - range 78.2 30 - 130 99.7 71 - 125 - -
Dauleh 1995 A - range 97.3 50 - 150 48.2 20 - 120 - -
Demirer 2000 M - range 40 25 - 50 59 35 - 75 - -
Dionigi 1994 A - SD 89 29 78 20 3.07 3.9
Engin 1998 A - SD 82.4 26.64 79.5 31.23 3.09 2.55
Table 6. Operative time LC versus OC: all available data (Continued)
Essen 1995 A - SD 87 36 79 22 2.42 3.59
Gal 1997 - - - - - - -
Galizia 2001 A - SEM 66 and 70 4.8 and 4.5 60 1.6 (3.6*) 4.63 16.67
(14.7*)
Garcia-Ca- - - - - - - -
ballero 1993
Hasukic 2002 A - SD 77.83 12.01 71.48 8.26 6.48 8.65
Hendolin A - range 90 45 - 160 90 60 - 150 - -

2000
Huang 1996 A - SD 93.3 25.3 176.3 26.1 3.69 6.75
Jan 1993 A - SD 85.7 25.2 48 13.9 3.40 3.45
Karayiannakis A - SD 105 25 98 17 4.2 5.76

1997
Kjaersgaard A - range 103 93 - 112 53 46 - 61 - -

1994
Koprulu 1996 - - - - - - -
Lausten 1999 A - SD 121 14 129 23 8.64 5.61

(1)
Lausten 1999 A - SD 112 12 90 7 9.33 12.86

(2)
Lujan 1998 A - range 75 20 - 180 70.9 49 - 115 - -
Luo 2003 M - SEM 50.9 8.9 (33.3*) 58.5 6.3 (21.8*) 1.53 2.68
Milheiro 1994 A - SD 60 21 88 15 2.86 5.87
Mimica 2000 A - SD 102 20 110 32 5.1 3.44
Ortega 1996 A - SD 70 6 77 6.3 11.67 12.22
Prisco 2000 A - SD 115 22 105 19 5.23 5.53
Putensen- A - SD 104 25 112 37 4.16 3.03

Himmer 1992
Rovina 1996 A - SD 155 27 46 13 5.74 3.54
Table 6. Operative time LC versus OC: all available data (Continued)
Trondsen M - range 100 52 - 180 50 15 - 115 - -

1993
Volpino 1998 A - SD 86.6 22 81 24.79 3.94 3.27
Zajac 1998 A - SD 54 5 47 4 10.8 11.75
Zulfikaroglu A - SD 69.2 17.2 66.8 16.8 4.02 3.98

2002
* SD calcu- A: Average / M: Median SD: standard SEM:

lated from mean deviation standard error
SEM (hand- of mean
book page 89)
Table 7. Hospital stay LC versus OC: all available data
Trial Type of data LC - mean/ LC - SD/ OC - mean/ OC - SD/ Skewness LC Skewness OC

median range median range
Agnifili 1993 A - SD 3.2 1.2 7.3 3.2 2.67 2.28
Bellon 1998 A- 2.3 - 6.2 - - -
Berggren A - SD 1.8 0.56 2.83 0.84 3.21 3.33

1994
Blanc-Louvry A - SEM 2.5 0.2 (1.0*) 4.6 0.3 (1.2*) 2.5 3.83
2000
Bukan 2004 A - SD 2 0.2 5 0.4 10 12.5
Charlo 1995 A - SD 3 1.01 7 2.63 2.97 2.66
Chaudhary - - - - - - -
1999
Chumillas A - SD 3.25 0.71 10.57 4.67 4.58 2.26

1998
Coelho 1993 A - range 1 0 2 2-3 - -
Coskun 2000 - - - - - - -
Dauleh 1995 A - range 3.4 2-5 6.5 3 - 15 - -
Demirer 2000 M - range 2 1-3 7 5 - 15 - -
Table 7. Hospital stay LC versus OC: all available data (Continued)
Dionigi 1994 A - SD 3.1 0.5 7.1 1.6 6.2 4.44
Engin 1998 A - SD 1.68 0.60 3.06 0.77 2.8 3.97
Essen 1995 A - SD 1.3 0.5 2.5 0.6 2.6 4.17
Gal 1997 - - - - - - -
Galizia 2001 A - SD 1 0.01 5.2 2.2 100 2.36
Garcia-Ca- - - - - - - -
ballero 1993
Hasukic 2002 - - - - - - -
Hendolin A - range 2 1 - 15 4 2 - 19 - -
2000
Huang 1996 A - SD 3.93 1.71 7.92 0.79 2.29 9.88
Jan 1993 A - SD 4.5 1.4 5.6 1.3 3.21 4.31
Karayiannakis A - SD 2 0.6 5.6 1.1 3.33 5.09

1997
Kjaersgaard A - CI 2.5 2.0 - 3.1 (1. 4.9 3.4 - 6.3 (4. 1.55 1.15
1994 61*) 25*)
Koprulu 1996 - - - - - - -
Lausten 1999 A - SD 2.9 0.3 5.3 0.3 9.67 17.67

(1)
Lausten 1999 A - SD 2.7 0.3 4.6 0.2 9 23

(2)
Lujan 1998 A - range 3.71 1 - 27 9.9 5 - 33 - -
Luo 2003 A - SEM 3.2 0.3 (1.12*) 6.7 0.2 (0.69*) 2.86 9.71
Milheiro 1994 - - - - - - -
Mimica 2000 - - - - - - -
Ortega 1996 A - SD 1.2 0.2 1.1 0.1 6 11
Prisco 2000 A - SD 2 0.01 5.6 0.52 200 10.77
Table 7. Hospital stay LC versus OC: all available data (Continued)
Putensen- - - - - - - -
Himmer 1992
Rovina 1996 - - - - - - -
Trondsen M - range 2 1-9 4 2 - 22 - -

1993
Volpino 1998 A - SD 4.6 2.9 7.77 3.1 1.59 2.51
Zajac 1998 A - SD 1 0.01 9.1 2.8 100 3.25
Zulfikaroglu - - - - - - -
2002
* A: Average / M: Median SD: standard SEM:

SD calculated mean deviation standard error
from SEM / of mean
CI
APPENDICES
Appendix 1. Search strategies
Database Time span of search Search strategy Hits Titles selected
The Cochrane Hep- 6 April 2004 “cholelithiasis OR gall- 843 65

ato-Biliary Group Con- stones OR cholecystec-
trolled Trials Register tomy”
The Cochrane Database Issue 1, 2004 “cholecystectomy” 33 0

of Systematic Reviews in
The Cochrane Library
Database of Abstracts of Issue 1, 2004 “cholecystectomy” 17 5

Reviews of Effects in The
Cochrane Library
The Cochrane Central Issue 1, 2004 “cholecystectomy” 1343 146

Register of Controlled
Trials in The Cochrane
(Continued)
Library
Health Technology As- Issue 1, 2004 “cholecystectomy” 11 4

sessment Database in
The Cochrane Library
NHS Economic Evalu- Issue 1, 2004 “cholecystectomy” 43 6

ation Database in The
Cochrane Library
MEDLINE 1966 to January 2004 (((Gallbladder[Tiab] 8354 347

AND (Surgery[Tiab]
OR Endoscopy[Tiab]
OR Surgical[Tiab] OR
Laparoscopy[Tiab])
) OR Cholecystec-
tomy[Tiab]) OR ((
(“Gallbladder”[MeSH]
OR “Gallbladder Dis-
eases”[MeSH]) AND
(“Surgery”[MeSH] OR
“surgery”[Subheading]
OR “Endoscopy, Gas-
trointestinal”[MeSH]
OR “Surgical Procedures,
Operative”[MeSH] OR
“Surgical Procedures,
Minor”[MeSH] OR
“Laparoscopy”[MeSH])
) OR “Cholecystec-
tomy”[MeSH])) AND
(randomized controlled
trial[PTYP] OR ran-
domized controlled trials
OR controlled clinical
trial[PTYP] OR clinical
trial[PTYP] OR clinical
trials OR (clinical AND
trial) OR random allo-
cation OR random* OR
double blind method
OR single blind method
OR (singl* OR doubl*
OR trebl* OR tripl*) OR
blind* OR mask* OR
placebo* OR placebos
OR research design OR
comparative study OR
(Continued)
evaluation studies OR
follow up studies OR
prospective studies OR
control OR controlled
OR prospectiv* OR
volunteer*)
EMBASE 1980 to January 2004 “cholecystectomy” 685 131
Web of Science 1988 to January 2004 TS=(cholecystectomy 1163 148

AND random*)
CINAHL 1982 to January 2004 “cholecystectomy” 740 9
Total 13232 586
WHAT’S NEW
Last assessed as up-to-date: 7 August 2006.
Date Event Description
23 October 2008 Amended One reference in excluded studies corrected.
CONTRIBUTIONS OF AUTHORS
F Keus: literature searches and selection, data extraction, statistical analysis, and text writing.
JAF de Jong: literature selection and data extraction.
HG Gooszen: text editing and supervision.
CJHM van Laarhoven: data extraction, statistical analysis, text writing, and final supervision.
DECLARATIONS OF INTEREST
We (FK, HG, CL) are the coordinating authors of an unpublished trial (Keus 2006), which will be published in the near future.
SOURCES OF SUPPORT
Internal sources
• Department of Surgery, University Medical Center, Utrecht, Netherlands.
• Department of Surgery, St. Elisabeth Hospital, Tilburg, Netherlands.
External sources
• No sources of support supplied
NOTES
The protocol for this systematic review was first published in Issue 3, 1997 of The Cochrane Library. The reviewers, Dr T Jørgensen and
H Laugesen have abandoned the preparation of the systematic review. This necessitated that an update of the protocol and preparation
of the review be performed by a new team of reviewers. They are F Keus, JAF de Jong, HG Gooszen, and CJHM van Laarhoven. Due
to the large number of identified trials it was considered wiser in terms of clarity and usability to produce three separate reviews. Thus
this review is one of the three.
Correction of name
Eric Keus, the lead author of the protocol, and Frederik Keus, the lead author of the review, is one and the same person.
INDEX TERMS
Medical Subject Headings (MeSH)

Cholecystectomy [adverse effects; ∗ methods]; Cholecystectomy, Laparoscopic [adverse effects]; Cholecystolithiasis [∗ surgery]; Ran-
domized Controlled Trials as Topic
MeSH check words

Humans

Laparoscopic Versus Open Cholecystectomy For Patients With

Diunggah oleh

Informasi Dokumen

Judul Asli

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Laparoscopic Versus Open Cholecystectomy For Patients With

Diunggah oleh

Hak Cipta:

Cochrane Database of Systematic Reviews

Laparoscopic versus open cholecystectomy for patients with

Keus F, de Jong J, Gooszen HG, Laarhoven CJHM

Keus F, de Jong J, Gooszen HG, Laarhoven CJHM.

Laparoscopic versus open cholecystectomy for patients with

Frederik Keus1 , Jeroen de Jong2 , H G Gooszen3 , C JHM Laarhoven4

Editorial group: Cochrane Hepato-Biliary Group.

PLAIN LANGUAGE SUMMARY

BACKGROUND like non-severe complications, pulmonary outcomes, differences

The primary outcome measures are mortality, complication pro-

The total complication proportions were 5.4% and 10.1% in the

Wani 2002 {published data only} Higgins 2002

Characteristics of included studies [ordered by study ID]

Methods Single-centre randomised trial.

Participants Elective cholecystectomy.

Interventions LC versus OC.

Outcomes Primary and secondary outcome (endpoints): not mentioned.

Bias Authors’ judgement Support for judgement

Allocation concealment? Unclear risk B - Unclear

Blinding? High risk

Free of selective reporting? High risk

Free of other bias? High risk short FU

Methods Single-centre randomised trial.

Participants Having cholelithiasis without previous complications.

Interventions LC versus OC.

Outcomes Primary and secondary outcome (endpoints): not mentioned.

Bias Authors’ judgement Support for judgement

Allocation concealment? Unclear risk B - Unclear

Blinding? High risk

Free of selective reporting? High risk

Free of other bias? High risk short FU

Methods Single-centre randomised trial.

Interventions LC versus OC.

Outcomes Primary and secondary outcome (endpoints): not defined.

Bias Authors’ judgement Support for judgement

Allocation concealment? Low risk A - Adequate

Blinding? High risk

Free of selective reporting? High risk

Free of other bias? Low risk adequate FU

Methods Single-centre randomised trial.

Participants Painful cholelithiasis.

Interventions LC versus OC.

Outcomes Primary and secondary outcome (endpoints): not described.

Bias Authors’ judgement Support for judgement

Adequate sequence generation? Low risk

Allocation concealment? Unclear risk B - Unclear

Blinding? High risk

Free of selective reporting? High risk

Free of other bias? High risk short FU

Methods Single-centre trial.

Participants Elective cholecystectomy for symptomatic cholelithiasis.

Interventions LC versus OC.

Outcomes Primary and secondary outcome (endpoints): not described.

Bias Authors’ judgement Support for judgement

Allocation concealment? Unclear risk B - Unclear

Blinding? High risk

Free of selective reporting? High risk

Free of other bias? High risk short FU

Methods Single-centre trial.

Participants Elective cholecystectomy for symptomatic cholelithiasis.

Interventions LC versus OC.

Outcomes Primary and secondary outcome (endpoints): not described.

Bias Authors’ judgement Support for judgement

Adequate sequence generation? Low risk

Allocation concealment? Unclear risk B - Unclear

Blinding? High risk