Acute Cholecystitis - Early vs Delayed Intervention Met Analysis

8/8/2019 Acute Cholecystitis - Early vs Delayed Intervention Met Analysis

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Meta-analysis

Meta-analysis of randomized controlled trials on the safety

and effectiveness of early versus delayed laparoscopic

cholecystectomy for acute cholecystitis

K. Gurusamy1, K. Samraj2, C. Gluud4, E. Wilson3 and B. R. Davidson1

1Hepatopancreatobiliary and Liver Transplant Surgery, University Department of Surgery, Royal Free and University College School of Medicine,

London, 2Department of Surgery, Milton Keynes General Hospital, Milton Keynes, and 3Health Economics Group, School of Medicine, Health Policy

and Practice, University of East Anglia, Norwich, UK, and 4Copenhagen Trial Unit, Centre for Clinical Intervention Research, Rigshospitalet,

Copenhagen University Hospital, Copenhagen, Denmark

Correspondence to: Mr K. Gurusamy, c/o Professor B. R. Davidson, 9th Floor, University Department of Surgery, Royal Free Hospital, Pond Street,

London NW3 2QG, UK (e-mail: [email protected])

Background: In many countries laparoscopic cholecystectomy for acute cholecystitis is mainly performed

after the acute episode has settled because of the anticipated increased risk of morbidity and higher

conversion rate from laparoscopic to open cholecystectomy.

Methods: A systematic review was performed with meta-analysis of randomized clinical trials of early

laparoscopic cholecystectomy (ELC; performed within 1 week of onset of symptoms) versus delayed

laparoscopic cholecystectomy (performed at least 6 weeks after symptoms settled) for acute cholecystitis.

Trials were identified from The Cochrane Library trials register, Medline, Embase, Science Citation

Index Expanded and reference lists. Risk ratio (RR) or mean difference was calculated with 95 per cent

confidence intervals (c.i.) based on intention-to-treat analysis.

Results: Five trials with 451 patients were included. There was no significant difference between the

two groups in terms of bile duct injury (RR 064 (95 per cent c.i. 015 to 265)) or conversion to open

cholecystectomy (RR 088 (95 per cent c.i. 062 to 125)). The total hospital stay was shorter by 4 days

for ELC (mean difference 412 (95 per cent c.i. 522 to 303) days).

Conclusion: ELC during acute cholecystitis appears safe and shortens the total hospital stay.

Paper accepted 27 August 2009

Published online 24 December 2009 in Wiley InterScience (www.bjs.co.uk). DOI: 10.1002/bjs.6870

Introduction

About 1015 per cent of the adult Western population

have gallstones1 4. Between 1 and 4 per cent become

symptomatic each year4,5. In the UK, some 50 000

cholecystectomies are performed annually6, of which

70 90 per cent are carried out laparoscopically710 and

a third are performed for acute cholecystitis11. Thus,approximately 13 000 laparoscopic cholecystectomies are

performed annually in the UK for acute cholecystitis.

There is considerable controversy over the timing of

laparoscopic cholecystectomy in acute cholecystitis. In

the era of open cholecystectomy, early surgery (within

7 days of onset of symptoms) had no increased morbidity

or mortality over delayed surgery (at least 6 weeks

after symptoms settled)12. Delaying surgery increases the

risks of further gallstone-related complications12,13. With

laparoscopic cholecystectomy, there are concerns about

higher morbidityrates in an emergency procedure1416 and

the higher conversion rate to an open procedure during

the acute phase8,17. The main reason for conversion in

early laparoscopic cholecystectomy (ELC) is inflammation

obscuring the view of Calots triangle18, whereas in

delayed laparoscopic cholecystectomy (DLC) it is fibrotic

adhesions18,19. Severe inflammation and fibrotic adhesions

are associated with bile duct injury20.

In the USA, about 30 per cent of patients with acute

cholecystitis undergo cholecystectomy during the acute

attack8. In the UK, only 20 per cent of surgeons perform

laparoscopic cholecystectomy during acute cholecystitis21.

The remainder allow the symptoms to settle for at

least 6 weeks before performing DLC21. Meta-analyses

Copyright 2009 British Journal of Surgery Society Ltd British Journal of Surgery 2010; 97: 141150Published by John Wiley & Sons Ltd


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142 K. Gurusamy, K. Samraj, C. Gluud, E. Wilson and B. R. Davidson

of randomized clinical trials (RCTs) of ELC versus DLCduring acute cholecystitis have concluded that ELC is safeand decreases the length of hospital stay22,23. The presentarticle is an update of the authors Cochrane Hepato-Biliary Group (CHBG) systematic review published in

200622, with additional outcomes included. The aim ofthis systematic review with meta-analysis was to determine

whether patients with acute cholecystitis should be offeredELC or should undergo a delayed procedure.

Methods

Identification of trials and data extraction

Only RCTs (irrespective of language, blinding, samplesize or publication status) that compared ELC (within7 days of onset of symptoms) with DLC (intended to beperformed after an interval of at least 6 weeks after the

index attack of acute cholecystitis) were included. Quasi-randomized trials (in which the methods of allocatingparticipants to a treatment were not strictly random, suchas by date of birth, hospital record number or alternation)

were excluded. Only trials that reported at least one of theprimary outcomes (mortality; surgery-related morbiditysuch as bile duct injury, bile leak, reoperation rate,infection, bleeding; complications during waiting timesuch as pancreatitis, recurrent episodes of cholecystitis,obstructive jaundice; conversion to open cholecystectomy)or secondary outcomes (operating time, incidence ofcommon bile duct stones, hospital stay, number of work

days lost, quality of life) were included. Hospital stay wasdefined as the time spent in hospital from all hospitaladmissions starting from the onset of symptoms until thecompletion of surgery, including those for surgery- anddisease-related complications.

The CHBG Controlled Trials Register, the CochraneCentral Register of Controlled Trials (CENTRAL) in

The Cochrane Library, Medline, Embase and ScienceCitation Index Expanded were searched up to November2008 using the medical subject headings (MeSH) termscholecystectomy, laparoscopic and cholecystitis, acute.Equivalent free text search terms were used in the searchstrategy. A filter for identifying RCTs recommended by

The Cochrane Collaboration24 was used to filter outnon-randomized studies in Medline and Embase. Thereferences of the included trials were searched to identifyfurther trials.

Two authors (K.G. and K.S.) independently identifiedthe trials for inclusion, extracted data related to theoutcomes mentioned above and assessed the risk of biasin trials as described below. There were no discrepanciesin the selection of the trials or in data extraction between

the reviewers except in the assessment of blinding. Bothreviewers agreed that blinding was unethical or impossibleto achieve. However, there was disagreement with regardto whether the trials should be classified as having a highor low risk of bias. Primary outcomes such as surgical

morbidity and decision to convert to open cholecystectomyare based on subjective criteria and lack of blinding is apotential source of bias for these outcomes. It was thereforeagreed that lack of blinding would result in the trialsbeing classified as having a high risk of bias. Any unclearor missing information was obtained by contacting theauthors of the individual trials.

Assessment of risk of bias

There is a risk of overestimation of beneficial treatmenteffects in RCTs with a high risk of bias2528. The risk

of bias was assessed according to the guidelines of TheCochrane Collaboration and the CHBG Module24,29,30.

The assessment of risk of bias in the trials was based onsequence generation; allocation concealment; blinding ofparticipants, personnel and outcome assessors; incompleteoutcome data; selective outcome reporting; and othersources of bias such as baseline imbalance, early stoppingbias, academic bias and source of funding bias24,29,30.Considering that the period of follow-up was short andthe incidence of complications low, any trial that reportedloss to follow-up of any patient was considered to sufferfrom bias owing to incomplete outcome data.

Statistical analysis

The software package RevMan 531 provided by TheCochrane Collaboration was used for analysis. The riskratio (RR) with 95 per cent confidence interval (c.i.)

was calculated for dichotomous variables, and the meandifference with 95 per cent c.i. for continuous variables.If the mean values were not available for continuousoutcomes, median values were used for meta-analysis.If the standard deviation was not available, it wascalculated according to the guidelines of The CochraneCollaboration24. This involves assumptions that bothgroups have the same variance, which may not be true.

The random-effects model32 and the fixed-effect model33

were used. In case of heterogeneity only the results ofthe random-effects model were reported. Heterogeneity

was explored using the 2 test, with significance set atP< 0100, and quantified34 using I2, with a maximumvalue of 30 per cent identifying low heterogeneity24.

All analyses were based on the intention-to-treatprinciple35 using good-outcome analysis (assuming that

Copyright 2009 British Journal of Surgery Society Ltd www.bjs.co.uk British Journal of Surgery 2010; 97: 141150Published by John Wiley & Sons Ltd


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Early versus delayed laparoscopic cholecystectomy for acute cholecystitis 143

Potentially relevant RCTs identified and

screened for retrieval

n= 535

RCTs excluded n= 524Duplicates n= 158Irrelevant from titles and abstracts n= 366

RCTs excluded n= 4Non-randomized n= 1Out of scope n= 3

RCTs excluded from meta-analysis n= 2Multiple reports n= 2

RCTs withdrawn, by outcome n= 0

RCTs retrieved for more detailed

evaluation

n= 11

Potentially appropriate RCTs to be

included in the meta-analysis

n= 7

RCTs included in meta-analysis

n= 5

RCTs with usable information, by

outcome

n= 5

Fig. 1 QUOROM diagram for the study. *Interventions did not fall within the definitions used for early and/or delayed laparoscopic

cholecystectomy in this review. RCT, randomized controlled trial

morbidity would not have occurred in patients whodropped out after randomization and did not actuallyundergo surgery) for all outcomes, except conversion

to open cholecystectomy where different scenarios wereused, such as good-outcome analysis (none of thepostrandomization dropouts in either group would haverequired conversion to open cholecystectomy), poor-outcome analysis (all postrandomization dropouts inboth groups would have required conversion to opencholecystectomy), extreme case favouring ELC (noneof the postrandomization dropouts in the early group

would have required conversion to open cholecystectomybut all those in the delayed group would have requiredconversion) and extreme case favouring DLC (the oppositeof extreme case favouring ELC). This is because ofthe low incidence of morbidity in both groups in theauthors previous review22, leaving conversion to opencholecystectomy the only primary outcome suitable for theother scenarios. Available-case analysis24 of the primaryoutcomes was also performed to check whether the resultschanged.

A subgroup analysis of the primary outcomes wasperformed to determine whether trials that includedonly patients who had symptoms for less than 4 days

yielded different results from those that included patients

with symptoms for 7 days. A further subgroup analysisexamined whether the results varied with surgical

experience. The 2 test of subgroup differences was

used to identify differences in the effect estimates in thesubgroups24. Sensitivity analysis (reanalysis of the data

after excluding one or more trials to assess whether theeffect estimates are altered) was carried out, with inclusionof trials with a low risk of bias in domains other than

blinding.A funnel plot was used to explore publication bias36,37.

Asymmetry in the funnel plot of study size againsttreatment effect was used to identify publication bias.

Results

A total of 535 references were identified through theelectronic searches (Fig. 1).No new trialswereidentifiedby

searching references. In total, seven publications describingfive completed randomized trials fulfilled the inclusioncriteria19,3843.

All the trials included patients with acute cholecystitis

due to gallstones. Two trials excluded patients withcommon bile duct stones42,43. Some 223 patients wererandomized to ELC and 228 to DLC. There was no



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Table 1 Characteristics of included trials

Reference Year

Timing

of ELC

(days)

Timing

of DLC

(weeks)

Surgeons

experience

No. of

patients

(ELC : DLC)

Postrandomization

dropouts

(ELC : DLC)*

Early

surgery

required in

DLC group

D avila et al.38 1999


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Reference

Dvila et al.38

Johansson et al.39

Kolla et al.42

Lai et al.43

Lo et al.19

Total

Heterogeneity: 2= 132, 3 d.f., P= 073, I2= 0%

Test for overall effect: Z= 062, P= 054

Bile duct injury

ELC

0 of 27

0 of 74

1 of 20

0 of 530 of 49

1 of 223

1 of 36 269 044 (002, 1041)

032 (001, 773)

300 (013, 6952)

Not estimable034 (001, 815)

064 (015, 265)

001 01

Favours ELC Favours DLC

1 10 100

318

104

309

1000

1 of 71

0 of 20

0 of 511 of 50

3 of 228

DLC Weight (%) Risk ratio Risk ratio

Fig. 2 Meta-analysis of bile duct injury in early (ELC) versusdelayed (DLC) laparoscopic cholecystectomy groups. Risk ratios are shown

with 95 per cent confidence intervals

Table 3 Conversion and bile duct injury

Conversion to open surgery Bile duct injury

Reference ELC DLC Crossover* Elective ELC DLC

D avila et al.38 1 of 27 (4) 6 of 36 (17) 4 of 5 (80) 2 of 31 (6) 0 of 27 (0) 1 of 36 (3)

Johansson et al.39 23 of 74 (31) 20 of 69 (29) 10 of 18 (56) 10 of 51 (20) 0 of 74 (0) 1 of 69 (1)

Kolla et al.42 5 of 20 (25) 5 of 20 (25) 0 of 20 (0) 5 of 20 (25) 1 of 20 (5) 0 of 20 (0)

Lai et al.43 11 of 53 (21) 11 of 46 (24) 2 of 8 (25) 9 of 38 (24) 0 of 53 (0) 0 of 46 (0)

Lo et al.19 5 of 48 (10) 9 of 45 (20) 2 of 9 (22) 7 of 36 (19) 0 of 48 (0) 1 of 45 (2)

All studies 45 of 222 (203) 51 of 216 (236) 18 of 40 (45) 33 of 176 (188) 1 of 222 (05) 3 of 216 (14)

Values in parentheses are percentages. Dropouts (did not undergo surgery) were excluded. *Those belonging to the delayed laparoscopic cholecystectomy

(DLC) group who had worsening, non-resolution or recurrence of acute cholecystitis. Those belonging to DLC group who were successfully managed

conservatively. ELC, early laparoscopic cholecystectomy.

calculated for these purposes. The pooled odds ratio wasinfinity (95 per cent c.i. 142 to infinity; P = 001). Thepooled odds ratio was infinity because this complicationdid not occur in any patient undergoing DLC. Some32 per cent (seven of 222) required ERCP in the earlygroup compared with 0 per cent (none of 216) in thedelayed group.

Other complications There was no significant difference between the twogroups regarding intra-abdominal collections requiringintervention (RR 182 (95 per cent c.i. 057 to 587); P =031), superficial wound infections (RR 137 (95 per centc.i. 058 to 323); P = 048) or deep wound infections (RR044 (95 per cent c.i. 010 to 196); P = 028).

Gallstone-related morbidity during waiting periodTwo patients in the delayed group developed cholangitisduring the waiting time, but there were no reports ofpancreatitis. In 40 (175 per cent) of 228 patients in theDLC group symptoms either did not resolve or recurredbefore the planned operation and emergency laparoscopic

cholecystectomy was necessary. The proportion ofoperations converted to open cholecystectomy was 18 of

40 in this group (Table 3).

Conversion to open cholecystectomyThere was no significant difference between the two groupsregarding conversion to open cholecystectomy (RR 088

(95 per cent c.i. 062 to 125); P = 047) (Fig. 3). The

conversion rate was 203 per cent (45 of 222) in the early

group and 236 per cent (51 of 216) in the delayed group(Table 3). There was no change in the results when two

scenarios of the intention-to-treat analysis were applied:

poor-outcome analysis and worst-case ELC analysis.

However, in the best-case ELC analysis, the rate of

conversion to open cholecystectomy was significantlylowerin the early group than in the delayed group (RR 071

(95 per cent c.i. 051 to 099); P = 004).

Two trials included only patients fewer than 4 days from

onset of symptoms38,42 and three included patients fewerthan 7 days from onset of symptoms19,39,43. There was no

significant difference in the conversion or complication



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Reference

Dvila et al.38

Johansson et al.39

Kolla et al.42

Lai et al.43

Lo et al.19

Total


Test for overall effect: Z= 072, P= 047

Conversion

ELC

1 of 27

23 of 74

5 of 20

11 of 535 of 49

45 of 223

6 of 36 101 022 (003, 174)

110 (067, 182)

100 (034, 293)

096 (046, 202)057 (020, 157)

088 (062, 125)

005 02


1 5 20

403

99

221176

1000

20 of 71

5 of 20

11 of 519 of 50

51 of 228

DLC Weight (%) Risk ratio Risk ratio

Fig. 3 Meta-analysis of bile duct injury in early (ELC) versusdelayed (DLC) laparoscopic cholecystectomy groups. Risk ratios are shown

with 95 per cent confidence intervals

Reference

Johansson et al.39

Kolla et al.42

Lai et al.43

Lo et al.19

Total


Test for overall effect: Z= 738, P< 0001

ELC

n

74

20

53

49

50(91) 137 300 (596, 004)

600 (1062, 138)

400 (535, 265)

500 (788, 212)

412 (522, 303)


0510 5 10

56

662

145

1000

41(86)

76(36)

60(73)

71

20

51

50

80(91)

101(61)

116(34)

110(73)

192196

Mean(s.d.) (days) Weight (%) Mean difference (days) Mean difference (days)

DLC

n Mean(s.d.) (days)

Fig. 4 Meta-analysis of hospital stay in early (ELC) versusdelayed (DLC) laparoscopic cholecystectomy groups. Mean differences are

shown with 95 per cent confidence intervals

rate in the patients operated on fewer than 4 days or fewerthan 7 days after the onset of symptoms.

Secondary outcomes

Operating time Two trials42,43 reported the mean and three19,38,39 themedian operating time. The median was used in themeta-analysis. There was no significant difference in theoperating time between the two groups (mean difference

133 (95 per cent c.i. 325 to 059) days; P = 018). The median operating time reported in two trials waslonger in the early group than in the delayed groupby 21 min19 and 30 min38. The median operating timein one trial, in which laparoscopic common bile ductexploration was used for suspected common bile ductstones on routine peroperative cholangiography (withsurgical residents carrying outthese procedures), was2 minshorter in the early group39. Excluding this trial, the totaloperating time was longer in the early group than in thedelayed group (mean difference 1836 (95 per cent c.i. 778

to 2895) min; P< 0001). Excluding the three trials thatreported median values, mean operating time was longerin the ELC group (mean difference 1510 (95 per cent c.i.258 to 2762) min; P = 002).

Incidence of common bile duct stones Two trials excluded patients with common bile ductstones42,43. Meta-analysis of the remaining trialsshowed nosignificant difference in the incidence of common bile ductstones (RR 090 (95 per cent c.i. 032 to 257); P = 084).

Hospital stayThe mean total hospital stay ranged from 41 to 76 daysin the early group and from 80 to 116 days in the delayedgroup. One trial did not report total hospital stay38. Twotrials42,43 reported the mean(s.d.) hospital stay and two19,39

provided a median value. The median was used in the meta-analysis after imputing the standard deviation from the P

value. The total hospital stay was shorter in the early groupthan in the delayed group by 4 days (mean difference 412(95 per cent c.i. 522 to 303); P< 0001) (Fig. 4). The



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median hospital stay reported in two trials was shorterin the early group than in the delayed group by 3 days19

and 5 days39. Excluding these trials did not alter the meandifference in the total hospital stay (416 (95 per cent c.i.545 to 286); P< 0001).

Number of work days lostThe total number of work days lost was significantly lowerwith ELC than DLC by 11 days in the only trial19 thatreported this outcome in 36 patients who were in activeemployment during the trial period (15 versus 26 days;mean difference 1100 (95 per cent c.i. 1961to 239);

P = 001)19.

Quality of lifeOnly one trial reported this outcome40. Quality of life wasmeasured 1, 3 and 6 months after surgery in both groupsusing a gastrointestinal symptom rating scale and genericpsychological well-being index.At 1 monthafteroperation,quality of life measured by means of the gastrointestinalsymptom rating scale was significantly better after ELCthan DLC (P< 001 in the dimensions of indigestion,diarrhoea and abdominal pain). There was no significantdifference in the scores on this scale between the groupsat 3 and 6 months, nor was there any difference in thepsychological well-being index at any time (P = 011).

Heterogeneity

Subgroup and sensitivity analyses

All the trials had a high risk of bias. This was mainlydue to the lack of blinding. Considering that blindingis unethical or impossible to achieve in this setting, asensitivity analysis was performed of trials that had a lowrisk of bias in other important domains19,39,42,43. This didnot change the results.

Subgroup analysis of trials including only patients withfewer than 4 days since onset of symptoms and those alsoincluding patients with symptoms for more than 4 days inthe early group showed no significant difference betweenthe ELC and DLC groups in any of the outcome measures.

Subgroup analysis was performed of trials in which

the surgeons had experience of a minimum of 2550laparoscopic cholecystectomies. There was no significantdifference between the early and delayed group in anyoutcome measure in spite of the varying surgical experienceof the surgeons.

Funnel plot The funnel plot did not reveal any publication bias.However, there were too few trials to perform the Eggerstest for exploration of bias.

Discussion

This systematic review with meta-analysis of RCTs foundno significant difference in complication or conversionrates whether laparoscopic cholecystectomy had been

performed at presentation with acute cholecystitis or6 12 weeks after the symptoms had settled. The earlystrategy had the advantage of decreased hospital stay andavoided the risk of emergency surgery for non-resolved orrecurrent symptoms with a high rate of conversion to opencholecystectomy. Open cholecystectomy is associated withan increase in morbidity, pain and time to return to work44.

Bile duct injury is the most feared complication duringcholecystectomy and can be fatal45. Corrective surgeryfor bile duct injury has a high morbidity rate and isnot without mortality45,46; quality of life can be pooreven 3 years after corrective surgery47. Cholecystitis hasbeen considered as a risk factor for bile duct injury20,48.

Observational studies have suggested a larger number ofbile duct injuries49,50 with early surgery, but this wasnot evident from the randomized trials. Larger studiesare required to demonstrate small differences in bile ductinjury rates between an early or delayed approach to acutecholecystitis.

Bile leakage is a complication in about 1 per cent oflaparoscopic cholecystectomies51,52. These are usually dueto cystic stump leaks5254 and the majority are successfullymanaged by endoscopic sphincterotomy with or without atemporary stent53,54. In the present analysis, leaks occurredin about 3 per cent of patients in the ELC group and

were successfully managed endoscopically. No patient inthe delayed group experienced this complication. Possiblereasons for this difference in bile leakage between thegroups include the friability of the oedematous tissue or alower threshold for ERCP for suspected bile leaks in theearly group.

Another important issue is gallstone-related morbidityduring the waiting period for cholecystectomy. Themost important is the non-resolution or recurrence ofcholecystitis. Forty patients (175 per cent) in the delayedgroup underwent emergency surgery during the waitingperiod, with a very high conversion rate. Although there

were few instances of gallstone-related morbidity in thetrials included in the meta-analysis, cholecystectomy inthe delayed group was performed within 12 weeks in allthe trials. However, the reality of elective cholecystectomyoutside trials is likely to be different11,13. Patients awaitingsurgery for longer than 12 weeks have a significant risk ofdeveloping complications of gallstones13,55.

Observational studies have suggested a higher conver-sion rate to open surgery in the early group whereasrandomized trials have shown no difference between the



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groups. This may be due to lack of intention-to-treat analy-sis in observational studies, with patients from the delayed

surgery group who had to undergo emergency surgerybeing included in the early surgery group (treatment-received analysis).

The total hospital stay was shorter by 4 days with ELCthan with delayed surgery. This was due to patients in

the delayed group requiring two treatment episodes, onefor the conservative treatment of acute cholecystitis andanother for definitive surgical treatment. In addition, manyof the patients in the delayed group required emergencyreadmission owing to recurrent symptoms. The number of

work days lost was also less with ELC in the only trial that

reported this outcome19.Although there are reports of an increased conversion

rate if cholecystectomy is delayed for more than 4896 hafter the onset of symptoms18,5658, this has not been

confirmed in other studies59,60

. In this review comparableresults were found for patients operated on within 4 days

or within 7 days after symptom onset, suggesting thatlaparoscopic cholecystectomy is possible and appropriateup to 7 days after the onset of symptoms.

Another issue is experience of the surgeons39. Although

subgroup analysis did not reveal a significant differencein outcomes after early versus delayed cholecystectomy in

relation to the experience of the surgeons, the techniqueshad to be modified and gallbladder decompression wasnecessary more often in the early group than in thedelayed group, suggesting more complex surgery19,42,43.

Laparoscopic cholecystectomy performed by upper gastro-intestinal surgeons has a lower rate of conversion to

open cholecystectomy and shorter hospital stay than thatperformed by non-upper gastrointestinal surgeons61. ELCshould therefore be performed in units with appropriatesurgical expertise.

The quality-of-life data reported in this meta-analysisincluded postoperative quality of life in only onetrial. This demonstrated better quality of life in termsof gastrointestinal symptoms 1 month after ELC thanDLC, but no differences thereafter40. Considering costsincurred up to 1 year after presentation, ELC could save

approximately 8 million (895 million) annually in theUK National Health Service62. The recommendation ofthe economic analysis is, therefore, that a policy of ELCshould be adopted in preference to DLC.

All the trials in this review had a high risk of bias.

However, blinding can be impossible to achieve in thissituation and it is unlikely that trials with a low risk of biascan be designed. There is a high risk of type I (erroneouslyconcluding that an intervention is beneficial when it is not)and type II (erroneously concluding that an intervention

is not beneficial when it actually is) errors because of thefew trials included and the small sample size in each trial63.New trials with adequate sample size are needed to decreasethe risk of type I and type II errors.

The findings of this review are applicable to patients

with acute cholecystitis due to gallstones, who are eligiblefor laparoscopic cholecystectomy and have had symptomsfor fewer than 7 days, with or without common bileduct stones. ELC during acute cholecystitis appears tobe safe and shortens the total hospital stay. Surgery ismore complex and conversion rates are higher in acutecholecystitis than in uncomplicated symptomatic gallstonedisease. Although this meta-analysis showed no effect ofsurgeons experience between early and delayed surgery onany of the outcome measures, including bile duct injuryand conversion to open operation, surgeons with adequatelaparoscopic experience are likely to perform better when

dealing with acute cholecystitis.

Acknowledgements

This paper is a substantially shortened version of aCochrane review submitted to the CHBG. Cochranereviews are regularly updated as new evidence emerges,and in response to comments and criticisms. TheCochrane Library should be consulted for the mostrecent version of the review. The results of a Cochranereview can be interpreted differently, depending onpeoples perspectives and circumstances. Please consider

the conclusions presented carefully. They are the opinionsof authors, and are not necessarily shared by The CochraneCollaboration.

The authors thank the CHBG for the support and advicethat they provided for the preparation of this review. Theauthors declare no conflict of interest.

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Acute Cholecystitis - Early vs Delayed Intervention Met Analysis

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