laparoscopic versus open surgery for suspected appendicitis

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Laparoscopic versus open surgery for suspected appendicitis

(Review)

Sauerland S, Jaschinski T, Neugebauer EAM

This is a reprint of a Cochrane review, prepared and maintained by The Cochrane Collaboration and published in The Cochrane Library2010, Issue 10

http://www.thecochranelibrary.com

Laparoscopic versus open surgery for suspected appendicitis (Review)

Copyright 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
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T A B L E O F C O N T E N T S

1HEADER . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1ABSTRACT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

2PLAIN LANGUAGE SUMMARY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2BACKGROUND . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .3OBJECTIVES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .3METHODS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .5RESULTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Figure 1. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 79DISCUSSION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

10AUTHORS CONCLUSIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .11ACKNOWLEDGEMENTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .11REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .22CHARACTERISTICS OF STUDIES . . . . . . . . . . . . . . . . . . . . . . . . . . . . .90DATA AND ANALYSES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Analysis 1.1. Comparison 1 Laparoscopic versus conventional appendectomy in adults or adolescents, Outcome 1 Wound

infections. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 94Analysis 1.2. Comparison 1 Laparoscopic versus conventional appendectomy in adults or adolescents, Outcome 2Intraabdominal abscesses. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 97

Analysis 1.3. Comparison 1 Laparoscopic versus conventional appendectomy in adults or adolescents, Outcome 3Operation time (minutes). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 99

Analysis 1.4. Comparison 1 Laparoscopic versus conventional appendectomy in adults or adolescents, Outcome 4Operation time (minutes, median data). . . . . . . . . . . . . . . . . . . . . . . . . . 101

Analysis 1.5. Comparison 1 Laparoscopic versus conventional appendectomy in adults or adolescents, Outcome 5Anaesthesia time (minutes). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 102

Analysis 1.6. Comparison 1 Laparoscopic versus conventional appendectomy in adults or adolescents, Outcome 6Anaesthesia time (minutes, median data). . . . . . . . . . . . . . . . . . . . . . . . . 102

Analysis 1.7. Comparison 1 Laparoscopic versus conventional appendectomy in adults or adolescents, Outcome 7 Painintensity on day 1 (cm VAS). . . . . . . . . . . . . . . . . . . . . . . . . . . . . 103

Analysis 1.8. Comparison 1 Laparoscopic versus conventional appendectomy in adults or adolescents, Outcome 8 Painintensity on day 1 (cm VAS, median data). . . . . . . . . . . . . . . . . . . . . . . . . 104Analysis 1.9. Comparison 1 Laparoscopic versus conventional appendectomy in adults or adolescents, Outcome 9 Length

of hospital stay (days, mean data)). . . . . . . . . . . . . . . . . . . . . . . . . . . 105Analysis 1.10. Comparison 1 Laparoscopic versus conventional appendectomy in adults or adolescents, Outcome 10 Length

of hospital stay (days, median data). . . . . . . . . . . . . . . . . . . . . . . . . . . 107Analysis 1.11. Comparison 1 Laparoscopic versus conventional appendectomy in adults or adolescents, Outcome 11 Time

until reintroduction of liquid diet (days). . . . . . . . . . . . . . . . . . . . . . . . . 108Analysis 1.12. Comparison 1 Laparoscopic versus conventional appendectomy in adults or adolescents, Outcome 12 Time

until reintroduction of liquid diet (days, median data). . . . . . . . . . . . . . . . . . . . . 109Analysis 1.13. Comparison 1 Laparoscopic versus conventional appendectomy in adults or adolescents, Outcome 13 Time

until reintroduction of solid diet (days). . . . . . . . . . . . . . . . . . . . . . . . . . 110Analysis 1.14. Comparison 1 Laparoscopic versus conventional appendectomy in adults or adolescents, Outcome 14 Time

until reintroduction of solid diet (days, median data). . . . . . . . . . . . . . . . . . . . . 111Analysis 1.15. Comparison 1 Laparoscopic versus conventional appendectomy in adults or adolescents, Outcome 15 Timeuntil first stool (days). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 112

Analysis 1.17. Comparison 1 Laparoscopic versus conventional appendectomy in adults or adolescents, Outcome 17 Timeuntil return to normal activity (days). . . . . . . . . . . . . . . . . . . . . . . . . . . 113

Analysis 1.18. Comparison 1 Laparoscopic versus conventional appendectomy in adults or adolescents, Outcome 18 Timeuntil return to normal activity (days, median data). . . . . . . . . . . . . . . . . . . . . . 114

Analysis 1.19. Comparison 1 Laparoscopic versus conventional appendectomy in adults or adolescents, Outcome 19 Timeuntil return to work (days). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 115

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Analysis 1.20. Comparison 1 Laparoscopic versus conventional appendectomy in adults or adolescents, Outcome 20 Timeuntil return to work (days, median data). . . . . . . . . . . . . . . . . . . . . . . . . 116

Analysis 1.22. Comparison 1 Laparoscopic versus conventional appendectomy in adults or adolescents, Outcome 22 Timeuntil return to sport (days, median data). . . . . . . . . . . . . . . . . . . . . . . . . 117

Analysis 1.23. Comparison 1 Laparoscopic versus conventional appendectomy in adults or adolescents, Outcome 23

Cosmesis (cm VAS). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 117Analysis 1.24. Comparison 1 Laparoscopic versus conventional appendectomy in adults or adolescents, Outcome 24Cosmesis (cm VAS, median data). . . . . . . . . . . . . . . . . . . . . . . . . . . . 118

Analysis 1.25. Comparison 1 Laparoscopic versus conventional appendectomy in adults or adolescents, Outcome 25 Costsof the operation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 119

Analysis 1.26. Comparison 1 Laparoscopic versus conventional appendectomy in adults or adolescents, Outcome 26 Costsof the operation (median data). . . . . . . . . . . . . . . . . . . . . . . . . . . . . 119

Analysis 1.27. Comparison 1 Laparoscopic versus conventional appendectomy in adults or adolescents, Outcome 27 Costswithin hospital stay (incl. the operation). . . . . . . . . . . . . . . . . . . . . . . . . 120

Analysis 1.28. Comparison 1 Laparoscopic versus conventional appendectomy in adults or adolescents, Outcome 28 Costswithin hospital stay (incl. the operation, median data). . . . . . . . . . . . . . . . . . . . . 121

Analysis 1.29. Comparison 1 Laparoscopic versus conventional appendectomy in adults or adolescents, Outcome 29 Costsoutside hospital. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 121

Analysis 1.30. Comparison 1 Laparoscopic versus conventional appendectomy in adults or adolescents, Outcome 30 Costsoutside hospital (median data). . . . . . . . . . . . . . . . . . . . . . . . . . . . . 122Analysis 2.1. Comparison 2 Laparoscopic versus conventional appendectomy in children, Outcome 1 Wound infections

(rate). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 123Analysis 2.2. Comparison 2 Laparoscopic versus conventional appendectomy in children, Outcome 2 Intraabdominal

abscesses (rate). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 124Analysis 2.3. Comparison 2 Laparoscopic versus conventional appendectomy in children, Outcome 3 Operation time

(minutes). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 125Analysis 2.4. Comparison 2 Laparoscopic versus conventional appendectomy in children, Outcome 4 Anaesthesia time

(minutes). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 126Analysis 2.5. Comparison 2 Laparoscopic versus conventional appendectomy in children, Outcome 5 Pain intensity on day

1 (cm VAS). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 127Analysis 2.6. Comparison 2 Laparoscopic versus conventional appendectomy in children, Outcome 6 Length of hospital

stay (days). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 128Analysis 2.10. Comparison 2 Laparoscopic versus conventional appendectomy in children, Outcome 10 Time untilmobilisation (days). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 129

Analysis 2.11. Comparison 2 Laparoscopic versus conventional appendectomy in children, Outcome 11 Time until returnto normal activity (days). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 130

Analysis 2.12. Comparison 2 Laparoscopic versus conventional appendectomy in children, Outcome 12 Time until returnto sport (days). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 131

Analysis 2.14. Comparison 2 Laparoscopic versus conventional appendectomy in children, Outcome 14 Costs of theoperation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 132

Analysis 2.15. Comparison 2 Laparoscopic versus conventional appendectomy in children, Outcome 15 Costs withinhospital stay (incl. the operation). . . . . . . . . . . . . . . . . . . . . . . . . . . . 133

Analysis 3.1. Comparison 3 Diagnostic laparoscopy (and laparoscopic or open appendectomy if necessary) versus immediateopen appendectomy, Outcome 1 Negative appendectomy (rate). . . . . . . . . . . . . . . . . 134

Analysis 3.2. Comparison 3 Diagnostic laparoscopy (and laparoscopic or open appendectomy if necessary) versus immediateopen appendectomy, Outcome 2 Patients with diagnosis not established. . . . . . . . . . . . . . 135Analysis 4.1. Comparison 4 Diagnostic laparoscopy (and open appendectomy if necessary) versus immediate open

appendectomy, Outcome 1 Wound infections. . . . . . . . . . . . . . . . . . . . . . . 136Analysis 4.2. Comparison 4 Diagnostic laparoscopy (and open appendectomy if necessary) versus immediate open

appendectomy, Outcome 2 Intraabdominal abscesses. . . . . . . . . . . . . . . . . . . . . 137Analysis 4.3. Comparison 4 Diagnostic laparoscopy (and open appendectomy if necessary) versus immediate open

appendectomy, Outcome 3 Operation time (minutes). . . . . . . . . . . . . . . . . . . . . 138

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Analysis 4.6. Comparison 4 Diagnostic laparoscopy (and open appendectomy if necessary) versus immediate openappendectomy, Outcome 6 Length of hospital stay (days). . . . . . . . . . . . . . . . . . . 139

139WHATS NEW . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .139HISTORY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .140CONTRIBUTIONS OF AUTHORS . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

140DECLARATIONS OF INTEREST . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 140DIFFERENCES BETWEEN PROTOCOL AND REVIEW . . . . . . . . . . . . . . . . . . . . .140INDEX TERMS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

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[Intervention Review]

Laparoscopic versus open surgery for suspected appendicitis

Stefan Sauerland

1

, Thomas Jaschinski

2

, Edmund AM Neugebauer

3

1Department of Non-Drug Interventions, Institute for Quality and Efficiency in Health Care, Cologne, Germany. 2Institute forResearch in Operative Medicine, University of Witten/Herdecke, Cologne, Germany. 3Institute for Research in Operative Medicine,Medical Faculty, University of Witten/Herdecke, Cologne-Merheim, Germany

Contact address: Stefan Sauerland, Department of Non-Drug Interventions, Institute for Quality and Efficiency in Health Care,Dillenburger Str. 27, Cologne, 51105, Germany. [email protected]. [email protected].

Editorial group: Cochrane Colorectal Cancer Group.Publication status and date: New search for studies and content updated (conclusions changed), published in Issue 10, 2010.Review content assessed as up-to-date: 25 August 2010.

Citation: Sauerland S, Jaschinski T, Neugebauer EAM. Laparoscopic versus open surgery for suspected appendicitis. CochraneDatabase

of Systematic Reviews2010, Issue 10. Art. No.: CD001546. DOI: 10.1002/14651858.CD001546.pub3.


A B S T R A C T

Background

Laparoscopic surgery for acute appendicitis has been proposed to have advantages over conventional surgery.

Objectives

To compare the diagnostic and therapeutic effects of laparoscopic and conventional open surgery.

Search methods

We searched the Cochrane Library, MEDLINE, EMBASE, LILACS, CNKI, SciSearch, study registries, and the congress proceedingsof endoscopic surgical societies.

Selection criteria

We included randomized clinical trials comparing laparoscopic (LA) versus open appendectomy (OA) in adults or children. Studiescomparing immediate OA versus diagnostic laparoscopy (followed by LA or OA if necessary) were separately identified.

Data collection and analysis

Two reviewers independently assessed trial quality. Missing information or data was requested from the authors. We used odds ratios(OR), relative risks (RR), and 95% confidence intervals (CI) for analysis.

Main results

We included 67 studies, of which 56 compared LA (with or without diagnostic laparoscopy) vs. OA in adults. Wound infections wereless likely after LA than after OA (OR 0.43; CI 0.34 to 0.54), but the incidence of intraabdominal abscesses was increased (OR 1.87;CI 1.19 to 2.93). The duration of surgery was 10 minutes (CI 6 to 15) longer for LA. Pain on day 1 after surgery was reduced afterLA by 8 mm (CI 5 to 11 mm) on a 100 mm visual analogue scale. Hospital stay was shortened by 1.1 day (CI 0.7 to 1.5). Return tonormal activity, work, and sport occurred earlier after LA than after OA. While the operation costs of LA were significantly higher, thecosts outside hospital were reduced. Seven studies on children were included, but the results do not seem to be much different whencompared to adults. Diagnostic laparoscopy reduced the risk of a negative appendectomy, but this effect was stronger in fertile women(RR 0.20; CI 0.11 to 0.34) as compared to unselected adults (RR 0.37; CI 0.13 to 1.01).

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mailto:[email protected]:[email protected]:[email protected]:[email protected]


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Authors conclusions

In those clinical settings where surgical expertise and equipment are available and affordable, diagnostic laparoscopy and LA (eitherin combination or separately) seem to have various advantages over OA. Some of the clinical effects of LA, however, are small andof limited clinical relevance. In spite of the mediocre quality of the available research data, we would generally recommend to uselaparoscopy and LA in patients with suspected appendicitis unless laparoscopy itself is contraindicated or not feasible. Especially young

female, obese, and employed patients seem to benefit from LA.

P L A I N L A N G U A G E S U M M A R Y

Laparoscopic (key-hole) surgery for appendicitis

In the right lower part of the abdomen there is a small blind ending intestinal tube, called appendix. Inflammation of the appendixis called appendicitis and is usually acute in onset. Appendicitis is most frequent in children and young adults. Most cases requireemergency surgery, in order to avoid rupture of the appendix into the abdomen. During the operation, called appendectomy, theinflamed appendix is surgically removed. The traditional surgical approach involves a small incision (about 5 cm or 2 inches) in theright lower abdominal wall. Alternatively, it is possible to perform the operation by laparoscopy. This operation, called laparoscopic

appendectomy, requires 3 very small incisions (each about 1 cm or 1/2 inch). The surgeon then introduces a camera and someinstruments into the abdomen and removes the appendix as in the conventional operation.

This reviewanalysed 67 clinical studies, in which surgical technique (conventional open or laparoscopic) foreach patient wasdeterminedby chance. The majority of studies were done on adults, but there were also 7 studies on children. The main advantages of laparoscopicover conventional appendectomy were reduced risk of wound infection, reduced postoperative pain, shorter hospital stay (-1 day),and more rapid return to normal activities. As disadvantages of laparoscopic appendectomy a longer duration of the operation (+10minutes) and a higher rate of intraabdominal abscesses were identified. The results for children were similar to those seen in adults.An additional benefit of the laparoscopic approach is the possibility to inspect the inside of the abdomen. Especially in women ofchildbearing age, in whom many other conditions can mimic appendicitis, laparoscopy therefore reduces the risk of an unnecessaryappendectomy.

In summary, laparoscopic surgery for suspected appendicitis has diagnostic and therapeutic advantages as compared to conventionalsurgery. However, conventional appendectomy should not be considered wrong, because the difference between the two techniques

is rather small and strongly depends on patient characteristics and the treating surgeons expertise.

B A C K G R O U N D

Since its introduction by McBurney in 1894 appendectomy is thetreatment of choice for acute appendicitis (McBurney 1894). Itsoon became one of the most frequently performed surgical proce-dures. Today, in developed countries about 8% of the population

is appendectomized for acute appendicitis during their lifetime(Addiss 1990). The surgical technique remainednearly unchangedfor over a century, as it combines therapeutic efficacy with lowmorbidity and mortality rates (Eriksson 1995). The evolution ofendoscopic surgery led to the idea of performing appendectomy inlaparoscopy, which was first described by Semm in 1983 (Semm1983). Nevertheless, the new method has only partly gained ac-ceptance (Faiz 2008; Paterson 2008; Van Hove 2008), because theadvantages of laparoscopic appendectomy were not as obvious as

for laparoscopic cholecystectomy, e.g..While somestudies claimedlaparoscopic appendectomy to be superior to open appendectomyin terms of a quicker and less painful recovery, less postoperativecomplications, and better cosmesis, other studies found no suchadvantages or even favoured the traditional approach.

Beside these therapeutic effects of LA, laparoscopyper semay of-fer valuable diagnostic opportunities. Since surgical removal of anun inflamed, normal (innocent) appendix occurs in up to 50%of patients, it has been proposed not to remove the appendix inthose situations, where other pathologies can be diagnosed duringlaparoscopy. Some surgeons therefore have used laparoscopy as adiagnostic tool only, and perform conventional appendectomy af-ter laparoscopy in those patients, where the appendix macroscop-




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ically has an abnormal appearance. However, it is not yet clari-fied, in which situations a normal looking appendix should be leftin place, although non-randomized studies indicate this (van denBroek 2001).

The large number of published trials and the still ongoing debate

prompted us to undertake a systematic review of all randomizedtrials which compared therapeutic and diagnostic advantages ofboth techniques.

O B J E C T I V E S

This review compares laparoscopic and conventional surgery withregard to several peri- and post-operative variables. It addressesdiagnostic and therapeutic laparoscopy separately. Furthermore, itaims at identifying certain subgroups of patients, in which one ofthe techniques might be more appropriate than the other.

M E T H O D S

Criteria for considering studies for this review

Types of studies

All randomized controlled trials comparing laparoscopic surgery

and open appendectomy for acute appendicitis. Trials that allocatepatients depending on the availability of staff or instruments oron the number of the day (odd or even) were excluded from theanalysis. Due to the large number of studies available, we decidedto also exclude trials that had no concealment of allocation.If a trial was reported only as an abstract, or if no measure ofdispersion was given for an outcome variable, or if the methodof randomizations was not stated, the authors were contacted toprovide full details of their trial. If the authors of an abstract didnot provide full information on their trial, the trial was excludedfrom further analysis. The decision about inclusion of studies wasdiscussed between two observers, and disagreements were resolvedby discussion.All interventions within the primary studies should be analysedon an intention-to-treat (ITT) basis, and we tried to obtain ITTdata from the study authors. For each study, we list in the studycharacteristics table the number of patients not treated accordingto study protocol, and we state whether these patients were or werenot analysed on ITT. This usually includes patients, who wereconverted from LA to OA, or who were not appendectomisedbecause of other diagnosis found on laparoscopy.

Types of participants

Patients with symptoms and signs of acute appendicitis. If a studyreported a rate of lesser than 50% appendix specimens withouthistological signs of inflammation, we assumed that this studymainly dealtwith incidental appendectomies and therefore should

be excluded.Studies which evaluated LA in children or one gender only, werenot excluded, but studies in children were analysed separately.Similarly, studies on diagnostic effects of laparoscopy in fertilewomen were analysed separately.

Types of interventions

(1) Laparoscopic versus conventional appendectomy in adults:The classical muscle-splitting appendectomy was compared withlaparoscopic appendectomy. Usually this technique requires theinsertion of three trocars into the abdominal cavity. The appendixcan be dissected by using either a stapling device (EndoGIA) or

ligatures, theso-calledRoeder or EndoLoops. Both techniquescanbe seen upon as comparable, although costs differ (Klima 1998;Kazemier 2006). Studies included in this section may (but notnecessarily so) have performed diagnostic laparoscopy.(2) Laparoscopic versus conventional appendectomy in children:Same interventions as (1).(3) Diagnostic laparoscopy (followed by open or laparoscopic ap-pendectomy if necessary) versus immediate open appendectomy:Conventional appendectomy was compared with diagnostic la-paroscopy followed by laparoscopic or conventional appendec-tomy if necessary. Studies were included only if they clearly de-scribed under what circumstances they refrained from appen-dectomy. This included patients, in whom other intraabdominal

pathologies were found and the appendix looked normal, but alsopatients, in whom no pathology was found. This section addressesonly the diagnostic effect of laparoscopy without paying attentionto therapeutic effects, which depend on the type of appendectomythat was performed after laparoscopy. The therapeutic effects ofthe studies included in (3) are summarized under section (1) whenLA andunder section (4)when OAwas performed after diagnosticlaparoscopy.(4) Diagnostic laparoscopy (followed by open appendectomy ifnecessary) versus immediate open appendectomy:Surgical techniques are described in section (3).

Types of outcome measures

The therapeuticoutcome measures (with theiraccording measure-ment units) are:(1) wound infections (rate);(2) intraabdominal abscesses (rate);(3) operation time (minutes)(4) anaesthesia time (minutes)(5) pain intensity on postoperative day 1 (cm VAS);




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(6) length of hospital stay (days);(7) time until reintroduction of liquid diet (days);(8) time until reintroduction of solid diet (days);(9) time until first stool (days);(10) time until return to normal activities (days);

(11) time until return to full activity (days);(12) time until return to sport (days);(13) cosmesis (cm VAS);(14) costs of the operation;(15) costs within hospital stay (including the operation); and(16) costs outside hospital stay.In children, the postoperative mobilisation time was assessed in-stead of return to work.The diagnostic outcome measures (with their according measure-ment units) are:(1) negative appendectomy (rate);(2) patients with diagnosis not established (rate).

Search methods for identification of studies

In order to be as comprehensive as possible, the following searchstrategies wereemployed to identify all relevant studies irrespectiveof language. Studies predating 1983 were not searched for, becausethe first laparoscopic appendectomy was described in that year.Electronically, we searched the Cochrane Library, MEDLINE(PubMed), EMBASE, SciSearch and Biosis. Additionally, wescanned foreignlanguage Databases, such as LILACS (Literatura Latinoamericanay delCaribe en Ciencias de la Salud)and CNKI (Chinese NationalKnowledge Infrastructure). Cochrane Library and MEDLINEsearches were repeated until April 15th 2010, all other databases

were last searched in August 2009. In MEDLINE, we combinedthe Cochrane Collaboration search strategy for randomized con-trolled trials with the MeSH term appendectomy. EMBASEwas searched using the controlled terms appendectomy and la-paroscopy (Emtree medical descriptors).In otherdatabases simi-lar strategies were employed.The WHO international clinical trialregistry platform was used to identify planned or ongoing stud-ies (http://apps.who.int/trialsearch/). The Science Citation Indexwas checked for papers citing K. Semm (Semm 1983). The on-line catalogues of the German (http://www.zbmed.de/index.html)and French National Medical Library (http://www.bium.univ-paris5.fr/) were searched for dissertations. The reference lists of allrelevant primary studies and review article were screened for fur-ther studies (ANDEM 1997; Golub 1998; Slim 1998; Fingerhut1999; Chung 1999; Garbutt 1999; Barth 1999; Temple 1999;Kim 2004;Aziz 2006; Kapischke 2006; Bennett 2007; Sadr-Azodi2009). Additionally, authors of relevant articles and known inter-national experts in the field of laparoscopic surgery were contactedto obtain information on any past, present, or future studies.Abstracts presented to the following international scientific so-cieties were handsearched: European Association of Endoscopic

Surgery (EAES), Society of American Gastrointestinal EndoscopicSurgeons (SAGES), American Society for Gastrointestinal En-doscopy (ASGE), Asian Surgical Association (ASA), InternationalSociety for Surgery (ISS), Endoscopic and Laparoscopic Societyof Asia (ELSA), Surgical Infection Society (SIS), and the German

Society for Surgery (Deutsche Gesellschaft fr Chirurgie, DGCh).Authors of abstracts were asked to provide full information usinga four-page data extraction form.

Data collection and analysis

All studies were assessed by two reviewers, who read the articles in-dependently from each other. For each trial, the two reviewers as-sessed three main criteria of study design and analysis: (1) methodof randomisation and allocation concealment, (2) blinding of out-come assessment, and (3) dealing with protocol violations, for in-stance converted procedures. In the Risk of Bias table, violationsof the ITT principle are described in the Other Bias column.

Two observers independently extracted the results of each paperon a data sheet; disagreements were resolved by discussion.Fordichotomousvariablesrelativerisks(RR)with95%confidenceintervals (95% CIs) were the preferred measure. For complicationrates, however, Petos odds ratios (OR) were calculated, becausesimulation studies by Deeks et al. have shown, that this effectmeasureisthemostrobustwhendealingwithrareorextremelyrareevents (Deeks1999). For dichotomous outcomes we also calculatethe number of patients that needs to be treated to prevent onecomplication (NNT). We expected complication rate to vary onlyby a very small degree, and therefore used fixed-effects models(Hardy 1998), unless heterogeneity was present.In the analysis of continuous variables, generally means with their

corresponding standard deviations (SDs) are needed to calculateweighted or standardized mean differences with 95% CIs. How-ever, some of the variables, e.g. hospital stay or length of surgery,tend to have non-Gaussian distributions. Thus, authors under-standably use nonparametric statistics and give their data as medi-ans with ranges. Although this is correct for a single study, meta-analysis cannot use this data. On the other hand, it can be mis-leading to request means and SDs from all trial authors, becausethis would simply ignore the non-Gaussian distribution. In con-clusion, we present mean and median data separately, but we useonly mean data for statistical pooling. In case a study failed toreport SDs for an outcome measure, we assumed that the SD isequal to the mean value itself. This approach produces relativelyconservative results, since studies without reporting of SDs tendedto receive less weight. We pooled the effect measures within a ran-dom effects model (DerSimonian 1986), because these outcomesare heavily influenced by the context of care.Studies on diagnostic laparoscopy were divided into those per-formed on unselected patients and those on fertile women. Sen-sitivity analyses were a priori planned to compare the study re-sults for their inclusion criteria (i.e. sex ratio, percentage of perfo-




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rated or gangrenous cases), technique of laparoscopic appendec-tomy (loops vs stapler for closure of appendix stump, learning-curve apparent vs not) and study design and reporting (adequatevs unclear allocation concealment, studies that reported means vsmedians). To control the influence of a possible publication bias

we test funnel plot asymmetry as proposed by Egger et al. ( Egger1997).

R E S U L T S

Description of studies

See: Characteristicsofincludedstudies; Characteristicsofexcludedstudies; Characteristics of ongoing studies.All included studies used similar subjective clinical criteria to iden-

tify patients suspected to suffer from acute appendicitis. The agerange and the gender ratio, however, were quite different amongthe studies, since most studies on diagnostic laparoscopy includedfertilewomenonly. Some of the studies excludedpatientsin whoma perforated appendix was suspected. Although this was not ex-plicitly described in all studies, we assume that all studies excludedpregnant women and patients in whom laparoscopy was preoper-atively believed impractical.The interventions were very similar among the studies. Laparo-scopic appendectomy was usually performed with the use of threetrocars for access and ligatures for stump closure. A stapling devicefor securing the appendix stump was routinely used by only a fewtrialists (Hall Long 2000; Heikkinen 1998; Henle 1996; Kaiser

2006; Katkhouda 2005; Laine 1997; Martin 1995; Moberg 2005;Nordentoft 2000; Simon 2009; Williams 1996; Witten 1998).The trial by Ortega et al. (Ortega 1996) had a three-armed de-sign to compare stapling and loops for appendiceal stump closure.While some trials used disposable instruments (which are quite ex-pensive), other used reusable ones. One further three-armed trialused needlescopic instruments with 2mm ports (Huang 2001).Nearly all studies described that both treatment groups receivedthe same single dose of antibiotics. Those studies that used la-paroscopy for diagnosing appendicitis had different criteria, whento remove the appendix or not.Most trials assessed several cl inical outcomes within hospital stay,although some trials had a follow-up examination of one monthafter surgery. The most commonly examined outcomes were op-erating time, complication rates, hospital stay, pain, and return tonormal activities. Some studies were interested in return of bowelfunction, cosmetic result and costs. Other outcomes, which arenot assessed in this review (but in some primary trials), includequality of life (Kaplan 2009; Vallribera 2003), the rate of bac-teraemia (Sezeur 1997; Nordentoft 2000), the rate of postopera-tive adhesions on second-look laparoscopy (DeWilde 1991), and

somepathophysiological parameters (Perner1999; Karadayi2003;Simon 2009).Three trials presented their results in combination with other re-sults. One trial (Settmacher 1995) compared laparoscopic appen-dectomy and cholecystectomy against the corresponding conven-

tional techniques. A second very small trial (n= 11; Perner 1999)reported on LA and OA, but also on laparoscopic colectomy. Athird trial (Williams 1996) reported results for randomized andnon-randomized patients. In all these cases, we used only the rel-evant part of the data.One trial was described only in a meta-analysis, of which the pri-mary trialist was a coauthor (Barth 1999). We met the trialist, buthe failed to provide us with further data. We decided to includethe trial results, that were reported in the meta-analysis.Several trials were reported on in more than just one publication.Of note, the two articles by Lintula et al. described different stagesof the same trial (Lintula 2004), with 73 and 87 patients. We usedthe most complete information, wherever possible. One trial was

reported in three different publications (Henle 1996). We wereunable to resolve the discrepancies in complication rates amongthe three papers (Neugebauer 1999). We decided not to use thetrial results on infectious complications, but we included the trialsother outcome data, which were reported consistently.

Risk of bias in included studies

The quality of all included studies was moderate to poor (Figure1). Most studies had very similar flaws. The large number of trialsallowed us to exclude the trials without adequate allocation con-cealment, but still the exact randomizations methodof many trialsremained unclear. In total, 42 trials (63%) were judged to have an

adequatelyconcealed process of randomisation. Notunexpectedly,only nine trials (Ortega 1996; Lejus 1996; Lintula 2004; Huang2001; Ignacio 2003; Katkhouda 2005; Moberg 2005; Ricca2007;YIn 1996) took measures to blind investigator and/or patientagainst treatment received. This represents 13% of all trials.In nearly all studies, protocol violations occurred, which subse-quently were or were not analysed on intention-to-treat (ITT) ba-sis. Patients who were intraoperatively converted from LA to OA(or vice versa) were excluded from analysis in six studies (Bauwens1999; Hart 1996; Henle 1996; Nordentoft 2000; Williams 1996;Karadayi 2003) and analysed separately in seven studies (Hansen1996; Hebebrand 1994; Heikkinen 1998; Jadallah 1994; Navarra2000; Ortega 1996; Witten 1998). In the latter group, we wereable to calculate ITT data. However, otherpatient subgroups, suchas patients with perforated appendicitis (Huang 2001; Karadayi2003; Kum 1993a; Simon 2009), a histologically normal ap-pendix (Huang 2001; Karadayi 2003; Kum 1993a; Nordentoft2000; Reiertsen 1997), conversion to midline laparotomy (Huang2001; Kald 1999, Nordentoft 2000; Reiertsen 1997; Sezeur1997; Williams 1996), non-protocol medication (Minn 1997;Nordentoft 2000; Sezeur 1997), or inadequate follow-up period




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(Kald 1999; Ortega 1996) were also excluded after randomiza-tions in some of the trials. In total, we were able to use ITT datafrom 33 of 67 studies (50%).Study patients were usually followed only over the first postoper-ative weeks (up to a maximum of 6 months in one trial ( Kaplan

2009)). The only study with a long-term follow-up was done byvan Dalen et al. (van Dalen 2003). However, there are no long-term data available to describe the effects of LA and OA on theoccurrence of incisional hernia or intraabdominal adhesions.Furthermore, only some of the studies described how many pa-tients presented with suspected acute appendicitis during the trialperiod, how many of these patients were primarily eligible for thetrial, and how many subsequently refused trial participation.Data extraction on pain was difficult, since we had to identify theprespecified time point of 24 hr after operation in figures, that hadother or unclear schedules of pain measurement. Furthermore,

one study (Ortega 1996) reported only a summary pain score thatwas calculated from the VAS measurement, but also from paintablets consumed. Since this study was blinded, we tried to use theavailable data and estimated VAS scores by halving the summaryscores. Cost analyses in the trials were done by various methods.

We had to exclude the results of two trials (Kum 1993a; Ignacio2003), since costs were only reported as absolute differences. Thetrial by Helmy (Helmy 2001) described the occurrence of twowound infections, but failed to mention in which group they wereobserved.Differential expertise bias could be ruled out for 38 trials (57%),and in 11 trials (16%) the trialists admitted the presence of alearning curve bias. In turn, this means that 18 trial reports failedto discuss the importance of surgical expertise for the results of thetrial.




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Figure 1. Methodological quality summary: review authors judgements about each methodological quality

item for each included study.




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Effects of interventions

Included studies

A total of 67 studies were included in this review, but not all themreported clinically relevant data which contributed to the resultsof this review. Of these 67 studies, the vast majority (56 stud-ies) compared LA and OA in adults. Seven studies of OA versusLA were on children (Bolla 2008; Lavonius 2001; Lejus 1996;Lintula 2004; Little 2002; Simon 2009; Yeung 1997) (and onefurther study is ongoing (Paya 2000)). Fourteen studies addressedthe diagnostic effects of laparoscopy specifically. Of these fourteenstudies, four examined only the diagnostic effects of laparoscopy,and performed OA if appendicitis could not be ruled out duringlaparoscopy (Jadallah 1994; Larsson 2001; Olsen1993; van Dalen2003). In the remaining ten studies, LA was performed after diag-nostic laparoscopy. Therefore, the therapeutic effects of these tenstudies are included in the 67 studies comparing LA and OA.

Therapeutic effects in adults

Out of the various complications that were described after OAand LA, we examined only two specific complications. It was im-possible to extract data on overall complication rates from theincluded studies, because definition and reporting of complica-tions was inconsistent. Wound infections were about half as likely(Analysis 1.1; Peto OR 0.43; 95%-CI 0.34 to 0.54) after LA thanafter OA,- a highly significant result based on nearly 6000 oper-ated cases. Despite the large number of studies with differencesin surgical expertise, antibiotic regimens, and cl inical setting, low

heterogeneity was detectable (I2 11%). On the other hand, in-traabdominal abscesses were increased nearly threefold after LA(Analysis 1.2; Peto OR 1.77; 95%-CI 1.14 to 2.76). In this case,moderate heterogeneity (I2 33%) was detectable among the 46studies that contributed data to this overall result. There were nonotable differences in the results of trials using stapler vs. loopsfor stump closure. The funnel plot showed no signs of publicationbias.The duration of surgery was 10 minutes (95%-CI 6 to 15) longerforLA(Analysis 1.3). The results for anaesthesia time or operatingtime were similarly prolonged. Not unexpectedly, strong hetero-geneity was present in these analyses. It seems as if the differencebetween LA and OA has become smaller during the more recent

years. A possible interaction between the presence of a learningcurve bias and trial results was not detectable.Pain measurements on day 1 after surgery showed a reductionof pain by 8 mm (95%-CI 5 to 11 mm; Analysis 1.7) on a 100mm VAS. This finding is hampered by the fact that strong het-erogeneity was found among the studies and also the absolutepain levels varied between 5.9 cm and 2.9 cm. Less pain was also

found in most of those trials that measured pain over one or twoweeks after surgery (Bauwens 1999; Hart 1996; Hebebrand 1994;Hellberg 1999; Katkhouda 2005; Moberg 2005; Reiertsen 1997;Ricca 2007), although the absolute differences became smallerwith time. Various studies described that LA requires less analgesicdrugs doses and/or a shorter duration of analgesia. When restrict-ing the analysis of pain intensity only to the three trials that didused blinding and reported mean data, the pooled result was stillsignificantly in favour of LA.Hospital stay also showed large variations among the absolutelengths of stay in the various studies (range 1 to 7 days) and alsofor the LA versus OA differences (range 0 to 4 days reduction).Not a single study reported a significant increase in hospital stay.In the summary statistics, therefore, a significant reduction of 1.1days was calculated (95%-CI 0.7 to 1.5; Analysis 1.9). However,the two biggest studies (Pedersen 2001; Hellberg 1999), reported

that hospital stay was similar after LA and OA, but these resultscould not be used in the meta-analysis, because medians were pre-sented by the study authors. The fact that study results are highlyheterogeneous can be partly explained by the absolute durationof hospital stay, which ranged between 1 and 10 days. The trialswith long hospital stay after OA reported clearly higher reductionsin length of stay after LA as compared to those trials, in whichhospital stay was already very short after OA.After LA, bowel function returned more quickly than after OA,but this finding is based on a smaller number of studies and also isof borderline significance only. Furthermore, the results on rein-troduction of liquid and solid diet were highly heterogeneous.Three studies used indices of bodily function and quality-of-life

to compare LA and OA (Hellberg 1999; Kaplan 2009; Vallribera2003). All three trials reported significant advantages for LA.Return to normal activity was 5 days (95%-CI 4 to 7; Analysis1.17) earlier after LA than after OA, but again heterogeneity waspresent, although it was caused by only a single trial. Return towork was quite similar after LA and OA with a difference of 2 daysin favour of LA (95%-CI -2 to +5; Analysis 1.19), but the twolarge but excluded trialsfound quicker recovery after LA (Pedersen2001; Hellberg 1999). Both trials found a significant differenceof 6 and 3 days earlier return to work, respectively. Return tosporting activities was found to be possible earlier after LA in thetwo trials assessing this outcome. Only two studies assessed thecosmeticresultbytheuseofaVAS.Bothnotedasignificantbenefit

(quantified as 10 mm on the VAS) for LA versus OA.Operation and hospital costs of LA were significantly higher thanthat of OA, but this finding is strongly heterogeneous (Analysis1.25). Whencomparingthe total costs withinhospitalstay andthecosts outside hospital, it seems as cost increase and decrease cancelout each other. Although LA causes more in-hospital costs, it savescosts outside the hospital on the society level. In consequence,




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Hall-Long et al., Heikkinen et al., and Macarulla et al. describedthat LA is cost-saving from a societal perspective,- especially inemployed patients.

Therapeutic effects in children

In children, less data is available, but the result do not seem tobe much different when compared to adults. Again, laparoscopicsurgery took longer to perform (+11 minutes; 95%-CI +6to +16).Wound infections were significantlyreduced (PetoOR 0.20; 95%-CI 0.08 to 0.54). There were only three single cases of intraab-dominal abscess formation, which precludes meaningful analysisof this outcome. Since pain wasmeasuredblindly in two paediatrictrials, this outcome deserves special attendance. The trial by Lejuset al. failed to find a reduction inpain, but the trial by Lintula et al.described significantly less pain at various time points. Shouldertippain,however,wasmorefrequentafterLA(Lejus 1996; Lintula2004). In the study by Lintula (Lintula 2004), blinding lasted forseven days and a significant reduction in hospital stay was noted(-0.7 days; 95%-CI -0.3 to -1.1 days). This result is similar tothe pooled estimate, but between-trial differences were large (I2

52%). The trial Hay et al. (Hay 1998), which we excluded dueto its clearly unconcealed randomizations, also obtained similarresults. Controversial data exist on postoperative reconvalescence.Two trials consistently found higher costs within hospital stay, butdata on out-of-hospital savings are lacking.

Diagnostic effects

In trials on unselected patients, diagnostic laparoscopy led to vari-able reductions in the rate of negative appendectomies. Althoughthe overall result is nearly significant (RR 0.37; 95%-CI 0.13 to

1.01; Analysis 3.1), it is influenced strongly by a recently pub-lished large trial (Pedersen 2001). It seems as if older trials weremore reluctant to leave an uninflamed appendix in situ. One fur-ther study on unselected adults (Reiertsen 1997) stated, that thelaparoscopic procedure was found to havea significantly lower riskof unnecessary appendicectomy (p= 0.03), but we were unableto extract raw data from this study. In parallel to the reduction innegative appendectomy rate, the rate of unestablished diagnoseswas also decreased after laparoscopy (RR 0.43; 95%-CI 0.17 to1.08).In fertile women, in whom appendectomy was deemed necessary,diagnostic laparoscopy reduced the number of unnecessary appen-dectomies largely (RR 0.20; 95%-CI 0.11 to 0.34). Consequently,the number of patients without a final diagnosis established wassmaller after laparoscopy (RR 0.27; 95%-CI 0.17 to 0.44). Bothresults are based on six similar trials without any signs of hetero-geneity. No data are available on the role of diagnostic laparoscopyin children with suspected appendicitis.The therapeutic effects of laparoscopy followed by OA vs. directOA have been reported only in a few trials. All outcomes shownon-significant results.

D I S C U S S I O N

Laparoscopy can serve as a diagnostic and therapeutic tool in pa-tients with suspected appendicitis. We tried to disentangle thesetwo aspects, because diagnostic laparoscopy and laparoscopic ap-pendectomy can each be performed with or without performing

the other.The diagnostic effects were analysed separately for unselected pa-tients and young women. In both groups large reductions of un-necessaryappendectomiesandanimproveddiagnosticefficacywasseen, although the effect was a little more pronounced in youngwomen. Clinically, we therefore believe it justified to recommenddiagnostic laparoscopy in many if not all cases of suspected appen-dicitis. This interpretation, however, also depend on further stud-ies, that will elucidate the situations in which a normal-lookingappendix can safely be left in situ. To date, the studies includedin this review did not remove a macroscopically normal appendixonly if another cause of abdominal pain was found. If future stud-ies prove that a macroscopically normal appendix could also beleft unresected, if no other pathology is found, this would furtherincrease the therapeutic advantage of laparoscopy. We believe thatthe diagnostic effects of laparoscopy are still undervalued (Flum2001), because many surgeons are reluctant to leave an uninflamedappendix in situ.

The reduction of the rate of patients without definite diagnosis isdifficult to value, since some of these patients are likely to haveno serious intraabdominal disease. On the other hand, there willalso be cases, in whom conventional appendectomy overlooks aserious, perhaps even malignant disease. Such cases will most likelyreceive a definite diagnosis within or after hospital stay. However,since most trials (except for van Dalen et al. (van Dalen 2003))

did not extend follow-up beyond hospital discharge, these case ofrecurrent diseases could have been missed in the trials.

The therapeutic effects of LA are much more difficult to value,because the overall differences are only very small and some ofthe effects are in opposite direction. If we can avoid 3 woundinfections, but have to accept 1 intraabdominal abscess more inreturn, which complications are more important? We also wereunable to provide global complication data, which could serve asa more robust indicator of intra- and postoperative safety.

It is important to remember that the diagnostic efficacy of la-paroscopy also affects the therapeutic outcomes. It is well imag-inable that LA was faster completed in some trials, just because

appendectomy was nevercarried out. Patients in whom diagnosticlaparoscopy was the only procedure might also be less likely to suf-fer from postoperative complications. The comparison betweentrials that did leave or did not leave a normal-looking appendix insitu, however, is difficult, because some trials seemed to have noclear policy about what to do with an innocent appendix.

The heterogeneity in postoperative hospital stay andreturn to nor-mal activity allows only some very cautious conclusions, although




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there is a uniform tendency to quicker reconvalescence after LA.When looking closer at the raw data, some of the trials reportsurprisingly long hospital stay after OA. This suggests that dis-charge after OA in some trials depended more on tradition thanon clinical needs. It has been shown that hospital stay after OA

can be shortened to one day or less (Ramesh 1993). One mightalso argue that the reductions in postoperative pain and hospitalstay and also the quicker return to normal bowel function are -though significant - not clinically relevant, because the differenceswere so small. A reduction of pain by 10 mm on a 100 mm VASscale - as it was found here - has been shown to be under thelevel of pain that an average patient is able to perceive. However,the absolute pain intensity and its duration also have to be takeninto account as well as the possibly reduced number of analgesics.When assessing pain, it is extremely important to note that manyof the trials in adults were unblinded. The majority of blindedtrials gave similar results as the unblinded ones, but some of theblinded trials were excluded from the statistical analysis because

median data on pain were reported. In conclusion, one may stilldoubt on justified grounds whether pain is truly less after LA, andif so, whether this is of clinical relevance (Eypasch 1996).

The effect of blinding was of critical importance in the evalua-tion of laparoscopic cholecystectomy (Majeed 1996). It may wellbe possible that patients who were randomized to LA and theircaregivers had high expectations, since LA is the more modernprocedure. Therefore, since nearly all results might have been in-fluenced by such effects (Neugebauer 1991), these results all haveto be confirmed by blinded studies.

The costs of LA have had strong influence on a hospitals choicebetween LA and OA. From a hospitals perspective, LA is likely to

be the more expensive procedure, even if in future the costs of theoperation and the equipment (single use vs. reusable; Endo-GIAvs. Roeder loops) may decrease. From the societys perspective,however, the quicker reconvalescence may balance or even super-sede the increased in-hospital costs. Still, these considerations aredifficult to generalize, since the studies were carried out in differ-ent health care systems, they used different materials, and werevery heterogeneous among each other. Therefore readers perhapsshould pay closer attention only to those studies that were per-formed in their own country or other countries with similar healthcare settings.

In 2000, Benson and Hartz (Benson 2000) have raised doubtsagainst the paradigm that non-randomized studies provide weakerevidence than randomized ones. To illustrate this, they also havecompared randomized and non-randomized studies of LA ver-sus OA, while this review excluded non- and pseudo-randomisedstudies as well as studies without allocation concealment, becausethis has been shown to have influence on trial results. Still, wethink that prospective trials can provide good evidence, especiallyif the allocation to treatments is determined by presence or absenceof an experienced surgeon. Under these circumstances, therefore

the methodological difference between such prospective and trulyrandomized trials is possibly only very small, but it still exists. Alarge database analysis of over 40.000 patients in the U.S. foundthat laparoscopic appendectomy halved the risk of postoperativeinfection and reduced hospital stay from 2.9 to 2.1 days (Guller

2004). A similar analysis confirmed this shortening of hospitalstay and described slightly higher costs of LA as compared to OA(Sporn 2009). All these findings are consistent with the results ofour analyses and support the generalisability of our results.

When compared to various other systematic reviews on LA (Barth1999; Chung 1999; Fingerhut 1999; Garbutt 1999; Golub 1998;McCall 1997; Slim 1998; Temple 1999; Uhl 2000; Aziz 2006;Kapischke 2006; Bennett 2007; Sadr-Azodi 2009), our analysisincluded some additional studies, that were either published onlyas abstracts, book chapters or even theses, or were excluded inthese reviews for language or other reasons. As we found some ofsuch studies, we cannot entirely rule out that we have missed otherstudies, but it can be reasonably assumed that such studies are

very small in size and therefore have little impact on our results.Furthermore, the funnel plot analysis of the wound infection rateshowed no signs of asymmetry. Still, it is disturbing as a researcherto know of abstracts, that were presented many years ago, andnever were published in full (Barth 1999; Loh 1992; Hoff 1995;Rohr 1994).

Methodologically, meta-analysis has its problems when dealingwith non-Gaussian data, which require non-parametric statistics.We decided to make a distinction between means and medians,but this sometimes may exclude the more valid trials from meta-analysis. Therefore, we listed these trials in the analyses, so thatreaders cancompare theresults amongthese trials. For anytrial that

reported mean values but without giving SDs, we also estimatedSDs, which is an accepted technique (Follmann 1992). Therefore,we believe that all formats of data were adequately represented inthe analyses.

A U T H O R S C O N C L U S I O N S

Implications for practice

Although the overall effects of laparoscopic surgery for suspectedappendicitis are impressing, one must not forget that most of thelaparoscopic surgeons involved in these trials were well-trained

experts in laparoscopy. Therefore, surgical expertise with laparo-scopic techniques is a basic prerequisite before surgeons can justlyexpect clinical benefits from LA. The still ongoing disseminationof the various laparoscopic techniques, however, renders it likelythat the majority of future surgeons will be able to obtain trainingmore easily.

Within the same process, laparoscopic equipment is becomingmore and more available, too. This is important, since the routine




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availability of laparoscopic devices even in night hours is essential.In parallel, the operative costs will probably decrease.

In those clinical settings where surgical expertise and equipmentare available and affordable, we would generally recommend touse laparoscopy and LA in all patients with suspected appendicitis

unless laparoscopy itself is contraindicated or not feasible. Thisrecommendation, however, does not pertain to perforated or gan-grenous cases, since intraabdominal abscesses are more likely tooccur after LA in general and there is some evidence that suchcases run a higher risk (Pedersen 2001). Since the overall benefitsof LA are very small, those who continue to operate on appendici-tis by conventional techniques might continue to do so, but la-paroscopic surgery shouldroutinely be employed at least in specialcases, for instance young femaleor obese patients (Hellberg 1999),because the diagnostic and therapeutic advantages of laparoscopyare clearly larger in these cases.

Implications for research

Since a large number of studies was available for most comparisonsinthis review, futureresearch shouldeither usebetter study designsor focus on more specific aspects of the issue, such as specificoutcomes or specific patient subgroups.

With regard to diagnostic laparoscopy, future studies should focuson specific patient groups, in whom a normal-looking appendixcan be left in situ. It also remains to be clarified, what to do inpatients, in whom no intraabdominal pathology (neither at theappendix,noratanyotherorgan)canbefoundduringlaparoscopy.Is appendectomy required in such situations? More recent, butstill preliminary data have shown that it is probably safe to leave anormal looking appendix in situ (van Dalen 2003; van den Broek

2001).

Mostofthestudiesincludedinthisreviewhadafollow-upbetweena few days of hospital stay and a month. A much longer follow-up period of present and future studies is necessary to find outwhether the lower rate of adhesions found by DeWilde (DeWilde1991) translates into a clinically relevant reduction of adhesion-related complications, such as ileus.

The assessment of pain (and also other outcomes) should be donein a blinded manner in future studies. Furthermore, standard reg-imens of pain therapy should be employed in both study arms.Researchers should decide whether to measure pain and standard-ize pain therapy, or to measure analgesics consumption and keep

patients below a standard level of pain. Studies, where both, anal-gesics and pain intensity vary, are difficult to interpret when theresults for both are in opposite direction. It is likely that needle-scopic instruments reduce postoperative pain (Huang 2001), butthis has to be proven separately for appendectomy.

Those who use LA as a standard technique should concentrateon measures to reduce the risk of intraabdominal abscesses. Thequestion whether LA is justifiable in patients with perforated organgrenous appendicitis remains controversial. It seems impracti-cal, however, to identify such cases preoperatively and enrol theminto a trial. Finally, the comparative effectiveness of staplers versusloops for stump closure needs to be examined further.

A C K N O W L E D G E M E N T S

We would like to thank all trialists who providedus with additionaldata, preliminary manuscripts, details of trialdesign andreferencesto further studies. The names of these trialists are (in alphabeticalorder): Dr. R.L. DeWilde (Oldenburg, Germany), Prof. S.A. Hay(Cairo, Egypt), Dr. M.T. Huang (Taipei, Taiwan), Dr. K. Karadayi(Sivas, Turkey), Dr. H. Kokki (Kuopio, Finland), Dr. M. Lavonius(Turku, Finland), Capt. Paul Lucha (Portsmouth/VA, USA), Dr.E. Macarulla (Barcelona, Spain), Dr. M. Milewczyk (Wejherowo,

Poland), Dr. G. Navarra (Ferrara, Italy), Dr. K. Paya (Vienna, Aus-tria), Prof. M.G. Sarr (Rochester/MN, USA), Dr. U. Settmacher(Berlin, Germany), Prof. A. Sezeur (Paris, France), Dr. R. Stare(Varazdin, Croatia), Dr. G. Tzovaras (Larissa, Greece), Dr. F. Vall-ribera Valls (Barcelona, Spain), Dr. P. Wara (Aarhus, Denmark),Prof. B.L. Warren (Tygerberg, South Africa), Dr. I. Witten andProf. H.F. Weiser (Rotenburg/Wmme, Germany), and Dr. C.K.Yeung (Hongkong, Hongkong).

R E F E R E N C E S

References to studies included in this review

Al-Mulhim 2002 {published data only} Al-Mulhim AS, Al-Mulhim FM, Al-Suwaiygh AA, Al-Masaud NA. Laparoscopic versus open appendectomy infemales with a clinical diagnosis of appendicitis. Saudi MedJ2002;23:133942.

Attwood 1992 {published data only} Attwood SEA, Hill ADK, Murphy PG, Thornton J,Stephens RB. A prospective randomized trial of laparoscopic

versus open appendectomy. Surgery1992;112:497501.

Hill ADK, Coleman JE, Attwood SEA, Stephens RB.Laparoscopic versus open appendicectomy - a randomisedtrial [abstract]. 3rd World Congress of Endoscopic Surgery.Bordeaux, 1992:47.

Barth 1999 {published data only} Meynaud-Kraemer L, Colin C, Vergnon P, Barth X.

Wound infection in open versus laparoscopicappendectomy.Int J Technol Assess Health Care1999;15(2):38091.




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Bauwens 1999 {published data only} Bauwens K, Schwenk W, Bhm B, Hasart O, Neudecker

J, Mller JM. Convalescence and time to return towork after laparoscopic and open appendectomy; aprospective randomized study [Rekonvaleszenz und

Arbeitsunfhigkeitsdauer nach laparoskopischer und

konventioneller Appendekotmie. Eine prospektivrandomisierte Studie]. Chirurg1998;69:5415.Hasart O. Rekonvaleszenz und Arbeitsunfhigkeitsdauernach laparoskopischer undkonventioneller Appendektomie:

eine prospektiv-randomisierte Studie [dissertation]. Berlin,Germany: Humboldt Univ. of Berlin, 2000.Schwenk W, Bauwens K, Neudecker J, Bhm B. Durationof reconvalecense and inability to work after laparoscopicand conventional appendectomy - a prospective randomisedstudy [Rekonvaleszenz und Arbeitsunfhigkeitsdauer nachlaparoskopischer und konventioneller Appendektomie eine prospektivrandomisierte Studie [abstract]]. ZentralblChir1998;123:424425.

Bolla 2008 {published data only}

Bolla G, Tuzzato G. Post-appendectomy immunologiccompetence in pediatric age. The results do not alwaysmatch expectations. Laparoscopy versus laparotomy.Pediatr Med Chir2008;30(2):8993.

Bruwer 2000 {published data only}Bruwer F, Coetzer M, Warren BL. Early results of arandomized controled study of laparoscopic vs open surgicalexploration in pre-menopausal women with suspected acuteappendicitis [abstract]. Surg Endosc2000;14(Suppl.1):S110. Bruwer F, Coetzer M, Warren BL. Laparoscopic versusopen surgical exploration in premenopausal women withsuspected acute appendicitis. S Afr J Surg2003;41:8285.

Cox 1996 {published data only} Cox MR, McCall JL, Toouli J, Padbury RTA, WilsonTG, Wattchow DA, Langcake M. Prospective randomizedcomparison of open versus laparoscopic appendectomy inmen. World J Surg1996;20:2636.Langcake M, Cox MR, McCall JL, Padbury RTA, WattchowDA, Wilson TG, Toouli J. A prospective randomized trialcomparing open vs laparoscopic appendicectomy in males[abstract]. Austr NZ J Surg. 1995:424.

DeWilde 1991 {published data only (unpublished sought but notused)}

DeWilde RL. Goodbye to late bowel obstruction afterappendicectomy [letter]. Lancet1991;338:1012.

Eichen 1994 {published and unpublished data} Eichen R, Heuser H, Nitschke B. Laparoscopicor conventional appendectomy:a prospective study[Prospektive Studie: laparoskopische Appendektomie vs.konventionelle Appendektomie]. Langenbecks Arch ChirSuppl Kongressb 1994;111:223225.

Frazee 1994 {published data only} Frazee RC, Roberts JW, Symmonds RE, Snyder SK,Hendricks JC, Smith RW, Custer MD III, Harrison JB.

A prospective randomized trial comparing open versuslaparoscopic appendectomy. Ann Surg1994;219:72531.

Hall Long 2000 {unpublished data only}Bannon MP, Zietlow SP, Harmsen WS, Sarr MG, SmithCD, Ilstrup DM, Baerga-Varela Y, Beal AL, Devine RM,Donohue JH, Farley DR, Farnell MB, Grant CS, NelsonH, Que FG, Thompson GB. Prospective randomizedcomparison of laparoscopic and open appendectomy[abstract]. Gastroenterology. 1997; Vol. 112. Hall Long K, Bannon MP, Zietlow SP, Helgeson ER,Harmsen WS, Smith CD, Ilstrup DM, Baerga-Varela Y,Beal AL, Devine RM, Donohue JH, Farley DR, FarnellMB, Grant CS, Nelson H, Que FG, Thompson GB, SarrMG. A prospective randomized comparison of laparoscopicappendectomy with open appendectomy: clinical andeconomic analysis. Surgery2001;129:390400.

Hansen 1996 {published data only} Hansen JB, Smithers BM, Schache D, Wall DR, MillerBJ, Menzies BL. Laparoscopic versus open appendectomy:

prospective randomized trial. World J Surg1996;20:1720.Smithers BM, Hansen J, Schache D, Wall D.Prospective randomized trial of laparoscopic versus openappendicectomy for acute appendicitis [abstract]. SurgEndosc. 1994; Vol. 8:565.

Hart 1996 {published data only} Hart R, Rajgopal C, Plewes A, Sweeney J Davies W, GrayD, Taylor B. Laparoscopic versus open appendectomy : aprospective randomized trial of 81 patients. Can J Surg1996;39:45762.

Hebebrand 1994 {published and unpublished data}Eypasch E, Menningen R, Paul A, Troidl H. Diagnosticand therapeutic laparoscopy for acute abdominal disorders[Die Bedeutung der Laparoskopie bei der Diagnostik und

Therapie des akuten Abdomens]. Zentralbl Chir1993;118:726732. Hebebrand D, Troidl H, Spangenberger W, NeugebauerE, Schwalm T, Gnther MW. [Laparoscopic or classicalappendectomy? A prospective randomized study][Laparoskopische oder klassische Appendektomie? Eineprospektiv randomisierte Studie]. Chirurg1994;65:11220.Neugebauer E, Eypasch E, Hebebrand D, Spangenberger W,Troidl H. [Laparoscopic versus conventional appendectomy a prospective randomized study [abstract]]. Proceedingsof the 1st European Congress of the European Associationfor Endoscopic Surgery. 1993:371.Schwalm T. Laparoskopische oder konventionelleAppendektomie - eine prospektive, randomisierte Therapiestudie

unter besonderer Bercksichtigung der relevanten ZielkriterienSicherheit und Patientenkomfort [dissertation]. Cologne,Germany: Univ. of Cologne, 1995.

Heikkinen 1998 {published data only}Heikkinen T, Haukipuro K, Hulkko A. Cost-effectiveappendectomy. Open or laparoscopic? A prospectiverandomized study [abstract]. Surg Endosc1998;12:571. Heikkinen TJ, Haukipuro K, Hulkko A. Cost-effectiveappendectomy. Open or laparoscopic? A prospective




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randomized study. Surg Endosc1998;12:12041208.

Hellberg 1999 {published data only}Enochsson L, Hellberg A, Rudberg C, Feny G,Gudbjartson T, Kullman E, Ringqvist I, Srensen S, Wenner

J. Laparoscopic vs open appendectomy in overweightpatients. Surg Endosc2001;15:387392.Hellberg A, Rudberg C, Enochsson L, Gudbjartson T,

Wenner J, Kullman E, Feny G, Ringqvist I, Srensen S.Conversion from laparoscopic to open appendicectomy: apossible drawback of the laparoscopic technique?. Eur JSurg2001;167:209213. Hellberg A, Rudberg C, Kullman E, Enochsson L, FenyG, Graffner H, Hallerbck B, Johansson B, AnderbergB, Wenner J, Ringqvist I, Srensen S. Prospectiverandomized multicentre study of laparoscopic versus openappendicectomy. Br J Surg1999;86:4853.

Helmy 2001 {published data only} Helmy MA. A comparative study between laparoscopicversus open appendicectomy in men. J Egypt Soc Parasitol

2001;31

(2):55562..Henle 1996 {published data only} Henle KP, Beller S, Rechner J, Zerz A, Klingler A.Laparoscopic versus open appendectomy: a prospecitverandomized trial [Laparoskopische versus konventionelle

Appendektomie: eine prospektive, randomisierte Studie].Chirurg1996;67:526530.Klingler A, Henle KP, Beller S, Rechner J, Zerz A, WetscherGJ, Szinicz G. Laparoscopic appendectomy does not changethe incidence of postoperative infectious complications. AmJ Surg1998;175:232235.Szinicz G, Henle KP, Beller S, Rechner J, Zerz A, Klingler

A. Laparoskopische Appendektomie: Pro. In: Boeckl O,Waclawiczek HW editor(s). Standards in der Chirurgie.

Munich: Zuckschwerdt, 1995:312319.Huang 2001 {published and unpublished data}

Huang MT, Wei PL, Wu CC, Lai IR, Chen RJ, Lee WJ.Needlescopic, laparoscopic, and open appendectomy: acomparative study. Surg Laparosc Endosc Percutan Tech2001;11:306312.

Ignacio 2003 {published data only} Ignacio RC, Burke R, Spencer D, Bissell C, Dorsainvil C,Lucha PA. Laparoscopic vs open appendectomy. What isthe real difference? Results of a prosepctive randomizeddouble-blinded trial. Surg Endosc2004;18:334337.Ignacio RC, Lucha PA Jr, Burke R, Newman J, SheppsC, Spencer D, Bissell C, Archer UK, Dorsainvil C.Laparoscopic versus open appendectomy - What is the real

difference? Results of a prospective randomized double-blinded trial [abstract]. Surg Endosc2003;17 (Suppl):S239.

Jadallah 1994 {published data only}Jadallah FA, Abdul-Ghani AA, Tibblin S. Diagnosticlaparoscopy reduces unneccessary appendicectomy in fertilewomen. Eur J Surg1994;160:415.

Kaiser 2006 {published data only} Kaiser M. Laparoskopische und konventionelleAppendektomie im Vergleich unter besonderer Bercksichtigung

immunologischer Parameter - eine prospektive Studie

[dissertation]. Magdeburg, Germany: Univ. of Magdeburg,1996.

Kald 1999 {published data only} Kald A, Kullman E, Anderberg B, Wirn M, Carlsson

P, Ringqvist I, Rudberg C. Cost-minimisation analysis oflaparoscopic and open appendicectomy. Eur J Surg1999;165:57982.

Kaplan 2009 {published data only} Kaplan M, Salman B, Yilmaz TU, Oguz M. A quality oflife comparison of laparoscopic and open approaches inacute appendicitis: a randomised prospective study. ActaChir Belg2009;109:35663. [PUBMED: 19943593]

Karadayi 2003 {published and unpublished data} Karadayi K, Turan M, Canbay E, Topcu O, Sen M.Laparoscopic versus open appendectomy: analysis ofsystemic acute-phase responses in a prospective randomizedstudy. Chir Gastroenterol2003;19:396400.

Katkhouda 2005 {published data only} Katkhouda N, Mason RJ, Towfigh S, Gevorgyan A, EssaniR. Laparoscopic versus open appendectomy: a prospectiverandomized double-blind study. Ann Surg2005;242(3):439-450.

Kazemier 1997 {published data only}de Zeeuw GR, Kazemier G, Hop WCJ, Lange JF, Bonjer HJ.Laparoscopic treatment of acute appendicitis: less pain andwound infection but longer operating time; a randomizedtrial [Laparoscopische behandling van appendicitis acuta:minder pijn en wondinfecties, maar langere operatietijd; eengerandomiseerd onderzoek]. Ned Tijdschr Geneesk 1998;

142:45963.Kazemier G, de Zeeuw GR, Bonjer HJ, Lange JF.Laparoscopic vs open appendectomy. A randomized clinicaltrial [abstract]. Surg Endosc1995;9:213.Kazemier G, de Zeeuw GR, Bonjer HJ, Lange JF.Laparoscopic vs open appendectomy. A randomized clinicaltrial [abstract]. Surg Endosc1995;9:606.Kazemier G, de Zeeuw GR, Bonjer HJ, Lange JF.Laparoscopic vs open appendectomy. A randomized clinicaltrial [abstract]. Surg Endosc1996;10:550. Kazemier G, de Zeeuw GR, Lange JF, Hop WCJ, BonjerHJ. Laparoscopic vs open appendectomy. A randomizedclinical trial. Surg Endosc1997;11:33640.

Kehagias 2009 {published and unpublished data}Kehagias I, Karamanakos S, Panagiotopoulos S, Vagenas K,Kalfarentzos F. Laparoscopic versus open appendectomyfor complicated disease - a prospective randomized trial[abstract]. Surg Endosc2009;23(Suppl.1):13.

Kum 1993a {published data only (unpublished sought but not used)} Kum CK, Ngoi SS, Goh PM, Tekant Y, Isaac JR.Randomized controlled trial comparing laparoscopic andopen appendicectomy. Br J Surg1993;80:1599600.




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Laine 1997 {published data only} Laine S, Rantala A, Gullichsen R, Ovaska J. Laparoscopicappendectomy-is it worthwhile? A prospective, randomizedstudy in young women. Surg Endosc1997;11:957.Laine S, Rantala A, Gullichsen R, Ovaska J. Laparoscopicversus conventional appendectomy: a prospective,

randomized study in young women [abstract]. Surg Endosc1996;10:243.

Larsson 2001 {published data only} Larsson PG, Henriksson G, Olsson M, Boris J, Strberg P,Tronstad SE, Skullman S. Laparoscopy reduces unnecessaryappendicectomies and improves diagnosis in fertile women.

A randomized study. Surg Endosc 2001;15(2):2002.[MEDLINE: 11285968]

Lavonius 2001 {published and unpublished data} Lavonius MI, Liesjrvi S, Ovaska J, Pajulo O, RistkariS, Alanen M. Laparoscopic versus open appendectomy inchildren: a prospective randomised study. Eur J Pediatr Surg2001;11:235238.

Lejus 1996 {published data only}Delile L. Etude comparative de lanalgesie post-operatoireapres appendectomie par incision de MacBurney ou par voie

coelioscopique chez lenfant [dissertation]. Nantes, France:Univ. of Nantes, 1994.Heloury Y, Lejus C, Delile L, Plattner V, Baron M, SouronR. Post-operative pain after appendicectomy: Laparoscopicversus MacBurney [abstract]. Surg Endosc1994;8:958. Lejus C, Delile L, Plattner V, Baron M, Guillou S,Heloury Y, Souron R. Randomized, single-blinded trial oflaparoscopic versus open appendectomy in children: effectson postoperative analgesia. Anesthesiology1996;84:8016.

Lintula 2004 {published and unpublished data}Lintula H, Kokki H, Vanamo K. Single-blind randomized

clinical trial of laparoscopic versus open appendicectomy inchildren. Br J Surg2001;88:5104.Lintula H, Kokki H, Vanamo K, Antila P, Eskelinen M.Laparoscopy in children with complicated appendicitis. JPediatr Surg2002;37:13171320. Lintula H, Kokki H, Vanamo K, Valtonen H, MattilaM, Eskelinen M. The costs and effects of laparoscopicappendectomy in children. Arch Pediatr Adolesc Med2004;158:3437.

Little 2002 {published data only} Little DC, Custer MD, May BH, Blalock SE, Cooney DR.Laparoscopic appendectomy: an unnecessary and expensiveprocedure in children?. J Pediatr Surg2002;37:310317.

Macarulla 1995 {published data only (unpublished sought but notused)}

Macarulla E, Hassan H, Abad JM, Vallet J, Claveria R,Besora P, Basas J, Feliu X, Camps J, Vias X, FernndezE. Laparoscopic vs open appendectomy for suspectedappendicitis [abstract]. Br J Surg1995;82(Suppl.1):67. Macarulla E, Vallet J, Abad JM, Hussein H, FernandezE, Nieto B. Laparoscopic versus open appendectomy: aprospective randomized trial. Surg Laparosc Endosc1997;7:3359.

Martin 1995 {published data only} Martin LC, Puente I, Sosa JL, Bassin A, Breslaw R,McKenney MG, Ginzburg E, Sleeman D. Open versuslaparoscopic appendectomy. A prospective randomizedcomparison. Ann Surg1995;222:25662.

Minn 1997 {published data only}Jones B, Ratzer E, Clark J, Zeren F, Haun W. Does peer-reviewed publication change the habits of surgeons?. Am JSurg2000;180:5669. Minn L, Varner D, Burnell A, Ratzer E, Clark J, Haun

W. Laparoscopic vs open appendectomy. Prospectiverandomized study of outcomes. Arch Surg 1997;132:70812.

Moberg 2005 {published data only}Moberg AC, Berndsen F, Palmquist I, Petersson U, Resch T,Montgomery A. Randomized clinical trial of laparoscopicversus open appendicectomy for confirmed appendicitis. BrJ Surg2005;92(3):298304.

Moirangthem 2008 {published data only}

Moirangthem GS, Arunkumar CH, Marak AB, LokendraK, Singh LD. A comparative study between laparoscopicversus open appendicectomy. JMS2008;22(2):5862.

Mutter 1996 {published data only} Mutter D, Vix M, Bui A, Evrard S, Tassetti V, Breton JF,Marescaux J. Laparoscopy not recommended for routineappendectomy in men: results of a prospective randomizedstudy. Surgery1996;120:714.Spiegel JN. Lappendicectomie chez lhomme MacBurneyou coelioscopie? Etude prospective randomise. Strasbourg,France: Univ. of Strasbourg, 2001.

Navarra 2000 {published and unpublished data} Navarra G, Ascanelli S, Turini A, Carcoforo P, ToniniG, Pozza E. Laparoscopic appendectomy versus open

appendectomy in suspected acute appendicitis infemale patients [Appendicectomia laparoscopica versusappendicectomia aperta nel sospetto di appendicite acuta inpazienti di sesso femminile]. Ann Ital Chir2002;73:5963.Navarra G, Ascanelli S, Turini A, Tonini G, Pozza E.Laparoscopic versus open appendectomy in females withpain in right iliac fossa [abstract]. Surg Endosc2000;14Suppl 1:S128.

Nordentoft 2000 {published data only} Nordentoft T, Bringstrup FA, Bremmelgaard A, Stage JG.Effect of laparoscopy on bacteremia in acute appendicitis: arandomized controlled study. Surg Laparosc Endosc PercutanTech 2000;10:3024.

Olsen 1993 {published data only}Olsen JB, Myren CJ, Haahr PE. Randomized trial on thevalue of diagnostic laparoscopy before appendectomy.Ugeskr Laeger1995;157:584585. Olsen JB, Myrn CJ, Haahr PE. Randomized study ofthe value of laparoscopy before appendicectomy. Br J Surg1993;80:9223.

Ortega 1996 {published data only} Ortega AE, Hunter JG, Peters JH, Swanstrom LL,Schirmer B, Laparoscopic Appendectomy Study Group.




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A prospective, randomized comparison of laparoscopicappendectomy with open appendectomy. Am J Surg1995;169:20813.

Pedersen 2001 {published data only} Pedersen AG, Petersen OB, Wara P, Rnning H, Qvist N,Laurberg S. Randomised controlled trial of laparoscopicversus open appendicectomy. Br J Surg2001;88:2005.

Perner 1999 {published data only} Perner A, Bugge K, Lyng KM, Schulze S, Kristensen PA,Bendtsen A. Changes in plasma potassium concentrationduring carbon dioxide pneumoperitoneum. Br J Anaesth1999;82:1379.

Pozo 1996 {published data only}Pozo JC, Martinez S, Negri C, Rachadell JJ, BellosoR. not available [ESTUDIO PROSPECTIVO

Y CONTROLADO, COMPARANDO LAAPENDICECTOMIA LAPAROSCOPICA Y LAAPENDICECTOMIA CONVENCIONAL, ENUN PROGRAMA DE ENTRENAMIENTO DE

POSTGRADO EN CIRUGIA GENERAL]. Rev Soc VenezGastroenterol1996;50:22530.

Reiertsen 1997 {published data only} Reiertsen O, Larsen S, Trondsen E, Edwin B, Frden AE,Rosseland AR. Randomized controlled trial with sequentialdesign of laparoscopic versus conventional appendicectomy.Br J Surg1997;84:8427.

Ricca 2007 {published and unpublished data} Ricca R, Schneider JJ, Brar H, Lucha PA. Laparoscopicappendectomy in patients with a body mass index of 25 orgreater: results of a double blind, prospective, randomizedtrial. JSLS2007;11:548. [PUBMED: 17663093]

Schippers 1997 {published data only} May PJ. Laparoskopische versus konventionelleAppendektomie - eine prospektiv randomisierte Studie

[dissertation]. Aachen, Germany: Univ. of Aachen, 1998.Schippers E. Appendicectomy - laparoscopic vs open[Appendektomie laparoskopisch vs konventionell].Langenbecks Arch Chir Suppl Kongressbd1993;110:142145.Schippers E, Pier A, May P, Schumpelick V. Laparoscopic vsopen appendectomy - a comparison of postoperative painand respiratory function [abstract]. Surg Endosc1994;8:561.

Settmacher 1995 {published data only} Settmacher U, Manger T, Liebenthal C, Neuhaus K,Volk HD. Immunological modifications after open andlaparoscopic surgery. Minimal Invasive Chirurgie1995;4:

95102.

Sezeur 1997 {published data only} Sezeur A, Bure-Rossier AM, Rio D, Savigny B, TricotC, Martel P, Baubion O. Does laparoscopy increasethe bacteriological risk of appendectomy? Results of arandomized prospective study [La clioscopie augmentetelle le risque bactriologique de lappendicectomie?Rsultats dune tude prospective randomise]. Ann Chir1997;51:2437.

Simon 2009 {published data only}Simon P, Burkhardt U, Sack U, Kaisers UX, MuenstererOJ. Inflammatory response is no different in childrenrandomized to laparoscopic or open appendectomy. JLaparoendosc Adv Surg Tech A 2009;19 Suppl 1:S716.[PUBMED: 18999981]

Stare 1998 {published data only (unpublished sought but not used)}Stare R, Kocman I, Povic Cevra Z. Results of a prospectiverandomised study of laparoscopic appendectomy incommunity hospital [abstract]. Surg Endosc1998;12:573. Stare R, Kocman I, Povic Cevra Z, Zgrebec Z, Kovacic D.Results of a prospective randomised study of laparoscopicappendectomy in community hospital. In: Montori A,Lirici MM, Montori J editor(s). 6th World Congress ofEndoscopic Surgery. Rome, Italy: Monduzzi, 1998:4415.

Sun 1998 {published data only} Sun XL, Xu HB. Comparative study among openlaparoscopic and video-assisted appendectomies. WorldChinese Journal of Digestion 1998;6:710711.

Tate 1993a {published data only} Tate JJT, Dawson JW, Chung SCS, Lau WY, Li AKC.Laparoscopic versus open appendicectomy: prospectiverandomised trial. Lancet1993;342:6337.

Tzovaras 2007 {published and unpublished data} Tzovaras G, Liakou P, Baloyiannis I, Spyridakis M,Mantzos F, Tepetes K, Athanassiou E, Hatzitheofilou C.Laparoscopic appendectomy: differences between male andfemale patients with suspected acute appendicitis. World JSurg2007;31:409413.

Vallribera 2003 {published and unpublished data} Vallribera Valls F, Sala Pedrs J, Aguilar Teixedor F, EspnBassany E. Influence of laparoscopic surgery on perceptionof quality of life after appendectomy [Influencia de la

ciruga laparoscpica en la percepcin de la claidad de vidatras apendicectomia]. Cir Esp 2003;73:8894.

van Dalen 2003 {published data only} van Dalen R, Bagshaw PF, Dobbs BR, Robertson GM,Lynch AC, Frizelle FA. The utility of laparoscopy in thediagnosis of acute appendicitis in women of reproductiveage: a prospective randomized controlled trial with long-term follow-up. Surg Endosc2003;17:13113.

Wei 2010 {published data only}Wei HB, Huang JL, Zheng ZH, Wei B, Zheng F, Qiu WS,Guo WP, Chen TF, Wang TB. Laparoscopic versus openappendectomy: a prospective randomized comparison. SurgEndosc2010;24:2669. [PUBMED: 19517167]

Williams 1996 {published data only} Williams MD, Collins JN, Wright TF, Fenoglio ME.Laparoscopic versus open appendectomy. South Med J1996;89:66874.

Witten 1998 {published data only}Birth M, Witten I, Gadzepko E, Weiser HF. Laparoscopicvs open appendectomy for acute appendicitis: a prospectiverandomized trial [abstract]. Br J Surg1998;85(Suppl.2):39. Witten KI. Die chirurgische Behandlung der akutenAppendizitis: ein Methodenvergleich zwischen laparoskopischer




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und konventioneller Appendektomie im Rahmen einer

prospektiv randomisierten Studie an zweihundert Patienten

[dissertation]. Gttingen, Germany: Univ. of Gttingen,2001.

Yeung 1997 {published data only (unpublished sought but not used)} Yeung CK, Yip KF, Lee KH, Lau WY. The role ofminimally invasive surgery in the management of acuteappendicitis in children: a prospective randomized trialof laparoscopic vs conventional appendectomy [abstract].Asian J Surg1997;20:S55.

YIn 1996 {published data only}Yin WY, Lee MC, Cheng TJ, Chen HT, Huang SM.Laparo

laparoscopic versus open surgery for suspected appendicitis

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