Laparoscopic versus open surgery for suspected appendicitis

Thomas Jaschinski; Christoph G Mosch; Michaela Eikermann; Edmund AM Neugebauer; Stefan Sauerland

doi:10.1002/14651858.CD001546.pub4

. 2018 Nov 28;2018(11):CD001546. doi: 10.1002/14651858.CD001546.pub4

Laparoscopic versus open surgery for suspected appendicitis

Thomas Jaschinski ^1,^✉, Christoph G Mosch ¹, Michaela Eikermann ², Edmund AM Neugebauer ³, Stefan Sauerland ⁴

Editor: Cochrane Colorectal Cancer Group

PMCID: PMC6517145 PMID: 30484855

Abstract

Background

The removal of the acute appendix is one of the most frequently performed surgical procedures. Open surgery associated with therapeutic efficacy has been the treatment of choice for acute appendicitis. However, in consequence of the evolution of endoscopic surgery, the operation can also be performed with minimally invasive surgery. Due to smaller incisions, the laparoscopic approach may be associated with reduced postoperative pain, reduced wound infection rate, and shorter time until return to normal activity.  This is an update of the review published in 2010.

Objectives

To compare the effects of laparoscopic appendectomy (LA) and open appendectomy (OA) with regard to benefits and harms.

Search methods

We searched the Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE and Embase (9 February 2018). We identified proposed and ongoing studies from World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP), ClinicalTrials.gov and EU Clinical Trials Register (9 February 2018). We handsearched reference lists of identified studies and the congress proceedings of endoscopic surgical societies.

Selection criteria

We included randomised controlled trials (RCTs) comparing LA versus OA in adults or children.

Data collection and analysis

Two review authors independently selected studies, assessed the risk of bias, and extracted data. We performed the meta‐analyses using Review Manager 5. We calculated the Peto odds ratio (OR) for very rare outcomes, and the mean difference (MD) for continuous outcomes (or standardised mean differences (SMD) if researchers used different scales such as quality of life) with 95% confidence intervals (CI). We used GRADE to rate the quality of the evidence.

Main results

We identified 85 studies involving 9765 participants. Seventy‐five trials included 8520 adults and 10 trials included 1245 children. Most studies had risk of bias issues, with attrition bias being the largest source across studies due to incomplete outcome data.

In adults, pain intensity on day one was reduced by 0.75 cm on a 10 cm VAS after LA (MD ‐0.75, 95% CI ‐1.04 to ‐0.45; 20 RCTs; 2421 participants; low‐quality evidence). Wound infections were less likely after LA (Peto OR 0.42, 95% CI 0.35 to 0.51; 63 RCTs; 7612 participants; moderate‐quality evidence), but the incidence of intra‐abdominal abscesses was increased following LA (Peto OR 1.65, 95% CI 1.12 to 2.43; 53 RCTs; 6677 participants; moderate‐quality evidence).  The length of hospital stay was shortened by one day after LA (MD ‐0.96, 95% CI ‐1.23 to ‐0.70; 46 RCTs; 5127 participant; low‐quality evidence). The time until return to normal activity occurred five days earlier after LA than after OA (MD ‐4.97, 95% CI ‐6.77 to ‐3.16; 17 RCTs; 1653 participants; low‐quality evidence). Two studies showed better quality of life scores following LA, but used different scales, and therefore no pooled estimates were presented. One used the SF‐36 questionnaire two weeks after surgery and the other used the Gastro‐intestinal Quality of Life Index six weeks and six months after surgery (both low‐quality evidence).

In children, we found no differences in pain intensity on day one (MD ‐0.80, 95% CI ‐1.65 to 0.05; 1 RCT; 61 participants; low‐quality evidence), intra‐abdominal abscesses after LA (Peto OR 0.54, 95% CI 0.24 to 1.22; 9 RCTs; 1185 participants; low‐quality evidence) or time until return to normal activity (MD ‐0.50, 95% CI ‐1.30 to 0.30; 1 RCT; 383 participants; moderate‐quality evidence). However, wound infections were less likely after LA (Peto OR 0.25, 95% CI 0.15 to 0.42; 10 RCTs; 1245 participants; moderate‐quality evidence) and the length of hospital stay was shortened by 0.8 days after LA (MD ‐0.81, 95% CI ‐1.01 to ‐0.62; 6 RCTs; 316 participants; low‐quality evidence). Quality of life was not reported in any of the included studies.

Authors' conclusions

Except for a higher rate of intra‐abdominal abscesses after LA in adults, LA showed advantages over OA in pain intensity on day one, wound infections, length of hospital stay and time until return to normal activity in adults. In contrast, LA showed advantages over OA in wound infections and length of hospital stay in children. Two studies reported better quality of life scores in adults. No study reported this outcome in children. However, the quality of evidence ranged from very low to moderate and some of the clinical effects of LA were small and of limited clinical relevance. Future studies with low risk of bias should investigate, in particular, the quality of life in children.

Plain language summary

Laparoscopic surgery compared to open surgery for suspected appendicitis

Review question

We reviewed the evidence about the effects of the open operation technique and the minimally invasive procedure in persons with suspected appendicitis.

Background

In the right lower part of the abdomen there is a small blind ending intestinal tube, called the appendix. Inflammation of the appendix is called appendicitis which is most frequent in children and young adults. Most cases require emergency surgery in order to avoid rupture of the appendix into the abdomen. During the operation, called appendectomy, the inflamed appendix is surgically removed. The traditional surgical approach involves a small incision (about 5 cm or 2 inches) in the right lower abdominal wall. Alternatively, it is possible to remove the inflamed appendix using another surgical technique, known as laparoscopic appendectomy. This operation requires three very small incisions (each about 1 cm or 1/2 inch). Then the surgeon introduces a camera and instruments into the abdomen and removes the appendix.

Study characteristics

We included 85 studies involving 9765 participants, of which 75 trials compared laparoscopic appendectomy versus open appendectomy in adults. The remaining 10 studies included only children. The evidence is current to February 2018.

Key results

The main advantages of laparoscopic compared to open appendectomy were reduced postsurgical pain, reduced risk of wound infection, shorter hospital stay, and more rapid return to normal activities in adults. In contrast, laparoscopic appendectomy showed advantages over open appendectomy in wound infections and shorter hospital stay in children. Two studies reported that adults who received laparoscopic appendectomy had better quality of life two weeks, six weeks, and six months after surgery. Data from children were not available. As for disadvantages of laparoscopic appendectomy, a higher rate of intra‐abdominal abscesses were identified in adults but not in children. Except for a trend towards decreased intra‐abdominal abscesses after LA, the results for children were similar to those seen in adults.

Quality of the evidence

The quality of the evidence varied from moderate to low because of poorly conducted studies.

Summary of findings

Background

Description of the condition

Acute appendicitis is an inflammation of the appendix and it is the most common cause of acute abdominal pain (Cheng 2015; Rehman 2011; Wilms 2011), with an individual lifetime incidence ranging from 6% to 16% (Addiss 1990; Lee 2010). The mortality rate following appendectomy (surgical removal of the appendix) is less than 1% (Andreu‐Ballester 2009; Bregendahl 2013; Kotaluoto 2017; Lin 2015; Weiser 2015).

Description of the intervention

Since the first recorded appendectomy performed by Claudius Amyand in 1735 and its description by McBurney in 1894, appendectomy is the treatment of choice for acute appendicitis (McBurney 1894). It soon became one of the most frequently performed surgical procedures. The surgical technique remained nearly unchanged for over a century, as it combines therapeutic efficacy with low morbidity (diseases affecting the health conditions) and mortality rates (Eriksson 1995). The evolution of endoscopic (using an instrument to look inside the body) surgery led to the idea of performing appendectomy via laparoscopy (surgery using small incisions), which was first described by Semm in 1983 (Semm 1983). In the past, the new method had only partly gained acceptance (Faiz 2008; Paterson 2008; Van Hove 2008). While some studies claimed laparoscopic appendectomy to be superior to open appendectomy in terms of a quicker and less painful recovery, fewer postoperative complications, and better cosmesis (appearance of the incisions after surgery), other studies found no such advantages or even favoured the open approach. Nowadays, laparoscopic appendectomy has gained wide acceptance (Bulian 2013; Ingraham 2010; Van Rossem 2016). It may happen that a non‐inflamed appendix is discovered during surgery. Therefore, preoperative imaging techniques are essential for confirming a suspected appendicitis (Webb 2011) because postoperative complications also occur after negative appendectomies (Jeon 2017).

How the intervention might work

Laparoscopic appendectomy offers several theoretical advantages compared to open appendectomy. Due to smaller incisions, it may be associated with reduced postsurgical pain, a lower wound infection rate and faster return to normal activity.

Why it is important to do this review

Laparoscopic appendectomy has gained wide acceptance and is the treatment of choice for acute appendicitis. Therefore, the superiority of laparoscopic appendectomy compared to open appendectomy should be established by performing a systematic review based on randomised controlled trials.

Objectives

To compare the effects of laparoscopic appendectomy (LA) and open appendectomy (OA) with regard to benefits and harms.

Methods

Criteria for considering studies for this review

Types of studies

We included all randomised (including cluster‐randomised) controlled trials comparing laparoscopic surgery and open appendectomy for acute appendicitis. Quasi‐randomised trials that allocated participants depending on the availability of staff or instruments or on the number of the day (odd or even) were excluded from the analysis. Due to the large number of studies available, we decided to also exclude trials that had no concealment of allocation.  If a trial was reported only as an abstract, or if no standard deviation was given for an outcome variable, or if the method of randomisation was not stated, the authors were contacted to provide full details of their trial. If the authors of an abstract did not provide information to determine whether it met the inclusion criteria, the abstract was excluded from further analysis.

Types of participants

We included all participants regardless of age with symptoms and signs of acute appendicitis. If a study reported a rate of more than 50% of appendix specimens without histological signs of inflammation, we assumed that this study mainly dealt with incidental appendectomies. Therefore, these studies were not included.

Types of interventions

We performed comparisons of laparoscopic versus open appendectomy in adults and in children.  The classical muscle‐splitting appendectomy and further open approaches were compared with laparoscopic appendectomy. Usually, this technique requires the insertion of three trocars into the abdominal cavity (Baird 2017). The appendix can be dissected by using either a stapling device (EndoGIA) or ligatures, the so‐called Roeder or EndoLoops. Both techniques can be seen as comparable (Mannu 2017).

Types of outcome measures

Primary outcomes

(1) Pain intensity on day one (any validated score such as visual analogue scale);  (2) Wound infections (defined by the study authors as a rate) up to 14 days after surgery;  (3) Intra‐abdominal abscesses (defined by the study authors as a rate) up to 14 days after surgery.

Secondary outcomes

(4) Length of hospital stay (days);  (5) Time until return to normal activities (days);  (6) Quality of life (any validated score, such as SF‐36 questionnaire) up to one year after surgery.

Search methods for identification of studies

Electronic searches

We conducted a comprehensive literature search to identify published and unpublished randomised controlled trials with no language restrictions. The Colorectal Cancer Group (CCCG) performed the searches in the following electronic databases:

Cochrane Central Register of Controlled Trials (CENTRAL, Issue 2, 2018) (The Cochrane Library) (Appendix 1);
Ovid MEDLINE (1950 to 9 February 2018) (Appendix 2);
Ovid Embase (1974 to 9 February 2018) (Appendix 3).

We also searched the following clinical trial registers:

World Health Organization (WHO) ICTRP portal (9 February 2018);
EU Clinical Trials Register (9 February 2018);
ClinicalTrials.gov (9 February 2018).

Searching other resources

We screened the reference lists of all relevant primary studies and review article for further studies (ANDEM 1997; Aziz 2006; Bennett 2007; Chung 1999; Dai 2017; Fingerhut 1999; Garbutt 1999; Golub 1998; Jaschinski 2015, Kapischke 2006; Kim 2004; Li 2010; Liu 2010; Meynaud‐Kraemer 1999; Ohtani 2012, Sadr‐Azodi 2009; Slim 1998; Temple 1999; Ukai 2016; Wei 2011). Additionally, authors of relevant articles and known international experts in the field of laparoscopic surgery were contacted to obtain information on any past, present, or future studies.

We handsearched abstracts presented to the following international scientific societies (February 2018): European Association of Endoscopic Surgery (EAES), Society of American Gastrointestinal Endoscopic Surgeons (SAGES), American Society for Gastrointestinal Endoscopy (ASGE), Asian Surgical Association (ASA), International Society for Surgery (ISS), Endoscopic and Laparoscopic Society of Asia (ELSA), Surgical Infection Society (SIS), and the German Society for Surgery (Deutsche Gesellschaft für Chirurgie, DGCh).

Data collection and analysis

We conducted the review according to the recommendations of the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). We used Review Manager 5.3 software (Review Manager 2014).

Selection of studies

At least two review authors assessed all studies (CM, MEI, StS, TJ) and read the titles and abstracts independently from each other. After the retrieval of potentially relevant studies, review authors independently assessed the full text of the papers to determine whether they met the inclusion criteria for this review. We resolved disagreements by consultation with a third review author. We contacted original study authors if the available data were insufficient to permit a judgement on inclusion.

Data extraction and management

Two review authors independently extracted the relevant data (CM, StS, TJ). We resolved any differences by discussion. Data from the included studies were entered in the table Characteristics of included studies. We listed excluded studies with reasons for their exclusion in the table Characteristics of excluded studies.

Assessment of risk of bias in included studies

We used the Cochrane 'Risk of bias' tool for assessing the risk of bias of the included studies (Chapter 8, Higgins 2011). Two review authors assessed the risk of bias of the following domains (CM, StS, TJ):

Random sequence generation;
Allocation concealment;
Blinding of participants and personnel;
Blinding of outcome assessment;
Incomplete outcome data;
Selective reporting bias; and
Evidence of learning curve bias that might influence the internal validity of trial results.

We judged each domain as low risk, high risk, or unclear risk of bias according to criteria used in the Cochrane 'Risk of bias' tool (see Appendix 4) (Chapter 8.5.d, Higgins 2011).

Measures of treatment effect

We performed analyses in Review Manager 5.3. provided by Cochrane (Review Manager 2014). We calculated Peto odds ratio (OR) with 95% confidence intervals (CIs) for dichotomous outcomes, and mean differences (MDs) and 95% CIs for continuous outcomes. For continuous outcomes, such as quality of life based on different measurement scales, we calculated standardised mean differences (SMDs) with 95% CIs.

Unit of analysis issues

We used individual participants as the unit of analysis. We did not identify any cluster‐randomised trials. We will include these trials in subsequent versions of this review by using an estimate of the intra‐cluster correlation co‐efficient (ICC) according to the Cochrane Handbook for Systematic Reviews of Interventions (Chapter 16.3, Higgins 2011).

Dealing with missing data

We contacted authors when key information was missing. If missing data became available, we included them in the analysis. If a study failed to report the standard deviation (SD) for an outcome measure, we used the mean of the trial as value for the SD (Follmann 1992). This approach produces relatively conservative results, since studies that did not report SDs tended to receive less weight.

Assessment of heterogeneity

Clinical heterogeneity caused by differences in participant characteristics and surgeons is likely to be moderate as studies had different inclusion criteria and some authors admitted the presence of a learning curve bias. The presence of statistical heterogeneity of treatment effects among trials was determined using the Chi² test and the I² statistic. If a P value was less than 0.05 in the Chi² test, we explored the causes of heterogeneity by conducting subgroup analyses. .

We classified the degree of heterogeneity as follows (Deeks 2011):

0% to 40%: might not be important;
30% to 60%: may represent moderate heterogeneity*;
50% to 90%: may represent substantial heterogeneity*;
75% to 100%: considerable heterogeneity*.

*The importance of the observed value of I² depends on (i) magnitude and direction of effects and (ii) strength of evidence for heterogeneity (e.g. P value from the chi‐squared test, or a confidence interval for I²).

Assessment of reporting biases

To control for the influence of a possible publication bias, we tested funnel plot asymmetry, as proposed by Egger and colleagues (Egger 1997) for comparisons that included at least 10 trials.

Data synthesis

We performed statistical analyses by using Review Manager 5.3 software (Review Manager 2014). After considering details from the Characteristics of included studies table, we assumed that the true treatment effect might differ between studies because of differences in participants, surgical skills, and outcome measurements. Therefore, we preferred the random‐effects model. However, we used the fixed‐effects model to calculate the Peto odds ratio. We considered a P value less than 0.05 to be statistically significant. We presented the results of meta‐analyses for each outcome graphically as forest plots.

Subgroup analysis and investigation of heterogeneity

Studies which evaluated LA in children or one sex only were not excluded, but studies in children were analysed separately. Additionally, we performed subgroup analyses for studies published within the last decade (from 2007), in order to consider the changes in laparoscopy and imaging.

Sensitivity analysis

Following sensitivity analyses were planned:

Including only studies with all domains at low risk of bias.

Summary of Findings table

We assessed the quality of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach in 'Summary of Findings' Table(s). In randomised controlled trials, the evidence can be downgraded from 'high quality' by one level for serious (or by two levels for very serious) limitations, depending on assessments for risk of bias, inconsistency of results, indirectness of evidence, imprecision or publication bias. Therefore, the evidence of randomised controlled trials could be downgraded to 'moderate' (on level), 'low' (two levels) and 'very low' (three levels).

The GRADE system classifies the quality of evidence in one of four grades:

Grade	Definition
High	Further research is very unlikely to change our confidence in the estimate of effect
Moderate	Further research is likely to have an impact on our confidence in the estimate of effect and may change the estimate
Low	Further research is very likely to have an important impact on our confidence on the estimate of effect and is likely to change the estimate
Very low	Any estimate of effect is very uncertain

Downgrades the evidence	Upgrades the evidence
Study limitation	Large magnitude of effect
Inconsistency of results	All plausible confounding would reduce the demonstrated effect
Indirectness of evidence	Dose‐response gradient
Imprecision
Publication bias

Laparoscopic versus open appendectomy in adults or adolescents for suspected appendicitis
Patient or population: patients with suspected appendicitis  Settings: most trials were single institutions across Europe, Asia, North America, South America, Australia and South Africa (frequency in descending order)  Intervention: laparoscopic versus open appendectomy in adults or adolescents
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect  (95% CI)	No of Participants  (studies)	Quality of the evidence  (GRADE)	Comments
	open appendectomy	laparoscopic appendectomy
Pain intensity on day 1	The mean pain intensity on day 1 ranged from 1.36 to 5.9.	The mean pain intensity on day 1 in the laparoscopic groups was  0.75 cm lower (on a 10‐cm VAS scale) (1.04 to 0.45 lower)		2421  (20 studies)	⊕⊕⊝⊝  low¹
Wound infections	Study population		Peto OR   0.42 (0.35 to 0.51)	7612  (63 studies)	⊕⊕⊕⊝  moderate²	Two studies reported no events
	86 per 1000	38 per 1000  (32 to 46)
Intra‐abdominal abscesses	Study population		Peto OR   1.65 (1.12 to 2.43)	6677  (53 studies)	⊕⊕⊕⊝  moderate²	Twenty‐eight studies reported no events
	12 per 1000	20 per 1000  (13 to 29)
Length of hospital stay (days)	The mean length of hospital stay (days) ranged from 0.88 to 11.9.	The mean length of hospital stay (days) in the laparoscopic groups was 0.96 shorter  (1.23 to 0.7 shorter)		5127  (46 studies)	⊕⊕⊝⊝  low¹
Time until return to normal activities (days)	The mean time until return to normal activities (days) ranged from 3.2 to 32.4.	The mean time until return to normal activity (days) in the laparoscopic groups was  4.97 shorter  (6.77 to 3.16 shorter)		1653  (17 studies)	⊕⊕⊝⊝  low¹
Quality of life Scale used: 1) Gastro‐intestinal Quality of Life Index 2) SF‐36 questionnaire	Kaplan 2009 used the Gastro‐intestinal Quality of Life Index questionnaire and found significant differences in favour of laparoscopic appendectomy 6 weeks and 6 months after surgery (each, P < 0.05). Katkhouda 2005 used the SF‐36 questionnaire 2 weeks after surgery. The quality of life scores were significantly better in the laparoscopic group for 2 out of 8 domains: physical functioning (P < 0.001) and general health (P = 0.018)				⊕⊕⊝⊝  low³
The basis for the assumed risk* (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).  CI: Confidence interval; Peto OR: Peto odds ratio; SF‐36: Short form‐36
GRADE Working Group grades of evidence  High quality: Further research is very unlikely to change our confidence in the estimate of effect.  Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.  Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.  Very low quality: We are very uncertain about the estimate.

Subgroup analysis (publication date) ‐ Laparoscopic versus open appendectomy in adults or adolescents for suspected appendicitis
Patient or population: patients with suspected appendicitis  Settings: most trials were single institutions across Europe, Asia, North America, South America, Australia, and South Africa (frequency in descending order)  Intervention: subgroup analysis (publication date) ‐ laparoscopic versus open appendectomy in adults or adolescents
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect  (95% CI)	No of Participants  (studies)	Quality of the evidence  (GRADE)	Comments
	open appendectomy	laparoscopic appendectomy
Pain intensity on day 1	The mean pain intensity on day 1 ranged from 1.36 to 4.53.	The mean pain intensity on day 1 in the laparoscopic groups was  0.52 cm lower (on a 10‐cm VAS scale)  (0.98 to 0.06 lower)		613  (7 studies)	⊕⊕⊝⊝  low¹
Wound infections	Study population		Peto OR 0.37   (0.27 to 0.51)	2217  (19 studies)	⊕⊕⊕⊝  moderate²	One study reported no events
	121 per 1000	49 per 1000  (36 to 66)
Intra‐abdominal abscesses	Study population		Peto OR 0.82   (0.44 to 1.51)	1466  (11 studies)	⊕⊕⊝⊝  low³	Four studies reported no events
	31 per 1000	26 per 1000  (14 to 46)
Length of hospital stay	The mean length of hospital stay (days) ranged from 0.88 to 11.9.	The mean length of hospital stay (days) in the laparoscopic groups was  0.84 day shorter  (1.23 to 0.44 shorter)		1977  (17 studies)	⊕⊕⊝⊝  low¹
Time until return to normal activity	The mean time until return to normal activities (days) ranged from 3.2 to 8.7.	The mean time until return to normal activity (days) in the laparoscopic groups was  2.27 days shorter  (5.81 shorter to 1.26 longer)		380  (3 studies)	⊕⊝⊝⊝  very low⁴
Quality of life Scale used: Gastro‐intestinal Quality of Life Index	Kaplan 2009 used the Gastro‐intestinal Quality of Life Index questionnaire and found significant differences in favour of laparoscopic appendectomy 6 weeks and 6 months after surgery (each, P < 0.05).				⊕⊕⊝⊝  low⁵
The basis for the assumed risk* (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).  CI: Confidence interval; Peto OR: Peto Odds ratio
GRADE Working Group grades of evidence  High quality: Further research is very unlikely to change our confidence in the estimate of effect.  Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.  Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.  Very low quality: We are very uncertain about the estimate.

Date	Event	Description
9 February 2018	New search has been performed	This is an update of the review from 2010
9 February 2018	New citation required but conclusions have not changed	Literature searches updated; 18 new trials added; risk of bias assessment updated; summary of findings tables added; flow chart diagram added; two new authors added in the byline.

Date	Event	Description
26 August 2010	New search has been performed	review from 2004 updated
26 August 2010	New citation required and conclusions have changed	Literature searches updated, 13 new trials added, risk of bias assessment updated, analyses and conclusion slightly changed, author exchanged.
5 August 2008	Amended	Converted to new review format.
22 July 2004	New citation required and conclusions have changed	Substantive amendment

RANDOM SEQUENCE GENERATION Selection bias (biased allocation to interventions) due to inadequate generation of a randomised sequence
Criteria for a judgement of ‘Low risk’ of bias.	The investigators describe a random component in the sequence generation process such as: · Referring to a random number table; · Using a computer random number generator; · Coin tossing; · Shuffling cards or envelopes; · Throwing dice; · Drawing of lots; · Minimization. Minimization may be implemented without a random element, and this is considered to be equivalent to being random.
Criteria for the judgement of ‘High risk’ of bias.	The investigators describe a non‐random component in the sequence generation process. Usually, the description would involve some systematic, non‐random approach, for example: · Sequence generated by odd or even date of birth; · Sequence generated by some rule based on date (or day) of admission; · Sequence generated by some rule based on hospital or clinic record number. · Other non‐random approaches happen much less frequently than the systematic approaches mentioned above and tend to be obvious. They usually involve judgement or some method of non‐random categorization of participants, for example: · Allocation by judgement of the clinician; · Allocation by preference of the participant; · Allocation based on the results of a laboratory test or a series of tests; · Allocation by availability of the intervention.
Criteria for the judgement of ‘Unclear risk’ of bias.	Insufficient information about the sequence generation process to permit judgement of ‘Low risk’ or ‘High risk’.
ALLOCATION CONCEALMENT Selection bias (biased allocation to interventions) due to inadequate concealment of allocations prior to assignment
Criteria for a judgement of ‘Low risk’ of bias.	Participants and investigators enrolling participants could not foresee assignment because one of the following, or an equivalent method, was used to conceal allocation: · Central allocation (including telephone, web‐based and pharmacy‐controlled randomisation); · Sequentially numbered drug containers of identical appearance; · Sequentially numbered, opaque, sealed envelopes.
Criteria for the judgement of ‘High risk’ of bias.	Participants or investigators enrolling participants could possibly foresee assignments and thus introduce selection bias, such as allocation based on: · Using an open random allocation schedule (e.g. a list of random numbers); · Assignment envelopes were used without appropriate safeguards (e.g. if envelopes were unsealed or nonopaque or not sequentially numbered); · Alternation or rotation; · Date of birth; · Case record number; · Any other explicitly unconcealed procedure.
Criteria for the judgement of ‘Unclear risk’ of bias.	Insufficient information to permit judgement of ‘Low risk’ or ‘High risk’. This is usually the case if the method of concealment is not described or not described in sufficient detail to allow a definite judgement – for example, if the use of assignment envelopes is described, but it remains unclear whether envelopes were sequentially numbered, opaque and sealed.
BLINDING OF PARTICIPANTS AND PERSONNEL Performance bias due to knowledge of the allocated interventions by participants and personnel during the study
Criteria for a judgement of ‘Low risk’ of bias.	Any one of the following: · No blinding or incomplete blinding, but the review authors judge that the outcome is not likely to be influenced by lack of blinding; · Blinding of participants and key study personnel ensured, and unlikely that the blinding could have been broken.
Criteria for the judgement of ‘High risk’ of bias.	Any one of the following: · No blinding or incomplete blinding, and the outcome is likely to be influenced by lack of blinding; · Blinding of key study participants and personnel attempted, but likely that the blinding could have been broken, and the outcome is likely to be influenced by lack of blinding.
Criteria for the judgement of ‘Unclear risk’ of bias.	Any one of the following: · Insufficient information to permit judgement of ‘Low risk’ or ‘High risk’; · The study did not address this outcome.
BLINDING OF OUTCOME ASSESSMENT Detection bias due to knowledge of the allocated interventions by outcome assessors
Criteria for a judgement of ‘Low risk’ of bias.	Any one of the following: · No blinding of outcome assessment, but the review authors judge that the outcome measurement is not likely to be influenced by lack of blinding; · Blinding of outcome assessment ensured, and unlikely that the blinding could have been broken.
Criteria for the judgement of ‘High risk’ of bias.	Any one of the following: · No blinding of outcome assessment, and the outcome measurement is likely to be influenced by lack of blinding; · Blinding of outcome assessment, but likely that the blinding could have been broken, and the outcome measurement is likely to be influenced by lack of blinding.
Criteria for the judgement of ‘Unclear risk’ of bias.	Any one of the following: · Insufficient information to permit judgement of ‘Low risk’ or ‘High risk’; · The study did not address this outcome.
INCOMPLETE OUTCOME DATA Attrition bias due to amount, nature or handling of incomplete outcome data
Criteria for a judgement of ‘Low risk’ of bias.	Any one of the following: · No missing outcome data; · Reasons for missing outcome data unlikely to be related to true outcome (for survival data, censoring unlikely to be introducing bias); · Missing outcome data balanced in numbers across intervention groups, with similar reasons for missing data across groups; · For dichotomous outcome data, the proportion of missing outcomes compared with observed event risk not enough to have a clinically relevant impact on the intervention effect estimate; · For continuous outcome data, plausible effect size (difference in means or standardised difference in means) among missing outcomes not enough to have a clinically relevant impact on observed effect size; · Missing data have been imputed using appropriate methods.
Criteria for the judgement of ‘High risk’ of bias.	Any one of the following: · Reason for missing outcome data likely to be related to true outcome, with either imbalance in numbers or reasons for missing data across intervention groups; · For dichotomous outcome data, the proportion of missing outcomes compared with observed event risk enough to induce clinically relevant bias in intervention effect estimate; · For continuous outcome data, plausible effect size (difference in means or standardised difference in means) among missing outcomes enough to induce clinically relevant bias in observed effect size; · ‘As‐treated’ analysis done with substantial departure of the intervention received from that assigned at randomisation; · Potentially inappropriate application of simple imputation.
Criteria for the judgement of ‘Unclear risk’ of bias.	Any one of the following: · Insufficient reporting of attrition/exclusions to permit judgement of ‘Low risk’ or ‘High risk’ (e.g. number randomised not stated, no reasons for missing data provided); · The study did not address this outcome.
SELECTIVE REPORTING Reporting bias due to selective outcome reporting
Criteria for a judgement of ‘Low risk’ of bias.	Any of the following: · The study protocol is available and all of the study’s prespecified (primary and secondary) outcomes that are of interest in the review have been reported in the prespecified way; · The study protocol is not available but it is clear that the published reports include all expected outcomes, including those that were prespecified (convincing text of this nature may be uncommon).
Criteria for the judgement of ‘High risk’ of bias.	Any one of the following: · Not all of the study’s prespecified primary outcomes have been reported; · One or more primary outcomes is reported using measurements, analysis methods or subsets of the data (e.g. subscales) that were not prespecified; · One or more reported primary outcomes were not prespecified (unless clear justification for their reporting is provided, such as an unexpected adverse effect); · One or more outcomes of interest in the review are reported incompletely so that they cannot be entered in a meta‐analysis; · The study report fails to include results for a key outcome that would be expected to have been reported for such a study.
Criteria for the judgement of ‘Unclear risk’ of bias.	Insufficient information to permit judgement of ‘Low risk’ or ‘High risk’. It is likely that the majority of studies will fall into this category.
OTHER BIAS Evidence of learning curve bias that might influence the internal validity of trial results
Criteria for a judgement of ‘Low risk’ of bias.	The study appeared to be free of learning curve bias.
Criteria for the judgement of ‘High risk’ of bias.	There is a potential source of bias. For example: · The surgeons were not experienced in the surgical approaches; · The authors identified a learning curve bias in their study.
Criteria for the judgement of ‘Unclear risk’ of bias.	There may be a risk of bias, but: · Insufficient information to assess whether a learning curve bias exists.

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Pain intensity on day 1	20	2421	Mean Difference (IV, Random, 95% CI)	‐0.75 [‐1.04, ‐0.45]
1.1 Studies reporting mean data	20	2421	Mean Difference (IV, Random, 95% CI)	‐0.75 [‐1.04, ‐0.45]
2 Wound infections	63	7612	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.42 [0.35, 0.51]
3 Intra‐abdominal abscesses	53	6677	Peto Odds Ratio (Peto, Fixed, 95% CI)	1.65 [1.12, 2.43]
4 Length of hospital stay	46	5127	Mean Difference (IV, Random, 95% CI)	‐0.96 [‐1.23, ‐0.70]
4.1 Studies reporting outcome	46	5127	Mean Difference (IV, Random, 95% CI)	‐0.96 [‐1.23, ‐0.70]
5 Time until return to normal activity	17	1653	Mean Difference (IV, Random, 95% CI)	‐4.97 [‐6.77, ‐3.16]
5.1 Studies reporting outcome	17	1653	Mean Difference (IV, Random, 95% CI)	‐4.97 [‐6.77, ‐3.16]

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Pain intensity on day 1 (cm VAS)	1	61	Mean Difference (IV, Random, 95% CI)	‐0.8 [‐1.65, 0.05]
1.1 Studies reporting outcome	1	61	Mean Difference (IV, Random, 95% CI)	‐0.8 [‐1.65, 0.05]
2 Wound infections	10	1245	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.25 [0.15, 0.42]
3 Intra‐abdominal abscesses	9	1185	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.54 [0.24, 1.22]
4 Length of hospital stay	6	316	Mean Difference (IV, Fixed, 95% CI)	‐0.81 [‐1.01, ‐0.62]
4.1 Studies reporting outcome	6	316	Mean Difference (IV, Fixed, 95% CI)	‐0.81 [‐1.01, ‐0.62]
5 Time until return to normal activity	1	383	Mean Difference (IV, Random, 95% CI)	‐0.5 [‐1.30, 0.30]
5.1 Studies reporting outcome	1	383	Mean Difference (IV, Random, 95% CI)	‐0.5 [‐1.30, 0.30]

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Pain intensity on day 1	7	613	Mean Difference (IV, Random, 95% CI)	‐0.52 [‐0.98, ‐0.06]
1.1 Studies reporting mean data	7	613	Mean Difference (IV, Random, 95% CI)	‐0.52 [‐0.98, ‐0.06]
2 Wound infections	19	2217	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.37 [0.27, 0.51]
3 Intra‐abdominal abscesses	11	1466	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.82 [0.44, 1.51]
4 Length of hospital stay	17	1977	Mean Difference (IV, Random, 95% CI)	‐0.84 [‐1.23, ‐0.44]
4.1 Studies reporting outcome	17	1977	Mean Difference (IV, Random, 95% CI)	‐0.84 [‐1.23, ‐0.44]
5 Time until return to normal activity	3	380	Mean Difference (IV, Random, 95% CI)	‐2.27 [‐5.81, 1.26]
5.1 Studies reporting outcome	3	380	Mean Difference (IV, Random, 95% CI)	‐2.27 [‐5.81, 1.26]

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Wound infections	5	783	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.27 [0.14, 0.52]
2 Intra‐abdominal abscesses	4	723	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.45 [0.19, 1.07]
3 Time until return to normal activity	1	383	Mean Difference (IV, Random, 95% CI)	‐0.5 [‐1.30, 0.30]
3.1 Studies reporting outcome	1	383	Mean Difference (IV, Random, 95% CI)	‐0.5 [‐1.30, 0.30]
4 Length of hospital stay	3	140	Mean Difference (IV, Fixed, 95% CI)	‐0.88 [‐1.11, ‐0.66]
4.1 Studies reporting outcome	3	140	Mean Difference (IV, Fixed, 95% CI)	‐0.88 [‐1.11, ‐0.66]

Methods	Randomised controlled trial Centres: two (USA)
Participants	Participants: "children 0‐18 years old with appendicitis" Gender: 39% females Age: 9.6 and 9.7 years (mean) in LA and OA Histology: not reported
Interventions	LA: three trocar technique (12, 5, and 5 mm), stump closure technique not described (n = 177) OA: right lower quadrant open incision (n = 206) Antibiotics: all children preoperatively: second‐generation cephalosporin (cefotetan or cefoxitin) IV only children labelled as having complicated appendicitis: additionally ampicillin, ceftazidime and clindamycin IV
Outcomes	Primary outcomes: wound infection; intra‐abdominal abscess Further outcomes: time to tolerate first oral intake; post‐anaesthesia recovery room pain medication; inpatient intravenous and oral opioid doses; inpatient nonsteroidal anti‐inflammatory medication doses; outpatient oral opioid and non‐opioid doses; pain scores (VAS); length of hospital stay; parental estimate of total time to participant recovery; participant and parental satisfaction scores (5‐point scale after 7 and 30 days); visits to other healthcare providers; visits to the emergency department; reoperation or re‐intervention; wound hematoma; urinary tract infection; pneumonia; bowel obstruction; diarrhoea
Notes	Follow‐up: 7 and 30 days postoperatively No appendectomy: none reported Declaration of interest: none of the authors had anything to disclose Funding: Oregon Health and Science University Preoperative imaging: not reported Analgesia requirements: not reported Sample size calculation: partly reported
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	"Randomization was performed using block technique. An independent statistician with no patient contact and with access only to de‐identified data at programmed, periodic reviews, generated blocks of 6‐10 sealed envelopes per round for each institution."
Allocation concealment (selection bias)	Low risk	"These were numbered sequentially and stored in a single location at each institution. The randomisation envelope and relevant surgical instruments were opened only once the child had undergone induction of general anesthesia."
Blinding of participants and personnel (performance bias)   All outcomes	Low risk	"... healthcare team, family, and data collectors remained blinded to the operation performed until post‐operative day 7." "The double dressings were designed to minimize unblinding due to leaking of wound fluid through the first gauze. Four total dressings were placed to hide the type of operation..." "Documented or potential unblinding such as wound fluid strike‐through or dressing dislodgement occurred in 17 (10%) of the laparoscopic group and 13 (6%) of the open group."
Blinding of outcome assessment (detection bias)   All outcomes	Low risk	"... healthcare team, family, and data collectors remained blinded to the operation performed until post‐operative day 7." "The double dressings were designed to minimize unblinding due to leaking of wound fluid through the first gauze. Four total dressings were placed to hide the type of operation..." "Documented or potential unblinding such as wound fluid strike‐through or dressing dislodgement occurred in 17 (10%) of the laparoscopic group and 13 (6%) of the open group."
Incomplete outcome data (attrition bias)   All outcomes	Low risk	There were no conversions and analyses were done following the ITT principle. Losses to follow‐up occurred in 2 of 177 (LA) and 1 of 206 (OA).
Selective reporting (reporting bias)	Low risk	Data on main results appeared to be complete.
Other bias	Unclear risk	"The standardized open surgical technique coupled with operative times that were nearly identical to laparoscopy suggested that neither variation in surgical method or expertise was a contributor. Alternatively, the presence of different level trainees may have impacted operative outcomes."

Methods	Randomised controlled trial Centres: one (Italy)
Participants	Participants: children "treated for acute appendicitis, with or without localized peritonitis"  Gender: 53% females  Age: 6 years (mean)  Histology: not reported
Interventions	LA: "three access points: umbilical, hypogastric and left iliac", trocar sizes and dissection technique for appendix stump not described (n = 20)  OA: McBurney incision (n = 20)  Antibiotics: cephalosporin, metronidazole
Outcomes	Wound infection; duration of operation; immunological markers
Notes	Follow‐up: not reported  No appendectomy: not reported Declaration of interest: not reported Funding: not reported Preoperative imaging: not reported Analgesia requirements: not reported Sample size calculation: not reported
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	"[The 40 children] were randomly allocated..."
Allocation concealment (selection bias)	Unclear risk	Not reported
Blinding of participants and personnel (performance bias)   All outcomes	Unclear risk	Not reported
Blinding of outcome assessment (detection bias)   All outcomes	Unclear risk	Not reported
Incomplete outcome data (attrition bias)   All outcomes	Unclear risk	No reporting of number and reasons for exclusions or completeness of follow‐up
Selective reporting (reporting bias)	Unclear risk	No distinction between primary and secondary outcome
Other bias	Unclear risk	The surgeon's skills were not described.

Methods	Randomised controlled trial Centres: one (South Africa)
Participants	Participants: premenopausal women with suspected acute appendicitis  Gender: 100% females  Age: 26 years (mean)  Histology: 15 of 34 participants had an inflamed appendix
Interventions	LAP: diagnostic laparoscopy followed by LA when acute appendicitis was visible or no other diagnosis was found; three‐trocar technique, stump closure by catgut ligatures (n = 18)  OA: open exploration either via right iliac fossa incision or lower midline laparotomy at the discretion of the operating surgeon. Appendix removed in all iliac fossa incisions (n = 16)  Antibiotics: not mentioned
Outcomes	Rates of unnecessary appendectomies; hospital stay; return to full activities and work; complication rates; duration of operation; number of analgesic doses; analgesia duration
Notes	Follow‐up: personal or telephonic interview 4 weeks postoperatively  No appendectomy: all appendices were resected Declaration of interest: not reported Funding: not reported Preoperative imaging: not reported Analgesia requirements: "Postoperatively, pethidine in a dose approximating 1 mg/kg was prescribed, and offered 6‐hourly." No difference in the consumption of analgesia Sample size calculation: not reported
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	"computer‐generated randomisation list"
Allocation concealment (selection bias)	Low risk	"numbered envelopes containing the instruction open or laparoscopic"
Blinding of participants and personnel (performance bias)   All outcomes	Unclear risk	Not reported
Blinding of outcome assessment (detection bias)   All outcomes	Unclear risk	Not reported
Incomplete outcome data (attrition bias)   All outcomes	Low risk	"Complete follow‐up data to 4 weeks were available for all randomised patients." The single converted case was analysed according to ITT.
Selective reporting (reporting bias)	Unclear risk	No distinction between primary and secondary outcome
Other bias	Low risk	Inexperienced surgical registrars were superceded as operators.

Methods	Randomised controlled trial Centres: one (Australia)
Participants	Participants: men with a clinical diagnosis of acute appendicitis  Gender: only men  Age: 25 years (median) in LA and OA  Histology: 88% inflamed
Interventions	LA: three trocar technique, stump closure with endo loop (n = 33)  OA: via muscle splitting incision (n = 31)  Antibiotics: ceftriaxone 1g IV and metronidazole 500mg IV
Outcomes	Hospital stay; return to full activities; complication rates; duration of operation; number of doses of narcotic analgesia
Notes	Follow‐up: "10 to 18 days after discharge" followed later by a telephone interview; 13 participants lost to follow‐up  No appendectomy: was done in one LA case with colitis, also analysed by ITT Declaration of interest: not reported Funding: not reported Preoperative imaging: not reported Analgesia requirements: "Postoperative analgesia was with intramuscular narcotic injection, oral analgesia, or both on a patient‐request basis." "There was no significant difference in the mean number of parenteral narcotic doses required during the postoperative period." Sample size calculation: not reported
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	"were randomized"
Allocation concealment (selection bias)	Unclear risk	Not reported
Blinding of participants and personnel (performance bias)   All outcomes	Unclear risk	Not reported
Blinding of outcome assessment (detection bias)   All outcomes	Unclear risk	Not reported
Incomplete outcome data (attrition bias)   All outcomes	Unclear risk	"Thirteen patients (7 with open and 6 with laparoscopic procedures) were lost to follow‐up." Converted cases (n = 4) and those receiving other surgery were analysed by ITT.
Selective reporting (reporting bias)	Unclear risk	No distinction between primary and secondary outcome
Other bias	Low risk	"Our study was performed after the initial learning phase of LA."

Methods	Randomised controlled trial Centre: one (India)
Participants	Participants: "...age range of 12‐48 years, with features which were suggestive of acute appendicitis..." Gender: 48% females Age: 23.9 years and 24.5 years (mean) in LA and OA Histology: three participants with negative appendicitis
Interventions	LA: three trocar technique (10, 5, and 5 mm); stump closure by endoloops (n = 114) OA: via McBurney or Lanz incision (n = 120) Antibiotics: not reported
Outcomes	Time of surgery; pain (first three days, VAS); length of hospital stay; wound infection, intra‐abdominal abscess, seroma, paralytic ileus
Notes	Follow‐up: on the 8th day No appendectomy: not reported Declaration of interest: "No competing interest" Funding: not reported Preoperative imaging: "...ultrasound of the abdomen were routinely performed in all the cases." Analgesia requirements: need for analgesics was not different between the two groups (details not reported) Sample size calculation: not reported
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	"All patients were randomly divided into..."
Allocation concealment (selection bias)	Unclear risk	Not reported
Blinding of participants and personnel (performance bias)   All outcomes	High risk	"This study was not blinded ..."
Blinding of outcome assessment (detection bias)   All outcomes	High risk	"This study was not blinded ..."
Incomplete outcome data (attrition bias)   All outcomes	High risk	Conversions (n = 6, 5%) were excluded from the study, which violates the ITT principle.
Selective reporting (reporting bias)	High risk	No primary outcome measure was defined. Pain measured for the first three consecutive days were not reported for the single days.
Other bias	Unclear risk	The surgeon's skills were not described.

Methods	Randomised controlled trial Centres: not reported (Austria)
Participants	Participants: presenting with acute appendicitis  Gender: 51% females  Age: 30 and 24 years (median) in LA and OA  Histology: 75% inflamed
Interventions	LA: three trocars (12, 10, and 5 mm); stump closure by stapling device (n = 87)  OA: via muscle splitting incision (n = 83)  Antibiotics: given selectively to 4 participants (2 in each group)
Outcomes	Hospital stay; return to full activities and sport; duration of operation; duration of analgesia; length of incision(s); participant satisfaction
Notes	Follow‐up: 5 and 30 days after surgery (completeness not stated). 6 to 26 months, median 6 months (42% complete)  Declaration of interest: not reported Funding: not reported Preoperative imaging: not reported Analgesia requirements: not reported Sample size calculation: not reported Comments: Due to inconsistencies in the three published reports on this study, the data on complications were considered unreliable (see text of review for further details).
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	"using a table of random numbers."
Allocation concealment (selection bias)	Unclear risk	Not reported
Blinding of participants and personnel (performance bias)   All outcomes	Unclear risk	Not reported
Blinding of outcome assessment (detection bias)   All outcomes	Unclear risk	Not reported
Incomplete outcome data (attrition bias)   All outcomes	High risk	No reporting of losses of follow‐up. One participant was excluded from all analyses after conversion from OA to LA. Thus, the study was not analysed ITT.
Selective reporting (reporting bias)	Unclear risk	No distinction between primary and secondary outcome
Other bias	High risk	A surgical learning curve must be assumed, as 60% of surgical complications after LA occurred in the first 18 participants (21%).

Methods	Randomised controlled trial Centers: one (Germany)
Participants	Participants: with a clinical diagnosis of acute appendicitis  Gender: 66% females  Age: only distribution into age groups reported  Histology: 56% inflamed (38% no inflammation, 6% missing)
Interventions	LA: three trocar technique (12, 10, and 5 mm); stump closure by EndoGIA (in > 95% of cases) (n = 61)  OA: via muscle splitting incision (n = 75)  Antibiotics: selected participants (13 LA and 20 OA cases) received antibiotics at the induction of anaesthesia (described on page 27). In most cases, antibiotic therapy was continued postoperatively.
Outcomes	Hospital stay; return to full activities; return to normal diet; complication rates; duration of operation; participant satisfaction; cosmesis; various laboratory and immunological parameters
Notes	Follow‐up: until hospital discharge. All participants received a postal questionnaire to elicit subjective outcomes, but only 33 of 136 participants replied.  No appendectomy: not reported Declaration of interest: not reported Funding: not reported Preoperative imaging: not reported Analgesia requirements: not reported Sample size calculation: not reported
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	A block randomisation was described, but no details were provided on the generation of the sequence. Randomisation was stratified for weight, gender, and age (all as dichotomous variables).
Allocation concealment (selection bias)	Low risk	"Randomisation aimed at achieving structural similarity between groups and was done by using sealed envelopes." ("Die Randomisierung mit dem Ziel der Strukturgleichheit erfolgte mit verschlossenen Briefumschlägen.")
Blinding of participants and personnel (performance bias)   All outcomes	Unclear risk	Not reported
Blinding of outcome assessment (detection bias)   All outcomes	Unclear risk	Not reported
Incomplete outcome data (attrition bias)   All outcomes	Low risk	In the LA group, converted cases (6/61, 10%) were analysed according to ITT. In both groups, a similarly low proportion of participants sent back the postal questionnaire (25% vs. 24%), but this does not affect the main outcomes of the study.
Selective reporting (reporting bias)	Low risk	One primary outcome (overall complication rate) was described. Other analyses were designated as being exploratory.
Other bias	High risk	All laparoscopic procedures were done by surgical registrars ("Oberarzt"), while open procedures were performed by registrars or experienced assistant surgeons.

Methods	Randomised controlled trial Centres: 10 centres (USA)  Comment: The study was three‐armed, as it compared two laparoscopic techniques versus open surgery.
Participants	Participants: patients with a clinical diagnosis of acute, chronic, or perforated appendicitis. Pregnant women were excluded.  Gender: 29% female  Age: 25 years (mean)  Histology: 84% inflamed
Interventions	LA: three trocar technique; stump closure by ligature or stapler (n = 89 + n = 78)  OA: via "transverse muscle‐splitting incision (5 to 6 cm)" (n = 86)  Antibiotics: not reported
Outcomes	Hospital stay; return to normal activities; complication rates; duration of operation; pain (VAS + analgesic dosages)
Notes	Follow‐up: "patients came back for their postoperative visit"; no time point given  No appendectomy: not reported Declaration of interest: not reported Funding: "This study was supported with a grant from the U.S. Surgical Corporation, Norwalk, Connecticut." Preoperative imaging: not reported Analgesia requirements: "A pain score of 4 received an intramuscular injection of meperidine; 3 elicited two acetaminophen with codeine tablets, 2 was given one tablet of acetaminophen with codeine; and 1 got plain acetaminophen." "The mean number of days for which patients required pain medication..." [...was similar between the groups (P = NS).] Sample size calculation: not reported
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	"Randomization was executed by a computer‐generated random numbers table..."
Allocation concealment (selection bias)	Low risk	"...administered centrally via a toll‐free telephone connection on a 24‐hour basis."
Blinding of participants and personnel (performance bias)   All outcomes	Low risk	In a subgroup where pain was measured "the patients' abdominal wounds were concealed by two army battle dressings applied at the conclusion of surgery."
Blinding of outcome assessment (detection bias)   All outcomes	Low risk	The nurse, who measured pain with the VAS was also blinded.
Incomplete outcome data (attrition bias)   All outcomes	Low risk	For most outcomes, no exclusions or losses to follow‐up were reported. Converted cases (n = 11, 7%) were analysed by ITT. However, data analysis on hospital stay excluded 5 participants, who stayed longer than 9 days.
Selective reporting (reporting bias)	Unclear risk	No distinction between primary and secondary outcome
Other bias	Low risk	Operations were performed by "residents with attending surgeons experienced in laparoscopic and open surgical techniques".

Methods	Randomised controlled trial Centres: three departments in two university hospitals (Denmark)
Participants	Participants: "patients with a clinical diagnosis of acute appendicitis"; children were included at one of the three centres  Gender: 53% females  Age: 26 and 27 years (median) in LA and OA  Histology: 79% inflamed
Interventions	LA: three trocar technique (10, 10, and 5 mm); stump closure by ligature (n = 282)  OA: via muscle‐splitting incision (n = 301)  Antibiotics: only given in perforated or gangrenous cases
Outcomes	Hospital stay; return to normal activities; return to work; complication rates; duration of operation; cosmesis (VAS)
Notes	Follow‐up: 80.3% of participants were seen in the outpatient clinic four weeks after discharge.  No appendectomy: was necessary in 50 laparoscopy participants Declaration of interest: not reported Funding: "Jacob and Olga Madsen's Fund provided financial support." Preoperative imaging: not reported Analgesia requirements: not reported Sample size calculation: not reported
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	"using computer‐generated, numbered,..."  Randomisation was stratified for age.
Allocation concealment (selection bias)	Low risk	"...opaque and sealed envelopes"
Blinding of participants and personnel (performance bias)   All outcomes	Unclear risk	Not reported
Blinding of outcome assessment (detection bias)   All outcomes	Unclear risk	Not reported
Incomplete outcome data (attrition bias)   All outcomes	Unclear risk	Converted cases (n = 65; 23%) were analysed according to ITT. For most outcomes, no losses to follow‐up were visible. Four‐week follow‐up was possible in 80.3% of participants, but no information was provided on whether the completeness of follow‐up differed between the groups.
Selective reporting (reporting bias)	Low risk	Primary outcome (hospital stay) was adequately described.
Other bias	Low risk	Trial surgeons were "of comparable experience" and were "equally divided between registrars and senior registrars".

Study	Reason for exclusion
Ablassmaier 1996	Choice of surgical procedure depended on the availability of surgeon and technical equipment. Thus, the study was nonrandomised, although an accompanying editorial falsely called the study randomised.
Ali 2017	In an email, Prof. Akhtar stated that "randomization was done by finding from already list of computer generated number, as to which group patient will be assigned." Thus, the study was randomised, but without allocation concealment..
Almond 2004	Choice of surgical procedure depended on the surgeon. Three of twelve surgeons routinely performed LA.
Alvarado‐Aparicio 2003	In the abstract, the study was said to be randomised, but retrospectively. Obviously, the study was not randomised.
Askarpour 2012	In an email dated October 15th, 2012, the first author stated: "We used simple alternation. [...] Patients were placed in the OA and LA group alternatively." Thus, the study was pseudo‐randomised.
Azaro 1999	The study was not randomised.
Barrat 1998	The study was retrospective.
Borgstein 1997	The study had no control group.
Buanes 1993	Choice of surgical procedure depended on the availability of surgeon and technical equipment. "Randomization after informed consent was not possible."
Busch 2011	The study was not randomised, as surgical technique was selected "according to departmental policy and surgeon preference".
Champault 1993	Choice of surgical procedure depended on the availability of surgeon and technical equipment.
Chen 2007	Although the abstract claimed that group allocation was "randomly", the study was judged to be pseudo‐randomised by the review authors. Consecutive participants received numbers (1 to 200) and were then allocated into the groups according to number (odd versus even). This mechanism produces alternation but no formal randomisation.
Chiarugi 1996	The study was pseudo‐randomised, and therefore without allocation concealment: "The patients were allocated to the two groups depending on whether the date of admission was an odd or even number."
Darzi 1994	"There was no formal randomization in the study because of instrument and surgeon availability."
Decadt 1999	This randomised study compared early laparoscopy versus observation.
Deutsch 1982	The study had no control group.
Fang 2006	Because of the imbalance in group size (LA, n = 53, versus OA, n = 77) the study was considered to be nonrandomised.
Gilchrist 1992	Study was not randomised: "Selection for OA or LA was done by surgeon availability, according to the staff paediatric surgeon on‐call schedule. When the laparoscopy‐trained surgeon was available, all patients (regardless of the severity of their illness) were offered the laparoscopic procedure."
Hanning 2006	Allocation was pseudo‐randomised since parents decided the operative procedure.
Hay 1998	In an email, Prof. Hay stated that "an open list of random codes" was used. Thus, the study was randomised, but without allocation concealment. As the uneven distribution between the group suggested, the study was not analysed according to intention‐to‐treat.
Herman 2000	In an email, the first author stated that the study was retrospective.
Herman 2003	The study was not randomised.
Hill 1991	"Selection of the procedure in these patients depended on the availability of staff, equipment and theatre time." (One year later, the same group performed a randomised trial, published by Attwood in 1992.)
Jan 2011	In an email dated December 8th, 2014, the first author stated: "We used simple alternation techniques". Thus, the study was pseudo‐randomised.
Karaorman 1994	Choice of surgical procedure depended on participants' symptoms. Cases with unclear symptoms underwent laparoscopy, if a skilled surgeon was available.
Klima 1998	In the 1998 publication, a randomised clinical trial with three different techniques of appendix stump closure was reported. In the 1996 publication, these three laparoscopic groups were compared against conventional appendectomy, but the choice between open or laparoscopic technique depended on the availability of laparoscopically experienced surgeons.
Kollias 1994	"True randomization was not formally obtained", because patients "were prospectively assigned to either open appendicectomy (OA) if admitted under Surgical Unit B or laparoscopic appendicectomy (LA) if admitted under Surgical Unit A."
Koluh 2010	In an email dated October 18th, 2012, the first author stated: "A simple randomization of the ABABAB type was used." Thus, the study was pseudo‐randomised.
Konstadoulakis 2006	Comparison of two open techniques.
Kotlobovskii 2003	The study was excluded because it had included children with appendicular peritonitis. Average disease duration was over two days, and postoperative admission to the intensive care unit was necessary in most cases. The study still seems to be important, since it was obviously randomised, although the method of randomisation was not described.
Kum 1993b	The study was not randomised, because surgeon availability determined choice of procedure.
Kumar 2004	Comparison of open techniques.
Lamparelli 2000	Control participants were "under the care of the other surgical teams in our unit during the study period".
Lansdown 1993	Study was not randomised. Control group was matched.
Lau 2005	Comparison between needlescopic appendectomy and conventional laparoscopic appendectomy.
Li 2005	Study was not randomised: "For every patient, the patients or their parents were the ones to choose the approach,..." (LA, n = 69, versus OA, n = 91).
Lujan Mompean 1994	Study was not randomised: "Formal randomization was precluded by instrument availability, but the time of day did not influence allocation."
Malik 2007	Comparison of two open techniques.
Malik 2009	Statistical analyses included nonrandomised participants: "The patients were divided into group A (OA) and group B (VAECA) on patient choice and by coin toss, where patients did not opt for any particular technique."
Mantoglu 2013	Study was only pseudo‐randomised: "The patients were randomized into two groups [...] according to admitting day. Patients who were admitted on odd days were treated with LA the others with OA."
Marzouk 2002	Study was not randomised: "The patients were assigned [to LA or OA] according to insurance company approval."
McAnena 1992	Study was not randomised: "Formal randomization was precluded on occasions by instrument availability but not by the time of day at which the operation was performed."
Milewczyk 1998	In a letter from 1999, Dr. Michalik explained that an open list of random codes was used. Thus, the study was randomised, but without allocation concealment. The 2003 publication reported on 200 participants (instead of 80 as before), but the trial periods overlapped. Therefore, this is one large study with an interim analysis.
Moberg 1998	The study had no control group.
Moldovanu 2010	The study was retrospective.
Mugomba 2001	Choice of surgical procedure was made nonrandomly by the senior surgeon.
Naver 1994	Choice of surgical procedure depended on the availability of a laparoscopic surgeon: "In the presence of a surgeon with laparoscopic experience laparoscopy was performed".
Niebuhr 1992	Choice of surgical procedure depended on the availability of surgeon and technical equipment.
Näf 1996	The study was retrospective.
Oka 2004	Choice of surgical procedure was "based on the schedule of the attending surgeon on call".
Padankatti 2008	In the abstract, it was described that "children were allocated randomly". In the main text, however, it was stated that "cases were allocated into open and laparoscopic groups based on surgeon preference".
Planells Roig 1993	Choice of surgical procedure depended on the surgical team being on call.
Prado 1997	Control group consisted of cases operated on in a different hospital.
Pruett 1994	Study used historical control group.
Raakow 1993	Choice of surgical procedure depended on the availability of surgeon and technical equipment.
Rashid 2013	In an email dated December 5th, 2014, the first author stated: "We had an open random list hanging on the wall in the surgical consultancy room. This random list was generated by a computer." Thus, the study was randomised, but without allocation concealment. In addition, the study investigated interval rather than acute appendectomy. Operations took place about 2 months after the initial appendicitis episode which was managed conservatively.
Reiertsen 1994	The study was non‐randomised: "The patients were selected for a conventional or laparoscopic procedure by the surgeon on call."
Richards 1993	Study used a parallel control group, but "a randomized trial of open versus laparoscopic appendectomy could not be completed in Nashville."
Ritter 1998	Choice of surgical procedure depended on the availability of surgeon and technical equipment.
Rückert 1993	This short abstract described a "prospective randomized" study, in which 51 LA and 150 OA cases were compared. No results were given. Considering the imbalance of the groups, the study seemed not to be randomised. A letter to the first author in November 2001 failed to elicit any answer.
Sarihan 1994	This randomised controlled trial compared peritoneal drainage versus no drainage in perforated appendicitis.
Sayed Hassen 1996	Choice of surgical procedure depended on the availability of surgeon and technical equipment. Assignment depended "on whether the surgeon on call was an 'open' or 'laparoscopic' surgeon for the purpose of the study."
Schramm 1994	The study was non‐randomised, because choice of surgical technique depended on the availability of a laparoscopic surgeon and severity of symptoms.
Schroder 1993	Study was non‐randomised: "The selection of traditional or laparoscopic appendectomy was based on the availability of laparoscopic equipment and the surgeon's experience. No patient was denied laparoscopic surgery based on severity of disease."
Schäfer 1997	The study used a historical control group.
Sfez 1993	The authors described the study as "prospective". The two groups of 18 and 20 cases had comparable baseline characteristics, but randomisation was not mentioned anywhere in the text. A letter to the author remained unanswered.
Shalaby 2001	This randomised clinical trial compared three techniques of closing the appendix stump in laparoscopic appendectomy. Conventional appendectomy was not evaluated.
Shen 2012	The assignment to the groups was not randomised. "Some of the insurance companies are approving only OA..., in most cases, the patient was the one to choose the approach after the surgeon explained the procedure...".
Shirazi 2010	Study was only pseudo‐randomised: "quasi‐experimental study" and "alternatively assigned to group A or B".
Sosa 1993	The study has a retrospective design. The control cases (open appendectomy) were randomly selected from all patients who had undergone open appendectomy.
St Peter 2010	The study compared an operative with a conservative approach.
Tarnoff 1998	The study was not randomised.
Tate 1993b	"Patients were not randomized: laparoscopy was performed when a suitably trained surgeon and laparoscopic instruments were available."
Thon 1996	The study was not randomised.
Thorell 1999	The study was not randomised.
Till 1994	The assignment to conventional or laparoscopic appendectomy was based on the availability of laparoscopically experienced surgeons.
Ure 1992	The control group consisted only of the converted cases.
Van den Broek 2000	The assignment to groups was made according to severity of symptoms.
Varlet 1994	The study was retrospective.
Whitworth 1998	The study was not randomised.
Wullstein 2001	The study was retrospective.
Zaninotto 1995	In the 1994 abstract, the authors claimed that participants were "randomly assigned to open or laparoscopic surgery". In the full paper, however, the study appeared to be at best pseudo‐randomised: "Four surgeons [...] were allocated to laparoscopic treatment (LAP) or open (OPEN) treatment. [...] Each surgeon always performed only one type of operation."

Trial name or title	Impact of children laparoscopic appendectomy on gastrointestinal function: a randomized controlled trial
Methods	Randomised parallel control
Participants	1. the diagnosis of appendicitis in children; 2. older than 3 years old, less than 16 years old; 3. informed consent.
Interventions	LA (n = 60) versus OA (n = 60)
Outcomes	Incidence of residual pus of peritoneal fluid; wound infection; incidence of abdominal abscess; occurrence of incisional hernia; recovery of gastrointestinal function; incidence of postoperative fever; incidence of postoperative ileus.
Starting date	2014/08/01
Contact information	Name: Zhong Wenyi E‐Mail: dbzhongwy@163.com Address: Department of Minimally Invasive Surgery, Da‐bu People hospital; Meizhou City, Guangdong Province, China
Notes	Main ID: ChiCTR‐TRC‐14005067 Primary sponsor: Department of Minimally Invasive Surgery, Da‐bu People hospital, Meizhou City, Guangdong Source of funding: by raised

Trial name or title	Laparoscopic versus open appendectomy: compare outcomes and complications in the treatment of complicated appendicitis
Methods	Randomised controlled trial
Participants	All patients suspected of having complicated acute appendicitis
Interventions	LA versus OA (n = 96)
Outcomes	Primary outcome: duration of surgery Secondary outcome: surgical site infection; intra‐abdominal abscess; pain, complications such as nosocomial infections, hernia incisional; length of hospitalisation; need for further surgery
Starting date	2015/11/22 (no longer recruiting)
Contact information	Name: Amir Mangouri E‐Mail: amir.mangouri@gmail.com Adress: Azadi Ave, Hafez Square, Sina hospital Tabriz, Iran
Notes	Main ID: http://en.irct.ir/trial/20823 Primary sponsor: Vice Chancellor for research, Tabriz University of Medical Sciences Source of funding: Vice Chancellor for research, Tabriz University of Medical Sciences

Trial name or title	Comparison of complications and outcomes of three methods of laparoscopic appendectomy: single incision and open appendectomy in paediatric patients
Methods	Randomised controlled trial
Participants	In paediatric age group (from 8 years old to 14 years old)
Interventions	The interventions consisted of: group 1 to undergo open conventional appendectomy, group 2 to be treated by laparoscopic appendectomy, group 3 appendectomy to be done using single incision appendectomy.
Outcomes	Duration of surgery; wound infection; size of the scar; hospital stay time
Starting date	2017/08/07 (recruitment completed)
Contact information	Name: Dr Amir Kazem Vejdan E‐Mail: vejdan_sa@bums.ac.ir Address: Birjand University of Medical Sciences, Imam Reza hospital, Birjand, Iran
Notes	Main ID: http://en.irct.ir/trial/8854 Primary sponsor: Birjand University of Medical Sciences Source of funding: Birjand University of Medical Sciences

Trial name or title	Open appendectomy versus laparoscopic appendectomy ‐ the outcomes of various appendectomy techniques in a high‐volume centre
Methods	Randomised controlled trial
Participants	Patients with a preoperative diagnosis of acute appendicitis
Interventions	LA (appendiceal stump secured by metal endoclips; n = 50) versus LA (appendiceal stump secured by intracorporeal suture ligation; n = 50) versus OA (n = 50)
Outcomes	Primary outcome: quality of life after various appendectomy procedures to be measured by a specific quality‐of‐life index (after 1 month) Secondary outcome: cost‐effectiveness
Starting date	2010/10/01
Contact information	Name: Halil Alis E‐Mail: not reported Address: Dr. Sadi Konuk Training and Research Hospital, Istanbul, Turkey, 34147
Notes	Main ID: NCT01260064 Primary sponsor: Bakirkoy Dr. Sadi Konuk Research and Training Hospital Source of funding: Bakirkoy Dr. Sadi Konuk Research and Training Hospital

PERMALINK

Laparoscopic versus open surgery for suspected appendicitis

Thomas Jaschinski

Christoph G Mosch

Michaela Eikermann

Edmund AM Neugebauer

Stefan Sauerland

Abstract

Background

Objectives

Search methods

Selection criteria

Data collection and analysis

Main results

Authors' conclusions

Plain language summary

Summary of findings

Background

Description of the condition

Description of the intervention

How the intervention might work

Why it is important to do this review

Objectives

Methods

Criteria for considering studies for this review

Types of studies

Types of participants

Types of interventions

Types of outcome measures

Primary outcomes

Secondary outcomes

Search methods for identification of studies

Electronic searches

Searching other resources

Data collection and analysis

Selection of studies

Data extraction and management

Assessment of risk of bias in included studies

Measures of treatment effect

Unit of analysis issues

Dealing with missing data

Assessment of heterogeneity

Assessment of reporting biases

Data synthesis

Subgroup analysis and investigation of heterogeneity

Sensitivity analysis

Summary of Findings table

Results

Description of studies

Results of the search

1.

Included studies

Excluded studies

Risk of bias in included studies

2.

3.

Allocation

Blinding

Incomplete outcome data

Selective reporting

Other potential sources of bias

Effects of interventions

Summary of findings for the main comparison. Laparoscopic versus open appendectomy in adults or adolescents for suspected appendicitis.

Summary of findings 2. Laparoscopic versus open appendectomy in children for suspected appendicitis.

Summary of findings 3. Subgroup analysis (publication date) ‐ Laparoscopic versus open appendectomy in adults or adolescents for suspected appendicitis.

Summary of findings 4. Subgroup analysis (publication date) ‐ Laparoscopic versus open appendectomy in children for suspected appendicitis.

Laparoscopic versus open appendectomy in adults or adolescents

Primary outcomes

Pain intensity on day one

1.1. Analysis.

3.1. Analysis.

Wound infections

1.2. Analysis.

3.2. Analysis.

Intra‐abdominal abscesses

1.3. Analysis.

3.3. Analysis.

Secondary outcomes

Length of hospital stay

1.4. Analysis.

Trial name or title	Value of laparoscopic appendectomy in perforated appendicitis ‐ a randomised trial
Methods	Parallel randomised
Participants	Patients diagnosed as having complicated appendicitis with peritonitis or abscess formation, by abdominal examination, laboratory data, or CT
Interventions	LA (n = 50) versus OA (n = 50)
Outcomes	Primary outcome: occurrence of postoperative infectious complications Secondary outcomes: rate of reoperation; indices of postoperative recovery (analgesic use, oral intake restart, physical activity, bowel movement); duration of hospital stay; operating time
Starting date	2008/10/01 (no longer recruiting)
Contact information	Name: Shunichiro Komatsu E‐Mail: skomat@nagoya2.jrc.or.jp Address: 2‐9, Myokencho, Showaku, Nagoya City, Aichi Pref. Japan
Notes	Main ID: JPRN‐UMIN000003711 Primary sponsor: Nagoya Daini Red Cross Hospital Source of funding: Nagoya Daini Red Cross Hospital