Early versus delayed appendicectomy for appendiceal phlegmon or abscess

Abstract

Background

This is an update of a Cochrane review first published in 2017.

Acute appendicitis (inflammation of the appendix) can be simple or complicated. Appendiceal phlegmon and appendiceal abscess are examples of complicated appendicitis. Appendiceal phlegmon is a diffuse inflammation in the bottom right of the appendix, while appendiceal abscess is a discrete inflamed mass in the abdomen that contains pus.

Appendiceal phlegmon and abscess account for 2% to 10% of acute appendicitis. People with appendiceal phlegmon or abscess usually need an appendicectomy to relieve their symptoms (e.g. abdominal pain, loss of appetite, nausea, and vomiting) and avoid complications (e.g. peritonitis (infection of abdominal lining)). Surgery for people with appendiceal phlegmon or abscess may be early (immediately after hospital admission or within a few days of admission), or delayed (several weeks later in a subsequent hospital admission). The optimal timing of appendicectomy for appendiceal phlegmon or abscess is debated.

Objectives

To assess the effects of early appendicectomy compared to delayed appendicectomy on overall morbidity and mortality in people with appendiceal phlegmon or abscess.

Search methods

We searched CENTRAL, MEDLINE, Embase, two other databases, and five trials registers on 11 June 2023, together with reference checking to identify additional studies.

Selection criteria

We included all individual and cluster‐randomised controlled trials (RCTs), irrespective of language, publication status, or age of participants, comparing early versus delayed appendicectomy in people with appendiceal phlegmon or abscess.

Data collection and analysis

We used standard methodological procedures expected by Cochrane.

Main results

We included eight RCTs that randomised 828 participants to early or delayed appendicectomy for appendiceal phlegmon (7 trials) or appendiceal abscess (1 trial). The studies were conducted in the USA, India, Nepal, and Pakistan. All RCTs were at high risk of bias because of lack of blinding and lack of published protocols. They were also unclear about methods of randomisation and length of follow‐up.

1. Early versus delayed open or laparoscopic appendicectomy for appendiceal phlegmon

We included seven trials involving 788 paediatric and adult participants with appendiceal phlegmon: 394 of the participants were randomised to the early appendicectomy group (open or laparoscopic appendicectomy as soon as the appendiceal mass resolved within the same admission), and 394 were randomised to the delayed appendicectomy group (initial conservative treatment followed by delayed open or laparoscopic appendicectomy several weeks later).

There was no mortality in either group. The evidence is very uncertain about the effect of early appendicectomy on overall morbidity (risk ratio (RR) 0.74, 95% confidence interval (CI) 0.19 to 2.86; 3 trials, 146 participants; very low‐certainty evidence), the proportion of participants who developed wound infections (RR 0.99, 95% CI 0.48 to 2.02; 7 trials, 788 participants), and the proportion of participants who developed faecal fistulas (RR 1.75, 95% CI 0.36 to 8.49; 5 trials, 388 participants). Early appendicectomy may reduce the abdominal abscess rate (RR 0.26, 95% CI 0.08 to 0.80; 4 trials, 626 participants; very low‐certainty evidence), reduce the total length of hospital stay by about two days (mean difference (MD) −2.02 days, 95% CI −3.13 to −0.91; 5 trials, 680 participants), and increase the time away from normal activities by about five days (MD 5.00 days; 95% CI 1.52 to 8.48; 1 trial, 40 participants), but the evidence is very uncertain.

2. Early versus delayed laparoscopic appendicectomy for appendiceal abscess

We included one trial involving 40 paediatric participants with appendiceal abscess: 20 were randomised to the early appendicectomy group (emergent laparoscopic appendicectomy), and 20 were randomised to the delayed appendicectomy group (initial conservative treatment followed by delayed laparoscopic appendicectomy 10 weeks later). There was no mortality in either group. The trial did not report on overall morbidity, various complications, or time away from normal activities. The evidence is very uncertain about the effect of early appendicectomy on the total length of hospital stay (MD −0.20 days, 95% CI −3.54 to 3.14; very low‐certainty evidence).

Authors' conclusions

For the comparison of early versus delayed open or laparoscopic appendicectomy for paediatric and adult participants with appendiceal phlegmon, very low‐certainty evidence suggests that early appendicectomy may reduce the abdominal abscess rate. The evidence is very uncertain whether early appendicectomy prevents overall morbidity or other complications. Early appendicectomy may reduce the total length of hospital stay and increase the time away from normal activities, but the evidence is very uncertain.

For the comparison of early versus delayed laparoscopic appendicectomy for paediatric participants with appendiceal abscess, data are sparse, and we cannot rule out significant benefits or harms of early versus delayed appendicectomy.

Further trials on this topic are urgently needed and should specify a set of criteria for use of antibiotics, percutaneous drainage of the appendiceal abscess prior to surgery, and resolution of the appendiceal phlegmon or abscess. Future trials should include outcomes such as time away from normal activities and length of hospital stay.

Plain language summary

Early or delayed surgical removal of the appendix: which works better to treat an appendiceal mass (lump on the appendix)?

Key messages

‐ Early open or keyhole (where surgery is performed through a very small cut) removal of the appendix (a tube at the connection of the small and the large intestines) may reduce the rate of abdominal abscess (a collection of pus in the abdomen) in people with appendiceal phlegmon (a diffuse inflammation in the bottom right of the appendix), but we are very uncertain about the results.

‐ We do not know if early open or keyhole removal of the appendix has an important effect on the overall complication rate or on other complications in people with appendiceal phlegmon. Early open or keyhole removal of the appendix may reduce the total length of hospital stay and may increase the time away from normal activities, but we are very uncertain about the results.

‐ We do not know if early keyhole removal of the appendix has an important effect on outcomes in children with appendiceal abscess.

What is an appendiceal mass?

The appendix is a tube located at the connection between the small and large intestines. 'Appendicitis' is when the appendix becomes swollen and painful (inflamed). In some cases, appendicitis can cause a lump called an appendiceal mass to form on the appendix. This could be a 'phlegmon', which is a diffuse inflammation in the bottom right of the appendix, or an 'abscess', which is a collection of pus in the stomach.

How is appendiceal mass treated?

People with appendiceal masses usually need surgical removal of the appendix to relieve their symptoms (abdominal pain, loss of appetite, nausea, and vomiting) and avoid complications (such as peritonitis). The timing of the surgery is controversial. Immediate surgery is difficult because it is challenging to suture (stitch up) the inflamed appendix stump. However, some experts think that removing the appendix weeks later (delayed surgery) is unnecessary, as people are unlikely to experience recurrence after successful non‐surgical treatment. However, it is sometimes difficult to find the cause of the lump on the appendix, and waiting to remove the appendix could delay the diagnosis of any underlying disease.

What did we want to find out?

We wanted to find out if early removal of the appendix (immediately after hospital admission or within a few days) was better than delayed removal of the appendix (several weeks later in a subsequent hospital admission), in terms of:

‐ overall complication rate, including wound infection, abdominal abscess, faecal fistula (an abnormal opening between the intestine and the abdomen);

‐ death rate;

‐ total length of hospital stay;

‐ time away from normal activities.

What did we do?

We searched for studies that looked at early removal of the appendix compared with delayed removal of the appendix in people with appendiceal phlegmon or abscess. We compared and summarised the results of the studies and rated our confidence in the evidence, based on factors such as study methods and sizes.

What did we find?

We identified eight studies, involving 828 participants, that compared early versus delayed appendicectomy for either appendiceal phlegmon (7 studies) or appendiceal abscess (1 study).

People with phlegmon

We found seven studies with 788 children and adults with appendiceal phlegmon. Of these, 394 had early open or keyhole and 394 had delayed open or keyhole removal of the appendix.

We do not know if early removal of the appendix has an effect on overall complications (including wound infection and faecal fistula).

Compared with delayed removal of the appendix, early removal of the appendix may reduce abdominal abscesses (43 fewer abdominal abscesses per 1000 participants), and reduce the total length of hospital stay by about two days, but we are very uncertain about these results.

There were no deaths in the studies.

Early removal of the appendix may increase the time away from normal activities by about five days, but we are very uncertain about this result.

People with abscess

We found one study with 40 children. Twenty children had early keyhole removal of the appendix and 20 children had delayed keyhole removal of the appendix.

The study did not report overall complications (including wound infection, abdominal abscess, and faecal fistula), or time away from normal activities.

There were no deaths in the study.

We do not know if early removal of the appendix has an effect on the total length of hospital stay.

What are the limitations of the evidence?

We are not confident in the evidence because it is possible that people in the studies were aware of what treatment they were getting, and because not all of the studies provided information about everything we were interested in. In addition, some studies did not clearly report how they were conducted, and there are not enough studies available for us to be certain about the results.

How up to date is this evidence?

This review updates our previous review. The evidence is current to June 2023.

Summary of findings

Summary of findings 1. Early versus delayed open or laparoscopic appendicectomy for appendiceal phlegmon.

Early versus delayed open or laparoscopicappendicectomy for appendiceal phlegmon
Patient or population: paediatric and adult participants with appendiceal phlegmon Setting: secondary and tertiary care Intervention: early open or laparoscopic appendicectomy Comparison: delayed open or laparoscopic appendicectomy
Outcomes	Anticipated absolute effects* (95% CI)		Relative effect (95% CI)	Number of participants (trials)	Certainty of the evidence (GRADE)	Comments
	Risk with delayed appendicectomy	Risk with early appendicectomy
Overall morbidity Median follow‐up: 33.5 monthsk	342 per 1000	253 per 1000 (65 to 979)	RR 0.74 (0.19 to 2.86)	146 (3)	⊕⊝⊝⊝ Verylowa,b,c	—
Wound infection Median follow‐up: 33.5 monthsk	94 per 1000	93 per 1000 (45 to 190)	RR 0.99 (0.48 to 2.02)	788 (7)	⊕⊝⊝⊝ Verylowa,d,e	—
Abdominal abscess Median follow‐up: 33.5 monthsk	58 per 1000	15 per 1000 (5 to 46)	RR 0.26 (0.08 to 0.80)	626 (4)	⊕⊝⊝⊝ Verylowa,f	—
Faecal fistula Median follow‐up: 33.5 monthsk	5 per 1000	9 per 1000 (2 to 44)	RR 1.75 (0.36 to 8.49)	388 (5)	⊕⊝⊝⊝ Verylowa,g	—
Mortality Median follow‐up: 33.5 monthsk	See comment	See comment	Not estimable	788 (7)	⊕⊝⊝⊝ VeryLowa,h	There was no mortality in either group.
Total length of hospital stay (days) Follow‐up: 33.5 weeksk	The mean total length of hospital stay in the delayed appendicectomy group was 5.41 to 14.7 days	The mean total length of hospital stay in the early appendicectomy group was 2.02 fewer (3.13 to 0.91 fewer)	MD −2.02 (−3.13 to −0.91)	680 (5)	⊕⊝⊝⊝ Very Lowa,i	Two additional trials did not report mean or SD values that were suitable for pooling (Khan 2021b; Kumar 2018). Both trials (108 participants) reported that early appendicectomy was associated with a shorter hospital stay than delayed appendicectomy.
Time away from normal activities (days) Median follow‐up: 33.5 monthsk	The mean time away from normal activities in the delayed appendicectomy group was 20 days	The mean time away from normal activities in the early appendicectomy group was 5 days more (1.52 to 8.48 more)	MD 5.00 (1.52 to 8.48)	40 (1 study)	⊕⊝⊝⊝ Very lowa,j	—
*The basis for the assumed risk is the mean baseline risk from the studies in the meta‐analysis. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; RR: risk ratio; MD: mean difference; SD: standard deviation
GRADE Working Group grades of evidence High certainty: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect. Very low certainty: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect.

^aDowngraded 2 levels for very serious risk of bias: all trials with unclear risk of bias for random sequence generation, allocation concealment, blinding of outcome assessment, and selective reporting; all trials at high risk of bias for blinding of participants and personnel
^bDowngraded 2 levels for very serious imprecision: small sample size and a confidence interval that included both potential benefit and potential harm from the intervention
^cDowngraded 1 level for serious inconsistency: unexplained statistical heterogeneity (I² = 72%)
^dDowngraded 1 level for serious imprecision: a confidence interval that included both potential benefit and potential harm from the intervention
^eDowngraded 1 level for serious inconsistency: unexplained statistical heterogeneity (I² = 47%)
^fDowngraded 1 level for serious imprecision: few events and a wide confidence interval
^gDowngraded 2 levels for very serious imprecision: small sample size, few events, and a confidence interval that included both potential benefit and potential harm from the intervention
^hDowngraded 1 level for serious imprecision: no events
ⁱDowngraded 2 levels for very serious inconsistency: unexplained statistical heterogeneity (I² = 89%)
^jDowngraded 2 levels due to very serious imprecision (very small sample size)
^kThe length of follow‐up is based on one trial because the other trials did not report it.

Summary of findings 2. Early versus delayed laparoscopic appendicectomy for appendiceal abscess.

Early versus delayed laparoscopic appendicectomy for appendiceal abscess
Patient or population: paediatric participants with appendiceal abscess Setting: secondary and tertiary care Intervention: early laparoscopic appendicectomy Comparison: delayed laparoscopic appendicectomy
Outcomes	Anticipated absolute effects* (95% CI)		Relative effect (95% CI)	Number of participants (trials)	Certainity of the evidence (GRADE)	Comments
	Risk with delayed appendicectomy	Risk with early appendicectomy
Overall morbidity	Not reported
Wound infection	Not reported
Abdominal abscess	Not reported
Faecal fistula	Not reported
Mortality Follow‐up: 12 weeks	See comment	See comment	Not estimable	40 (1)	⊕⊝⊝⊝ Very lowa,b	There were no deaths in either group.
Total length of hospital stay (days) Follow‐up: 12 weeks	The mean total length of hospital stay in the delayed appendicectomy group was 6.7 days	The mean total length of hospital stay in the early appendicectomy group was 0.2 days fewer (3.54 fewer to 3.14 more)	MD −0.20 (−3.54 to 3.14)	40 (1)	⊕⊝⊝⊝ Very lowa,b	—
Time away from normal activities (days)	Not reported
*The basis for the assumed risk is the mean baseline risk from the studies in the meta‐analysis. 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; MD: mean difference
GRADE Working Group grades of evidence High certainty: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect. Very low certainty: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect.

^aDowngraded 2 levels for very serious risk of bias: unclear risk of bias for random sequence generation, allocation concealment, and blinding of outcome assessment; high risk of bias for blinding of participants and personnel
^bDowngraded 2 levels due to very serious imprecision: very small sample size

Background

This is an update of a Cochrane review first published in 2017 (Cheng 2017).

Description of the condition

Appendicitis refers to inflammation of the appendix. Acute appendicitis is the most common cause of acute abdominal pain (Cervellin 2016). The overall incidence of acute appendicitis is approximately 100 to 230 cases per 100,000 people per year globally (Coward 2016; Ferris 2017; Wickramasinghe 2021;Yang 2022). The overall lifetime risk for acute appendicitis is approximately 7% to 8% in the USA and 16% in South Korea (Addiss 1990; Lee 2010). It affects all age groups, with the highest incidence in the second decade of life (Addiss 1990; Wickramasinghe 2021).

Acute appendicitis can be broadly divided into two subgroups: simple and complicated. The most common type of acute appendicitis is simple appendicitis, for example, early or uncomplicated appendicitis (Hoffmann 2021; Talan 2021). In some cases, the appendix may become gangrenous, potentially leading to perforation and localised or generalised peritonitis (inflammation of the peritoneum), resulting in complicated appendicitis, for example, gangrenous appendicitis, appendiceal phlegmon, appendiceal abscess, and perforated appendicitis (Atema 2015; Hoffmann 2021).

Appendiceal phlegmon and appendiceal abscess present as a mass, resulting from both inflammation and walled‐off perforation of the appendix (Hayes 2021; Panahi 2020). A walled‐off appendiceal perforation differs from a simple inflammatory mass – consisting of the inflamed appendix, its adjacent viscera, and the greater omentum (an appendiceal phlegmon) – in that it contains pus (an appendiceal abscess) (Hayes 2021; Panahi 2020). The proportion of appendiceal masses (phlegmon or abscess) in acute appendicitis ranges from 2% to 10% in different cohort studies and meta‐analyses (Akingboye 2021; Andersson 2007; Hayes 2021; Panahi 2020), with a higher risk in children and elderly individuals (Bocanegra 2021; Livingston 2007).

The prognosis for patients with an appendiceal phlegmon or abscess is good (Akingboye 2021; Santacroce 2023). The overall mortality rate of appendiceal phlegmon or abscess is less than 1% (Blomqvist 2001; Cueto 2006). However, appendiceal phlegmon or abscess is associated with higher morbidity than simple appendicitis (Andert 2017; Cueto 2006). Common postoperative complications include wound infections, intra‐abdominal abscesses, incisional hernias, and bowel obstructions (Blakely 2011; Calis 2018; Khan 2021a; Khan 2021b; Pathan 2018; Ravi 2018).

Description of the intervention

Appendicectomy, or surgical removal of the appendix, is performed primarily as an emergency procedure to treat acute appendicitis (Sippola 2020; Talan 2021). People with simple appendicitis usually need either antibiotic treatment or an appendicectomy to relieve their symptoms and avoid complications (Sippola 2020; Talan 2021). Appendicectomy is one of the most common emergency surgical procedures worldwide, with approximately eight million performed each year (Ferris 2017; Wickramasinghe 2021). There are two types of appendicectomy: open appendicectomy (removal of the appendix by laparotomy) and laparoscopic appendicectomy (removal of the appendix by keyhole surgery) (Quah 2019; Talha 2020). Various methods can be used to close the appendix stump during appendicectomy, such as ligature, clips, or stapler (Mannu 2017).

Surgery for people with complicated appendicitis may be early or delayed (Abdulraheem 2021; Israr 2021). While there is no universally accepted definition of early appendicectomy (Khan 2016; Khan 2021a; Khan 2021b; Kumar 2004; Kumar 2018; Pathan 2018; Ravi 2018; St Peter 2010), for people with appendiceal phlegmon or abscess, we considered any appendicectomy performed immediately or within a few days of admission as 'early' appendicectomy. 'Delayed' appendicectomy (also known as interval appendicectomy) is defined as initial conservative (non‐surgical) treatment followed by appendicectomy several weeks later in a subsequent hospital admission. The place of delayed appendicectomy for patients with appendiceal phlegmon or abscess is controversial: some authors have suggested that delayed appendicectomy is not necessary unless the person presents with recurrent symptoms (Hall 2017; Tanaka 2016), while others do not agree (Fouad 2020; Hayes 2021; Peltrini 2021). Patients in the delayed appendicectomy group usually need antibiotics to relieve their symptoms and sometimes require percutaneous drainage of appendiceal abscesses (St Peter 2010). Overall, surgical morbidity rates in the early appendicectomy group ranging from 2% to 30% have been reported in different cohort studies (Abdulraheem 2021; Blakely 2011; Calis 2018; St Peter 2010; Israr 2021).

How the intervention might work

Usual management of appendiceal phlegmon or abscess involves initial conservative treatment with antibiotics followed by delayed appendicectomy (Abdulraheem 2021; Israr 2021; Ravichandran 2021). In theory, initial conservative treatment localises the inflammatory process and decreases the risk of surgical complications when compared with early appendicectomy during the acute inflammatory phase (Abdulraheem 2021; Israr 2021; Ravichandran 2021). Delayed appendicectomy can prevent the recurrence of appendicitis, which may occur if no appendicectomy is performed (Fouad 2020; Hayes 2021; Peltrini 2021). However, delayed appendicectomy involves waiting several weeks, during which time, the appendicitis may worsen, and the patient may develop complications or recurrence following the temporary success of conservative treatment (Kumar 2004; St Peter 2010). Overall, the success rate of conservative treatment is approximately 90% (Kumar 2004; St Peter 2010), but when conservative treatment fails, patients may experience substantial morbidity (Kumar 2004; St Peter 2010). Moreover, the true diagnosis could be uncertain in some cases, and postponing surgery could delay a diagnosis of underlying cancer or Crohn's disease (Fouad 2020; Hayes 2021; Peltrini 2021).

With the growing experience of surgeons and the continuous development of surgical instruments, authors have increasingly reported the safety and feasibility of early appendicectomy in cases of appendiceal phlegmon or abscess (Blakely 2011; Israr 2021; Ravichandran 2021; St Peter 2010). Early appendicectomy can address appendiceal phlegmon or abscess in a single admission without the risk of recurrent appendicitis (Israr 2021; Ravichandran 2021), and it may reduce the patient’s time away from normal activities (Blakely 2011; Pathan 2018). However, there are concerns about the high morbidity associated with early appendicectomy (e.g. challenges in wound closure, suture of the inflamed appendix stump) (Israr 2021; Ravichandran 2021), with the potential for unnecessary ileocaecal (ileum and caecum) resection or right‐sided hemicolectomy (surgical removal of the right side of the colon) due to a technical problem or suspicion of malignancy (Abdulraheem 2021; Kumar 2004; Simillis 2010).

Why it is important to do this review

Given the pros and cons of both early and delayed appendicectomy, the timing of appendicectomy for appendiceal phlegmon or abscess remains controversial (Panahi 2020). The choice of surgical procedure for removal of phlegmon or abscess appendicitis (e.g. open versus laparoscopic) is of interest but is outside the scope of this review; it is the topic of another Cochrane review (Jaschinski 2018). This is an update of a Cochrane review first published in 2017 (Cheng 2017). In the last version of this review, we found that it was unclear whether early appendicectomy prevented complications compared to delayed appendicectomy for people with appendiceal phlegmon or abscess. We could not rule out significant benefits or harms of early versus delayed appendicectomy because the available data were sparse. Further studies evaluating early and delayed appendicectomy for appendiceal phlegmon or abscess have been published since the 2017 review, and these studies have now been assessed for inclusion and presented in this update.

Objectives

To assess the effects of early appendicectomy compared to delayed appendicectomy on overall morbidity and mortality in people with appendiceal phlegmon or abscess.

Methods

Criteria for considering studies for this review

Types of studies

We included individual and cluster‐randomised controlled trials (RCTs) comparing early versus delayed appendicectomy in people with appendiceal phlegmon or abscess. We excluded quasi‐randomised trials (in which allocation is based on a pseudo‐random sequence, e.g. odd or even hospital number, date of birth, alternation), and non‐randomised studies because of the high risk of bias in such studies (Reeves 2023).

Types of participants

We included participants (both children and adults, irrespective of sex or ethnicity) who underwent appendicectomy (elective and emergent) for appendiceal phlegmon or abscess. Preoperative diagnosis of appendiceal phlegmon or abscess was established using medical history, physical examination, and imaging results (e.g. ultrasonography, computer tomography). Use of antibiotics and percutaneous drainage of appendiceal abscess were allowed for participants in both groups.

Types of interventions

We included trials comparing early appendicectomy with delayed appendicectomy (irrespective of whether the surgical procedure was open or laparoscopic). We defined early appendicectomy as appendicectomy performed immediately or within a few days of hospital admission. Delayed appendicectomy was performed several weeks after initial diagnosis in a later admission.

Types of outcome measures

We included trials irrespective of whether outcomes listed below were reported or not. We analysed appendiceal phlegmon and appendiceal abscess separately.

Primary outcomes

• Overall morbidity (overall complication rate defined by trial authors and graded by the Clavien‐Dindo complications classification system) (Clavien 2009)

  • Wound infection (14 days postoperative)

  • Abdominal abscess (14 days postoperative)

  • Bowel obstruction (14 days postoperative)

  • Incisional hernia (30 days postoperative)

  • Faecal fistula (14 days postoperative)

  • Unplanned bowel resection (ileocaecal resection/right‐sided hemicolectomy, 14 days postoperative)

• Mortality (death rate after operation, 90 days postoperative)

Secondary outcomes

• Length of hospital stay

  • Duration of first hospitalisation

  • Total length of hospital stay

• Time away from normal activities

• Quality of life (90 days postoperative, any validated score)

• Pain (days with pain)

Search methods for identification of studies

The lead review author (YC) designed and updated the search strategies with the help of a Cochrane information specialist before searching. We conducted the searches irrespective of language, year, or publication status.

Electronic searches

One review author (SZ) conducted the searches. We searched the following electronic databases with no language or date of publication restrictions.

• Cochrane Central Register of Controlled Trials (CENTRAL; 2023, Issue 6) in the Cochrane Library (searched 11 June 2023)

• MEDLINE Ovid (1950 to 11 June 2023)

• Embase Ovid (1974 to 11 June 2023)

• Science Citation Index Expanded in the Web of Science (1900 to 11 June 2023)

• Chinese Biomedical Literature Database (CBM) (1978 to 11 June 2023)

The search strategies can be found in Appendix 1. In MEDLINE, we combined the subject‐specific strategy with the sensitivity‐maximising version of the Cochrane highly sensitive search strategy for identifying randomised trials (2008 revision) (Lefebvre 2023). We combined the Embase search with the Ovid Embase filter developed by the UK Cochrane Centre (Lefebvre 2023).

Searching other resources

We searched the following databases on 11 June 2023 to identify ongoing trials.

• World Health Organization (WHO) International Clinical Trials Registry Platform search portal (apps.who.int/trialsearch)

• ClinicalTrials.gov (www.clinicaltrials.gov)

• Current Controlled Trials (www.isrctn.com/)

• Chinese Clinical Trial Register (www.chictr.org)

• EU Clinical Trials Register (www.clinicaltrialsregister.eu)

The search strategies for these databases can be found in Appendix 1. We searched the meeting abstracts via the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) (www.sages.org), the Society for Surgery of the Alimentary Tract (SSAT) (www.ssat.com), and Conference Proceedings Citation Index to explore further relevant clinical trials. We communicated with trial authors where necessary to obtain more information for the review. We also searched the reference lists of our included trials and any relevant systematic reviews that we identified.

Data collection and analysis

We conducted the systematic review according to the guidance provided in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2023).

Selection of studies

After completing the searches, we merged the search results using Endnote X7 reference management software and removed duplicate records. Two review authors (SZ, YC) independently scanned the title and abstract of every record identified by the search. We retrieved the full text for further assessment if we were unable to determine if the study met the inclusion criteria from the abstract. We detected duplicate publications by identifying common authors, centres, details of the interventions, numbers of participants, and baseline data (Higgins 2023). We identified and collated multiple reports of the same trial, so that each trial, rather than each report, was the unit of interest in the review. We excluded papers not meeting the inclusion criteria and listed the reasons for the exclusion in the Characteristics of excluded studies table. We included all eligible trials irrespective of whether they reported measured outcome data. The two review authors resolved any disagreements by discussion with a third review author (BT).

Data extraction and management

To extract trial characteristics and outcome data, we used a standard data collection form that we had piloted on at least one trial in the review. Two review authors (NC, JG) independently extracted the following study characteristics from the included trials.

• Methods: trial design, duration, number of centres, location, setting, withdrawals, date

• Participants: total number of participants, mean age, age range, sex, severity of condition, diagnostic criteria, inclusion criteria, exclusion criteria

• Interventions: early appendicectomy, delayed appendicectomy, use of antibiotics, percutaneous drainage of appendiceal mass

• Outcomes: primary and secondary outcomes specified and collected, time points reported

• Notes: funding for trial, notable conflicts of interest of trial authors

Two review authors (NC, JG) independently extracted outcome data from the included trials. We resolved disagreements by consensus or by involving a third person (BT). One review author (SZ) copied the data from the data collection form into Review Manager Web (RevMan Web) (RevMan 2023). We double‐checked that the data were entered correctly by comparing the trial reports with the presentation of the data in the systematic review. A second review author (BT) spot‐checked trial characteristics for accuracy against the trial report.

Assessment of risk of bias in included studies

Two review authors (SZ, YC) independently assessed the risk of bias in the included trials, using Cochrane's RoB 1 tool for randomised trials (Chapter 8, Higgins 2017). We assessed the risk of bias for the following domains: random sequence generation; allocation concealment; blinding of participants and personnel; blinding of outcome assessment; incomplete outcome data; selective reporting; and differences in baseline characteristics (Appendix 2). Following evaluation of these domains as low, high or unclear risk, we assigned an overall 'low risk of bias' judgement to included trials with a low risk of bias in all of the assessed domains, and an overall 'high risk of bias' judgement for trials with an unclear or high risk of bias for any domain. We resolved any difference in opinion by discussion. In cases of unsettled disagreements, a third review author (BT) adjudicated. We presented the results of the risk of bias assessment across and within studies graphically, in two figures that we generated using RevMan Web (RevMan 2023).

Assessment of bias in conducting the systematic review

We conducted the review according to the published protocol (Cheng 2015), and reported any deviations from it in the Differences between protocol and review section.

Measures of treatment effect

We performed meta‐analysis using RevMan Web (RevMan 2023). For dichotomous outcomes, we calculated the risk ratio (RR) with 95% confidence interval (CI) (Deeks 2023). In case of rare events (e.g. mortality), we planned to calculate the Peto odds ratio (OR) (Deeks 2023). For continuous outcomes, we calculated the mean difference (MD) with 95% CI (Deeks 2023). For continuous outcomes using different measurement scales in different trials, we planned to calculate the standardised mean difference (SMD) with 95% CI (Deeks 2023).

Where multiple trial arms were reported in a single trial, we included only the relevant arms. If two comparisons (e.g. drug A versus placebo and drug B versus placebo) were entered into the same meta‐analysis, we halved the control group to avoid double counting.

Unit of analysis issues

The unit of analysis was the individual participant. We did not find any cluster‐randomised trials for this review. In the case of a cluster‐randomised trial, we had intended to analyse the data adjusted for clustering using the generic inverse‐variance method in RevMan Web (Higgins 2023; RevMan 2023).

Dealing with missing data

We contacted the original investigators to request key unpublished information that was missing from reports of included studies. However, there was no reply. Thus, we performed the analyses based on the intention‐to‐treat (ITT) principle, if possible. Otherwise, we used only the available data in the analyses.

Assessment of heterogeneity

We described the statistical heterogeneity in the data using the Chi² test (Higgins 2023). We considered a P value less than 0.10 to indicate statistically significant heterogeneity (Higgins 2023). We also used the I² statistic to measure the quantity of statistical heterogeneity as follows:

• 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.

In cases of substantial or considerable statistical heterogeneity, we performed the meta‐analysis but interpreted the result cautiously and investigated potential sources of the heterogeneity. In cases of significant clinical heterogeneity, we did not perform meta‐analysis.

Assessment of reporting biases

We planned to use funnel plots to assess reporting biases, using visual asymmetry to determine the presence of reporting biases (Sterne 2011). We also planned to perform linear regression to determine funnel plot asymmetry (Egger 1997). We did not create funnel plots to assess reporting biases, as the number of trials included was fewer than 10 (Sterne 2011).

Data synthesis

We undertook meta‐analysis only if we judged participants, interventions, comparisons, and outcomes to be sufficiently similar (low clinical heterogeneity). We performed meta‐analysis using RevMan Web (RevMan 2023), using the random‐effects model.

Subgroup analysis and investigation of heterogeneity

We would have performed the following subgroup analyses if we had found enough trials.

• Laparoscopic versus open appendicectomy

• Adults versus children

• One type of appendix stump closure versus another

Sensitivity analysis

We performed sensitivity analysis by consecutively excluding every study from each meta‐analysis to explore the impact of individual studies on the overall effect.

We would have performed the following sensitivity analyses had they been applicable.

• Excluding trials with a high or unclear risk of bias

• Changing between worst/best‐case scenario analysis and best/worst‐case scenario analysis for the binary outcomes in the case of missing data

Summary of findings and assessment of the certainty of the evidence

We evaluated the certainty of evidence for the following outcomes using the GRADE approach: overall morbidity, wound infection, abdominal abscess, faecal fistula, mortality, total length of hospital stay, and time away from normal activities (Schünemann 2023). We presented the certainty of evidence in the summary of findings tables for the following comparisons: early versus delayed open or laparoscopic appendicectomy for appendiceal phlegmon and early versus delayed laparoscopic appendicectomy for appendiceal abscess. We downgraded the certainty of evidence by one level (serious concern) or two levels (very serious concern) for the following reasons: risk of bias, inconsistency (unexplained heterogeneity, inconsistency of results), indirectness (indirect population, intervention, control, outcomes), imprecision (wide confidence intervals), and publication bias. Two review authors (SZ, BT) independently justified all decisions to downgrade or upgrade the certainty of the trials. We justified, documented, and incorporated our judgements about the certainty of the evidence (high, moderate, low or very low) into the reporting of the results for each outcome.

Results

Description of studies

See Characteristics of included studies; Characteristics of excluded studies; Characteristics of ongoing studies.

Results of the search

We identified a total of 16,062 records through electronic searches: 1555 in the Cochrane Library, 4581 in MEDLINE Ovid, 4805 in Embase Ovid, 3747 in Science Citation Index Expanded in the Web of Science and 1374 in the Chinese Biomedical Literature Database (CBM). We did not identify any records by scanning the reference lists of the identified trials. We identified one ongoing study by searching five trial registers in the updated search (ChiCTR1900021559). Of the 16,063 records, we excluded 1085 duplicates. Of the remaining 14,978 records, we excluded 14,959 clearly irrelevant records through reading titles and abstracts. We retrieved the remaining 19 records for further assessment. We excluded 10 studies (11 records) for the reasons listed in the Characteristics of excluded studies table. There was one ongoing trial (ChiCTR1900021559). Six new trials (seven records)fulfilled the inclusion criteria for this update (Khan 2016; Khan 2021a; Khan 2021b; Kumar 2018; Pathan 2018; Ravi 2018). Two trials (three records) were brought forward from the last version of the review, so we included eight trials reported in 10 articles in total. One excluded study from the previous version of the review was brought forward into this version. The study flow diagram is shown in Figure 1.

1.

Study flow diagram

Included studies

We included eight trials, all of which provided data for the analyses (Khan 2016; Khan 2021a; Khan 2021b; Kumar 2004; Kumar 2018; Pathan 2018; Ravi 2018; St Peter 2010). Details are shown in the Characteristics of included studies table. We contacted the main authors of the included trials to request missing information. However, we received no responses.

Settings

Four trials were conducted in India (Kumar 2004; Kumar 2018; Pathan 2018; Ravi 2018), two in Pakistan (Khan 2016; Khan 2021a), one in Nepal (Khan 2021b), and one in the USA (St Peter 2010). Seven trials were conducted in single centres (Khan 2021a; Khan 2021b; Kumar 2004; Kumar 2018; Pathan 2018; Ravi 2018; St Peter 2010), and one was conducted in two centres (Khan 2016).

Interventions

Seven trials compared early appendicectomy with delayed appendicectomy for paediatric and adult participants with appendiceal phlegmon. Three trials performed open appendicectomy (Khan 2021b; Kumar 2004; Kumar 2018); one trial included both open and laparoscopic appendicectomy (Khan 2021a); and the other three trials did not mention the type of appendicectomy (Khan 2016; Pathan 2018; Ravi 2018).

One trial compared early laparoscopic appendicectomy with delayed laparoscopic appendicectomy for paediatric participants with appendiceal abscess (St Peter 2010).

Participants

Overall, the eight trials included 828 participants. Participant age ranged from 1 to 84 years. Most of the participants were male adults. The mean proportion of female participants ranged from 5% to 47.5%. There was no difference in the characteristics of the participants in the intervention and control groups in any of the trials. Overall, 782 (94.4%) participants had appendiceal phlegmon, and 46 (5.6%) had appendiceal abscess. A total of 10 participants crossed from the delayed appendicectomy group to the early appendicectomy group in three trials (Khan 2021b; Ravi 2018; St Peter 2010).

Outcomes

Primary outcome measures included overall morbidity (three trials: Kumar 2004; Kumar 2018; Ravi 2018), wound infection (seven trials: Khan 2016; Khan 2021a; Khan 2021b; Kumar 2004; Kumar 2018; Pathan 2018; Ravi 2018), abdominal abscess (four trials: Khan 2016; Khan 2021a; Kumar 2018; Pathan 2018), bowel obstruction (two trials: Kumar 2018; Ravi 2018), faecal fistula (five trials: Khan 2021a; Khan 2021b; Kumar 2004; Kumar 2018; Ravi 2018), unplanned bowel resection (two trials: Kumar 2018; St Peter 2010), and mortality (eight trials: Khan 2016; Khan 2021a; Khan 2021b; Kumar 2004; Kumar 2018; Pathan 2018; Ravi 2018; St Peter 2010). Secondary outcome measures included total length of hospital stay (eight trials: Khan 2016; Khan 2021a; Khan 2021b; Kumar 2004; Kumar 2018; Pathan 2018; Ravi 2018; St Peter 2010), time away from normal activities (one trial: Kumar 2004), and quality of life (one trial: St Peter 2010). Other outcome measures used in the trials that were not pertinent to our review included total operative time (four trials: Khan 2021a; Kumar 2004; Kumar 2018; St Peter 2010), operative difficulty (three trials: Kumar 2004; Kumar 2018; Ravi 2018), total hospital costs (one trial: St Peter 2010), functional recovery (two trials: Pathan 2018; Ravi 2018), and number of hospital visits (two trials: Kumar 2004; St Peter 2010).

Two trials reported the length of follow‐up and time points for measurements (Kumar 2004; St Peter 2010). The other six trials did not report the time points for measurements (Khan 2016; Khan 2021a; Khan 2021b; Kumar 2018; Pathan 2018; Ravi 2018).

Funding sources

One trial had no funding sources (Kumar 2018). The other seven trials gave no information about funding sources (Khan 2016; Khan 2021a; Khan 2021b; Kumar 2004; Pathan 2018; Ravi 2018; St Peter 2010).

Conflicts of interest

One trial declared no conflicts of interest (Kumar 2018). The other seven trials did not report whether there were conflicts of interest (Khan 2016; Khan 2021a; Khan 2021b; Kumar 2004; Pathan 2018; Ravi 2018; St Peter 2010).

Excluded studies

We excluded one trial because it focused on perforated appendicitis without appendiceal abscess (Blakely 2011). We excluded one trial because it compared interval appendicectomy versus no interval appendicectomy for appendiceal phlegmon or appendiceal abscess (Hall 2017). We excluded another trial because it compared early appendicectomy versus conservative management without interval appendicectomy for appendiceal phlegmon or appendiceal abscess (Abdulraheem 2021).

None of the other excluded studies were RCTs (Demetrashvili 2019; Dhaded 2016; Elsaady 2019; Goh 2005; Israr 2021; Patel 2015; Ravichandran 2021; Shinde 2020).

Risk of bias in included studies

The risk of bias in the included trials is shown in Figure 2 and Figure 3. None of the trials were at low risk of bias across all domains. We contacted trial authors where information was missing, but we received no responses.

2.

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

3.

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

Allocation

None of the trials provided information regarding the methods used for random sequence generation or allocation concealment. We therefore judged all trials to be at unclear risk of selection bias (Khan 2016; Khan 2021a; Khan 2021b; Kumar 2004; Kumar 2018; Pathan 2018; Ravi 2018; St Peter 2010).

Blinding

All trials were at high risk of performance bias because it is impossible to blind the participants or healthcare providers to which intervention participants are receiving.

None of the trials provided information regarding the blinding of outcome assessment. We therefore judged all trials to be at unclear risk of detection bias (Khan 2016; Khan 2021a; Khan 2021b; Kumar 2004; Kumar 2018; Pathan 2018; Ravi 2018; St Peter 2010).

Incomplete outcome data

We judged all trials to be at low risk of bias of attrition bias because there were no postrandomisation dropouts (Khan 2016; Khan 2021a; Khan 2021b; Kumar 2004; Kumar 2018; Pathan 2018; Ravi 2018; St Peter 2010). Although a total of 10 participants crossed from the delayed appendicectomy group to the early appendicectomy group in three trials, the study authors analysed the data on an intention‐to‐treat basis (Khan 2021b; Ravi 2018; St Peter 2010). Data were available for all participants for the outcomes at relevant time points.

Selective reporting

The trial protocol was available for one trial; in that trial, all prespecified outcomes were reported (St Peter 2010). Thus, we considered that trial to be at low risk of reporting bias. The trial protocols were not available for the other seven trials (Khan 2016; Khan 2021a; Khan 2021b; Kumar 2004; Kumar 2018; Pathan 2018; Ravi 2018), and some outcomes of interest in this review (e.g. quality of life and pain) were not reported; therefore we judged these trials to be at unclear risk of reporting bias.

Other potential sources of bias

We did not observe any imbalance in participant characteristics at baseline; therefore, we considered all trials to be at low risk for this domain (Khan 2016; Khan 2021a; Khan 2021b; Kumar 2004; Kumar 2018; Pathan 2018; Ravi 2018; St Peter 2010).

Effects of interventions

See: Table 1; Table 2

Early versus delayed open or laparoscopic appendicectomy for appendiceal phlegmon

Seven trials (N = 788) compared early open or laparoscopic appendicectomy with delayed open or laparoscopic appendicectomy in paediatric and adult participants with appendiceal phlegmon (Khan 2016; Khan 2021a; Khan 2021b; Kumar 2004; Kumar 2018; Pathan 2018; Ravi 2018). The trials randomised 394 participants to the early appendicectomy groups and 394 participants to the delayed appendicectomy groups. A total of six participants crossed from the delayed appendicectomy group to the early appendicectomy group in two trials (Khan 2021b; Ravi 2018). We summarise the results in Table 1.

Primary outcomes

Overall morbidity

Three trials (73 participants in the early appendicectomy group, 73 participants in the delayed appendicectomy group) reported overall morbidity (Kumar 2004; Kumar 2018; Ravi 2018). Overall, 42 participants suffered surgical complications: 17 in the early appendicectomy group and 25 in the delayed appendicectomy group. The evidence is very uncertain about the effect of early appendicectomy compared with delayed appendicectomy on overall morbidity (RR 0.74, 95% CI 0.19 to 2.86; I² = 72%; 3 trials, 146 participants; very low‐certainty evidence; Analysis 1.1). Approximately 89 fewer per 1000 participants developed surgical complications after early appendicectomy (277 fewer to 637 more) than after delayed appendicectomy.

1.1. Analysis.

Comparison 1: Early versus delayed open or laparoscopic appendicectomy for appendiceal phlegmon, Outcome 1: Overall morbidity

Wound infection

Seven trials (394 participants in the early appendicectomy group, 394 participants in the delayed appendicectomy group) reported the wound infection rate (Khan 2016; Khan 2021a; Khan 2021b; Kumar 2004; Kumar 2018; Pathan 2018; Ravi 2018). Overall, 73 participants suffered wound infections: 36 in the early appendicectomy group and 37 in the delayed appendicectomy group. The evidence is very uncertain about the effect of early appendicectomy compared with delayed appendicectomy on the wound infection rate (RR 0.99, 95% CI 0.48 to 2.02; I² = 47%; 7 trials, 788 participants; very low‐certainty evidence; Analysis 1.2). Approximately one fewer per 1000 participants developed wound infection after early appendicectomy (49 fewer to 96 more) than after delayed appendicectomy.

1.2. Analysis.

Comparison 1: Early versus delayed open or laparoscopic appendicectomy for appendiceal phlegmon, Outcome 2: Wound infection

Abdominal abscess

Four trials (313 participants in the early appendicectomy group, 313 participants in the delayed appendicectomy group) reported the abdominal abscess rate (Khan 2016; Khan 2021a; Khan 2021b; Pathan 2018). Overall, 21 participants suffered abdominal abscesses: 3 in the early appendicectomy group and 18 in the delayed appendicectomy group. Early appendicectomy may reduce the abdominal abscess rate compared with delayed appendicectomy, but the evidence is very uncertain (RR 0.26, 95% CI 0.08 to 0.80; I² = 0%; 4 trials, 626 participants; very low‐certainty evidence; Analysis 1.3). Approximately 43 fewer per 1000 participants developed abdominal abscesses after early appendicectomy (12 fewer to 53 fewer) than after delayed appendicectomy.

1.3. Analysis.

Comparison 1: Early versus delayed open or laparoscopic appendicectomy for appendiceal phlegmon, Outcome 3: Abdominal abscess

Bowel obstruction

Two trials (53 participants in the early appendicectomy group, 53 participants in the delayed appendicectomy group) reported the bowel obstruction rate (Kumar 2018; Ravi 2018). Overall, six participants suffered bowel obstructions: zero in the early appendicectomy group and six in the delayed appendicectomy group. The evidence is very uncertain about the effect of early appendicectomy compared with delayed appendicectomy on the bowel obstruction rate (RR 0.16, 95% CI 0.02 to 1.34; I² = 0%; 2 trials, 106 participants; very low‐certainty evidence; Analysis 1.4). Approximately 95 fewer per 1000 participants developed bowel obstructions after early appendicectomy (111 fewer to 39 more) than after delayed appendicectomy.

1.4. Analysis.

Comparison 1: Early versus delayed open or laparoscopic appendicectomy for appendiceal phlegmon, Outcome 4: Bowel obstruction

Incisional hernia

None of the studies reported this outcome.

Faecal fistula

Five trials (194 participants in the early appendicectomy group, 194 participants in the delayed appendicectomy group) reported the faecal fistula rate (Khan 2021a; Khan 2021b; Kumar 2004; Kumar 2018; Ravi 2018). Overall, four participants suffered faecal fistulas: three in the early appendicectomy group and one in the delayed appendicectomy group. The evidence is very uncertain about the effect of early appendicectomy compared with delayed appendicectomy on the faecal fistula rate (RR 1.75, 95% CI 0.36 to 8.49; I² = 0%; 5 trials, 388 participants; very low‐certainty evidence; Analysis 1.5). Approximately 4 more per 1000 participants developed faecal fistulas after early appendicectomy (3 fewer to 39 more) than after delayed appendicectomy.

1.5. Analysis.

Comparison 1: Early versus delayed open or laparoscopic appendicectomy for appendiceal phlegmon, Outcome 5: Faecal fistula

Unplanned bowel resection

One trial (23 participants in the early appendicectomy group, 23 participants in the delayed appendicectomy group) reported the unplanned bowel resection rate. Overall, six participants suffered unplanned bowel resections: three in the early appendicectomy group and three in the delayed appendicectomy group. The evidence is very uncertain about the effect of early appendicectomy compared with delayed appendicectomy on the unplanned bowel resection rate (RR 1.00, 95% CI 0.22 to 4.45; 1 trial, 46 participants; very low‐certainty evidence; Analysis 1.6). Approximately 130 fewer per 1000 participants suffered unplanned bowel resections after early appendicectomy (29 fewer to 580 more) than after delayed appendicectomy.

1.6. Analysis.

Comparison 1: Early versus delayed open or laparoscopic appendicectomy for appendiceal phlegmon, Outcome 6: Unplanned bowel resection

Mortality

Seven trials (394 participants in the early appendicectomy group, 394 participants in the delayed appendicectomy group) reported mortality (Khan 2016; Khan 2021a; Khan 2021b; Kumar 2004; Kumar 2018; Pathan 2018; Ravi 2018). There were no deaths in either group in any trial.

Secondary outcomes

Length of hospital stay (total hospital stay)

Five trials (340 participants in the early appendicectomy group, 340 participants in the delayed appendicectomy group) reported the total length of hospital stay (Khan 2016; Khan 2021a; Kumar 2004; Pathan 2018; Ravi 2018). The mean total length of hospital stay was 2.44 to 21.4 days in the early appendicectomy group and 5.41 to 14.7 days in the delayed appendicectomy group. For the participants in the delayed appendicectomy group, the total length of hospital stay was the sum of the lengths of the stays during the first and second admissions. Early appendicectomy may reduce the total length of hospital stay by about two days (1 to 3 days) compared with delayed appendicectomy, but the evidence is very uncertain (MD −2.02 days, 95% CI −3.13 to −0.91; I² = 89%; 5 trials, 680 participants; very low‐certainty evidence; Analysis 1.7). Two studies did not report mean values or standard deviations and were not suitable for pooling (Khan 2021b; Kumar 2018). Both of those studies (108 participants) reported that the early appendicectomy group was associated with a shorter total length of hospital stay than the delayed appendicectomy group (Analysis 1.8).

1.7. Analysis.

Comparison 1: Early versus delayed open or laparoscopic appendicectomy for appendiceal phlegmon, Outcome 7: Total length of hospital stay (days)

1.8. Analysis.

Comparison 1: Early versus delayed open or laparoscopic appendicectomy for appendiceal phlegmon, Outcome 8: Total length of hospital stay (days)

Total length of hospital stay (days)
Study	Number in study	Comparison	Results	Comment
Khan 2021b	62 (31 versus 31)	Early appendicectomy versus delayed appendicectomy	Early appendicectomy versus delayed appendicectomy: mean (days): 4.8 versus 7.1, P = 0.045	Trial authors reported that early appendicectomy was associated with a shorter hospital stay than delayed appendicectomy.
Kumar 2018	46 (23 versus 23)	Early appendicectomy versus delayed appendicectomy	Early appendicectomy versus delayed appendicectomy: less than 7 days (1 versus 0); 8 to 14 days (16 versus 5); 15 to 21 days (5 versus 11); 21 to 28 days (1 versus 4); more than 28 days (0 versus 3)	Trial authors reported that the early appendicectomy was associated with a shorter hospital stay than delayed appendicectomy.

Time away from normal activities

One trial (20 participants in the early appendicectomy group, 20 participants in the delayed appendicectomy group) reported time away from normal activities (Kumar 2004). The mean time away from normal activities was 25.0 days in the early appendicectomy group and 20.0 days in the delayed appendicectomy group. Early appendicectomy may increase the time away from normal activities by about five days (1.5 to 8.5 days) compared with delayed appendicectomy, but the evidence is very uncertain (MD 5.00 days, 95% CI 1.52 to 8.48; 1 trial, 40 participants; very low‐certainty evidence; Analysis 1.9).

1.9. Analysis.

Comparison 1: Early versus delayed open or laparoscopic appendicectomy for appendiceal phlegmon, Outcome 9: Time away from normal activities (days)

Quality of life

None of the studies reported this outcome.

Pain

None of the studies reported this outcome.

Early versus delayed laparoscopic appendicectomy for appendiceal abscess

One trial (N = 40) compared early laparoscopic appendicectomy with delayed laparoscopic appendicectomy in paediatric participants with appendiceal abscess (St Peter 2010). Twenty participants were randomised to the early appendicectomy group (emergent laparoscopic appendicectomy), and 20 participants were randomised to the delayed appendicectomy group (initial conservative treatment followed by interval appendicectomy 10 weeks later). Four participants crossed from the delayed appendicectomy group to the early appendicectomy group. Eleven participants in the delayed appendicectomy group underwent percutaneous drainage of the appendiceal abscess. There was no clinical or statistical heterogeneity, as the analysis included only one trial. We summarise the results in Table 2.

Primary outcomes

Overall morbidity

St Peter 2010 did not report this outcome.

Wound infection

St Peter 2010 did not report this outcome.

Abdominal abscess

St Peter 2010 did not report this outcome.

Bowel obstruction

St Peter 2010 did not report this outcome.

Incisional hernia

St Peter 2010 did not report this outcome.

Faecal fistula

St Peter 2010 did not report this outcome.

Unplanned bowel resection

One participant suffered unplanned bowel resection in the early appendicectomy group and none in the delayed appendicectomy group. The evidence is very uncertain about the effect of early appendicectomy compared with delayed appendicectomy on the unplanned bowel resection rate (RR 3.00, 95% CI 0.13 to 69.52; 1 trial, 40 participants; very low‐certainty evidence; Analysis 2.1).

2.1. Analysis.

Comparison 2: Early versus delayed laparoscopic appendicectomy for appendiceal abscess, Outcome 1: Unplanned bowel resection

Mortality

There were no deaths at 12 weeks in either group.

Secondary outcomes

Length of hospital stay (total hospital stay)

The mean length of hospital stay was 6.7 days in the early appendicectomy group and 6.5 days in the delayed appendicectomy group. For the participants in the delayed appendicectomy group, the total length of hospital stay was the sum of the lengths of the stays during the first and second admissions. The evidence is very uncertain about the effect of early appendicectomy on the total length of hospital stay (3.5 days shorter to 3.1 days longer) compared with delayed appendicectomy (MD −0.20 days, 95% CI −3.54 to 3.14; 1 trial, 40 participants; very low‐certainty evidence; Analysis 2.2).

2.2. Analysis.

Comparison 2: Early versus delayed laparoscopic appendicectomy for appendiceal abscess, Outcome 2: Total length of hospital stay (days)

Time away from normal activities

St Peter 2010 did not report this outcome.

Quality of life

St Peter 2010 used the Pediatric Quality of Life Scale‐Version 4.0 to assess quality of life, a scale of 0 to 100 with higher values indicating better quality of life. The mean quality of life score at 12 weeks after appendicectomy was 96.77 points in the early appendicectomy group and 84.37 points in the delayed appendicectomy group. Early appendicectomy may increase the quality of life score about 12 points (10 to 15 points) at 12 weeks compared with delayed appendicectomy, but the evidence is very uncertain (MD 12.40 points, 95% CI 9.78 to 15.02; 1 trial, 40 participants; very low‐certainty evidence; Analysis 2.3).

2.3. Analysis.

Comparison 2: Early versus delayed laparoscopic appendicectomy for appendiceal abscess, Outcome 3: Quality of life (score on a scale from 0 to 100)

Pain

St Peter 2010 did not report this outcome.

Subgroup analysis

We were unable to perform the planned subgroup analyses of different types of appendicectomy (laparoscopic versus open), different types of participants (adults versus children), and different types of appendix stump closure, as there were not enough trials.

Sensitivity analysis

We performed the following planned sensitivity analyses.

• Consecutively excluding every trial from the meta‐analysis to explore the impact of individual trials on the overall effect.

Three outcomes (overall morbidity, abdominal abscess, and total length of hospital stay) changed when we consecutively excluded every trial from the meta‐analysis in the comparison of early versus delayed open or laparoscopic appendicectomy for appendiceal phlegmon (Table 3). These three outcomes were considered to have high variability and were not robust.

1. Sensitivity analyses for comparison 1: early versus delayed open or laparoscopic appendicectomy for appendiceal phlegmon.

Outcome	Main analysis (95% CI); I2	Sensitivity analysis excludingKumar 2004	Sensitivity analysis excludingKhan 2016	Sensitivity analysis excludingKumar 2018	Sensitivity analysis excludingPathan 2018	Sensitivity analysis excludingRavi 2018	Sensitivity analysis excludingKhan 2021a	Sensitivity analysis excludingKhan 2021b
Overall morbidity	RR 0.74 (0.19 to 2.86); I2 = 72%	RR 0.45 (0.21 to 1.00); I2 = 40%	‐	RR 1.58 (0.03 to 90.11); I2 = 87%	‐	RR 2.25 (0.08 to 62.71); I2 = 81%	‐	‐
Wound infection	RR 0.99 (0.48 to 2.02); I² = 47%	RR 0.85 (0.44 to 1.66); I² = 40%	RR 0.90 (0.38 to 2.13); I² = 46%	RR 1.09 (0.46 to 2.56); I² = 55%	RR 1.23 (0.56 to 2.72); I² = 36%	RR 0.96 (0.43 to 2.16); I² = 54%	RR 1.20 (0.54 to 2.65); I² = 47%	RR 0.86 (0.44 to 1.67); I² = 41%
Abdominal abscess	RR 0.26 (0.08 to 0.80); I² = 0%	‐	RR 0.13 (0.03 to 0.58); I² = 0%	RR 0.28 (0.07 to 1.07); I² = 12%	RR 0.42 (0.11 to 1.64); I² = 0%	‐	RR 0.24 (0.06 to 0.92); I² = 17%	‐
Bowel obstruction	RR 0.16 (0.02 to 1.34); I² = 0%	‐	‐	RR 0.33 (0.01 to 7.87)	‐	RR 0.09 (0.01 to 1.55)	‐	‐
Faecal fistula	RR 1.75 (0.36 to 8.49); I² = 0%	RR 1.45 (0.23 to 9.07); I² = 0%	‐	RR 1.75 (0.36 to 8.49); I² = 0%	‐	RR 1.46 (0.23 to 9.06); I² = 0%	RR 3.00 (0.49 to 18.55); I² = 0%	RR 1.46 (0.23 to 9.06); I² = 0%
Total length of hospital stay	MD −2.02 (−3.13 to −0.91); I² = 89%	MD −2.67 (−3.39 to −1.95); I² = 77%	MD −1.11 (−3.14 to 0.93); I² = 91%	‐	MD −2.45 (−3.57 to −1.34); I² = 87%	MD −1.58 (−2.95 to −0.20); I² = 92%	MD −1.18 (−3.03 to 0.67); I² = 91%	‐

CI: confidence interval; RR: risk ratio; MD: mean difference

We also performed a post hoc sensitivity analysis by consecutively excluding every trial from the meta‐analysis to explore the impact of individual trials on the statistical heterogeneity. We found that the unexplained statistical heterogeneity of three outcomes (overall morbidity, wound infection, and total length of hospital stay) decreased significantly when we excluded Kumar 2004 from our first comparison (early versus delayed open or laparoscopic appendicectomy for appendiceal phlegmon) (Table 3). We had planned to conduct sensitivity analyses based on risk of bias and data imputation; these were unnecessary as all trials were at high risk of bias but had no missing data.

Discussion

Summary of main results

This review includes eight randomised controlled trials (RCTs) involving 828 paediatric and adult participants who underwent open or laparoscopic appendicectomy for appendiceal phlegmon (7 trials) or abscess (1 trial). All trials provided data for one of our primary outcomes, mortality. There was no mortality in any trial. For the comparison of early versus delayed open or laparoscopic appendicectomy for appendiceal phlegmon, the evidence is very uncertain about the effect of early appendicectomy on overall morbidity (including wound infection, bowel obstruction, faecal fistula, and unplanned bowel resection). Early appendicectomy may reduce the abdominal abscess rate (43 fewer per 1000 participants), but the evidence is very uncertain. Early appendicectomy may reduce the total length of hospital stay by about two days and may increase the time away from normal activities by about five days, but the evidence is very uncertain. For the comparison of early versus delayed laparoscopic appendicectomy for appendiceal abscess, the trial did not report on overall morbidity. The evidence is very uncertain about the effect of early laparoscopic appendicectomy on unplanned bowel resection and total length of hospital stay. Early laparoscopic appendicectomy appears to be better than delayed laparoscopic appendicectomy in terms of health‐related quality of life for paediatric participants with appendiceal abscess, but the evidence is very uncertain.

Overall completeness and applicability of evidence

The optimal treatment strategy for participants with appendiceal phlegmon or abscess is unclear (Akingboye 2021; Simillis 2010; Veeralakshmanan 2020). There are three common treatment methods: early appendicectomy, conservative (non‐surgical) treatment followed by interval appendicectomy (delayed appendicectomy), and conservative treatment without interval appendicectomy (Akingboye 2021; Simillis 2010; Veeralakshmanan 2020). The need for an appendicectomy after successful conservative treatment of complicated appendicitis remains controversial (Fouad 2020; Hall 2017; Hayes 2021; Peltrini 2021). Because of the risk of recurrent appendicitis and missed findings of malignancy, interval appendicectomy is a common treatment for appendiceal phlegmon or abscess (Hayes 2021; Peltrini 2021). This review focused solely on early versus delayed appendicectomy for the treatment of appendiceal phlegmon or abscess in both paediatric and adult participants.

For the comparison of early versus delayed appendicectomy for appendiceal phlegmon, we identified seven trials involving 788 paediatric and adult participants who underwent open or laparoscopic appendicectomy. Most of the participants were male adults who underwent open appendicectomy. Thus, the results of this comparison are applicable to participants who are about to undergo emergent or elective appendicectomy for appendiceal phlegmon, especially for male adults undergoing open appendicectomy.

For the comparison of early versus delayed appendicectomy for appendiceal abscess, we identified only one trial involving 40 paediatric participants who underwent laparoscopic appendicectomy. Most of the participants with appendiceal abscesses underwent percutaneous drainage of the abscess before the delayed laparoscopic appendicectomy. Thus, the results of this comparison are applicable to paediatric participants who are about to undergo emergent or elective laparoscopic appendicectomy for appendiceal abscess. In addition, participants who are about to undergo delayed appendicectomy require percutaneous drainage of appendiceal abscesses (when possible). We cannot rule out significant benefits or harms of early versus delayed laparoscopic appendicectomy for paediatric participants because the available data are sparse. Furthermore, the benefits and harms of early versus delayed open appendicectomy for adult participants remain unknown.

We are not able to draw any strong conclusions from our findings. First, this review included eight trials with only 828 participants, and therefore may not have had the statistical power to detect clinically meaningful differences between early appendicectomy and delayed appendicectomy for appendiceal phlegmon or abscess, even if such differences were present. Second, where differences were detected, confidence in these results is very low, as the small number of participants means that the results could be spurious, and the impact of a bias can be exacerbated in underpowered analyses. Third, a single trial formed the basis of the analysis for some of the outcomes. Some of the outcomes were rare, or the follow‐up time was not long enough for the events to occur, and there were no data or no events reported. Furthermore, the trials were conducted in Asia and North America, and this might make it problematic to extrapolate the findings to countries in Africa, Europe, and South America.

Quality of the evidence

For early versus delayed open or laparoscopic appendicectomy for appendiceal phlegmon, we found very low‐certainty evidence for overall morbidity (including wound infection, abdominal abscess, bowel obstruction, faecal fistula, and unplanned bowel resection), mortality, total length of hospital stay, and time away from normal activities. We downgraded the certainty of evidence for all outcomes by two levels for very serious risk of bias relating to random sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessment, and selective reporting in all studies. The certainty of evidence for wound infection was downgraded one level for serious imprecision (a confidence interval that included both potential benefit and potential harm from the intervention). The certainty of evidence for abdominal abscess was downgraded one level for serious imprecision (few events and a wide confidence interval). We downgraded the certainty of evidence for overall morbidity, bowel obstruction, faecal fistula, unplanned bowel resection, mortality, and time away from normal activities by two levels for very serious imprecision (small sample size, few events, or a confidence interval that included both potential benefit and potential harm from the intervention). We downgraded the certainty of evidence for overall morbidity and wound infection by one level for serious inconsistency (unexplained statistical heterogeneity). We downgraded the certainty of evidence for the total length of hospital stay by two levels for very serious inconsistency (considerable statistical heterogeneity). There was no indirectness of evidence, as the included studies assessed the appropriate population, intervention, comparisons, and outcomes. Too few studies were included in this comparison to assess publication bias (Table 1).

For early versus delayed laparoscopic appendicectomy for appendiceal abscess, we found very low‐certainty evidence for unplanned bowel resection, mortality, total length of hospital stay, and quality of life. We downgraded the certainty of evidence for all outcomes by one level for serious risk of bias relating to random sequence generation, allocation concealment, blinding of participants and personnel, and blinding of outcome assessment. The certainty of evidence for all outcomes was downgraded by two levels for very serious imprecision (very small sample size). There was no indirectness of evidence, as the included studies assessed the appropriate population, intervention, comparisons, and outcomes. Too few studies were included in this comparison to assess publication bias (Table 2).

Potential biases in the review process

There were several potential biases in the review process. First, we performed a comprehensive search of English and Chinese databases to identify RCTs. However, there is a possibility that some studies that were published in other languages without English abstracts may have been missed. Second, participant selection processes and blinding were unclear for all trials. We contacted the study investigators to request further information about characteristics and numerical outcome data but did not receive any replies. Thus, there was incomplete correspondence with trial investigators. Third, we analysed only data from published trials, and the lack of data from unpublished trials may have contributed to bias. Fourth, due to the small number of included trials and small number of included participants, we were unable to perform prespecified subgroup analyses or create funnel plots to assess potential publication bias as described in the published protocol of this review (Cheng 2015).

Agreements and disagreements with other studies or reviews

The systematic review by Akingboye and colleagues, Akingboye 2021, included two RCTs (Kumar 2004; St Peter 2010) and four non‐randomised studies comparing early versus delayed appendicectomy for the management of appendiceal phlegmon and abscess. Akingboye 2021 concluded that early appendicectomy increased operative time and overall morbidity. The current Cochrane review included the two RCTs identified by Akingboye and colleagues, as well as six additional RCTs identified by a comprehensive search (Khan 2016; Khan 2021a; Khan 2021b; Kumar 2018; Pathan 2018; Ravi 2018). Our findings, that the evidence is very uncertain about the effect of early appendicectomy on the overall morbidity and that early appendicectomy may reduce the abdominal abscess rate, do not agree with the findings of Akingboye 2021.

Another systematic review, Veeralakshmanan 2020, included one RCT and four non‐randomised studies comparing early versus delayed appendicectomy for perforated appendicitis without appendiceal abscess in children. That RCT was not included in this review because it focused on perforated appendicitis without appendiceal abscess (Blakely 2011). Veeralakshmanan 2020 found that early appendicectomy provides better clinical outcomes in terms of lower overall morbidity and shorter total length of hospital stay for perforated appendicitis without appendiceal abscess in children. We studied a different group of participants than Veeralakshmanan 2020. We found that early laparoscopic appendicectomy may improve health‐related quality of life for children with appendiceal abscess.

Authors' conclusions

Implications for practice.

For the comparison of early versus delayed open or laparoscopic appendicectomy for paediatric and adult participants with appendiceal phlegmon, very low‐certainty evidence suggests that early appendicectomy may reduce the abdominal abscess rate. The evidence is very uncertain whether early appendicectomy prevents overall morbidity or other complications. Early appendicectomy may reduce the total length of hospital stay, and it may increase the time away from normal activities, but the evidence is very uncertain. For the comparison of laparoscopic appendicectomy for paediatric participants with appendiceal abscess, data are sparse, and we cannot rule out significant benefits or harms of early versus delayed appendicectomy.

Implications for research.

Although one randomised controlled trial (RCT) is ongoing and its results should add to the evidence regarding complicated appendicitis (ChiCTR1900021559), there is an urgent need for more RCTs to assess the effects of early appendicectomy compared with delayed appendicectomy on overall morbidity and mortality in people with appendiceal phlegmon or abscess. Investigators should employ adequate methods of randomisation, allocation concealment, and blinding of outcome assessors, to reduce the risk of bias. Future trials should specify a set of criteria for the use of antibiotics, percutaneous drainage of the appendiceal abscess, and resolution of the appendiceal mass. Researchers should define all of the patient‐important outcomes (e.g. time away from normal activities) more accurately and report them in accordance with validated criteria.

What's new

Date	Event	Description
2 May 2024	New citation required and conclusions have changed	Review updated with six new trials with 748 participants included in analyses. Author byline changed. Contact author changed to Dr Bing Tu. Conclusions about abdominal abscess rate and total length of hospital stay changed in favour of early appendicectomy in our comparison of early versus delayed open or laparoscopic appendicectomy for appendiceal phlegmon.
2 May 2024	New search has been performed	Searches rerun. Six new trials identified.

History

Protocol first published: Issue 4, 2015
Review first published: Issue 6, 2017

Date	Event	Description
2 June 2017	Amended	Contact author changed to Dr Yao Cheng

Appendices

Appendix 1. Search strategies

CENTRAL search strategy

#1 MeSH descriptor: [Appendectomy] explode all trees
#2 MeSH descriptor: [Appendicitis] explode all trees
#3 appendectom* or appendic*:ti,ab,kw
#4 (#1 or #2 or #3)
#5 MeSH descriptor: [Gangrene] explode all trees
#6 MeSH descriptor: [Intestinal Perforation] explode all trees
#7 MeSH descriptor: [Rupture, Spontaneous] explode all trees
#8 MeSH descriptor: [Abdominal Abscess] explode all trees
#9 MeSH descriptor: [Peritonitis] explode all trees
#10 (complicat* or gangren* or perforat* or ruptur* or phlegmon* or abscess* or periton*):ti,ab,kw
#11 (#5 or #6 or #7 or #8 or #9 or #10)
#12 (#4 and #11)

MEDLINE search strategy

1. exp Appendectomy/
2. exp Appendicitis/
3. (appendectom* or appendic*).mp.
4. 1 or 2 or 3
5. exp Gangrene/
6. exp Intestinal Perforation/
7. exp Rupture, Spontaneous/
8. exp Abdominal Abscess/
9. exp Peritonitis/
10. (complicat* or gangren* or perforat* or ruptur* or phlegmon* or abscess* or periton*).mp.
11. 5 or 6 or 7 or 8 or 9 or 10
12. 4 and 11
13. randomized controlled trial.pt.
14. controlled clinical trial.pt.
15. random*.ab.
16. placebo.ab.
17. drug therapy.fs.
18. trial.ab.
19. groups.ab.
20. 13 or 14 or 15 or 16 or 17 or 18 or 19
21. exp animals/ not humans.sh.
22. 20 not 21
23. 12 and 22

Embase search strategy

1. exp appendectomy/
2. exp acute appendicitis/
3. exp appendicitis/
4. (appendectom* or appendic*).mp.
5. 1 or 2 or 3 or 4
6. exp gangrene/
7. exp intestinal perforation/ or expphlegmon/
8. exp rupture/ or exp abdominal organ rupture/
9. exp abscess/ or exp abdominal abscess/
10. exp peritonitis/ or exp bacterial peritonitis/
11. (complicat* or gangren* or perforat* or ruptur* or phlegmon* or abscess* or periton*).mp.
12. 6 or 7 or 8 or 9 or 10 or 11
13. 5 and 12
14. Randomized controlled trial/
15. Controlled clinical study/
16. Random$.ti,ab.
17. randomization/
18. intermethod comparison/
19. placebo.ti,ab.
20. (compare or compared or comparison).ti.
21. ((evaluated or evaluate or evaluating or assessed or assess) and (compare or compared or comparing or comparison)).ab.
22. (open adj label).ti,ab.
23. ((double or single or doubly or singly) adj (blind or blinded or blindly)).ti,ab.
24. double blind procedure/
25. parallel group$1.ti,ab.
26. (crossover or cross over).ti,ab.
27. ((assign$ or match or matched or allocation) adj5 (alternate or group$1 orintervention$1 or patient$1 or subject$1 or participant$1)).ti,ab.
28. (assigned or allocated).ti,ab.
29. (controlled adj7 (study or design or trial)).ti,ab.
30. (volunteer or volunteers).ti,ab.
31. trial.ti.
32. or/14‐31
33. (exp animal/ or animal.hw. or nonhuman/) not (exp human/ or human cell/ or (human or humans).ti.)
34. 32 not 33
35. 13 and 34

Science Citation Index Expanded search strategy

#1 Topic=(appendectom* OR appendic*)
#2 Topic=(complicat* or gangren* or perforat* or ruptur* or phlegmon* or abscess* or periton*)
#3 Topic=(random* OR control* OR RCT* OR placebo OR trial* OR group*)
#4 (#3 AND #2 AND #1)

Chinese Biomedical Literature Database search strategy

1. 主题词:随机对照试验/全部树/全部副主题词

2. 主题词:临床对照试验/全部树/全部副主题词

3. 主题词:临床试验/全部树/全部副主题词

4. 主题词:病例对照研究/全部树/全部副主题词

5. 主题词:随机分配/全部树/全部副主题词

6. 主题词:对比研究/全部树/全部副主题词

7. 主题词:前瞻性研究/全部树/全部副主题词

8. 主题词:安慰剂/全部树/全部副主题词

9. 全部字段:随机

10. 全部字段:单盲

11. 全部字段:双盲

12. 全部字段:盲法

13. (#1 OR #2 OR #3 OR #4 OR #5 OR #6 OR #7 OR #8 OR #9 OR #10 OR #11 OR #12)

14. 主题词:阑尾切除术/全部树/全部副主题词

15. 主题词:阑尾炎/全部树/全部副主题词

16. 全部字段:阑尾

17. (#14 OR #15 OR #16)

18. 主题词:坏疽/全部树/全部副主题词

19. 主题词:肠穿孔/全部树/全部副主题词

20. 主题词:自发性穿孔/全部树/全部副主题词

21. 主题词:脓肿/全部树/全部副主题词

22. 主题词:腹膜炎全部树/全部副主题词

23. 全部字段:复杂

24. 全部字段:坏疽

25. 全部字段:穿孔

26. 全部字段:蜂窝组织炎

27. 全部字段:脓肿

28. 全部字段:腹膜炎

29. (#18 OR #19 OR #20 OR #21 OR #22 OR #23 OR #24 OR #25 OR #26 OR #27 OR #28)

30. (#13 AND #17 AND #29)

World Health Organization International Clinical Trials Registry Platform search portal

appendectom* OR appendic*

ClinicalTrials.gov

appendectomy OR appendicitis

Current Controlled Trials

appendectomy OR appendicitis

European (EU) Clinical Trials Register

appendectomy OR appendicitis

Chinese Clinical Trial Registry

阑尾炎 OR 阑尾切除术

Appendix 2. Criteria for judging risk of bias within each domain

Sequence generation

• Low risk of bias: the method used was either adequate (e.g. computer‐generated random numbers, table of random numbers) or unlikely to introduce confounding.

• Unclear risk of bias: there was insufficient information to assess whether the method used was likely to introduce confounding.

• High risk of bias: the method used was improper and likely to introduce confounding (e.g. quasi‐randomised studies). We excluded such studies.

Allocation concealment

• Low risk of bias: the method used was unlikely to induce bias on the final observed effect (e.g. central allocation).

• Unclear risk of bias: there was insufficient information to assess whether the method used was likely to induce bias on the estimate of effect.

• High risk of bias: the method used was likely to induce bias on the final observed effect (e.g. open random allocation schedule).

Blinding of participants and personnel

• Low risk of bias: blinding was performed adequately, or the outcome measurement was not likely to be influenced by lack of blinding.

• Unclear risk of bias: there was insufficient information to assess whether the type of blinding used was likely to induce bias on the estimate of effect.

• High risk of bias: no blinding or incomplete blinding, and the outcome or outcome measurement was likely to be influenced by lack of blinding.

Blinding of outcome assessors

• Low risk of bias: blinding was performed adequately, or the outcome measurement was not likely to be influenced by lack of blinding.

• Unclear risk of bias: there was insufficient information to assess whether the type of blinding used was likely to induce bias on the estimate of effect.

• High risk of bias: no blinding or incomplete blinding, and the outcome or the outcome measurement was likely to be influenced by lack of blinding.

Incomplete outcome data

• Low risk of bias: the underlying reasons for missing data were unlikely to make treatment effects depart from plausible values, or proper methods were employed to handle missing data.

• Unclear risk of bias: there was insufficient information to assess whether the missing data mechanism in combination with the method used to handle missing data was likely to induce bias on the estimate of effect.

• High risk of bias: the crude estimate of effect was clearly biased due to the underlying reasons for missing data, and the methods used to handle missing data were unsatisfactory (e.g. complete case estimate).

Selective outcome reporting

• Low risk of bias: the trial protocol was available and all of the trial's prespecified outcomes that were of interest to this review were reported; if the trial protocol was not available, all the primary outcomes in this review were reported.

• Unclear risk of bias: there was insufficient information to assess whether the magnitude and direction of the observed effect was related to selective outcome reporting.

• High risk of bias: not all of the trial's prespecified primary outcomes were reported.

Differences in baseline characteristics

• Low risk of bias: there was no baseline imbalance in important characteristics.

• Unclear risk of bias: the baseline characteristics were not reported.

• High risk of bias: there was a baseline imbalance due to chance or due to imbalanced exclusion after randomisation.

Data and analyses

Comparison 1. Early versus delayed open or laparoscopic appendicectomy for appendiceal phlegmon.

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1.1 Overall morbidity	3	146	Risk Ratio (M‐H, Random, 95% CI)	0.74 [0.19, 2.86]
1.2 Wound infection	7	788	Risk Ratio (M‐H, Random, 95% CI)	0.99 [0.48, 2.02]
1.3 Abdominal abscess	4	626	Risk Ratio (M‐H, Random, 95% CI)	0.26 [0.08, 0.80]
1.4 Bowel obstruction	2	106	Risk Ratio (M‐H, Random, 95% CI)	0.16 [0.02, 1.34]
1.5 Faecal fistula	5	388	Risk Ratio (M‐H, Random, 95% CI)	1.75 [0.36, 8.49]
1.6 Unplanned bowel resection	1		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only
1.7 Total length of hospital stay (days)	5	680	Mean Difference (IV, Random, 95% CI)	‐2.02 [‐3.13, ‐0.91]
1.8 Total length of hospital stay (days)	0		Other data	No numeric data
1.9 Time away from normal activities (days)	1		Mean Difference (IV, Random, 95% CI)	Subtotals only

Comparison 2. Early versus delayed laparoscopic appendicectomy for appendiceal abscess.

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
2.1 Unplanned bowel resection	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
2.2 Total length of hospital stay (days)	1		Mean Difference (IV, Random, 95% CI)	Subtotals only
2.3 Quality of life (score on a scale from 0 to 100)	1		Mean Difference (IV, Random, 95% CI)	Subtotals only

Characteristics of studies

Characteristics of included studies [ordered by study ID]

Khan 2016.

Study characteristics
Methods	Study design: parallel‐group RCT Number of centres: 2 Country: Pakistan Study dates: from 2013 to 2016
Participants	Inclusion criteria Participants with appendiceal mass Exclusion criteria People less than 15 years old Number randomised: 300 Postrandomisation dropout: 0 Intention‐to‐treat‐analysis: yes Description of sample size calculation: no Mean age: 26.0 years (range 15 to 65) Numbers of children and adults: not mentioned Sex: female 119 (39.7%) Appendiceal phlegmon: 300 (100%) Appendiceal abscess: 0 Method of diagnosis: not mentioned Type of appendicectomy: not mentioned Appendix stump closure method: not mentioned
Interventions	Participants with appendiceal mass (N = 300) were randomly assigned to 2 groups. Group 1: early appendicectomy (N = 150) ‐ emergent (immediate) laparoscopic or open appendicectomy Use of antibiotics: not mentioned Percutaneous drainage of appendiceal mass: not mentioned Group 2: delayed appendicectomy (N = 150) ‐ initial conservative treatment followed by interval laparoscopic or open appendicectomy 4 to 6 weeks later Use of antibiotics: not mentioned Percutaneous drainage of appendiceal mass: not mentioned
Outcomes	Primary outcomes Wound infection rate and abdominal abscess rate Mortality Secondary outcomes Total length of hospital stay Other outcomes Efficacy of treatment (without definition） Time point for measurements: not mentioned Length of follow‐up: not mentioned
Notes	Funding source: no information provided Conflicts of interest: no information provided We contacted the contact author to request missing information but received no answer. Published data only (unpublished not sought)
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Comment: no information provided
Allocation concealment (selection bias)	Unclear risk	Comment: no information provided
Blinding of participants and personnel (performance bias) All outcomes	High risk	Comment: it is not possible to blind the participants and healthcare providers unless sham surgery is provided, which may be unethical.
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Comment: no information provided
Incomplete outcome data (attrition bias) All outcomes	Low risk	Comment: there were no postrandomisation dropouts.
Selective reporting (reporting bias)	Unclear risk	Comment: the trial protocol was not available. Some outcomes of interest in the review were not reported, so the trial was considered to be unclear risk of bias for selective reporting.
Differences in baseline characteristics	Low risk	Comment: there was no baseline imbalance in important characteristics.

Khan 2021a.

Study characteristics
Methods	Study design: parallel‐group RCT Number of centres: 1 Country: Pakistan Study dates: from 2019 to 2020
Participants	Inclusion criteria Participants with appendiceal mass Exclusion criteria PIleo‐caecal tuberculosis Carcinoid tumour People who did not agree to take part Number randomised: 180 Postrandomisation dropout: 0 Intention‐to‐treat‐analysis: yes Description of sample size calculation: no Mean age: 24.4 years (range not mentioned) Numbers of children and adults: not mentioned Sex: not mentioned Appendiceal phlegmon: 180 (100%) Appendiceal abscess: 0 Method of diagnosis: not mentioned Type of appendicectomy: laparoscopic 126 (70%), open 54 (30%) Appendix stump closure method: not mentioned
Interventions	Participants with appendiceal mass (N = 180) were randomly assigned to 2 groups. Group 1: early appendicectomy (N = 90) ‐ emergent (immediate) laparoscopic or open appendicectomy Use of antibiotics: not mentioned Percutaneous drainage of appendiceal mass: not mentioned Group 2: delayed appendicectomy (N = 90) ‐ initial conservative treatment followed by interval laparoscopic or open appendicectomy Use of antibiotics: not mentioned Percutaneous drainage of appendiceal mass: not mentioned
Outcomes	Primary outcomes Wound infection rate, abdominal abscess rate, and faecal fistula rate Mortality Secondary outcomes Total length of hospital stay Other outcomes Total operative time Frequency of satisfaction Time point for measurements: not mentioned Length of follow‐up: not mentioned
Notes	Funding source: no information provided Conflicts of interest: no information provided We contacted the contact author to request missing information but received no answer. Published data only (unpublished not sought)
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Comment: no information provided
Allocation concealment (selection bias)	Unclear risk	Comment: no information provided
Blinding of participants and personnel (performance bias) All outcomes	High risk	Comment: it is not possible to blind the participants and healthcare providers unless sham surgery is provided, which may be unethical.
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Comment: no information provided
Incomplete outcome data (attrition bias) All outcomes	Low risk	Comment: there were no postrandomisation dropouts.
Selective reporting (reporting bias)	Unclear risk	Comment: the trial protocol was not available. Some outcomes of interest in the review were not reported, so the trial was considered to be unclear risk of bias for selective reporting.
Differences in baseline characteristics	Low risk	Comment: there was no baseline imbalance in important characteristics.

Khan 2021b.

Study characteristics
Methods	Study design: parallel‐group RCT Number of centres: 1 Country: Nepal Study dates: from 2018 to 2021
Participants	Inclusion criteria People with appendiceal mass Exclusion criteria History of recurrent appendicitis Appendicular lump for more than 7 days Diffuse peritonitis Number randomised: 62 Postrandomisation dropout: 0 Intention‐to‐treat‐analysis: yes Description of sample size calculation: no Mean age: not mentioned (range 7 to 14 years) Numbers of children and adults: children 62 (100%), adults 0 Sex: female 20 (32.3%) Appendiceal phlegmon: 62 (100%) Appendiceal abscess: 0 Method of diagnosis: medical history, physical examination, laboratory test, and abdominal ultrasonography Type of appendicectomy: laparoscopic 0, open 62 (100%) Appendix stump closure method: not mentioned
Interventions	Participants with appendiceal mass (N = 62) were randomly assigned to 2 groups. Two participants crossed from group 2 to group 1 (intention‐to‐treat analysis used). Group 1: early open appendicectomy (N = 31) ‐ emergent (immediate) open appendicectomy within 1 day of admission Use of antibiotics: broad‐spectrum antibiotics Percutaneous drainage of appendiceal mass: not mentioned Group 2: delayed open appendicectomy (N = 31) ‐ initial conservative treatment followed by interval open appendicectomy 6 weeks later Use of antibiotics: not mentioned Percutaneous drainage of appendiceal mass: not mentioned
Outcomes	Primary outcomes Wound infection rate and faecal fistula rate Mortality Secondary outcomes Total length of hospital stay Time point for measurements: not mentioned Length of follow‐up: not mentioned
Notes	Funding source: no information provided Conflicts of interest: no information provided We contacted the contact author to request missing information but received no answer. Published data only (unpublished not sought)
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Comment: no information provided
Allocation concealment (selection bias)	Unclear risk	Comment: no information provided
Blinding of participants and personnel (performance bias) All outcomes	High risk	Comment: it is not possible to blind the participants and healthcare providers unless sham surgery is provided, which may be unethical.
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Comment: no information provided
Incomplete outcome data (attrition bias) All outcomes	Low risk	Comment: there were no postrandomisation dropouts.
Selective reporting (reporting bias)	Unclear risk	Comment: the trial protocol was not available. Some outcomes of interest in the review were not reported, so the trial was considered to be unclear risk of bias for selective reporting.
Differences in baseline characteristics	Low risk	Comment: there was no baseline imbalance in important characteristics.

Kumar 2004.

Study characteristics
Methods	Study design: 3‐arm parallel‐group RCT (2 arms used) Number of centres: 1 Country: India Study dates: from 1998 to 2001
Participants	Inclusion criteria People with appendiceal mass determined on medical history, physical examination, and imaging results (e.g. ultrasonography, plain abdominal X‐ray) Exclusion criteria Free air in the peritoneal cavity (on plain films) Pus collection in the right iliac fossa or pelvis Colonic malignancy or ileocaecal tuberculosis Number randomised: 60 Postrandomisation dropout: 0 Intention‐to‐treat‐analysis: yes Description of sample size calculation: no Mean age: 27.6 years (range not mentioned) Numbers of children and adults: not mentioned Sex: female 3 (5%) Appendiceal phlegmon: 60 (100%) Appendiceal abscess: 0 Method of diagnosis: medical history, physical examination, laboratory test, plain abdominal X‐ray, and abdominal ultrasonography Type of appendicectomy: laparoscopic 0, open 60 (100%) Appendix stump closure method: not mentioned
Interventions	Participants with appendiceal mass (N = 60) were randomly assigned to 3 groups. Group 1: early open appendicectomy (N = 20) ‐ open appendicectomy as soon as appendiceal mass resolved within the same admission Use of antibiotics: ampicillin, gentmicin, and metronidazole Percutaneous drainage of appendiceal mass: not mentioned Group 2: delayed open appendicectomy (N = 20) ‐ initial conservative treatment followed by interval open appendicectomy 6 weeks later Use of antibiotics: ampicillin, gentmicin, and metronidazole Percutaneous drainage of appendiceal mass: not mentioned Group 3: conservative treatment without appendicectomy (N = 20). Group excluded from review Use of antibiotics: ampicillin, gentmicin, and metronidazole Percutaneous drainage of appendiceal mass: not mentioned
Outcomes	Primary outcomes Overall morbidity (overall complication rate) Wound infection rate and faecal fistula rate Mortality Secondary outcomes Total length of hospital stay Time away from normal activities Other outcomes Total operative time Operative difficulty Number of hospital visits made Presence of severe incisional pain Scar appearance Participants with recurrent appendicitis Time point for measurements: median 33.5 weeks Length of follow‐up: median 33.5 weeks (24 to 52 weeks)
Notes	Funding source: no information provided Conflicts of interest: no information provided We contacted the contact author to request missing information but received no answer. Published data only (unpublished not sought)
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Comment: no information provided
Allocation concealment (selection bias)	Unclear risk	Comment: no information provided
Blinding of participants and personnel (performance bias) All outcomes	High risk	Comment: it is not possible to blind the participants and healthcare providers unless sham surgery is provided, which may be unethical.
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Comment: no information provided
Incomplete outcome data (attrition bias) All outcomes	Low risk	Comment: there were no postrandomisation dropouts.
Selective reporting (reporting bias)	Unclear risk	Comment: the trial protocol was not available. Some outcomes of interest in the review were not reported, so the trial was considered to be unclear risk of bias for selective reporting.
Differences in baseline characteristics	Low risk	Comment: there was no baseline imbalance in important characteristics.

Kumar 2018.

Study characteristics
Methods	Study design: parallel‐group RCT Number of centres: 1 Country: India Study dates: not mentioned
Participants	Inclusion criteria People diagnosed with appendicular mass in absence of other obvious pathology People more than 12 years old Exclusion criteria People with other obvious pathology People less than 12 years old Number randomised: 46 Postrandomisation dropout: 0 Intention‐to‐treat‐analysis: yes Description of sample size calculation: no Mean age: not mentioned (range not mentioned) Numbers of children and adults: children 10 (21.7%), adults 36 (78.3%) Sex: female 15 (32.6%) Appendiceal phlegmon: 43 (93.5%) Appendiceal abscess: 3 (6.5%) Method of diagnosis: medical history, physical examination, and abdominal ultrasonography Type of appendicectomy: laparoscopic 0, open 46 (100%) Appendix stump closure method: not mentioned
Interventions	Participants with appendiceal mass (N = 46) were randomly assigned to 2 groups. Group 1: early open appendicectomy (N = 20) ‐ open appendicectomy within 1 to 2 days of admission Use of antibiotics: not mentioned Percutaneous drainage of appendiceal mass: not mentioned Group 2: delayed open appendicectomy (N = 20) ‐ initial conservative treatment followed by interval open appendicectomy 6 to 8 weeks later Use of antibiotics: not mentioned Percutaneous drainage of appendiceal mass: not mentioned
Outcomes	Primary outcomes Overall morbidity (overall complication rate) Wound infection rate, abdominal abscess rate, bowel obstruction rate, faecal fistula rate, and unplanned bowel resection Mortality Secondary outcomes Total length of hospital stay Other outcomes Total operative time Operative difficulty (difficulty in localising appendix, difficulty in adhesiolysis, minor trauma to bowel, bleeding) Time point for measurements: not mentioned Length of follow‐up: not mentioned
Notes	Funding source: no funding sources Conflicts of interest: none declared We contacted the contact author to request missing information but received no answer. Published data only (unpublished not sought)
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Comment: no information provided
Allocation concealment (selection bias)	Unclear risk	Comment: no information provided
Blinding of participants and personnel (performance bias) All outcomes	High risk	Comment: it is not possible to blind the participants and healthcare providers unless sham surgery is provided, which may be unethical.
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Comment: no information provided
Incomplete outcome data (attrition bias) All outcomes	Low risk	Comment: there were no postrandomisation dropouts.
Selective reporting (reporting bias)	Unclear risk	Comment: the trial protocol was not available. Some outcomes of interest in the review were not reported, so the trial was considered to be unclear risk of bias for selective reporting.
Differences in baseline characteristics	Low risk	Comment: there was no baseline imbalance in important characteristics.

Pathan 2018.

Study characteristics
Methods	Study design: parallel‐group RCT Number of centres: 1 Country: India Study dates: from 2016 to 2017
Participants	Inclusion criteria People with appendicular mass People more than 10 years of age Exclusion criteria Severe septicaemia Unstable blood pressure People less than 10 years of age Number randomised: 100 Postrandomisation dropout: 0 Intention‐to‐treat‐analysis: yes Description of sample size calculation: no Mean age: not mentioned (range not mentioned) Numbers of children and adults: children 24 (24%), adults 76 (76%) Sex: female 21 (21%) Appendiceal phlegmon: 100 (100%) Appendiceal abscess: 0 Method of diagnosis: medical history, physical examination, laboratory test, and abdominal ultrasonography Type of appendicectomy: not mentioned Appendix stump closure method: not mentioned
Interventions	Participants with appendiceal mass (N = 46) were randomly assigned to 2 groups. Group 1: early appendicectomy (N = 20) ‐ emergent (immediate) appendicectomy Use of antibiotics: not mentioned Percutaneous drainage of appendiceal mass: not mentioned Group 2: delayed appendicectomy (N = 20) ‐ initial conservative treatment followed by interval appendicectomy 4 to 6 weeks later Use of antibiotics: not mentioned Percutaneous drainage of appendiceal mass: not mentioned
Outcomes	Primary outcomes Overall morbidity (overall complication rate) Wound infection rate and abdominal abscess rate Mortality Secondary outcomes Total length of hospital stay Other outcomes Functional recovery (without definition) Time point for measurements: not mentioned Length of follow‐up: not mentioned
Notes	Funding source: no information provided Conflicts of interest: no information provided We contacted the contact author to request missing information but received no answer.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Comment: no information provided
Allocation concealment (selection bias)	Unclear risk	Comment: no information provided
Blinding of participants and personnel (performance bias) All outcomes	High risk	Comment: it is not possible to blind the participants and healthcare providers unless sham surgery is provided, which may be unethical.
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Comment: no information provided
Incomplete outcome data (attrition bias) All outcomes	Low risk	Comment: there were no postrandomisation dropouts.
Selective reporting (reporting bias)	Unclear risk	Comment: the trial protocol was not available. Some outcomes of interest in the review were not reported, so the trial was considered to be unclear risk of bias for selective reporting.
Differences in baseline characteristics	Low risk	Comment: there was no baseline imbalance in important characteristics.

Ravi 2018.

Study characteristics
Methods	Study design: parallel‐group RCT Number of centres: 1 Country: India Study dates: from 2016 to 2017
Participants	Inclusion criteria People with appendicular mass Exclusion criteria Pregnancy Not fit for surgery Peigns of diffuse peritonitis Number randomised: 60 Postrandomisation dropout: 0 Intention‐to‐treat‐analysis: yes Description of sample size calculation: no Mean age: 27.6 years (range not mentioned) Numbers of children and adults: children 12 (20%), adults 48 (80%) Sex: female 18 (30%) Appendiceal phlegmon: 57 (95%) Appendiceal abscess: 3 (5%) Method of diagnosis: medical history, physical examination, laboratory test, and abdominal ultrasonography Type of appendicectomy: not mentioned Appendix stump closure method: not mentioned
Interventions	Participants with appendiceal mass (N = 60) were randomly assigned to 2 groups. Four participants crossed from group 2 to group 1 (intention‐to‐treat analysis used). Group 1: early appendicectomy (N = 30) ‐ emergent (immediate) appendicectomy within 1 day of admission Use of antibiotics: not mentioned Percutaneous drainage of appendiceal mass: not mentioned Group 2: delayed appendicectomy (N = 30) ‐ initial conservative treatment followed by interval appendicectomy 6 to 8 weeks later Use of antibiotics: not mentioned Percutaneous drainage of appendiceal mass: not mentioned
Outcomes	Primary outcomes Overall morbidity (overall complication rate) Wound infection rate, bowel obstruction rate, and faecal fistula rate Mortality Secondary outcomes Total length of hospital stay Other outcomes Operative difficulty (difficulty in localising appendix, difficulty in adhesiolysis, minor trauma to bowel, bleeding) Functional recovery (without definition) Time point for measurements: not mentioned Length of follow‐up: not mentioned
Notes	Funding source: no information provided Conflicts of interest: no information provided We contacted the contact author to request missing information but received no answer. Published data only (unpublished not sought)
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Comment: no information provided
Allocation concealment (selection bias)	Unclear risk	Comment: no information provided
Blinding of participants and personnel (performance bias) All outcomes	High risk	Comment: it is not possible to blind the participants and healthcare providers unless sham surgery is provided, which may be unethical.
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Comment: no information provided
Incomplete outcome data (attrition bias) All outcomes	Low risk	Comment: there were no postrandomisation dropouts.
Selective reporting (reporting bias)	Unclear risk	Comment: the trial protocol was not available. Some outcomes of interest in the review were not reported, so we considered the trial to be unclear risk of bias for selective reporting.
Differences in baseline characteristics	Low risk	Comment: there was no baseline imbalance in important characteristics.

St Peter 2010.

Study characteristics
Methods	Study design: parallel‐group RCT Number of centres: 1 Country: USA Study dates: from 2006 to 2009
Participants	Inclusion criteria 7 to 18 years old Well‐defined abdominal abscess determined on CT imaging Exclusion criteria People with a postoperative abscess People with a comorbid condition Number randomised: 40 Postrandomisation dropout: 0 (0%) Intention‐to‐treat‐analysis: yes Description of sample size calculation: yes Mean age: 9.5 years (range not mentioned) Numbers of children and adults: children 40 (100%), adults 0 Sex: female 19 (47.5%) Appendiceal phlegmon: 0 Appendiceal abscess: 40 (100%) Method of diagnosis: CT imaging Type of appendicectomy: laparoscopic 40 (100%), open 0 Appendix stump closure method: not mentioned
Interventions	Participants with appendiceal abscess (N = 40) were randomly assigned to 2 groups. Four participants crossed from group 2 to group 1 (intention‐to‐treat analysis used). Group 1: early laparoscopic appendicectomy (N = 20) ‐ emergent (immediate) laparoscopic appendicectomy Use of antibiotics: ceftriaxone and metronidazole Percutaneous drainage of appendiceal mass: not mentioned Group 2: delayed laparoscopic appendicectomy (N = 20) ‐ initial conservative treatment and percutaneous drainage of the abscess (when possible), followed by interval laparoscopic appendicectomy approximately 10 weeks later. Use of antibiotics: ceftriaxone and metronidazole Percutaneous drainage of appendiceal mass: 11 (55%)
Outcomes	Primary outcomes Unplanned bowel resection Mortality Secondary outcomes Total length of hospital stay Quality of life (measured with the Pediatric Quality of Life Scale‐Version 4.0 questionnaire; a scale of 0 to 100 with higher values indicating a better quality of life) Other outcomes Total hospital costs Total operative time Number of hospital visits made Time point for measurements: approximately 12 weeks Length of follow‐up: median 12 weeks
Notes	Funding source: no information provided Conflicts of interest: no information provided We contacted the contact author to request missing information but received no answer. Published data only (unpublished not sought)
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Comment: no information provided
Allocation concealment (selection bias)	Unclear risk	Quote: "the randomisation sequence was accessed to identify the next allotment" Comment: no information provided about the method of allocation concealment
Blinding of participants and personnel (performance bias) All outcomes	High risk	Comment: it is not possible to blind the participants and healthcare providers unless sham surgery is provided, which may be unethical.
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Comment: no information provided
Incomplete outcome data (attrition bias) All outcomes	Low risk	Comment: there were no postrandomisation dropouts.
Selective reporting (reporting bias)	Low risk	Comment: the study protocol is available. All of the study's prespecified outcomes were reported.
Differences in baseline characteristics	Low risk	Comment: no baseline imbalance in important characteristics

CT: computed tomography; N: number of participants; RCT: randomised controlled trial

Characteristics of excluded studies [ordered by study ID]

Study	Reason for exclusion
Abdulraheem 2021	Randomised controlled trial comparing early appendicectomy versus conservative management without interval appendicectomy for appendiceal phlegmon or appendiceal abscess
Blakely 2011	Randomised controlled trial about perforated appendicitis without appendiceal abscess
Demetrashvili 2019	A non‐randomised study
Dhaded 2016	A non‐randomised study
Elsaady 2019	A non‐randomised study
Goh 2005	A non‐randomised study
Hall 2017	Randomised controlled trial comparing interval appendicectomy versus no interval appendicectomy for appendiceal phlegmon or appendiceal abscess
Israr 2021	A non‐randomised study
Patel 2015	A non‐randomised study
Ravichandran 2021	A non‐randomised study
Shinde 2020	A non‐randomised study

Characteristics of ongoing studies [ordered by study ID]

ChiCTR1900021559.

Study name	A randomised controlled prospective study for comparing delayed surgery with emergency surgery for complicated appendicitis
Methods	Study design: parallel RCT, unblinded, computer randomisation Number of centres: 1 Country: China Planned study dates: June 2019 to June 2024
Participants	Inclusion criteria Age 0 to 18 years Diagnosis of complicated appendicitis Exclusion criteria Complicated other diseases General condition is poor, appeared to have sepsis or symptom such as septic shock Number being randomised: 200
Interventions	Early versus delayed appendicectomy Group 1: early appendicectomy Group 2: delayed appendicectomy
Outcomes	Primary outcomes Total length of hospital stay Operative time Morbidity Secondary outcome Rate of conversion to open surgery
Starting date	June 2019
Contact information	Principal investigator: Chunbao Guo, Children’s Hospital of Chongqing Medical University, Chongqing, China, 400014 Email: guochunbao@foxmail.com
Notes

RCT: randomised controlled trial

Differences between protocol and review

2017 review

• We made clarifications to the types of participants according to the reviewer's suggestion (e.g. use of antibiotics and percutaneous drainage of appendiceal abscess were allowed for participants in both groups), and added a diagnosis definition.

• The participant cohort among studies was heterogenous (appendiceal phlegmon versus appendiceal abscess), which were so dissimilar that the peer reviewer suggested they should not be combined in the same meta‐analysis. Thus, we analysed participants with appendiceal phlegmon and appendiceal abscess in separate comparisons instead of using subgroup analysis for all outcome measures to answer specific questions about particular patient groups.

• Hospital costs are neither comparable nor reliable among included studies due to inflation and inter‐country economic differences. Thus, we did not include hospital costs as an outcome in the review stage.

• We applied the GRADE approach for evaluating the quality of evidence for each outcome, which we had not stated in the protocol.

2024 update

• We updated the search strategies with the help of an information specialist and searched the reference lists of included studies and any relevant systematic reviews identified.

• We added definitions for outcome measures.

• We added 'unplanned bowel resection' as a morbidity outcome measure.

• We employed a random‐effects model to obtain an overall weighted average of treatment effect, regardless of the number of studies.

• We revised the interpretation of the I² statistic when we measured the statistical heterogeneity.

• We conducted the systematic review according to the latest guidance in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2023).

• We performed a posthoc sensitivity analysis by consecutively excluding every study from the meta‐analysis to explore the impact of individual studies on the statistical heterogeneity according to the peer reviewer's suggestion.

• We applied the GRADE approach for evaluating the certainty of evidence for seven outcomes and presented these in the summary of findings tables: overall morbidity, wound infection, abdominal abscess, faecal fistula, mortality, total length of hospital stay, and time away from normal activities. This was not specified in the protocol and was different from the 2017 version where our SoF tables included overall morbidity, wound infection, faecal fistula, mortality, total length of hospital stay, time away from normal activities, quality of life, and pain.

• We did not use some methods due to the small number of studies or lack of data (specifically, Peto OR for mortality, funnel plots for publication bias, subgroup analyses).

Contributions of authors

All authors in this updated review fulfilled all four of the following authorship criteria.

• Substantial contributions to the conception or design of the work, or the acquisition of data for the work, or analysis of data for the work, or interpretation of data for the work

• Drafting the work or revising it critically for important intellectual content

• Final approval of the version to be published

• Agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved

Conceiving the review: Bing Tu (BT)
Designing the review: Yao Cheng (YC)
Co‐ordinating the review: Shiyi Zhou (SZ)
Designing search strategies: YC
Conducting the searches: SZ
Selecting studies: SZ, YC
Extracting data: Nansheng Cheng (NC), Jianping Gong (JG)
Assessing the risk of bias in the studies: SZ, YC 
Judging the certainty of the evidence: SZ, BT 
Writing the updated review: SZ, YC
Providing general advice on the review: NC, JG, BT
Securing funding for the review: YC
Performing previous work that was the foundation of the current study: YC

Sources of support

Internal sources

• Chongqing Medical University, China

  Review authors are employed in the Departments of Pharmacy and Hepatobiliary Surgery.

External sources

• National Natural Science Foundation of China, China

  Yao Cheng is the recipient of grants from the National Natural Science Foundation of China (grant number 81701950, 82172135).

• Natural Science Foundation of Chongqing, China

  Yao Cheng is the recipient of grants from the Natural Science Foundation of Chongqing (grant number CSTB2022NSCQ‐MSX0058).

• Medical Research Projects of Chongqing, China

  Yao Cheng is the recipient of grants from the Medical Research Projects of Chongqing (grant number 2018MSXM132).

• Kuanren Talents Program, China

  Yao Cheng is the recipient of grants from the Kuanren Talents Program of the second affiliated hospital of Chongqing Medical University (grant number KY2019Y002).

Declarations of interest

Shiyi Zhou: none known
Yao Cheng: none known
Nansheng Cheng: none known
Jianping Gong: none known
Bing Tu: none known

New search for studies and content updated (conclusions changed)