Surgical Endoscopy (2023) 37:8933–8990 and Other Interventional Techniques

https://doi.org/10.1007/s00464-023-10456-5

SAGES/EAES OFFICIAL PUBLICATION

Diagnosis and treatment of appendicitis: systematic review

and meta‑analysis
Ryan Lamm1 · Sunjay S. Kumar1,15 · Amelia T. Collings2 · Ivy N. Haskins3 · Ahmed Abou‑Setta4 · Nisha Narula5 ·
Pramod Nepal6 · Nader M. Hanna7 · Dimitrios I. Athanasiadis8 · Stefan Scholz9 · Joel F. Bradley 3rd10 ·
Arianne T. Train11 · Philip H. Pucher12 · Francisco Quinteros13 · Bethany Slater14

Received: 18 August 2023 / Accepted: 7 September 2023 / Published online: 1 November 2023
© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2023

Abstract
Background The optimal diagnosis and treatment of appendicitis remains controversial. This systematic review details the
evidence and current best practices for the evaluation and management of uncomplicated and complicated appendicitis in
adults and children.
Methods Eight questions regarding the diagnosis and management of appendicitis were formulated. PubMed, Embase,
CINAHL, Cochrane and clinicaltrials.gov/NLM were queried for articles published from 2010 to 2022 with key words
related to at least one question. Randomized and non-randomized studies were included. Two reviewers screened each
publication for eligibility and then extracted data from eligible studies. Random effects meta-analyses were performed on
all quantitative data. The quality of randomized and non-randomized studies was assessed using the Cochrane Risk of Bias
2.0 or Newcastle Ottawa Scale, respectively.
Results 2792 studies were screened and 261 were included. Most had a high risk of bias. Computerized tomography scan
yielded the highest sensitivity (> 80%) and specificity (> 93%) in the adult population, although high variability existed. In
adults with uncomplicated appendicitis, non-operative management resulted in higher odds of readmission (OR 6.10) and
need for operation (OR 20.09), but less time to return to work/school (SMD − 1.78). In pediatric patients with uncomplicated
appendicitis, non-operative management also resulted in higher odds of need for operation (OR 38.31). In adult patients
with complicated appendicitis, there were higher odds of need for operation following antibiotic treatment only (OR 29.00),
while pediatric patients had higher odds of abscess formation (OR 2.23). In pediatric patients undergoing appendectomy
for complicated appendicitis, higher risk of reoperation at any time point was observed in patients who had drains placed at
the time of operation (RR 2.04).
Conclusions This review demonstrates the diagnosis and treatment of appendicitis remains nuanced. A personalized approach
and appropriate patient selection remain key to treatment success. Further research on controversies in treatment would be
useful for optimal management.

Keywords Appendicitis · Appendectomy · Meta-analysis · Systematic review · Antibiotic treatment

Acute appendicitis remains one of the most common pathol-
ogies resulting in hospital admission. Lifetime risk of appen-
dicitis in the United States (US) is estimated to be around
9% [1]. This rate is similar in Europe (8%), but lower in
Africa (2%) with peak presentation occurring between the
ages of 10 and 30 years old [2]. Complicated appendicitis
upon presentation has a rate of 16–40% with higher rates
being reported in both younger age groups and patients older
than 50 years [3]. While the mortality rate for uncomplicated
Extended author information available on the last page of the article
appendicitis is around 0.1%, complicated appendicitis car-
ries a far higher mortality risk at 5%, emphasizing the
importance of timely diagnosis and treatment [4].
From a resource utilization standpoint, managing appen-
dicitis is burdensome. One study estimates hospitalization
cost in the US alone at $3 billion annually [5]. High vari-
ability regarding the diagnosis and treatment of acute appen-
dicitis has contributed to high resource utilization within
the US and globally [6]. This variability contributes to high
cost, poorer outcomes which have been linked to country

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income and reveals the need for data to streamline practices
and reduce costs [6].
Due to the high variability and controversies surround-
ing ‘best practices’ concerning the diagnosis and treatment
of acute appendicitis, key questions were identified by this
research group and data were explored.
Clinical diagnosis of appendicitis remains challenging
due to the fact that many of its signs and symptoms mimic
other abdominal pathologies [7, 8]. While imaging stud-
ies undoubtedly increase the sensitivity and specificity of
diagnosis, debate still exists on which modality to use when
considering resources required to perform the exams, time-
liness of the exams, and the amount of radiation exposure,
especially in the pediatric population [9]. Nevertheless, as
the treatment for uncomplicated and complicated appendici-
tis can be drastically different, selecting the optimal imaging
modality to differentiate between them is critical.
Once the diagnosis is made, controversy persists regard-
ing the best treatment strategy. Specifically, multicenter,
non-inferiority trials such as the Appendicitis acuta trial
reported antibiotic only treatment to be safe and effective in
adults with first episode uncomplicated appendicitis, which
has been corroborated in additional systematic reviews and
meta-analyses [10–12]. Similar data, albeit more limited, has
also been demonstrated in children [13, 14]. While approxi-
mately 90% of patients in these studies were able to avoid
initial surgery for uncomplicated appendicitis, recurrence
was estimated to be roughly 20–30% at 5-year follow-up
[15–17]. Because the long-term nonoperative management
of uncomplicated appendicitis may not be successful in all
patients, it is commonly suggested that treatment options
should be presented to the patient, allowing for shared
decision-making.
Patients with complicated appendicitis are often treated
based on clinical presentation with some being trialed on
antibiotic treatment while others undergo immediate surgical
intervention [18]. If treated nonoperatively, many surgeons
recommend interval appendectomy, but approaches vary and
are not universally agreed upon [19, 20].
Operative approach and post-operative management also
vary. Questions persist regarding timing of operation fol-
lowing diagnosis [21], drain placement during surgery for
complicated appendicitis [22], suction versus suction and
lavage for perforated appendicitis [23], as well as duration
of postoperative antibiotics in cases of complicated appen-
dicitis [24].
In an attempt to better characterize and consolidate the
current data detailing the diagnosis and treatment of appen-
dicitis, to clarify some of the controversies surrounding
the management of appendicitis, and to inform a Society
of American Gastrointestinal and Endoscopic Surgeons
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Surgical Endoscopy (2023) 37:8933–8990
(SAGES) guideline with evidence-based recommendations,
a systematic review and meta-analysis were conducted.
Materials and methods
A systematic review and meta-analysis comparing diag-
nostic and treatment options for appendicitis was per-
formed by members of the SAGES guidelines committee
according to the Preferred Reporting Items for Systematic
Reviews and Meta-Analyses (PRISMA) guidelines [25].
Eight key questions (KQs) were created by the guidelines
committee according to the Population, Intervention, Com-
parator, and Outcomes format. The KQs were as follows:
Key Question 1 (KQ 1): Should abdominal/pelvis CT
scan versus alternative imaging be used for diagnosing
acute appendicitis?
Outcomes: true positive, false positive, false negative,
and true negative values, sensitivity, specificity, rate of
needing additional imaging following initial imaging,
rate of negative appendectomy following false positive
initial imaging, rate of nondiagnostic finding following
initial imaging.
Key Question 2 (KQ 2): Should adult and pediatric
patients with acute, uncomplicated appendicitis be man-
aged nonoperatively with antibiotics versus laparoscopic
appendectomy?
Outcomes: abscess formation, cost, need for percutane-
ous drain placement, intensive care unit (ICU) admission,
length of hospital stay, mortality, need for new course of
antibiotics, quality of life, readmission, reoperation/need
for operation within 30 days, reoperation/need for opera-
tion between 30 days and 1 year, reoperation (at any time
point), time to return to work/school.
Key Question 3 (KQ 3): In adult and pediatric patients
with complicated appendicitis, should operative manage-
ment versus nonoperative management be used?
Outcomes: abscess formation, cost, drain placement, ICU
admission, length of hospital stay, mortality, need for new
course of antibiotics, quality of life, readmission, reopera-
tion/need for operation (at any time point), time to return
to work/school.
Key Question 4 (KQ 4): In adult and pediatric patients
with uncomplicated appendicitis undergoing appendec-
tomy, do outcomes differ based on early (< 12 h from
diagnosis) versus late (> 12 h from diagnosis) surgical
intervention?
Outcomes: abscess formation, drain placement, length of
hospital stay, readmission, reoperation/need for operation
(at any time point).
Surgical Endoscopy (2023) 37:8933–8990
Key Question 5 (KQ 5): In adult and pediatric patients
undergoing appendectomy for perforated appendicitis,
should suction and lavage versus suction alone be used?
Outcomes: abscess formation, drain placement, length of
hospital stay, mortality, readmission, reoperation/need for
operation (at any time point).
Key Question 6 (KQ 6): In adult and pediatric patients
undergoing appendectomy for complicated appendicitis,
should routine drain placement versus selective drain
placement be used?
Outcomes: abscess formation, drain placement, need for
new course of antibiotics, readmission, reoperation/need
for operation (at any time point).
Key Question 7 (KQ 7): Should adult and pediatric
patients who undergo appendectomy for complicated
appendicitis be given postoperative antibiotics for short
term vs. long term (based on study authors’ criteria)?
Outcomes: abscess formation, contraction of Clostridium
difficile, drain placement, length of hospital stay, need for
new course of antibiotics, readmission, reoperation/need
for operation (at any time point), total complications.
Key Question 8 (KQ 8): In asymptomatic adult and pedi-
atric patients with previous complicated appendicitis
treated nonoperatively, should an interval appendectomy
be performed versus observation?
Outcomes: abscess formation, drain placement, length of
hospital stay, mortality, readmission, rate of neoplasm/
missed neoplasm, reoperation/need for operation within
30 days, reoperation/need for operation between 30 days
and 1 year.
Subgroup analysis
For each of the KQs a subgroup analysis was performed for
the adult and pediatric population when data was available.
Literature search and eligibility criteria
Assisted by a professional librarian, an extensive search
of PubMed, Embase, CINAHL, and Cochrane as well as
clinicaltrials.gov/NLM was performed for each KQ. Eligi-
ble studies included those published in English between the
years of 2010 and 2021. Studies included in the analysis
consisted of randomized control trials (RCTs), as well as
non-randomized comparative studies. All identified studies
were combined and uploaded using Covidence for screen-
ing and data extraction purposes [26]. An updated search
was performed in 2022 to capture published studies since
8935
our initial search. Full search strategies can be found in the
Supplementary material, Appendix B.
Study selection
To calibrate guideline committee member responses, review-
ers were asked to rate 50 abstracts on Abstrackr (Brown Uni-
versity, Providence, Rhode Island) and discuss any discrep-
ancies in scoring during a scheduled conference call. After
calibration, all identified titles and abstracts in the screen-
ing process were reviewed by a minimum of two committee
members for relevance and eligibility using Covidence. Any
discrepancies were addressed by a third reviewer/consensus
discussion. Publications deemed irrelevant to the key ques-
tions, duplicate studies, and/or had only a non-English lan-
guage version available were excluded. Additional exclusion
criteria included: case reports, single-arm studies with less
than 50 patients, articles with patients who were pregnant,
and studies where greater than 50% of the operations were
performed open. Next, full text review was conducted on
all eligible and available published manuscripts. Previously
published systematic reviews’ reference lists were hand
checked to identify additional relevant articles.
Risk of bias
The Cochrane Risk of Bias 2.0 tool was used for qual-
ity assessment of included RCTs [27]. Criteria included
sequence generation, allocation concealment, blinding of
participants and personnel, blinding of outcome assessors,
incomplete data, non-comparable groups, performance bias,
and detection bias. Non-randomized studies were evaluated
using the Newcastle–Ottawa Scale [28]. Criteria included
selection bias, comparability of groups, and outcome report-
ing. Two independent investigators scored each study for
all appropriate criteria. For each study a final risk of bias
assessment was determined, with any discrepancies resolved
by a discussion between the two reviewers or a third part
tie-breaker where necessary.
Data extraction
Covidence was again used to complete data extraction forms
for included studies. These forms included data points for
study characteristics, methods, population, interventions,
and outcomes. These forms were completed by two inde-
pendent reviewers. Outcomes of interest included time to
return to work/school, readmission, mortality, ICU admis-
sion, organ space infection (defined as abscess found on
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8936 Surgical Endoscopy (2023) 37:8933–8990

imaging), hospital length of stay (LOS), requirement of new
course of antibiotics, drain placement, reoperation (defined
as reoperation or conversion of nonoperative management
to surgical management), cost-effectiveness, and quality of
life. Outcomes for diagnostic imaging comparison included
sensitivity, specificity, and negative appendectomy rate, true
positive, false positive, false negative, and true negative val-
ues, sensitivity, specificity, rate of needing additional imag-
ing following initial imaging, rate of negative appendectomy
following false positive initial imaging, and rate of nondiag-
nostic finding following initial imaging.
Data synthesis and analysis
RevMan (Version 5.3.5) [29] was used to perform meta-
analysis using a random-effects model. Risk ratios (RR) and
odds ratios (OR) were calculated for dichotomous outcomes
from randomized and non-randomized studies, respectively,
using a Mantel–Haenszel random effects model. Inverse

Table 1  Risk of bias for the

observational studies included
under KQ1 as assessed by a
modified Newcastle Ottawa
Scale

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Surgical Endoscopy (2023) 37:8933–8990
Table 1  (continued)
variance weighted mean difference for continuous outcomes
was utilized. For continuous outcomes using multiple scales,
a standardized mean difference (SMD) was used. Hetero-
geneity between studies was assessed using measures of I2
and χ2. All comparative studies, including observational and
high risk of bias, are presented, but results and conclusions
focus on randomized controlled trials and low risk of bias
studies when available.
Results
2792 studies were identified following database and hand-
searching queries. 261 studies met inclusion criteria and
were included to answer KQ1-8. 155 of the studies involved
8937
adult patient populations and 106 studies involved pediatric
patients. 26 studies included were RCTs, while the remain-
ing 235 were observational studies. A PRISMA flow dia-
gram showing screening results and exclusion rationale can
be found in Appendix A.
Key Question 1 (KQ 1): Should abdominal CT
versus alternative imaging be used for diagnosing
acute appendicitis?
Adults
A total of 94 studies met inclusion criteria for KQ1 in the
adult subpopulation composed of all observational studies.
Of the studies included 26 (28%) were determined to have
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8938 Surgical Endoscopy (2023) 37:8933–8990

Table 1  (continued)

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Surgical Endoscopy (2023) 37:8933–8990
Table 1  (continued)
low risk of bias, 47 had high (50%) and the remaining 21
(22%) had an unclear risk of bias (Table 1).
Twenty-seven studies reported sensitivity and specificity
for computed tomography (CT) scan with all reporting a
sensitivity higher than 80% and specificity varying from 35
to 100% (Fig. 1a, b) [30–56].
Three studies reported sensitivity and specificity for low
dose CT scan with all reporting a sensitivity higher than
95% and specificity varying from 93 to 100% (Fig. 1c, d)
[38, 39, 57].
Five studies reported sensitivity and specificity for non-
contrast CT scan with sensitivity ranging from 59 to 92%
and specificity varying from 83 to 100% (Fig. 1e, f) [34,
37, 58–60].
8939
Eighteen studies reported sensitivity and specificity for
magnetic resonance imaging (MRI) with all reporting a sen-
sitivity higher than 80% and specificity varying from 0 to
100% (Fig. 1g, h) [31, 36, 40, 50, 59–72].
Sixty-two studies reported sensitivity and specificity for
ultrasound (US) studies with sensitivity ranging from 37 to
100% and specificity varying from 0 to 100% (Fig. 1i, j)
[30, 31, 35, 40, 43–45, 47–49, 51–53, 55, 58, 60, 68, 69,
73–116].
Twelve studies reported sensitivity and specificity for
point of care ultrasound (POCUS) studies with sensitivity
ranging from 43 to 100% and specificity varying from 32 to
98% (Fig. 1k, l) [42, 63, 87, 93, 113, 117–123].
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8940
Fig. 1  a Forest plot for CT scan sensitivity and specificity. b Punnett square for CT
scan sensitivity and specificity (based on prevalence of 70%). c Forest plot for low
dose CT scan sensitivity and specificity. d Punnett square for low dose CT scan sen-
sitivity and specificity (based on prevalence of 70%). e Forest plot for non-contrast
CT scan sensitivity and specificity. f Punnett square for non-contrast CT scan sensi-
tivity and specificity (based on prevalence of 70%). g Forest plot for MRI sensitiv-
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Surgical Endoscopy (2023) 37:8933–8990
ity and specificity. h Punnett square for MRI sensitivity and specificity (based on
prevalence of 70%). i Forest plot for ultrasound sensitivity and specificity. j Punnett
square for ultrasound sensitivity and specificity (based on prevalence of 70%). k For-
est plot for POCUS sensitivity and specificity. l Punnett square for POCUS sensitiv-
ity and specificity (based on prevalence of 70%). TP true positive, FP false positive,
FN false negative, TN true negative
Surgical Endoscopy (2023) 37:8933–8990 8941

Fig. 1  (continued)

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8942 Surgical Endoscopy (2023) 37:8933–8990

Fig. 1  (continued)

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Surgical Endoscopy (2023) 37:8933–8990
Fig. 1  (continued)
Pediatric
A total of 57 studies met inclusion criteria for KQ1 in the
pediatric subpopulation composed of 1 RCTs and 56 obser-
vational studies. Of the studies included the one RCT was
determined to be low risk of bias (100%) (Table 2). Of the
observational studies, 12 (21%) were determined to have low
risk of bias, 37 had high (66%) and the remaining 7 (13%)
had an unclear risk of bias (Table 3).
8943
For pediatric patients, rate of needing additional imag-
ing was 0.3% (Range 0–1.6%) for CT scan, 3.6% (No range
1 study) for low dose CT scan, 17.3% (Range 0–49.4%)
for ultrasound, 64.2% (Range 45–83.3%) for POCUS, and
0.7% (Range 0–3.4%) for MRI (Table 4). Rate of negative
diagnostic laparoscopy following imaging was 6.7% (Range
1.2–15%) for CT scan, 0% (No range 1 study) for low dose
CT scan, 9.6% (Range 0–35.5%) for ultrasound, 3.2%
(Range 0–12.9%) for POCUS, and 8.4% (Range 0–23.3%)
for MRI (Table 5). Rate of nondiagnostic finding on imaging
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8944
Table 2  Risk of bias for the RCTs included under KQ1 as assessed by
a Cochrane Risk of Bias tool
was 5.5% (Range 0–13.3%) for CT scan, not available for
low dose CT scan, 35.7% (Range 0–80.8%) for ultrasound,
43.6% (Range 17.5–69.3%) for POCUS, and 13.9% (Range
0–62.5%) for MRI (Table 6) [116, 124–177].
Key Question 2 (KQ 2): Should adult and pediatric
patients with acute, uncomplicated appendicitis
be managed nonoperativelywith antibiotics
versus appendectomy?
Adults
A total of 18 studies met inclusion criteria for KQ2 in the
adult subpopulation composed of 6 RCTs and 12 observa-
tional studies. Of the six RCTs, three (50%) were determined
to have a low risk of bias, one was determined to have a
high risk of bias (17%), and the remaining two (33%) had
an unclear risk of bias (Table 7). Of the observational stud-
ies, 2 (17%) were determined to have low risk of bias, 8 had
high (67%) and the remaining 2 (17%) had an unclear risk
of bias (Table 8).
Three RCTs reported on abscess formation compar-
ing antibiotics (201 patients) versus appendectomy (198
patients). These studies demonstrated no statistical differ-
ence in abscess formation. Five cohort studies reported on
abscess formation which also showed no statistical differ-
ence (Fig. 2a) [124, 178–185].
One RCT reported on cost comparing antibiotics (91
patients) versus appendectomy (89 patients) which demon-
strated lower cost with antibiotics (SMD − 1.01, 95% CI
− 1.32, − 0.70). Six cohort studies reported on cost which
also showed lower cost with antibiotics (SMD − 0.41,
95% CI − 0.68, − 0.14) with high heterogeneity ­(I2 = 100)
(Fig. 2b) [44, 179, 181, 186–189].
One RCT reported on drain placement comparing anti-
biotics (676 patients) versus appendectomy (656 patients)
which demonstrated higher rates of drain placement in anti-
biotics (OR 4.02, 95% CI 1.66, 9.71). Two cohort studies
reported on drain placement which showed no statistical
difference (Fig. 2c) [179, 182, 190].
Five RCTs reported on length of hospital stay com-
paring antibiotics (852 patients) versus appendectomy
(839 patients). These studies demonstrated no statistical
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Surgical Endoscopy (2023) 37:8933–8990
difference in length of hospital stay. Eight cohort studies
reported on length of hospital stay which also showed no
statistical difference (Fig. 2d) [179, 180, 182, 184, 187–194].
One RCT reported on mortality comparing antibiotics
(676 patients) versus appendectomy (676 patients). This
study demonstrated zero mortality for either. Six cohort
studies reported on mortality which demonstrated higher
mortality in antibiotics (OR 37.19, 95% CI 19.37, 71.38)
with high heterogeneity (­ I2 = 97) (Fig. 2e) [178, 179, 182,
185, 188, 190, 191].
One RCT reported on need for new course of antibiotics
comparing antibiotics (16 patients) versus appendectomy
(14 patients). This study demonstrated no statistical differ-
ence in need for new course of antibiotics. One cohort study
reported on need for new course of antibiotics which showed
lower odds of needing a new course of antibiotics following
antibiotics (OR 0.30, 95% CI 0.21, 0.42) (Fig. 2f) [179, 183].
One RCT reported on quality of life comparing antibiot-
ics (683 patients) versus appendectomy (664 patients). This
study demonstrated no statistical difference in quality of life.
No cohort studies reported on quality of life (Fig. 2g) [190].
Two RCTs reported on readmission comparing antibiotics
(726 patients) versus appendectomy (702 patients). These
studies demonstrated higher odds of readmission following
antibiotics (OR 6.10, 95% CI 4.21, 8.84) with low hetero-
geneity ­(I2 = 0). Six cohort studies reported on readmis-
sion which showed no statistical difference in readmission
(Fig. 2h) [179, 181, 182, 185, 188–190, 195].
Four RCTs reported on reoperation at any time point
comparing antibiotics (191 patients) versus appendectomy
(190 patients). These studies demonstrated higher odds of
reoperation at any time point following antibiotics (OR
20.09, 95% CI 5.39, 74.90) with low heterogeneity (­ I2 = 0).
Four cohort studies reported on reoperation at any time point
which showed higher odds of reoperation following antibiot-
ics (OR 26.91, 95% CI 4.33, 167.37) with high heterogeneity
­(I2 = 57) (Fig. 2i) [180, 182, 183, 189, 191–193, 195].
One RCT reported on reoperation within 30 days com-
paring antibiotics (19 patients) versus appendectomy (22
patients). This study no statistical difference in reoperation
within 30 days. Three cohort studies reported on reoperation
within 30 days which showed higher odds of reoperation fol-
lowing antibiotics (OR 11.37, 95% CI 1.66, 77.74) with high
heterogeneity ­(I2 = 52) (Fig. 2j) [182, 191–193].
Two RCTs reported on reoperation between 30 days and
1 year comparing antibiotics (156 patients) versus appen-
dectomy (154 patients). These studies demonstrated higher
odds of reoperation between 30 days and 1 year following
antibiotics (OR 30.37, 95% CI 5.77, 159.77) with low het-
erogeneity ­(I2 = 0). Two cohort studies reported on reop-
eration between 30 days and 1 year which showed higher
odds of reoperation following antibiotics (OR 74.69, 95%
Surgical Endoscopy (2023) 37:8933–8990 8945

Table 3  Risk of bias for the

observational studies included
under KQ1 as assessed by a
modified Newcastle Ottawa
Scale

CI 10.18, 548.13) with low heterogeneity (­ I2 = 0) (Fig. 2k)
[180, 182, 189, 193].
Four RCTs reported on return to work/school compar-
ing antibiotics (708 patients) versus appendectomy (703
patients). These studies demonstrated less time to return
to work/school following antibiotics (SMD − 1.78, 95%
CI − 3.48, − 0.08) with low heterogeneity ­(I2 = 0). One
cohort study reported on return to work/school which
also showed less time to return to work/school following

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8946 Surgical Endoscopy (2023) 37:8933–8990

Table 3  (continued)

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Surgical Endoscopy (2023) 37:8933–8990 8947

Table 3  (continued)

Table 4  Rate of needing for additional imaging following initial Table 6  Rate of nondiagnostic finding following initial imaging
imaging
Outcome variable CT % Low US % POCUS % MRI %
Outcome CT % Low dose US % POCUS % MRI % dose CT
variable CT % %

N studies 5 1 25 2 8 N studies 7 0 30 4 14
Range (lower) 0.0% 3.6% 0.0% 45.0% 0.0% Range (lower) 0.0% NE 0.0% 17.5% 0.0%
Range (upper) 1.6% 3.6% 49.4% 83.3% 3.4% Range (upper) 13.3% NE 80.8% 69.3% 62.5%
Mean 0.3% 3.6% 17.3% 64.2% 0.7% Mean 5.5% NE 35.7% 43.6% 13.9%
LCI − 0.3% NE 11.8% 26.6% − 0.1% LCI 1.5% NE 27.3% 19.5% 3.7%
UCI 0.9% NE 22.7% 101.7% 1.6% UCI 9.4% NE 44.1% 67.6% 24.2%

Table 5  Rate of negative diagnostic laparoscopy following false posi-

tive initial imaging Table 7  Risk of bias for the RCTs included under KQ2 as assessed by
a Cochrane Risk of Bias tool
Outcome CT % Low dose US % POCUS % MRI %
variable CT %

N studies 6 1 30 4 14
Range (lower) 1.2% 0.0% 0.0% 0.0% 0.0%
Range (upper) 15.0% 0.0% 35.5% 12.9% 23.3%
Mean 6.7% 0.0% 9.6% 3.2% 8.4%
LCI 2.9% NE 6.3% − 3.1% 5.2%
UCI 10.4% NE 12.9% 9.5% 11.7%

antibiotics (SMD − 8.64, 95% CI − 10.65, − 6.63) (Fig. 2l)

[184, 189–192].

Pediatric
A total of 17 studies met inclusion criteria for KQ2 in the
pediatric subpopulation composed of 4 RCTs and 13 obser-
vational studies. Of the four RCTs, two (50%) were deter-
mined to have a low risk of bias, one was determined to have
a high risk of bias (25%), and the remaining one (25%) had
an unclear risk of bias (Table 9). Of the observational stud-
ies, 2 (15%) were determined to have low risk of bias, 8 had
high (62%) and the remaining 3 (23%) had an unclear risk
of bias (Table 10).
No RCTs reported on abscess formation comparing anti-
biotics versus appendectomy. Four cohort studies reported

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8948
Table 8  Risk of bias for the observational studies included under
KQ2 as assessed by a modified Newcastle Ottawa Scale
on abscess formation which showed no statistically signifi-
cant difference (Fig. 3a) [196–199].
One RCT reported on cost comparing antibiotics (24
patients) versus appendectomy (26 patients). This study
demonstrated no statistically significant difference in cost.
Three cohort studies reported on cost also which showed
no statistically significant difference in cost (Fig. 3b) [187,
200–202].
No RCTs reported on need for drain placement compar-
ing antibiotics versus appendectomy. Two cohort studies
reported on need for drain placement which showed no sta-
tistically significant difference (Fig. 3c) [198, 199].
No RCTs reported on ICU admission comparing antibiot-
ics versus appendectomy. One cohort study reported on ICU
admission which showed no statistically significant differ-
ence (Fig. 3d) [197].
No RCTs reported on length of hospital stay comparing
antibiotics versus appendectomy. Six cohort study reported
on length of hospital stay which showed no statistically sig-
nificant difference (Fig. 3e) [187, 196, 200, 201, 203, 204].
One RCT reported on mortality comparing antibiotics
versus appendectomy. This study had no mortality in either
treatment arm. No cohort studies reported on mortality
(Fig. 3f) [205].
One RCT reported on need for new course of antibiotics
comparing antibiotics (27 patients) versus appendectomy
(27 patients). This study demonstrated no statistically sig-
nificant difference in need for new course of antibiotics. Two
cohort studies reported on need for new course of antibiotics
which showed no statistically significant difference (Fig. 3g)
[196, 197, 205].
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Surgical Endoscopy (2023) 37:8933–8990
No RCTs reported on quality of life comparing antibiotics
versus appendectomy. Two cohort studies reported on qual-
ity of life which showed no statistically significant difference
(Fig. 3h) [199, 201].
Four RCTs reported on readmission comparing antibiot-
ics (95 patients) versus appendectomy (98 patients). These
studies demonstrated higher odds of readmission following
antibiotics (OR 10.57, 95% CI 2.30, 48.69) with moderate
heterogeneity ­(I2 = 36). Nine cohort studies reported on
readmission which also showed higher odds of readmission
following antibiotics (OR 5.49, 95% CI 2.60, 11.56) with
high heterogeneity ­(I2 = 79) (Fig. 3i) [14, 197–199, 201–203,
205–209].
Two RCTs reported on need for reoperation at any time
point comparing antibiotics (48 patients) versus appendec-
tomy (52 patients). These studies demonstrated higher odds
of reoperation at any time point following antibiotics (OR
38.31, 95% CI 4.90, 299.69) with low heterogeneity ­(I2 = 0).
Six cohort studies reported on need for reoperation at any
time point which also showed higher odds of reoperation
at any time point following antibiotics (OR 54.37, 95%
CI 25.13, 117.66) with low heterogeneity ­(I2 = 0) (Fig. 3j)
[196–199, 201, 202, 209, 210].
Two RCTs reported on reoperation within 30 days com-
paring antibiotics (48 patients) versus appendectomy (52
patients). These studies demonstrated no statistically signifi-
cant difference. Seven cohort studies reported on reoperation
within 30 days which showed higher odds of reoperation
within 30 days following antibiotics (OR 11.15, 95% CI
2.81, 44.25) with moderate heterogeneity ­(I2 = 36) (Fig. 3k)
[196–199, 201, 202, 204, 209, 210].
Two RCTs reported on reoperation between 30 days and
1 year comparing antibiotics (48 patients) versus appen-
dectomy (52 patients). These studies demonstrated higher
odds of reoperation between 30 days and 1 year following
antibiotics (OR 22.71, 95% CI 2.87, 179.78) with low het-
erogeneity ­(I2 = 0). Six cohort studies reported on reopera-
tion between 30 days and 1 year which also showed higher
odds of reoperation following antibiotics (OR 31.67, 95%
CI 14.17, 70.82) with low heterogeneity ­(I2 = 0) (Fig. 3l)
[196–199, 201, 202, 209, 210].
One RCT reported on time to return to work/school com-
paring antibiotics (20 patients) versus appendectomy (19
patients). This study demonstrated no statistically significant
difference. Four cohort studies reported on time to return
to work/school which showed less time to return to work/
school following antibiotics (SMD − 1.98, 95% CI − 3.15,
− 0.81) with high heterogeneity (­ I2 = 65) (Fig. 3m) [14, 203,
207, 208, 210].
Surgical Endoscopy (2023) 37:8933–8990 8949

Fig. 2  a Forest plot for abscess formation. b Forest plot for cost. c Forest plot for reoperation (any time point). j Forest plot for reopera-
Forest plot for drain placement. d Forest plot for length of hospital tion (< 30 days). k Forest plot for reoperation (30 days–1 year). l For-
stay. e Forest plot for mortality. f Forest plot for new course of antibi- est plot for return to work/school
otics. g Forest plot for quality of life. h Forest plot for readmission. i

13
8950 Surgical Endoscopy (2023) 37:8933–8990

Fig. 2  (continued)

13
Surgical Endoscopy (2023) 37:8933–8990 8951

Fig. 2  (continued)

13
8952
Fig. 2  (continued)
Key Question 3 (KQ 3): In adult and pediatric
patients with complicated appendicitis, should
operative management versusnonoperative
management be used?
Adults
A total of 11 studies met inclusion criteria for KQ3 in the
adult subpopulation composed of 1 RCTs and 10 obser-
vational studies. The one RCT was determined to have a
low risk of bias (Table 11). Of the observational studies, 1
(10%) were determined to have low risk of bias, 6 had high
(60%) and the remaining 3 (30%) had an unclear risk of bias
(Table 12).
One RCT reported on abscess formation comparing anti-
biotics (30 patients) versus appendectomy (30 patients). This
study demonstrated no statistically significant difference.
Eight cohort studies reported on abscess formation which
13
Surgical Endoscopy (2023) 37:8933–8990
also showed no statistically significant difference (Fig. 4a)
[211–219].
One cohort study reported on cost comparing antibiotics
and appendectomy which showed no statistically significant
difference (Fig. 4b) [214].
One RCT reported on need for drain placement com-
paring antibiotics (30 patients) versus appendectomy (30
patients). This study demonstrated no statistically significant
difference. Four cohort studies reported on need for drain
placement which showed higher odds of drain placement fol-
lowing antibiotics (OR 16.28, 95% CI 4.21, 62.98) with high
heterogeneity ­(I2 = 75) (Fig. 4c) [213, 215, 216, 219, 220].
One cohort study reported on ICU admission comparing
antibiotics versus appendectomy which showed lower odds
of ICU admission following antibiotics (OR 0.16, 95% CI
0.03, 0.80) (Fig. 4d) [220].
One RCT reported on hospital LOS comparing antibiot-
ics (30 patients) versus appendectomy (30 patients). This
Surgical Endoscopy (2023) 37:8933–8990
Table 9  Risk of bias for the RCTs included under KQ2 as assessed by
a Cochrane Risk of Bias tool
Table 10  Risk of bias for the observational studies included under
KQ2 as assessed by a modified Newcastle Ottawa Scale
study demonstrated longer hospital lengths of stay following
antibiotics (SMD 1.12, 95% CI 0.65, 1.59). Five cohort stud-
ies reported on hospital LOS which showed no statistically
significant difference (Fig. 4e) [213–215, 217, 218, 220].
One RCT reported on mortality comparing antibiotics
(30 patients) versus appendectomy (30 patients). This study
demonstrated no statistically significant difference. Three
cohort studies reported on mortality which also showed no
statistically significant difference (Fig. 4f) [214, 215, 217,
221].
One RCT reported on readmission comparing antibiot-
ics (30 patients) versus appendectomy (30 patients). This
study demonstrated higher odds of readmission following
antibiotics (OR 10.55, 95% CI 1.23, 90.66). Eight cohort
8953
studies reported on readmission which also showed higher
odds of readmission following antibiotics (OR 3.22, 95% CI
1.30, 8.02) with high heterogeneity ­(I2 = 80) (Fig. 4g) [211,
213–217, 219, 220, 222].
One RCT reported on reoperation at any time point com-
paring antibiotics (30 patients) versus appendectomy (30
patients). This study demonstrated higher odds of reopera-
tion at any time point following antibiotics (OR 29.00, 95%
CI 3.49, 241.13). Four cohort studies reported on reopera-
tion at any time point comparing antibiotics and appendec-
tomy which also showed higher odds of reoperation at any
time point following antibiotics (OR 47.46, 95% CI 12.94,
174.11) with low heterogeneity (­I2 = 0) (Fig. 4h) [212,
214–216, 219].
Pediatric
A total of 12 studies met inclusion criteria for KQ3 in the
pediatric subpopulation composed of 3 RCTs and 9 obser-
vational studies.
Of the three RCTs, one (33%) was determined to have a
low risk of bias, none were determined to have a high risk
of bias (0%), and the remaining two (67%) had an unclear
risk of bias (Table 13). Of the observational studies, 3
(33%) were determined to have low risk of bias, 4 had high
(44%) and the remaining 2 (22%) had an unclear risk of bias
(Table 14).
Two RCTs reported on abscess formation comparing
antibiotics (87 patients) versus appendectomy (84 patients).
These studies demonstrated higher odds of abscess forma-
tion following antibiotics (OR 2.23, 95% CI 1.10, 4.50) with
low heterogeneity ­(I2 = 0). Four cohort studies reported on
abscess formation comparing antibiotics and appendectomy
which showed no statistically significant difference (Fig. 5a)
[129, 223–227].
One RCT reported on cost comparing antibiotics (67
patients) versus appendectomy (64 patients). This study
demonstrated no statistically significant differences. One
cohort study reported on cost comparing antibiotics and
appendectomy which showed higher cost following antibi-
otics (SMD 6700.00, 95% CI 255.47, 13,144.53) (Fig. 5b)
[129, 224].
Two cohort studies reported on need for drain placement
comparing antibiotics (196 patients) versus appendectomy
(215 patients). These studies demonstrated higher odds of
drain placement following antibiotics (OR 5.94, 95% CI
1.50, 23.54) with high heterogeneity ­(I2 = 87) (Fig. 5c) [225,
228].
Two RCTs reported on length of hospital stay comparing
antibiotics (87 patients) versus appendectomy (84 patients).
These studies demonstrated no statistically significant
13
8954 Surgical Endoscopy (2023) 37:8933–8990

13
 Surgical Endoscopy (2023) 37:8933–8990 8955

◂ Fig. 3  a Forest plot for abscess formation. b Forest plot for cost. c Forest plot for drain placement. d Forest plot for ICU admission. e Forest
plot for length of hospital stay. f Forest plot for mortality. g Forest plot for new course of antibiotics. h Forest plot for quality of life. i For-
est plot for readmission. j Forest plot for reoperation (any time point). k Forest plot for reoperation (< 30 days). l Forest plot for reoperation
(30 days–1 year). m Forest plot for return to work/school

Fig. 3  (continued)

13
8956 Surgical Endoscopy (2023) 37:8933–8990

Fig. 3  (continued)

13
Surgical Endoscopy (2023) 37:8933–8990 8957

Fig. 3  (continued)

13
8958
Table 11  Risk of bias for the RCTs included under KQ3 as assessed
by a Cochrane Risk of Bias Tool
Table 12  Risk of bias for the observational studies included under
KQ3 as assessed by a modified Newcastle Ottawa Scale
difference. Six cohort studies reported on abscess forma-
tion comparing antibiotics and appendectomy which showed
longer length of hospital stay following antibiotics (OR
2.94, 95% CI 1.71, 4.18) with high heterogeneity ­(I2 = 96)
(Fig. 5d) [129, 224, 225, 227–231].
One cohort study reported on need for new course of anti-
biotics comparing antibiotics (148 patients) versus appen-
dectomy (168 patients). This study demonstrated higher
odds for needing a new course of antibiotics following anti-
biotics (OR 2.42, 95% CI 1.01, 5.84) (Fig. 5e) [223].
One RCT reported on quality of life comparing antibiot-
ics (20 patients) versus appendectomy (20 patients). This
study demonstrated higher quality of life following antibiot-
ics (SMD − 2.88, 95% CI − 3.79, − 1.97). One cohort study
reported on quality of life which showed no statistically sig-
nificant difference (Fig. 5f) [226, 232].
One RCT reported on readmission comparing antibiot-
ics (67 patients) versus appendectomy (64 patients). This
13
Surgical Endoscopy (2023) 37:8933–8990
study demonstrated higher odds of readmission following
antibiotics (OR 5.39, 95% CI 1.89, 15.37). Six cohort stud-
ies reported on readmission which also showed higher odds
of readmission following antibiotics (OR 6.90 95% CI 1.27,
37.67) with high heterogeneity ­(I2 = 93) (Fig. 5g) [199, 224,
225, 228, 230, 233, 234].
One RCT reported on reoperation at any time point com-
paring antibiotics (20 patients) versus appendectomy (20
patients). This study demonstrated no statistically significant
difference. Three cohort studies reported on reoperation at
any time point which also showed no statistically significant
difference (Fig. 5h) [199, 223, 227, 234].
One RCT reported on time to return to work/school com-
paring antibiotics (67 patients) versus appendectomy (64
patients). This study demonstrated longer times to return to
work/school following antibiotics (SMD 5.60, 95% CI 2.82,
8.38) (Fig. 5i) [224].
Key Question 4 (KQ 4): In adult and pediatric
patients with uncomplicated appendicitis
undergoing appendectomy, do outcomes differ
based on early (< 12 h from diagnosis) versus late
(> 12 h from diagnosis) surgical intervention?
Adults
A total of 9 studies met inclusion criteria for KQ4 in the
adult subpopulation composed of all observational studies.
Of these, 3 (33%) were determined to have low risk of bias,
5 had high (55%) and the remaining 1 (11%) had an unclear
risk of bias (Table 15).
Eight cohort studies reported on abscess formation
which showed no statistically significant difference between
surgery within 12 h or after 12 h of diagnosis (Fig. 6a)
[235–242].
One cohort study reported on need for drain placement
which showed no statistically significant difference between
surgery within 12 h or after 12 h of diagnosis (Fig. 6b) [235].
One cohort study reported on length of hospital stay
which favored surgery within 12 h (SMD 0.59, 95% CI 0.17,
1.00) (Fig. 6c) [241].
Four cohort studies reported on need for readmission
which showed no statistically significant difference between
surgery within 12 h or after 12 h of diagnosis (Fig. 6d) [235,
236, 239, 242].
One cohort study reported on reoperation at any time
point which showed no statistically significant difference
between surgery within 12 h or after 12 h of diagnosis
(Fig. 6e) [241].
Surgical Endoscopy (2023) 37:8933–8990 8959

Fig. 4  a Forest plot for abscess formation. b Forest plot for cost. c Forest plot for drain placement. d Forest plot for ICU admission. e Forest plot
for length of hospital stay. f Forest plot for mortality. g Forest plot for readmission. h Forest plot for reoperation (any time point)

13
8960 Surgical Endoscopy (2023) 37:8933–8990

Fig. 4  (continued)

13
Surgical Endoscopy (2023) 37:8933–8990 8961

Fig. 4  (continued)

Pediatric
Table 13  Risk of bias for the RCTs included under KQ3 as assessed
by a Cochrane Risk of Bias tool
A total of 3 studies met inclusion criteria for KQ4 in the
pediatric subpopulation composed of all observational stud-
ies. Of these, 1 (33%) were determined to have low risk of
bias, none had high (0%) and the remaining 2 (67%) had an
unclear risk of bias (Table 16).
Two cohort studies reported on abscess formation com-
paring surgery within 12 h (1871 patients) or after 12 h
(1133 patients) of diagnosis which no statistical difference
if surgery was performed before or after 12 h of diagnosis
(Fig. 7a) [243, 244].

13
8962
Table 14  Risk of bias for the observational studies included under
KQ3 as assessed by a modified Newcastle Ottawa Scale
One cohort study reported on readmission comparing sur-
gery within 12 h (1653 patients) or after 12 h (1103 patients)
of diagnosis which showed lower odds of abscess formation
if surgery was performed after 12 h of diagnosis (OR 0.66,
95% CI 0.45, 0.96) (Fig. 7b) [243].
One cohort study reported on reoperation at any time
point comparing surgery within 12 h (1653 patients) or after
12 h (1103 patients) of diagnosis which showed no statisti-
cally significant difference (Fig. 7c) [243].
Key Question 5 (KQ 5): In adult and pediatric
patients undergoing appendectomy for perforated
appendicitis, should suction and lavage
versus suction alone be used?
Adults
A total of 6 studies met inclusion criteria for KQ5 in the
adult subpopulation composed of 4 RCTs and 2 observa-
tional studies. Of the four RCTs, three (75%) was determined
to have a low risk of bias, one was determined to have a high
13
Surgical Endoscopy (2023) 37:8933–8990
risk of bias (25%), and none (0%) had an unclear risk of
bias (Table 17). Of the observational studies, 1 (50%) was
determined to have low risk of bias and one had high (50%)
risk of bias (Table 18).
Four RCTs reported on abscess formation comparing
suction and lavage (324 patients) versus suction alone (389
patients). These studies demonstrated no statistically sig-
nificant difference in abscess formation. Two cohort studies
reported on abscess formation which again showed no sta-
tistically significant difference (Fig. 8a) [245–250].
Three RCTs reported on need for drain placement com-
paring suction and lavage (194 patients) versus suction alone
(259 patients). These studies demonstrated no statistically
significant difference in abscess formation (Fig. 8b) [246,
248, 249].
Two RCTs reported on length of hospital stay comparing
suction and lavage (242 patients) versus suction alone (304
patients). These studies did not demonstrate a statistically
significant difference (Fig. 8c) [246, 250].
One RCT reported on mortality comparing suction and
lavage (112 patients) versus suction alone (174 patients).
This study demonstrated no statistically significant differ-
ence in mortality (Fig. 8d) [246].
Two RCTs reported on readmission comparing suction
and lavage (152 patients) versus suction alone (215 patients).
These studies demonstrated no statistically significant dif-
ference in readmission (Fig. 8e) [246, 249].
Three RCTs reported on reoperation at any time point
comparing suction and lavage (194 patients) versus suction
alone (259 patients). These studies demonstrated no statis-
tically significant difference in abscess formation (Fig. 8f)
[246, 248, 249].
Pediatric
A total of 5 studies met inclusion criteria for KQ5 in the
pediatric subpopulation composed of 3 RCTs and 2 obser-
vational studies. Of the three RCTs, all three (100%) was
determined to have a low risk of bias (Table 19). Of the
observational studies both (100%) had an unclear risk of
bias (Table 20).
Surgical Endoscopy (2023) 37:8933–8990 8963

Fig. 5  a Forest plot for abscess formation. b Forest plot for cost. c ity of life. g Forest plot for readmission. h Forest plot for reoperation
Forest plot for drain placement. d Forest plot for length of hospital (any time point). i Forest plot for return to work/school
stay. e Forest plot for new course of antibiotics. f Forest plot for qual-

13
8964 Surgical Endoscopy (2023) 37:8933–8990

Fig. 5  (continued)

13
Surgical Endoscopy (2023) 37:8933–8990
Fig. 5  (continued)
Three RCTs reported on abscess formation comparing
suction and lavage (204 patients) versus suction alone (202
patients). These studies demonstrated no statistically sig-
nificant difference in abscess formation. Two cohort stud-
ies reported on abscess formation which again showed no
statistically significant difference (Fig. 9a) [23, 251–254].
Two RCTs reported on need for drain placement compar-
ing suction and lavage (160 patients) versus suction alone
(160 patients). These studies demonstrated no statistically
significant difference in abscess formation (Fig. 9b) [23,
251].
Two RCTs reported on length of hospital stay comparing
suction and lavage (160 patients) versus suction alone (160
patients). These studies demonstrated no statistically sig-
nificant difference in abscess formation (Fig. 9c) [23, 251].
Three RCTs reported on mortality comparing suction and
lavage (642 patients) versus suction alone (363 patients),
none of which had any mortalities (Fig. 9d) [23, 252, 254].
8965
Two RCTs reported on readmission comparing suction
and lavage (160 patients) versus suction alone (160 patients).
These studies demonstrated no statistically significant dif-
ference in readmission (Fig. 9e) [23, 251].
Four RCTs reported on reoperation at any time point
comparing suction and lavage (692 patients) versus suction
alone (413 patients). These studies demonstrated no statisti-
cally significant difference in reoperation at any time point
(Fig. 9f) [23, 251, 252, 254].
Key Question 6 (KQ 6): In adult and pediatric
patients undergoing appendectomy for complicated
appendicitis, should routine drain placement
versus no routine drain placement be used?
Adults
A total of 6 studies met inclusion criteria for KQ6 in the
adult subpopulation composed of all observational studies.
13
8966
Table 15  Risk of bias for the observational studies included under
KQ4 as assessed by a modified Newcastle Ottawa Scale
Of these, 1 (17%) was determined to have low risk of bias,
4 had high (67%) and the remaining 1 (17%) had an unclear
risk of bias (Table 21).
Six cohort studies reported on abscess formation compar-
ing drain placement (583 patients) and no drain placement
(1144 patients). These studies demonstrated no statisti-
cally significant difference in abscess formation (Fig. 10a)
[255–260].
Three cohort studies reported on drain placement com-
paring drain placement in initial operation (116 patients) and
no drain placement in initial operation (360 patients). These
studies demonstrated no statistically significant difference
in subsequent drain placement (Fig. 10b) [257, 259, 260].
Two cohort studies reported on need for new course of
antibiotics comparing drain placement (72 patients) and no
drain placement (255 patients). These studies demonstrated
no statistically significant difference in need for new course
of antibiotics (Fig. 10c) [257, 260].
Two cohort studies reported on readmission comparing
drain placement (337 patients) and no drain placement (654
patients). These studies demonstrated no statistically signifi-
cant difference in abscess formation (Fig. 10d) [256, 258].
One cohort study reported on reoperation at any time
point comparing drain placement (56 patients) and no drain
placement (169 patients). This study demonstrated no statis-
tically significant difference in abscess formation (Fig. 10e)
[259]. Two cohort studies reported on length of stay com-
paring drain placement (59 patients) and no drain place-
ment (191 patients). These studies did not demonstrate a
13
Surgical Endoscopy (2023) 37:8933–8990
statistically significant difference in length of stay (Fig. 10f)
[257, 260].
Pediatric
A total of 3 studies met inclusion criteria for KQ6 in the
pediatric subpopulation composed of all observational stud-
ies. Of these, two (67%) were determined to have a low risk
of bias and one was determined to have a high risk of bias
(Table 22).
Three cohort studies reported on abscess formation com-
paring drain placement (803 patients) and no drain place-
ment (1530 patients). These studies demonstrated no statisti-
cally significant difference in abscess formation (Fig. 11a)
[261–263].
One cohort study reported on subsequent drain placement
comparing initial drain placement (24 patients) and no ini-
tial drain placement (109 patients). This study demonstrated
no statistically significant difference in need for subsequent
drain placement (Fig. 11b) [261].
Two cohort studies reported on readmission comparing
drain placement (728 patients) and no drain placement (1413
patients). These studies demonstrated no statistically signifi-
cant difference in readmission (Fig. 11c) [261, 263].
Two cohort studies reported on reoperation at any time
point comparing drain placement (728 patients) and no drain
placement (1413 patients). These studies demonstrated
higher risk of reoperation at any time point in patients who
had drains placed (RR 2.04, 95% CI 1.06, 3.94) with low
heterogeneity ­(I2 = 15) (Fig. 11d) [261, 263].
Key Question 7 (KQ 7): Should adult and pediatric
patients who undergo appendectomy
for complicated appendicitis be given postoperative
antibiotics for short term vs. long term?
Adults
A total of 8 studies met inclusion criteria for KQ7 in the
adult subpopulation composed of 1 RCTs and 7 observa-
tional studies.
The one RCT (100%) had an unclear risk of bias
(Table 23). Of the observational studies, 3 (43%) were deter-
mined to have low risk of bias and 4 had high (57%) risk of
bias (Table 24).
One RCT reported on abscess formation comparing
short-term postoperative antibiotics (39 patients) versus
long-term postoperative antibiotics (41 patients). This study
demonstrated no statistically significant difference in abscess
Surgical Endoscopy (2023) 37:8933–8990 8967

Fig. 6  a Forest plot for abscess formation. b Forest plot for drain placement. c Forest plot for length of hospital stay. d Forest plot for readmis-
sion. e Forest plot for reoperation (any time point)

13
8968 Surgical Endoscopy (2023) 37:8933–8990

Table 16  Risk of bias for the observational studies included under Table 17  Risk of bias for the RCTs included under KQ5 as assessed
KQ4 as assessed by a modified Newcastle Ottawa Scale by a Cochrane Risk of Bias tool

formation. Six cohort studies reported on abscess formation

which also showed no statistically significant difference in Table 18  Risk of bias for the observational studies included under
abscess formation (Fig. 12a) [96, 264–269]. KQ5 as assessed by a modified Newcastle Ottawa Scale
Two cohort studies reported on risk of contracting
Clostridium difficile comparing short-term postoperative
antibiotics (235 patients) versus long-term postoperative
antibiotics (401 patients). These studies demonstrated no
statistically significant difference in contracting Clostridium
difficile (Fig. 12b) [266, 270].
One RCT reported on drain placement comparing short-
term postoperative antibiotics (39 patients) versus long-
term postoperative antibiotics (41 patients). This study

Fig. 7  a Forest plot for abscess formation. b Forest plot for readmission. c Forest plot for reoperation (any time point)

13
Surgical Endoscopy (2023) 37:8933–8990 8969

Fig. 8  a Forest plot for abscess formation. b Forest plot for drain placement. c Forest plot for length of hospital stay. d. Forest plot for mortality.
e Forest plot for readmission. f Forest plot for reoperation (any time point)

13
8970
Table 19  Risk of bias for the RCTs included under KQ5 as assessed
by a Cochrane Risk of Bias tool
Table 20  Risk of bias for the observational studies included under
KQ5 as assessed by a modified Newcastle Ottawa Scale
demonstrated no statistically significant difference in drain
placement (Fig. 12c) [268].
One RCT reported on length of hospital stay compar-
ing short-term postoperative antibiotics (39 patients) versus
long-term postoperative antibiotics (41 patients). This study
demonstrated shorter length of hospital stays in patients
receiving short term hospital stays (SMD − 0.90, 95% CI
− 1.65, − 0.15). One cohort study reported on length of hos-
pital stay which showed no statistically significant difference
(Fig. 12d) [265, 268].
One RCT reported on need for new course of antibiotics
comparing short-term postoperative antibiotics (39 patients)
versus long-term postoperative antibiotics (41 patients). This
study demonstrated no statistically significant difference in
need for new course of antibiotics (Fig. 12e) [268].
One RCT reported on readmission comparing short-term
postoperative antibiotics (39 patients) versus long-term post-
operative antibiotics (41 patients). This study demonstrated
no statistically significant difference in readmission. Six
13
Surgical Endoscopy (2023) 37:8933–8990
Fig. 9  a Forest plot for abscess formation. b Forest plot for drain ◂
placement. c Forest plot for length of hospital stay. d Forest plot for
mortality. e Forest plot for readmission. f Forest plot for reoperation
(any time point)
cohort studies reported on readmission which showed no
statistically significant difference (Fig. 12f) [96, 264–269].
Two cohort studies reported on reoperation at any time
point comparing short-term postoperative antibiotics (231
patients) versus long-term postoperative antibiotics (654
patients). These studies demonstrated no statistically sig-
nificant difference in reoperation at any time point (Fig. 12g)
[264, 269].
One RCT and one cohort study reported on total com-
plications comparing short-term postoperative antibiotics
(114 patients) versus long-term postoperative antibiotics
(232 patients). These studies demonstrated no statistically
significant difference in total complications (Fig. 12h) [268,
269].
Pediatric
A total of 8 studies met inclusion criteria for KQ7 in the
pediatric subpopulation composed of 2 RCTs and 6 obser-
vational studies.
Of the two RCTs, one (50%) was determined to have a
low risk of bias and one (50%) had an unclear risk of bias
(Table 25). Of the observational studies, 2 (33%) were deter-
mined to have low risk of bias and 4 had high (67%) risk of
bias (Table 26).
Two RCTs reported on abscess formation comparing
short-term postoperative antibiotics (82 patients) versus
long-term postoperative antibiotics (386 patients). These
studies demonstrated no statistically significant difference
in abscess formation. Six cohort studies reported on abscess
formation which also showed no statistically significant dif-
ference in abscess formation (Fig. 13a) [271–278].
One RCT reported on contracting Clostridium diffi-
cile comparing short-term postoperative antibiotics (350
patients) versus long-term postoperative antibiotics (336
patients). This study demonstrated no statistically significant
difference in abscess formation. One cohort study reported
Surgical Endoscopy (2023) 37:8933–8990 8971

13
8972
on contracting Clostridium difficile which also showed no
statistically significant difference (Fig. 13b) [276, 278].
Three cohort studies need for drain placement compar-
ing short-term postoperative antibiotics (477 patients) ver-
sus long-term postoperative antibiotics (533 patients). These
studies demonstrated no statistically significant difference in
need for drain placement (Fig. 13c) [271, 274, 278].
Two RCTs reported on length of hospital stay comparing
short-term postoperative antibiotics (402 patients) versus
long-term postoperative antibiotics (386 patients). These
studies demonstrated no statistically significant difference
in LOS. Three cohort studies reported on length of hospital
stay which also did not demonstrate a statistically significant
difference (Fig. 13d) [271–273, 278].
One cohort study reported on need for new course of
antibiotics comparing short-term postoperative antibiotics
(97 patients) versus long-term postoperative antibiotics (82
patients). This study demonstrated no statistically significant
difference in need for new course of antibiotics (Fig. 13e)
[271].
One RCT reported on readmission comparing short-term
postoperative antibiotics (350 patients) versus long-term
postoperative antibiotics (336 patients). This study demon-
strated lower risk of readmission with short-term postopera-
tive antibiotics (RR 0.44, 95% CI 0.21, 0.91). Four cohort
studies reported on readmission which showed no statisti-
cally significant difference (Fig. 13f) [271, 274–276, 278].
One RCT reported on reoperation at any time point com-
paring short-term postoperative antibiotics (350 patients)
versus long-term postoperative antibiotics (336 patients).
This study demonstrated no statistically significant differ-
ence in reoperation at any time point. One cohort study
reported no reoperations at any time point for both short-
term and long-term postoperative antibiotic time courses
(Fig. 13g) [271, 276].
Key Question 8 (KQ 8): In asymptomatic adult
and pediatric patients with previous complicated
appendicitis treated nonoperatively, should
an interval appendectomy be performed
versus observation?
Adults
A total of 3 studies met inclusion criteria for KQ8 in the
adult subpopulation composed of 1 RCTs and 2 observa-
tional studies.
The one RCT was determined to have a low risk of bias
(100%) (Table 27). Of the observational studies, 1 had high
(50%) and one had an unclear (23%) risk of bias (Table 28).
One RCT reported on abscess formation comparing
interval appendectomy (25 patients) versus observation (27
13
Surgical Endoscopy (2023) 37:8933–8990
patients). This study demonstrated no statistically significant
difference in abscess formation (Fig. 14a) [279].
One RCT reported on need for drain placement compar-
ing interval appendectomy (25 patients) versus observation
(27 patients). This study demonstrated no statistically sig-
nificant difference in drain placement (Fig. 14b) [279].
One cohort study reported on length of hospital stay com-
paring interval appendectomy (9 patients) versus observa-
tion (26 patients). This study demonstrated no statistically
significant difference in length of hospital stay (Fig. 14c)
[221].
One cohort study reported on mortality comparing inter-
val appendectomy (64 patients) versus observation (106
patients). This study demonstrated no statistically significant
difference in mortality (Fig. 14d) [280].
One RCT reported on neoplasm formation comparing
interval appendectomy (25 patients) versus observation (27
patients). This study demonstrated no statistically significant
difference in neoplasm formation (Fig. 14e) [279].
One RCT reported on reoperation within 30 days of diag-
nosis comparing interval appendectomy (25 patients) versus
observation (27 patients). This study demonstrated no statis-
tically significant difference in reoperation within 30 days of
diagnosis. One cohort study reported on reoperation within
30 days of diagnosis which also showed no statistically sig-
nificant difference (Fig. 14f) [221, 279].
One RCT reported on reoperation between 30 days and
1 year following diagnosis comparing interval appendec-
tomy (25 patients) versus observation (27 patients). This
study demonstrated lower odds of reoperation between
30 days and 1 year for patient who received interval appen-
dectomy (OR 0.03, 95% CI 0.00, 0.43) (Fig. 14g) [279].
Pediatric
A total of 1 study met inclusion criteria for KQ8 in the
pediatric subpopulation composed of a single observational
Table 21  Risk of bias for the observational studies included under
KQ6 as assessed by a modified Newcastle Ottawa Scale
Surgical Endoscopy (2023) 37:8933–8990 8973

Fig. 10  a Forest plot for abscess formation. b Forest plot for drain placement. c Forest plot for new course of antibiotics. d Forest plot for read-
mission. e Forest plot for reoperation (any time point) f Forest plot for length of stay

13
8974 Surgical Endoscopy (2023) 37:8933–8990

Table 22  Risk of bias for the observational studies included under Table 23  Risk of bias for the RCTs included under KQ7 as assessed
KQ6 as assessed by a modified Newcastle Ottawa Scale by a Cochrane Risk of Bias tool

Fig. 11  a Forest plot for abscess formation. b Forest plot for drain placement. c Forest plot for readmission. d Forest plot for reoperation (any
time point)

13
Surgical Endoscopy (2023) 37:8933–8990
Table 24  Risk of bias for the observational studies included under
KQ7 as assessed by a modified Newcastle Ottawa Scale
study. The one observational study had an unclear (100%)
risk of bias (Table 29).
One observation study reported on readmission compar-
ing interval appendectomy (16 patients) versus observation
(29 patients). This study demonstrated lower odds of read-
mission for patients who received an interval appendectomy
(OR 0.03, 95% CI 0.00, 0.43) (Fig. 15) [229].
Discussion
Appendicitis is one of the most commonly treated surgi-
cal diagnoses worldwide. Despite its high incidence, con-
troversy exists regarding optimal diagnostic and treatment
pathways, as well as ideal postoperative management. The
goal of this systematic review was to summarize and assess
the published literature on the diagnosis and treatment of
appendicitis.
Appendicitis is one of the most commonly treated dis-
eases across the world. Despite this, controversy exists
regarding optimal diagnostic and treatment pathways, and
ideal postoperative management. Our systematic review syn-
thesized the available literature and produced evidence for
eight key questions regarding the diagnosis and management
of appendicitis in adults and children.
8975
Summary of evidence
KQ1: CT scan yielded the highest sensitivity (> 80%) and
specificity (> 93%) in the adult population compared to
other modalities, although high variability existed within
the pediatric population.
KQ2: In adults with uncomplicated appendicitis, when
nonoperative management was attempted, consisting of
antibiotic treatment rather than appendectomy, there was
six times higher odds of readmission and 20 times higher
odds of requiring an operation following initial treatment,
especially within the first year. On the other hand, for
patients where nonoperative treatment with antibiotics
was successful, adult patients were able to return to work/
school a median of 1.8 days sooner. Pediatric patients
with acute uncomplicated appendicitis experienced 38
times higher odds of requiring an operation at any time
point, and did not, on average, return to school faster.
KQ3: Adult patients treated nonoperatively with antibi-
otics for complicated appendicitis had 29 times higher
odds of requiring an additional surgery following initial
treatment and pediatric patients were twice as likely to
form a new abscess.
KQ4: There were no significant differences in outcomes
between performing an appendectomy within 12 h or
greater than 12 h after initial diagnosis of acute uncom-
plicated appendicitis.
KQ5: There were no significant differences in outcomes
of complicated appendicitis between suction only and
suction and lavage.
KQ6: In pediatric patients undergoing appendectomy for
complicated appendicitis, patients who had drains placed
at the time of operation were twice as likely to require
reoperation. In adults, no significant differences in out-
comes were found between patients who did or did not
have drains placed at the time of operation.
KQ7: There were no significant differences in outcomes
of complicated appendicitis when short- versus long-term
postoperative antibiotics were prescribed. Duration of
antibiotics for ‘short-term’ ranged from 1 to 7 days, while
‘long-term’ ranged from 4 to 21 days postoperatively.
KQ8: There were no significant differences in outcomes
in adult or pediatric patients with complicated appendi-
citis who did and did not undergo interval appendectomy
after treatment with antibiotics. Rates of neoplasm were
reported between 3 and 34% across all studies included.
13
8976 Surgical Endoscopy (2023) 37:8933–8990

Fig. 12  a Forest plot for abscess formation. b. Forest plot for con- antibiotics. f Forest plot for readmission. g Forest plot for reoperation
tracting Clostridium difficile. c Forest plot for drain placement. d (any time point). h Forest plot for total complications
Forest plot for length of hospital stay. e Forest plot for new course of

13
Surgical Endoscopy (2023) 37:8933–8990
Fig. 12  (continued)
Follow-up with patients following diagnosis ranged from
3 to 108 months.
Relationship to literature
The findings of this systematic review are consistent with
existing, systematic reviews addressing some of the ques-
tions similar to KQ 1–8. Bhangu et al. evaluated the data
8977
regarding treating patients with acute appendicitis with
antibiotics alone [281]. The rate of failure (25–30%) within
1 year reported by this group matches the data found in this
review [281]. A systematic review by Cameron et al. found
level 3–4 evidence that appendectomies performed within
24 h of admission in pediatric patients with acute appendici-
tis does not appear to be associated with increased perfora-
tion rates or other adverse events which is corroborated by
13
8978
Table 25  Risk of bias for the RCTs included under KQ7 as assessed
by a Cochrane Risk of Bias tool
Table 26  Risk of bias for the observational studies included under
KQ7 as assessed by a modified Newcastle Ottawa Scale
the data reported here (in both adult and pediatric patients)
[21]. The same study found level 4 evidence that time from
admission to appendectomy, as long as it is within 24 h, does
not increase hospital cost or LOS in pediatric patients [21].
The key question in this review compared appendectomy
within the first 12 h and greater than twelve hours and con-
cluded similarly. Finally, this review found duration of post-
operative antibiotics equivocal when comparing short-term
versus long-term postoperative antibiotics, which is consist-
ent with a previous systematic review conclusion exploring
antibiotic duration and incidence of intra-abdominal abscess
by van den Boom et al. [282].
Limitations
There are a number of limitations with this review. Most
of the included studies were found to have a moderate to
high degree risk of bias. For those that had a low risk of
bias, often a high level of heterogeneity existed within any
given key question. The most common weakness within the
RCT studies themselves was difficulty with randomization
and blinding patients and providers due to the drastically
13
Surgical Endoscopy (2023) 37:8933–8990
Fig. 13  a Forest plot for abscess formation. b Forest plot for contract- ▸
ing Clostridium difficile. c Forest plot for drain placement. d Forest
plot for length of hospital stay. e Forest plot for new course of antibi-
otics. f Forest plot for readmission. g Forest plot for reoperation (any
time point)
different treatment algorithms. For cohort studies, selection
bias was the most cited source of bias. These studies may
have suffered from confounding by indication as clinicians
may have favored non-operative management in patients that
are elderly or comorbid.
Additionally, it is important to acknowledge the inherent
limitations within a systematic review. One limitation is fail-
ure to capture all relevant studies based on selected search
term criteria. This was partially combatted with the use of
a librarian and hand searching relevant systematic reviews
and guidelines to ensure thoroughness. Finally, many of the
temporal variables/definitions (i.e., short-term versus long-
term postoperative antibiotics) were created a priori; how-
ever, various studies chose different time points by which to
anchor their study, which may introduce misclassification
bias. This limitation, amongst the others listed, may limit
generalizability of results reported in this study.
Relevance to clinical practice
Findings from this systematic review explored the debate
regarding operative versus nonoperative appendicitis treat-
ment; unfortunately, the answer is likely more nuanced
than expected. The rate of antibiotic only treatment failure
is high, with many patients progressing to operative man-
agement. However, this does not occur in the majority of
patients, and for those successfully treated with nonopera-
tive management, patients are able to return to work/school
faster. This highlights the importance of informed consent,
shared decision making, and both surgeon and patient risk
tolerance. What is essential is continued data analysis to
inform these conversations, so patients and families are pro-
vided with the most up-to-date and reliable information to
make their decision. The findings of this review are likely
not generalizable to all patient populations afflicted with
appendicitis, including pregnant patients (high nonopera-
tive risk rate), elderly/co-morbid patients (high operative
risk rate), in cases where administration of general anesthe-
sia alone can be higher risk, immunocompromised patients,
those with limited access to care, and others.
CT scan was the imaging modality with the highest sensi-
tivity and specificity in the adult population consistent with
current practice at most institutions, while which study to
choose for pediatric patients is less clear. Data revealed little
difference between performing an appendectomy within or
Surgical Endoscopy (2023) 37:8933–8990 8979

13
8980 Surgical Endoscopy (2023) 37:8933–8990

Fig. 13  (continued)

Table 27  Risk of bias for the RCTs included under KQ8 as assessed Table 28  Risk of bias for the observational studies included under
by a Cochrane Risk of Bias tool KQ8 as assessed by a modified Newcastle Ottawa Scale

13
Surgical Endoscopy (2023) 37:8933–8990 8981

Fig. 14  a Forest plot for abscess formation. b Forest plot for drain placement. c Forest plot for length of hospital stay. d Forest plot for mortality.
e Forest plot for neoplasm formation. f Forest plot for reoperation (< 30 days). g Forest plot for reoperation (30 days–1 year)

13
8982
Table 29  Risk of bias for the observational studies included under
KQ8 as assessed by a modified Newcastle Ottawa Scale
after 12 h of the diagnosis. While it is common practice to
perform an appendectomy shortly after presentation, even
overnight, this may not be necessary. However, we did not
have an upper limit on performing an appendectomy and
cannot comment on longer delays (i.e., substantially greater
than 12 h) and the safety of this. In complicated appendi-
citis, no significant differences were seen between suction
versus suction and lavage techniques. Routine drain place-
ment in children, but not adults, may lead to higher odds of
reoperation. This requires further investigation, but if true,
could challenge the practice of routinely placing drains for
perforated appendicitis. Findings showed there is likely no
benefit to ‘long-term’ antibiotic use (which ranged from 4 to
21 days postoperatively in the included studies) after appen-
dectomy for complicated appendicitis, in terms of abscess
formation. Finally, interval appendectomy should likely be
pursued in patients treated initially with antibiotics alone for
complicated appendicitis as this study found a sizeable neo-
plasm rate discovered on final pathology with special con-
sideration for the paucity of data concerning neoplasm rates
for pediatric patients who do not undergo interval appendec-
tomy and patients with a family history of colorectal/other
gastrointestinal malignancy.
Fig. 15  Forest plot for readmission
13
Surgical Endoscopy (2023) 37:8933–8990
Future research recommendations
High-quality data are essential to continue to inform this
discussion. Along the same lines, there is a paucity of qual-
ity-of-life measure-based studies, as well as cost-effective
analyses that could augment the clinical outcome data
presented in this review. The patient perspective on both
short- and long-term outcomes would be helpful in studies
going forward. These data are required to fully illustrate the
risk versus benefit profile in any of the decisions posed in
the key questions of this study. Large database studies may
provide some additional insight without the inherent chal-
lenges of randomized controlled trials [283, 284]. However,
these studies have additional sets of limitations which can
limit the interpretability and generalizability of conclusions
drawn from them.
Conclusion
Comparative evidence available from this review revealed
that diagnosis with CT scan is superior in adults, but is
less clear in children. Antibiotic treatment of appendicitis
alone is associated with high failure rates, but is a reason-
able option in select patients willing to accept the risk. This
study revealed timing of surgery, postoperative antibiotic
duration, and suctioning/lavage techniques were equivocal
in the investigated outcomes. High-quality data describing
quality of life and cost-effectiveness is necessary to charac-
terize superior diagnostic and treatment algorithms.
Surgical Endoscopy (2023) 37:8933–8990
Supplementary Information The online version contains supplemen-
tary material available at https://d​ oi.o​ rg/1​ 0.1​ 007/s​ 00464-0​ 23-1​ 0456-5.
Acknowledgements The authors would like to acknowledge Holly
Ann Burt for her contribution in performing the literature search for
all included studies. We would also like to acknowledge Sarah Colón
for her help in organizing the guidelines committee meetings and
communications.
Funding No external funding was used for this study. SAGES provided
partial salary support for the fellows, statistician, and librarian involved
in the project.
Declarations
Disclosures Ivy N. Haskins has received royalties or licenses from
UpToDate, Inc. Francisco Quinteros has received payments from
Medtronic, THD America, and Applied Medical. Bethany Slater has
received consulting fees from Hologic and Cook Medical. Ryan Lamm,
Sunjay S. Kumar, Amelia T. Collings, Ahmed Abou-Setta, Nisha
Narula, Pramod Nepal, Nader M. Hanna, Dimitrios I. Athanasiadis,
Stefan Scholz, Joel F. Bradley 3rd, Arianne T. Train, and Philip H.
Pucher have no conflicts of interest or financial ties to disclose.
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Authors and Affiliations

Ryan Lamm1 · Sunjay S. Kumar1,15 · Amelia T. Collings2 · Ivy N. Haskins3 · Ahmed Abou‑Setta4 · Nisha Narula5 ·
Pramod Nepal6 · Nader M. Hanna7 · Dimitrios I. Athanasiadis8 · Stefan Scholz9 · Joel F. Bradley 3rd10 ·
Arianne T. Train11 · Philip H. Pucher12 · Francisco Quinteros13 · Bethany Slater14

9
* Sunjay S. Kumar Division of General and Thoracic Pediatric Surgery,
Sunjay.kumar@jefferson.edu Department of Surgery, University of Pittsburgh, Pittsburgh,
PA, USA
1
Department of Surgery, Thomas Jefferson University 10
Division of General Surgery, Department of Surgery,
Hospital, Philadelphia, PA, USA
Vanderbilt University Medical Center, Nashville, TN, USA
2
Hiram C. Polk, Jr Department of Surgery, University 11
Department of Surgery, Penn Medicine Lancaster General
of Louisville, Louisville, KY, USA
Health, Lancaster, PA, USA
3
Department of Surgery, University of Nebraska Medical 12
Department of Surgery, Queen Alexandra Hospital,
Center, Omaha, NE, USA
Portsmouth Hospitals University NHS Trust, Portsmouth,
4
Centre for Healthcare Innovation, University of Manitoba, UK
Winnipeg, MB, Canada 13
Division of Colorectal Surgery, Advocate Lutheran General
5
Department of Surgery, Rutgers, New Jersey Medical School, Hospital, Park Ridge, IL, USA
Newark, NJ, USA 14
Division of Pediatric Surgery, University of Chicago
6
Division of Colon and Rectal Surgery, University of Illinois Medicine, Chicago, IL, USA
at Chicago, Chicago, IL, USA 15
Thomas Jefferson University, 1015 Walnut Street, 613 Curtis,
7
Department of Surgery, Queen’s University, Kingston, ON, Philadelphia, PA 19107, USA
Canada
8
Department of Surgery, Indiana University School
of Medicine, Indianapolis, IN, USA

13