Di Saverio et al. World Journal of Emergency Surgery
https://doi.org/10.1186/s13017-020-00306-3(2020) 15:27

REVIEW

Open Access

Diagnosis and treatment of acuteappendicitis: 2020 update of the WSES
Jerusalem guidelines
Salomone Di Saverio1,2*, Mauro Podda3, Belinda De Simone4, Marco Ceresoli5, Goran Augustin6, Alice Gori7,
Marja Boermeester8, Massimo Sartelli9, Federico Coccolini10, Antonio Tarasconi4, Nicola de’ Angelis11,
Dieter G. Weber12, Matti Tolonen13, Arianna Birindelli14, Walter Biffl15, Ernest E. Moore16, Michael Kelly17,
Kjetil Soreide18, Jeffry Kashuk19, Richard Ten Broek20, Carlos Augusto Gomes21, Michael Sugrue22,
Richard Justin Davies1, Dimitrios Damaskos23, Ari Leppäniemi13, Andrew Kirkpatrick24, Andrew B. Peitzman25,
Gustavo P. Fraga26, Ronald V. Maier27, Raul Coimbra28, Massimo Chiarugi10, Gabriele Sganga29, Adolfo Pisanu3,
Gian Luigi de’ Angelis30, Edward Tan20, Harry Van Goor20, Francesco Pata31, Isidoro Di Carlo32, Osvaldo Chiara33,
Andrey Litvin34, Fabio C. Campanile35, Boris Sakakushev36, Gia Tomadze37, Zaza Demetrashvili37, Rifat Latifi38,
Fakri Abu-Zidan39, Oreste Romeo40, Helmut Segovia-Lohse41, Gianluca Baiocchi42, David Costa43, Sandro Rizoli44,
Zsolt J. Balogh45, Cino Bendinelli45, Thomas Scalea46, Rao Ivatury47, George Velmahos48, Roland Andersson49,
Yoram Kluger50, Luca Ansaloni51 and Fausto Catena4

Abstract
Background and aims: Acute appendicitis (AA) is among the most common causes of acute abdominal pain.
Diagnosis of AA is still challenging and some controversies on its management are still present among different
settings and practice patterns worldwide.
In July 2015, the World Society of Emergency Surgery (WSES) organized in Jerusalem the first consensus conference
on the diagnosis and treatment of AA in adult patients with the intention of producing evidence-based guidelines.
An updated consensus conference took place in Nijemegen in June 2019 and the guidelines have now been
updated in order to provide evidence-based statements and recommendations in keeping with varying clinicalpractice: use of clinical scores and imaging in diagnosing AA, indications and timing for surgery, use of nonoperative management and antibiotics, laparoscopy and surgical techniques, intra-operative scoring, and perioperative antibiotic therapy.
(Continued on next page)* Correspondence: salo75@inwind.it; salomone.disaverio@gmail.com
1
Cambridge Colorectal Unit, Cambridge University Hospitals NHS Foundation
Trust, Addenbrooke’s Hospital, Cambridge Biomedical Campus, Hills Road,
Cambridge CB2 0QQ, UK
2
Department of General Surgery, University of Insubria, University Hospital of
Varese, ASST Sette Laghi, Regione Lombardia, Varese, Italy
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Di Saverio et al. World Journal of Emergency Surgery(2020) 15:27

Page 2 of 42(Continued from previous page)

Methods: This executive manuscript summarizes the WSES guidelines for the diagnosis and treatment of AA.
Literature search has been updated up to 2019 and statements and recommendations have been developed
according to the GRADE methodology. The statements were voted, eventually modified, and finally approved by
the participants to the consensus conference and by the board of co-authors, using a Delphi methodology forvoting whenever there was controversy on a statement or a recommendation. Several tables highlighting the
research topics and questions, search syntaxes, and the statements and the WSES evidence-based
recommendations are provided. Finally, two different practical clinical algorithms are provided in the form of a flow
chart for both adults and pediatric (< 16 years old) patients.
Conclusions: The 2020 WSES guidelines on AA aim to provide updated evidence-based statements andrecommendations on each of the following topics: (1) diagnosis, (2) non-operative management for uncomplicatedAA, (3) timing of appendectomy and in-hospital delay, (4) surgical treatment, (5) intra-operative grading of AA, (6),management of perforated AA with phlegmon or abscess, and (7) peri-operative antibiotic therapy.
Keywords: Acute appendicitis, Appendicitis guidelines, Jerusalem guidelines, Consensus conference, Alvarado score,
Appendicitis diagnosis score, Adult Appendicitis Score, Imaging, CT scan appendicitis, Non-operative management,
Antibiotics, Complicated appendicitis, Appendectomy, Laparoscopic appendectomy, Diagnostic laparoscopy,
Phlegmon, Appendiceal abscessBackground
Acute abdominal pain accounts for 7–10% of all emergency department accesses [1]. Acute appendicitis (AA) is
among the most common causes of lower abdominal pain
leading patients to attend the emergency department andthe most common diagnosis made in young patients admitted to the hospital with an acute abdomen.
The incidence of AA has been declining steadily since
the late 1940s. In developed countries, AA occurs at a
rate of 5.7–50 patients per 100,000 inhabitants per year,with a peak between the ages of 10 and 30 [2, 3].
Geographical differences are reported, with a lifetime
risk for AA of 9% in the USA, 8% in Europe, and 2% in
Africa [4]. Moreover, there is great variation in the presentation, severity of the disease, radiological workup,
and surgical management of patients having AA that is
related to country income [5].
The rate of perforation varies from 16% to 40%, with ahigher frequency occurring in younger age groups (40–57%) and in patients older than 50 years (55–70%) [6].
Appendiceal perforation is associated with increased
morbidity and mortality compared with non-perforating
AA. The mortality risk of acute but not gangrenous AA
is less than 0.1%, but the risk rises to 0.6% in gangrenous
AA. On the other hand, perforated AA carries a higher
mortality rate of around 5%. Currently, growing evidence
suggests that perforation is not necessarily the inevitable
result of appendiceal obstruction, and an increasing
amount of evidence now suggests not only that not all
patients with AA will progress to perforation, but eventhat resolution may be a common event [7].
The clinical diagnosis of AA is often challenging andinvolves a synthesis of clinical, laboratory, and radiological findings. The diagnostic workup could be

improved by using clinical scoring systems that involve
physical examination findings and inflammatory
markers. Many simple and user-friendly scoring systems
have been used as a structured algorithm in order to aid
in predicting the risk of AA, but none has been widely
accepted [8–10]. The role of diagnostic imaging, such as
ultrasound (US), computed tomography (CT), or magnetic resonance imaging (MRI), is another major controversy [11, 12].
Since surgeons started performing appendectomies in
the nineteenth century, surgery has been the mostwidely accepted treatment, with more than 300,000 appendectomies performed annually in the USA [13].
Current evidence shows laparoscopic appendectomy(LA) to be the most effective surgical treatment, being
associated with a lower incidence of wound infection
and post-intervention morbidity, shorter hospital stay,and better quality of life scores when compared to open
appendectomy (OA) [14, 15].
Despite all the improvements in the diagnostic
process, the crucial decision as to whether to operate or
not remains challenging. Over the past 20 years, there
has been renewed interest in the non-operative management of uncomplicated AA, probably due to a more reliable analysis of postoperative complications and costs ofsurgical interventions, which are mostly related to thecontinuously increasing use of minimally invasive techniques [16–18].
The most common postoperative complications, suchas wound infection, intra-abdominal abscess, and ileus,
vary in frequency between OA (overall complication rateof 11.1%) and LA (8.7%) [19].
In August 2013, the Organizational Board of the 2ndWorld Congress of the World Society of Emergency

(2020) 15:27

Page 3 of 42

Surgery (WSES) endorsed its president to organize thefirst Consensus Conference on AA, in order to develop
the WSES Guidelines on this topic. The Consensus Conference on AA was held in Jerusalem, Israel, on July 6,
2015, during the 3rd World Congress of the WSES, following which, the WSES Jerusalem guidelines for diagnosis and treatment of AA were published [20].
Over the last 4 years, major issues still open to debate
in the management of AA have been reported concerning the timing of appendectomy, the safety of in-hospitaldelay, and the indications to interval appendectomy following the resolution of AA with antibiotics [21–24].
Therefore, the board of the WSES decided to convene
an update of the 2016 Jerusalem guidelines.

The search results were selected and categorized toallow comprehensive published abstract of randomized
clinical trials, non-randomized studies, consensus conferences, congress reports, guidelines, government publications, systematic reviews, and meta-analyses.
In the 2016 Jerusalem guidelines, the Oxford classification was used to grade the evidence level (EL) and thegrade of recommendation (GoR) for each statement. In
this updated document, quality of evidence and strengthof recommendations have been evaluated according to
the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system.
The GRADE system is a hierarchical, evidence-based
tool, which systematically evaluates the available literature and focuses on the level of evidence based upon thetypes of studies included. The quality of evidence (QoE)
can be marked as high, moderate, low, or very low. This
could be either downgraded in case of significant bias or
upgraded when multiple high-quality studies showed
consistent results. The highest quality of evidence studies (systematic reviews with meta-analysis of randomized
controlled trials) was assessed first. If the meta-analysis
was of sufficient quality, it was used to answer the research question. If no meta-analysis of sufficient quality
was found, randomized controlled trials (RCTs) andnon-randomized cohort studies (n-RCS) were evaluated.
The strength of the recommendation (SoR) was basedon the level of evidence and qualified as weak or strong(Table 2) [25–28].
The first draft of the updated statements and recommendations was commented on by the steering group of
the guidelines and the board of governors of the WSES
during the 6th WSES congress held in Nijmegen, Holland (26–28 June 2019). Amendments were made based
upon the comments, from which a second draft of theconsensus document was generated. All finalized statements and recommendations with QoE and SoR wereentered into a web survey and distributed to all the authors and the board of governor’s members of the WSESby e-mail. The web survey was open from December 1,
2019, until December 15, 2019. The authors were asked
to anonymously vote on each statement and recommendation and indicate if they agreed, (≥ 70% “yes” was categorized as agreement), leading to the final version of the
document.

Di Saverio et al. World Journal of Emergency Surgery

Materials and methods
These updated consensus guidelines were written under
the auspices of the WSES by the acute appendicitis
working group.
The coordinating researcher (S. Di Saverio) invited six
experienced surgeons (G. Augustin, A. Birindelli, B. De
Simone, M. Podda, M. Sartelli, and M. Ceresoli) withhigh-level experience in the management of AA to serveas experts in this 2020 update of the WSES Jerusalem
guidelines. The experts reviewed and updated the original list of key questions on the diagnosis and treatmentof AA addressed in the previous version of the guidelines. The subject of AA was divided into seven main
topics: (1) diagnosis, (2) non-operative management of
uncomplicated AA, (3) timing of appendectomy and inhospital delay, (4) surgical treatment, (5) intra-operative
grading of AA, (6) management of perforated AA withphlegmon or abscess, and (7) antibiotic prophylaxis andpostoperative antibiotic treatment.
Both adults and pediatric populations were consideredand specific statements and recommendations weremade for each of two groups. Pediatric patients were defined as including children and adolescents aged between 1 and 16 years old. Infants were excluded fromthis review.
Based upon the list of topics, research questions (Patients/Population, Intervention/Exposure, Comparison,
Outcome (PICO)) were formulated, reviewed, andadopted as guidance to conduct an exploratory literaturesearch (Table 1).
The searches were conducted in cooperation with a
medical information specialist from the University of
Bologna (A. Gori). A computerized search of different
databases (MEDLINE, Scopus, Embase, Web of Science,and the Cochrane Central Register of Controlled Trials),
and new citations were included for the period April
2015 to June 2019. No search restrictions were imposed.
Search syntaxes have been reported in (Supplemetary
material file 1).

Results
The literature search yielded 984 articles. The titles, abstracts, and full text were reviewed. In total, 157 articles
were selected and reviewed in detail to define 48 statements and 51 recommendations addressing seven topics
and 30 research questions. A summary of the updated
2020 guidelines statements and recommendations has
been reported in Table 3.

Key questions
Q.1.1: What is the value of clinical scoring systems in the management of adult patients with suspected appendicitis? Can they be used as abasis for a structured management?
Q.1.2: In pediatric patients with suspected acute appendicitis could the diagnosis be based only on clinical scores?
Q.1.3: What is the role of serum biomarkers in evaluating adult patients presenting with clinical features evocative of acute appendicitis?
Q.1.4: What is the role of serum biomarkers in evaluating pediatric patients presenting clinical features highly suggestive of acute appendicitis?
Q.1.5: What is the optimum pathway for imaging in adult patients with suspected acute appendicitis?
Q.1.6: What is the optimum pathway for imaging in pediatric patients with suspected acute appendicitis?
Q.2.1: Is non-operative management with or without antibiotics a safe and effective treatment option for adult patients with uncomplicatedacute appendicitis?
Q.2.2: Is non-operative management with or without antibiotics a safe and effective treatment option for pediatric patients with uncomplicated acute appendicitis?
Q.2.3: What is the best non-operative management of patients with uncomplicated acute appendicitis?
Q.3.1: Does in-hospital delay increase the rate of complications or perforation for adult patients with uncomplicated acute appendicitis?
Q.3.2: Does in-hospital delay increase the rate of complications or perforation for pediatric patients with uncomplicated acute appendicitis?
Q.4.1: Does laparoscopic appendectomy confer superior outcomes compared with open appendectomy for adult patients with acuteappendicitis?
Q.4.2: Does laparoscopic appendectomy confer superior outcomes compared with open appendectomy for pediatric patients with acuteappendicitis?
Q.4.3: Does laparoscopic single-incision surgery confer any advantage over the three-trocar technique in performing laparoscopic appendectomy for adult patients with acute appendicitis?
Q.4.4: Does laparoscopic single-incision surgery confer any advantage over the three-trocar technique in performing laparoscopic appendectomy for pediatric patients with acute appendicitis?
Q.4.5: Is outpatient laparoscopic appendectomy safe and feasible for patients with uncomplicated acute appendicitis?
Q.4.6: Is laparoscopic appendectomy indicated over open appendectomy in specific patient groups?
Q.4.7: Does aspiration alone confer clinical advantages over lavage and aspiration for patients with complicated acute appendicitis?
Q.4.8: Does the type of mesoappendix dissection technique (endoclip, endoloop, electrocoagulation, Harmonic Scalpel, or LigaSure) produce
different clinical outcomes for patients with acute appendicitis undergoing appendectomy?
Q.4.9: Does the type of stump closure technique (stapler or endoloop, ligation or invagination of the stump) produce different clinicaloutcomes for patients with acute appendicitis undergoing appendectomy?
Q.4.10: Is the use of abdominal drains recommended after appendectomy for complicated acute appendicitis in adult patients?
Q.4.11: Is the use of abdominal drains recommended after appendectomy for complicated acute appendicitis in pediatric patients?
Q.4.12: What are the best methods to reduce the risk of SSI in open appendectomies with contaminated/dirty wounds?
Q.5.1: What is the value of scoring systems for intra-operative grading of acute appendicitis?
Q.5.2: Should the macroscopically normal appendix be removed during laparoscopy for acute right iliac fossa pain when no other explanatory
pathology is found?
Q.6.1: Is early appendectomy an appropriate treatment compared with delayed appendectomy for patients with perforated acute appendicitis
with phlegmon or abscess?
Q.6.2: Is interval appendectomy always indicated for patients with acute appendicitis following successful NOM?
Q.7.1: Is preoperative antibiotic therapy recommended for patients with acute appendicitis?
Q.7.2: Are postoperative antibiotics always indicated in adult patients following appendectomy?
Q.7.3: Are postoperative antibiotics always indicated in pediatric patients following appendectomy?

Topic

1. Diagnosis

2. Non-operative management of uncomplicatedacute appendicitis

3. Timing of appendectomy and in-hospital delay

4. Surgical treatment

5. Intra-operative grading of acute appendicitis

6. Management of perforated appendicitis withphlegmon or abscess

7. Perioperative antibiotic therapy

Table 1 Research topics and key questions

Di Saverio et al. World Journal of Emergency Surgery(2020) 15:27
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Desirable effects clearly outweigh undesirable
effects or vice versa

Very low-quality evidence, strong recommendation (rarely
applicable)

Evidence for at least one critical outcome from unsystematicclinical observations or very indirect evidence

Evidence for at least one critical outcome from observational
studies, RCTs with serious flaws or indirect evidence

Other alternatives may be equally reasonable. Any estimateof effect, for at least one critical outcome, is very uncertain

Evidence for at least one critical outcome from unsystematicclinical observations or very indirect evidence

Very low-quality evidence, weakrecommendation

Major uncertainty in the estimates of desirable
effects, harms, and burden; desirable effects
may or may not be balanced with undesirable
effects

Other alternatives may be equally reasonable. Further
research is very likely to have an important impact on ourconfidence in the estimate of effect and is likely to change
the estimate

Alternative approaches likely to be better for some patients
under some circumstances. Further research (if performed) islikely to have an important impact on our confidence in theestimate of effect and may change the estimate

The best action may differ depending on circumstances or
patients or societal values. Further research is unlikely tochange our confidence in the estimate effectRecommendation may change when higher quality
evidence becomes available; any estimate of effect for atleast one critical outcome is very uncertain

Recommendation may change when higher quality
evidence becomes available. Further research (if performed)
is likely to have an important impact on our confidence inthe estimate of effect and is likely to change the estimate

Recommendation can apply to most patients in mostcircumstances. Further research (if performed) is likely tohave an important impact on our confidence in theestimate of effect and may change the estimate

Recommendation can apply to most patients in mostcircumstances. Further research is unlikely to change ourconfidence in the estimate effect

Implications

Low-quality evidence, Uncertainty in the estimates of desirable effects, Evidence for at least one critical outcome from observational
weak recommendation harms, and burden; desirable effects, harms, and studies, RCTs with serious flaws or indirect evidence
burden may be closely balanced

Desirable effects closely balanced with
undesirable effects

Evidence from RCTs with important limitations (inconsistent
results, methodological flaws, indirectness, imprecision) or
exceptionally strong evidence from unbiased observational
studiesDesirable effects clearly outweigh undesirable
effects or vice versa

Low-quality evidence,strongrecommendation

Evidence from RCTs with important limitations (inconsistent
results, methodological flaws, indirectness, imprecision) or
exceptionally strong evidence from unbiased observational
studiesModerate quality
evidence, weakrecommendation

Desirable effects clearly outweigh undesirable
effects or vice versa

Moderate quality
evidence, strong
recommendation

Consistent evidence from well-performed RCTs or exceptionally strong evidence from unbiased observational studies

Consistent evidence from well-performed RCTs or exceptionally strong evidence from unbiased observational studies

Desirable effects clearly outweigh undesirable
effects or vice versa

High-quality evidence,strongrecommendation

Methodological quality of supporting evidenceHigh-quality evidence, Desirable effects closely balanced withweak recommendation undesirable effects

Clarity of balance between desirable andundesirable effects

Quality of evidence
and strength ofrecommendation

Table 2 GRADE Quality of evidence and strength of recommendations

Di Saverio et al. World Journal of Emergency Surgery(2020) 15:27
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Recommendation 1.3 We suggest against the use of Alvarado score to positively
confirm the clinical suspicion of acute appendicitis in adults [QoE: Moderate;
Strength of recommendation: Weak; 2B].

Statement 1.2 Clinical scores alone, e.g. Alvarado score, AIR score, and the new
Adult Appendicitis Score are sufficiently sensitive to exclude acute appendicitis,
accurately identifying low-risk patients and decreasing the need for imaging andthe negative appendectomy rates in such patients.

Statement 1.3 The Alvarado score is not sufficiently specific in diagnosing acuteappendicitis in adults, seems unreliable in differentiating complicated fromuncomplicated acute appendicitis in elderly patients and is less sensitive inpatients with HIV.

Recommendation 1.6.1 In evaluating children with suspected appendicitis, werecommend to request routinely laboratory tests and serum inflammatory
biomarkers [QoE: Very Low; Strength of recommendation: Strong: 1D].
Recommendation 1.6.2 In pediatric patients with suspected acute appendicitis,
we suggest adopting both biomarker tests and scores in order to predict theseverity of the inflammation and the need for imaging investigation [QoE: Very
Low; Strength of recommendation: Weak: 2D].
Recommendation 1.7 We recommend the routine use of a combination ofclinical parameters and US to improve diagnostic sensitivity and specificity andreduce the need for CT scan in the diagnosis of acute appendicitis. The use ofimaging diagnostics is recommended in patients with suspected appendicitis after
an initial assessment and risk stratification using clinical scores [QoE: Moderate;
Strength of recommendation: Strong; 1B].
Recommendation 1.8 We suggest proceeding with timely and systematic
diagnostic imaging in patients with intermediate-risk of acute appendicitis [QoE:
Moderate; Strength of recommendation: Weak; 2B].
Recommendation 1.9 We suggest that cross-sectional imaging (i.e., CT scan) inStatement 1.8 Combination of US and clinical (e.g. AIR, AAS scores) parameters
forming combined clinico-radiological scores may significantly improve diagnostic
sensitivity and specificity and eventually replace the need for a CT scan in adultpatients with suspected acute appendicitis.

Statement 1.9 Intermediate-risk classification identifies patients likely to benefit
from observation and systematic diagnostic imaging.

Statement 1.10 Patients with strong signs and symptoms and high-risk of

Recommendation 1.5 In pediatric patients with suspected acute appendicitis, wesuggest against making a diagnosis based on clinical scores alone [QoE: Low;
Strength of recommendation: Weak: 2C].

Statement 1.7 White blood cell count, the differential with the calculation of theabsolute neutrophil count, and the CRP are useful lab tests in predicting acuteappendicitis in children; moreover, CRP level on admission ≥ 10 mg/L andleucocytosis ≥ 16,000/mL are strong predictive factors for appendicitis in pediatricpatients.

Statement 1.6 Biochemical markers represent a promising reliable diagnostic tool
for the identification of both negative cases or complicated acute appendicitis in
adults. However, further high-quality evidence is needed [QoE: Low; No
recommendation].

Statement 1.5 In pediatric patients with suspected acute appendicitis, theAlvarado score and Pediatric Appendicitis Score are useful tools in excluding
acute appendicitis.

Statement 1.4 The AIR score and the AAS score seem currently to be the best
Recommendation 1.4 We recommend the use of AIR score and AAS score as
performing clinical prediction scores and have the highest discriminating power
clinical predictors of acute appendicitis [QoE: High; Strength of recommendation:in adults with suspected acute appendicitis. The AIR and AAS scores decrease
Strong; 1A].
negative appendectomy rates in low-risk groups and reduce the need for imaging
studies and hospital admissions in both low and intermediate-risk groups.

Recommendation 1.2.1 We recommend the use of clinical scores to exclude
acute appendicitis and identify intermediate-risk patients needing of imaging
diagnostics [QoE: High; Strength of recommendation: Strong; 1A]. Recommendation 1.2.2 We suggest not making the diagnosis of acute appendicitis in pregnant
patients on symptoms and signs only. Laboratory tests and inflammatory serum
parameters should always be requested [QoE: Very Low; Strength of recommendation: Weak; 2C].

Statement 1.1 Establishing the diagnosis of acute appendicitis based on clinicalpresentation and physical examination may be challenging. As the value ofindividual clinical variables to determine the likelihood of acute appendicitis in apatient is low, a tailored individualized approach is recommended, depending on
disease probability, sex, and age of the patient.

1. Diagnosis

Recommendation
Recommendation 1.1 We recommend to adopt a tailored individualized
diagnostic approach for stratifying the risk and disease probability and planningan appropriate stepwise diagnostic pathway in patients with suspected acuteappendicitis, depending on age, sex and clinical signs and symptoms of thepatient [QoE: Moderate; Strength of recommendation: Strong; 1B].

Statement

Topic

Table 3 Summary of the updated 2020 guidelines statements and recommendations

Di Saverio et al. World Journal of Emergency Surgery(2020) 15:27
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2. Non-operative management of uncomplicatedacute appendicitis.

Topic

Recommendation 1.13.1 We suggest graded compression trans-abdominal ultrasound as the preferred initial imaging method for suspected acute appendicitis
during pregnancy [QoE: Very Low; Strength of Recommendation: Weak; 2C]. Recommendation 1.13.2 We suggest MRI in pregnant patients with suspected appendicitis, if this resource is available, after inconclusive US [QoE: Moderate;
Strength of recommendation: Weak; 2B].
Recommendation 1.14.1 In pediatric patients with suspected appendicitis, wesuggest the use of US as first-line imaging. In pediatric patients with inconclusive
US, we suggest choosing the second-line imaging technique based on local availability and expertise, as there are currently no strong data to suggest a best diagnostic pathway due to a variety of options and dependence on local resources[QoE: Moderate; Strength of recommendation: Weak: 2B]. Recommendation
1.14.2 Since in pediatric patients with equivocal CT finding the prevalence of true
acute appendicitis is not negligible, we suggest against the routine use of CT asfirst-line imaging in children with right iliac fossa pain [QoE: Moderate; Strength ofrecommendation: Weak; 2B].

Statement 1.13 In patients with normal investigations and symptoms unlikely tobe acute appendicitis but which do not settle, cross-sectional imaging is recommended before surgery. Laparoscopy is recommended to establish/exclude thediagnosis of acute appendicitis and eventually treat the disease.

Statement 1.14 MRI is sensitive and highly specific for the diagnosis of acuteappendicitis during pregnancy. However, a negative or inconclusive MRI does not
exclude appendicitis and surgery should be still considered if high clinicalsuspicion.

Statement 1.15 The use of US in children is accurate and safe in terms of
perforation rates, emergency department re-visits, and negative appendectomy
rates. CT use may be decreased by using appropriate clinical and/or staged algorithm with US/MRI. MRI has at least the same sensitivity and specificity as CT and,
although higher costs, should be preferred over CT as second-line imaging inchildren.

Recommendation 2.2 We suggest discussing NOM with antibiotics as a safe andeffective alternative to surgery in children with uncomplicated acute appendicitis
in the absence of an appendicolith, advising of the possibility of failure andmisdiagnosing complicated appendicitis [QoE: Moderate; Strength of

Recommendation 1.12 We recommend cross-sectional imaging before surgery
for patients with normal investigations but non-resolving right iliac fossa pain.
After negative imaging, initial non-operative treatment is appropriate. However, inpatients with progressive or persistent pain, explorative laparoscopy is recommended to establish/exclude the diagnosis of acute appendicitis or alternative
diagnoses [QoE: High; Strength of recommendation: Strong; 1A].

Statement 1.12 When it is indicated, contrast-enhanced low-dose CT scan should
be preferred over contrast-enhanced standard-dose CT scan. Diagnostic accuracyof contrast-enhanced low-dose CT is not inferior to standard CT in diagnosing AA
or distinguishing between uncomplicated and complicated acute appendicitis
and enables significant radiation dose reduction.

Statement 2.2 NOM for uncomplicated acute appendicitis in children is feasible,
safe and effective as initial treatment. However, failure rate increases in thepresence of appendicolith, and surgery is recommended in such cases.

Recommendation 1.11 We recommend the use of contrast-enhanced low-dose
CT scan over contrast-enhanced standard-dose CT scan for adolescents and young
adults with suspected acute appendicitis and negative US findings [QoE: High;Strength of recommendation: Strong; 1A].

Statement 1.11 POCUS (Point-of-care Ultrasound) is a reliable initial investigation
with satisfactory sensitivity and specificity in diagnosing acute appendicitis, easing
swift decision-making by the emergency physicians or surgeons. POCUS, if performed by an experienced operator, should be considered the most appropriate
first-line diagnostic tool in both adults and children.

Recommendation 2.1.1 We recommend discussing NOM with antibiotics as asafe alternative to surgery in selected patients with uncomplicated acuteappendicitis and absence of appendicolith, advising of the possibility of failure
and misdiagnosing complicated appendicitis [QoE: High; Strength of
Recommendation: Strong; 1A]. Recommendation 2.1.2 We suggest against
treating acute appendicitis non-operatively during pregnancy until further highlevel evidence is available [QoE: Very Low; Strength of Recommendation: Weak;
2C].

Recommendation 1.10 We recommend POCUS as the most appropriate first-line
diagnostic tool in both adults and children, if an imaging investigation is indicatedbased on clinical assessment [QoE: Moderate; Strength of recommendation:
Strong; 1B].

appendicitis according to AIR score/Alvarado score/AAS score and younger than
40 years may not require cross-sectional pre-operative imaging (i.e., CT scan).

Statement 2.1 The antibiotic-first strategy can be considered safe and effective inselected patients with uncomplicated acute appendicitis. Patients who wish to
avoid surgery must be aware of a risk of recurrence of up to 39% after 5 years.
Most recent data from meta-analyses of RCTs showed that NOM with antibiotics
achieves a significantly lower overall complication rate at 5 years and shorter sickleave compared to surgery.

Recommendation
high-risk patients younger than 40 years old (with AIR score 9–12 and Alvarado
score 9–10 and AAS ≥ 16) may be avoided before proceeding to diagnostic +/−therapeutic laparoscopy [QoE: Moderate; Strength of recommendation: Weak; 2B].

Statement

Table 3 Summary of the updated 2020 guidelines statements and recommendations (Continued)

Di Saverio et al. World Journal of Emergency Surgery(2020) 15:27
Page 7 of 42

4. Surgical treatment

3. Timing of appendectomy
and in-hospital delay

Topic

Recommendation
recommendation: Weak; 2B].

Recommendation 4.2 We recommend laparoscopic appendectomy should be
preferred over open appendectomy in children where laparoscopic equipment
and expertise are available [QoE: Moderate; Strength of recommendation: Strong;
1B].
Recommendation 4.3 We recommend conventional three-port laparoscopic appendectomy over single-incision laparoscopic appendectomy, as the conventional
laparoscopic approach is associated with shorter operative times, less postoperative pain, and lower incidence of wound infection [QoE: High; Strength of recommendation: Strong; 1A].
Recommendation 4.4 In pediatric patients with acute appendicitis and favorable
anatomy, we suggest performing single incision/transumbilical extracorporeal
laparoscopic assisted appendectomy or traditional three-port laparoscopic appendectomy based on local skills and expertise [QoE: Low; Strength of recommendation: Weak; 2C].
Recommendation 4.5 We suggest the adoption of outpatient laparoscopic
appendectomy for uncomplicated appendicitis, provided that an ambulatory

Statement 4.2 Laparoscopic appendectomy is associated with lower
postoperative pain, lower incidence of SSI and higher quality of life in children.

Statement 4.3 Single-incision laparoscopic appendectomy is basically feasible,safe, and as effective as conventional three-port laparoscopic appendectomy, operative times are longer, requires higher doses of analgesia, and is associated witha higher incidence of wound infection.

Statement 4.4 In children with acute appendicitis, the single incision/transumbilical extracorporeal laparoscopic-assisted technique is as safe as the laparoscopic three-port technique.

Statement 4.5 Outpatient laparoscopic appendectomy for uncomplicated acuteappendicitis is feasible and safe without any difference in morbidity andRecommendation 3.3 We suggest against delaying appendectomy for pediatricpatients with uncomplicated acute appendicitis needing surgery beyond 24 hfrom the admission. Early appendectomy within 8 h should be performed in caseof complicated appendicitis [QoE: Low; Strength of Recommendation: Weak; 2C].

Statement 3.3 Appendectomy performed within the first 24 h from presentationin the case of uncomplicated appendicitis is not associated with an increased riskof perforation or adverse outcomes. Early appendectomy is the best management
in complicated appendicitis.

Recommendation 4.1 We recommend laparoscopic appendectomy as thepreferred approach over open appendectomy for both uncomplicated andcomplicated acute appendicitis, where laparoscopic equipment and expertise areavailable [QoE: High; Strength of recommendation: Strong; 1A].

Recommendation 3.2 We recommend against delaying appendectomy for acuteappendicitis needing surgery beyond 24 h from the admission [QoE: Moderate;
Strength of recommendation: Strong; 1B].

Statement 3.2 Delaying appendectomy for uncomplicated acute appendicitis for
up to 24 h after admission does not appear to be a risk factor for complicatedappendicitis, postoperative surgical site infection or morbidity. Conversely,
appendectomies performed after 24 h from admission are related to an increased
risk of adverse outcomes.

Statement 4.1 Laparoscopic appendectomy offers significant advantages overopen appendectomy in terms of less pain, lower incidence of surgical site
infection, decreased length of hospital stay, earlier return to work, overall costs,
and better quality of life scores.

Recommendation 3.1 We recommend planning laparoscopic appendectomy forthe next available operating list within 24 h in case of uncomplicated acuteappendicitis, minimizing the delay wherever possible [QoE: Moderate; Strength ofrecommendation: Strong; 1B].

Statement 3.1 Short, in-hospital surgical delay up to 24 h is safe in uncomplicatedacute appendicitis and does not increase complications and/or perforation rate inadults. Surgery for uncomplicated acute appendicitis can be planned for the next
available list minimizing delay wherever possible (better patient comfort, etc.).
Short, in-hospital delay with observation and repeated trans-abdominal US in
pregnant patients with equivocal appendicitis is acceptable and does not seem toincrease the risk of maternal and fetal adverse outcomes.

Statement 2.4 Uncomplicated acute appendicitis may safely resolve
spontaneously with similar treatment failure rates, shorter length of stay and costs
compared with antibiotics. However, there is still limited data for the panel toexpress in favor of or against the symptomatic treatment without antibiotics [QoE:
Moderate; No recommendation].

Statement 2.3 Current evidence supports initial intravenous antibiotics with
Recommendation 2.3 In the case of NOM, we recommend initial intravenous
subsequent conversion to oral antibiotics until further evidence from ongoing RCT antibiotics with a subsequent switch to oral antibiotics based on patient's clinicalis available.
conditions [QoE: Moderate; Strength of recommendation: Strong; 1B].

Statement

Table 3 Summary of the updated 2020 guidelines statements and recommendations (Continued)

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TopicRecommendation 4.6 We suggest laparoscopic appendectomy in obese patients,
older patients and patients with high peri- and postoperative risk factors [QoE:
Moderate; Strength of recommendation: Weak; 2B].

Recommendation 4.7 We suggest laparoscopic appendectomy should be
preferred to open appendectomy in pregnant patients when surgery is indicated.
Laparoscopy is technically safe and feasible during pregnancy where expertise oflaparoscopy is available [QoE: Moderate; Strength of recommendation: Weak; 2B].

readmission rates. It is associated with potential benefits of earlier recovery after
surgery and lower hospital and social costs.

Statement 4.6 Laparoscopic appendectomy seems to show relevant advantages
compared to open appendectomy in obese adult patients, older patients, andpatients with comorbidities. Laparoscopic appendectomy is associated with
reduced mortality, reduced overall morbidity, reduced superficial wound
infections, shorter operating times and postoperative length of hospital stay insuch patients.

Statement 4.7 Laparoscopic appendectomy during pregnancy is safe in terms ofrisk of fetal loss and preterm delivery and it is preferable to open surgery as
associated to shorter length of hospital stay and lower incidence of surgical site
infection.

Recommendation 4.10 We recommend the use of endoloops/suture ligation or
polymeric clips for stump closure for both adults and children in either
uncomplicated or complicated appendicitis, whereas endostaplers may be used
when dealing with complicated cases depending on the intra-operative judgmentof the surgeon and resources available [QoE: Moderate; Strength of recommendation: Strong; 1B].

Statement 4.10 There are no clinical advantages in the use of endostaplers overendoloops for stump closure for both adults and children in either simple orcomplicated appendicitis, except for a lower incidence of wound infection whenusing endostaplers in children with uncomplicated appendicitis. Polymeric clips
may be the cheapest and easiest method (with shorter operative times) for stumpclosure in uncomplicated appendicitis.

Recommendation 4.13 We suggest against the prophylactic use of abdominal
drainage after laparoscopic appendectomy for complicated appendicitis inchildren [QoE: Low; Strength of recommendation: Weak; 2C].
Recommendation 4.14 We recommend wound ring protectors in open
appendectomy to decrease the risk of SSI [QoE: Moderate; Strength ofrecommendation: Strong; 1B].

Statement 4.13 The prophylactic use of abdominal drainage after laparoscopic
appendectomy for perforated appendicitis in children does not prevent
postoperative complications and may be associated with negative outcomes.

Statement 4.14 The use of wound ring protectors shows some evidence of
surgical site infection reduction in open appendectomy, especially in case ofcomplicated appendicitis with contaminated/dirty wounds.

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Statement 4.15 Delayed primary skin closure increases the length of hospital stay Recommendation 4.15 We recommend primary skin closure with a uniqueand overall costs in open appendectomies with contaminated/dirty wounds andabsorbable intradermal suture for open appendectomy wounds [QoE: Moderate;
does not reduce the risk of SSI. Subcuticular suture seems preferable in open
Strength of recommendation: Weak; 2B].

Recommendation 4.12 We recommend against the use of drains following
appendectomy for complicated appendicitis in adult patients [QoE: Moderate;
Strength of recommendation: Strong; 1B].

Statement 4.12 In adult patients, the use of drains after appendectomy for
perforated appendicitis and abscess/peritonitis should be discouraged. Drains areof no benefit in preventing intra-abdominal abscess and lead to longer length of
hospitalization and there is also low-quality evidence of increased 30-day morbidity and mortality rates in patients in the drain group.

Statement 4.11 Simple ligation should be preferred to stump inversion, either in Recommendation 4.11 We recommend simple ligation over stump inversion
open or laparoscopic surgery, as the major morbidity and infectious complications either in open and laparoscopic appendectomy [QoE: High; Strength ofrecommendation: Strong; 1A].
are similar. Simple ligation is associated with shorter operative times, lesspostoperative ileus and quicker recovery.

Recommendation 4.9 We suggest the use of monopolar electrocoagulation andbipolar energy as they are the most cost-effective techniques, whereas other energy devices can be used depending on the intra-operative judgment of the surgeon and resources available [QoE: Moderate; Strength of recommendation: Weak;
2B].

Statement 4.9 There are no clinical differences in outcomes, length of hospital
stay and complications rates between the different techniques described formesentery dissection (monopolar electrocoagulation, bipolar energy, metal clips,
endoloops, LigaSure, Harmonic Scalpel, etc.).

Statement 4.8 Peritoneal irrigation does not have any advantage over suction
Recommendation 4.8 We recommend performing suction alone in complicatedalone in complicated appendicitis in both adults and children. The performance
appendicitis patients with intra-abdominal collections undergoing laparoscopicof irrigation during laparoscopic appendectomy does not seem to prevent the
appendectomy [QoE: Moderate; Strength of recommendation: Strong; 1B].
development of IAA and wound infections in neither adults nor pediatric patients.

Recommendation
pathway with well-defined ERAS protocols and patient information/consent are locally established [QoE: Moderate; Strength of recommendation: Weak; 2B].

Statement

Table 3 Summary of the updated 2020 guidelines statements and recommendations (Continued)

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appendectomy for acute appendicitis as it is associated with lower risk ofcomplications (surgical site infection/abscess and seroma) and lower costs.

Statement

Recommendation

Recommendation 7.2 We recommend against prolonging antibiotics longer
than 3–5 days postoperatively in case of complicated appendicitis with adequate
source-control [QoE: High; Strength of recommendation: Strong; 1A].

Statement 7.2 In patients with complicated acute appendicitis, postoperative
broad-spectrum antibiotics are suggested, especially if complete source control
has not been achieved. For adult patients deemed to require them, discontinuation of antibiotics after 24 h seems safe and is associated with shorter length of

Recommendation 6.4 We suggest both colonic screening with colonoscopy andinterval full-dose contrast-enhanced CT scan for patients with appendicitis treated
non-operatively if ≥ 40 years old [QoE: Low; Strength of recommendation: Weak;
2C].

Statement 6.4 The incidence of appendicular neoplasms is high (3–17%) in adultpatients ≥ 40 years old) with complicated appendicitis.

Recommendation 7.1 We recommend a single preoperative dose of broadspectrum antibiotics in patients with acute appendicitis undergoing appendectomy. We recommend against postoperative antibiotics for patients with uncomplicated appendicitis [QoE: High; Strength of recommendation: Strong; 1A].

Recommendation 6.3 We recommend against routine interval appendectomy
after NOM for complicated appendicitis in young adults (< 40 years old) andchildren. Interval appendectomy is recommended for those patients withrecurrent symptoms [QoE: Moderate; Strength of recommendation: Strong; 1B].

Statement 6.3 The reported rate of recurrence after non-surgical treatment for
perforated AA and phlegmon ranges from 12% to 24%. Interval appendectomy
and repeated NOM in case of recurrence of appendiceal phlegmon are associatedwith similar morbidity. However, elective interval appendectomy is related to additional operative costs to prevent recurrence in only one of eight patients, such as
not to justify the routine performance of appendectomy.

Statement 7.1 A single dose of broad-spectrum antibiotics given preoperatively(from 0 to 60 min before the surgical skin incision) has been shown to be effective
in decreasing wound infection and postoperative intra-abdominal abscess, regardless of the degree of inflammation of the removed appendix.

Recommendation 6.2 We suggest the laparoscopic approach as treatment ofchoice for patients with complicated appendicitis with phlegmon or abscesswhere advanced laparoscopic expertise is available, with a low threshold forconversion. [QoE: Moderate; Strength of recommendation: Weak; 2B].

Recommendation 6.1 We suggest non-operative management with antibiotics
and—if available—percutaneous drainage for complicated appendicitis with periappendicular abscess, in settings where laparoscopic expertise is not available[QoE: Moderate; Strength of recommendation: Weak; 2B].

Statement 6.2 Operative management of acute appendicitis with phlegmon orabscess is a safe alternative to non-operative management in experienced hands,
and may be associated with shorter LOS, reduced need for readmissions andfewer additional interventions than conservative treatment.

6. Management ofStatement 6.1 Non-operative management is a reasonable first-line treatment for
perforated appendicitis with appendicitis with phlegmon or abscess. Percutaneous drainage as an adjunct tophlegmon or abscess
antibiotics, if accessible, could be beneficial, although there is a lack of evidence
for its use on a routine basis. Laparoscopic surgery in experienced hands is a safeand feasible first-line treatment for appendiceal abscess, being associated withfewer readmissions and fewer additional interventions than conservative treatment, with a comparable hospital stay.

7. Perioperative antibiotic
therapy

Recommendation 5.2 We suggest the routine adoption of an intra-operative
grading system for acute appendicitis (e.g., WSES 2015 grading score or AAST EGS
grading score) based on clinical, imaging and operative findings [QoE: Moderate;
Strength of recommendation: Weak; 2B].

Statement 5.3 Surgeon’s macroscopic judgment of early grades of acute
Recommendation 5.3 We suggest appendix removal if the appendix appears
appendicitis is inaccurate and highly variable. The variability in the intra-operative “normal” during surgery and no other disease is found in symptomatic patientsclassification of appendicitis influences the decision to prescribe postoperative an- [QoE: Low; Strength of recommendation: Weak; 2C].
tibiotics and should be therefore prevented/avoided.

Statement 5.2 Operative findings and intra-operative grading seem to correlatebetter than histopathology with morbidity, overall outcomes, and costs, both inadults and children. Intra-operative grading systems can help the identification ofhomogeneous groups of patients, determining optimal postoperative management according to the grade of the disease and ultimately improve the utilizationof resources.

5. Intra-operative grading of Statement 5.1 The incidence of unexpected findings in appendectomy
Recommendation 5.1 We recommend routine histopathology after
acute appendicitis
specimens is low. The intra-operative diagnosis alone is insufficient for identifying appendectomy [QoE: Moderate; Strength of recommendation: Strong; 1B].
unexpected disease. From the currently available evidence, routine histopathology
is necessary.

Topic

Table 3 Summary of the updated 2020 guidelines statements and recommendations (Continued)

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TopicRecommendation 7.3 We recommend early switch (after 48 h) to oral
administration of postoperative antibiotics in children with complicatedappendicitis, with an overall length of therapy shorter than 7 days [QoE:
Moderate; Strength of recommendation: Strong; 1B].
Recommendation 7.4 In pediatric patients operated for uncomplicated acuteappendicitis, we suggest against using postoperative antibiotic therapy [QoE: Low;
Strength of recommendation: Weak; 2C].

Statement 7.4 Postoperative antibiotics after appendectomy for uncomplicatedacute appendicitis in children seems to have no role in reducing the rate ofsurgical site infection.

Recommendation

Statement 7.3 Administering postoperative antibiotics orally in children withcomplicated appendicitis for periods shorter than 7 days postoperatively seems to
be safe and it is not associated with increased risk of complications. Earlytransition to oral antibiotics is safe, effective, and cost-efficient in the treatment ofcomplicated appendicitis in the child.

hospital stay and lower costs. In patients with intra-abdominal infections who had
undergone an adequate source control, the outcomes after fixed-duration antibiotic therapy (approximately 3–5 days) are similar to those after a longer courseof antibiotics.

Statement

Table 3 Summary of the updated 2020 guidelines statements and recommendations (Continued)

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(2020) 15:27

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Topic 1: Diagnosis
Q.1.1: What is the value of clinical scoring systems in the
management of adult patients with suspected appendicitis?
Can they be used as basis for a structured management?

first study evaluating the utility of the RIPASA score inpredicting AA in a Western population. At a value of 7.5(a cut of score suggestive of AA in the Eastern population), the RIPASA demonstrated reasonable sensitivity(85.39%), specificity (69.86%), positive predictive value(84.06%), negative predictive value (72.86%), and diagnostic accuracy (80%) in Irish patients with suspected
AA and was more accurate than the Alvarado score [34].
The Adult Appendicitis Score (AAS) stratifies patients
into three groups: high, intermediate, and low risk of
AA. The score has been shown to be a reliable tool for
stratification of patients into selective imaging, which results in a low negative appendectomy rate. In a prospective study enrolling 829 adults presenting with clinicalsuspicion of AA, 58% of patients with histologically confirmed AA had score value at least 16 and were classified
as high probability group with 93% specificity. Patientswith a score below 11 were classified as low probabilityof AA. Only 4% of patients with AA had a score below
11, and none of them had complicated AA. In contrast,
54% of non-AA patients had a score below 11. The area
under ROC curve was significantly larger with the newscore 0.882 compared with AUC of Alvarado score0.790 and AIR score 0.810 [11].
In the validation study by Sammalkorpi et al., the AAS
score stratified 49% of all AA patients into a high-risk
group with the specificity of 93.3%, whereas in the lowrisk group the prevalence of AA was 7%. The same study
group demonstrated that diagnostic imaging has limited
value in patients with a low probability of AA according
to the AAS [35].
Tan et al. recently performed a prospective data collection on 350 consecutive patients with suspected AA
for whom the Alvarado score for each patient wasscored at admission and correlated with eventual histology and CT findings. The positive likelihood ratio of
disease was significantly greater than 1 only in patientswith an Alvarado score of 4 and above. An Alvarado
score of 7 and above in males and 9 and above in females had a positive likelihood ratio comparable to thatof CT scan [36].
Nearly all clinical signs and symptoms, as isolated parameters, do not significantly discriminate between thosepregnant women with and without AA [37–39].
Of 15 validated risk prediction models taken into consideration in a recently published study enrolling 5345
patients with right iliac fossa pain across 154 UK hospitals, the AAS performed best for women (cutoff score 8
or less, specificity 63.1%, failure rate 3.7%), whereas the
AIR score performed best for men (cutoff score 2 or less,specificity 24.7%, failure rate 2.4%) [40].
The Alvarado score can be higher in pregnant women
due to the higher WBC values and the frequency of nausea and vomiting, especially during the first trimester,

Di Saverio et al. World Journal of Emergency Surgery

Risk stratification of patients with suspected AA by clinical scoring systems could guide decision-making to reduce admissions, optimize the utility of diagnostic
imaging, and prevent negative surgical explorations.
Clinical scores alone seem sufficiently sensitive to identify low-risk patients and decrease the need for imaging
and negative surgical explorations (such as diagnostic
laparoscopy) in patients with suspected AA.
The RCT by Andersson et al. demonstrated that,in low-risk patients, the use of an AIR (Appendicitis
Inflammatory Response) score-based algorithm resulted in less imaging (19.2% vs 34.5%, P < 0.001),
fewer admissions (29.5% vs 42.8%, P < 0.001), fewer
negative explorations (1.6% vs 3.2%, P = 0.030), andfewer surgical operations for non-perforated AA(6.8% vs 9.7%, P = 0.034). Intermediate-risk patientsrandomized to the imaging and observation strategies had the same proportion of negative appendectomies (6.4% vs 6.7%, P = 0.884), number of hospital
admissions, rates of perforation, and length of hospital stay, but routine imaging was associated withan increased proportion of patients treated for AA(53.4% vs 46.3%, P = 0.020) [29].
Among the many available clinical prediction models
for the diagnosis of AA, the AIR score appears to be thebest performer and most pragmatic. The review by
Kularatna et al. recently summarized the results fromvalidation studies, showing that the overall best performer in terms of sensitivity (92%) and specificity (63%)
is the AIR score [30].
Although the Alvarado score is not sufficiently specificin diagnosing AA, a cutoff score of < 5 is sufficiently
sensitive to exclude AA (sensitivity of 99%). The Alvarado score could, therefore, be used to reduce emergency
department length of stay and radiation exposure in patients with suspected AA. This is confirmed by a large
retrospective cohort study that found 100% of maleswith Alvarado score of 9 or greater, and 100% of femaleswith an Alvarado score of 10 had AA confirmed by surgical pathology. Conversely, 5% or less of female patientswith an Alvarado score of 2 or less and 0% of male patients with an Alvarado score of 1 or less were diagnosed
with AA at surgery [31].
However, the Alvarado score is not able to differentiate complicated from uncomplicated AA in elderly patients and seems less sensitive in HIV+ patients [32, 33].
The RIPASA (Raja Isteri Pengiran Anak Saleha Appendicitis) score has shown to achieve better sensitivity andspecificity than the Alvarado score in Asian and Middle
Eastern population. Malik et al. recently published the(2020) 15:27

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implicating lower accuracy compared to the nonpregnant population. Studies show Alvarado score (cutoff 7 points) sensitivity of 78.9% and specificity of 80.0%
in pregnant patients [41, 42]. The RIPASA score has a
specificity (cutoff 7.5 points) of 96%, but the score
should be validated in larger studies. There are no studies of the Alvarado score discriminating between uncomplicated and complicated AA during pregnancy.
The preoperative distinction between uncomplicatedand complicated AA is challenging. Recently, prediction
models based on temperature, CRP, presence of free
fluids on ultrasound, and diameter of the appendix havebeen shown to be useful for the identification of “highrisk” patients for complicated AA. Atema et al. foundthat, with the use of scoring systems combining clinicaland imaging features, 95% of the patients deemed tohave uncomplicated AA were correctly identified [43].
Statement 1.1 Establishing the diagnosis of acute appendicitis based on clinical presentation and physicalexamination may be challenging. As the value of individual clinical variables to determine the likelihood of acuteappendicitis in a patient is low, a tailored individualized
approach is recommended, depending on disease probability, sex, and age of the patient. Recommendation
1.1 We recommend to adopt a tailored individualized
diagnostic approach for stratifying the risk and diseaseprobability and planning an appropriate stepwise diagnostic pathway in patients with suspected acute appendicitis, depending on age, sex, and clinical signs andsymptoms of the patient [QoE: Moderate; Strength ofrecommendation: Strong; 1B].
Statement 1.2 Clinical scores alone, e.g., Alvarado
score, AIR score, and the new Adult Appendicitis
Score are sufficiently sensitive to exclude acute appendicitis, accurately identifying low-risk patientsand decreasing the need for imaging and the negative appendectomy rates in such patients. Recommendation 1.2.1 We recommend the use of clinicalscores to exclude acute appendicitis and identify
intermediate-risk patients needing of imaging diagnostics [QoE: High; Strength of recommendation:
Strong; 1A]. Recommendation 1.2.2 We suggest not
making the diagnosis of acute appendicitis in pregnant patients on symptoms and signs only. Laboratory tests and inflammatory serum parameters (e.g.,
CRP) should always be requested [QoE: Very Low;
Strength of recommendation: Weak; 2C].
Statement 1.3 The Alvarado score is not sufficiently
specific in diagnosing acute appendicitis in adults, seems
unreliable in differentiating complicated from uncomplicated acute appendicitis in elderly patients, and is lesssensitive in patients with HIV. Recommendation 1.3
We suggest against the use of Alvarado score to positively confirm the clinical suspicion of acute appendicitis

in adults [QoE: Moderate; Strength of recommendation:
Weak; 2B].
Statement 1.4 The AIR score and the AAS score seemcurrently to be the best performing clinical prediction
scores and have the highest discriminating power in
adults with suspected acute appendicitis. The AIR andAAS scores decrease negative appendectomy rates in
low-risk groups and reduce the need for imaging studies
and hospital admissions in both low- and intermediaterisk groups. Recommendation 1.4 We recommend theuse of AIR score and AAS score as clinical predictors of
acute appendicitis [QoE: High; Strength of recommendation: Strong; 1A].

Di Saverio et al. World Journal of Emergency Surgery

Q.1.2: In pediatric patients with suspected acuteappendicitis could the diagnosis be based only on clinicalscores?

AA is the most common surgical emergency in children,
but early diagnosis of AA remains challenging due toatypical clinical features and the difficulty of obtaining a
reliable history and physical examination. Several clinicalscoring systems have been developed, the two mostpopular for use in children being the Alvarado score andSamuel’s Pediatric Appendicitis Score (PAS).
PAS includes similar clinical findings to the Alvarado
score in addition to a sign more relevant in children:right lower quadrant pain with coughing, hopping, or
percussion. Several studies comparing the PAS with theAlvarado score have validated its use in pediatric patients. However, in a systematic review by Kulik et al.
both scores failed to meet the performance benchmarksof CRP (C-reactive protein). On average, the PAS would
over-diagnose AA by 35%, and the Alvarado score would
do so by 32% [44].
If we consider patients of preschool age, AA often presents with atypical features, more rapid progression, andhigher incidence of complications. This age group is
more likely to have lower PAS and Alvarado score thanthose of school-aged children [45]. This is the reason
why Macco et al. retrospectively analyzed data from 747
children (mean age of 11 years) suspected of AA toevaluate the predictive value of the Alvarado score andPAS compared with the AIR score, which includes fewer
symptoms than the Alvarado score and PAS, but adds
the CRP value and allows for different severity levels ofrebound pain, leukocytosis, CRP, and polymorphonucleocytes. The study showed that the AIR had the highest discriminating power and outperformed the othertwo scores in predicting AA in children [46].
The use of PAS seems to be useful to rule out or in
AA in pediatric female patients. A retrospective observational study demonstrated that at a cutoff of ≥ 8, thePAS showed a specificity of 89% for adolescent females
and 78% for all other patients, although the specificities

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did not differ at a cutoff of ≥ 7. At both cutoffs, the positive predictive values were poor in both groups. At acutoff of ≥ 3, the PAS showed similar sensitivities inboth groups [47].
Recently, the new Pediatric Appendicitis Laboratory
Score (PALabS) including clinical signs, leucocyte andneutrophil counts, CRP, and calprotectin levels has beenshown to accurately predict which children are at low
risk of AA and could be safely managed with close observation. A PALabS ≤ 6 has a sensitivity of 99.2%, anegative predictive value of 97.6%, and a negative likelihood ratio of 0.03 [48].
The preoperative clinical scoring system to distinguishperforation risk with pediatric AA proposed by Bonadio
et al., based on the duration of symptoms (> 1 day), fever(> 38.0 C), and WBC absolute count (> 13,000/mm3), resulted in a multivariate ROC curve of 89% for perforation (P < 0.001), and the risk for perforation was
additive with each additional predictive variable exceeding its threshold value, linearly increasing from 7% withno variable present to 85% when all 3 variables arepresent [49].
In assessing if the clinical scores can predict disease
severity and the occurrence of complications, a retrospective study on the Alvarado score validity in pediatricpatients showed that a higher median score was foundin patients who suffered postoperative complications.
The eight items in the scoring system were analyzed fortheir sensitivities. Fever, right lower quadrant tenderness,
and neutrophilia were found to be the three most sensitive markers in predicting complicated AA (88.6%,
82.3%, and 79.7%). On the other hand, rebound tenderness was found to have the highest positive predictive
value (65%) among the eight items to predict complicated AA [50].
Statement 1.5 In pediatric patients with suspected
acute appendicitis, the Alvarado score and Pediatric Appendicitis Score are useful tools in excluding acute appendicitis. Recommendation 1.5 In pediatric patientswith suspected acute appendicitis, we suggest against
making a diagnosis based on clinical scores alone [QoE:
Low; Strength of recommendation: Weak: 2C].

combination with the modified Alvarado score in patients with clinically suspected AA in the prospective observational study by Msolli et al. Early change of CRP
had a moderate diagnostic value in patients with suspected AA, and even combining CRP values to themodified Alvarado score did not improve diagnostic accuracy [52]. Recently, ischemia-modified albumin (IMA)
levels have been used to determine the prediction of severity in AA patients. Kilic et al. found a strong positive
correlation between IMA levels and CT findings in distinguishing gangrenous/perforated AA from uncomplicated AA [53]. A combination of clinical parameters,laboratory tests, and US may significantly improve diagnostic sensitivity and specificity and eventually replace
the need for CT scan in both adults and children [54].
Statement 1.6 Biochemical markers represent a promising reliable diagnostic tool for the identification of both
negative cases or complicated acute appendicitis in
adults. However, further high-quality evidence is needed[QoE: Low; No recommendation].

Di Saverio et al. World Journal of Emergency Surgery

Q.1.3: What is the role of serum biomarkers in evaluating
adult patients presenting with clinical features evocative ofacute appendicitis?

The diagnostic accuracy of several biomarker panels has
been prospectively validated, showing high sensitivity
and negative predictive values for AA in large cohorts ofpatients with right iliac fossa pain, thereby potentially reducing the dependence on CT for the evaluation of possible AA [51].
The diagnostic value of baseline and early change of
CRP concentrations has been evaluated separately or in

Q.1.4: What is the role of serum biomarkers in evaluating
pediatric patients presenting clinical features highlysuggestive of acute appendicitis?

In pediatric patients, routine diagnostic laboratory
workup for suspected AA should include WBC, the differential with the calculation of the absolute neutrophil
count (ANC), CRP, and urinalysis.
Although not widely available, the addition of procalcitonin and calprotectin to the above tests may significantly improve diagnostic discrimination [55].
Biomarkers have also been shown to be useful whenused in association with the systematic adoption of scoring systems, as the addition of negative biomarker test
results to patients with a moderate risk of AA based on
the Pediatric Appendicitis Score (PAS) can safely reclassify many patients to a low-risk group. This may allow
surgeons to provide more conservative management inpatients with suspected AA and decrease unnecessary
resource utilization [56].
Zouari et al. highlighted the value of CRP ≥ 10
mg/L as a strong predictor of AA in children < 6years old [57].
Yu et al. reported that PCT had little value in diagnosing AA, with lower diagnostic accuracy than CRP and
WBC, but a greater diagnostic value in identifying complicated AA [58]. In a recent meta-analysis, it was confirmed that PCT was more accurate in diagnosing
complicated AA, with a pooled sensitivity of 0.89 (95%
CI 0.84–0.93), specificity of 0.90 (95% CI 0.86–0.94), anddiagnostic odds ratio of 76.73 (95% CI 21.6–272.9) [59].
Zani et al. retrospectively analyzed data from 1197
children admitted for AA and reported that patientswith complicated AA had higher CRP and WBC levels

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than normal patients and those with uncomplicated AA.
The authors found a CRP > 40 mg/L in 58% of patientswith complicated AA and 37% of patients with uncomplicated AA, and WBC > 15 × 109/L in 58% of patientswith complicated AA and 43% of patients with uncomplicated AA [60].
One recent study identified a panel of biomarkers, theAPPY1 test, consisting of WBC, CRP, and myeloidrelated protein 8/14 levels that have the potential toidentify, with great accuracy, children and adolescentswith abdominal pain who are at low risk for AA. The
biomarker panel exhibited a sensitivity of 97.1%, a negative predictive value of 97.4%, and a negative likelihood
ratio of 0.08, with a specificity of 37.9% for AA [51].
Benito et al. prospectively evaluated the usefulness of
WBC and ANC and other inflammatory markers such as
CRP, procalcitonin, calprotectin, and the APPY1 test
panel of biomarkers, to identify children with abdominal
pain at low risk for AA. The APPY1 test panel showed
the highest discriminatory power, with a sensitivity of
97.8, negative predictive value of 95.1, negative likelihood ratio of 0.06, and specificity of 40.6. In the multivariate analysis, only the APPY1 test and ANC > 7500/
mL were significant risk factors for AA [55].
More recently the Appendictis-PEdiatric score (APPE)
was developed with the aim of identifying the risk of
AA. Patients with an APPE score ≤ 8 were at low risk ofAA (sensitivity 94%); those with a score ≥ 15 were athigh risk for AA (specificity 93%). Those between 8 and
15 were defined at intermediate-risk [61].
A number of prospective studies of children were conducted to find urinary biomarkers for AA, such as
leucine-rich α-2-glycoprotein (LRG), not to be usedalone but combined with PAS and routine blood tests.
LRG in conjunction with PAS showed 95% sensitivity,
90% specificity, 91% positive predictive value, and 95%
negative predictive value for AA in children [62].
Among the new laboratory biomarkers developed, theAppendicitis Urinary Biomarker (AuB—leucine-richalpha-2-glycoprotein) appears promising as a diagnostic
tool for excluding AA in children, without the need forblood sampling (negative predictive value 97.6%) [63].
Statement 1.7 White blood cell count, the differential
with the calculation of the absolute neutrophil count,and the CRP are useful lab tests in predicting acute appendicitis in children; moreover, CRP level on admission≥ 10 mg/L and leucocytosis ≥ 16,000/mL are strong predictive factors for appendicitis in pediatric patients. Recommendation 1.6.1 In evaluating children withsuspected appendicitis, we recommend to request routinely laboratory tests and serum inflammatory biomarkers [QoE: Very Low; Strength of recommendation:
Strong: 1D]. Recommendation 1.6.2 In pediatric patients with suspected acute appendicitis, we suggest

adopting both biomarker tests and scores in order topredict the severity of the inflammation and the need for
imaging investigation [QoE: Very Low; Strength of recommendation: Weak: 2D].

Di Saverio et al. World Journal of Emergency Surgery

Q.1.5: What is the optimum pathway for imaging in adultpatients with suspected acute appendicitis?

Estimating pre-image likelihood of AA is important intailoring the diagnostic workup and using scoring systems to guide imaging can be helpful: low-risk adult patients according to the AIR/Alvarado scores could bedischarged with appropriate safety netting, whereas
high-risk patients are likely to require surgery rather
than diagnostic imaging. Intermediate-risk patients arelikely to benefit from systematic diagnostic imaging [64].
A positive US would lead to a discussion of appendectomy and a negative test to either CT or further clinicalobservation with repeated US. A conditional CT strategy, where CT is performed after the negative US, ispreferable, as it reduces the number of CT scans by 50%
and will correctly identify as many patients with AA as
an immediate CT strategy.
Point-of-care ultrasonography (POCUS) has proven to
be a valuable diagnostic tool in diagnosing AA and has apositive impact on clinical decision-making. Overall sensitivity and specificity of US is 76% and 95% and for CT
is 99% and 84% respectively [65].
The meta-analysis by Matthew Fields et al. found thatthe sensitivity and specificity for POCUS in diagnosing
AA were 91% and 97%, respectively. The positive andnegative predictive values were 91% and 94%, respectively [66]. US reliability for the diagnosis of AA can be
improved through standardized results reporting. In the
study by Sola et al., following the adoption of a diagnostic algorithm that prioritized US over CT and encompassed standardized templates, the frequency ofindeterminate results decreased from 44.3% to 13.1%
and positive results increased from 46.4% to 66.1% in patients with AA [67].
Recent studies from the Finnish group led by Salminen
demonstrated that the diagnostic accuracy of contrastenhanced low-dose CT is not inferior to standard CT in
diagnosing AA or distinguishing between uncomplicatedand complicated AA, enabling significant radiation dose
reduction. The OPTICAP randomized trial has shownthat a low-dose protocol using intravenous contrast
media was not inferior to the standard protocol in termsof diagnostic accuracy (79% accurate diagnosis in lowdose and 80% in standard CT by a primary radiologist)
and accuracy to categorize AA severity (79% for bothprotocols). However, the mean radiation dose of lowdose CT was significantly lower compared with standard
CT (3.33 and 4.44 mSv, respectively) [12]. The radiationdose of appendiceal CT for adolescents and young adults

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can be reduced to 2 mSv without impairing clinical outcomes and reducing the potential risk of exposure toionizing radiation simultaneously [68]. The recently published Cochrane systematic review on CT scan for diagnosis of AA in adults identified 64 studies including 71
separate study populations with a total of 10280 participants (4583 with and 5697 without AA). Summary sensitivity of CT scan was 0.95, and summary specificity was
0.94. At the median prevalence of AA (0.43), the probability of having AA following a positive CT result was
0.92, and the probability of having AA following a negative CT result was 0.04. In subgroup analyses according
to contrast enhancement, summary sensitivity was
higher for CT with intravenous contrast (0.96), CT withrectal contrast (0.97), and CT with intravenous and oral
contrast enhancement (0.96) than for non-enhanced CT(0.91). Summary sensitivity for low-dose CT (0.94) was
similar to summary sensitivity for standard-dose orunspecified-dose CT (0.95). Summary specificity did not
differ between low-dose and standard-dose orunspecified-dose CT [69].
The usefulness of CT for determining perforation in
AA is limited [70]. Methods to improve precision in
identifying patients with complicated AA should be explored, as these may help improve risk prediction for the
failure of treatment with antibiotic therapy and guide patients and providers in shared decision-making for treatment options. In cases with equivocal CT features,
repeat US and detection of specific US features (presence of non-compressibility and increased vascular flowof the appendix wall) can be used to discriminate AAfrom a normal appendix [71].
MRI has at least the same sensitivity and specificity as CT and, although has higher costs and issues
around availability in many centers, should be preferred over CT as a first-line imaging study in pregnant women.
The American College of Radiology AppropriatenessCriteria for pregnant women recommend graded compression grayscale US as a preferred initial method incase of suspected AA. These criteria recommend MRI as
a second-line imaging method in inconclusive cases, although MRI can be used as a first-line imaging modality
if available [72]. Others also recommend MRI after nonvisualization or inconclusive US [73]. Despite some excellent US accuracy findings, the main drawback of US
is the rate of non-visualization, which goes from 34.1%
up to 71% with positive AA on the pathology reports[74, 75]. Low US accuracy for the diagnosis of AA in
pregnant patients beyond the 1st trimester of pregnancy
is evident and 30% of pregnant women with suspected
AA have potentially avoidable surgery. Given the low
yield of US, second-line imaging should be considered inthose cases with an inconclusive US before surgery. A

high rate (8%) of false-negative US results are positiveon MRI [73, 76].
From 2011, there are three meta-analyses reporting on
the use of MRI for AA during pregnancy with the following results: sensitivity 90.5%, 94%, and 91.8%; specificity 98.6%, 97%, and 97.9%; positive predictive value
86.3%; and negative predictive value 99.0% [77, 78]. Unfortunately, non-visualization of the appendix is up to
30–43% in some single-center series [79–82]. The rateof non-visualization is higher during the 3rd trimester
when the largest degree of anatomic distortion occurs
due to the gravid uterus [81].
Although a negative or inconclusive MRI does not exclude AA during pregnancy, many authors suggest MRI
as the gold standard in all female patients during theirreproductive years, mostly because of its high specificity
and sensitivity (100% and 89%, respectively) and the highnegative (96–100%) and positive (83.3–100%) predictive
values [73, 83, 84].
Statement 1.8 Combination of US and clinical (e.g.,
AIR, AAS scores) parameters forming combined clinicoradiological scores may significantly improve diagnostic
sensitivity and specificity and eventually replace the needfor a CT scan in adult patients with suspected acute appendicitis. Recommendation 1.7 We recommend theroutine use of a combination of clinical parameters and
US to improve diagnostic sensitivity and specificity andreduce the need for CT scan in the diagnosis of acuteappendicitis. The use of imaging diagnostics is recommended in patients with suspected appendicitis after an
initial assessment and risk stratification using clinicalscores [QoE: Moderate; Strength of recommendation:
Strong; 1B].
Statement 1.9 Intermediate-risk classification identifies patients likely to benefit from observation and systematic diagnostic imaging. Recommendation 1.8 Wesuggest proceeding with timely and systematic diagnostic
imaging in patients with intermediate-risk of acute appendicitis [QoE: Moderate; Strength of recommendation:
Weak; 2B].
Statement 1.10 Patients with strong signs and symptoms and high risk of appendicitis according to AIR
score/Alvarado score/AAS and younger than 40 years
old may not require cross-sectional pre-operative imaging (i.e., CT scan). Recommendation 1.9 We suggestthat cross-sectional imaging (i.e., CT scan) for high-riskpatients younger than 40 years old (AIR score 9–12,
Alvarado score 9–10, and AAS ≥ 16) may be avoided before diagnostic +/− therapeutic laparoscopy [QoE: Moderate; Strength of recommendation: Weak; 2B].
Comment: This statement and recommendation has
raised an intense debate among the panel of experts andconsensus was difficult to reach, especially in view of thestrong opinions from two parties: one advocating the

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need of routine imaging with CT scan for all high-riskpatients before any surgery and the other advocating thevalue of the clinical scores and thorough clinical assessment and risk stratification as being enough for proceeding to diagnostic and therapeutic laparoscopy in thesubset of patients younger than 40 years old and scoringhigh in all Alvarado, AIR, and AAS scores.
The results of the first round of the Delphi consensus
modified the previous recommendation from 2016 guidelines (see graphs included as Supplementary Material files
2, 3, 4, 5 and 6) as follows: “We suggest appendectomy
without pre-operative imaging for high-risk patients younger than 50 years old according to the AIR score”, 8.3%
agreement; “We suggest diagnostic +/− therapeutic laparoscopy without pre-operative imaging for high-risk patients younger than 40 years old, AIR score 9–12,
Alvarado score 9–10, and AAS ≥ 16”, 70.8% agreement;“Delete recommendation”, 20.8% agreement) were discussed in a further consensus due to the strong opposition
by few of the expert panelists who were still not keen to
accept the results of the first Delphi and the recommendation despite being already labeled as a weak recommendation (“suggestion” according to GRADE Criteria).
A further revision of the statement was proposed
and a second round of Delphi was performed before
endorsing the final recommendation “We suggestthat cross-sectional imaging i.e. CT scan for highrisk patients younger than 40 years old, AIR score 9–
12 and Alvarado score 9–10 and AAS ≥ 16 may be
avoided before diagnostic +/− therapeutic laparoscopy” which obtained the 68.0% of agreement,
whereas the statement “We suggest diagnostic +/−therapeutic laparoscopy without pre-operative imaging for high-risk patients younger than 40 years
old and AIR score 9–12; Alvarado score 9–10; AAS≥ 16” reached 26% and the option “delete the statement and recommendations reached 6%. Some authors also added that cross-sectional imaging, i.e.,
CT scan for high-risk patients younger than 40 years
old may be skipped or imaging may be avoided atall, before diagnostic +/− therapeutic laparoscopy foryoung male patients. Some also emphasized that the
responsible surgeon (not PGY1 trainee) should
examine the patient prior to the decision for CT
scanning and recommended a highly value-based
surgical care. WSES supports this recommendationof a value-based surgical care and these further comments will be the ground for the next future editionsof the guidelines, when hopefully further and stronger evidence will be available from the literature
about this challenging subgroup of high-risk scoring
patients. All the graphs reporting the results of theadditional Delphi are reported within the Supplementary Material files 2, 3, 4, 5 and 6.

Statement 1.11 POCUS (Point-of-care Ultrasound) isa reliable initial investigation with satisfactory sensitivity
and specificity in diagnosing acute appendicitis, easing
swift decision-making by the emergency physicians orsurgeons. POCUS, if performed by an experienced operator, should be considered the most appropriate firstline diagnostic tool in both adults and children. Recommendation 1.10 We recommend POCUS as the mostappropriate first-line diagnostic tool in both adults andchildren, if an imaging investigation is indicated basedon clinical assessment [QoE: Moderate; Strength of recommendation: Strong; 1B].
Statement 1.12 When it is indicated, contrastenhanced low-dose CT scan should be preferred overcontrast-enhanced standard-dose CT scan. Diagnostic
accuracy of contrast-enhanced low-dose CT is notinferior to standard CT in diagnosing AA or distinguishing between uncomplicated and complicatedacute appendicitis and enables significant radiationdose reduction. Recommendation 1.11 We recommend the use of contrast-enhanced low-dose CT
scan over contrast-enhanced standard-dose CT scanin patients with suspected acute appendicitis andnegative US findings [QoE: High; Strength of recommendation: Strong; 1A].
Statement 1.13 In patients with normal investigations and symptoms unlikely to be acute appendicitis but which do not settle, cross-sectional imaging
is recommended before surgery. Laparoscopy is recommended to establish/exclude the diagnosis ofacute appendicitis and eventually treat the disease.
Recommendation 1.12 We recommend crosssectional imaging before surgery for patients withnormal investigations but non-resolving right iliac
fossa pain. After negative imaging, initial nonoperative treatment is appropriate. However, inpatients with progressive or persistent pain, explorative laparoscopy is recommended to establish/exclude the diagnosis of acute appendicitis oralternative diagnoses [QoE: High; Strength of recommendation: Strong; 1A].
Statement 1.14 MRI is sensitive and highly specificfor the diagnosis of acute appendicitis during pregnancy.
However, a negative or inconclusive MRI does not exclude appendicitis and surgery should be still consideredif high clinical suspicion. Recommendation 1.13.1 Wesuggest graded compression trans-abdominal ultrasoundas the preferred initial imaging method for suspected
acute appendicitis during pregnancy [QoE: Very Low;
Strength of Recommendation: Weak; 2C]. Recommendation 1.13.2 We suggest MRI in pregnant patients withsuspected appendicitis, if this resource is available, afterinconclusive US [QoE: Moderate; Strength of recommendation: Weak; 2B].

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Di Saverio et al. World Journal of Emergency Surgery(2020) 15:27

Q.1.6: What is the optimum pathway for imaging inpediatric patients with suspected acute appendicitis?

US is currently the recommended initial imaging studyof choice for the diagnosis of AA in pediatric and young
adult patients. US has been shown to have high diagnostic accuracy for AA as an initial imaging investigationand to reduce or obviate the need for further imaging
without increased complications or unacceptable increases in length of stay [85].
However, the sensitivity and specificity of US for the
diagnosis of pediatric AA varies across studies: it is wellknown that US is operator dependent and may be
dependent on patient-specific factors, including BMI [86].
A retrospective study assessing the ability of US to
identify complicated AA or an appendicolith showedthat US has a high specificity and negative predictive
value to exclude complicated AA and the presence of an
appendicolith in children being considered for nonoperative management of uncomplicated AA [87].
The study by Bachur et al. found that, among children
with suspected AA, the use of US imaging has increased
substantially (from 24.0% in 2010 to 35.3% in 2013),
whereas the use of CT has decreased (from 21.4% in2010 to 11.6% in 2013). However, important conditionspecific quality measures, including the frequency ofappendiceal perforation and readmissions, remained
stable, and the proportion of negative appendectomy declined slightly [88].
The use of CT in the pediatric population can be
reduced by using appropriate clinical and/or staged
algorithm based on US/MRI implementation, with asensitivity up to 98% and a specificity up to 97% andby applying imaging scoring system, such as the
Appy-Score for reporting limited right lower quadrant US exams, that performs well for suspectedpediatric AA [89–91].
A systematic literature review was performed to evaluate the effectiveness of abdominal US and abdominal CT
in diagnosing AA in adult and pediatric patients. Data
reported that for US, the calculated pooled values ofsensitivity, specificity, positive predictive value, andnegative predictive value were 86%, 94%, 100%, and 92%,
respectively. For CT, the calculated pooled values of sensitivity, specificity, positive predictive value, and negative
predictive value were 95%, 94%, 95%, and 99%, respectively. These results suggest that US is an effective firstline diagnostic tool for AA and that CT should be
performed for patients with inconclusive ultrasonographic finding [92]. Recently, a meta-analysis was carried out to compare the accuracy of US, CT, and MRI
for clinically suspected AA in children. The area under
the receiver operator characteristics curve of MRI(0.995) was a little higher than that of US (0.987) andCT (0.982) but with no significant difference [93].

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Lee et al. compared US and CT in terms of negative
appendectomy rate and appendiceal perforation rate inadolescents and adults with suspected appendicitis toevaluate the diagnostic performance as preoperative imaging investigations with a propensity score method.
This analysis reported that the use of US instead of CT
may increase the negative appendectomy rate but does
not significantly affect the rate of perforation [94].
A low dose CT, when indicated, can be an adequate
method compared to US and standard dose CT in diagnosing AA in children in terms of sensitivity (95.5% vs95.0% and 94.5%), specificity (94.9% vs 80.0% and 98.8%),
positive-predictive value (96.4% vs 92.7%), and negativepredictive value (93.7% vs 85.7% and 91.3%) [95].
The diagnostic performance of staged algorithms involving US followed by conditional MRI imaging for the
diagnostic workup of pediatric AA has proven to be high(98.2% sensitive and 97.1% specific) [90]. MRI is a feasible alternative to CT for secondary imaging in AA inchildren, and it can differentiate perforated from nonperforated AA with a high specificity [96].
MRI plays a role as an imaging investigation to avoid
CT radiation dose in children with inconclusive US findings. Moore et al. reported sensitivity of 96.5%, specificity of 96.1%, positive predictive value of 92.0%, andnegative predictive value of 98.3% for MRI [97].
In a prospective study conducted by Kinner et al.,when the diagnostic accuracy of MRI was compared toCT, sensitivity and specificity were 85.9% and 93.8% for
non-enhanced MRI, 93.6% and 94.3% for contrastenhanced MRI, and 93.6% and 94.3% for CT [98].
However, the costs and the availability of MRI often
prevent its use as the initial imaging investigation incases of suspected AA.
As second-line imaging modalities after initial US for
assessing AA in children and adults, repeated US, CT,
and MRI showed comparable and high accuracy in children and adults. These three modalities may be valid assecond-line imaging in a clinical imaging pathway for
diagnosis of AA. In particular, pooled sensitivities andspecificities of second-line US for the diagnosis of AA inchildren were 91.3% and 95.2%, respectively. Regarding
second-line CT, the pooled sensitivities and specificities
were 96.2% and 94.6%. Regarding second-line MRI,
pooled sensitivities and specificities were 97.4% and97.1% [99].
Statement 1.15 The use of US in children is accurate
and safe in terms of perforation rates, emergency department re-visits, and negative appendectomy rates. CT use
may be decreased by using appropriate clinical and/or
staged algorithm with US/MRI. MRI has at least thesame sensitivity and specificity as CT and, althoughhigher costs, should be preferred over CT as second-line
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pediatric patients with suspected appendicitis, we suggest the use of US as first-line imaging. In pediatric patients with inconclusive US, we suggest choosing thesecond-line imaging technique based on local availability
and expertise, as there are currently no strong data tosuggest a best diagnostic pathway due to a variety of options and dependence on local resources [QoE: Moderate; Strength of recommendation: Weak: 2B].
Recommendation 1.14.2 Since in pediatric patientswith equivocal CT finding the prevalence of true acuteappendicitis is not negligible, we suggest against the routine use of CT as first-line imaging in children with rightiliac fossa pain [QoE: Moderate; Strength of recommendation: Weak; 2B].

antibiotic group, 27.3% of patients underwent appendectomy within 1 year of initial presentation for
AA. Of the 256 patients available for follow-up in
the antibiotic group, 72.7% did not require surgery.
Of the 70 patients randomized to antibiotic treatment who subsequently underwent appendectomy,
82.9% had uncomplicated AA, 10.0% had complicated AA, and 7.1% did not have AA but received
appendectomy for suspected recurrence. There were
no intra-abdominal abscesses or other major complications associated with delayed appendectomy in patients randomized to antibiotic treatment [103].
The 5-year follow-up results of the APPAC trial reported that, among patients who were initially treatedwith antibiotics, the likelihood of late recurrence was
39.1%. Only 2.3% of patients who had surgery for recurrent AA were diagnosed with complicated forms of thedisease. The overall complication rate was significantly
reduced in the antibiotic group compared to the appendectomy group (6.5% vs 24.4%). This long-term
follow-up supports the feasibility of NOM with antibiotics as an alternative to surgery for uncomplicated AA[104]. Furthermore, patients receiving antibiotic therapy
incur lower costs than those who had surgery [105].
The presence of an appendicolith has been identified
as an independent prognostic risk factor for treatment
failure in NOM of uncomplicated AA. When presenting
together with AA, the presence of appendicoliths is associated with increased perforation risk. The recently published study by Mällinen et al. further corroborates theprevious clinical hypothesis showing that the presence ofan appendicolith is an independent predictive factor forboth perforation and the failure of NOM of uncomplicated AA [106–108].
Case reports show that it may be possible to manage
uncomplicated AA non-operatively (definitively or as abridge therapy) during pregnancy [109, 110]. There is asingle study, with 25% of pregnant patients with uncomplicated AA treated conservatively. The failure rate was15%. Recurrence rate during the same pregnancy was
12% [111]. A small number of published cases had different antibiotic regimens which include different antibiotics or their combinations and different durations ofinitial intravenous administration with different durationof antibiotic continuation in the form of oral administration (3–7 days in total) [102, 111].
Statement 2.1 The antibiotic-first strategy can be considered safe and effective in selected patients with uncomplicated acute appendicitis. Patients who wish to
avoid surgery must be aware of a risk of recurrence ofup to 39% after 5 years. Most recent data from metaanalyses of RCTs showed that NOM with antibiotics
achieves a significantly lower overall complication rate at
5 years and shorter sick leave compared to surgery.

Di Saverio et al. World Journal of Emergency Surgery

Topic 2: Non-operative management of uncomplicatedacute appendicitis
Q.2.1: Is non-operative management with or without
antibiotics a safe and effective treatment option for adultpatients with uncomplicated acute appendicitis?

Recent systematic reviews and meta-analyses of RCTs
have concluded that the majority of patients with uncomplicated AA can be treated with an antibiotic-first
approach [16, 18, 100].
The recent meta-analysis by Harnoss et al. reported arecurrence rate of symptoms within 1 year of 27.4% following antibiotic-first treatment. Taking into consideration any kind of post-interventional complication(including treatment failure), the complication-freetreatment success rate of antibiotic therapy was significantly inferior to the rate after surgery (68.4 vs 89.8%).
There is also evidence that NOM for uncomplicated AA
does not statistically increase the perforation rate inadult patients receiving antibiotic treatment. NOM with
antibiotics may fail during the primary hospitalization inabout 8% of cases, and an additional 20% of patientsmight need a second hospitalization for recurrent AAwithin 1 year from the index admission [16, 17].
The success of the non-operative approach requires
careful patient selection and exclusion of patients withgangrenous AA, abscesses, and diffuse peritonitis. Hansson et al. in their study on 581 patients with AA published in 2014 found that patients with assumed AA
who fulfilled all criteria with CRP < 60 g/L, WBC < 12 ×
109/L, and age < 60 years had an 89% of chance of recovery with antibiotics without surgery [101]. In another recent study, patients with a longer duration of symptoms
prior to admission (> 24 h) were more likely to have successful NOM. Other independent predictors of NOM
success included lower temperature, imaging-confirmed
uncomplicated AA with lower modified Alvarado score(< 4), and smaller diameter of the appendix [102].
In the APPAC randomized trial appendectomy resulted in an initial success rate of 99.6%. In the(2020) 15:27

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Recommendation 2.1.1 We recommend discussing
NOM with antibiotics as a safe alternative to surgery inselected patients with uncomplicated acute appendicitis
and absence of appendicolith, advising of the possibilityof failure and misdiagnosing complicated appendicitis[QoE: High; Strength of Recommendation: Strong; 1A].
Recommendation 2.1.2 We suggest against treating
acute appendicitis non-operatively during pregnancy
until further high-level evidence is available [QoE: Very
Low; Strength of Recommendation: Weak; 2C].

ranged from 0 to 13% for NOM versus 0–17% forappendectomy. NOM avoided an appendectomy in 62–
81% of children after 1-year follow-up. The authors concluded that NOM can avoid an appendectomy in a large
majority of children after 1-year follow-up but evidence
was insufficient to suggest NOM in all children with uncomplicated AA [121].
In the meta-analysis by Kessler et al. NOM showed areduced treatment efficacy (relative risk 0.77, 95% CI
0.71–0.84) and an increased readmission rate (relativerisk 6.98, 95% CI 2.07–23.6), with a comparable rate ofcomplications (relative risk 1.07, 95% CI 0.26–4.46). Exclusion of patients with appendicoliths improved treatment efficacy in conservatively treated patients. The
authors concluded that NOM was associated with ahigher readmission rate [122].
Considering these results, NOM can be suggested only
for selected pediatric patients presenting with uncomplicated AA.
Minneci et al. conducted a prospective patient choicecohort study enrolling 102 patients aged 7 to 17 years
and showed that the incidence of complicated AA was
2.7% in the NOM group and 12.3% in the appendectomy
group. After 1 year, children managed nonoperatively
had fewer disability days and lower appendicitis-related
health care costs compared with those who underwent
appendectomy [114].
Statement 2.2 NOM for uncomplicated acute appendicitis in children is feasible, safe, and effective as initial
treatment. However, the failure rate increases in thepresence of appendicolith, and surgery is recommended
in such cases. Recommendation 2.2 We suggest discussing NOM with antibiotics as a safe and effective alternative to surgery in children with uncomplicatedacute appendicitis in the absence of an appendicolith,advising of the possibility of failure and misdiagnosing
complicated appendicitis [QoE: Moderate; Strength ofrecommendation: Weak; 2B].

Di Saverio et al. World Journal of Emergency Surgery

Q.2.2: Is non-operative management with or without
antibiotics a safe and effective treatment option for
pediatric patients with uncomplicated acute appendicitis?

Less than 19% of children have a complicated acuteappendicitis; hence, the majority of children with uncomplicated AA may be considered for either a nonoperative or an operative management [112].
The antibiotic-first strategy appears effective as an initial treatment in 97% of children with uncomplicatedAA (recurrence rate 14%), with NOM also leading toless morbidity, fewer disability days, and lower costs
than surgery [113, 114].
A systematic review of all evidence available comparing appendectomy to NOM for uncomplicated AA inchildren included 13 studies, 4 of which were retrospective studies, 4 prospective cohort studies, 4 prospective
non-randomized comparative trials, and 1 RCT. The initial success of the NOM groups ranged from 58 to
100%, with 0.1–31.8% recurrence at 1 year [115].
The meta-analysis by Huang et al. showed that antibiotics as the initial treatment for pediatric patientswith uncomplicated AA may be feasible and effective
without increasing the risk of complications. However, surgery is preferred for uncomplicated AA withthe presence of an appendicolith as the failure rate
in such cases is high [116].
The prospective trial by Mahida et al. reported thatthe failure rate of NOM with antibiotics in children affected by uncomplicated AA with appendicolith washigh (60%) at a median follow-up of less than 5 months[117]. The presence of an appendicolith has also been
associated with high failure rates in the reports published by Tanaka et al. (failure rate, 47%), Svensson et al.
(failure rate, 60%), and Lee et al., concluding that patients with evidence of an appendicolith on imaging had
an initial NOM failure rate of more than twice that ofpatients without an appendicolith [118–120].
Gorter et al. investigated the risk of complications following NOM and appendectomy for uncomplicated AA
in a systematic review. Five studies (RCT and cohort
studies) were analyzed, including 147 children (NOM)
and 173 children (appendectomy) with 1-year follow-up.
The percentage of children experiencing complications

Q.2.3: What is the best non-operative management ofpatients with uncomplicated acute appendicitis?

The implementation of treatment and follow-up protocols based on outpatient antibiotic management andnew evidence indicating safety and feasibility of sameday laparoscopic appendectomy for uncomplicated AA
may result in optimization of the resource used by reducing inpatient admissions and hospital costs for both
NOM and surgical treatment in the future. Although thepilot trial by Talan et al. assessed the feasibility ofantibiotics-first strategy including outpatient management (intravenous ertapenem greater than or equal to
48 h and oral cefdinir and metronidazole), the majorityof RCTs published to date included 48 h minimum of inpatient administration of intravenous antibiotics,

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followed by oral antibiotics for a total length of 7–10
days [123].
The empiric antibiotic regimens for non-critically illpatients with community-acquired intra-abdominal infections as advised by the 2017 WSES guidelines are thefollowing: Amoxicillin/clavulanate 1.2–2.2 g 6-hourly or
ceftriazone 2 g 24-hourly + metronidazole 500 mg 6hourly or cefotaxime 2 g 8-hourly + metronidazole 500
mg 6-hourly.
In patients with beta-lactam allergy: Ciprofloxacin 400
mg 8-hourly + metronidazole 500 mg 6-hourly or moxifloxacin 400 24-hourly. In patients at risk for infection
with community-acquired ESBL-producing Enterobacteriacea: Ertapenem 1 g 24-hourly or tigecycline 100 mg
initial dose, then 50 mg 12-hourly [124].
Currently, the APPAC II trial is running, with the aim
to assess the safety and feasibility of per-oral antibiotic
monotherapy compared with intravenous antibiotic therapy continued by per oral antibiotics in the treatment of
uncomplicated AA. Early results of the APPAC II are expected to be published in 2020 [125].
The results of the RCT by Park et al. challenged theneed for antibiotic therapy in uncomplicated AA and reported promising results regarding possible spontaneous
resolution of uncomplicated AA with supportive care
only. Analysis of the primary outcome measure indicatedthat treatment failure rates in patients presenting with
CT-confirmed uncomplicated AA were similar among
those receiving supportive care with either a nonantibiotic regimen or a 4-day course of antibiotics, withno difference in the rates of perforated AA between thetwo groups reported [126]. Whether recovery from uncomplicated AA is the result of antibiotic therapy or natural clinical remission, and so whether antibiotics aresuperior to simple supportive care remains to beestablished.
The APPAC III multicenter, double-blind, placebocontrolled, superiority RCT comparing antibiotic therapy
with placebo in the treatment of CT scan-confirmed uncomplicated AA is now in its enrollment phase. This new
RCT aims to evaluate the role of antibiotics in the resolution of CT-diagnosed uncomplicated AA by comparing
antibiotic therapy with placebo to evaluate the role of antibiotic therapy in the resolution of the disease [127].
If future research demonstrates that antibiotics do notprovide any advantage over observation alone in uncomplicated AA, this could have a major impact on reducing
the use of antimicrobial agents, especially in this era ofincreasing antimicrobial resistance worldwide.
Statement 2.3 Current evidence supports initial intravenous antibiotics with subsequent conversion to oral
antibiotics until further evidence from ongoing RCT isavailable. Recommendation 2.3 In the case of NOM,
we recommend initial intravenous antibiotics with asubsequent switch to oral antibiotics based on patient's
clinical conditions [QoE: Moderate; Strength of recommendation: Strong; 1B].
Statement 2.4 Uncomplicated acute appendicitis may
safely resolve spontaneously with similar treatment failure rates and shorter length of stay and costs comparedwith antibiotics. However, there is still limited data forthe panel to express in favor of or against the symptomatic treatment without antibiotics [QoE: Moderate; No
recommendation].

Di Saverio et al. World Journal of Emergency Surgery

Topic 3: Timing of appendectomy and in-hospital delay
Q.3.1: Does in-hospital delay increase the rate ofcomplications or perforation for adult patients with
uncomplicated acute appendicitis?

The theory hypothesizing that perforated AA might
be a different disease entity from uncomplicated AA,
rather than being the natural evolution of the disease, has some support in the recent meta-analysis
by van Dijk et al., demonstrating that delaying appendectomy for up to 24 h after admission does notappear to be a risk factor for complicated AA, postoperative morbidity, or surgical-site infection. Pooled
adjusted ORs revealed no significantly higher risk forcomplicated AA when appendicectomy was delayedfor 7–12 or 13–24 h, and meta-analysis of unadjusted data supported these findings by yielding no
increased risk for complicated AA or postoperativecomplications with a delay of 24–48 h [22].
Data from the American College of Surgeons NSQIP
demonstrated similar outcomes of appendectomy for
AA when the operation was performed on hospital day 1
or 2. Conversely, appendectomies performed on hospitalday 3 had significantly worse outcomes, as demonstrated
by increased 30-day mortality (0.6%) and all major postoperative complications (8%) in comparison with operations taking place on hospital day 1 (0.1%; 3.4%) or 2
(0.1%; 3.6%). Patients with decreased baseline physicalstatus assessed by the ASA Physical Status class had theworst outcomes (1.5% mortality; 14% major complications) when an operation was delayed to hospital day 3.
However, logistic regression revealed higher ASA Physical Status class and open operations as the only predictors of major complications [128].
In the study by Elniel et al., a significant increasein the likelihood of perforated AA occurred after 72
h of symptoms, when compared to 60–72 h. The authors argued that it may be reasonable to prioritize
patients approaching 72 h of symptoms for operative
management [129].
In a large retrospective series of pregnant women withsuspected AA (75.9% with uncomplicated AA, 6.5% withcomplicated AA, and 17.6% with normal appendix), initial US was diagnostic in 57.9% of patients, whereas(2020) 15:27

Page 22 of 42

55.8% of patients underwent a delayed repeat study. In
this cohort, performing a delayed repeat US during aperiod of observation in those patients who remained
otherwise equivocal increased the diagnostic yield of theUS, whereas delaying surgery did not affect maternal or
fetal safety. Such algorithm increased the diagnostic yield
without increasing the proxies of maternal or fetal morbidity. There was no increased rate of perforated appendices in patients with delayed surgery. Still, the negative
appendectomy rate was 17.7% [130].
Statement 3.1 Short, in-hospital surgical delay up to
24 h is safe in uncomplicated acute appendicitis anddoes not increase complications and/or perforation rate
in adults. Surgery for uncomplicated acute appendicitis
can be planned for the next available list minimizing
delay wherever possible (better patient comfort, etc.).
Short, in-hospital delay with observation and repeatedtrans-abdominal US in pregnant patients with equivocal
appendicitis is acceptable and does not seem to increase
the risk of maternal and fetal adverse outcomes. Recommendation 3.1 We recommend planning laparoscopic
appendectomy for the next available operating list within
24 h in case of uncomplicated acute appendicitis, minimizing the delay wherever possible [QoE: Moderate;
Strength of recommendation: Strong; 1B].
Statement 3.2 Delaying appendectomy for uncomplicated acute appendicitis for up to 24 h after admission
does not appear to be a risk factor for complicated appendicitis, postoperative surgical site infection, or morbidity. Conversely, appendectomies performed after 24 hfrom admission are related to increased risk of adverse
outcomes. Recommendation 3.2 We recommend
against delaying appendectomy for acute appendicitis
needing surgery beyond 24 h from the admission [QoE:
Moderate; Strength of recommendation: Strong; 1B].

department triage and appendectomy (11.5 h vs 9.7 h, P
= 0.36) and similar times from admission to appendectomy (5.5 h vs 4.3 h, P = 0.36). Independent risk factors
for SSI were complicated AA, longer symptom duration,and presence of sepsis/septic shock [133].
Gurien et al. retrospectively analyzed data from 484 children who underwent appendectomy at 6, 8, and 12 h fromadmission for AA and reported a mean elapsed time fromadmission to theatre of 394 min. SSIs, appendiceal perforations, and small bowel obstructions were similar between early and delayed groups, and no statisticallysignificant differences were found for SSIs in the nonperforated delayed versus immediate groups. Time fromadmission to theatre did not predict perforation, whereas
WBC count at the time of admission was a significant predictor of perforation (OR 1.08; P < 0.001) [134].
Recently, the American Pediatric Surgical Association
Outcomes and Evidence-Based Practice Committee developed recommendations regarding time to appendectomy for AA in children by a systematic review of the
published articles between January 1, 1970, and November 3, 2016. The committee stated that appendectomy
performed within the first 24 h from presentation is not
associated with an increased risk of perforation or adverse outcomes [135].
Regarding complicated AA, some authors support initial antibiotics with delayed operation whereas others
support immediate operation. Regarding complicatedappendicitis, some authors support initial antibiotics
with delayed operation whereas others support immediate operation. A population-level study with a 1-year
follow-up period found that children undergoing late appendectomy were more likely to have a complication
than those undergoing early appendectomy. These data
support that early appendectomy is the best management in complicated AA [136].
Statement 3.3 Appendectomy performed within thefirst 24 h from presentation in the case of uncomplicatedappendicitis is not associated with an increased risk of
perforation or adverse outcomes. Early appendectomy is
the best management in complicated appendicitis. Recommendation 3.3 We suggest against delaying appendectomy for pediatric patients with uncomplicated acuteappendicitis needing surgery beyond 24 h from the admission. Early appendectomy within 8 h should be performed in case of complicated appendicitis [QoE: Low;
Strength of Recommendation: Weak; 2C].

Di Saverio et al. World Journal of Emergency Surgery

Q.3.2: Does in-hospital delay increase the rate ofcomplications or perforation for pediatric patients with
uncomplicated acute appendicitis?

In children appendectomy performed within the first 24
h from presentation is not associated with an increased
risk of perforation or adverse outcomes [131]. Similarly,
in the multivariate logistic regression analysis by Almstrom et al., increased time to surgery was not associatedwith increased risk of histopathologic perforation, andthere was no association between the timing of surgery
and postoperative wound infection, intra-abdominal abscess, reoperation, or readmission [132].
Data from NSQIP-Pediatrics demonstrated that a 16-h
delay from emergency department presentation or a 12h delay from hospital admission to appendectomy was
not associated with an increased risk of SSI. Comparedwith patients who did not develop an SSI, patients whodeveloped an SSI had similar times between emergency

Topic 4: Surgical treatment
Q.4.1: Does laparoscopic appendectomy confer superior
outcomes compared with open appendectomy for adultpatients with acute appendicitis?

Several systematic reviews of RCTs comparing laparoscopic appendectomy (LA) versus open appendectomy(2020) 15:27

Page 23 of 42(OA) have reported that the laparoscopic approach for
AA is often associated with longer operative times andhigher operative costs, but it leads to less postoperative
pain, shorter length of stay, and earlier return to workand physical activity [137]. LA lowers overall hospitaland social costs [138], improves cosmesis, and significantly decreases postoperative complications, in particular SSI.
The 2018 updated Cochrane review on LA versus OA
showed that, except for a higher rate of IAA (intra-abdominal abscess) after LA in adults, laparoscopic demonstrates advantages over OA in pain intensity on day
one, SSI, length of hospital stay, and time until return tonormal activity [139].
In the meta-review by Jaschinski et al. including ninesystematic reviews and meta-analyses (all moderate tohigh quality), the pooled duration of surgery was 7.6 to
18.3 min shorter with OA. Pain scores on the first postoperative day were lower after LA in two out of three reviews. The risk of IAA was higher for LA in half of six
meta-analyses, whereas the occurrence of SSI pooled by
all reviews was lower after LA. LA shortened hospital
stay from 0.16 to 1.13 days in seven out of eight metaanalyses [14].
The evidence regarding treatment effectiveness of LA
versus OA in terms of postoperative IAA, however,changed over the last decade. The cumulative metaanalysis by Ukai et al. demonstrated that, of the 51 trials
addressing IAA, trials published up to and including
2001 showed statistical significance in favor of OA. The
effect size in favor of OA began to disappear after 2001,
leading to an insignificant result with an overall cumulative OR of 1.32 (95% CI 0.84–2.10) when LA was compared with OA [140].
LA appears to have significant benefits with improved
morbidity compared to OA in complicated AA as well,
as demonstrated in the meta-analysis by Athanasiou
et al. In the pooled analysis, LA had significantly less
SSI, with reduced time to oral intake, and length of
hospitalization. There was no significant difference in
IAA rates. Operative time was longer during LA but did
not reach statistical significance in the RCT subgroup
analysis [141].
Statement 4.1 Laparoscopic appendectomy offers significant advantages over open appendectomy in terms ofless pain, lower incidence of surgical site infection, decreased length of hospital stay, earlier return to work,overall costs, and better quality of life scores. Recommendation 4.1 We recommend laparoscopic appendectomy as the preferred approach over open
appendectomy for both uncomplicated and complicatedacute appendicitis, where laparoscopic equipment andexpertise are available [QoE: High; Strength of recommendation: Strong; 1A].

Q.4.2: Does laparoscopic appendectomy confer superior
outcomes compared with open appendectomy for pediatricpatients with acute appendicitis?

Di Saverio et al. World Journal of Emergency Surgery

The laparoscopic approach to AA seems to be safe andeffective in children.
Zhang et al. conducted a meta-analysis of nine studies
to compare the influence of different surgical procedureson perforated AA in the pediatric population and foundthat LA was associated with lower incidence of SSI andbowel obstruction, but the rate of IAA was higher thanin OA [142].
Yu et al. conducted a meta-analysis of two RCTs and
14 retrospective cohort studies, showing that LA forcomplicated AA reduces the rate of SSIs (OR 0.28; 95%
CI 0.25–0.31) without increasing the rate of postoperative IAA (OR 0.79; 95% CI 0.45–1.34). The results
showed that the operating time in the LA group was
longer than that of the OA groups (WMD 13.78, 95% CI
8.99–18.57), whereas the length of hospital stay in the
LA groups was significantly shorter (WMD − 2.47, 95%
CI − 3.75 to − 1.19), and the time to oral intake wasshorter in the LA group than in the OA group (WMD −0.88, 95% CI − 1.20 to − 0.55) [15].
Statement 4.2 Laparoscopic appendectomy is associated with lower postoperative pain, lower incidence ofSSI, and higher quality of life in children. Recommendation 4.2 We recommend laparoscopic appendectomy
should be preferred over open appendectomy in children
where laparoscopic equipment and expertise are available [QoE: Moderate; Strength of recommendation:
Strong; 1B].
Q.4.3: Does laparoscopic single-incision surgery confer any
advantage over the three-trocar technique in performing
laparoscopic appendectomy for adult patients with acuteappendicitis?

Recent studies provide level 1a evidence that singleincision laparoscopic appendectomy (SILA) is as feasible,
effective, and safe as the conventional three-port LA.
High-level meta-analyses conducted in adults, althoughdemonstrating no significant difference in the safety of
SILA versus that of three-port LA, have not supported
the application of SILA because of its significantly longer
operative times and the higher doses of analgesia required compared with those for three-port LA [143]. A
total of 8 RCTs published between 2012 and 2014 with a
total of 995 patients were included in the meta-analysis
by Aly et al. No significant differences between SILA
and conventional three-port laparoscopic appendectomy(CLA) was found in terms of complication rates, postoperative ileus, length of hospital stay, return to work, or
postoperative pain. CLA was significantly superior to
SILA with reduced operating time (mean difference 5.81
[2.01, 9.62], P = 0.003) and conversion rates (OR 4.14

(2020) 15:27

Page 24 of 42[1.93, 8.91], P = 0.0003). Conversely, SILA surgery had
better wound cosmesis (mean difference 0.55 [0.33,
0.77], P = 0.00001) [144].
Statement 4.3 Single-incision laparoscopic appendectomy is basically feasible, safe, and as effective as conventional three-port laparoscopic appendectomy,
operative times are longer, requires higher doses of analgesia, and is associated with a higher incidence of wound
infection. Recommendation 4.3 We recommend conventional three-port laparoscopic appendectomy oversingle-incision laparoscopic appendectomy, as the conventional laparoscopic approach is associated withshorter operative times, less postoperative pain, andlower incidence of wound infection [QoE: High; Strengthof recommendation: Strong; 1A].

assisted technique is as safe as the laparoscopic three-port
technique. Recommendation 4.4 In pediatric patientswith acute appendicitis and favorable anatomy, we suggest
performing single-incision/transumbilical extracorporeal
laparoscopic assisted appendectomy or traditional threeport laparoscopic appendectomy based on local skills andexpertise [QoE: Low; Strength of recommendation: Weak;
2C].

Di Saverio et al. World Journal of Emergency Surgery

Q.4.4: Does laparoscopic single-incision surgery confer any
advantage over the three-trocar technique in performing
laparoscopic appendectomy for pediatric patients withacute appendicitis?

In children, two recent RCTs showed that SILA is
feasible with an acceptable margin of safety, although
it does not produce any significant difference interms of analgesic use and length of hospital stay[145], and it is associated with longer operative
times and more severe surgical trauma comparedwith the three-port technique, as measured by CRP
and IL-6 levels [146]. In the large meta-analysis by
Zhang et al., no significant differences were observed
between SILA and CLA with respect to the incidence of total postoperative complications, IAA,
ileus, wound hematoma, length of hospital stay, or
the frequency of use of additional analgesics. However, SILA was associated with a higher incidence of
SSI compared with three-port LA and required alonger operative time [147].
Karam et al. conducted a retrospective study with theaim to compare surgical outcomes of children with AA
treated with the transumbilical laparoscopically assisted
appendectomy (TULAA) versus the CLA and showedthat TULAA had a shorter operative time (median, 40 vs
67 min; P < 0.001), a shorter length of stay (median, 20
vs 23 h; P < 0.001), and lower costs (median $6266 vs$8927; P < 0.001), even if SSI rate was slightly higher in
the TULAA group (6% vs 4%; P = 0.19) [148].
Sekioka et al. reported that mean operative time wassignificantly shorter in TULAA than in CLA for both
uncomplicated and complicated AA. In addition, complication rates in complicated AA were significantly
lower in TULAA than in CLA. Moreover, the postoperative hospital stay was significantly shorter in TULAA
than in CLA [149].
Statement 4.4 In children with acute appendicitis, thesingle incision/transumbilical extracorporeal laparoscopic-

Q.4.5: Is outpatient laparoscopic appendectomy safe andfeasible for patients with uncomplicated acute appendicitis?

In the USA, outpatient LA protocols are currently applied at multiple institutions with the aim to reduce thelength of stay and decrease overall health care costs for
AA. Results from these experiences demonstrate that
outpatient LA can be performed with a high rate of success, low morbidity, and low readmission rate in the caseof non-perforated AA [150]. In the study by Frazee
et al., 484 patients with uncomplicated AA were managed as outpatients. Only seven patients (1.2%) were readmitted after outpatient management for transient
fever, nausea/vomiting, migraine headache, urinary tract
infection, partial small bowel obstruction, and deep venous thrombosis. There were no mortalities or reoperations. Including the readmissions, overall success with
outpatient management was 85% [151]. The recent RCT
by Trejo-Avila et al. stated that ERAS implementation
for appendectomy is associated with a significantly
shorter LOS, allowing for the ambulatory managementof patients with uncomplicated AA. The authors concluded that ambulatory LA is safe and feasible with similar rates of morbidity and readmissions compared withconventional care [152].
Statement 4.5 Outpatient laparoscopic appendectomy
for uncomplicated acute appendicitis is feasible and safe
without any difference in morbidity and readmission
rates. It is associated with potential benefits of earlier recovery after surgery and lower hospital and social costs.
Recommendation 4.5 We suggest the adoption of outpatient laparoscopic appendectomy for uncomplicatedappendicitis, provided that an ambulatory pathway withwell-defined ERAS protocols and patient information/consent are locally established [QoE: Moderate; Strengthof recommendation: Weak; 2B].
Q.4.6: Is laparoscopic appendectomy indicated over open
appendectomy in specific patient groups?

LA is a safe and effective method to treat AA in specificsettings such as the elderly and the obese. LA can berecommended for patients with complicated AA evenwith higher risk categories. In the retrospective cohort
study by Werkgartner et al. investigating the benefits of
LA in patients with high peri- and postoperative risk factors (ASA 3 and 4), LA was associated with slightly(2020) 15:27

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longer operative times and shorter hospital stay. Overall
complications, graded according to the Clavien-Dindo
classification, were slightly more frequent in patients
after LA, whereas severe complications occurred more
frequently in patients after OA [153]. For high-risk patients, LA has proven to be safe and feasible and was
also associated with decreased rates of mortality, postoperative morbidity, and shorter hospitalization.
In the recent meta-analysis by Wang et al., 12 studies
with 126,237 elderly patients in the LA group and 213,
201 patients in the OA group were analyzed. Postoperative mortality, as well as postoperative complications
and SSI were reduced following LA. IAA rate was similar
between LA and OA. Duration of surgery was longer following LA, and the length of hospital stay was shorter
following LA [154].
Results from the American College of Surgeons
NSQIP (pediatric database) demonstrated that obesity
was not found to be an independent risk factor for postoperative complications following LA. Although operative time was increased in obese children, obesity did
not increase the likelihood of 30-day postoperative complications [155].
LA also appears to be a safer alternative approach to
OA in obese adult patients. In the systematic review byDasari et al. including seven retrospective cohort studies
and one randomized controlled trial, LA in obese patients was associated with reduced mortality (RR 0.19),
reduced overall morbidity (RR 0.49), reduced superficial
SSI (RR 0.27), and shorter operating times and postoperative length of hospital stay, compared to OA [156].
Despite concerns about the safety of LA during pregnancy being highlighted over the last 10 years due to apossible increase in fetal loss rate, more recent large systematic reviews and meta-analyses of comparative studies concluded that it is not reasonable to state that LA
in pregnant women might be associated with a greaterrisk of fetal loss. Twenty-two comparative cohort studies
were included in the pooled analysis by Lee et al., which
involved 4694 women of whom 905 underwent LA and3789 underwent OA. Fetal loss was significantly higher
among those who underwent LA compared with those
who underwent OA, with a pooled OR of 1.72. However,the sensitivity analysis showed that the effect size was influenced by one of the studies because its removal resulted in there being no significant difference between
LA and OA with respect to the risk of fetal loss (OR1.16). A significant difference was not evident between
LA and OA with respect to preterm delivery (OR 0.76),
and patients who underwent LA had shorter hospital
stays and a lower SSI risk compared with those who
underwent OA [157].
Statement 4.6 Laparoscopic appendectomy seems toshow relevant advantages compared to open

appendectomy in obese adult patients, older patients,
and patients with comorbidities. Laparoscopic appendectomy is associated with reduced mortality, reduced overall morbidity, reduced superficial wound infections, andshorter operating times and postoperative length of hospital stay in such patients. Recommendation 4.6 Wesuggest laparoscopic appendectomy in obese patients,
older patients, and patients with high peri- and postoperative risk factors [QoE: Moderate; Strength of recommendation: Weak; 2B].
Statement 4.7 Laparoscopic appendectomy during
pregnancy is safe in terms of risk of fetal loss and preterm delivery and it is preferable to open surgery as associated to shorter length of hospital stay and lower
incidence of surgical site infection. Recommendation
4.7 We suggest laparoscopic appendectomy should be
preferred to open appendectomy in pregnant patients
when surgery is indicated. Laparoscopy is technicallysafe and feasible during pregnancy where expertise oflaparoscopy is available [QoE: Moderate; Strength of recommendation: Weak; 2B].

Di Saverio et al. World Journal of Emergency Surgery

Q.4.7: Does aspiration alone confer clinical advantages overlavage and aspiration for patients with complicated acuteappendicitis?

The best available evidence suggests that peritoneal irrigation with normal saline during LA does not provide
additional benefits compared with suction alone in termsof IAA, SSI, and length of stay, but it may prolong theoperative time.
The recent meta-analysis by Siotos et al., including
more than 2500 patients from five studies, has shownthat the use of irrigation, despite adding 7 min to theduration of the operation, overall did not demonstrate asignificant decrease in IAA. Both for the adult andpediatric subpopulations, the use of irrigation was associated with a non-significant lower odd of IAA [158].
In the same way, the large meta-analysis by Hajibandeh et al. (three RCTs and two retrospective observational studies included) demonstrated that there was nodifference between peritoneal irrigation and suction
alone in terms of IAA rate, SSI, and length of stay. These
results remained consistent when RCTs, adult patients,
and pediatric patients were analyzed separately [159].
However, the quality of the best available evidence on
this point is moderate; therefore, high-quality, adequately powered randomized studies are required toprovide a more robust basis for definite conclusions.
Statement 4.8 Peritoneal irrigation does not have any
advantage over suction alone in complicated appendicitis
in both adults and children. The performance of irrigation during laparoscopic appendectomy does not seem
to prevent the development of IAA and wound infections in neither adults nor pediatric patients.

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Recommendation 4.8 We recommend performing suction alone in complicated appendicitis patients withintra-abdominal collections undergoing laparoscopic appendectomy [QoE: Moderate; Strength of recommendation: Strong; 1B].

initially reported advantages with routine use of endostaplers in terms of complication and operative times, more
recent studies have repeatedly demonstrated no differences in intra- or postoperative complications between
either endostapler or endoloops stump closure [166].
Recent evidence shows that the use of Hem-O-Lok(HOL) clips is safe and reduced the costs of the procedurein comparison to the use of endoloops. In the study by AlTermini et al., HOL clip use was associated with lower
overall complications rate compared with endoloops. The
minimum endoloop cost per single appendectomy was$273.13, while HOL clip cost was $32.14 [167].
The multicenter prospective observational study by
Van Rossem et al. has demonstrated that the infectious
complication rate is not influenced by the type of appendicular stump closure when comparing endoloops or an
endostapler. Median operating time was not different between endoloop and endostapler use (42.0 vs 44.0 min)and no significant effect of stump closure type was observed for any infectious complication or IAA. In multivariable analysis, complicated AA was identified as the
only independent risk factor for IAA [168].
In the same way, the large systematic review andmeta-analysis by Ceresoli et al. showed that in complicated AA, the stump closure technique did not affectoutcomes. A total of 5934 patients from 14 studies were
included in the analysis. Overall, endostapler use was associated with a similar IAA rate but a lower incidence ofSSI, whereas the length of stay and readmission and reoperation rates were similar [169].
The most recent Cochrane review comparing mechanical appendix stump closure (stapler, clips, or electrothermal devices) versus ligation (endoloop, Roeder loop,
or intracorporeal knot techniques) for uncomplicatedAA included eight RCTs encompassing 850 participants.
Five studies compared titanium clips versus ligature, twostudies compared an endoscopic stapler device versus
ligature, and one study compared an endoscopic stapler
device, titanium clips, and ligature. No differences intotal complications, intra-operative complications, or
postoperative complications between ligature and alltypes of mechanical devices were found. However, theanalyses of secondary outcomes revealed that the use of
mechanical devices saved approximately 9 min of thetotal operating time when compared with the use of aligature, even though this result did not translate into aclinically or statistically significant reduction in inpatient
hospital stay [170].
Recently, 43 randomized controlled trials enrolling over
5,000 patients were analyzed in the network meta-analysis
by Antoniou et al. The authors concluded that the use of
suture ligation of the appendix in LA seems to be superior
to other methods for the composite parameters of organ/space and superficial operative site infection [171].

Di Saverio et al. World Journal of Emergency Surgery

Q.4.8: Does the type of mesoappendix dissection technique(endoclip, endoloop, electrocoagulation, Harmonic Scalpel,
or LigaSure) produce different clinical outcomes for patientswith acute appendicitis undergoing appendectomy?

Simplified and cost-effective techniques for LA havebeen described. They use either two endoloops, securing
the blood supply, or a small number of endoclips.
In the case of an inflamed and edematous mesoappendix, it has been suggested that the use of LigaSureTM, especially in the presence of gangrenous tissue, may be
advantageous [160, 161]. Despite the potential advantages,
LigaSure TM represents a high-cost option and it may belogical using endoclips if the mesoappendix is not edematous. Diamantis et al. compared LigaSureTM and Harmonic Scalpel with monopolar electrocoagulation andbipolar coagulation: the first two caused more minimal
thermal injury of the surrounding tissue than other techniques [162]. Recently, significantly higher thermal damage was found on the mesoappendix and appendiceal basein patients treated with LigaSure TM than in patients forwhom Harmonic Scalpel was used during LA [163].
Monopolar electrocoagulation, being safe, quick, andrelated to very low rates of complications and conversion to OA, can be considered the most cost-effective
method for mesoappendix dissection in LA [164]. A recent retrospective cohort study by Wright et al. has proposed that the use of a single stapler line for transectionof the mesoappendix and appendix as a safe and efficienttechnique that results in reduced operative duration withexcellent surgical outcomes [165].
Statement 4.9 There are no clinical differences in outcomes, length of hospital stay, and complication rates between the different techniques described for mesentery
dissection (monopolar electrocoagulation, bipolar energy,
metal clips, endoloops, LigaSure, Harmonic Scalpel, etc.).
Recommendation 4.9 We suggest the use of monopolarelectrocoagulation and bipolar energy as they are the mostcost-effective techniques, whereas other energy devices
can be used depending on the intra-operative judgment of
the surgeon and resources available [QoE: Moderate;
Strength of recommendation: Weak; 2B].
Q.4.9: Does the type of stump closure technique (stapler or
endoloop, ligation or invagination of the stump) produce
different clinical outcomes for patients with acuteappendicitis undergoing appendectomy?

The stump closure may vary widely in practice and theassociated costs can be significant. While earlier studies

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Current evidence suggests that polymeric clips are aneffective and cost-efficient method for stump closure in
LA for AA. In the recent meta-analysis by Knight et al.
including over 700 patients, polymeric clips were foundto be the cheapest method (€20.47 average per patient)and had the lowest rate of complications (2.7%) compared to other commonly used closure methods. Meanwhile, operative time and duration of in-patient staywere similar between groups [172].
Many studies compared the simple ligation and thestump inversion and no significant difference was found.
Eleven RCTs (2634 patients) were included in the systematic review and meta-analysis by Qian et al. Postoperative
pyrexia and infections were similar between simple
ligation and stump inversion groups, respectively, but theformer group had a shorter operative time, less incidenceof postoperative ileus, and quicker postoperative recovery.
The clinical results revealed that simple ligation was significantly superior to stump inversion [173].
Statement 4.10 There are no clinical advantages in
the use of endostaplers over endoloops for stump closure for both adults and children in either simple or complicated appendicitis, except for a lower incidence ofwound infection when using endostaplers in children
with uncomplicated appendicitis. Polymeric clips may be
the cheapest and easiest method (with shorter operative
times) for stump closure in uncomplicated appendicitis.
Recommendation 4.10 We recommend the use ofendoloops/suture ligation or polymeric clips for stumpclosure for both adults and children in either uncomplicated or complicated appendicitis, whereas endostaplers
may be used when dealing with complicated cases depending on the intra-operative judgment of the surgeon
and resources available [QoE: Moderate; Strength of recommendation: Strong; 1B].
Statement 4.11 Simple ligation should be preferred tostump inversion, either in open or laparoscopic surgery,as the major morbidity and infectious complications are
similar. Simple ligation is associated with shorter operative times, less postoperative ileus and quicker recovery.
Recommendation 4.11 We recommend simple ligation
over stump inversion either in open and laparoscopic
appendectomy [QoE: High; Strength of recommendation: Strong; 1A].

peritoneal abscess or for SSI at 14 days. The increased
risk of a 30-day overall complication rate in the drainage
group was rated as very low-quality evidence, as well as
the evidence that drainage increases hospital stay by
2.17 days compared to the no drainage group. Thus,
there is no evidence for any clinical improvement byusing abdominal drainage in patients undergoing OA forcomplicated AA [174].
Low-quality studies have reported that routine drainage has not proven its utility and seems to cause more
complications, higher length of hospital stay, and transit
recovery time [175]. In the large retrospective cohort
study by Schlottmann et al. the placement of intraabdominal drains in complicated AA did not present
benefits in terms of reduced IAA and even lengthened
hospital stay [176].
Statement 4.12 In adult patients, the use of drains
after appendectomy for perforated appendicitis and abscess/peritonitis should be discouraged. Drains are of nobenefit in preventing intra-abdominal abscess and leadto longer length of hospitalization, and there is also lowquality evidence of increased 30-day morbidity andmortality rates in patients in the drain group. Recommendation 4.12 We recommend against the use ofdrains following appendectomy for complicated appendicitis in adult patients [QoE: Moderate; Strength of recommendation: Strong; 1B].

Di Saverio et al. World Journal of Emergency Surgery

Q.4.10: Is the use of abdominal drains recommended after
appendectomy for complicated acute appendicitis in adultpatients?

The updated 2019 Cochrane review on the issue included six RCTs (521 participants), comparing abdominal drainage and no drainage in patients undergoing
emergency OA for complicated AA. The authors foundthat there was insufficient evidence to determine the effects of abdominal drainage and no drainage on intra-

Q.4.11: Is the use of abdominal drains recommended after
appendectomy for complicated acute appendicitis inpediatric patients?

The prophylactic use of abdominal drainage after LA for
perforated AA in children does not prevent postoperative complications and may be associated with negative
outcomes.
Aneiros Castro et al. retrospectively analyzed 192
pediatric patients (mean age of 7.77 ± 3.4 years) undergoing early LA for perforated AA and reported that
there were no statistically significant differences between
the drain and no drain groups in the rate of IAA, SSI,
and bowel obstruction. However, drains were statisticallyassociated with an increased requirement for antibiotic
and analgesic medication, fasting time, operative time,and length of hospital stay [177].
Statement 4.13 The prophylactic use of abdominal
drainage after laparoscopic appendectomy for perforated
appendicitis in children does not prevent postoperativecomplications and may be associated with negative outcomes. Recommendation 4.13 We suggest against theprophylactic use of abdominal drainage after laparoscopic appendectomy for complicated appendicitis inchildren [QoE: Low; Strength of recommendation:
Weak; 2C].

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Q.4.12: What are the best methods to reduce the risk of SSI
in open appendectomies with contaminated/dirty wounds?

lower costs. Recommendation 4.15 We recommend
primary skin closure with a unique absorbable intradermal suture for open appendectomy wounds [QoE: Moderate; Strength of recommendation: Weak; 2B].

Di Saverio et al. World Journal of Emergency Surgery

Wound edge protectors significantly reduce the rate of
SSI in open abdominal surgery. The systematic review
and meta-analysis by Mihaljevic et al. (16 randomized
controlled trials including 3695 patients investigating
wound edge protectors published between 1972 and2014) showed that wound edge protectors significantly
reduced the rate of SSI (RR 0.65). A similar effect size
was found in the subgroup of patients undergoing colorectal surgery (RR 0.65). Of the two common types ofwound protectors, double-ring devices were found to exhibit a greater protective effect (RR 0.29) than singlering devices (RR 0.71) [178].
The use of ring retractors showed some evidence of
SSI reduction (RR 0.44) in the meta-analysis by Ahmed
et al., which included four RCTs with 939 patients. On
subgroup analysis, ring retractor was more effective inmore severe degrees of appendiceal inflammation (contaminated group) [179].
A recent RCT comparing primary and delayed primarywound closure in complicated AA showed that thesuperficial SSI rate was lower in patients who underwent
primary wound closure than delayed primary woundclosure (7.3% vs 10%), although the risk difference of −2.7% was not statistically significant. Postoperative pain,
length of stay, recovery times, and quality of life werenonsignificantly different with corresponding risk differences of 0.3, − 0.1, − 0.2, and 0.02, respectively. However, costs for primary wound closure were lower thandelayed primary wound closure [180].
In the RCT by Andrade et al. comparing skin closure
with a unique absorbable intradermal stitch and traditional closure technique (non-absorbable separated
stitches), OA skin closure with the former has shown tobe safe, with a reduced seroma and abscess incidence
and an equivalent dehiscence and superficial SSI incidence. Furthermore, the relative risk of complications
with traditional skin closure was 2.91 higher, comparedto this new technique [181].
Statement 4.14 The use of wound ring protectors
shows some evidence of surgical site infection reduction
in open appendectomy, especially in case of complicatedappendicitis with contaminated/dirty wounds. Recommendation 4.14 We recommend wound ring protectors
in open appendectomy to decrease the risk of SSI [QoE:
Moderate; Strength of recommendation: Strong; 1B].
Statement 4.15 Delayed primary skin closure increases the length of hospital stay and overall costs inopen appendectomies with contaminated/dirty wounds
and does not reduce the risk of SSI. Subcuticular sutureseems preferable in open appendectomy for acute appendicitis as it is associated with a lower risk of complications (surgical site infection/abscess and seroma) and

Topic 5: Intra-operative grading of acute appendicitis
Q.5.1: What is the value of scoring systems for intraoperative grading of acute appendicitis?

There is considerable variability in the intra-operativeclassification of AA. In the multicenter cohort study byStrong et al. involving 3,138 patients, the overall disagreement between the surgeon and the pathologist wasreported in 12.5% of cases (moderate reliability, k 0.571).
Twenty-seven percent of appendices assessed as normal
by the surgeon revealed inflammation at histopathological assessment, while 9.6% of macroscopicallyappearing inflamed AA revealed to be normal [182].
In 2018, a survey among Dutch surgeons demonstrated that a clear standard of care is missing both inpatient selection and in determining the length of antibiotic treatment following appendectomy. However, theauthors assessed the inter-observer variability in theclassification of AA during laparoscopy and demonstrated that agreement was minimal for both the classification of AA (κ score 0.398) and the decision toprescribe postoperative antibiotic treatment (κ score0.378) [183].
The definition of complicated AA varies among studies. Apart from the common component of perforation,
it may or may not also include non-perforated gangrenous AA, the presence of a fecalith and/or AA in thepresence of pus, or purulent peritonitis, or abscess.
Although most surgeons agree that AA with perforation, intra-abdominal abscess, or purulent peritonitis
can be defined as complicated AA, for which postoperative antibiotic therapy is indicated, there is still a considerable variation in the indications for prolonged
antibiotic therapy after appendectomy, and the antibiotic
regimen that should be used [184].
As the intra-operative classification of AA dictates thepatient’s postoperative management, such variation inpractice may influence clinical outcomes, andstandardization may impact the appropriate use of antibiotics worldwide given the issue of rising antimicrobial
resistance.
In order to evaluate the appendix during diagnostic
laparoscopy, in 2013, Hamminga et al. proposed the
LAPP (Laparoscopic APPendicitis) score (six criteria),
with a single-center prospective pilot study (134 patients), reporting high positive and negative predictive
values (99% and 100%, respectively) [185]. In 2015,
Gomes et al. proposed a grading system for AA that incorporates clinical presentation, imaging, and laparoscopic findings. The system, encompassing four grades

(2020) 15:27

Page 29 of 42(0 = normal looking appendix, 1 = inflamed appendix, 2= necrosis, 3 = inflammatory tumor, 4 = diffuse peritonitis) provides a standardized classification to allow more
uniform patient stratification for AA research and to aid
in determining optimal management according to thegrade of the disease [186].
In 2018, the WSES grading system was validated in aprospective multicenter observational study, performedin 116 worldwide surgical departments from 44 countries over a 6-month period, which showed that 3.8% of
patients had grade 0, while 50.4% had grade 1, 16.8%
grade 2a, 3.4% grade 2b, 8.8% grade 3a, 4.8% grade 3b,1.9% grade 3c, and 10.0% grade 4. About half of the patients were grade 1 (inflamed appendix), and this isprobably the most common situation for an emergency
surgeon [186, 187].
In 2014, the AAST also proposed a system for grading
the severity of emergency general surgery diseases basedon several criteria encompassing clinical, imaging, endoscopic, operative, and pathologic findings, for eight commonly encountered gastrointestinal conditions, including
AA, ranging from grade I (mild) to grade V (severe)[188]. In 2017, Hernandez et al. validated this system ina large cohort of patients with AA, showing that increased AAST grade was associated with open procedures, complications, and length of stay. AAST grade in
emergency for AA determined by preoperative imaging
strongly correlated with operative findings [189]. In
2018, the same researchers assessed whether the AAST
grading system corresponded with AA outcomes in a US
pediatric population. Results showed that increased
AAST grade was associated with increased ClavienDindo severity of complications and length of hospital
stay [190].
Moreover, increasing anatomic severity, as defined by
AAST grade, has shown to be associated with increasing
costs. Length of stay exhibited the strongest association
with costs, followed by AAST grade, Clavien-Dindo
Index, age-adjusted Charlson score, and surgical woundclassification [191]. In 2019, a study by Mällinen et al.
corroborated the known clinical association of an appendicolith to complicated AA. The study’s purpose was toassess differences between uncomplicated CT confirmed
AA and AA presenting with appendicolith with two prospective patient cohorts. Using multivariable logistic regression models adjusted for age, gender, and symptom
duration, statistically significant differences were detected in the depth of inflammation ≤ 2.8 mm (adjusted
OR 2.18 (95% CI 1.29–3.71, P = 0.004), micro-abscesses(adjusted OR 2.16 (95% CI 1.22–3.83, P = 0.008), thenumber of eosinophils and neutrophils ≥ 150/mm2 (adjusted OR 0.97 (95% CI 0.95–0.99, P = 0.013), and adjusted OR 3.04 (95% CI 1.82–5.09, P < 0.001,
respectively) between the two groups of patients [108].

The Sunshine Appendicitis Grading System score(SAGS) can be used to simply and accurately classify theseverity of AA, to independently predict the risk of
intra-abdominal collection and guide postoperative antibiotic therapy [192].
Based on the results of a large retrospective cohort
study, Farach et al. concluded that in children operative
findings are more predictive of clinical course than histopathologic results. The authors found there was poor
agreement between intra-operative findings and histopathologic findings, and, although 70% of patients withintra-operative findings of uncomplicated AA were labeled as complex pathology, 86% followed a fast track
protocol (same-day discharge) with a low complication
rate (1.7%) [193].
Statement 5.1 The incidence of unexpected findings inappendectomy specimens is low. The intra-operative diagnosis alone is insufficient for identifying unexpected disease.
From the currently available evidence, routine histopathology is necessary. Recommendation 5.1 We recommend
routine histopathology after appendectomy [QoE: Moderate; Strength of recommendation: Strong; 1B].
Statement 5.2 Operative findings and intra-operative
grading seem to correlate better than histopathology
with morbidity, overall outcomes and costs, both inadults and children. Intra-operative grading systems canhelp the identification of homogeneous groups of patients, determining optimal postoperative management
according to the grade of the disease and ultimately improve utilization of resources. Recommendation 5.2
We suggest the routine adoption of an intra-operative
grading system for acute appendicitis (e.g., WSES 2015
grading score or AAST EGS grading score) based onclinical, imaging and operative findings [QoE: Moderate;
Strength of recommendation: Weak; 2B].

Di Saverio et al. World Journal of Emergency Surgery

Q.5.2: Should the macroscopically normal appendix beremoved during laparoscopy for acute right iliac fossa pain
when no other explanatory pathology is found?

Laparoscopic management of normal appendix still represents a dilemma for the surgeon, as no high-level
evidence-based recommendations are available to date.
The Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) 2010 guidelines stated that, if
no other pathology is identified, the decision to remove
the appendix should be considered, but based on the individual clinical scenario [194]. In the same way, theEuropean Association of Endoscopic Surgery (EAES)
2016 guidelines recommended performing an appendectomy in the case of a normal appearing appendix during
surgery for suspected AA [195].
Intra-operative macroscopic distinction between a normal appendix and AA during surgery can be challenging.
Several studies have shown a 19% to 40% rate of(2020) 15:27

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pathologically abnormal appendix in the setting of novisual abnormalities [182, 196]. Therefore, the risk ofleaving a potentially abnormal appendix must be
weighed against the risk of appendectomy in each individual scenario. Cases of postoperative symptoms requiring reoperation for appendectomy have been describedin patients whose normal appendix was left in place atthe time of the original procedure. The risks of leavingin situ an apparently normal appendix are related tolater AA, subclinical or endo-appendicitis with persisting
symptoms, and missed appendiceal malignancy.
According to the retrospective study by Grimes et al.,including 203 appendectomies performed with normal
histology, fecaliths may be the cause of right iliac fossa
pain in the absence of obvious appendiceal inflammation. In this study, the policy of routine removal of anormal-looking appendix at laparoscopy in the absenceof any other obvious pathology appeared to be an effective treatment for recurrent symptoms [197]. In the sameway, Tartaglia et al. supported an appendectomy in patients undergoing laparoscopy for acute right lower
quadrant abdominal pain even when the appendix appears normal on visual inspection, based on the resultsof a study in which 90% of the removed normal-looking
appendices at laparoscopy for abdominal pain and noother intra-abdominal acute disease harbored inflammatory changes at the definitive pathology [198].
Recently, Sørensen et al. performed a retrospective
cohort analysis of patients who underwent a diagnostic laparoscopy due to clinical suspicion of AA
where no other pathology was found, and the appendix was not removed. Of the 271 patients included,
56 (20.7%) were readmitted with right iliac fossa
pain after a median time of 10 months. Twenty-two
patients (8.1%) underwent a new laparoscopic procedure, and the appendix was removed in 18 patients, of which only one showed histological signsof inflammation. Based on results from this study,
the authors did not consider that it is necessary to
remove a macroscopic normal appendix during
laparoscopy for clinically suspected AA [199]. This
year, Allaway et al. published the results of a singlecentre retrospective case note review of patients
undergoing LA for suspected AA. Patients were divided into positive and negative appendectomy
groups based on histology results. The authors reported an overall negative appendectomy rate of
36.0% among 1413 patients who met inclusion criteria (904 in the positive group and 509 in the negative group). Morbidity rates (6.3% vs 6.9%; P = 0.48)
and types of morbidity were the same for negative
appendicectomy and uncomplicated AA, and there
was no significant difference in complication severityor length of stay (2.3 vs 2.6 days; P = 0.06) between

negative appendicectomy and uncomplicated AA
groups [200].
The 2014 Cochrane review on the use of laparoscopy
for the management of acute lower abdominal pain inwomen of childbearing age showed that laparoscopy was
associated with an increased rate of specific diagnoses. A
significant difference favoring the laparoscopic procedure in the rate of removal of normal appendix comparedto open appendectomy was found [201].
Statement 5.3 Surgeon's macroscopic judgment ofearly grades of acute appendicitis is inaccurate andhighly variable. The variability in the intra-operativeclassification of appendicitis influences the decision toprescribe postoperative antibiotics and should be therefore prevented/avoided. Recommendation 5.3 We suggest appendix removal if the appendix appears “normal”
during surgery and no other disease is found in symptomatic patients [QoE: Low; Strength of recommendation: Weak; 2C].

Di Saverio et al. World Journal of Emergency Surgery

Topic 6: Management of perforated appendicitis withphlegmon or abscessQ.6.1: Is early appendectomy an appropriate treatmentcompared with delayed appendectomy for patients withperforated acute appendicitis with phlegmon or abscess?

The optimal approach to complicated AA with phlegmon or abscess is a matter of debate.
In the past, immediate surgery has been associatedwith a higher morbidity if compared with conservative
treatment, while the non-surgical treatment of appendicular abscess or phlegmon has been reported to succeed in over 90% of patients, with an overall risk ofrecurrence of 7.4% and only 19.7% of cases of abscess requiring percutaneous drainage [202].
The meta-analysis by Similis et al. (including 16
non-randomized retrospective studies and one nonrandomized prospective study for a total of 1572
patients, of whom 847 treated with conservative
treatment and 725 with appendectomy) revealed thatconservative treatment was associated with significantly less overall complications (wound infections,abdominal/pelvic abscesses, ileus/bowel obstructions,and re-operations) if compared to immediate appendectomy [203].
In the large series from the National Inpatient Sample(NIS) by Horn et al., 25.4% of a total of 2,209 adult patients with appendiceal abscesses who received drains
failed conservative management and underwent operative intervention [204].
Current evidence shows that surgical treatment of patients presenting with appendiceal phlegmon or abscessis preferable to NOM with antibiotic oriented treatmentin the reduction of the length of hospital stay and needfor readmissions when laparoscopic expertise is available(2020) 15:27

Page 31 of 42[205]. In the retrospective study by Young et al., early
appendectomy has shown superior outcomes comparedwith initial NOM. Of 95 patients presenting with complicated AA, 60 underwent early appendectomy, and 35
initially underwent NOM. All patients who experienced
failed NOM (25.7%) had an open operation with mostrequiring bowel resection. Early appendectomy demonstrated a lower incidence of bowel resection (3.3% vs17.1%, P = 0.048) when compared to all patients initially
undergoing NOM [206].
Recently, the cumulative meta-analysis by Gavriilidis
et al. has shown a more widespread use of the laparoscopic approach for the management of complicated
AA. Although overall complications, abdominal/pelvic
abscesses, wound infections, and unplanned procedures
were significantly lower in the conservative treatment
cohort in the general analysis, on the contrary, the subgroup analysis of three RCTs revealed no significant difference in abdominal/pelvic abscesses (OR 0.46). Highquality RCTs demonstrated shorter hospital stay by 1
day for the LA cohort compared to conservative treatment [207].
According to the results of the Cochrane review
published by Cheng et al. in 2017, it is unclear
whether early appendectomy shows any benefit interms of complications compared to delayed appendectomy for people with appendiceal phlegmon or abscess. The review included only two RCTs with a
total of 80 participants. The comparison between
early versus delayed open appendectomy for appendiceal phlegmon included 40 participants (pediatricand adults), randomized either to early appendectomy (appendectomy as soon as appendiceal mass
resolved within the same admission, n = 20) or todelayed appendectomy (initial conservative treatment
followed by interval appendectomy 6 weeks later, n= 20). There was insufficient evidence to determine
the effect of using either early or delayed open appendectomy on overall morbidity (RR 13.00), theproportion of participants who developed wound infection (RR 9.00), or fecal fistula (RR 3.00). Even thequality of evidence for increased length of hospital
stay and time away from normal activities in theearly appendectomy group was of very low quality.
The comparison between early versus delayed laparoscopic appendectomy for appendiceal abscess included 40 pediatric patients, randomized either toearly appendectomy (emergent laparoscopic appendicectomy, n = 20) or to delayed appendectomy (initialconservative treatment followed by interval laparoscopic appendicectomy 10 weeks later, n = 20).
Health-related quality of life score measured at 12
weeks after appendectomy was higher in the early
appendectomy
group
than
in
the
delayedappendectomy group, but the quality of evidence wasvery low [208].
The high-quality RCT by Mentula et al. (not includedin the Cochrane review), conversely, demonstrated that
LA in experienced hands is a safe and feasible first-line
treatment for appendiceal abscess. In this study, early
LA was associated with fewer readmissions and fewer
additional interventions than conservative treatment,with a comparable hospital stay. Patients in the laparoscopy group had a 10% risk of bowel resection and 13%
risk of incomplete appendectomy. There were significantly fewer patients with unplanned readmissions following LA (3% versus 27%, P = 0.026). Additional
interventions were required in 7% of patients in thelaparoscopy group (percutaneous drainage) and 30% of
patients in the conservative group (appendectomy). Conversion to open surgery was required in 10% of patientsin the laparoscopy group and 13% of patients in the conservative group. The rate of uneventful recovery was
90% in the laparoscopy group versus 50% in the conservative group (P = 0.002) [209].
Luo et al. analyzed the outcomes of 1,225 patients
under 18 years of age who had non-surgical treatment
for an appendiceal abscess between 2007 and 2012 in
Taiwan. The authors compared outcomes of percutaneous drainage with antibiotics or antibiotics alone. Of 6,
190 children having an appendiceal abscess, 1,225 patients received non-operative treatment. Patients treatedwith percutaneous drainage and antibiotics had a significantly lower rate of recurrent AA, significantly smaller
chance of receiving an interval appendectomy, and significantly fewer postoperative complications after theinterval appendectomy than those without percutaneous
drainage treatment. In addition, patients treated withpercutaneous drainage were significantly less indicatedto receive an interval appendectomy later [210].
Two recent meta-analyses addressed the role of early
appendectomy in children with appendiceal phlegmon
or abscess. The meta-analysis by Fugazzola et al. foundthat children with appendiceal abscess/phlegmon reported better results in terms of complication rate andreadmission rate if treated with NOM [211]. Similarly,
the meta-analysis by Vaos et al. reported that NOM wasassociated with lower rates of complications and wound
infections, whereas the development of IAA and postoperative ileus was not affected by the treatment of choice[212]. In both the meta-analyses, early appendectomy
was associated with reduced length of hospital stay.
Statement 6.1 Non-operative management is a reasonable first-line treatment for appendicitis withphlegmon or abscess. Percutaneous drainage as an
adjunct to antibiotics, if accessible, could be beneficial, although there is a lack of evidence for its use
on a routine basis. Laparoscopic surgery in

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experienced hands is a safe and feasible first-line
treatment for appendiceal abscess, being associatedwith fewer readmissions and fewer additional interventions than conservative treatment, with a comparable hospital stay. Recommendation 6.1 We suggest
non-operative management with antibiotics and—ifavailable—percutaneous drainage for complicated appendicitis with a periappendicular abscess, in settings
where laparoscopic expertise is not available [QoE:
Moderate; Strength of recommendation: Weak; 2B].
Statement 6.2 Operative management of acute appendicitis with phlegmon or abscess is a safe alternative to
non-operative management in experienced hands andmay be associated with shorter LOS, reduced need forreadmissions, and fewer additional interventions thanconservative treatment. Recommendation 6.2 We suggest the laparoscopic approach as treatment of choicefor patients with complicated appendicitis with phlegmon or abscess where advanced laparoscopic expertiseis available, with a low threshold for conversion. [QoE:
Moderate; Strength of recommendation: Weak; 2B].

interval appendectomy after successful NOM of an appendix mass in children. Results showed that more than
three-quarters of children could avoid appendectomy
during early follow-up after successful NOM of an appendix mass. The proportion of children with histologically proven recurrent AA under active observation was
12%, and the proportion of children with severe complications related to interval appendicectomy was 6%.
Although the risk of complications after interval appendectomy was low, adoption of a wait-and-see approach, reserving appendectomy for patients whodevelop AA recurrence or recurrent symptoms, should
be considered a most cost-effective management strategy
compared with routine interval appendectomy [215].
In the study by Renteria et al., unexpected malignancy
was 3% in the elderly (mean age 66 years) and 1.5% in
the young (mean age 39 years) cohorts of patients who
underwent appendectomy as primary treatment for AA[216]. Adult patients with complicated AA treated withinterval appendectomy can be diagnosed with appendiceal neoplasm in up to 11% of cases, in contrast to 1.5%of the patients who have early appendectomy [217]. Recently, the RCT by Mällinen et al. comparing interval
appendectomy and follow-up with MRI after initial successful nonoperative treatment of periappendicular abscess was prematurely terminated owing to ethicalconcerns following the unexpected finding at the interim
analysis of a high rate of neoplasm (17%), with all neoplasms in patients older than 40 years [218]. If this significant rate of neoplasms after periappendicular abscessis validated by future studies, it would argue for routineinterval appendectomy in this setting.
Statement 6.3 The reported rate of recurrence after
non-surgical treatment for perforated AA and phlegmon
ranges from 12% to 24%. Interval appendectomy and repeated NOM in case of recurrence of appendiceal phlegmon are associated with similar morbidity. However,elective interval appendectomy is related to additional operative costs to prevent recurrence in only one of eight patients, such as not to justify the routine performance ofappendectomy. Recommendation 6.3 We recommend
against routine interval appendectomy after NOM forcomplicated appendicitis in young adults (< 40 years old)and children. Interval appendectomy is recommended for
those patients with recurrent symptoms [QoE: Moderate;
Strength of recommendation: Strong; 1B].
Statement 6.4 The incidence of appendicular neoplasms is high (3–17%) in adult patients ≥ 40 years
old) with complicated appendicitis. Recommendation 6.4 We suggest both colonic screening withcolonscopy and interval full-dose contrast-enhanced
CT scan for patients with appendicitis treated nonoperatively if ≥ 40 years old [QoE: Low; Strength ofrecommendation: Weak; 2C].

Di Saverio et al. World Journal of Emergency Surgery

Q.6.2: Is interval appendectomy always indicated forpatients with acute appendicitis following successful NOM?

The reported rate of recurrence after non-surgical treatment for perforated AA and phlegmon is up to 12%[213]. In order to avoid this quite high chance of recurrence, some authors recommend routine elective interval
appendectomy following initial conservative management. However, this procedure is associated with a nonnegligible rate of morbidity of 12.4% [202]. The
systematic review by Hall et al., including three retrospective studies for a total of 127 cases of non-surgicaltreatment of appendix mass in children, showed thatafter successful non-operative treatment the risk of recurrent AA was found to be 20.5%. Overall, the complications reported included SSI, prolonged postoperative
ileus, hematoma formation, and small bowel obstruction,
but the incidence of any individual complication was notdetermined [23].
In the recent systematic review by Darwazeh et al.,interval appendectomy and repeated NOM in thecase of recurrence of appendiceal phlegmon were associated with similar morbidity. However, elective
interval appendectomy was related to additional operative costs to prevent recurrence in only one ofeight patients, such as not to justify the routine performance of appendectomy [213].
In the same way, Rushing et al., who found a risk ofrecurrence of 24.3% in patients, managed with NOM for
appendiceal abscess or phlegmon and recommended
against routine interval appendectomy in otherwise
asymptomatic patients [214]. The CHINA RCT recently
compared the outcomes of active observation versus

Di Saverio et al. World Journal of Emergency Surgery(2020) 15:27

Topic 7: Perioperative antibiotic therapy
Q.7.1: Is preoperative antibiotic therapy recommended forpatients with acute appendicitis?

In 2001, a Cochrane meta-analysis supported thatbroad-spectrum antibiotics given preoperatively are effective in decreasing SSI and abscesses. RCTs and nonrandomized comparative studies in which any antibiotic
regime was compared to placebo in patients undergoing
appendectomy were analyzed. Forty-four studies including 9,298 patients were included in this review. Antibiotics were superior to placebo for preventing wound
infection and intra-abdominal abscess, with no apparent
difference in the nature of the removed appendix [219].
The same final results have been obtained by the 2005
updated version of the review, including 45 studies with
9,576 patients [220]. The timing of pre-operative antibiotics does not affect the frequency of SSI after appendectomy for AA. Therefore, the optimal timing of
preoperative antibiotic administration may be from 0 to
60 min before the surgical skin incision [221].
Statement 7.1 A single dose of broad-spectrum antibiotics given preoperatively (from 0 to 60 min before thesurgical skin incision) has been shown to be effective indecreasing wound infection and postoperative intraabdominal abscess, with no apparent difference in thenature of the removed appendix. Recommendation 7.1
We recommend a single preoperative dose of broadspectrum antibiotics in patients with acute appendicitis
undergoing appendectomy. We recommend against
postoperative antibiotics for patients with uncomplicatedappendicitis [QoE: High; Strength of recommendation:
Strong; 1A].
Q.7.2: Are postoperative antibiotics always indicated in
adult patients following appendectomy?

Prospective trials demonstrated that patients with perforated AA should receive postoperative antibiotic treatment, especially if complete source control has not beenachieved. Cho et al. recently demonstrated in a large cohort of patients that the role of antibiotic treatment for
preventing post-appendectomy IAA seems to be relatedwith achieving intraperitoneal infectious source control.
The authors found that the mean durations of postoperative antibiotic therapy were 3.1 days for the non-IAA
group and 3.3 days for the IAA group, with no significant difference between the groups [222].
In the large observational study by McGillen et al., patients with complicated AA were significantly more
likely to be started on antibiotics after surgery (83.9%
versus 33.3%; P < 0.001) compared with patients withsimple AA. The development of a SSI was significantly
associated with a clinical diagnosis of diabetes, the presence of free fluid, abscess, or perforation on preoperative imaging [223].

Page 33 of 42

The optimal course of antibiotics remains to be identified, but current evidence suggests that longer postoperative courses do not prevent SSI compared with 2 daysof antibiotics.
The meta-analysis by Van den Boom et al., including ninestudies with more than 2,000 patients with complicatedAA, revealed a statistically significant difference in IAA incidence between the antibiotic treatment of ≤ 5 vs > 5 days
(OR 0.36), but not between ≤ 3 vs > 3 days (OR 0.81) [224].
A total of 80 patients were enrolled in a recent RCT
comparing the outcomes of short (24 h) and the extended (> 24 h) postoperative antibiotic therapy in complicated AA. The overall rate of complications was
17.9% and 29.3% in the short and extended group, respectively (P = 0.23). Mean complication index did not
differ between the study groups (P = 0.29), whereas hospital length of stay was significantly reduced in the shorttherapy group (61 ± 34 h vs 81 ± 40 h, P = 0.005). Basedon the results of this RCT, 24 h of antibiotic therapy following appendectomy does not result in worse primary
outcomes in complicated AA, but results in a significant
reduction in length of hospitalization, with a major costsaving and antibacterial stewardship benefits [225].
Although discontinuation of antimicrobial treatment
should be based on clinical and laboratory criteria, aperiod of 3–5 days for adult patients is generally sufficient following appendectomy for complicated AA. The
2015 “STOP-IT” RCT by Sawyer et al. on 518 patientswith complicated intra-abdominal infection, including
also complicated AA, undergoing adequate source control demonstrated that outcomes after fixed-duration
antibiotic therapy (approximately 4 days) were similar to
those after a longer course of antibiotics (approximately
8 days) that extended until after the resolution of physiological abnormalities [226].
Statement 7.2 In patients with complicated acute appendicitis, postoperative broad-spectrum antibiotics aresuggested, especially if complete source control has notbeen achieved. For adult patients deemed to require them,discontinuation of antibiotics after 24 h seems safe and isassociated with shorter length of hospital stay and lower
costs. In patients with intra-abdominal infections who had
undergone an adequate source control, the outcomes after
fixed-duration antibiotic therapy (approximately 3–5 days)
are similar to those after a longer course of antibiotics. Recommendation 7.2 We recommend against prolonging antibiotics longer than 3–5 days postoperatively in case ofcomplicated appendicitis with adequate source control[QoE: High; Strength of recommendation: Strong; 1A].
Q.7.3: Are postoperative antibiotics always indicated inpediatric patients following appendectomy?

A retrospective review conducted by Litz et al. demonstrated that antibiotic administration within 1 h of(2020) 15:27

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appendectomy in pediatric patients with AA who receive
antibiotics at diagnosis did not change the incidence of
postoperative infectious complications [227].
Children with non-perforated AA should receive asingle broad-spectrum antibiotic. Second- or thirdgeneration cephalosporins, such as cefoxitin or cefotetan, may be used in uncomplicated cases.
In complicated AA, intravenous antibiotics that are effective against enteric gram-negative organisms and anaerobes including E. coli and Bacteroides spp. should beinitiated as soon as the diagnosis is established. Broaderspectrum coverage is obtained with piperacillintazobactam, ampicillin-sulbactam, ticarcillin-clavulanate,
or imipenem-cilastatin. For perforated AA, the mostcommon combination is ampicillin, clindamycin (ormetronidazole), and gentamicin. Alternatives include
ceftriaxone-metronidazole or ticarcillin-clavulanate plus
gentamicin, in accordance with the epidemiology ofbacteria [228]. Metronidazole is not indicated whenbroad-spectrum antibiotics such as aminopenicillins with
β-lactam inhibitors or carbapenems and selectcephalosporins are used [229]. In a recent retrospective
cohort study of 24,984 children aged 3 to 18 years, Kronman et al. compared the effectiveness of extendedspectrum versus narrower-spectrum antibiotics for children with AA. The exposure of interest was receipt ofsystemic extended-spectrum antibiotics (piperacillin ±tazobactam, ticarcillin ± clavulanate, ceftazidime, cefepime, or a carbapenem) on the day of appendectomy or
the day after. The primary outcome was 30-day readmission for SSI or repeat abdominal surgery. The authors
reported that extended-spectrum antibiotics seem tooffer no advantage over narrower-spectrum agents forchildren with surgically managed acute uncomplicatedor complicated AA [230].
Broad-spectrum, single, or double agent therapy isequally efficacious as but more cost-effective thantriple agent therapy. It was reported that dual therapy consisting of ceftriaxone and metronidazole onlyoffers a more efficient and cost-effective antibiotic
management compared with triple therapy, but prospective studies are required to determine whether

Di Saverio et al. World Journal of Emergency Surgery

Fig. 1 Practical WSES algorithm for diagnosis and treatment of adult patients with suspected acute appendicitis

(2020) 15:27

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this policy is associated with higher rates of wound
infections and change in antibiotic therapy [231].
Postoperative antibiotics can be administered orally if
the patient is otherwise well enough to be discharged.
Arnold et al. conducted a RCT of 82 pediatric patients
to compare the effect of home intravenous versus oral
antibiotic therapy on complication rates and resource
utilization following appendectomy for perforated AA.
Fosrty-four patients (54%) were randomized to the IV
group and 38 (46%) to the oral group. The study showed
no difference in length of stay (4.4 ± 1.5 versus 4.4 ± 2.0
days), postoperative abscess rate (11.6% vs 8.1%), or readmission rate (14.0% vs 16.2%), whereas hospital andoutpatient charges were higher in the IV group [232].
Other retrospective cohort studies have confirmedthat after apspendectomy for perforated AA in children, oral antibiotics show equivalent outcomescompared with intravenous antibiotics, but withshorter length of hospitalizations and less medical
encounters required [233].
Compared to pediatric patients who receive intravenous antibiotics, those who are treated with oral antibiotics have statistically lower rates of repeated US
imaging (49.6% vs 35.1%) and PICC placement (98.3% vs9.1%), whereas the rates of IAA are similar (20.9% vs16.0%). Moreover, early transition to oral antibiotics allows shorter hospital times and decreased hospitalcharges, with similar total antibiotic days and readmission rate [234].
Statement 7.3 Administering postoperative antibiotics
orally in children with complicated appendicitis for periods shorter than 7 days postoperatively seems to besafe and it is not associated with increased risk of complications. Early transition to oral antibiotics is safe, effective, and cost-efficient in the treatment ofcomplicated appendicitis in the child. Recommendation
7.3 We recommend early switch (after 48 h) to oral administration of postoperative antibiotics in children withcomplicated appendicitis, with an overall length of therapy shorter than seven days [QoE: Moderate; Strength ofrecommendation: Strong; 1B].
Statement 7.4 Postoperative antibiotics after appendectomy for uncomplicated acute appendicitis in children
seems to have no role in reducing the rate of surgicalsite infection. Recommendation 7.4 In pediatric patients operated for uncomplicated acute appendicitis, wesuggest against using postoperative antibiotic therapy[QoE: Low; Strength of recommendation: Weak; 2C].

Di Saverio et al. World Journal of Emergency Surgery

Fig. 2 Practical WSES algorithm for diagnosis and treatment of pediatric patients with suspected acute appendicitis

Di Saverio et al. World Journal of Emergency Surgery(2020) 15:27

Conclusions
The current evidence-based guidelines are the updated
2020 International Comprehensive Clinical Guidelines
for the diagnosis and management of acute appendicitis.
After reaching consensus on each of the above mentioned, the panel experts and the scientific committee
members developed two WSES flow-chart algorithm forthe diagnosis and management of acute appendicits to
be used for adults and pediatric patient population, reported respectively in Figs. 1 and 2.
Supplementary information
Supplementary information accompanies this paper at https://doi.org/10.
1186/s13017-020-00306-3.
Additional file 1. Search Syntaxes.
Additional file 2.
Additional file 3.
Additional file 4.
Additional file 5.
Additional file 6.

Acknowledgements
Not applicable
Authors’ contributions
SDS and MP contributed equally to the manuscript and both share the firstauthorship. The WSES president was supported by the Scientific Secretariat
in establishing the timetable of the Consensus Document and choosing thesix experts who were asked to participate in the Scientific Committee. The
Scientific Committee had the assignment to select the literature and toelaborate, in co-working to Scientific Secretariat and Organization Committee, the statements. The Scientific Secretariat supported the WSES President,
establishing the agenda, choosing the working tools and finally collaboratingwith Organization Committee and Scientific Secretariat. The WSES board
reviewed the draft and made critical appraisals. All the statements were discussed and approved during the 6th WSES congress held in Nijmegen, Holland (26–28 June 2019). The manuscript was further reviewed by Scientific
Secretariat, Organization Committee and Scientific Committee according tocongress comments and was then approved by the WSES board. SDS, MP,
BDS, MC, GA, AB, MS: conception, design, and coordination of the study; dataacquisition, analysis, and interpretation; and draft the manuscript. The authors
read and approved the final manuscript.
AG: bibliographic research.
Authors’ information
Scientific Secretariat members: Salomone Di Saverio, Mauro Podda, GoranAugustin, Belinda De Simone, Alice Gori.
Organization Committee members: Salomone Di Saverio, Mauro Podda,
Fausto Catena, Micheal D. Kelly, Dieter Weber, Federico Coccolini, Massimo
Sartelli, Luca Ansaloni, Ernest E Moore, Jeffry Kashuk, Yoram Kluger.
Scientific Committee members: Salomone Di Saverio, Mauro Podda, GoranAugustin, Arianna Birindelli, Marco Ceresoli, Antonio Tarasconi, Dieter G.
Weber, Massimo Sartelli, Federico Coccolini, Marja Boermeester, Carlos
Augusto Gomes, Michael Sugrue, Nicola de'Angelis, Walter Biffl, Ernest E.
Moore, Michael Kelly, Kjetil Soreide, Jeffry Kashuk, Richard Ten Broek, Justin R.
Davies, Dimitrios Damaskos, Edward Tan, Harry Van Goor, Ari Leppäniemi,
Andrew Kirkpatrick, Raul Coimbra, Matti Tolonen, Gianluigi de'Angelis,
Massimo Chiarugi, Gabriele Sganga, Adolfo Pisanu, Francesco Pata, Isidoro Di
Carlo, Osvaldo Chiara, Andrey Litvin, Fabio C. Campanile, Boris Sakakushev,
Gia Tomadze, Zaza Demetrashvili, Rifat Latifi, Fakri Abu-Zidan, Oreste Romeo,
Helmut Segovia-Lohse, Andrew B. Peitzman, Gianluca Baiocchi, Gustavo P.
Fraga, Ronald V. Maier, David Costa, Sandro Rizoli, Zsolt J Balogh, Cino Bendinelli, Thomas Scalea.

Page 36 of 42

Funding
No authors received any funding resource. The paper received a WSES
Institutional waiver for this publication.
Availability of data and materials
There are no individual author data that reach the criteria for availability.
Ethics approval and consent to participate
Not applicable
Consent for publication
Not applicableCompeting interests
The authors declare that they have no competing interests.
Author details
1
Cambridge Colorectal Unit, Cambridge University Hospitals NHS Foundation
Trust, Addenbrooke’s Hospital, Cambridge Biomedical Campus, Hills Road,
Cambridge CB2 0QQ, UK. 2Department of General Surgery, University ofInsubria, University Hospital of Varese, ASST Sette Laghi, Regione Lombardia,
Varese, Italy. 3Department of General and Emergency Surgery, Cagliari
University Hospital, Cagliari, Italy. 4Emergency and Trauma Surgery
Department, Maggiore Hospital of Parma, Parma, Italy. 5Emergency andGeneral Surgery Department, University of Milan-Bicocca, Milan, Italy.
6
Department of Surgery, University Hospital Centre of Zagreb, Zagreb,
Croatia. 7Maggiore Hospital Regional Emergency Surgery and Trauma Center,
Bologna Local Health District, Bologna, Italy. 8Department of Surgery,
University of Amsterdam, Amsterdam, The Netherlands. 9Macerata Hospital,
Macerata, Italy. 10General, Emergency and Trauma Surgery, Pisa University
Hospital, Pisa, Italy. 11Department of Digestive, Hepato-Pancreato-Biliary
Surgery and Liver Transplantation, Henri Mondor University Hospital, Paris,
France. 12Trauma and General Surgeon Royal Perth Hospital & The Universityof Western Australia, Perth, Australia. 13Department of Abdominal Surgery,
Abdominal Center, University of Helsinki and Helsinki University Central
Hospital, Helsinki, Finland. 14Department of General Surgery, Azienda Socio
Sanitaria Territoriale, di Valle Camonica, Italy. 15Queen’s Medical Center,
University of Hawaii, Honolulu, HI, USA. 16Denver Health System – Denver
Health Medical Center, Denver, USA. 17Acute Surgical Unit, Canberra Hospital,
ACT, Canberra, Australia. 18Department of Gastrointestinal Surgery, Stavanger
University Hospital, Stavanger, Norway. 19Department of Surgery, Universityof Jerusalem, Jerusalem, Israel. 20Department of Surgery, Radboud University
Medical Center, Nijmegen, The Netherlands. 21Department of Surgery
Hospital Universitario, Universidade General de Juiz de Fora, Juiz de Fora,
Brazil. 22Letterkenny Hospital, Donegal, Ireland. 23Department of Upper GI
Surgery, Royal Infirmary of Edinburgh, Edinburgh, Scotland, UK. 24General,
Acute Care, Abdominal Wall Reconstruction, and Trauma Surgery, Foothills
Medical Centre, Calgary, Alberta, Canada. 25Department of Surgery, Universityof Pittsburgh School of Medicine, UPMC-Presbyterian, Pittsburgh, USA.
26
Faculdade de Ciências Médicas (FCM) – Unicamp, Campinas, SP, Brazil.
27
Department of Surgery, University of Washington, Harborview Medical
Center, Seattle, WA, USA. 28UCSD Health System - Hillcrest Campus
Department of Surgery Chief Division of Trauma, Surgical Critical Care, Burns,
and Acute Care Surgery, San Diego, CA, USA. 29Department of Emergency
Surgery, “A. Gemelli Hospital”, Catholic University of Rome, Rome, Italy.
30
Gastroenterology and Endoscopy Unit, University Hospital of Parma,
University of Parma, Parma, Italy. 31Department of Surgery, Nicola
Giannettasio Hospital, Corigliano-Rossano, and La Sapienza University ofRome, Rome, Italy. 32Department of Surgical Sciences and Advanced
Technologies “GF Ingrassia”, Cannizzaro Hospital, University of Catania,
Catania, Italy. 33Niguarda Hospital Trauma Center, Milan, Italy. 34Departmentof Surgery, Immanuel Kant Baltic Federal University, Kaliningrad, Russia.
35
Department of Surgery, San Giovanni Decollato Andosilla Hospital, Viterbo,
Italy. 36General Surgery Department, Medical University, University Hospital St
George, Plovdiv, Bulgaria. 37Department of Surgery, Tbilisi State Medical
University, TSMU, Tbilisi, Georgia. 38Section of Acute Care Surgery,
Westchester Medical Center, Department of Surgery, New York Medical
College, Valhalla, NY, USA. 39Department of Surgery, College of Medicine and
Health Sciences, UAE University, Al-Ain, United Arab Emirates. 40Bronson
Trauma Surgery, Kalamazoo, USA. 41Hospital de Clinicas, Universidad Nacionalde Asuncion, Asuncion, Paraguay. 42Surgical Clinic, Department of

(2020) 15:27

Page 37 of 42

Experimental and Clinical Sciences, University of Brescia, Brescia, Italy.
43
Hospital universitario de Alicante, departamento de Cirugia General,
Alicante, Spain. 44Department of Surgery, St. Michael Hospital, University ofToronto, Toronto, Canada. 45Department of Traumatology, John Hunter
Hospital and University of Newcastle, Newcastle, NSW, Australia. 46R. Adams
Cowley Trauma Center, Baltimore, MD, USA. 47Professor Emeritus Virginia
Commonwealth University, Richmond, VA, USA. 48Harvard Medical School,
Massachusetts General Hospital, Boston, USA. 49Department of Surgery,
Linkoping University, Linkoping, Sweden. 50Division of General Surgery,Rambam Health Care Campus, Haifa, Israel. 51Department of General Surgery
and Trauma, Bufalini Hospital, Cesena, Italy.

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Di Saverio et al. World Journal of Emergency Surgery

Received: 9 January 2020 Accepted: 30 March 2020

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