MEDICINE

Acute Appendicitis in Childhood and

Adulthood
An Everyday Clinical Challenge

Patrick Téoule, Jan de Laffolie, Udo Rolle, and Christoph Reissfelder

Department of Sur-
gery, Universitäts-
medizin Mannheim, Summary
Medical Faculty
Mannheim, Heidel- Background: Acute appendicitis is the most common cause of the acute abdomen, with an incidence of 1 per 1000 persons per
berg University: year. It is one of the main differential diagnoses of unclear abdominal conditions.
Dr. med. Patrick
Téoule, Prof. Dr. med Methods: This review is based on pertinent publications that were retrieved by a selective search in the PubMed and Cochrane
Christoph Reissfelder
Library databases.
Department of
General Pediatrics Results: In addition to the medical history, physical examination and laboratory tests, abdominal ultrasonography should be
and Neonatology,
Pediatric Gastroente- performed to establish the diagnosis (and sometimes computed tomography [CT] or magnetic resonance imaging [MRI], if ultra-
rology, University of sonography is insufficient). Before any treatment is provided, appendicitis is classified as either uncomplicated or complicated.
Giessen, Germany:
PD Dr. med. Jan de
In both types of appendicitis, the decision to treat surgically or conservatively must be based on the overall clinical picture and
Laffolie the patient’s risk factors. Appendectomy is the treatment of choice for acute appendicitis in all age groups. In Germany,
Department of appendectomy is mainly performed laparoscopically in patients with low morbidity. Uncomplicated appendicitis can, alternatively,
Pediatric Surgery, be treated conservatively under certain circumstances. A meta-analysis of five randomized, controlled trials has revealed that
University Hospital ca. 37% of adult patients treated conservatively undergo appendectomy within one year. Complicated appendicitis is a serious
Frankfurt, Goethe-
University Frankfurt disease; it can also potentially be treated conservatively (with antibiotics, with or without placement of a drain) as an alternative
am Main, Frankfurt, to surgical treatment.
Germany: Prof. Dr.
med. Udo Rolle
Conclusion: Conservative treatment is being performed more frequently, but the current state of the evidence does not justify a
change of the standard therapy from surgery to conservative treatment.

Cite this as:

Téoule P, de Laffolie J, Rolle U, Reissfelder C: Acute appendicitis in childhood and adulthood—an everyday clinical challenge.
Dtsch Arztebl Int 2020; 117: 764–74. DOI: 10.3238/arztebl.2020.0764

A
ppendectomy is among the more commonly per- the usual treatment, replacing conventional appendec-
formed operations in Germany, with more than tomy. Approximately 25% of appendectomies in
108 000 procedures per year (1). Acute appen- children are performed by open surgery, there being as
dicitis has an incidence of 100 new cases per 100 000 yet no unequivocal evidence for the superiority of the
persons per year and is the most common cause of the laparoscopic approach (3, 5). Appendectomy is associ-
acute abdomen (2, 3). The lifetime risk of acute appen- ated with very low surgical risk; the morbidity and
dicitis is slightly higher in men than in women (8.6% mortality of patients who have undergone appendec-
versus 6.7%), but women have a higher lifetime risk of tomy is largely determined by the severity of the
undergoing appendectomy (23.1% versus 12.0%) (4). appendicitis itself and its comorbidities (3, 6). The
Adolescent girls (age 12–16) are the group at greatest vermiform appendix plays a physiological role as a
risk for appendectomy (5). In Germany, laparoscopic reservoir for the intestinal flora (intestinal micro-
appendectomy is universally available and has become biome), e.g., after antibiotic treatment, as well as the

Incidence Surgical risk

Acute appendicitis has an incidence of 100 new cases per Appendectomy is associated with very low surgical risk; the
100,000 persons per year and is the most common cause of morbidity and mortality of patients who have undergone
the acute abdomen. appendectomy is largely determined by the severity of the
appendicitis itself and its comorbidities.

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site of origin of mesenchymal stem cells in the colon TABLE 1

(7–9). Three guidelines on appendicitis have been pub-
lished to date internationally (10–12), but none yet in Overview of critieria for uncomplicated vs. complicated appendicitis, adapted
from those of the European Association of Endoscopic Surgery (EAES), 2016
Germany. (12), and of diagnostic measures in suspected acute appendicitis

Method Uncomplicated Complicated

A selective literature search was carried out in the Criteria for uncomplicated vs. complicated appendicitis
PubMed and Cochrane Library databases, with the Inflammation + +
search terms “acute appendicitis,” “acute appendicitis
Gangrene − +
diagnostics,” “acute appendicitis therapy,” “appendec-
tomy,” “uncomplicated appendicitis,” “complicated Phlegmon − +
appendicitis,” “appendicitis in children,” and “appen- Perityphlitic abscess − +
dicitis in adults.” Free fluid − +
Learning objectives Perforation − +
This article should enable the reader to: Diagnostic measures
● distinguish uncomplicated and complicated appen- History + +
dicitis Physical examination, + +
● know the diagnostic and therapeutic options in including appendicitis pressure points
acute appendicitis in children and adults. Digital rectal examination − −
Classification Laboratory tests + +
Appendicitis is defined as an inflammation of the Body temperature measurement + +
vermiform appendix. The European Association of En- Urine test strip and pregnancy test*1 + +
doscopic Surgery (EAES) classifies acute appendicitis Gynecological consultation ± ±
as either “uncomplicated” or “complicated” (12). Un-
complicated appendicitis is defined as inflammation in Abdominal ultrasonography*2 + +
the absence of phlegmon, gangrene, free purulent fluid, Computed tomography − ±
or an abscess. Complicated appendicitis is accompa- Magnetic resonance imaging − ±
nied by a periappendiceal phlegmon with or without
perforation, gangrene, or a perityphlitic abscess + yes; − no; ± possible
(Table 1). Complicated appendicitis is present, by definition, if any criterion in addition to inflammation is met.
*1 In female patients of child-bearing age; *2 method of first choice.

Diagnostic evaluation
Cases of acute appendicitis vary widely in their clinical
presentation, and the diagnosis is made more difficult
by a multiplicity of differential diagnoses. Acute ap- A change in the localization of pain from the upper
pendicitis has been called the chameleon of surgery abdomen to the right lower quadrant is often associated
(13). Up to half of all cases in children present with with appendicitis (16). In children and adolescents, the
nonspecific symptoms. There is a wide range of differ- history and physical examination should be adapted to
ential diagnoses depending on age; the incidence peak the patient’s age and developmental stage. The experi-
is during the primary-school years and adolescence ence of the examiner is important, particularly when
(Table 2) (4, 14, 15). In our view, appendicitis should the patient is a small child. Appropriate analgesic medi-
already be classified before treatment as either cation does not mask the physical findings to any rel-
uncomplicated or complicated, in order to enable stage- evant extent (17). In children, the absence of nausea
appropriate treatment. and vomiting, abdominal tenderness, and leukocytosis
rules out appendicitis with 98% reliability (18). In
History, physical examination, and laboratory tests pregnant women, the appendix may be cranially dis-
The patient should always be asked about the time of placed by the enlarged uterus, with the result that pain
onset of symptoms and the site of the pain, as well as is felt in the upper abdomen, rather than the right lower
the past medical history and current medications (Table 1). quadrant; this can make the diagnosis more difficult.

The state of the evidence Clinical presentation

Three guidelines on appendicitis have been published to date Acute appendicitis has a highly variable clinical presentation
internationally, but none yet in Germany. and has therefore been called the chameleon of surgery.

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A diagram of the FIGURE

pain and pressure
points to be check-
ed when acute Designation Location
appendicitis is McBurney’s point A pressure point one-third of the distance from the right
suspected. anterior superior iliac spine to the umbilicus.
Lanz’s point A pressure point one-third of the distance from the right
anterior superior iliac spine to the left anterior superior
iliac spine.
Blumberg’s sign Ipsi- or contralateral rebound pain.
Rovsing’s sign Pain in the right lower quadrant induced by deep press-
ure exerted on the descending colon in the left lower
quadrant in a retrograde (i.e., upward) direction.
Psoas sign Pain in the right lower quadrant induced by flexion of the
right hip against resistance (mainly a sign of a retrocec-
ally located appendix)

* Some sources call the midpoint of the segment between these two points McBurney´s point

Whenever acute appendicitis is suspected, physical Appendicitis Inflammatory Response (AIR) score
examination for the known signs of appendicitis is (2008) (Table 3) (6). The criterion of an Alvarado score
mandatory (Figure, Table 1) in addition to blood tests ≥ 5 diagnoses appendicitis with 99% sensitivity, but
(19). only 43% specificity; setting the threshold higher (≥ 7)
Local guarding in the right lower abdominal quadrant leads to increased specificity (81%), at the cost of lower
indicates irritation of the parietal peritoneum, while dif- sensitivity (82%). The Alvarado score, therefore, is most
fuse guarding indicates a severe, complicated case of useful for ruling out appendicitis, rather than diagnosing
appendicitis. Leukocytosis/neutrophilia and an elevated it. In contrast, an AIR score >8 is both highly sensitive
serum concentration of C-reactive protein (CRP) are and highly specific (99%) for appendicitis (6, 11). In
considered nonspecific signs of inflammation (20, 21). Germany, scoring systems like these are not generally
Procalcitonin plays no role in routine diagnostic testing used as an aid to diagnosis in routine clinical practice.
(22, 23). The body temperature should be measured, and
a simple urinalysis with a test strip should be per- Imaging
formed, as should a pregnancy test in girls and women Ultrasonography, CT, and MRI are all used in the evalu-
of child-bearing age (20). These measures serve to rule ation of suspected acute appendicitis. Ultrasonography is
out a number of differential diagnoses of right lower the method of first choice, particularly for children (25). It
quadrant pain, for example, urolithiasis, urinary tract has the disadvantage that its diagnostic benefit depends on
infection, or an ectopic pregnancy. Gynecological con- the examiner’s experience, and a negative finding may not
sultation should be obtained for stable female patients suffice to rule out appendicitis (sensitivity 71–94%, spe-
with unclear clinical presentations in whom the diag- cificity 81–98%) (12, 26). In children, its sensitivity and
nosis remains uncertain. A digital rectal examination is specificity are higher: sensitivity 96% [83–99%], speci-
of low diagnostic yield and need not be performed (24). ficity 100% [87–100%] (25).
CT is superior to ultrasonography (sensitivity
Scoring systems 76–100%, specificity 83–100%) (12), yet its role in
A variety of scoring systems have been developed for the evaluation of suspected acute appendicitis is a
the purpose of investigating and objectifying a sus- matter of controversy in Western countries, and it is
pected diagnosis of acute appendicitis independently of used to a variable extent depending on location. In the
the clinical experience of the examiner. The most com- USA, CT is routinely performed in 20–95% of pa-
monly used ones are the Alvarado score (1986) and the tients, presumably contributing to the less than 5%

Findings on palpation Imaging techniques

Local guarding in the right lower abdominal quadrant Abdominal ultrasonography is the imaging method of first
indicates irritation of the parietal peritoneum, while diffuse choice for confirming a diagnosis, or evaluating a suspected
guarding indicates a severe, complicated case of diagnosis, of acute appendicitis.
appendicitis.

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TABLE 2

Modified list of differential diagnoses of appendicitis in childhood and adolescence,

after Stundner-Ladenlauf and Metzger (e57)

Children and adolescents Infants and children 6 –12 years old > 12 years old
in general <6 years old
– constipation – volvulus – functional abdominal pain – ovarian torsion
– gastroenteritis – intussusception – testicular or ovarian torsion – testicular torsion
– ileus – malrotation – epididymitis – ovarian cyst
– pneumonia – colic – Henoch-Schönlein purpura – ovulatory pain
– urinary tract infection – testicular torsion – intussusception – extrauterine pregnancy
– trauma – epididymitis – volvulus – infectious monomucleosis
– abuse – inguinal hernia – chronic inflammatory bowel
– Hirschsprung’s disease diseases
– constipation

rate of negative appendectomies (removal of a histo- Treatment

pathologically normal appendix) (27–29). In Europe, Guidelines and literature
on the other hand, the diagnosis is often made on According to the World Society of Emergency Surgery
clinical grounds, and there is a higher laparoscopy (WSES), the Society of Gastrointestinal and
rate as well as a higher rate of negative appendec- Endoscopic Surgeons (SAGES), and the European As-
tomies (up to 32%) (30, 31). The use of low-dose sociation for Endoscopic Surgery (EAES), appendec-
rather than conventional CT does not significantly af- tomy is the treatment of choice for uncomplicated acute
fect the negative appendectomy rate (difference 0.3%, appendicitis in all age groups (10–12). Harrison, in
95% confidence interval [−3.8; 4.6]); avoiding the 1953, was the first to propose conservative treatment
administration of oral contrast medium and giving in- for acute appendicitis (38). A few authors reported
travenous contrast medium lowers radiation exposure spontaneous cures (39). Now that many publications
while preserving diagnostic sensitivity (95% versus have documented the successful conservative treatment
92%) (32–36). Nonetheless, even though CT is both of uncomplicated appendicitis with antibiotics in child-
highly sensitive and highly specific, it may not be hood and adulthood, this approach is attracting
able to distinguish complicated from uncomplicated increased attention (12, 40, e1–e3). In a recent meta-
appendicitis. In obese persons (BMI >30 kg/m2), the analysis, children and adolescents with uncomplicated
ultrasonographic signs of appendicitis are hard to appendicitis who were treated conservatively became
evaluate; CT is performed more often in this patient free of symptoms in 92% ([88; 96]) of cases, although
group (12). The same holds for persons over age 65, 16% (10–22%) went on to undergo appendectomy be-
because their symptoms are usually atypical, and cause of a recurrence (follow-up: 8 weeks to 4.5 years)
because increasing age is associated with higher (e3). Another meta-analysis, in 2016, showed no differ-
comorbidity and thus also with a broader differential ence with regard to complications or length of hospital
diagnosis. stay (e4). In a comparative analysis, Kessler et al. found
MRI, compared to CT, has comparable sensitiv- that conservative management in childhood led to a
ity (97 versus 76–100%) and specificity (95 versus higher hospital readmission rate (relative risk [RR]
83–100%) for the diagnosis of acute appendicitis 6.98; [2.07; 23.6]) and a lower rate of becoming free of
(12), but it is not universally available in an em- symptoms (RR 0.77; [0.71; 0.84]) (e5). Because the
ergency. MRI is a safe alternative to CT for studies analyzed in these publications were not ran-
children and pregnant women, as it does not domized and recruited fewer patients than would have
involve ionizing radiation, and is thus preferable to been desirable, it can practically be assumed that the
CT, in our view, if the ultrasonographic findings children were more likely to be treated conservatively
are equivocal (37). Children under age 5 often if they were less clinically ill. The follow-up was inad-
require sedation or general anesthesia for MRI to equate as well, as shown by 5-year follow-up studies
be performed. both in children (appendectomy rate five years after

Obesity Children and pregnant women

2
In obese persons (BMI >30 kg/m ), the ultrasonographic signs MRI is a safe alternative to CT for children and pregnant
of appendicitis are hard to evaluate; CT is performed more women, as it does not involve ionizing radiation, and is thus
often in this patient group. preferable to CT, in our view, if the ultrasonographic findings
are equivocal.

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TABLE 3 primary conservative treatment of uncomplicated

appendicitis: 46%) (e6) and in adults (APPAC trial
Modified summary of the Alvarado (e58) and AIR scores (e59) appendectomy rates of 27% and 39% at one and five
for evaluating the possible presence of appendicitis
years, respectively) (e7, e8). Moreover, in the APPAC
Criterion Alvarado AIR trial, the non-inferiority criterion for antibiotic
Score Score treatment was not met at one year. In all three of the
Symptoms analyses mentioned above, the state of the evidence is
Vomiting – 1 insufficient to justify a change of clinical strategy, al-
though conservative treatment can be regarded as safe
Nausea or vomiting 1 –
(e3–e5). In a meta-analysis of five randomized and
Anorexia 1 – controlled trials published in 2019, appendectomy was
RLQ pain 2 1 found to be the more effective method for the definitive
Migratory RLQ pain 1 – treatment of uncomplicated appendicitis in adulthood
(37.4% appendectomy rate within one year after con-
Signs
servative treatment; treatment effectiveness [i.e., lack
RLQ rebound pain or guarding 1 – of recurence or appendectomy] with at least one year of
mild – 1 follow-up, 62.6% versus 96.3% in the surgical group,
moderate – 2 RR 0.65 [0.55; 0.76]) (e9). Current evidence is insuffi-
cient to enable the detection of any advantage for
severe – 3
conservative treatment, and surgery thus remains the
Body temperature >37.5°C 1 – treatment of choice for acute uncomplicated appendici-
>38.5°C – 1 tis in both children and adults (e3). The potential long-
Laboratory parameters
term adverse effects of conservative treatment (drug
side effects, antibiotic resistance) have not been
Leukocyte count >10 000/L 2 – adequately described to date and will be studied in
10 000–14 900/L – 1 upcoming trials (APPAC-III, MAPPAC) (e10, e11).
>15 000/L – 2 For all these reasons, the rest of this article will
deal mainly with the surgical treatment of acute un-
Leukocyte shift 1 –
complicated and complicated appendicitis in children
PMN granulocytes 70–84% – 1 and adults.
≥ 85% – 2
CRP value 10–49 mg/L – 1 Laparoscopy
In Germany, appendectomy is now performed lapa-
≥ 50 mg/L – 2
roscopically as a standard. The reasons for this are the
Sum 10 12 shorter hospital stay, lower wound infection rate, and
Alvarado score <5 low probability lower morbidity (1.5% versus 11.9% for wound-
5–6 unclear healing disturbances) and mortality (0.1 versus 1.2%)
compared to open surgery, although the negative selec-
7–8 likely
tion of seriously ill patients must be taken into account
>8 high probability (3). Laparoscopy enables abdominal exploration to
AIR score <5 low probability rule out various differential diagnoses, e.g., adnexitis
5–8 intermediate and Meckel’s diverticulitis. It remains controversial
probability whether a macroscopically normal appendix should be
>8 high probability removed if no alternative diagnosis can be made, just
as conservative treatment remains controversial (12,
AIR, Appendicitis Inflammatory Response; CRP, C-reactive protein; e12, e13). In our view, incidental appendectomy can be
RLQ, right lower abdominal quadrant; PMN, polymorphonuclear. performed if there is no contraindication. In 18–29%
of cases, histological study reveals appendicitis or
another type of appendiceal pathology, such as
endometriosis (0.0–0.9%), neoplasia (0.23–1.2%), or
obstruction by an appendicolith (2.7–6.0%) or

The treatment of choice Conservative treatment

Appendectomy is the treatment of choice for uncomplicated acute appendicitis in all Current evidence is insufficient to enable the detection of any
age groups. advantage for conservative treatment of acute uncomplicated
appendicitis.

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parasites (1.2–2.5%), despite a macroscopically what treatment is truly best for complicated appen-
normal appendix (e14, e15). dicitis in consideration of the patient’s risk factors and
clinical condition. It has been suggested that interval
Complicated appendicitis appendectomy might be best reserved for symp-
There is no standard evidence-based approach to the tomatic patients (e21), in view of the associated
treatment of complicated acute appendicitis. In prin- higher conversion rate (1.9 versus 0.13%; p <0.001),
ciple, it can either be treated with urgent surgery or and higher rates of intraoperative complications
managed conservatively (i.e., with antibiotics alone (2.8% versus 0.3%; p <0.001) and intra-abdominal re-
or with the interventional placement of a drain). tentions (4.7 versus 1.2%, p = 0.003) (e20).
Certainly, the clinical condition of the patient and any
risk factors that are present should be taken into ac- The management of a perityphlitic abscess (drainage
count in deciding upon the treatment (12). Moreover, before surgery)
if conservative management is adopted, the associ- In view of the heterogeneous data that are currently
ated risks must be borne in mind (e16, e17). In available, there is no uniform, evidence-based way to
Germany, the usual treatment is immediate appendec- proceed when a perityphlitic abscess is demonstrated
tomy (3). The EAES and WSES have not defined any (e16–e19, e22). In this situation, we recommend risk-
clear way to proceed in the management of compli- stratified interdisciplinary management, depending on
cated appendicitis (11, 12). They consider initial con- size. A macroabscess can be treated with the interven-
servative management a possible option but point out tional placement of a drain combined with antibiotic
the need for further studies to clarify the role of inter- treatment and, depending on the further course, an in-
val appendectomy, i.e., appendectomy during an terval appendectomy. A microabscess can be treated
inflammation-free interval (12). The WSES recom- with immediate surgery, because puncturing the ab-
mends primary conservative treatment for an abscess scess is generally not technically feasible.
or phlegmon, with the comment that laparoscopy is a
feasible alternative (11). Internationally, there is in- The timing of surgery
creasing evidence in favor of conservative treatment It was once the rule to operate on acute appendicitis as
for complicated appendicitis (mixed meta-analysis: rapidly as possible to avoid perforation and the ensuing
17 retrospective studies, one prospective study, and complications (12). To date, however, there have been
three randomized, controlled trials), with low rates of no randomized, controlled trials on this topic. Certain
complications (odds ratio [OR] 3.16; [1.73; 5.79], observations—such as a lower risk of perforation with
intra-abdominal retentions (OR 3.13; [1.18; 8.3]), and a longer wait before surgery—may well be related to
wound infections (OR 3.95; [1.95; 8.00]) compared to bias in the evidence, because patients who are
surgery. The subgroup analysis of the included ran- clinically more severely ill (those with perforation or
domized, controlled trials did not reveal any signifi- complicated appendicitis) have tended to be given
cant difference in intra-abdominal retentions (OR priority for rapid surgery (e23, e24). In a Swedish
0.46; [0.17; 1.29]) between conservative and multicenter study involving 1675 patients, the perfo-
laparoscopic treatment. On the other hand, these ration rate only rose significantly 12, 18, and 24 hours
high-quality randomized and controlled trials did after admission to the hospital (e23). Accordingly, in a
show laparoscopic appendectomy to be associated study from the USA, surgery at a delay of more than 12
with a hospital stay that was one day shorter (mean hours was associated with a longer length of hospital
difference [MD] −0.99; [−1.31; –0.67]), without any stay (44.6 versus 34.5 hours) and increased costs (e25).
elevation of the complication rate (e18). Another In an American study of 857 children in whom the
meta-analysis (three randomized, controlled trials initial CT revealed no evidence of perforation, a weak
[RCTs] and four controlled clinical studies) favored association was found between triage (i.e., a delay) till
immediate laparoscopic surgery for appendicitis in the incision was made and the intraoperative finding of
the presence of an abscess, rather than conservative a perforation (adjusted odds ratio 1.02 [1.00; 1.04] per
management, because of a higher rate of unproblem- hour of delay) (e26). It is also concluded in the up-to-
atic recovery (OR 11.91; [4.59; 30.88]), a shorter hos- date meta-analysis of Li et al. that a brief (<12-hour)
pital stay (weighted MD: −2.98; [−5.96; −0.01]), and delay is not associated with complicated appendicitis,
fewer recurrent abscesses (OR 0.07; [0.3; 0.20]) but that there is nonetheless a progressively strong
(e19). Future studies will be needed to determine association between the time since the onset of

Perityphlitic abscess Microabscess

Perityphlitic abscesses should be managed by an interdis- A microabscess can be treated with immediate surgery,
ciplinary team in risk-stratified fashion, depending on size. because puncturing the abscess is generally not techni-
A macroabscess can be treated with interventional drain cally feasible.
placement combined with antibiotic treatment and, depend-
ing on the further course, an interval appendectomy.

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elevate the morbidity of patients with uncomplicated

appendicitis to any relevant extent.
Adequate data are lacking concerning the
appropriate timing of surgery for complicated ap-
pendicitis; the timing of surgery depends on the
findings (phlegmon, free fluid, abscess) and on the
patient’s clinical condition and comorbidities. In a
meta-analysis comparing conservative and surgical
treatment of complicated appendicitis with a free
perforation in children, based on two randomized,
controlled trials and twelve observational studies,
the surgical group experienced significantly fewer
complications (RR 1.86; [1.20; 2.87]) and hospital
a readmissions (RR 3.33; [1.49; 7.44]) (e32). We do
not know of any comparable study in adults, but one
study has shown that the timing of surgery is
correlated with survival (e33). Thus, whenever free
intraperitoneal air is seen, in a child or adult patient,
surgery should be performed urgently.

Antibiotics
The conservative treatment of acute appendicitis is
based on the administration of antibiotics (Cochrane
Review: 45 studies, including RCTs and CCTs) (e34).
A cephalosporin combined with a nitroimidazole
(usually metronidazole) is most commonly used, fol-
lowed by a penicillin with a beta-lactamase inhibitor
b and by quinolones. The evidence base is derived from
the WSES guideline and a prospective, worldwide
Figure 1: Intraoperative view of gangrenous appendicitis
a) after exposure and b) before removal with a stapler.
multicenter observational study (6, 11). Antibiotics are
Arrow: base of appendix; polygon: tip of appendix; usually given parenterally for one to three days and
line: parallel to the dissector with which the surgeon is checking the freely exposed window of then orally for a further 5–7 days (11, e21). The optimal
the mesoappendix. duration of treatment is not clear; the length of treat-
ment generally depends on the clinical course and the
normalization of inflammatory parameters (12). Anti-
biotics should be given perioperatively as part of the
symptoms, or since hospital admission, and the likeli- treatment of any type of appendicitis (11, e34). A meta-
hood of perforated appendicitis—the odds ratio is 1.84 analysis of 12 randomized, controlled trials and one
([1.05; 3.21]) at 24 hours and 7.57 at 48 hours ([6.14; Cochrane Review (47 studies) showed that peri-
9.35]) (e27). In adults, delaying appendectomy by operative antibiotics can lower both the rate of wound
12–24 hours from the time of diagnosis, while giving infections (Peto OR: 0.33; [0.29; 0.38]) and the abscess
antibiotics, does not increase the perforation rate incidence (Peto OR: 0.43; [0.25; 0.73]) (e35). Continu-
(e28–e30). The operation should not be delayed by ing the antibiotics postoperatively is recommended in
more than 12 hours for patients with comorbidities or complicated appendicitis, particularly in case of an
who are age 65 or older. Appendectomy more than 48 abscess, peritonitis, or free perforation (e35).
hours after diagnosis is associated with a higher surgi-
cal infection rate (adjusted OR 2.24; p = 0.039) (e31). Postoperative and other complications
In view of the heterogeneous evidence base that is cur- The overall rate of postoperative complications after
rently available, we recommend a risk-stratified ap- appendectomy in Germany has been reported as up to
proach. A delay of up to 12 hours in children or 24 2.1% (e36). Postoperative complications can be cat-
hours in adults while antibiotics are given seems not to egorized as early or late. The former include wound

Therapeutic decision-making in acute appendicitis in Delayed appendectomy

persons belonging to special risk groups In adults with uncomplicated acute appendicitis, delaying
Conservative treatment has a higher risk of failure in patients appendectomy by 12 to 24 hours from the time of diag-
2
with a demonstrated appendicolith, obesity (BMI >30 kg/m ), nosis, while giving antibiotics, does not lead to an in-
age over 65, or immune suppression or acquired immune creased rate of perforation.
deficit, as well as in pregnant women.

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infection, hemorrhage, abdominal wall abscess, and appendicitis (Figures 1a and b). Laparoscopic appen-
appendiceal stump insufficiency, as well as intra- dectomy is considered a safe treatment in this
abdominal retentions (Douglas or loop abscess). The situation as well (12, e52). In pregnancy, too, acute
latter include incisional hernias, intra-abdominal ad- appendicitis is the most common cause of the acute
hesions possibly causing bowel obstruction, and abdomen, and spontaneous abortion is its most feared
stump appendicitis. Whenever a postoperative complication (e53). Miscarriage is more common in
complication is suspected, the patient should be complicated appendicitis than in uncomplicated
re-examined by the operating surgeon, and appendicitis (20% versus 1.5%) (e54, e55). The
further diagnostic studies should be undertaken threshold for operating should, therefore, be set low;
including laboratory testing and abdominal ultra- appendectomy can be carried out safely in all three tri-
sonography. mesters (e56).
Patient information on the conservative treatment
of appendicitis should include the fact that the inci- Discussion
dence of bowel cancer is slightly higher than in the In the diagnosis and treatment of acute appendicitis in
normal population (Swedish population cohort study, childhood and adulthood, there is increasing dis-
SIR: 4.1 [3.7; 4.6]) (e37). Nor is there yet any defini- cussion of the possibility of nonsurgical treatment, of
tive information from RCTs on the possible risk of ad- the optimal timing of surgery, and of the appropriate
hesion formation, or the potentially higher probability postoperative care (12, 40, e1, e2). Nonetheless, the
of infertility, after conservative treatment. A Swedish available evidence base does not suffice to justify a
study employing a historical cohort for comparison change from primarily surgical treatment, in either
did not reveal any higher frequency of infertility after children or adults (e3, e5, e9). Moreover, there have
perforated appendicitis in childhood than after appen- not yet been any randomized, placebo-controlled,
dectomy of an unperforated, or even healthy, appen- blinded trials investigating the long-term course with
dix (e38). regard to the undesired side effects of conservative
In 0.5% of children who undergo appendectomy, treatment; such trials are to begin soon (e10, e11).
histopathological study of the surgical specimen re- Thus, appendectomy remains the treatment of choice
veals a neuroendocrine tumor of the appendix, a so- for uncomplicated acute appendicitis in all age
called appendiceal carcinoid, as an incidental finding groups (10–12). In adults with uncomplicated acute
(e39). Depending on the size of the tumor, more ex- appendicitis, delaying appendectomy by 12 to 24
tensive surgery, such as an ileocecal resection or a hours from the time of diagnosis, while giving
hemicolectomy, may be necessary. The further course antibiotics, does not lead to an increased rate of per-
of treatment should always be decided upon in collab- foration (e28–e30). Surgery should not, however, be
oration with a pediatric oncologist (e40). delayed by more than 12 hours in children and
adolescents, patients over age 65, or patients with co-
Risk groups morbidities (e23–e27, e31).
Therapeutic decision-making should also take certain Complicated acute appendicitis is a severe illness
special risk groups into consideration. According to the that can be managed conservatively, as an alternative
pertinent literature, conservative treatment has a higher to surgical treatment, under certain circumstances.
risk of failure, and correspondingly higher morbidity, in The state of the evidence regarding the morbidity and
patients with a demonstrated appendicolith (e41), efficacy of conservative management is mixed (e18,
obesity (BMI > 30 kg/m2) (e42), age over 65 e19, e32). Future studies will be needed for a
(e43–e47), or immune suppression or acquired im- definitive determination of the best way to treat com-
mune deficit (e48), as well as in pregnant women plicated appendicitis in consideration of the patient’s
(e49–e51) (12). The demonstration of an appendicolith risk factors and clinical condition.
on an imaging study is highly likely to be followed by
the failure of conservative treatment (Mantel-Haenszel Conflict of interest statement
estimator RR: 10.43 [1.46; 74.26] (e41). Thus, these The authors state that they have no conflict of interest.
patients should be treated with early appendectomy
Manuscript submitted on 5 March 2020, revised version accepted on
(eCase Illustration with eFigures 1 and 2). 29 July 2020.
In this patient collective, high leukocyte counts and
CRP values are correlated with the risk of gangrenous Translated from the original German by Ethan Taub, M.D.

Overall postoperative complication rate Appendicitis and pregnancy

The overall rate of postoperative complications after appen- In pregnancy, too, acute appendicitis is the most common cause
dectomy in Germany has been reported as up to 2.1%. of the acute abdomen, and spontaneous abortion is its most
feared complication.

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12. Gorter RR, Eker HH, Gorter-Stam MA, et al.: Diagnosis and manage-
ment of acute appendicitis. EAES consensus development conference
Further information on CME 2015. Surg Endosc 2016; 30: 4668–90.
● Participation in the CME certification program is possible only 13. Zachariou Z: Appendizitis. In: von Schweinitz D, Ure B (eds.): Kinder-
chirurgie: Viszerale und allgemeine Chirurgie des Kindesalters. Berlin,
over the Internet: cme.aerzteblatt.de. This unit can be ac- Heidelberg: Springer 2009: 413–20.
cessed until 5 November 2021. Submissions by letter, e-mail 14. Stein GY, Rath-Wolfson L, Zeidman A, et al.: Sex differences in the epi-
or fax cannot be considered. demiology, seasonal variation, and trends in the management of patients
with acute appendicitis. Langenbecks Arch Surg 2012; 397: 1087–92.
● Once a new CME module comes online, it remains available 15. Almström M, Svensson JF, Svenningsson A, Hagel E, Wester T:
for 12 months. Results can be accessed 4 weeks after you Population-based cohort study on the epidemiology of acute appendicitis
start work on a module. Please note the closing date for each in children in Sweden in 1987–2013. BJS Open 2018; 2: 142–50.
module, which can be found at cme.aerzteblatt.de. 16. Humes D, Speake WJ, Simpson J: Appendicitis. BMJ Clin Evid 2007;
2007: 0408.
● This article has been certified by the North Rhine Academy 17. Kang K, Kim WJ, Kim K, et al.: Effect of pain control in suspected acute
for Continuing Medical Education. Participants in the CME appendicitis on the diagnostic accuracy of surgical residents. CJEM
2015; 17: 54–61.
program can manage their CME points with their 15-digit
18. Kharbanda AB, Taylor GA, Fishman SJ, Bachur RG: A clinical decision
“uniform CME number” (einheitliche Fortbildungsnummer, rule to identify children at low risk for appendicitis. Pediatrics 2005; 116:
EFN), which is found on the CME card 709–16.
(8027XXXXXXXXXXX). The EFN must be stated during 19. Humes DJ, Simpson J: Acute appendicitis. BMJ 2006; 333: 530–4.
registration on www.aerzteblatt.de (“Mein DÄ”) or else 20. Shogilev DJ, Duus N, Odom SR, Shapiro NI: Diagnosing appendicitis:
entered in “Meine Daten,” and the participant must agree to evidence-based review of the diagnostic approach in 2014. West J
Emerg Med 2014; 15: 859–71.
communication of the results.
21. Andersson RE: Meta-analysis of the clinical and laboratory diagnosis of
appendicitis. Br J Surg 2004; 91: 28–37.
22. Yu C-W, Juan L-I, Wu M-H, Shen C-J, Wu J-Y, Lee C-C: Systematic re-
view and meta-analysis of the diagnostic accuracy of procalcitonin,
C-reactive protein and white blood cell count for suspected acute
appendicitis. Br J Surg 2013; 100: 322–9.
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marker between uncomplicated and complicated acute appendicitis in
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adult patients. Eur J Trauma Emerg Surg 2019; 2020; 46:853–8.
statistik (DRG-Statistik) Operationen und Prozeduren der vollstationären
Patientinnen und Patienten in Krankenhäusern (4-Steller) 2018. Wies- 24. Takada T, Nishiwaki H, Yamamoto Y, et al.: The role of digital rectal
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meta-analysis. PLoS ONE 2015; 10: e0136996.
2. Buckius MT, McGrath B, Monk J, Grim R, Bell T, Ahuja V: Changing
epidemiology of acute appendicitis in the United States: study period 25. Soundappan SS, Karpelowsky J, Lam A, Lam L, Cass D: Diagnostic ac-
1993–2008. J Surg Res 2012; 175: 185–90. curacy of surgeon performed ultrasound (SPU) for appendicitis in
3. Sahm M, Koch A, Schmidt U, et al.: Akute Appendizitis – Klinische Ver- children. J Pediatr Surg 2018; 53: 2023–7.
sorgungsforschung zur aktuellen chirurgischen Therapie. Zentralbl Chir 26. Doria AS, Moineddin R, Kellenberger CJ, et al.: US or CT for diagnosis
2013; 138: 270–7. of appendicitis in children and adults? A meta-analysis. Radiology 2006;
4. Addiss DG, Shaffer N, Fowler BS, Tauxe RV: The epidemiology of 241: 83–94.
appendicitis and appendectomy in the United States. Am J Epidemiol 27. Expert Panel on Gastrointestinal Imaging, Garcia EM, Camacho MA, et
1990; 132: 910–25. al.: ACR Appropriateness Criteria® right lower quadrant pain-suspected
5. Rolle U, Maneck M: Versorgungstrends, regionale Variation und Qualität appendicitis. J Am Coll Radiol 2018; 15: 373–87.
der Versorgung bei Appendektomien. In: Klauber J, Günster C, Gerste 28. National Surgical Research Collaborative: Multicentre observational
B, Robra B-P, Schmacke N, Abbas S (eds.): Versorgungsreport study of performance variation in provision and outcome of emergency
2015/2016. Stuttgart: Schattauer 2016: 217–38. appendicectomy. Br J Surg 2013; 100: 1240–52.
6. Sartelli M, Baiocchi GL, Di Saverio S, et al.: Prospective observational 29. Pickhardt PJ, Lawrence EM, Pooler BD, Bruce RJ: Diagnostic perform-
study on acute appendicitis worldwide (POSAW). World J Emerg Surg ance of multidetector computed tomography for suspected acute appen-
2018; 13: 19. dicitis. Ann Intern Med 2011; 154: 789–96.
7. De Coppi P, Pozzobon M, Piccoli M, et al.: Isolation of mesenchymal 30. Lim J, Pang Q, Alexander R: One year negative appendicectomy rates
stem cells from human vermiform appendix. J Surg Res 2006; 135: at a district general hospital: A Retrospective Cohort Study. Int J Surg
85–91. 2016; 31: 1–4.
8. Bollinger RR, Barbas AS, Bush EL, Lin SS, Parker W: Biofilms in 31. Brockman SF, Scott S, Guest GD, Stupart DA, Ryan S, Watters DA:
the large bowel suggest an apparent function of the human vermiform Does an acute surgical model increase the rate of negative appendicec-
appendix. J Theor Biol 2007; 249: 826–31. tomy or perforated appendicitis? ANZ J Surg 2013; 83: 744–7.
9. Bollinger RR, Barbas AS, Bush EL, Lin SS, Parker W: Biofilms in the 32. Yun SJ, Ryu C-W, Choi NY, Kim HC, Oh JY, Yang DM: Comparison of
normal human large bowel: fact rather than fiction. Gut 2007; 56: low- and standard-dose CT for the diagnosis of acute appendicitis: a
1481–2. meta-analysis. AJR Am J Roentgenol 2017; 208: W198–207.
10. Korndorffer JR Jr, Fellinger E, Reed W: SAGES guideline for lapar- 33. Kim K, Kim YH, Kim SY, et al.: Low-dose abdominal CT for evaluating
oscopic appendectomy. Surg Endosc 2010; 24: 757–61. suspected appendicitis. N Engl J Med 2012; 366: 1596–605.
11. Di Saverio S, Birindelli A, Kelly MD, et al.: WSES Jerusalem guidelines 34. Ramalingam V, Bates DD, Buch K, et al.: Diagnosing acute appendicitis
for diagnosis and treatment of acute appendicitis. World J Emerg Surg using a nonoral contrast CT protocol in patients with a BMI of less than
2016; 11: 34. 25. Emerg Radiol 2016; 23: 455–62.

The timing of surgery

Surgery should not be delayed by more than 12 hours in
children and adolescents, patients over age 65, or patients
with comorbidities.

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35. Anderson BA, Salem L, Flum DR: A systematic review of whether oral contrast is
necessary for the computed tomography diagnosis of appendicitis in adults. Am J
Surg 2005; 190: 474–8.
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childhood: oral contrast does not improve CT diagnosis. Emerg Radiol 2018; 25:
257–63.
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magnetic resonance imaging for suspected acute appendicitis in pregnant patients.
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38. Harrison PW: Appendicitis and the antibiotics. Am J Surg 1953; 85: 160–3.
39. Andersson RE: The natural history and traditional management of appendicitis
revisited: spontaneous resolution and predominance of prehospital perforations
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World J Surg 2007; 31: 86–92.
40. Vons C, Barry C, Maitre S, et al.: Amoxicillin plus clavulanic acid versus
appendicectomy for treatment of acute uncomplicated appendicitis: an open-label,
non-inferiority, randomised controlled trial. Lancet 2011; 377: 1573–9.

Corresponding author
Dr. med. Patrick Téoule
Chirurgische Klinik, Universitätsmedizin Mannheim
Medizinische Fakultät Mannheim, Universität Heidelberg
Theodor-Kutzer-Ufer 1–3, 68167 Mannheim
patrick.teoule@umm.de

Cite this as:

Téoule P, de Laffolie J, Rolle U, Reißfelder C:
Acute appendicitis in childhood and adulthood—an everyday clinical challenge. Dtsch
Arztebl Int 2020; 117: 764–74. DOI: 10.3238/arztebl.2020.0764

►Supplementary material
For eReferences please refer to:
www.aerzteblatt-international.de/ref4520
eCase Illustration, eFigures:
www.aerzteblatt-international.de/20m0764

CLINICAL SNAPSHOT
Atraumatic Atlantoaxial Subluxation—Grisel Syndrome
A 5-year-old girl underwent parotidectomy for cystic, atypical mycobacterial infection (Myco-
bacterium malmoense). On postoperative day 2, the otherwise healthy girl developed—despite
orthotic treatment—progressive torticollis, for which she was seen for treatment. It was possible
to achieve a clinical improvement in the passive and active lateral inclination of the head, not,
however, in the anomalous rotation. An electrophysiological investigation was normal. On the
basis of a suspicious magnetic resonance imaging scan performed at another institution showing
cervical spinal cord swelling, computed tomography with 3D reconstruction was performed,
revealing atlantoaxial subluxation. The combination of findings enabled the diagnosis of Grisel
syndrome to be made. The successful treatment in this case was performed as appropriate to
type (type 3 according to Fielding and Hawkins), comprising several weeks of halo traction
followed by a halo vest. Based on antibiogram results, concomitant triple therapy was performed
to treat the atypical mycobacterial infection. The rare entity of atraumatic atlantoaxial subluxation
typically affects children following respiratory infection or ear, nose, or throat surgery. Other
associations with hereditary disorders, chromosome aberrations (trisomy 21), and autoimmune diseases have been described. Self-limiting
cases, as well as cases requiring surgery, are known. This is an important differential diagnosis in the case of unexplained torticollis.
Dr. med. Martin Schwarze, Dr. med. Stefan Hemmer, Klinik für Orthopädie und Unfallchirurgie, Zentrum für Orthopädie, Unfallchirurgie und Paraplegiologie,
Universitätsklinikum Heidelberg, martin.schwarze@med.uni-heidelberg.de
Prof. Dr. med. Michael Akbar, Clinic für Wirbelsäulenerkrankungen und -Therapien, MEOCLINIC GmbH
Conflict of interest statement: The authors declare that no conflict of interest exists.
Translated from the original German by Christine Rye.
Cite this as: Schwarze M, Hemmer S, Akbar M: Atraumatic atlantoaxial subluxation—Grisel syndrome. Dtsch Arztebl Int 2020; 117: 773. DOI: 10.3238/arztebl.2020.0773

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MEDICINE

CME credit for this unit can be obtained via cme.aerzteblatt.de until 5 November 2021.
Only one answer is possible per question. Please select the answer that is most appropriate.

Question 1 Question 6
Which of the following can be present in either of the two types of If acute appendicitis is suspected and free air is demon-
appendicitis (complicated and uncomplicated)? strated, what is the appropriate management?
a) perforation a) conservative, with antibiotics
b) phlegmon b) conservative, with antibiotics and interventional drain place-
c) inflammation ment
d) gangrene c) urgent surgery
e) abscess d) surgery within 24 hours
e) elective surgery

Question 2
What is an important differential diagnosis of appendicitis in Question 7
women and girls of child-bearing age? What percentage of appendectomies in children are still
a) adnexitis performed by open surgery?
b) endometriosis a) circa 10%
c) coprostasis b) circa 25%
d) volvulus c) circa 40%
e) pregnancy d) circa 60%
e) circa 75%

Question 3
What imaging finding is highly correlated with the failure of Question 8
conservative treatment of acute appendicitis? What is the imaging method of first choice?
a) free fluid a) MRI
b) appendicolith b) CT
c) appendiceal wall thickening c) abdominal ultrasonography
d) circumscribed intra-abdominal retention d) abdominal plain films
e) ileus e) contrast ultrasonography

Question 4 Question 9
According to current evidence, how many hours from the diag- Girls of what age are at highest risk for appendectomy?
nosis of uncomplicated appendicitis can surgery be delayed, a) 1–5 years
while antibiotics are given, in an adult patient with no risk factors, b) 5–9 years
without increasing the risk of perforation? c) 9–13 years
a) 1 to 4 hours d) 13–17 years
b) 4 to 8 hours e) 14–18 years
c) 8 to 12 hours
d) 12 to 24 hours
e) 24 to 48 hours Question 10
What combination of antibiotics is now used most
commonly in Germany and abroad in the conservative
Question 5 management of acute appendicitis?
When can an appendectomy be performed safely in a pregnant a) quinolones and nitroimidazole
woman? b) penicillin and a beta-lactamase inhibitor
a) first trimester c) cephalosporins and nitroimidazole
b) second trimester d) lincosamides and nitroimidazole
c) first and second trimesters e) glycopeptides and nitroimidazole
d) second and third trimesters
e) first, second, and third trimesters

►Participation is possible only via the Internet:

cme.aerzteblatt.de

774 Deutsches Ärzteblatt International | Dtsch Arztebl Int 2020; 117: 764–74
 MEDICINE

Supplementary material to:

Acute Appendicitis in Childhood and Adulthood

An Everyday Clinical Challenge
by Patrick Téoule, Jan de Laffolie, Udo Rolle, and Christoph Reissfelder
Dtsch Arztebl Int 2020; 117: 764–74. DOI: 10.3238/arztebl.2020.0764

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II Deutsches Ärzteblatt International | Dtsch Arztebl Int 2020; 117: 764–74 | Supplementary material
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eCASE ILLUSTRATION

A 22-year-old man presented to the emergency department complaining of

feeling unwell since the morning, with a migrating pain in the right lower
abdominal quadrant. The further history was negative with respect to past
medical illnesses, past operations, medications taken, and allergies. Lab-
oratory tests revealed a leukocytosis of 22 000/L, a core body temperature

b
eFigure 1: a) intraoperative view a) before and b) after exposure.
Arrow: base of appendix; polygon: tip of appendix, star: mesoappendix;
white border: window created in the mesoappendix.

of 37.6°C, and an unremarkable urine test strip. Physical examination re-

vealed incipient peritoneal signs in the right lower quadrant, without guard-
ing but with positive appendicitis pressure points and contralateral rebound
pain. Ultrasonography revealed a small amount of periappendicular
echo-free fluid without any circumscribed mass. The appendix was 9 mm
in diameter, and an appendicolith was seen ultrasonographically. In view of
the free fluid and the overall clinical picture, the patient was deemed to
have a complicated case of appendicitis. After extensive discussion with
the patient, and because of the likelihood that conservative treatment would
fail, a decision was taken to perform a laparoscopic appendectomy.
Perioperatively, the patient was given antibiotic treatment based on a
cephalosporin and a nitroimidazole, and surgery ensued within 12 hours of
the diagnosis. The intraoperative findings confirmed acute appendicitis. A
laparoscopic appendectomy with clip application was performed.
eFigure 1 shows the intraoperative view before and after exposure of the
base of the appendix. eFigure 2 shows the twofold clip application at the

Deutsches Ärzteblatt International | Dtsch Arztebl Int 2020; 117: 764–74 | Supplementary material III
MEDICINE

base of the appendix, as well as the freely dissected appendicular artery be-
fore and after the artery was clipped and its distal portion removed together
with the appendix itself. No further antibiotics were given postoperatively.
The patient was discharged home on the second postoperative day after an
uneventful course, feeling well and with an unremarkable abdominal
examination.

b
eFigure 2: intraoperative view after a) clipping and b) division of the main structures.
Arrow: base of appendix; polygon: tip of appendix, star: mesoappendix;
rectangle: appendicular artery.

IV Deutsches Ärzteblatt International | Dtsch Arztebl Int 2020; 117: 764–74 | Supplementary material