Keywords appendectomy in pregnancy - appendicitis in pregnancy - cesarean section - surgical
intervention pregnancy - imaging diagnostics appendicitis
Schlüsselwörter Appendektomie in der Schwangerschaft - Appendizitis in der Schwangerschaft - Sectio
caesarea - operativer Eingriff in der Schwangerschaft - diagnostische Bildgebung und
Appendizitis
Introduction
One in 500 pregnant women requires a surgical intervention that is not primarily pregnancy
related [1 ]. Elective surgeries ought to be postponed until after delivery [2 ]. Nonobstetric surgeries that need to be performed due to urgency include abdominal,
dental, skin-related or bone-related surgeries [2 ]. An appendectomy is among the most frequent intraabdominal surgical procedures performed
during pregnancy [3 ]. In most cases appendectomy during pregnancy is performed in women who exhibit clinical
signs of appendicitis. Histopathologically, appendicitis is classified into 4 stages
as depicted in [Table 1 ]
[4 ]. In 0.1% of all pregnancies appendicitis is suspected [5 ]. Acute appendicitis with peritonitis is associated with higher rates of morbidity
and mortality for the mother and her offspring [6 ].
Table 1
Histopathological stages of appendicitis. Overview of classification of appendicitis
and associated histopathological changes.
Classification
Histopathological changes
Acute appendicitis
Erosive appendicitis
Inflammation limited to the mucosa or submucosa. It is usually not accompanied by
macroscopic changes.
Ulcerative phlegmonous appendicitis
Phlegmonous appendicitis is characterized by neutrophilic infiltration and often circumferential
involvement of the muscularis propria. The mucosa is usually inflamed, ulcerated and
often accompanied by edema, serositis and microabscesses.
Gangrenous appendicitis
Necrotic changes occur due to transmural inflammation of the wall layers. As the inflammation
progresses, the organ can perforate.
Chronic appendicitis
Chronic appendicitis is characterized by fibrosis and inflammatory infiltrates such
as lymphocytes, histiocytes and plasma cells. In addition, periappendicitous adhesions
and lipomatous transformations can be detected.
Due to changes in anatomy related to the growing uterus, physiological leukocytosis
and nonspecific or altered symptoms throughout gestation, diagnosing acute appendicitis
in pregnant women is challenging. Mentioned factors could cause a delay in diagnosis
and treatment [3 ]
[7 ]. Through the visualization of the vermiform appendix, ultrasound technology can
aid in the more precise classification of suspected non-obstetrical illnesses affecting
the abdomen [8 ]. Unfortunately, it frequently lacks conclusiveness and is heavily dependent on the
operator [1 ]
[9 ]. Magnetic resonance imaging (MRI) is advised as the preferred imaging
modality after an inconclusive ultrasound in order to visualize and evaluate the appearance
of the appendix in pregnant women [10 ]
[11 ].
In some cases chronic or even acute appendicitis do not present clinically but are
suspected when looking at the vermiform appendix during elective cesarean delivery.
However, visual diagnosis and histopathological analysis might not match.
We conducted a retrospective data analysis from January 2013 to January 2023 on the
performance of appendectomy during pregnancy beyond 24 0/7 weeks of gestation. The
primary aim of this study was to assess surgical access and pregnancy outcome. Secondary
outcomes were clinical symptoms and diagnostics as well as histopathological analysis
([Fig. 1 ]).
Fig. 1
Flowchart describing the study population.
Methods and Material
Study design
This is a single-center retrospective data analysis conducted at a tertiary perinatal
center in the metropolitan region of Berlin, Germany. Selection of study population
is shown in [Fig. 1 ]. The study was approved by the local Ethics Committee (Eth-23/23, June 2nd, 2023)
(Clinical Trial Registration: drks.de, DRKS number: DRKS00032003). Due to the retrospective
nature of the study, written patient consent was not necessary. This study was performed
in accordance with the ethical standards of the institutional and/or national research
committee and with the 1964 Helsinki declaration and its later amendments or comparable
ethical standards. The analysis period was January 2013 to January 2023. A digital
search of the hospital record archive for obstetrical cases encoding for German operation
and procedure code numbers 5–470 (appendectomy), 5–470.0 (open appendectomy), 5–470.1
(laparoscopic appendectomy), 5–470.10
(laparoscopic appendectomy via ligature), 5–470.11 (laparoscopic appendectomy via
stapler), 5–470.1x (other laparoscopic appendectomy), 5–470.2 (changing from laparoscopic
appendectomy to open appendectomy), 5–470.x (other appendectomy) was conducted.
Baseline variables
Baseline characteristics were obtained and recorded anonymously in a data base. Baseline
characteristics included maternal age, gestational age, past obstetric history, existence
of symptoms of appendicitis (maternal fever, lower right abdominal pain, upper abdominal
pain), elevated inflammation parameters including white blood cell count > 10.5/nl
and C-reactive protein > 5 mg/l according to hospital laboratory standards, sonographic
reference of appendicitis, performance of computer tomography, performance of magnetic
resonance imaging, preoperative application of antibiotics and application of antenatal
corticosteroid therapy.
Obstetrical management as well as maternal and fetal outcome
Outcome of interest were spontaneous vaginal delivery, operative vaginal delivery,
cesarean delivery, 5 minutes APGAR, umbilical cord arterial pH and maternal or fetal
admission to Intensive Care Unit (ICU) or Neonatal Intensive Care Unit (NICU).
Surgical outcome
The surgical technique as well as intra- and postoperative complications were recorded.
Histopathological analysis
Appendices underwent routine clinical examination consisting of storage at 4 °C prior
to fixation, fixation in 4% buffered formalin, measurement, trimmed weight, sectioning,
and examination of the cut surface. Sections underwent routine processing, embedding,
sectioning at 2 µm and staining with hematoxylin and eosin strain. Histologic examination
was performed by authorized pathologists.
Statistical analysis
Descriptive statistical analysis was performed, calculating means and standard deviation
for continuous variables and actual values or percentages for categorical variables.
Analyses were conducted in SPSS Version 24.
Results
The clinic recorded 31057 deliveries between January 2013 and January 2023, of which
20 deliveries (0.06%) were complicated by appendectomy during pregnancy with gestational
age beyond 24 0/7 weeks of pregnancy.
Baseline variables
Baseline variables are shown in [Table 2 ]. Mean patient age at the time of surgery was 32.1 years (± 6.25 years).
Table 2
Baseline variables and obstetrical outcome.
Appendectomy in pregnancy > 24 0/7 weeks of gestation
n = 20
Results are shown in absolute numbers and percentages respectively mean and standard
deviation when applicable.
d = days; ICU = intensive care unit; min = minute; n = number; NICU = neonatal intensive
care unit; Perc. = percentile
Maternal characteristics
Nullipara (n)
12 (60.0%)
Smoker (n)
1 (5.0%)
BMI (kg/m2 )
25.8 (± 7.4)
In-hospital stay (d)
7.4 (± 3.4)
Gestational week at time of appendectomy
37 (± 3.8)
Gestational week at time of birth
38 (± 3.3)
Mode of delivery
Vaginal
1 (5.0%)
Vaginal operative
0
Cesarean delivery
19 (95.0%)
Neonatal outcome
Weight (Perc.)
50.7 (± 27.2)
APGAR < 7 5 min (n)
1 (5.0%)
Arterial pH umbilical cord < 7.15 (n)
0
Preterm delivery
6 (30.0%)
Admission NICU
5 (25.0%)
Maternal outcome
Admission ICU
0
Clinical symptoms and diagnostic methods
13/20 patients (65.0%) presented with clinical symptoms. Mentioned symptoms are shown
in [Table 3 ]. In 10/20 cases (50.0%) a conciliar presentation to the surgical attending had occurred
prior to surgery. Performance of imaging diagnostics is shown in [Table 3 ]. An ultrasound of the vermiform appendix was performed in 6/20 patients (30.0%).
In two cases the sonography was positive and substantiated suspicion of appendicitis
which was confirmed in histopathologic work-up. In 66.7% of the cases the performed
ultrasound was inconclusive.
Table 3
Overview of clinical and paraclinical symptoms of appendicitis in pregnant women.
Appendectomy in pregnancy > 24 0/7 weeks of gestation
n = 20
Results are presented in absolute numbers and percentages respectively mean and standard
deviation when applicable.
h = hour; n = number
Symptoms
Fever
5 (25.0%)
Right abdominal pain
11 (55.0%)
Upper abdominal pain
4 (20.0%)
Defensive tension
6 (30.0%)
Nausea
5 (25.0%)
Vomiting
5 (25.0%)
Diarrhea
1 (5.0%)
Time interval of symptom onset to surgery in h
51.0 (± 39.3)
Laboratory findings
Leukocytes > 15
11 (55.0%)
C-reactive protein > 5
12 (60.0%)
Imaging
Performance of ultrasound
6 (30.0%)
Performance of computer tomography
0
Performance of magnetic resonance imaging
1 (5.0%)
One patient underwent an MRI due to an unclear clinical presentation that included
diffuse abdominal pain, elevated paraclinical inflammation parameters and incohesive
ultrasound. The MRI revealed a tubular structure with a retrocecal wall that was up
to 8 mm in diameter and basal surrounding adipose tissue, which corresponded to the
picture of phlegmonous appendicitis ([Fig. 2 ]).
Fig. 2
T2 weighted MR image of the mid abdominal axial plane displaying the fetus in the
middle of the image and the inflamed appendix (arrow).
Maternal and fetal outcome
The average week of pregnancy at the time of appendectomy was 37 weeks of gestation
(± 3.8 weeks of gestation). The average week of pregnancy at the time of birth was
38 weeks of gestation (± 3.3 weeks of gestation).
Details of obstetrical management as well as maternal and fetal outcome can be found
in [Table 2 ].
There were 6/20 cases (30.0%) of preterm delivery before 37 0/7 weeks of gestation.
In four cases the premature delivery took place before 34 0/7 weeks of gestation.
Of these women, only two received corticosteroids prior to delivery. Instead of the
standard two injections, each patient received a single intramuscular injection of
12 mg of betamethasone. These two preterm deliveries occurred in 33 0/7 weeks of gestation
and 30 4/7 weeks of gestation. Both patients required urgent therapy because they
presented in a significantly reduced general condition with an acute abdomen. In both
cases a cesarean delivery combined with open appendectomy was performed within two
hours after application of the first dose of betamethasone. The other two preterm
deliveries occurred in 33 4/7 weeks of gestation and 31 3/7 weeks of gestation. In
both cases, patients were in a significantly reduced general condition and presented
with an acute abdomen. Both patients required immediate
surgical care.
Only one patient delivered spontaneously in 41 6/7 weeks of gestation after appendectomy
had been performed at 32 weeks of gestation. In 7/20 cases (35.0%) the appendectomy
was performed due to an incidental visual finding of an altered vermiform appendix
in an asymptomatic patient during a planned cesarean delivery. Out of the 13/20 cases
(65.0%) where appendectomy occurred because the patient was symptomatic, 12/20 cases
(60.0%) had a simultaneous cesarean delivery due to fear of fetal impairment.
During the observation period all 20 appendectomies were performed as open appendectomies.
A perforated appendicitis was found in three cases (15.0%). There were neither intraoperative
complications such as injuries or increased bleeding nor postoperative complications
such as wound infections or events of thrombosis or embolisms. No repeat laparotomies
were performed within 30 days after surgery.
Histopathological analysis
Histopathology examination was performed in all cases. The histopathological analysis
of the 20 appendices revealed information as follows. [Table 4 ] gives an overview.
Table 4
Overview of histopathological findings.
Appendectomy in pregnancy > 24 0/7 weeks of gestation
n = 20
Results are shown in absolute numbers and percentages
n = number; WPF = without pathological findings
Histopathology examination
Acute appendicitis
11 (55.0%)
Chronic appendicitis
4 (20.0%)
Tumor
0
Other
1 (5.0%)
WPF
5 (25.0%)
Three appendectomy specimens showed catarrhal stage of appendicitis being described
as catarrhal appendicitis with cicatricial obliteration and fatty degeneration in
the apex.
In four cases pathological analysis showed appendicitis with ulcerated mucosa, streaked
lympho-follicular architecture, transmural granulocytes and focal wall necrosis corresponding
to an ulcero-phlegmonous appendicitis ([Fig. 3 ]
a, b ).
Fig. 3
a Histological specimen of appendix vermiformis, H.E. stain, 20× magnification: Purulent
exudate in the lumen, ulceration of the mucous membrane, phlegmonous inflammatory
infiltrates in all wall layers. b Histological specimen of appendix vermiformis, H.E. stain, 100× magnification: granulocytic
inflammatory infiltrate.
In one case in addition to diagnosing phlegmonous appendicitis, serosal decidual tissue
parts were noted compatible with endometriosis.
Gangrenous appendicitis was diagnosed in four cases showing appendix with a dense
transmural infiltrate of neutrophilic granulocytes with a completely necrotic wall
of the appendix.
Pathological work-up showed chronic inflammation in four cases described as chronic
recurrent cicatricial appendicitis with luminal obliteration, adipose tissue degeneration
and localized minimal fibrous serositis.
In five cases histopathological examinations showed no significant inflammation or
other abnormalities.
Discussion
Principal findings
Pregnancy rarely necessitates the need for appendectomies, according to this retrospective
analysis. Only open appendectomies were done on this small patient group. According
to our research, if an open appendectomy is required during pregnancy, it can be safely
done. From our data we were able to show low risk for adverse maternal as well as
fetal outcome and intraoperative and postoperative surgical complications for pregnancies
complicated by appendectomy. At the same time, cesarean deliveries increased in this
small patient cohort. In our cohort all of the symptomatic patients had histopathological
evidence of appendicitis.
Comparison with other studies
During pregnancy, appendicitis occurs more often during the second than during the
first and third trimester of pregnancy. It is therefore associated with increased
fetal morbidity [2 ]. However, in this patient collective appendicitis occurred during the third trimester
in all cases. Partially this can be explained by the study protocol which required
patients to have reached 24 0/7 weeks of gestations to be included in this study.
Fetal death rate has been described as 1.8% in women with appendicitis during pregnancy
[12 ]. Appendicitis complicated by peritonitis increases the fetal death rate of up to
10.9% [6 ]. In our study cohort no fetal death was noted.
If surgical intervention becomes necessary during pregnancy, appendectomy has been
described to be related to surgery-induced labor [6 ]. The rate of surgery-induced labor is around 4.6% which is 1.3 times higher than
in other non-obstetric related surgical interventions [6 ]. Only one case was recorded in which an appendectomy took place without parallel
delivery, which is consistent with the data mentioned above.
Appendix perforation rate was low and comparable to other studies [13 ]. However, this has to be seen in contrast to the high rate of surgical removal of
unaffected appendices. 7/20 patients (35.0%) did not show any symptoms of appendicitis.
In all of these cases appendectomy was performed during cesarean delivery due to visual
impression. In 5/20 cases (25.0%) histological analysis revealed no significant inflammation
of the vermiform appendix. Negative appendectomy rate is higher in pregnant women
than in non-pregnant women [14 ]. It has been described as 23–36% before [13 ]
[14 ]. It is associated with risk of fetal loss [14 ]. This is comparable to the data of this study. So far, there is no universally accepted
guideline on whether or not to look for the vermiform appendix during cesarean delivery.
A Swedish registry study of 1991 indicated that in 64% of the cases of appendectomy
during pregnancy an acute appendicitis was proven histopathologically [12 ]. This is comparable to the data of this study.
In one case histological work-up showed a phlegmonous appendicitis as well as serosal
decidual tissue parts compatible with endometriosis. Deep infiltrating endometriosis
is the most severe form and can affect the intestines in up to 25% of cases [15 ]. Only very rarely does endometriosis manifest itself in the vermiform appendix [16 ].
Clinical and research implications
Irrespective of gestational age, pain in the lower right quadrant of the abdomen is
the most common sign of appendicitis in pregnant women which could also be shown in
this study [5 ].
When assessing pregnant women experiencing pain in the lower right abdomen, we recommend
using an accurate and safe imaging method in addition to clinical and laboratory testing
[7 ].
The usage of imaging methods lowers the negative appendectomy rate in young women
[17 ]. Sensitivity and specificity of ultrasound in diagnosing appendicitis is estimated
to be 77% and 86% [18 ]. Sensitivity and specificity can be increased to 100% and 86% by additional usage
of computer tomography [18 ]. However, risks of ionizing radiation associated with this imaging method limit
the usability in pregnant women [7 ]
[19 ]. Risks associated with fetal exposure to ionizing radiation depend on the gestational
age as well as the dose of radiation [20 ].
Fetuses are more susceptible to the dose-dependent teratogenic effects of ionizing
radiation like malformations, mental retardation or growth restrictions [20 ]. No profound data exist on the risk of carcinogenesis after in utero exposure to
ionizing radiation [19 ]. There seems to be a 1.5-fold increase in childhood leukemia dose-dependent after
in utero radiation exposure [19 ]
[21 ].
Radiation exposure can be avoided by the usage of magnetic resonance imaging compared
to computer tomography [22 ]
[23 ]. MRI performance can improve specificity and sensitivity of diagnosing appendicitis
in pregnancy up to 100.0% and 98.3%, respectively, for patients with inconclusive
ultrasound diagnostics [24 ].
To choose the optimal imaging technique, close collaboration with the supervising
radiologist should be sought after [25 ].
In this patient collective in all cases open appendectomy was performed when a pathology
of the vermiform appendix was suspected.
There are two ways of surgical access to perform appendectomy: conventional appendectomy
via lower midline transverse abdominal incision and laparoscopic appendectomy [3 ]
[26 ]. In their systematic review Adamani et al. recommend laparoscopic approach until
the 20th week of gestation or when the fundus uteri is below the level of the umbilicus
[27 ]. In cases of suspected appendicitis in pregnant women beyond 20 weeks of gestation
or in pregnant women with the fundus uteri being located above the level of the umbilicus
surgical access should depend on the expertise and preference of the surgeon [27 ]. Due to the later pregnancy dates of the appendectomies performed on this patient
group, the
technical challenges of performing laparoscopic surgery were considered significant
by the performing surgeons. After ruling out all differential diagnosis at any stage
of pregnancy, appendectomy should be performed when appendicitis is suspected [26 ]. If the appendix is not perforated, no simultaneous cesarean delivery is indicated
[26 ]. There is currently a lack of clarity regarding the effects of laparoscopic surgery
versus open appendectomy on preterm delivery and fetal loss [3 ]
[28 ]
[29 ]. An overview of recent systematic reviews on surgical access for appendectomy during
pregnancy is provided in [Table 5 ].
Table 5
Overview of recent systematic reviews on the topic of surgical access for appendectomy
during pregnancy.
Characteristics
Systematic review
Chakraborty 2019 [28 ]
Lee 2019 [3 ]
Frountzas 2019 [29 ]
CI = confidence interval; LA = laparoscopic appendectomy; NM = not mentioned; OA =
open appendectomy; OR = odds ratio; p = p-value
Study aim
Safety of laparoscopic surgery in pregnancy
Safety of laparoscopic appendectomy versus open appendectomy for suspected appendicitis
during pregnancy
Compare the surgical and obstetrical outcomes between laparoscopic and open appendectomy
during pregnancy
Databases that were searched
Medline and Embase
PubMed, Embase and Cochrane Library
Medline, SCOPUS, Clinicaltrials.gov, CENTRAL and Google Scholar
Search time range
2000–2017
NM
1996–2016
Number of studies included
16 retrospective non-randomized studies, 1 prospective observational study
19 comparative retrospective reviews of patients’ medical records, 3 comparative prospective
cohort studies
20 retrospective non-randomized studies, 1 prospective observational study
Number of women included
LA group: 1886 patients
OA group: 4261 patients
LA: 905 patients
OA: 3789 patients
LA: 1963 patients
OA: 4313 patients
Gestational week at appendectomy
LA 37.1–39.3 weeks
OA 36.7–39 weeks
NM
NM
Fetal loss
LA: pooled OR: 1.84 (95% CI: 1.31–2.58, p < 0.001)
LA: OR 1.16 (95% CI: 0.68–1.99; p = 0.581)
LA: OR: 2.11 (95% CI: 1.44–3.09, p = 0.0001)
Preterm delivery
LA: pooled OR: 0.39 (95% CI 0.27–0.55, p < 0.001)
LA: OR 0.76 (95% CI: 0.51–1.15)
LA: OR: 0.72 (95% CI 0.40–1.29, p = 0.27)
Wound infection
Wound infection (OR 0.40, 95% CI: 0.21–0.76)
Wound infection (OR 0.47, 95% CI 0.15–1.48, p = 0.20)
The sole use of antibiotics in treating appendicitis has not been analyzed methodically
in pregnant women so far [1 ]. In this study in five cases antibiotic treatment was initiated before surgery.
However, no patient received antibiotic therapy exclusively. Surgery was performed
in all cases. Further studies are needed to evaluate conservative treatment for appendicitis
in pregnancy.
Strengths
The findings of this study can be used to design prospective studies in the field
of imaging diagnostics as well as treatment of pregnant women with suspected appendicitis
or tumors of the vermiform appendix.
In addition, the study might suggest that all surgeries unrelated to pregnancy be
registered in a registry in order to monitor the frequency, results, and complications
among perinatal facilities.
Limitations
The study’s primary constraint is the small number of cases, which, however, can be
classified as large for a single perinatal center. For this reason, further statistical
analyses had to be omitted. Şahin et al. analyzed 11513 deliveries during 2015–2020
complicated by appendectomy during pregnancy. In their cohort they found 12 cases
[30 ]. This number of cases is comparable to our data. An acute appendicitis rate of 6.3
and 9.9 per 10000 person-years, respectively, was determined for the antepartum and
postpartum periods by Zingone et al. also supporting our case number [31 ].
In this small patient collective only open appendectomies were performed followed
by cesarean deliveries in almost all cases. In contrast to the procedures presented
in this case series, this study is intended to serve as a suggestion to reconsider
laparoscopic appendectomy even in more advanced weeks of pregnancy and to optimize
surgical skills accordingly. A careful assessment of the necessity of a simultaneous
cesarean delivery should be made. Due to the retrospective character of the study
findings of this study are limited.
Conclusion
This retrospective study showed that appendectomies rarely need to be performed during
pregnancy. In the event of appendicitis being suspected during pregnancy, we advise
pursuing additional diagnostic tests, such as ultrasound and MRI if needed, in addition
to a serological work-up and consulting with general surgery and neonatology. In this
small patient collective only open appendectomies were performed. Our data indicate
that it is safe to perform an open appendectomy during pregnancy if necessary. In
this small patient group, there was an increase in simultaneous cesarean deliveries.
