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Outcomes of Laparoscopic versus Open Appendectomy in Children-A Meta-Analysis of Randomize

Controlled Trials

Kimmie Xander T. Chua

Antonio Carlos N. Joven

Department of Surgery
Cardinal Santos Medical Center

January 2018

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Abstract
Objective: The objective of the study is to compare outcomes of laparoscopic vs open appendectomy
in children
Methods: A meta-analysis of randomize controlled trials comparing laparoscopic appendectomy (LA)
and open appendectomy (OA) was done to evaluate outcomes of each procedure in terms of
operative time (OT), hospital stay (LOS), wound infection and return to activity. (RTA)
Result: Seven studies including 1006 children (37.77% n=380 laparoscopic; 62.23% n=626 open)
were included. Heterogeneity was seen in the wound infection and return to activity group with I2 of 0%
for both outcomes. Wound infection was significantly reduced in the laparoscopic group compared to
the open technique (2.87 vs 4. 37%; odds ratio [OR]= 0.46 95% confidence interval [CI], 0.22-0.96; p-
value 0.04) as was return to activity favoring laparoscopic technique (WMD (WMD), -0.25; 95% CI,
-0.3 to -0.17; p-value <0.00001). Although results of operative time (WMD 14.55, 95% CI 6.53 to 22.56
p-value 0.0004) and days of hospitalization (WMD, -0.69, 95% CI -1.17 to -0.21, p-value 0.005)
showed significant difference with opeartive time showing less in open technique while hospitalization
favoring laparoscopic technique, the data did not show heterogeneity (I2 = 91% and 76%, respectively).
Conclusion: Results of this meta-analysis suggests that wound infection rate and return to activity
favored the laparoscopic group. Lack of high quality randomize controlled trial comparing laparoscopic
and open technique in children are significant limitation of this analysis.

Key words: laparoscopic appendectomy (LA); open appendectomy (OA); children; acute appendicitis;
randomize controlled trial (RCT); operative time; wound infection; hospital stay; return to activity

Abbreviations: LA= laparoscopic appendectomy; OA= open appendectomy; LOS= length of stay/length
of hospital stay,/hospital stay; RTA= return to activity; OT= opertative time; OR=odds ratio; CI=
confidence interval; WMD= weighted mean difference; RCT= randomize controlled trial

Introduction, Background, and Literature Search

Appendectomy is the most common cause of surgical abdomen in the emergency room in all age
group1. The first successful appendectomy (open) in humans was first performed by Claudius Amyand in
1735. For over a century, the open approach has been deemed the conventional, if not the only, surgical
approach to remove the appendix until in 1981, Kurt Semm performed the first laparoscopic
appendectomy, which started the evolution in surgical treatment of appendicitis3,4 However, despite the
availability, improvement and advancement in minimally invasive procedures, such as laparoscopy, there
is still debate as to the gold standard for treating acute appendicitis (laparoscopy vs open).

Laparoscopic surgery has been available for a long time and has been gaining popularity as the
preferred approach, if not the gold standard, in some abdominal surgeries such as cholecystectomy.
Studies have been conducted demonstrating benefits of laparoscopic approach in terms of shorter
hospital stay , less post operative site pain and faster overall recovery compared to open approach2.
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However, in the approach to acute appendicitis for pediatric age group, there is still no consensus among
pediatric surgeons as to which of the two techniques—laparoscopic appendectomy and open
appendectomy—has the more beneficial and favorable outcome . Laparoscopic appendectomy has not
been established as the gold standard because of its longer operative time, increase risk of intra-
abdominal abscess, and higher hospitalization cost2. The aim of this study is to evaluate and compare
outcomes of laparoscopic vs open appendectomy in children in terms of operative time, hospital stay,
wound infection and days of return to activity.

Meta-analysis is a statistical tool that is being used for evaluation and assessments of existing
literature in both a qualitative and quantitative by comparing and integrating the result of different studies.
Altho one meta-analyses15 of RCT has been done comparing laparoscopic appendectomy (LA) and open
appendectomy (OA) for adult population with results greatly showing benefits of the laparoscopic
technique in terms of overall post operative complications, length of stay and return to activity, the study
did not show any significant difference in the subgroup of children/pediatric population of the outcome
measured.

Materials and Methods

Study Selection: A literature search was performed using search engines Google and Safari and
databases such as PubMed and Cochrane using keywords such as “laparoscopic versus open
appendectomy”, “laparoscopic appendectomy in children” and “randomized control trial of laparoscopic
versus open appendectomy in children”. Studies were also lifted from the references of the meta-
analyses entitled Laparoscopic versus open appendectotmy in adults and children: a meta-analysis of
randomized controlled trials by Liping Dai and Jian Shuai published 2017, and Laparoscopic versus open
appaendectomy in children -a Meta analysis by Aziz et al. published 2006 for which this meta-analysis
was patterned after with focus on the outcomes and efficacy of LA vs OA in a particular age group—
pediatrics.

Data Extraction: Two reviewers (K.C. and A. J) independently extracted the following data from each
study: first author, year of publication, study population characteristic (number of participants, age,
male:female ratio, number of perforated cases for each group); and study design.

Inclusion Criteria: The studies included in this meta-analysis are: (a) randomize controlled trials; (b)
reporting on children/pediatric as study population; (c) comparing laparoscopic (LA) vs open (OA
appendectomy; (d) with result of atleast one of the outcome measure.

Exclusion Criteria: Studies were excluded based on the following criteria: (a) non randomized studies;
(b) study which do not report outcome of interest for the two techniques; (c) repeated reports of more than
one version of the same study by same author. Only most recent study was included; (d) studies with no
reportable standard deviation of the mean or range of data
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Outcomes of Interest and Definition: La and OA techniques were compared in terms of: (1) duration of
operative time defined as time taken from skin incision until last application of skin stitch (in minutes), (2)
length of hospital stay defined as day of admission of the patient until discharge from hospital (in days);
(3) return to activity measured in days it took for the patient to tolerate ambulation and return to routine
movement with minimal or negligible pain/discomfort; (4) rate of wound infection defined as infection in
the site of the surgical incision that may manifest up to 30 days from time of surgery/incision.

Statistical Analysis: RevMan 5.3 software will be used in the analysis of the studies. Summary
measures will be odds ratio for wound infection and WMD for length of hospital stay, operative time and
return to normal activity. Test of homogeneity will be determined using I2 with value less than 50% to be
considered as homogenous. Test for overall effect should have a p value of less than 0.05 for a
statistically significant result.
Odds ratio of less than one favors the treamtment group (LA), and the point estimate of the odds
ratio is considered statistically significant at the p-value of <0.05 if the 95% confidence interval does not
include the number 1. For continuous type of data, a fixed and random effect models were used. In fixed
effect models, treatment effect is assumed to be homogenous, while those showing heterogeneity (I2
≥50% of a p value of ≥0.50), a random effect models is best used. In outcomes such as operative time
and length of hospital stay, a random effect model was used as the effect showed heterogenous result
probably due to the fact that some studies included mentioned that some of the l surgeries were done by
residents and some by main attendings, and the intervention (laparoscopic) requires a certain level of skill
and learning curve (for the operative time) while heterogeneity in the length of hospital stay between
studies may be attributed to the fact that most studies reported having a higher rate of perforated
appendix in the OA group while one study included Hay8 did not mention number of perforated
appendicitis for each group and may also be due to the fact that children have different processing of pain
and different ability to tolerate post operative pain thus contributing to longer hospital stay.
In the forest plot alongside the meta-analysis figures below, the squares indicate point estimate of
treatment effect (WMD), with size of the square representing the weight attributed to each study and 95%
confidence interval (CI) indicated in the horizontal bars. The diamond shape in the forest plot represents
summary from pooled studies with 95% CI. A point estimate is considered statistically significant at the p
value of <0.05 level at 95% confidence interval.

Result
Initial search yielded 50 potential relevant studies. Twenty-six (26) studies did not satisfy the
eligibility criteria and were then excluded which leaves 23 studies to be reviewed in detailed by 2
investigators. Fifteen of the 23 studies were noted to be non randomized which rendered these studies
ineligible. Eight (8) studies published between 1996-2017 matched the inclusion criteria for systemic
review comparing LA versus OA in pediatric population with outcomes measuring atleast one of the
following: operative time, length of hospital stay, wound infection and return to activity. One study
(Khirallah20) was excluded because results did not show standard deviation of the mean for the outcomes
of interest. Figure 1 demonstrates the diagram of the study selection. Study characteristics of each study
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included are shown on Table 1. Age and number of participants of each study with perforated appendix
(except study done by Hay 1998 which did not mention number of perforated appendicitis done on each
group) were found to be homogenous (I2 = 29%, I2 = 0% respectively) as shown in Figures 3 and Figures
4. The seven RCT studies included in the meta-analysis had a total of 1006 pediatric patients of whom
380 underwent laparoscopy and 626 underwent open appendectomy. Four of the 7 studies mentioned the
male to female ratio for each intervention (Table 1). Risk of bias in individual studies will be assessed by
RevMan 5.3 (Table 2 and Figure 2)

Figure 1: study selection

potentially relevant studies

(n= 50)

studies excluded
(n=26)
not satisfying eligibility criteria
studies reviewed in detail
(n=23)
studies excluded
(n=15)
non-randomized study design

studies included in systematic review

(n=8)
studies excluded
(n=1)
incomplete data: no SD and range

studies included in systematic review

(n=7)
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Table 1: Study characteristics

Study Study Participants Age (year) Sex (M:F) Perforated

(first design appendicitis
Author,
year) LA (n=) OA (n=) LA OA LA (n=) OA (n=) LA (n=) OA (n=)

Roshan RCT 63 63 9.7 ± 2.1 9.8 ± 2.3 50:13 56:7 10 14

Ali17
2017

Lintula19 RCT 43 44 11 ±3 12 ±3 27:16 27:17 9 4

2004

Oka18 RCT 141 376 11 ±4.3 10.6 79:62 227:149 43 114

2003 ±3.5

Little11 RCT 44 44 10.5±3.5 12.02 ± - - 10 11

2002 3.75

Lavonius RCT 23 20 11.9 ± 12.5 ± 2 - - 3 5

9 2001 1.75

Hay8 RCT 34 48 8 ±4 8 ±4 - - - -
1998

Lejus7 RCT 32 31 10.9 ±1.6 11.3 18:14 16:15 3 4

1996 ±1.7

Table 2: Risk of Bias

Study first Randomizat allocation Blinding f Blinding of Incomplete selective other bias
author ion concealmen participants outcome outcome reporting
t (selection and assessment data (reporting
of bias) personnel (attribution bias)
bias)

Roshan yes low risk low risk unclear low risk low risk unclear
Ali17 2017

Lintula19 yes low risk low risk unclear low risk low risk unclear
2004

Oka18 2003 yes high risk low risk low risk low risk low risk unclear

Little11 2002 yes low risk low risk low risk low risk low risk unclear

Lavonius9 yes low risk low risk unclear low risk low risk unclear
2001

Hay8 1998 yes low risk high risk low risk low risk low risk unclear

Lejus7 1996 yes unclear low risk unclear low risk low risk unclear
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Figure 2: Risk of bias

Figure 3: Homogeneity test for Age of participants in study

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Figure 4: Homogeneity test for number of participants with perforated appendix

Operative time
All seven trials reported the duration of operation time (in minutes) for both LA and OA. A random
effects model was used because there was heterogeneity between the two groups (I2 = 91%, p
<0.00001). Open appendectomy was found to have a significantly less operative time than laparoscopic
appendectomy (WMD= 14.55, 95% CI: 6.53 to 22.56, p 0.0004) as shown in Figure 5.

Figure 5: Meta-analysis and forest plot of operative time

Length of hospital stay

Six of the 7 RCT included in the meta-analysis reported on the length of hospital stay (LOS)
measured in days for both LA and OA. Results showed that patient who underwent LA stayed in the
hospital for less number of days than patients who underwent OA (WMD= -0.69, 95% CI: -1.17 to -0.21, p
0.005) favoring LA group as shown in Figure 6. However, a random effect model was again used due to
the fact that effects showed heterogeneity between the two groups (I2 = 76% p =0.0008). (Figure 6)
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Figure 6: Meta-analysis and forest plot of length of hospital stay

Wound infection
Six trials reported on the incidence or event of wound infection for each group. LA group had a
3% infection rate with 10 patient out of 325 developing wound infection post operatively while the OA
group had a rate of 4.52% with 26 patients out of 575 who developed wound infection. LA group was
found to have significantly reduced incidence of wound infection (OR = 0.46; 95% CI 0.22-0.96, p 0.04).
This result favors the LA group as shown in FIgure 7. A fixed effect model was utilized because the effects
were homogenous between the two groups as is also shown in the Forest plot in Figure 7 (I2 = 0% p
=0.50)

Figure 7: Meta-analysis and forest plot of wound infection

Return to normal activity

Three trials showed return to activity in the outcome measures, however one study (Hay 1998)
was removed from the meta-analysis due to its data off-setting the heterogeneity of the effect because the
study reported an average of 7 days ranging from 6-10 days for the LA group and average of 12 days for
OA group with range of 10-15 days. The study was also excluded from the meta-analysis for this outcome
because it failed to mention male to female ratio and number of participants for each group with
perforated appendicitis as an operative findings as these findings might help explain the longer return to
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activity. Also the mean age of the participants of the Hay et al trial are far younger (8 ±4 for both OA and
LA group) than those of the the Lejus et al (10.9 ±1.6 LA group, 11.3 ±1.7 OA group) and Little et al (10.3
±3.5 LA group, 12.02±3.75 OA group) trial.

Figure 8: Meta-analysis with Forest plot of return to activity (including Hay 1998)

Figure 9: Meta-analysis with Forest plot of return to activity (without Hay 1998)

As shown in Figure 9, elimination of the Hay 1998 trial rendered the meta-analysis homogenous
(I2 = 0% p =0.45). The result showed that return to activity of patients under LA are significantly earlier
than those in the OA group (WMD= -0.25, 95% CI: -0.43 to -0.17, p <0.00001).

Discussion

Appendectomy is one of the most common emergencies in the pediatric age group. For over a
century, the open approach has been deemed the conventional, if not the only, surgical approach to
remove the appendix. However in 1981, Kurt Semm performed the first laparoscopic appendectomy,
which started the evolution in surgical treatment of appendicitis3,4 However despite the advancement in
technology, laparoscopic approach in the removal off the appendix has not yet become the gold standard.
Benefits of LA over OA remain inconclusive. This lack of consensus is probably due to the small study
size, sensitive population, lack of high quality randomize controlled trials, heterogeneity in the patient
characteritstis (age—toddler, child, teen, obese patients), pediatric surgeons or MIS surgeons with skills
to perform laparoscopy in children, and severity of appendicitis.

The results of this meta-analysis showed that laparoscopic appendectomy in children offered
some benefits in terms of decrease incidence of wound infection and earlier return to normal activity.
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Incidence of wound infection in the LA group is 3% (10 in 325) while that of the OA group, 4.52%
developed wound infection (26 in 575). The higher rate of wound infection in the open technique may be
explained by the fact that the infected appendix is extricated through the incision/ wound incision thereby
risking contamination of the wound site.
Meta-analysis of the return to normal activity showed significant difference favoring LA group in
that children who underwent laparoscopic appendectomy were found to be able to return to their routine/
daily activity earlier than those who underwent open appendectomy. This may be in account of the fact
that laparosopic technique eliminates the process of muscle splitting that is part of the step in the open
technique and thus rendering the OA to be more painful post operatively which translates to early
mobilization. Earlier return to activity may also be related to the fact that LA group have significantly less
incidence of wound infection than OA group and thus early mobilization. However, as seen in Figure 9,
sample size for both trials for LA and OA group are rather small ( n= 76, n= 65 respectivly) hence a more
high quality RCT comparing laparoscopic and open appendectomy in the pediatric age group is
recommended. It is also an observation in this study that return to activity has no standard definition and
that measurement of such outcome may be different for each trial or that measurement may be difficult
hence it is a recommendation of this study to standardize definition and process of measurement for
return of activity.
Although data included in the meta-analysis of operative time and length of hospital stay are not
homogenous, the overall effect showed a significant difference with operative time favoring the OA group
showing less duration ( FIgure 5) while patients in the LA group have reduced hospital stay compared to
the OA group (Figure 6). Heterogeneity in the operative time can be attributed to surgeon skills with
residents or less experienced surgeons taking longer operative time performing laparoscopic
appendectomy than more skilled surgeons. Heterogeneity in the LOS may be attributed to the study
population characteristic. It is not surprising that laparoscopic technique will take longer than the open
approach in that laparoscopic approach takes a certain level of skills and learning curve and the
instrumentation required during laparoscopic surgery. This study showed that LA took longer than LA by
14.55 minutes (WMD= 14.55, 95% CI: 6.53 to 22.56, p 0.0004).
Possibly the clearest benefit that LA offers over OA is earlier return to activity, quicker healing of
the smaller incision which translates to less hospital stay and in effect possibly less hospital cost which is
another aspect that is worth delving into. Meta-analysis of hospital stay showed LA group has a 0.69 less
days compared to OA group (Figure 6). However, this aspect warrants further research in the future due
to the heterogeneity of the data as previously mentioned.
In reference to the meta-analysis conducted by Aziz et al14 one limitation stated was the
recommendation to use studies that are of randomized design for which this study was based on.
However, upon extensive search, not much RCT was conducted comparing laparoscopic vs open
appendectomy in children since the 2004. There had only been 2 RCT that came up in my literature
search—Ali Roshan et al and Khirallah et al— however the latter was excluded in the meta-analysis due
to its failure to mention the SD for the mean of the outcomes of interest.
Conclusion
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This meta-analysis showed that although LA group has longer operative time compared to OA
group, this was offset by the significantly less incidence of wound infection, earlier return to activity and
thus less hospital stay of the patients in the LA group compare to the OA group. However, as mentioned
in the meta-analysis of Aziz et al, this study stresses the importance of a more high qulaity randomized
trials comparing LA to OA in the pediatric age group matched in not only in age, sex, body habitus,
severity of appendicitis and surgeon skills.
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