J Gastrointest Surg (2012) 16:1929–1939

DOI 10.1007/s11605-012-1972-9

ORIGINAL ARTICLE

Meta-analysis of the Results of Randomized Controlled

Trials that Compared Laparoscopic and Open Surgery
for Acute Appendicitis
Hiroshi Ohtani & Yutaka Tamamori & Yuichi Arimoto &
Yukio Nishiguchi & Kiyoshi Maeda & Kosei Hirakawa

Received: 13 May 2012 / Accepted: 15 July 2012 / Published online: 14 August 2012
# 2012 The Society for Surgery of the Alimentary Tract

Abstract
Purpose We conducted a meta-analysis to evaluate and compare the outcomes of laparoscopic and open surgery for the
treatment of patients with acute appendicitis.
Methods We searched MEDLINE, EMBASE, Science Citation Index, and the Cochrane Controlled Trial Register for
relevant papers published between January 1990 and February 2012. We analyzed 22 outcomes of laparoscopic and open
surgery for acute appendicitis.
Results We identified 39 papers reporting results from randomized controlled trials that compared laparoscopic
surgery with open surgery for acute appendicitis. Our meta-analysis included 5,896 patients with acute appendicitis;
2,847 had undergone laparoscopic surgery, and 3,049 had undergone open surgery. Compared with open surgery,
laparoscopic surgery was associated with longer operative time (by 13.12 min). However, compared with open
surgery, laparoscopic surgery for acute appendicitis was associated with earlier resumption of liquid and solid intake;
shorter duration of postoperative hospital stay; a reduction in dose numbers of parenteral and oral analgesics; earlier
return to normal activity, work, and normal life; decreased occurrence of wound infection; a better cosmesis; and
similar hospital charges.
Conclusions Laparoscopic surgery may now be the standard treatment for acute appendicitis.

Keywords Meta-analysis . Laparoscopic versus open Introduction

appendectomy . Acute appendicitis
Acute appendicitis is the most common inflammatory
disease of the abdominal cavity. Appendectomy remains
the mainstay of treatment for acute appendicitis. Open
appendectomy (OA) using a small incision in the right
lower quadrant has been the standard treatment for acute
H. Ohtani (*) : Y. Tamamori : Y. Arimoto
Department of Surgery, Osaka City Sumiyoshi Hospital,
appendicitis for more than a century, since it was first
1-2-16, Higashi-Kagaya, Suminoe-ku, described by McBurney1 in 1894. OA has been associ-
Osaka 559-0012, Japan ated with low morbidity and mortality rates, minimal
e-mail: m5051923@msic.med.osaka-cu.ac.jp pain, short hospital stay, and smooth recovery.2,3 Lapa-
Y. Nishiguchi
roscopic appendectomy (LA) for suspected appendicitis
Department of Surgery, Osaka City General Hospital, has been performed with increasing frequency world-
Osaka, Japan wide, since it was first described by Semm4 in 1983.
Some studies suggest that LA results in a shortened
K. Maeda : K. Hirakawa
Department of Surgical Oncology, Osaka City University Graduate
hospital stay, less postoperative pain, and earlier return
School of Medicine, to work.5–7 Others were unable to demonstrate a clear
Osaka, Japan advantage of LA.8,9 Laparoscopic cholecystectomy has
1930 J Gastrointest Surg (2012) 16:1929–1939

advantages of reduced pain and length of hospitalization,
better cosmesis, a more rapid return to work, and reduced
costs.10,11 While laparoscopic cholecystectomy has rapidly
become the standard treatment for acute cholecystitis, the
benefits of LA for acute appendicitis remain unproven.
Numerous randomized clinical trials (RCTs) comparing
LA to OA have been reported.3,5–9,12–44 To examine the
efficacy of LA for treatment of acute appendicitis, we
conducted a meta-analysis of the data from these RCTs
and compared the clinical outcomes of LA with those
of OA.
Materials and Methods
search was limited to articles that described the design of
the RCT. Appropriate data from such study series were
used for this meta-analysis. This meta-analysis was per-
formed in accordance with the PRISMA (Preferred
Reporting Items for Systemic Reviews and Meta-Analyses)
statement45 (Fig. 1).
Inclusion Criteria
For inclusion in our meta-analysis, studies had to (1) be
described in English; (2) be randomized controlled trials; (3)
compare laparoscopic and open surgery for suspected ap-
pendicitis; and (4) report on at least one of the outcome
measures mentioned below.

Literature Search Exclusion Criteria

To identify papers relevant to our study, we searched the
major medical databases MEDLINE, EMBASE, Science
Citation Index, and the Cochrane Controlled Trials Reg-
ister for studies published between January 1990 and
February 2012. The following search terms were used:
“laparoscopic appendectomy,” “acute appendicitis,”
“laparoscopic surgery,” and “appendectomy.” Our literature
Studies were excluded from this analysis if (1) they
were not published in English; (2) they were unpub-
lished RCTs, nonrandomized prospective trials, or retro-
spective comparative trials; (3) they were abstracts of
RCTs from national or international meetings; or (4) the
outcomes of interest were not reported for the two
surgical techniques.

Fig. 1 Flow diagram of this

identification

meta-analysis in accordance # of records identified through # of Additional records identified

with PRISMA Statement database searching (n=1768) through other sources (n=8)

# of records after duplicates removed (n=1772)

screening

# of records screened # of records excluded

(n=1772) nonrandomized trials (n=1354)
Reviews (n=174)
Meta-analysis (n=19)
letters to the editor or abstracts (n=129)
Eligibility

# of full-text articles # of full-text articles excluded,

assessed for eligibility with reasons
(n=96) Studies which do not compare LA with OA
(n=57)

# of studies included in
qualitative synthesis
included

(n=39)

# of studies included in
quantitative synthesis
(meta-analysis) (n=39)
J Gastrointest Surg (2012) 16:1929–1939 1931

Data Extraction principle of intention-to-treat, all patients converted from the

laparoscopic group to the open group remained in the laparo-
Three researchers (H.O., Y.T., and Y.A.) extracted data from scopic group for analysis. The following details were consid-
each article by using a structured sheet and entered the data into ered: perioperative results, perioperative analgesics, time to
a database. Because the analysis was performed on the recovery, morbidity, mortality, cosmetics of the wound scar,

Table 1 Characteristics of each randomized control trial

No. Reference, year Number of Conversion Study size (n) Randomization Double Withdrawals Jadad’s
reference ratio (%) blinding and dropouts score
LA OA

1 Attwood et al., 1992 12 6.6 (2/30) 30 32 2 0 1 3

2 Kum et al., 1993 13 U 52 57 1 0 1 2
3 Tate et al., 1993 14 20 (14/70) 70 70 2 0 1 3
4 Frazee et al., 1994 6 5.3 (2/38) 38 37 1 0 1 2
5 Martin et al., 1995 15 16 (13/81) 81 88 2 0 1 3
6 Ortega et al., 1995 16 6.6 (11/167) 167 86 2 0 1 3
7 Hansen et al., 1996 17 8.1 (7/86) 86 72 2 0 1 3
8 Cox et al., 1996 5 15 (5/33) 33 31 2 0 1 3
9 Mutter et al., 1996 18 12 (6/50) 50 50 1 0 1 2
10 Williams et al., 1996 9 10.5 (2/19) 19 18 1 0 1 2
11 Lejus et al., 1996 8 0 32 31 1 1 1 3
12 Hart et al., 1996 19 9 (4/44) 44 37 2 0 1 3
13 Macarulla et al., 1996 20 8.3 (9/106) 106 104 2 0 1 3
14 Minné et al., 1997 21 7.4 (2/27) 27 23 2 0 1 3
15 Kazemier et al., 1997 22 12 (12/97) 97 104 2 0 1 3
16 Reiertsen et al., 1997 23 0 42 42 2 0 1 3
17 Heikkinen et al., 1998 24 5 (1/19) 18 21 2 0 1 3
18 Klingler et al., 1998 25 0 87 82 1 0 1 2
19 Hellberg et al., 1999 26 12 (30/244) 244 256 2 0 1 3
20 Ozmen et al., 1999 27 U 35 35 1 0 1 2
21 Long et al., 2001 28 16 (15/93) 93 105 2 0 1 3
22 Pedersen et al., 2001 29 23 (65/282) 282 301 2 0 1 3
23 Lintula et al., 2001 30 0 30 31 2 0 1 3
24 Helmy et al., 2001 31 18 (9/50) 50 50 1 0 1 2
25 Huang et al., 2001 32 U 23 26 2 0 1 3
26 Al-Mulhim et al., 2002 33 10 (3/30) 30 30 2 0 1 3
27 Milewczyk et al., 2003 34 8.3 (8/96) 96 104 2 0 1 3
28 Bruwer et al., 2003 35 5.6 (1/18) 18 16 2 0 1 3
29 Oka et al., 2004 36 U 141 376 1 0 1 2
30 Ignacio et al., 2004 7 3.8 (1/26) 26 26 2 1 1 4
31 Moberg et al., 2004 37 2.5 (2/81) 81 82 2 1 1 4
32 Katkhouda et al., 2005 38 8 (9/113) 113 134 2 2 1 5
33 Olmi et al., 2005 39 0.6 (1/150) 150 138 2 0 1 3
34 Wei et al., 2009 40 0 112 108 2 0 1 3
35 Tzovaras et al., 2010 3 22.2 (16/72) 72 75 2 2 1 5
36 Kouhia et al., 2010 41 6.38 (3/47) 47 52 2 0 1 3
37 Shirazi et al., 2010 42 U 30 30 1 0 1 2
38 Khalil et al., 2011 43 1.3 (1/72) 72 75 1 0 1 2
39 Clarke et al., 2011 44 U 23 14 1 1 1 3
2,847 3,049
1932 J Gastrointest Surg (2012) 16:1929–1939

Fig. 2 Meta-analysis of the operative time (minutes): the entire period (1990-2012)
perioperative period LA OA Mean Difference Mean Difference
Study or Subgroup Mean SD Total Mean SD Total Weight IV, Random, 95% CI IV, Random, 95% CI
Al-Mulhim et al. 65 16.25 30 50 15 30 2.9% 15.00 [7.09, 22.91]
Attwood et al. 61 27.5 30 51 21.25 32 2.4% 10.00 [-2.29, 22.29]
Bruwer et al. 67.2 27.5 18 53.1 25.2 16 1.8% 14.10 [-3.62, 31.82]
Clarke et al. 90 49.25 23 70 25 14 1.3% 20.00 [-4.01, 44.01]
Cox et al. 58.9 4 33 50.6 3.7 31 3.4% 8.30 [6.41, 10.19]
Frazee et al. 87 26.25 38 65 47.5 37 1.8% 22.00 [4.57, 39.43]
Hart et al. 73.8 23.2 44 45 12.9 37 2.9% 28.80 [20.78, 36.82]
Helmy et al. 49 24.5 50 23 11.5 50 2.9% 26.00 [18.50, 33.50]
Huang et al. 69.1 48.8 23 55.4 28 26 1.4% 13.70 [-8.96, 36.36]
Ignacio et al. 77.4 27.1 26 66.9 21.6 26 2.2% 10.50 [-2.82, 23.82]
Katkhouda et al. 80 11.25 113 60 7.5 134 3.4% 20.00 [17.57, 22.43]
Kazemier et al. 61 24 97 42 18 104 3.1% 19.00 [13.10, 24.90]
Khalil et al. 47.54 12.82 72 31.36 11.43 75 3.3% 16.18 [12.25, 20.11]
Klingler et al. 35 32.5 87 31 23 82 2.8% 4.00 [-4.45, 12.45]
Kouhia et al. 65 27 47 38 18.5 52 2.7% 27.00 [17.79, 36.21]
Kum et al. 43.4 17.1 52 40.1 15.5 57 3.1% 3.30 [-2.85, 9.45]
Lejus et al. 54 17 32 39 18 31 2.8% 15.00 [6.35, 23.65]
Lintula et al. 34 18 30 30 11 31 2.9% 4.00 [-3.52, 11.52]
Long et al. 110.5 34.6 93 95.8 33 105 2.7% 14.70 [5.25, 24.15]
Macarulla et al. 55.2 26.16 106 44.68 16.63 104 3.1% 10.52 [4.60, 16.44]
Martin et al. 102.2 51.1 81 81.7 40.85 88 2.2% 20.50 [6.48, 34.52]
Milewczyk et al. 47.75 23.875 96 36.99 18.495 104 3.1% 10.76 [4.81, 16.71]
Minné et al. 81.7 40.85 27 66.8 33.4 23 1.5% 14.90 [-5.68, 35.48]
Moberg et al. 55 40.25 81 60 21.25 82 2.6% -5.00 [-14.90, 4.90]
Mutter et al. 45 15.9 50 25 12.6 50 3.1% 20.00 [14.38, 25.62]
Oka et al. 49.9 12.9 141 47.3 19.7 376 3.3% 2.60 [-0.32, 5.52]
Olmi et al. 38 8.75 150 45 22.5 138 3.3% -7.00 [-11.01, -2.99]
Ortega et al. 68 32 167 58 27 86 2.9% 10.00 [2.51, 17.49]
Pedersen et al. 60 8.75 282 40 7.5 301 3.4% 20.00 [18.67, 21.33]
Reiertsen et al. 51 2.75 42 25 2 42 3.4% 26.00 [24.97, 27.03]
Shirazi et al. 51.8 7.8 30 39.6 5.6 30 3.3% 12.20 [8.76, 15.64]
Tate et al. 70.3 21.9 70 46.5 25.9 70 2.9% 23.80 [15.85, 31.75]
Tzovaras et al. 60 25 72 45 17.5 75 3.0% 15.00 [8.00, 22.00]
Wei et al. 30 15.2 112 28.7 16.3 108 3.2% 1.30 [-2.87, 5.47]
Williams et al. 93 12 19 87 8 18 3.0% 6.00 [-0.54, 12.54]
Özmen et al 38 11.25 35 28 11.25 35 3.2% 10.00 [4.73, 15.27]

Total (95% CI) 2499 2700 100.0% 13.12 [9.72, 16.51]

Heterogeneity: Tau² = 88.06; Chi² = 803.20, df = 35 (P < 0.00001); I² = 96%
-50 -25 0 25 50
Test for overall effect: Z = 7.57 (P < 0.00001) Favours LA Favours OA

operative time (minutes): the earlier period (1990-2000)

LA OA Mean Difference Mean Difference
Study or Subgroup Mean SD Total Mean SD Total Weight IV, Random, 95% CI IV, Random, 95% CI
Attwood et al. 61 27.5 30 51 21.25 32 5.1% 10.00 [-2.29, 22.29]
Cox et al. 58.9 4 33 50.6 3.7 31 6.9% 8.30 [6.41, 10.19]
Frazee et al. 87 26.25 38 65 47.5 37 4.1% 22.00 [4.57, 39.43]
Hart et al. 73.8 23.2 44 45 12.9 37 6.0% 28.80 [20.78, 36.82]
Kazemier et al. 61 24 97 42 18 104 6.4% 19.00 [13.10, 24.90]
Klingler et al. 35 32.5 87 31 23 82 6.0% 4.00 [-4.45, 12.45]
Kum et al. 43.4 17.1 52 40.1 15.5 57 6.4% 3.30 [-2.85, 9.45]
Lejus et al. 54 17 32 39 18 31 5.9% 15.00 [6.35, 23.65]
Macarulla et al. 55.2 26.16 106 44.68 16.63 104 6.4% 10.52 [4.60, 16.44]
Martin et al. 102.2 51.1 81 81.7 40.85 88 4.8% 20.50 [6.48, 34.52]
Minné et al. 81.7 40.85 27 66.8 33.4 23 3.5% 14.90 [-5.68, 35.48]
Mutter et al. 45 15.9 50 25 12.6 50 6.5% 20.00 [14.38, 25.62]
Ortega et al. 68 32 167 58 27 86 6.1% 10.00 [2.51, 17.49]
Reiertsen et al. 51 2.75 42 25 2 42 6.9% 26.00 [24.97, 27.03]
Tate et al. 70.3 21.9 70 46.5 25.9 70 6.1% 23.80 [15.85, 31.75]
Williams et al. 93 12 19 87 8 18 6.3% 6.00 [-0.54, 12.54]
Özmen et al 38 11.25 35 28 11.25 35 6.5% 10.00 [4.73, 15.27]

Total (95% CI) 1010 927 100.0% 14.64 [9.17, 20.11]

Heterogeneity: Tau² = 112.02; Chi² = 377.53, df = 16 (P < 0.00001); I² = 96%
-50 -25 0 25 50
Test for overall effect: Z = 5.25 (P < 0.00001) Favours LA Favours OA

and cost of surgery. For the perioperative results, we collected
data on operative time, time to liquid intake, time to solid
intake, and duration of postoperative hospital stay. Operative
time was examined over the entire period (1990–2012), and in
earlier (1990–2000) and later periods (2001–2012). Both the
number of doses and duration of use were analyzed for paren-
teral and oral analgesics. Data on time to normal activity, work,
and normal life were collected. For morbidity, postoperative
overall complications, wound infection, intraabdominal ab-
scess, ileus, pulmonary infection, shoulder pain, and venous
thromboembolism (VTE) were examined. Operative and hos-
pital costs were examined to estimate cost of surgery. We used
the cost ratio (LA/OA) to adjust for inflation and to account for
differences among countries.
J Gastrointest Surg (2012) 16:1929–1939 1933

Fig. 2 (continued) operative time (minutes): the later period (2001-2012)

LA OA Mean Difference Mean Difference
Study or Subgroup Mean SD Total Mean SD Total Weight IV, Random, 95% CI IV, Random, 95% CI
Al-Mulhim et al. 65 16.25 30 50 15 30 5.5% 15.00 [7.09, 22.91]
Bruwer et al. 67.2 27.5 18 53.1 25.2 16 3.4% 14.10 [-3.62, 31.82]
Clarke et al. 90 49.25 23 70 25 14 2.4% 20.00 [-4.01, 44.01]
Helmy et al. 49 24.5 50 23 11.5 50 5.6% 26.00 [18.50, 33.50]
Huang et al. 69.1 48.8 23 55.4 28 26 2.6% 13.70 [-8.96, 36.36]
Ignacio et al. 77.4 27.1 26 66.9 21.6 26 4.2% 10.50 [-2.82, 23.82]
Katkhouda et al. 80 11.25 113 60 7.5 134 6.4% 20.00 [17.57, 22.43]
Khalil et al. 47.54 12.82 72 31.36 11.43 75 6.2% 16.18 [12.25, 20.11]
Kouhia et al. 65 27 47 38 18.5 52 5.2% 27.00 [17.79, 36.21]
Lintula et al. 34 18 30 30 11 31 5.6% 4.00 [-3.52, 11.52]
Long et al. 110.5 34.6 93 95.8 33 105 5.1% 14.70 [5.25, 24.15]
Milewczyk et al. 47.75 23.875 96 36.99 18.495 104 5.9% 10.76 [4.81, 16.71]
Moberg et al. 55 40.25 81 60 21.25 82 5.0% -5.00 [-14.90, 4.90]
Oka et al. 49.9 12.9 141 47.3 19.7 376 6.3% 2.60 [-0.32, 5.52]
Olmi et al. 38 8.75 150 45 22.5 138 6.2% -7.00 [-11.01, -2.99]
Pedersen et al. 60 8.75 282 40 7.5 301 6.5% 20.00 [18.67, 21.33]
Shirazi et al. 51.8 7.8 30 39.6 5.6 30 6.3% 12.20 [8.76, 15.64]
Tzovaras et al. 60 25 72 45 17.5 75 5.7% 15.00 [8.00, 22.00]
Wei et al. 30 15.2 112 28.7 16.3 108 6.2% 1.30 [-2.87, 5.47]

Total (95% CI) 1489 1773 100.0% 11.76 [7.10, 16.43]

Heterogeneity: Tau² = 87.21; Chi² = 341.48, df = 18 (P < 0.00001); I² = 95%
-50 -25 0 25 50
Test for overall effect: Z = 4.94 (P < 0.00001) Favours LA Favours OA

time to liquid intake (hours)

LA OA Mean Difference Mean Difference
Study or Subgroup Mean SD Total Mean SD Total Weight IV, Random, 95% CI IV, Random, 95% CI
Al-Mulhim et al. 8 1.5 30 18 3 30 15.5% -10.00 [-11.20, -8.80]
Clarke et al. 24 18 23 24 18 14 3.6% 0.00 [-11.96, 11.96]
Huang et al. 21 14.6 23 32.7 17 26 5.6% -11.70 [-20.55, -2.85]
Katkhouda et al. 23.5 5.5 113 24 5.5 134 15.3% -0.50 [-1.88, 0.88]
Kazemier et al. 31.2 4.8 97 33.6 7.2 104 15.0% -2.40 [-4.08, -0.72]
Kum et al. 21.6 4.8 52 28.8 9.6 57 13.5% -7.20 [-10.01, -4.39]
Shirazi et al. 6.6 1.3 30 10.4 2.3 30 15.7% -3.80 [-4.75, -2.85]
Tate et al. 33.6 2.4 70 36 2.4 70 15.8% -2.40 [-3.20, -1.60]

Total (95% CI) 438 465 100.0% -4.58 [-7.18, -1.99]

Heterogeneity: Tau² = 10.90; Chi² = 148.10, df = 7 (P < 0.00001); I² = 95%
-20 -10 0 10 20
Test for overall effect: Z = 3.47 (P = 0.0005) Favours LA Favours OA

time to solid intake (hours)

LA OA Mean Difference Mean Difference
Study or Subgroup Mean SD Total Mean SD Total Weight IV, Random, 95% CI IV, Random, 95% CI
Al-Mulhim et al. 24 1.5 30 24 3 30 11.0% 0.00 [-1.20, 1.20]
Katkhouda et al. 27 7 113 38 6.75 134 10.8% -11.00 [-12.72, -9.28]
Kazemier et al. 50.4 9.6 97 52.8 7.2 104 10.4% -2.40 [-4.76, -0.04]
Kum et al. 43.2 4.8 52 43.2 12 57 9.8% 0.00 [-3.38, 3.38]
Long et al. 1.6 2.5 93 2.3 2.3 105 11.1% -0.70 [-1.37, -0.03]
Macarulla et al. 38.4 33.84 106 55.44 38.64 104 5.0% -17.04 [-26.87, -7.21]
Shirazi et al. 8.8 1.9 30 15.4 1.8 30 11.0% -6.60 [-7.54, -5.66]
Tate et al. 52.8 3 70 55.2 3.6 70 11.0% -2.40 [-3.50, -1.30]
Wei et al. 20.2 12.4 112 36.5 10 108 10.1% -16.30 [-19.27, -13.33]
Williams et al. 23 4 19 39 6 18 9.8% -16.00 [-19.30, -12.70]

Total (95% CI) 722 760 100.0% -6.57 [-9.55, -3.60]

Heterogeneity: Tau² = 20.63; Chi² = 355.43, df = 9 (P < 0.00001); I² = 97%
-20 -10 0 10 20
Test for overall effect: Z = 4.33 (P < 0.0001) Favours LA Favours OA

Assessment of Study Quality
The quality of the randomized controlled trials was assessed
using Jadad’s scoring system.46 Two reviewers (H.O., Y.T.)
assessed all studies that met the inclusion criteria (Table 1).
Statistical Analysis
Weighted mean differences and odds ratios were used for the
analysis of continuous and dichotomous variables,
respectively. Random-effects models were used due to hetero-
geneity between the studies,47 and the degree of heterogeneity
was assessed using the χ2 test. The confidence interval (CI)
was established at 95 %, and p values of less than 0.05 were
considered to indicate statistical significance. For the compu-
tation of the CI, estimates of the mean and standard deviation
were obtained using formulas proposed by Hozo et al.48
Statistical analyses were performed using Review Manager
(RevMan) software, version 5.1.6, provided by the Cochrane
Collaboration, Copenhagen, Denmark.
1934 J Gastrointest Surg (2012) 16:1929–1939

Fig. 2 (continued) postoperative hospital stay (days)

LA OA Mean Difference Mean Difference
Study or Subgroup Mean SD Total Mean SD Total Weight IV, Random, 95% CI IV, Random, 95% CI
Al-Mulhim et al. 2 0.75 30 2 1.25 30 3.3% 0.00 [-0.52, 0.52]
Attwood et al. 2.5 1.25 30 3.8 1.9 30 2.8% -1.30 [-2.11, -0.49]
Bruwer et al. 3 1.6 18 3.7 1.1 16 2.6% -0.70 [-1.61, 0.21]
Clarke et al. 2 1.75 23 4 2.25 14 1.9% -2.00 [-3.38, -0.62]
Cox et al. 2.9 0.3 33 3.9 0.4 31 3.7% -1.00 [-1.17, -0.83]
Hart et al. 3.23 5.55 44 3.03 1.24 37 1.5% 0.20 [-1.49, 1.89]
Helmy et al. 5.3 2.65 50 4.9 2.45 50 2.5% 0.40 [-0.60, 1.40]
Huang et al. 2.8 1.4 23 3.6 1.8 23 2.6% -0.80 [-1.73, 0.13]
Ignacio et al. 0.896 0.783 26 1.217 0.6875 26 3.4% -0.32 [-0.72, 0.08]
Katkhouda et al. 2 0.5 113 3 0.5 134 3.7% -1.00 [-1.13, -0.87]
Kazemier et al. 3.7 2.5 97 4.4 3.9 104 2.6% -0.70 [-1.60, 0.20]
Khalil et al. 1.52 0.76 72 1.7 1.06 75 3.6% -0.18 [-0.48, 0.12]
Klingler et al. 3 5.25 87 4 5.75 82 1.6% -1.00 [-2.66, 0.66]
Kouhia et al. 1.5 1.5 47 1.5 2 52 3.0% 0.00 [-0.69, 0.69]
Kum et al. 3.2 0.6 52 4.2 1 57 3.5% -1.00 [-1.31, -0.69]
Lintula et al. 1.9 0.7 30 2.6 0.9 31 3.4% -0.70 [-1.10, -0.30]
Long et al. 2.6 3.3 93 3.4 3.3 105 2.6% -0.80 [-1.72, 0.12]
Macarulla et al. 3.42 1.86 106 4.75 2.65 104 3.1% -1.33 [-1.95, -0.71]
Martin et al. 2.2 1.1 81 4.3 2.15 88 3.3% -2.10 [-2.61, -1.59]
Milewczyk et al. 4.71 2.355 96 5.03 2.565 104 3.0% -0.32 [-1.00, 0.36]
Minné et al. 1.1 0.55 27 1.2 0.6 23 3.5% -0.10 [-0.42, 0.22]
Moberg et al. 2 2.5 81 2 5.5 82 2.0% 0.00 [-1.31, 1.31]
Mutter et al. 5.3 3 50 4.9 1.7 50 2.6% 0.40 [-0.56, 1.36]
Oka et al. 4.3 3.2 141 5.2 3.5 376 3.1% -0.90 [-1.54, -0.26]
Olmi et al. 3.4 1.5 150 5.5 2 138 3.4% -2.10 [-2.51, -1.69]
Pedersen et al. 2 0.75 282 2 0.5 301 3.7% 0.00 [-0.10, 0.10]
Reiertsen et al. 3.5 0.4 42 3.2 0.425 42 3.7% 0.30 [0.12, 0.48]
Shirazi et al. 1.5 0.06 30 4.1 0.8 30 3.6% -2.60 [-2.89, -2.31]
Tate et al. 3.5 0.2 70 3.6 0.2 70 3.7% -0.10 [-0.17, -0.03]
Tzovaras et al. 2 2.75 72 2 2 75 2.8% 0.00 [-0.78, 0.78]
Wei et al. 4.1 1.5 112 7.2 1.7 108 3.4% -3.10 [-3.52, -2.68]
Williams et al. 2.375 0.5 19 2.75 0.417 18 3.6% -0.38 [-0.67, -0.08]
Özmen et al 1.6 0.5 35 3.7 1.5 35 3.3% -2.10 [-2.62, -1.58]

Total (95% CI) 2262 2541 100.0% -0.79 [-1.06, -0.52]

Heterogeneity: Tau² = 0.52; Chi² = 916.64, df = 32 (P < 0.00001); I² = 97%
-4 -2 0 2 4
Test for overall effect: Z = 5.68 (P < 0.00001) Favours LA Favours OA

dose number of parenteral analgesics

LA OA Mean Difference Mean Difference
Study or Subgroup Mean SD Total Mean SD Total Weight IV, Random, 95% CI IV, Random, 95% CI
Al-Mulhim et al. 1 0.25 30 3 0.75 30 9.8% -2.00 [-2.28, -1.72]
Bruwer et al. 3.6 3.8 18 3.9 1.7 16 2.8% -0.30 [-2.24, 1.64]
Clarke et al. 3 4.75 23 3 6.25 14 0.9% 0.00 [-3.81, 3.81]
Cox et al. 2.4 0.4 33 3.4 0.5 31 10.0% -1.00 [-1.22, -0.78]
Hart et al. 4.05 6.39 44 5.58 3.36 37 2.4% -1.53 [-3.71, 0.65]
Huang et al. 0.5 0.8 23 1.3 1.2 26 8.4% -0.80 [-1.37, -0.23]
Katkhouda et al. 2 1 113 2 1.25 134 9.8% 0.00 [-0.28, 0.28]
Kum et al. 1 0.3 52 1.3 0.3 57 10.3% -0.30 [-0.41, -0.19]
Macarulla et al. 2.8 1.2 106 4.1 0.7 104 9.9% -1.30 [-1.57, -1.03]
Milewczyk et al. 2 1 96 4 2 104 9.1% -2.00 [-2.43, -1.57]
Reiertsen et al. 3.2 3.5 42 4.3 14.5 42 0.7% -1.10 [-5.61, 3.41]
Shirazi et al. 1.5 0.4 30 2.8 1.2 30 9.0% -1.30 [-1.75, -0.85]
Tate et al. 1.7 0.25 70 1.9 0.275 70 10.3% -0.20 [-0.29, -0.11]
Tzovaras et al. 0.5 1.5 50 0.5 3.5 75 6.6% 0.00 [-0.89, 0.89]

Total (95% CI) 730 770 100.0% -0.90 [-1.28, -0.51]

Heterogeneity: Tau² = 0.37; Chi² = 292.46, df = 13 (P < 0.00001); I² = 96%
-10 -5 0 5 10
Test for overall effect: Z = 4.60 (P < 0.00001) Favours LA Favours OA

dose number of oral analgesics

LA OA Mean Difference Mean Difference
Study or Subgroup Mean SD Total Mean SD Total Weight IV, Random, 95% CI IV, Random, 95% CI
Al-Mulhim et al. 1 0.75 30 4 1.5 30 13.2% -3.00 [-3.60, -2.40]
Clarke et al. 0 1.5 23 0 4 14 9.0% 0.00 [-2.18, 2.18]
Katkhouda et al. 2 1 113 2 1.5 134 13.5% 0.00 [-0.31, 0.31]
Kum et al. 2.8 1 52 5 1.2 57 13.4% -2.20 [-2.61, -1.79]
Macarulla et al. 3.91 1.31 106 6.9 1.21 104 13.5% -2.99 [-3.33, -2.65]
Reiertsen et al. 2.6 3.25 42 2.5 3.75 42 11.0% 0.10 [-1.40, 1.60]
Shirazi et al. 2.7 0.7 30 5.9 1.3 30 13.3% -3.20 [-3.73, -2.67]
Tzovaras et al. 1.5 1.5 56 1.5 2 75 13.2% 0.00 [-0.60, 0.60]

Total (95% CI) 452 486 100.0% -1.51 [-2.63, -0.38]

Heterogeneity: Tau² = 2.41; Chi² = 261.06, df = 7 (P < 0.00001); I² = 97%
-4 -2 0 2 4
Test for overall effect: Z = 2.62 (P = 0.009) Favours LA Favours OA
J Gastrointest Surg (2012) 16:1929–1939 1935

Fig. 2 (continued) return to normal activity (days)

LA OA Mean Difference Mean Difference
Study or Subgroup Mean SD Total Mean SD Total Weight IV, Random, 95% CI IV, Random, 95% CI
Bruwer et al. 14.5 6.2 18 18.4 6.4 16 5.8% -3.90 [-8.15, 0.35]
Cox et al. 10.4 0.9 27 19.8 2.4 24 9.1% -9.40 [-10.42, -8.38]
Frazee et al. 14 7 38 25 12.5 37 5.4% -11.00 [-15.60, -6.40]
Hart et al. 9 8.4 44 16.2 9.9 37 6.0% -7.20 [-11.24, -3.16]
Heikkinen et al. 7 7.25 18 14 10.5 21 4.5% -7.00 [-12.60, -1.40]
Hellberg et al. 15 12.75 244 22 20.25 256 7.2% -7.00 [-9.95, -4.05]
Klingler et al. 13 8.75 87 20 6 82 8.0% -7.00 [-9.25, -4.75]
Martin et al. 12.2 6.1 81 12.8 6.4 88 8.4% -0.60 [-2.48, 1.28]
Olmi et al. 7 2.5 150 15 8.25 138 8.8% -8.00 [-9.43, -6.57]
Pedersen et al. 7 2.5 282 10 2.25 301 9.4% -3.00 [-3.39, -2.61]
Reiertsen et al. 15 1.7 42 19.7 2.1 42 9.2% -4.70 [-5.52, -3.88]
Tzovaras et al. 6 3.25 72 7 3 75 9.1% -1.00 [-2.01, 0.01]
Wei et al. 9.1 4.2 112 13.7 5.8 108 8.9% -4.60 [-5.94, -3.26]

Total (95% CI) 1215 1225 100.0% -5.47 [-7.12, -3.82]

Heterogeneity: Tau² = 7.48; Chi² = 236.52, df = 12 (P < 0.00001); I² = 95%
-20 -10 0 10 20
Test for overall effect: Z = 6.51 (P < 0.00001) Favours LA Favours OA

return to work (days)

LA OA Mean Difference Mean Difference
Study or Subgroup Mean SD Total Mean SD Total Weight IV, Random, 95% CI IV, Random, 95% CI
Bruwer et al. 13.6 5.9 18 15.8 7.6 16 7.3% -2.20 [-6.81, 2.41]
Heikkinen et al. 10 3.5 18 19 6.5 21 9.3% -9.00 [-12.22, -5.78]
Hellberg et al. 15 10.5 244 21 10.25 256 11.3% -6.00 [-7.82, -4.18]
Ignacio et al. 11 4.9 26 9.5 3.9 26 10.5% 1.50 [-0.91, 3.91]
Klingler et al. 14 10 87 15 7.75 82 10.1% -1.00 [-3.69, 1.69]
Long et al. 14.6 11.1 93 14.6 9.8 105 9.7% 0.00 [-2.93, 2.93]
Martin et al. 23.3 11.65 81 23.6 11.8 88 8.8% -0.30 [-3.84, 3.24]
Minné et al. 14 7 27 14 7 23 8.3% 0.00 [-3.89, 3.89]
Pedersen et al. 10 3.25 282 16 5 301 12.5% -6.00 [-6.68, -5.32]
Wei et al. 21.2 3.5 112 27.7 4.9 108 12.1% -6.50 [-7.63, -5.37]

Total (95% CI) 988 1026 100.0% -3.18 [-5.09, -1.27]

Heterogeneity: Tau² = 7.50; Chi² = 83.55, df = 9 (P < 0.00001); I² = 89%
-20 -10 0 10 20
Test for overall effect: Z = 3.27 (P = 0.001) Favours LA Favours OA

wound infection
LA OA Odds Ratio Odds Ratio
Study or Subgroup Events Total Events Total Weight M-H, Random, 95% CI M-H, Random, 95% CI
Al-Mulhim et al. 0 30 3 30 1.0% 0.13 [0.01, 2.61]
Attwood et al. 0 30 1 32 0.9% 0.34 [0.01, 8.78]
Bruwer et al. 0 18 2 16 0.9% 0.16 [0.01, 3.53]
Clarke et al. 2 23 1 14 1.4% 1.24 [0.10, 15.05]
Cox et al. 0 33 2 31 1.0% 0.18 [0.01, 3.82]
Hansen et al. 2 86 8 72 3.4% 0.19 [0.04, 0.93]
Hart et al. 3 44 3 37 3.1% 0.83 [0.16, 4.38]
Heikkinen et al. 0 19 1 21 0.9% 0.35 [0.01, 9.13]
Huang et al. 4 23 7 26 4.3% 0.57 [0.14, 2.28]
Katkhouda et al. 7 113 9 134 7.3% 0.92 [0.33, 2.55]
Kazemier et al. 0 97 6 104 1.1% 0.08 [0.00, 1.40]
Khalil et al. 3 72 8 75 4.4% 0.36 [0.09, 1.43]
Klingler et al. 5 87 6 82 5.4% 0.77 [0.23, 2.63]
Kouhia et al. 1 47 6 52 1.9% 0.17 [0.02, 1.44]
Kum et al. 0 52 5 57 1.1% 0.09 [0.00, 1.69]
Lejus et al. 0 32 0 31 Not estimable
Lintula et al. 0 30 3 31 1.0% 0.13 [0.01, 2.70]
Long et al. 17 93 17 105 11.9% 1.16 [0.55, 2.42]
Macarulla et al. 1 106 5 104 1.9% 0.19 [0.02, 1.64]
Martin et al. 3 81 6 88 4.2% 0.53 [0.13, 2.17]
Milewczyk et al. 3 96 4 104 3.7% 0.81 [0.18, 3.70]
Moberg et al. 1 81 1 82 1.2% 1.01 [0.06, 16.47]
Oka et al. 3 141 15 376 5.2% 0.52 [0.15, 1.84]
Olmi et al. 0 150 11 138 1.1% 0.04 [0.00, 0.63]
Ortega et al. 4 167 11 86 5.8% 0.17 [0.05, 0.54]
Pedersen et al. 8 282 21 301 10.0% 0.39 [0.17, 0.89]
Shirazi et al. 0 30 8 30 1.1% 0.04 [0.00, 0.79]
Tate et al. 7 70 10 70 7.2% 0.67 [0.24, 1.86]
Tzovaras et al. 2 72 4 75 2.9% 0.51 [0.09, 2.86]
Wei et al. 0 112 14 108 1.1% 0.03 [0.00, 0.49]
Williams et al. 1 19 1 18 1.1% 0.94 [0.05, 16.33]
Özmen et al 2 35 3 35 2.5% 0.65 [0.10, 4.13]

Total (95% CI) 2371 2565 100.0% 0.46 [0.34, 0.62]

Total events 79 202
Heterogeneity: Tau² = 0.06; Chi² = 32.89, df = 30 (P = 0.33); I² = 9%
0.002 0.1 1 10 500
Test for overall effect: Z = 5.00 (P < 0.00001) Favours LA Favours OA
1936 J Gastrointest Surg (2012) 16:1929–1939

Results hospital charges

Mean Difference
Study or Subgroup IV, Random, 95% CI
We identified 39 papers reporting results of randomized
Heikkinen et al.
controlled trials that compared LA with OA for suspected Long et al.
appendicitis.3,5–9,12–44 The characteristics of each random- Macarulla et al.
Martin et al.
ized controlled trial are presented in Table 1. Our meta- Minné et al.
Wei et al.
analysis included 5,896 patients with suspected appendici- Williams et al.
tis; of these, 2,847 had undergone LA, and 3,049 had
Heterogeneity: Tau² = 0.05; Chi² = 144.88,
undergone OA.
df = 6 (P < 0.00001); I² = 96%
Test for overall effect: Z = 0.79 (P = 0.43) -1 -0.5 0 0.5 1
Favours LA Favours OA
Perioperative Results (n=457) (n=467)

The perioperative results are shown in Fig. 2. The operative

time for LA was significantly longer, by 13.12 min, than that
for OA over the entire period (weighted mean difference0
13.12; 95 % CI09.72–16.61; p<0.00001). It was signifi- operative charges
Mean Difference
cantly longer, by 14.64 and 11.76 min, than that for OA in Study or Subgroup IV, Random, 95% CI
the earlier and later periods, respectively (weighted mean Hansen et al.

difference 014.64 and 11.76; 95 % CI 09.17–20.11 and Heikkinen et al.

7.10–16.43; p<0.00001 and <0.00001, respectively). Two
studies in the later period and no studies in the earlier
period showed that the operating time for LA was
shorter than that for OA. Times to liquid and solid
intake were significantly earlier with LA than with OA
(p00.0005 and p <0.0001, respectively). The duration
of postoperative hospital stay was significantly shorter
with LA, by 0.79 day, than with OA (p<0.00001). The
duration of use of either parenteral or oral analgesics
did not differ significantly. However, the number of
doses of both parenteral and oral analgesics differed
significantly (p < 0.00001 and p 00.009, respectively);
the number of doses of both parenteral and oral analge-
sics was less in the LA group. We found significant
differences in time to normal activity, work, and normal
life between the groups (p<0.00001, p00.001, and p0
0.02, respectively). Regarding postoperative complica-
tions, no significant differences were observed in overall
complications, intraabdominal abscess, pulmonary infection,
shoulder pain, VTE, and postoperative ileus. The incidence of
wound infection for LA was significantly less than that for
OA (odds ratio00.44; 95 % CI00.32–0.60; p<0.00001).
Mortality did not differ significantly between the groups.
Two LA patients died of pulmonary embolus and acute
myocardial infarction, whereas three OA patients died of
respiratory failure, mesenteric thrombosis, and uncertain
cause.
Cost of Surgery
The cost of surgery is shown in Fig. 3. No significant differ-
ence was found in hospital charges between LA and OA. In a
breakdown of hospital charges, the operative charge for LA
was significantly higher (p00.008).
Macarulla et al.
Minné et al.
Williams et al.
Heterogeneity: Tau² = 1.12; Chi² = 1467.45,
df = 4 (P < 0.00001); I² = 100%
Test for overall effect: Z = 2.65 (P = 0.008) -4 -2 0 2 4
Favours LA Favours OA
(n=257) (n=238)
Fig. 3 Meta-analysis of the cost of surgery
Wound Scar
The number of patients who felt the wound scar had dis-
appeared or had no problem with the scar was significantly
higher in LA than in OA (odds ratio031.29; 95 % CI04.85–
201.980; p00.0003).
Heterogeneity
Significant heterogeneity was found among studies with
respect to operative time; time to liquid and solid intake;
duration of postoperative hospital stay; dose number and
duration of parenteral and oral analgesics; time to normal
activity, work, and normal life; overall postoperative com-
plications; incidence of postoperative intraabdominal ab-
scess; and charges for hospitalization and operation.
Discussion
In this meta-analysis, LA for suspected appendicitis was as-
sociated with a significantly longer operative time, by
13.12 min. Potential explanations include the time needed to
create a pneumoperitoneum, insert trocars, and use the instru-
ments during laparoscopic surgery. The mean difference in the
J Gastrointest Surg (2012) 16:1929–1939
operating time during the earlier period was 14.64 min, while
that during the later period was 11.76 min. Two studies in the
later period and no studies in the earlier period showed that the
operating time was shorter for LA than for OA. Therefore,
both surgical skill and instrument technology in laparoscopic
appendectomy have possibly progressed in this decade.
Patients who underwent LA resumed liquid and solid
intake significantly earlier and had significantly shorter hos-
pital stays than did patients who underwent OA. Time to
return to normal activity, work, and normal life were signif-
icantly shorter in LA (p<0.00001, p00.001, p00.02); these
findings suggest that LA leads to faster recovery. In this meta-
analysis, no significant difference in the duration of parenteral
and oral analgesic administration was observed between the
groups; however, the numbers of doses of postoperative par-
enteral (p<0.00001) and oral analgesics (p00.009) were sig-
nificantly lower in LA than in OA. The smaller surgical
wound in LA may reduce the postoperative analgesic require-
ments but not the duration of analgesic administration.
No significant difference was found for overall postoper-
ative complications, intraabdominal abscess, pulmonary in-
fection, shoulder pain, VTE, and postoperative ileus
between the two surgery groups. The incidence of wound
infection for LA was significantly lower than that for OA.
Two LA patients died of pulmonary embolus and acute
myocardial infarction, whereas three OA patients died of
respiratory failure, mesenteric thrombosis, and uncertain
cause. Thus, the causes of mortality are not associated with
surgical technique. These findings suggest that the safety
and feasibility of LA is similar to that of OA.
The cost of laparoscopic appendectomy depends on the
cost of the surgery, the length of hospital stay, complica-
tions, medications, and the loss of productivity resulting
from lost working days. We found that the operative charge
for LA was significantly higher than that for OA. The mean
difference in the operative time between the two groups is
only 13.12 min. Therefore, the reason for the higher opera-
tive charge for LA may be mainly the cost of disposable
instruments, ports, and sutures used in laparoscopic proce-
dure. Hospital charges depend on the surgery, length of stay,
complications, and medication. We found no significant
difference in hospital charges between LA and OA in this
meta-analysis. This finding may indicate that the increased
surgical cost for LA is offset by short hospital stay, low rate
of wound infection, and less number of postoperative anal-
gesic doses. In addition, earlier return to work following LA
may decrease the loss of productivity resulting from lost
working days.
The conversion rate was 0 % to 23 %. Katkhouda38 and
Kouhia41 reported that conversion is usually due to unclear
anatomy or difficult dissection. In the evaluation of cosm-
esis, more LA patients felt that the wound scar had disap-
peared or had no problem with the wound scar.
1937
Significant heterogeneity among studies was observed;
variable parameters included operative time; time to liquid
and solid intake; duration of postoperative hospital stay;
dose number and duration of parenteral and oral analgesics;
time to normal activity, work, and normal life; overall post-
operative complications; incidence of postoperative intra-
abdominal abscess; and charges for hospitalization and
surgery. Heterogeneity in operative time may be due to
variations in the skill of the surgeons, the condition of
appendicitis, and the lesion. Differences in clinical approach
at different institutions may have caused heterogeneity in
time to liquid and solid intake, duration of postoperative
hospital stay, and time to normal activity, work, and normal
life. Heterogeneity in dose number and duration of paren-
teral and oral analgesics may be caused by variations in the
condition of appendicitis and the lesion at surgery, and the
kinds of analgesics. Reasons for heterogeneity in the hospi-
tal and operative charges may include variations in operative
time and varying cost of laparoscopic instruments among
countries. A random-effect model was used due to hetero-
geneity among countries and ages.
Our meta-analysis showed that, as compared with OA,
LA for suspected appendicitis is associated with the follow-
ing: earlier resumption of liquid and solid intake; shorter
duration of postoperative hospital stay; a reduction in dose
numbers of parenteral and oral analgesics; earlier return to
normal activity, work, and normal life; decreased occurrence
of wound infection; better cosmesis. Hospitalization charges
did not differ between the procedures. A disadvantage of LA
is a longer operative time, but the mean difference is only
13.12 min.
Laparoscopic cholecystectomy has rapidly become the
standard treatment for symptomatic gall stone disease, be-
cause its advantages include reduced pain, shortened hospi-
talization, better cosmesis, and a more rapid return to active
life.10 The hospital charge for laparoscopic cholecystectomy
is less than that for open cholecystectomy because the
duration of hospital stay is shorter.11 Therefore, it appears
that LA has become the standard treatment for suspected
acute appendicitis.
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