Abstract
Objective
The aim of this study was to evaluate the differences of laparoscopic appendectomy (LA) versus open appendectomy (OA) in adults and children.
Methods
Randomized controlled trials (RCTs) comparing LA and OA in adults and children between January 1992–March 2016 were included in this study. A meta-analysis was performed to evaluate wound infection, intra-abdominal abscess, postoperative complications, reoperation rate, operation time, postoperative stay, and return to normal activity.
Result
Thirty-three studies including 3642 patients (1810 LA, 1832 OA) were included. Compared with OA, LA in adults was associated with lower incidence of wound infection, fewer postoperative complications, shorter postoperative stay, and earlier return to normal activity, but a longer operation time. There was no difference in levels of intra-abdominal abscess and reoperation between the groups. Subgroup analysis in children did not reveal significant differences between the two techniques in wound infection, postoperative complications, postoperative stay, and return to normal activity.
Conclusion
LA in adults is worth recommending as an effective and safe procedure for acute appendicitis, and further high-quality randomized trials comparing the two techniques in children are needed.
Keywords: Appendectomy, laparoscopic surgery, open surgery, meta-analysis
Introduction
Acute appendicitis is a common cause of acute abdominal pain with a life-time incidence between 7–9%.1 As a direct result, appendectomy is one of the most frequently performed surgical procedures. The open approach to appendectomy was originally described by McBurney.2 It has become the standard treatment of choice for acute appendicitis, remaining mainly unchanged for 100 years due to its favorable efficacy and safety. Since the advent of laparoscopy, appendectomy has increasingly been performed using a minimally invasive approach, following the first report by Semm in 1983.3 Although laparoscopic appendectomy (LA) has gained much popularity among some surgeons, others remain skeptical with regard to replacing the relatively straightforward open appendectomy (OA). Criticism of LA includes increased operative cost, primarily due to the use of disposable laparoscopic instruments,4 increased operation time, and concerns about a higher incidence of intra-abdominal abscesses, particularly after perforated appendicitis.5 Proponents of LA, however, claim that the advantages of the procedure include improved wound healing, reduced postoperative pain and, ultimately, earlier discharge from hospital, all translating to an earlier return to normal activity. Therefore, the use of LA remains controversial, in contrast to the wide acceptance of laparoscopic cholecystectomy since its innovation.
Meta-analysis is a useful statistical tool that can be used to evaluate the existing literature in both quantitative and qualitative ways by comparing and integrating the results of different studies, taking into account variations in characteristics that can influence the overall estimate of the outcome of interest. Previous meta-analyses have demonstrated a reduced incidence of surgical site infection and length of hospital stay following LA in adults.6,7 Some studies, however, have suggested that LA is associated with higher rates of intra-abdominal abscess formation, longer operative times, and higher surgical costs when compared to OA.
LA, however, is currently not universally accepted as the standard of care for the treatment of acute appendicitis in children and differences in the patient population mean that direct extrapolation of adult data to children is invalid.8,9 Although much research has been done to compare results from LA and OA in children, conclusions have been difficult to draw because of small study size, the presence of only a handful of randomized trials, and possible heterogeneity in patient characteristics, surgical practice, and severity of appendicitis between these studies. At present, there is no consensus between pediatric surgeons as to the benefits of LA over OA.
In order to guide future management decisions, we decided to conduct a meta-analysis of randomized controlled trials (RCTs) comparing LA and OA in adult and pediatric patients.
Methods
Selection criteria
A comprehensive literature search of the Cochrane Controlled Trials Register on The Cochrane Library, MEDLINE, EMBASE, and the China Biological Medicine Database (CBMdisc) under the headings of “appendicitis,” “appendectomy,” “laparoscopy,” and “laparoscopic appendectomy” was performed electronically for the period between January 1992–March 2016. The reference lists of pertinent reviews and retrieved articles was checked for additional study identification. In the meta-analysis, the following inclusive selection criteria were set and reviewed by two independent investigators: (a) each trial should be a prospective randomized controlled clinical trial; (b) compare LA and OA techniques; (c) report on at least one of the outcome measures mentioned below. The following exclusive selection criteria were set: (a) non-randomized studies; (b) repeated reports if more than one version of the same study was retrieved, only the most recent one was used; (c) studies in which the standard deviation of the mean for continuous outcomes of interest were not reported. The studies were independently evaluated by the two authors, outcome measures were wound infection, intra-abdominal abscess, postoperative complications, reoperation, operation time, postoperative stay, and return to normal activity. Discrepancies in the evaluation of some studies were resolved through discussion between the reviewers.
Assessment of study quality
Quality of included reports was scored using the Jadad composite scale,10 which assesses descriptions of randomization, blinding, and dropouts (withdrawals) in reports. The quality scale ranges from 0–5 points with a low quality report of score at two or less and a high quality report of score at least three.
Statistical analysis
The analysis was completed using Review Manager software (Rev Man 5.3) from the Cochrane collaboration. Continuous data presented in the same scale were analyzed using weight mean difference (WMD) with 95% confidence intervals (CIs). Due to the rarity of some events, dichotomous data were analyzed using Peto odds ratios (ORs). A randomized effect model was used due to the clinical heterogeneity of the included studies. Heterogeneity was evaluated using the chi-square test. All p values less than 0.05 were considered significant for heterogeneity. A p value less than 0.05 was considered significant for overall effects. Funnel plots were used to investigate any possible publication bias in the meta-analysis.
Results
Description of studies
The initial literature search identified 661 studies, based on the inclusion criteria 621 studies were excluded, giving a selection of 40 studies for more detailed review. Seven of those studies were subsequently excluded (Figure 1), and only 33 RCTs that exclusively evaluated LA and OA and fitted the inclusion and exclusion criteria were selected.11–43 Study characteristics and quality evaluation of each selected study are shown in Table 1, they were homogeneous in clinical and methodological criteria. The RCTs selected included 3642 patients, of whom 1810 were laparoscopic and 1832 were open procedures. There are only 426 children, all of the others are adults.
Figure 1.
Procedure for identification and selection of studies.
Table 1.
Study characteristics and quality evaluation of each selected study
| Study first author | Jadad score | Randomization | Double blind | Lost to follow-up | Sample size | Patients | Conversion rate (%) |
|---|---|---|---|---|---|---|---|
| Martin11 | 2 | 1 | 1 | 0 | 169 | Adults | 16.1 |
| Macarulla12 | 4 | 2 | 2 | 0 | 210 | Adults | 8.3 |
| Minne13 | 4 | 2 | 1 | 1 | 50 | Adults | 7.4 |
| Reiertsen14 | 3 | 2 | 1 | 0 | 84 | Adults | ND |
| Hellberg15 | 5 | 2 | 2 | 1 | 500 | Adults | 12 |
| Shirazi16 | 2 | 1 | 1 | 0 | 60 | Adults | ND |
| Moberg17 | 5 | 2 | 2 | 1 | 163 | Adults | 2.5 |
| Kaplan18 | 4 | 2 | 2 | 0 | 100 | Adults | 0 |
| Wei19 | 3 | 1 | 1 | 1 | 220 | Adults | 0 |
| Ignacio20 | 4 | 2 | 2 | 0 | 52 | Adults | 3.8 |
| Mutter21 | 3 | 1 | 2 | 0 | 100 | Adults | 12 |
| Cox22 | 3 | 1 | 1 | 1 | 64 | Adults | 15 |
| Tzovaras23 | 5 | 2 | 2 | 1 | 147 | Adults | 22 |
| Laine24 | 2 | 1 | 1 | 0 | 50 | Adults | 8 |
| Mulhim25 | 4 | 2 | 1 | 1 | 60 | Adults | 10 |
| Dalen26 | 3 | 2 | 1 | 0 | 63 | Adults | ND |
| Clarke27 | 3 | 1 | 2 | 0 | 37 | Adults | ND |
| Kargar28 | 4 | 2 | 2 | 0 | 100 | Adults | 0 |
| Schietroma29 | 4 | 2 | 2 | 0 | 147 | Adults | 5.4% |
| Khalil30 | 5 | 2 | 2 | 1 | 147 | Adults | 1.39% |
| Gilchrist31 | 2 | 1 | 1 | 0 | 64 | Children Not report | ND |
| Lejus32 | 3 | 1 | 2 | 0 | 63 | Children 8–15 years | 0 |
| Hay33 | 3 | 1 | 1 | 1 | 82 | Children 4–12 years | 0 |
| Lavonius34 | 4 | 2 | 1 | 1 | 43 | Children 7–15 years | 4 |
| Lintula35 | 5 | 2 | 2 | 1 | 61 | Children 4–15 years | ND |
| Little36 | 3 | 2 | 1 | 0 | 88 | Children 1–16 years | 7 |
| Lintula37 | 5 | 2 | 2 | 1 | 25 | Children 4–15 years | 0 |
| Kocatas38 | 4 | 2 | 1 | 1 | 96 | Adults | ND |
| Rashid39 | 3 | 2 | 1 | 0 | 100 | Adults | 0 |
| Thomson40 | 5 | 2 | 2 | 1 | 112 | Adults | 3.3 |
| Cipe41 | 3 | 2 | 1 | 0 | 241 | Adults | 0 |
| Mantoglu42 | 3 | 2 | 1 | 0 | 63 | Adults | ND |
| Taguchi43 | 5 | 2 | 2 | 1 | 81 | Adults | 2.4% |
ND: not described.
Wound infection
Twenty-nine trials reported the incidence of wound infection in adults and children, and the wound infection rate was 51 in 1696 (3.01%) patients in LA and 130 in 1727 (7.53%) patients in OA. A fixed-effects model was used because there was no heterogeneity between the two groups (I2 = 4%, p = 0.40). Wound infection was significantly reduced with LA versus OA (OR = 0.38, 95% CI: 0.28–0.53, p < 0.00001). A subcategory analysis of wound infection in adults was performed, the results showed that LA was associated with a significantly reduced incidence of wound infection (OR = 0.38, 95% CI: 0.27–0.54, p < 0.00001). However, a subcategory analysis of wound infection in children showed that there was no significant difference between the two groups (OR = 0.39, 95% CI: 0.12–1.25, p = 0.11) (Figure 2).
Figure 2.
Meta-analysis of wound infection. CI: confidence interval; LA: laparoscopic appendectomy; OA: open appendectomy.
Intra-abdominal abscess
Eighteen trials reported the incidence of intra-abdominal abscess in adults and children. A fixed-effects model was used because there was no heterogeneity between the two groups (I2 = 0%, p = 0.80). Thirty-three (3.17%) and 40 (3.77%) incidences of postoperative intra-abdominal abscess were seen in the laparoscopic and open procedure groups, respectively, and there was no significant difference between the two groups (OR = 0.84, 95% CI: 0.55–1.28, p = 0.41). A subcategory analysis of intra-abdominal abscess in adults or children showed that there was no significant difference between the two groups (OR = 0.78, 95% CI: 0.50–1.23, p = 0.29, and OR = 1.43, 95% CI: 0.40–5.14, p = 0.58, respectively) (Figure 3).
Figure 3.
Meta-analysis of intra-abdominal abscess. CI: confidence interval; LA: laparoscopic appendectomy; OA: open appendectomy.
Postoperative complications
Twenty-eight trials reported the incidence of postoperative complications in adults and children, and the postoperative complications rate was 151 in 1595 (9.47%) patients in LA and 240 in 1628 (14.74%) patients in OA. A random-effects model was used because there was heterogeneity between the two groups (I2 = 47%, p = 0.004), however, a subcategory analysis of postoperative complications in children showed that there was no heterogeneity between the two groups (I2 = 0%, p = 0.80). When we modified to the fixed-effects model, the results were the same to previous results, the p value not changed. Postoperative complications were significantly reduced with LA versus OA (OR = 0.64, 95% CI: 0.44–0.93, p = 0.02). A subcategory analysis of postoperative complications in adults was performed, and the results showed that LA was associated with a significantly reduced incidence of postoperative complications (OR = 0.62, 95% CI: 0.40–0.96, p = 0.03). However, a subcategory analysis of postoperative complications in children showed that there was no significant difference between the two groups (OR = 0.74, 95% CI: 0.34–1.59, p = 0.44) (Figure 4).
Figure 4.
Meta-analysis of postoperative complications. CI: confidence interval; LA: laparoscopic appendectomy; OA: open appendectomy.
Reoperation
Twelve trials reported the incidence of reoperation in adults and children. A fixed-effects model was used because there was no heterogeneity between the two groups (I2 = 0%, p = 0.90). Eighteen (2.36%) and 17 (2.11%) incidences of reoperation were seen in the laparoscopic and open procedure groups, respectively, and there was no significant difference between the two groups (OR = 1.08, 95% CI: 0.58–2.01, p = 0.80). A subcategory analysis of reoperation in adults or children showed that there was no significant difference between the two groups (OR = 1.01, 95% CI: 0.51–1.98, p = 0.99, and OR = 1.56, 95% CI: 0.35–6.86, p = 0.56, respectively) (Figure 5).
Figure 5.
Meta-analysis of reoperation. CI: confidence interval; LA: laparoscopic appendectomy; OA: open appendectomy.
Operation time
Eighteen trials reported the operation time in adults and children. A random-effects model was used because there was heterogeneity between the two groups (I2 = 96%, p < 0.00001), however, a subcategory analysis of operation time in children showed that there was no heterogeneity between the two groups (I2 = 0%, p = 0.60). When we modified to the fixed-effects model, the results were the same to previous results, the p value was not changed. LA was associated with a significantly increased length of operation time (WMD = 11.59, 95% CI: 6.65–16.53, p < 0.0001). A subcategory analysis of operation time in adults or children showed that LA was associated with a significantly increased length of operation (WMD = 10.49, 95% CI: 5.05–15.92, p = 0.0002, and WMD = 16.91, 95% CI: 11.96–21.86, p < 0.00001, respectively) (Figure 6).
Figure 6.
Meta-analysis of operation time. CI: confidence interval; LA: laparoscopic appendectomy; OA: open appendectomy.
Postoperative stay
Seventeen trials reported the postoperative stay time in adults and children, and postoperative stay time was significantly reduced with LA versus OA (WMD = −0.79, 95% CI: −1.35– −0.23, p = 0.006). A random-effects model was used because there was heterogeneity between the two groups (I2 = 98%, p < 0.00001). A subcategory analysis of postoperative stay time in adults was performed, and the results showed that LA was associated with a significantly reduced postoperative stay time (WMD = −0.78, 95% CI: −1.38– −0.17, p = 0.01). However, a subcategory analysis of postoperative stay time in children showed that there was no significant difference between the two groups (WMD = −0.83, 95% CI: −2.46−0.81, p = 0.32) (Figure 7).
Figure 7.
Meta-analysis of postoperative stay. CI: confidence interval; LA: laparoscopic appendectomy; OA: open appendectomy.
Return to normal activity
Nine trials reported the return to normal activity time in adults and children, and return to normal activity time was significantly reduced with LA versus OA (WMD = −5.45, 95% CI: −8.98– −1.91, p = 0.003). A random-effects model was used because there was heterogeneity between the two groups (I2 = 99%, p < 0.00001). A subcategory analysis of return to normal activity time in adults was performed, and the results showed that LA was associated with a significantly reduced return to normal activity time (WMD = −3.92, 95% CI: −6.15– −1.70, p = 0.0006). However, a subcategory analysis of return to normal activity time in children showed that there was no significant difference between the two groups (WMD = −11.43, 95% CI: −22.94–0.09, p = 0.05) (Figure 8).
Figure 8.
Meta-analysis of return to normal activity. CI: confidence interval; LA: laparoscopic appendectomy; OA: open appendectomy.
Sensitivity analysis
We carried out a sensitivity analysis by adding one study at a time and leaving one study out in turn, and the results were the same to previous results, the p value was not changed (data not shown).
Publication bias
Funnel plots were used to investigate any possible publication bias in the meta-analysis. Since there were only a small number of children studies discussing intra-abdominal abscess, postoperative stay, reoperation, and return to normal activity, a funnel-plot analysis was used to detect possible publication bias only for wound infection and postoperative complications. The included studies fell symmetrically on both sides of the horizontal line (real value), indicating that there was no obvious publication bias related to these studies, and also indicating that the meta-analysis was reliable (data not shown).
Discussion
In the wake of the spectacular success of laparoscopic cholecystectomy, many surgeons have been eager to extrapolate the proven benefits of minimal access surgery to other procedures, including appendectomy. First performed by Semm in 1983, LA increased in popularity throughout the 1990s. However, unlike cholecystectomy, the benefits of the laparoscopic approach have not been as apparent.
Meta-analysis is a relatively new and increasingly popular method of data analysis. It is especially valuable when previous studies have been unable to show significant differences between treatments because of small sample sizes, or when there is no consensus of opinion. The results of this meta-analysis show that, when compared with OA, LA in adults was associated with lower incidence of wound infection, fewer postoperative complications, shorter postoperative stay, and earlier return to normal activity, but a longer operation time, there was no difference in levels of intra-abdominal abscess and reoperation between the groups. However, subgroup analysis in children did not reveal significant differences between the two techniques in wound infection, postoperative complications, postoperative stay, and return to normal activity.
Wound infection is the most common complication after appendectomy, although the answer to the question as to why wound infection might be reduced during LA is unclear. A possible reason for this is that in open appendectomies the appendix is delivered directly through the wound, thereby risking contamination, whereas in laparoscopic surgery the inflamed appendix never comes in to contact with the wound as it is removed via a trocar or bag. This advantage might be magnified in obese patients, where a larger open incision would be necessary, with its attendant risks of greater infection and postoperative pain.44
The one serious disadvantage to LA is the possibly greater incidence of intra-abdominal abscess formation. In a retrospective review, Tang and coauthors5 evaluated the incidence of postoperative intra-abdominal abscess formation after LA and OA. In patients with perforated appendicitis, they found a strong trend toward an increased rate of abscesses in the patients treated laparoscopically. We were not able to analyze the incidence of intra-abdominal abscesses in the subset of patients with perforation because such data were not reported. This meta-analysis did not show a statistically significant increase in the rate of intra-abdominal abscess formation in the LA group.
Postoperative complications are usually considered in an assessment of a procedure’s safety. The common complications of appendectomy are wound infection, intra-abdominal abscess, postoperative ileus, bleeding, and the like. In this meta-analysis, we used the overall incidence of postoperative complications to assess the safety of LA. The meta-analysis results showed that the overall incidence of postoperative complications in LA group was lower than in the OA group (Z = 2.35; p = 0.02).
Results for meta-analysis of operation time showed that LA took longer than OA by 11.59 min (WMD = 11.59, 95% CI: 6.65–16.53, p < 0.00001). Considering the increased instrumentation used during laparoscopic surgery and the setup time involved, the concept of a laparoscopic procedure taking longer than its open equivalent is not surprising, however, the slightly longer operation time with the additional 11.59 min in LA will most probably be reduced over time, as surgeons become more adept at the procedure. Pier and associates45 reported a series of 625 LA cases in which the average operating time was 15–20 min. Length of postoperative stay results from the studies included in this meta-analysis showed that LA in adults significantly reduced length of postoperative stay as compared with OA by 0.79 days. These results may be due to the fact that mobilization following LA is improved, thereby facilitating recovery and subsequent discharge from hospital. Early return to normal activity is accepted as an obvious advantage of LA, which was supported by a large scale meta-analysis conducted by the Cochrane Colorectal Cancer Group.6 The trocar incisions of LA contribute to minimal trauma to the abdominal wall and less pain, allowing faster recovery.46
There are other potential benefits to performing LA, including the ability to perform routine diagnostic laparoscopy. This may be of value in equivocal cases or in women,47 and laparoscopy has been shown to reduce the incidence of negative appendectomies.48–51 The practice of not removing a normal looking appendix is controversial, however, and there is evidence that visual inspection at the time of surgery cannot accurately predict the true histopathologic findings.52
This study has several limitations. First, the different operation methods were performed by different surgeons in different countries; thus, different learning curves may have contributed to the reported difference between the two procedures. Second, because of ethical limitations or other reasons, the studies of children are few, and the sample size in some studies are rather small. Third, the Jadad composite scale of some studies are low, which indicates the quality of included reports are not high.
The current meta-analysis showed that although LA has a longer operative time, it results in faster postoperative rehabilitation, a shorter hospital stay, and fewer postoperative complications than OA. Thus the LA is a useful tool in the treatment of acute appendicitis and worth recommending as an effective and safe procedure for adults. However, the advantage of LA in children was not obvious. Therefore, the study further highlights that more large sample and high-quality randomized trials for children are needed.
Conflict of interest
None of the authors have any conflicts of interest to declare.
Funding
This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
References
- 1.Addiss DG, Shaffer N, Fowler BS, et al. The epidemiology of appendicitis and appendectomy in the United States. Am J Epidemiol 1990; 132: 910–925. [DOI] [PubMed] [Google Scholar]
- 2.McBurney C. IV. The incision made in the abdominal wall in cases of appendicitis, with a description of a new method of operating. Ann Surg 1894; 20: 38–43. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Semm K. Endoscopic appendectomy. Endoscopy 1983; 15: 59–64. [DOI] [PubMed] [Google Scholar]
- 4.Ortega AE, Hunter JG, Peters JH, et al. A prospective, randomized comparison of laparoscopic appendectomy with open appendectomy. Laparoscopic Appendectomy Study Group. Am J Surg 1995; 169: 208–12. discussion 12–13. [DOI] [PubMed] [Google Scholar]
- 5.Tang E, Ortega AE, Anthone GJ, et al. Intraabdominal abscesses following laparoscopic and open appendectomies. Surg Endosc 1996; 10: 327–328. [DOI] [PubMed] [Google Scholar]
- 6.Sauerland S, Lefering R, Neugebauer EA. Laparoscopic versus open surgery for suspected appendicitis. Cochrane Database Syst Rev 2004, pp. CD001546–CD001546. [DOI] [PubMed] [Google Scholar]
- 7.Bennett J, Boddy A, Rhodes M. Choice of approach for appendicectomy: A meta-analysis of open versus laparoscopic appendicectomy. Surg Laparosc Endosc Percutan Tech 2007; 17: 245–255. [DOI] [PubMed] [Google Scholar]
- 8.Horwitz JR, Custer MD, May BH, et al. Should laparoscopic appendectomy be avoided for complicated appendicitis in children? J Pediatr Surg 1997; 32: 1601–1603. [DOI] [PubMed] [Google Scholar]
- 9.Faiz O, Blackburn SC, Clark J, et al. Laparoscopic and conventional appendicectomy in children: Outcomes in English hospitals between (1996) and (2006). Pediatr Surg Int 2008; 24: 1223–1227. [DOI] [PubMed] [Google Scholar]
- 10.Jadad AR, Moore RA, Carroll D, et al. Assessing the quality of reports of randomized clinical trials: Is blinding necessary? Control Clin Trials 1996; 17: 1–12. [DOI] [PubMed] [Google Scholar]
- 11.Martin LC, Puente I, Sosa JL, et al. Open versus laparoscopic appendectomy. A prospective randomized comparison. Ann Surg 1995; 222: 256–261; discussion 61–62. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12.Macarulla E, Vallet J, Abad JM, et al. Laparoscopic versus open appendectomy: A prospective randomized trial. Surg Laparosc Endosc 1997; 7: 335–339. [PubMed] [Google Scholar]
- 13.Minne L, Varner D, Burnell A, et al. Laparoscopic vs open appendectomy. Prospective randomized study of outcomes. Arch Surg 1997; 132: 708–711; discussion 12. [DOI] [PubMed] [Google Scholar]
- 14.Reiertsen O, Larsen S, Trondsen E, et al. Randomized controlled trial with sequential design of laparoscopic versus conventional appendicectomy. Br J Surg 1997; 84: 842–847. [PubMed] [Google Scholar]
- 15.Hellberg A, Rudberg C, Kullman E, et al. Prospective randomized multicentre study of laparoscopic versus open appendicectomy. Br J Surg 1999; 86: 48–53. [DOI] [PubMed] [Google Scholar]
- 16.Shirazi B, Ali N, Shamim MS. Laproscopic versus open appendectomy: A comparative study. J Pak Med Assoc 2010; 60: 901–904. [PubMed] [Google Scholar]
- 17.Moberg AC, Berndsen F, Palmquist I, et al. Randomized clinical trial of laparoscopic versus open appendicectomy for confirmed appendicitis. Br J Surg 2005; 92: 298–304. [DOI] [PubMed] [Google Scholar]
- 18.Kaplan M, Salman B, Yilmaz TU, et al. A quality of life comparison of laparoscopic and open approaches in acute appendicitis: A randomised prospective study. Acta Chir Belg 2009; 109: 356–363. [DOI] [PubMed] [Google Scholar]
- 19.Wei B, Qi CL, Chen TF, et al. Laparoscopic versus open appendectomy for acute appendicitis: A metaanalysis. Surg Endosc 2011; 25: 1199–1208. [DOI] [PubMed] [Google Scholar]
- 20.Ignacio RC, Burke R, Spencer D, et al. Laparoscopic versus open appendectomy: What is the real difference? Results of a prospective randomized double-blinded trial. Surg Endosc 2004; 18: 334–337. [DOI] [PubMed] [Google Scholar]
- 21.Mutter D, Vix M, Bui A, et al. Laparoscopy not recommended for routine appendectomy in men: Results of a prospective randomized study. Surgery 1996; 120: 71–74. [DOI] [PubMed] [Google Scholar]
- 22.Cox MR, McCall JL, Toouli J, et al. Prospective randomized comparison of open versus laparoscopic appendectomy in men. World J Surg 1996; 20: 263–266. [DOI] [PubMed] [Google Scholar]
- 23.Tzovaras G, Baloyiannis I, Kouritas V, et al. Laparoscopic versus open appendectomy in men: A prospective randomized trial. Surg Endosc 2010; 24: 2987–2992. [DOI] [PubMed] [Google Scholar]
- 24.Laine S, Rantala A, Gullichsen R, et al. Laparoscopic appendectomy–is it worthwhile? A prospective, randomized study in young women. Surg Endosc 1997; 11: 95–97. [DOI] [PubMed] [Google Scholar]
- 25.Al-Mulhim AS, Al-Mulhim FM, Al-Suwaiygh AA, et al. Laparoscopic versus open appendectomy in females with a clinical diagnosis of appendicitis. Saudi Med J 2002; 23: 1339–1342. [PubMed] [Google Scholar]
- 26.van Dalen R, Bagshaw PF, Dobbs BR, et al. The utility of laparoscopy in the diagnosis of acute appendicitis in women of reproductive age. Surg Endosc 2003; 17: 1311–1313. [DOI] [PubMed] [Google Scholar]
- 27.Clarke T, Katkhouda N, Mason RJ, et al. Laparoscopic versus open appendectomy for the obese patient: A subset analysis from a prospective, randomized, double-blind study. Surg Endosc 2011; 25: 1276–1280. [DOI] [PubMed] [Google Scholar]
- 28.Kargar S, Mirshamsi MH, Zare M, et al. Laparoscopic versus open appendectomy; which method to choose? A prospective randomized comparison. Acta Med Iran 2011; 49: 352–356. [PubMed] [Google Scholar]
- 29.Schietroma M, Piccione F, Carlei F, et al. Peritonitis from perforated appendicitis: Stress response after laparoscopic or open treatment. Am Surg 2012; 78: 582–590. [PubMed] [Google Scholar]
- 30.Khalil J, Muqim R, Rafique M, et al. Laparoscopic versus open appendectomy: A comparison of primary outcome measures. Saudi J Gastroenterol 2011; 17: 236–240. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 31.Gilchrist BF, Lobe TE, Schropp KP, et al. Is there a role for laparoscopic appendectomy in pediatric surgery? J Pediatr Surg 1992; 27: 209–212; discussion 12–14. [DOI] [PubMed] [Google Scholar]
- 32.Lejus C, Delile L, Plattner V, et al. Randomized, single-blinded trial of laparoscopic versus open appendectomy in children: Effects on postoperative analgesia. Anesthesiology 1996; 84: 801–806. [DOI] [PubMed] [Google Scholar]
- 33.Hay SA. Laparoscopic versus conventional appendectomy in children. Pediatr Surg Int 1998; 13: 21–23. [DOI] [PubMed] [Google Scholar]
- 34.Lavonius MI, Liesjarvi S, Ovaska J, et al. Laparoscopic versus open appendectomy in children: A prospective randomised study. Eur J Pediatr Surg 2001; 11: 235–238. [DOI] [PubMed] [Google Scholar]
- 35.Lintula H, Kokki H, Vanamo K. Single-blind randomized clinical trial of laparoscopic versus open appendicectomy in children. Br J Surg 2001; 88: 510–514. [DOI] [PubMed] [Google Scholar]
- 36.Little DC, Custer MD, May BH, et al. Laparoscopic appendectomy: An unnecessary and expensive procedure in children? J Pediatr Surg 2002; 37: 310–317. [DOI] [PubMed] [Google Scholar]
- 37.Lintula H, Kokki H, Vanamo K, et al. Laparoscopy in children with complicated appendicitis. J Pediatr Surg 2002; 37: 1317–1320. [DOI] [PubMed] [Google Scholar]
- 38.Kocatas A, Gonenc M, Bozkurt MA, et al. Comparison of open and laparoscopic appendectomy in uncomplicated appendicitis: A prospective randomized clinical trial. Ulus Travma Derg 2013; 19: 200–204. [DOI] [PubMed] [Google Scholar]
- 39.Rashid A, Nazir S, Kakroo SM, et al. Laparoscopic interval appendectomy versus open interval appendectomy: A prospective randomized controlled trial. Surg Laparosc Endosc Percutan Tech 2013; 23: 93–96. [DOI] [PubMed] [Google Scholar]
- 40.Thomson JE, Kruger D, Jann-Kruger C, et al. Laparoscopic versus open surgery for complicated appendicitis: A randomized controlled trial to prove safety. Surg Endosc 2015; 29: 2027–2032. [DOI] [PubMed] [Google Scholar]
- 41.Cipe G, Idiz O, Hasbahceci M, et al. Laparoscopic versus open appendectomy: Where are we now? Chirurgia 2014; 109: 518–522. [PubMed] [Google Scholar]
- 42.Mantoglu B, Karip B, Mestan M, et al. Should appendectomy be performed laparoscopically? Clinical prospective randomized trial. Ulusal cerrahi dergisi 2015; 31: 224–228. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 43.Taguchi Y, Komatsu S, Sakamoto E, et al. Laparoscopic versus open surgery for complicated appendicitis in adults: A randomized controlled trial. Surg Endosc 2016; 30: 1705–1712. [DOI] [PubMed] [Google Scholar]
- 44.Lujan Mompean JA, Robles Campos R, Parrilla Paricio P, et al. Laparoscopic versus open appendicectomy: A prospective assessment. Br J Surg 1994; 81: 133–135. [DOI] [PubMed] [Google Scholar]
- 45.Pier A, Gotz F, Bacher C. Laparoscopic appendectomy in 625 cases: From innovation to routine. Surg Laparosc Endosc 1991; 1: 8–13. [PubMed] [Google Scholar]
- 46.Koontz CS, Smith LA, Burkholder HC, et al. Video-assisted transumbilical appendectomy in children. J Pediatr Surg 2006; 41: 710–712. [DOI] [PubMed] [Google Scholar]
- 47.Whitworth CM, Whitworth PW, Sanfillipo J, et al. Value of diagnostic laparoscopy in young women with possible appendicitis. Surg Gynecol Obstet 1988; 167: 187–190. [PubMed] [Google Scholar]
- 48.Kum CK, Sim EK, Goh PM, et al. Diagnostic laparoscopy: Reducing the number of normal appendectomies. Dis Colon Rectum 1993; 36: 763–766. [DOI] [PubMed] [Google Scholar]
- 49.Olsen JB, Myren CJ, Haahr PE. Randomized study of the value of laparoscopy before appendicectomy. Br J Surg 1993; 80: 922–923. [DOI] [PubMed] [Google Scholar]
- 50.Paterson-Brown S, Thompson JN, Eckersley JR, et al. Which patients with suspected appendicitis should undergo laparoscopy? Br Med J 1988; 296: 1363–1364. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 51.Jadallah FA, Abdul-Ghani AA, Tibblin S. Diagnostic laparoscopy reduces unnecessary appendicectomy in fertile women. Eur J Surg 1994; 160: 41–45. [PubMed] [Google Scholar]
- 52.Lau WY, Fan ST, Yiu TF, et al. The clinical significance of routine histopathologic study of the resected appendix and safety of appendiceal inversion. Surg Gynecol Obstet 1986; 162: 256–258. [PubMed] [Google Scholar]








