The American Journal of Surgery (2014) 207, 613-622
Review
Meta-analysis of randomized trials on single-incision laparoscopic versus conventional laparoscopic appendectomy Stavros A. Antoniou, M.D.a,b,*, Oliver O. Koch, M.D.c, George A. Antoniou, M.D., Ph.D.d, Konstantinos Lasithiotakis, M.D., Ph.D.b, George E. Chalkiadakis, M.D., Ph.D.b, Rudolph Pointner, M.D., Ph.D.e, Frank A. Granderath, M.D., Ph.D.a a
Center for Minimally Invasive Surgery, Neuwerk Hospital, Mo¨nchengladbach, Germany; bDepartment of General Surgery, University Hospital of Heraklion, University of Crete, Heraklion, Greece; cDepartment of General and Visceral Surgery, Hospital of Linz, Linz, Austria; dDepartment of Vascular Surgery, Hellenic Red Cross Hospital, Athens, Greece; e Department of General and Visceral Surgery, Hospital Zell am See, Zell am See, Austria
KEYWORDS: Single-incision; Single-access; Single-port; SILS; Laparoscopy; Appendectomy
Abstract BACKGROUND: Single-incision laparoscopic appendectomy has emerged as a less invasive alternative to conventional laparoscopic surgery. High-quality relevant evidence is limited. METHODS: A systematic review of electronic information sources was undertaken, with the objective of identifying randomized trials that compared single-incision with conventional laparoscopic appendectomy. Outcome measures included 30-day morbidity, abdominal abscess, wound infection, open conversion, reoperation, operative time, length of hospital stay, and postoperative pain. Fixed-effects and random-effects models were used to calculate combined overall effect sizes of pooled data. Data are presented as odds ratios or weighted mean differences with 95% confidence intervals (CIs). RESULTS: Five randomized trials were identified, with a total of 746 patients. Thirty-day morbidity (9.6% vs 8.6%; odds ratio, 1.14; 95% CI, .69 to 1.89) and wound infection rates were similar between single-incision and conventional laparoscopy (4.0% vs 4.8%; odds ratio, .83; 95% CI, .41 to 1.68), whereas the duration of surgery was longer in the single-incision group (46.3 vs 40.7 minutes; weighted mean difference, 6.01; 95% CI, 2.26 to 9.76). Available data were not adequately robust to reach conclusions regarding the remaining outcome measures. CONCLUSIONS: Similar postoperative morbidity and wound infection rates for single-incision and conventional laparoscopic appendectomy are supported by the current literature, but single-incision surgery requires longer operative time. Ó 2014 Elsevier Inc. All rights reserved.
The authors declare no conflicts of interest. * Corresponding author. Tel.: 130-6978-732791; fax: 130-2299068845. E-mail address: [email protected] Manuscript received May 8, 2013; revised manuscript June 28, 2013 0002-9610/$ - see front matter Ó 2014 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.amjsurg.2013.07.045
Laparoscopic surgery through a single incision has evolved with the objectives of minimizing surgical trauma, reducing postoperative pain, shortening convalescence, and providing improved cosmesis. Recent meta-analyses of
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The American Journal of Surgery, Vol 207, No 4, April 2014
single-incision laparoscopic cholecystectomy have demonstrated similar complication rates to conventional laparoscopy, but they have failed to provide uniform results regarding pain.1,2 Emerging evidence suggests that the appealing idea of minimizing surgical trauma must be weighed against associated direct and indirect risks.3 A systematic review of single-incision laparoscopic cholecystectomy has demonstrated increased risk for common bile duct injuries compared with historic complication rates of conventional cholecystectomy.4 Evidence demonstrates clear superiority of laparoscopic appendectomy over open surgery in terms of wound-related complications, although conflicting data suggest longer operative time for the laparoscopic approach.5,6 Similar operative morbidity for open and laparoscopic appendectomy has
Figure 1
rendered the latter an acceptable alternative. Insufficient high-quality data on single-incision laparoscopic appendectomy exist; nevertheless, many institutions have used the single-incision method outside a frame of randomization.7 A meta-analysis by the Cochrane Collaboration in 2011 could not identify any randomized studies comparing single-incision with conventional laparoscopic appendectomy.8 The aim of the present meta-analysis was to compare outcomes of single-incision laparoscopic appendectomy with those of conventional laparoscopic appendectomy, as expressed by the incidence of postoperative complications, the need for conversion to open surgery, duration of surgery, reoperation rate, overall cost, postoperative pain, and time to resume to normal diet.
Flow diagram of search history. RCT 5 randomized controlled trial.
S.A. Antoniou et al. Table 1
Single-incision vs conventional laparoscopic appendectomy
Study characteristics Year of publication
Country
Participating centers
Period of treatment
Inclusion criteria
2013
Spain
Single center
September 2009 to December 2010
Age .11 y, migrating pain, abdominal defense
Lee et al16 2013
Korea
Single center
March 2010 to September 2011
Study Frutos et al15
615
Sozutek et al17
2013
Turkey
Single center
September 2010 to May 2011
Teoh et al18
2012
China
Single center
October 2009 to March 2011
Spain, Egypt, Turkey
Multicenter
July 2009 to March 2010
Vilallonga 2012 et al19
Exclusion criteria
Cirrhosis, coagulation disorders, abscess or peritonitis, septic shock, contraindication to laparoscopic surgery, contraindication to general anesthesia, pregnancy Refusal of laparoscopic surgery, Age .16 y, migrating abscess, cirrhosis, coagulation pain, nausea, fever disorders, circulatory failure, .38 C or leukocyte contraindication to laparoscopic count .103/mL, guarding, tenderness surgery, contraindication to general anesthesia, pregnancy, neoplasm NR Age ,18 y, ASA score 4 or 5, anticoagulation treatment, absence of macroscopic findings of appendicitis Age 18–75 y, migrating Duration of symptoms .5 d, palpable mass in the right lower quadrant, pain, fever .38 C or cirrhosis, coagulation disorders, leukocyte count abscess or peritonitis, septic shock, .103/mL, guarding, tenderness contraindication to general anesthesia, pregnancy, previous abdominal surgery, ascites, malignancy NR NR
NR 5 not reported.
Methods Eligibility criteria and study selection A protocol was established before initiation of the study to determine the criteria for inclusion, the methods for analysis, and the investigated outcomes. Randomized studies in adult populations comparing single-incision with conventional laparoscopic appendectomy and reporting R1 of the predetermined outcome measures were considered for inclusion. Nonrandomized studies and studies including pediatric patient populations were excluded. The primary outcome Table 2
Patient allocation
Study
Patients Patients Patients Patients completing allocated allocated to included follow-up to SILA CLA
Frutos et al15 Lee et al16 Sozutek et al17 Teoh et al18 Vilallonga et al19
184 248 75* 200 87
184 224 75* 195 87
91 114 25 98 46
93 116 25 97 41
CLA 5 conventional laparoscopic appendectomy; SILA 5 singleincision laparoscopic appendectomy. *Includes a 3rd group of patients allocated to open appendectomy.
measure of the present analysis was the incidence of 30-day morbidity. Secondary outcome measures included the incidence of intra-abdominal abscess, wound infection rate, reoperation rate, conversion to open surgery, duration of surgery, overall cost, time to resume to liquid diet, time to resume to solid diet, length of hospital stay, and postoperative pain (6 to 24 hours after surgery).
Search strategy The electronic database of the National Library of Medicine (MEDLINE; provider Ovid, from 1966 to April 2013) was searched to identify relevant articles. No language restrictions were applied. The Medical Subject Headings ‘‘laparoscopy’’ and ‘‘appendectomy’’ and the terms ‘‘single incision,’’ ‘‘single port,’’ ‘‘single access,’’ ‘‘one access,’’ and ‘‘SILS’’ (single-incision laparoscopic surgery) were used combined with the Boolean operators AND and OR (Appendix). A second-level manual search included the reference lists of the retrieved articles. The last search was run on April 11, 2013. Eligibility assessment was performed independently in an unblinded standardized manner by 2 reviewers. Disagreements between reviewers were resolved by consensus. The literature review conformed to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses standards.9
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Table 3
Quality assessment of included randomized trials
Study
Description of Method of Method of Randomization Randomization Study Study described as double blinding double blinding withdrawal/ Jadad method described as method dropouts? score appropriate? appropriate? double blind? described? randomized? described?
Frutos et al15 Lee et al16 Sozutek et al17 Teoh et al18 Vilallonga et al19
Yes Yes Yes Yes Yes
Yes Yes Yes Yes No
No No No Yes NA
No No No Yes No
NA NA NA Yes NA
NA NA NA Yes NA
Yes Yes Yes Yes Yes
3 3 3 5 2
NA 5 not applicable.
Data collection An electronic data extraction sheet was developed and refined accordingly. One review author extracted the data from included studies, and a second author checked the extracted data. The latter included the name of the primary author, year of publication, country (or countries) of participating institution(s), number of participating centers, patient recruitment period, inclusion and exclusion criteria for patient enrollment in the studies, number of patients assigned to randomization, number of patients having completed follow-up, number of patients allocated to either group, method of closure of the appendiceal stump, method of specimen extraction, and results of the aforementioned outcome measures.
Methods of analysis A fixed-effects model was initially applied to synthesize the data; however, if significant heterogeneity among the included studies was identified, random-effects analysis according to DerSimonian and Laird10 was used. Weighted mean differences (WMDs) with 95% confidence intervals (CIs) were calculated to assess the size of the effect of each type of procedure on continuous variables. Pooled odds ratios (ORs) with 95% CIs were calculated to measure the effect of each type of procedure on categorical variables. Heterogeneity was assessed using the I2 statistic, a method expressing the percentage of variation across
Table 4
studies. I2 values between 0% and 25% suggest low heterogeneity, values .25% suggest moderate heterogeneity, and values .75% suggest high heterogeneity. Publication bias was assessed visually evaluating the symmetry of funnel plots. Statistical analysis was performed using Review Manager version 5.2 (The Nordic Cochrane Centre, Copenhagen, Denmark). Statistical expertise was provided by one of the study authors (G.A.A.).
Methodologic assessment To assess the methodologic quality of eligible randomized controlled trials, respective data from each study protocol were extracted, and the Jadad score was calculated.11 This scoring system takes into account the randomization process, the blind assessment of the outcome, and reporting of withdrawals or dropouts. The minimum score of 1 indicates poor methodologic quality, whereas the maximum score of 5 suggests excellent methodologic quality.
Results Search results and study selection The electronic search identified a total of 192 records. Some 185 articles were discarded on the basis of their titles or abstracts as not relevant studies (n 5 102), studies with pediatric patient populations (n 5 25), review articles (n 5 22), nonrandomized
Outcome data 30-d morbidity
Study 15
Frutos et al Lee et al16 Sozutek et al17 Teoh et al18 Vilallonga et al19
Abdominal abscess
Wound infection
Reoperation
SILA
CLA
SILA
CLA
SILA
CLA
SILA
CLA
4/91 15/114 1/25 14/98 2/46
4/93 18/116 1/25 9/97 0/41
0/91 6/114 0/25 4/98 0/46
0/93 2/116 0/25 9/97 0/41
0/91 6/114 1/25 8/98 0/46
0/93 12/116 1/25 5/97 0/41
0/91 0/114 0/25 NR 0/46
1/93 1/116 0/25 NR 0/41
CLA 5 conventional laparoscopic appendectomy; NR 5 not reported; SILA 5 single-incision laparoscopic appendectomy. *Standard deviation not reported.
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Single-incision vs conventional laparoscopic appendectomy
617
Figure 2 Forest plot of the OR for 30-day morbidity. SILA 5 single-incision laparoscopic appendectomy; CLA 5 conventional laparoscopic appendectomy; M-H 5 Mantel-Haenszel.
lists of the included articles. Finally, a total of 5 randomized trials entered the meta-analytic models (Fig. 1).15–19
Study characteristics and methodologic quality
Figure 3 morbidity.
Funnel plot for the outcome measure 30-day
studies (n 5 17), technical notes (n 5 9), comments (n 5 5), letters (n 5 3), and an article not reporting any of the investigated outcome parameters (n 5 1). A potentially eligible recent randomized trial could not be retrieved from national and international libraries, and the corresponding author did not respond to our request for the full text.12 The reports of 7 randomized trials were retrieved.13–19 Two studies had focused on pediatric patient populations and were therefore excluded.13,14 No additional eligible studies were identified in the reference Table 4
All studies were published in the English language in 2012 and 2013. The number of participating institutions ranged between 1 and 3. Inclusion and exclusion criteria were similar among studies (Table 1). The study population consisted of 794 patients, whereas 765 patients had completed follow-up. The single-incision and conventional laparoscopic groups included 374 and 372 patients, respectively (Table 2). The appendiceal stump was commonly secured using the ENDOLOOP (Ethicon Endo-Surgery, Cincinnati, OH) in both treatment arms, whereas in 4 studies, retrieval bags were used to extract the specimens.15–18 Four studies reported on methods of randomization, but only 1 study was double blinded (Table 3). Jadad scores ranged between 2 and 5, with an overall mean value of 3.2.
Synthesis of results and outcome Summary outcome data are presented in Table 4. No comparative data on hospitalization costs were provided. Furthermore, resumption of oral diet was either not reported15,16 or not specifically documented for liquid or solid diet.17–19 Therefore, the above outcome data could not enter the meta-analysis models.
(continued)
Conversion
Duration of surgery (min), mean 6 SD
Hospital stay (h), mean 6 SD SILA
CLA
SILA
CLA
18.86 6 9.77 72* 1.1 6 0.3 84.72 6 70.08 44.4*
21.32 6 11.72 72* 1.2 6 0.8 76.80 6 56.64 34.0*
2.76 6 1.64 NR 3.4 6 1.0 NR 2.8*
3.78 6 1.76 NR 2.89 6 0.86 NR 2.9*
SILA
CLA
SILA
0/91 0/114 0/25 8/98 1/46
0/93 0/116 0/25 3/97 0/41
38.13 43.8 32.6 63.0 40.4*
CLA 6 6 6 6
13.49 21.3 9.9 27.2
32.12 35.8 29.5 60.2 35.0*
6 6 6 6
12.44 18.9 6.8 31.7
Postoperative pain* (VAS score)
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Figure 4 Forest plot of the OR for abdominal abscess. SILA 5 single-incision laparoscopic appendectomy; CLA 5 conventional laparoscopic appendectomy; M-H 5 Mantel-Haenszel.
Figure 5 Forest plot of the OR for wound infection. SILA 5 single-incision laparoscopic appendectomy; CLA 5 conventional laparoscopic appendectomy; M-H 5 Mantel-Haenszel.
Figure 6 Forest plot of the OR for reoperation. SILA 5 single-incision laparoscopic appendectomy; CLA 5 conventional laparoscopic appendectomy; M-H 5 Mantel-Haenszel.
Thirty-day morbidity. The incidence of 30-day morbidity was 9.6% and 8.6% in the single-incision and conventional laparoscopic groups, respectively (OR, 1.14; 95% CI, .69 to 1.89; P 5 .60; Fig. 2). No significant heterogeneity among the studies was identified (I2 5 0%), and the likelihood of publication bias was low (Fig. 3). Abdominal abscess. Abdominal abscess developed in 2.7% of the single-incision and 1.3% of the conventional laparoscopy patients (OR, 2.06; 95% CI, .69 to 6.11; P 5
.20; Fig. 4). No heterogeneity existed among the studies (I2 5 0%). Wound infection. Surgical-site infections occurred in 4.0% and 4.8% in the single-incision and conventional laparoscopic groups, respectively (OR, .83; 95% CI, .41 to 1.68; P 5 .60; Fig. 5). No heterogeneity among the studies was found (I2 5 0%). Reoperation rate. Two patients in the conventional laparoscopy group underwent reoperation, whereas none of the
S.A. Antoniou et al.
Single-incision vs conventional laparoscopic appendectomy
619
Figure 7 Forest plot of the OR for conversion. SILA 5 single-incision laparoscopic appendectomy; CLA 5 conventional laparoscopic appendectomy; M-H 5 Mantel-Haenszel.
Figure 8 Forest plot of difference in means for operative time. SILA 5 single-incision laparoscopic appendectomy; CLA 5 conventional laparoscopic appendectomy; IV 5 interval.
patients in the single-incision group required reoperation (OR, .34; 95% CI, .03 to 3.26; P 5 .35; Fig. 6). No heterogeneity among the studies was identified (I2 5 0%). Conversion to open surgery. The conversion rates for the single-incision and conventional laparoscopy groups were 2.4% and .8%, respectively (OR, 2.78; 95% CI, .79 to 9.71; P 5 .11; Fig. 7). There was no evidence of heterogeneity (I2 5 0%).
Duration of surgery. The duration of single-incision surgery was an average of 5.6 minutes longer than that of conventional surgery (46.29 vs 40.73 minutes; WMD, 6.01; 95% CI, 2.26 to 9.76; P , .0001; Fig. 8). No significant heterogeneity among the studies was found (I2 5 0%), and the possibility of publication bias was low (Fig. 9). Hospital stay. The length of hospital stay was similar in the single-incision and conventional laparoscopy groups (48.9 vs 45.1 hours, respectively; WMD, 22.19; 95% CI, 25.05 to .68; P 5 .14; Fig. 10). There was no evidence of heterogeneity. Postoperative pain. No significant differences in visual analogue scale score between the 2 groups were identified (3.04 vs 3.41, respectively; WMD, 2.26; 95% CI, 21.76 to 1.24; P 5 .74; Fig. 11). Significant heterogeneity among the studies existed (I2 5 94%).
Comments
Figure 9 Funnel plot for the outcome measure operative time. MD 5 mean difference.
Data derived from randomized trials of single-incision laparoscopic appendectomy are deemed sufficiently robust to support similar 30-day morbidity compared with conventional laparoscopic surgery. An attempt was made to comparatively evaluate the incidence of postoperative abdominal abscess, but only 2 studies reporting on this
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Figure 10 Forest plot of difference in means for hospital stay. SILA 5 single-incision laparoscopic appendectomy; CLA 5 conventional laparoscopic appendectomy; IV 5 interval.
complication could enter the meta-analytic model.16,18 Although there was a trend toward a higher incidence of abdominal abscess for the single-incision group (2.7% vs 1.3%), this difference did not reach statistical significance. An adequate number of studies reported on the duration of surgery; in these terms, individual differences in means were constantly in favor of conventional laparoscopic surgery. This trend has also been confirmed for single-incision laparoscopic cholecystectomy compared with standard laparoscopy3 and may be associated to technical difficulties due to inadequate triangulation, difficulties manipulating laparoscopic instruments, and difficulty managing intraoperative complications. Furthermore, only 2 studies provided adequate data on postoperative pain, rendering comparative evidence of limited importance. Nevertheless, 4 of the 5 studies providing some data on this outcome measure reported no difference between the study groups. The lower incidence of surgical-site infection is one of the primary advantages of laparoscopic appendectomy over conventional surgery. Strong evidence provided by the present meta-analysis does not support lower wound infection rates for single-incision laparoscopic appendectomy. Relevant data were documented by all trials, but 2 studies with zero incidence of wound infection in both arms could not enter the meta-analytic model. It may thus be suggested that reducing the number of access sites in laparoscopic appendectomy does not result in a reduction of wound infection rates. The incidence of incisional hernia
was reported by 3 studies only,15,17,19 thus providing limited comparative evidence. A recent meta-analysis that compared this complication after single-incision or conventional laparoscopic appendectomy found no significant difference between the 2 approaches.3 Furthermore, because of the low frequency of the need for conversion and reoperation, synthesis of the results was inconclusive regarding these outcome measures. Two patients from the conventional laparoscopy group required reoperation (.5%) compared with none in the single-incision group, whereas the respective rates for conversion to open surgery were .8% and 2.4%. A potential significance of the latter result cannot be estimated by the present meta-analytic approach. Randomized studies of single-incision laparoscopic appendectomy were published exclusively within the past 2 years. The overall methodologic quality was fair, but only 1 trial was blinded to patients and assessors. The increasing interest and the limited evidence on single-incision surgery are expected to be expressed by the publication of further data on this field. It is of specific importance for novel trials to be of adequate quality and to report on a wide range of outcome measures, including postoperative pain, cost, time to resume to oral diet, and time of convalescence. Moreover, because the learning curve may have a significant effect on operative time and surgical outcomes, future randomized trials that adequately report on previous surgeons’ experience with single-incision laparoscopy surgery are essential. Furthermore, to detect potential
Figure 11 Forest plot of difference in means for postoperative pain. SILA 5 single-incision laparoscopic appendectomy; CLA 5 conventional laparoscopic appendectomy; IV 5 interval.
S.A. Antoniou et al.
Single-incision vs conventional laparoscopic appendectomy
differences in ORs for abdominal abscess and conversion to open surgery, larger patient populations are required. The best evidence suggests similar overall postoperative morbidity and similar wound infection rates for singleincision laparoscopic appendectomy compared with conventional laparoscopy; however, single-incision surgery requires longer operative time. Meta-analytic synthesis of data on other outcome measures was inconclusive. Further randomized trials in this field are warranted.
References 1. Arezzo A, Scozzari G, Famiglietti F, et al. Is single-incision laparoscopic cholecystectomy safe? Results of a systematic review and meta-analysis. Surg Endosc 2013;27:2293–304. 2. Pisanu A, Reccia I, Porceddu G, et al. Meta-analysis of prospective randomized studies comparing single-incision laparoscopic cholecystectomy (SILC) and conventional multiport laparoscopic cholecystectomy (CMLC). J Gastrointest Surg 2012;16:1790–801. 3. Trastulli S, Cirocchi R, Desiderio J, et al. Systematic review and meta-analysis of randomized clinical trials comparing singleincision versus conventional laparoscopic cholecystectomy. Br J Surg 2013;100:191–208. 4. Joseph M, Phillips MR, Farrell TM, et al. Single incision laparoscopic cholecystectomy is associated with a higher bile duct injury rate: a review and a word of caution. Ann Surg 2012;256:1–6. 5. Ohtani H, Tamamori Y, Arimoto Y, et al. Meta-analysis of the results of randomized controlled trials that compared laparoscopic and open surgery for acute appendicitis. J Gastrointest Surg 2012; 16:1929–39. 6. Woodham BL, Cox MR, Eslick GD. Evidence to support the use of laparoscopic over open appendicectomy for obese individuals: a meta-analysis. Surg Endosc 2012;26:2566–70. 7. Pisanu A, Porceddu G, Reccia I, et al. Meta-analysis of studies comparing single-incision laparoscopic appendectomy and conventional multiport laparoscopic appendectomy. J Surg Res 2012;183: e49–59.
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8. Rehman H, Rao AM, Ahmed I. Single incision versus conventional multi-incision appendicectomy for suspected appendicitis. Cochrane Database Syst Rev 2011;7:CD009022. 9. Liberati A, Altman DG, Tetzlaff J, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. BMJ 2009;339:b2700. 10. DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials 1986;7:177–88. 11. 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. 12. Kye BH, Lee J, Kim W, et al. Comparative study between singleincision and three-port laparoscopic appendectomy: a prospective randomized trial. J Laparoendosc Adv Surg Tech A 2013;23: 431–6. 13. Knott EM, Gasior AC, Holcomb III GW, et al. Impact of body habitus on single-site laparoscopic appendectomy for nonperforated appendicitis: subset analysis from a prospective, randomized trial. J Laparoendosc Adv Surg Tech A 2012;22:404–7. 14. St Peter SD, Adibe OO, Juang D, et al. Single incision versus standard 3-port laparoscopic appendectomy: a prospective randomized trial. Ann Surg 2011;254:586–90. 15. Frutos MD, Abrisqueta J, Lujan J, et al. Randomized prospective study to compare laparoscopic appendectomy versus umbilical singleincision appendectomy. Ann Surg 2013;257:413–8. 16. Lee WS, Choi ST, Lee JN, et al. Single-port laparoscopic appendectomy versus conventional laparoscopic appendectomy: a prospective randomized controlled study. Ann Surg 2013;257:214–8. 17. Sozutek A, Colak T, Dirlik M, et al. A prospective randomized comparison of single-port laparoscopic procedure with open and standard 3-port laparoscopic procedures in the treatment of acute appendicitis. Surg Laparosc Endosc Percutan Tech 2013;23:74–8. 18. Teoh AY, Chiu PW, Wong TC, et al. A double-blinded randomized controlled trial of laparoendoscopic single-site access versus conventional 3-port appendectomy. Ann Surg 2012;256:909–14. 19. Vilallonga R, Barbaros U, Nada A, et al. Single-port transumbilical laparoscopic appendectomy: a preliminary multicentric comparative study in 87 patients with acute appendicitis. Minim Invasive Surg 2012;2012:492409.
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Appendix Combination of search terms Search terms: [any A] AND [B] AND [any C] A. 1. single incision 2. single access 3. single port 4. one access 5. SILS B. laparoscopic C. 1. appendectomy 2. appendicectomy
The American Journal of Surgery, Vol 207, No 4, April 2014
Review
Meta-analysis of randomized trials on single-incision laparoscopic versus conventional laparoscopic appendectomy Stavros A. Antoniou, M.D.a,b,*, Oliver O. Koch, M.D.c, George A. Antoniou, M.D., Ph.D.d, Konstantinos Lasithiotakis, M.D., Ph.D.b, George E. Chalkiadakis, M.D., Ph.D.b, Rudolph Pointner, M.D., Ph.D.e, Frank A. Granderath, M.D., Ph.D.a a
Center for Minimally Invasive Surgery, Neuwerk Hospital, Mo¨nchengladbach, Germany; bDepartment of General Surgery, University Hospital of Heraklion, University of Crete, Heraklion, Greece; cDepartment of General and Visceral Surgery, Hospital of Linz, Linz, Austria; dDepartment of Vascular Surgery, Hellenic Red Cross Hospital, Athens, Greece; e Department of General and Visceral Surgery, Hospital Zell am See, Zell am See, Austria
KEYWORDS: Single-incision; Single-access; Single-port; SILS; Laparoscopy; Appendectomy
Abstract BACKGROUND: Single-incision laparoscopic appendectomy has emerged as a less invasive alternative to conventional laparoscopic surgery. High-quality relevant evidence is limited. METHODS: A systematic review of electronic information sources was undertaken, with the objective of identifying randomized trials that compared single-incision with conventional laparoscopic appendectomy. Outcome measures included 30-day morbidity, abdominal abscess, wound infection, open conversion, reoperation, operative time, length of hospital stay, and postoperative pain. Fixed-effects and random-effects models were used to calculate combined overall effect sizes of pooled data. Data are presented as odds ratios or weighted mean differences with 95% confidence intervals (CIs). RESULTS: Five randomized trials were identified, with a total of 746 patients. Thirty-day morbidity (9.6% vs 8.6%; odds ratio, 1.14; 95% CI, .69 to 1.89) and wound infection rates were similar between single-incision and conventional laparoscopy (4.0% vs 4.8%; odds ratio, .83; 95% CI, .41 to 1.68), whereas the duration of surgery was longer in the single-incision group (46.3 vs 40.7 minutes; weighted mean difference, 6.01; 95% CI, 2.26 to 9.76). Available data were not adequately robust to reach conclusions regarding the remaining outcome measures. CONCLUSIONS: Similar postoperative morbidity and wound infection rates for single-incision and conventional laparoscopic appendectomy are supported by the current literature, but single-incision surgery requires longer operative time. Ó 2014 Elsevier Inc. All rights reserved.
The authors declare no conflicts of interest. * Corresponding author. Tel.: 130-6978-732791; fax: 130-2299068845. E-mail address: [email protected] Manuscript received May 8, 2013; revised manuscript June 28, 2013 0002-9610/$ - see front matter Ó 2014 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.amjsurg.2013.07.045
Laparoscopic surgery through a single incision has evolved with the objectives of minimizing surgical trauma, reducing postoperative pain, shortening convalescence, and providing improved cosmesis. Recent meta-analyses of
614
The American Journal of Surgery, Vol 207, No 4, April 2014
single-incision laparoscopic cholecystectomy have demonstrated similar complication rates to conventional laparoscopy, but they have failed to provide uniform results regarding pain.1,2 Emerging evidence suggests that the appealing idea of minimizing surgical trauma must be weighed against associated direct and indirect risks.3 A systematic review of single-incision laparoscopic cholecystectomy has demonstrated increased risk for common bile duct injuries compared with historic complication rates of conventional cholecystectomy.4 Evidence demonstrates clear superiority of laparoscopic appendectomy over open surgery in terms of wound-related complications, although conflicting data suggest longer operative time for the laparoscopic approach.5,6 Similar operative morbidity for open and laparoscopic appendectomy has
Figure 1
rendered the latter an acceptable alternative. Insufficient high-quality data on single-incision laparoscopic appendectomy exist; nevertheless, many institutions have used the single-incision method outside a frame of randomization.7 A meta-analysis by the Cochrane Collaboration in 2011 could not identify any randomized studies comparing single-incision with conventional laparoscopic appendectomy.8 The aim of the present meta-analysis was to compare outcomes of single-incision laparoscopic appendectomy with those of conventional laparoscopic appendectomy, as expressed by the incidence of postoperative complications, the need for conversion to open surgery, duration of surgery, reoperation rate, overall cost, postoperative pain, and time to resume to normal diet.
Flow diagram of search history. RCT 5 randomized controlled trial.
S.A. Antoniou et al. Table 1
Single-incision vs conventional laparoscopic appendectomy
Study characteristics Year of publication
Country
Participating centers
Period of treatment
Inclusion criteria
2013
Spain
Single center
September 2009 to December 2010
Age .11 y, migrating pain, abdominal defense
Lee et al16 2013
Korea
Single center
March 2010 to September 2011
Study Frutos et al15
615
Sozutek et al17
2013
Turkey
Single center
September 2010 to May 2011
Teoh et al18
2012
China
Single center
October 2009 to March 2011
Spain, Egypt, Turkey
Multicenter
July 2009 to March 2010
Vilallonga 2012 et al19
Exclusion criteria
Cirrhosis, coagulation disorders, abscess or peritonitis, septic shock, contraindication to laparoscopic surgery, contraindication to general anesthesia, pregnancy Refusal of laparoscopic surgery, Age .16 y, migrating abscess, cirrhosis, coagulation pain, nausea, fever disorders, circulatory failure, .38 C or leukocyte contraindication to laparoscopic count .103/mL, guarding, tenderness surgery, contraindication to general anesthesia, pregnancy, neoplasm NR Age ,18 y, ASA score 4 or 5, anticoagulation treatment, absence of macroscopic findings of appendicitis Age 18–75 y, migrating Duration of symptoms .5 d, palpable mass in the right lower quadrant, pain, fever .38 C or cirrhosis, coagulation disorders, leukocyte count abscess or peritonitis, septic shock, .103/mL, guarding, tenderness contraindication to general anesthesia, pregnancy, previous abdominal surgery, ascites, malignancy NR NR
NR 5 not reported.
Methods Eligibility criteria and study selection A protocol was established before initiation of the study to determine the criteria for inclusion, the methods for analysis, and the investigated outcomes. Randomized studies in adult populations comparing single-incision with conventional laparoscopic appendectomy and reporting R1 of the predetermined outcome measures were considered for inclusion. Nonrandomized studies and studies including pediatric patient populations were excluded. The primary outcome Table 2
Patient allocation
Study
Patients Patients Patients Patients completing allocated allocated to included follow-up to SILA CLA
Frutos et al15 Lee et al16 Sozutek et al17 Teoh et al18 Vilallonga et al19
184 248 75* 200 87
184 224 75* 195 87
91 114 25 98 46
93 116 25 97 41
CLA 5 conventional laparoscopic appendectomy; SILA 5 singleincision laparoscopic appendectomy. *Includes a 3rd group of patients allocated to open appendectomy.
measure of the present analysis was the incidence of 30-day morbidity. Secondary outcome measures included the incidence of intra-abdominal abscess, wound infection rate, reoperation rate, conversion to open surgery, duration of surgery, overall cost, time to resume to liquid diet, time to resume to solid diet, length of hospital stay, and postoperative pain (6 to 24 hours after surgery).
Search strategy The electronic database of the National Library of Medicine (MEDLINE; provider Ovid, from 1966 to April 2013) was searched to identify relevant articles. No language restrictions were applied. The Medical Subject Headings ‘‘laparoscopy’’ and ‘‘appendectomy’’ and the terms ‘‘single incision,’’ ‘‘single port,’’ ‘‘single access,’’ ‘‘one access,’’ and ‘‘SILS’’ (single-incision laparoscopic surgery) were used combined with the Boolean operators AND and OR (Appendix). A second-level manual search included the reference lists of the retrieved articles. The last search was run on April 11, 2013. Eligibility assessment was performed independently in an unblinded standardized manner by 2 reviewers. Disagreements between reviewers were resolved by consensus. The literature review conformed to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses standards.9
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Table 3
Quality assessment of included randomized trials
Study
Description of Method of Method of Randomization Randomization Study Study described as double blinding double blinding withdrawal/ Jadad method described as method dropouts? score appropriate? appropriate? double blind? described? randomized? described?
Frutos et al15 Lee et al16 Sozutek et al17 Teoh et al18 Vilallonga et al19
Yes Yes Yes Yes Yes
Yes Yes Yes Yes No
No No No Yes NA
No No No Yes No
NA NA NA Yes NA
NA NA NA Yes NA
Yes Yes Yes Yes Yes
3 3 3 5 2
NA 5 not applicable.
Data collection An electronic data extraction sheet was developed and refined accordingly. One review author extracted the data from included studies, and a second author checked the extracted data. The latter included the name of the primary author, year of publication, country (or countries) of participating institution(s), number of participating centers, patient recruitment period, inclusion and exclusion criteria for patient enrollment in the studies, number of patients assigned to randomization, number of patients having completed follow-up, number of patients allocated to either group, method of closure of the appendiceal stump, method of specimen extraction, and results of the aforementioned outcome measures.
Methods of analysis A fixed-effects model was initially applied to synthesize the data; however, if significant heterogeneity among the included studies was identified, random-effects analysis according to DerSimonian and Laird10 was used. Weighted mean differences (WMDs) with 95% confidence intervals (CIs) were calculated to assess the size of the effect of each type of procedure on continuous variables. Pooled odds ratios (ORs) with 95% CIs were calculated to measure the effect of each type of procedure on categorical variables. Heterogeneity was assessed using the I2 statistic, a method expressing the percentage of variation across
Table 4
studies. I2 values between 0% and 25% suggest low heterogeneity, values .25% suggest moderate heterogeneity, and values .75% suggest high heterogeneity. Publication bias was assessed visually evaluating the symmetry of funnel plots. Statistical analysis was performed using Review Manager version 5.2 (The Nordic Cochrane Centre, Copenhagen, Denmark). Statistical expertise was provided by one of the study authors (G.A.A.).
Methodologic assessment To assess the methodologic quality of eligible randomized controlled trials, respective data from each study protocol were extracted, and the Jadad score was calculated.11 This scoring system takes into account the randomization process, the blind assessment of the outcome, and reporting of withdrawals or dropouts. The minimum score of 1 indicates poor methodologic quality, whereas the maximum score of 5 suggests excellent methodologic quality.
Results Search results and study selection The electronic search identified a total of 192 records. Some 185 articles were discarded on the basis of their titles or abstracts as not relevant studies (n 5 102), studies with pediatric patient populations (n 5 25), review articles (n 5 22), nonrandomized
Outcome data 30-d morbidity
Study 15
Frutos et al Lee et al16 Sozutek et al17 Teoh et al18 Vilallonga et al19
Abdominal abscess
Wound infection
Reoperation
SILA
CLA
SILA
CLA
SILA
CLA
SILA
CLA
4/91 15/114 1/25 14/98 2/46
4/93 18/116 1/25 9/97 0/41
0/91 6/114 0/25 4/98 0/46
0/93 2/116 0/25 9/97 0/41
0/91 6/114 1/25 8/98 0/46
0/93 12/116 1/25 5/97 0/41
0/91 0/114 0/25 NR 0/46
1/93 1/116 0/25 NR 0/41
CLA 5 conventional laparoscopic appendectomy; NR 5 not reported; SILA 5 single-incision laparoscopic appendectomy. *Standard deviation not reported.
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Figure 2 Forest plot of the OR for 30-day morbidity. SILA 5 single-incision laparoscopic appendectomy; CLA 5 conventional laparoscopic appendectomy; M-H 5 Mantel-Haenszel.
lists of the included articles. Finally, a total of 5 randomized trials entered the meta-analytic models (Fig. 1).15–19
Study characteristics and methodologic quality
Figure 3 morbidity.
Funnel plot for the outcome measure 30-day
studies (n 5 17), technical notes (n 5 9), comments (n 5 5), letters (n 5 3), and an article not reporting any of the investigated outcome parameters (n 5 1). A potentially eligible recent randomized trial could not be retrieved from national and international libraries, and the corresponding author did not respond to our request for the full text.12 The reports of 7 randomized trials were retrieved.13–19 Two studies had focused on pediatric patient populations and were therefore excluded.13,14 No additional eligible studies were identified in the reference Table 4
All studies were published in the English language in 2012 and 2013. The number of participating institutions ranged between 1 and 3. Inclusion and exclusion criteria were similar among studies (Table 1). The study population consisted of 794 patients, whereas 765 patients had completed follow-up. The single-incision and conventional laparoscopic groups included 374 and 372 patients, respectively (Table 2). The appendiceal stump was commonly secured using the ENDOLOOP (Ethicon Endo-Surgery, Cincinnati, OH) in both treatment arms, whereas in 4 studies, retrieval bags were used to extract the specimens.15–18 Four studies reported on methods of randomization, but only 1 study was double blinded (Table 3). Jadad scores ranged between 2 and 5, with an overall mean value of 3.2.
Synthesis of results and outcome Summary outcome data are presented in Table 4. No comparative data on hospitalization costs were provided. Furthermore, resumption of oral diet was either not reported15,16 or not specifically documented for liquid or solid diet.17–19 Therefore, the above outcome data could not enter the meta-analysis models.
(continued)
Conversion
Duration of surgery (min), mean 6 SD
Hospital stay (h), mean 6 SD SILA
CLA
SILA
CLA
18.86 6 9.77 72* 1.1 6 0.3 84.72 6 70.08 44.4*
21.32 6 11.72 72* 1.2 6 0.8 76.80 6 56.64 34.0*
2.76 6 1.64 NR 3.4 6 1.0 NR 2.8*
3.78 6 1.76 NR 2.89 6 0.86 NR 2.9*
SILA
CLA
SILA
0/91 0/114 0/25 8/98 1/46
0/93 0/116 0/25 3/97 0/41
38.13 43.8 32.6 63.0 40.4*
CLA 6 6 6 6
13.49 21.3 9.9 27.2
32.12 35.8 29.5 60.2 35.0*
6 6 6 6
12.44 18.9 6.8 31.7
Postoperative pain* (VAS score)
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Figure 4 Forest plot of the OR for abdominal abscess. SILA 5 single-incision laparoscopic appendectomy; CLA 5 conventional laparoscopic appendectomy; M-H 5 Mantel-Haenszel.
Figure 5 Forest plot of the OR for wound infection. SILA 5 single-incision laparoscopic appendectomy; CLA 5 conventional laparoscopic appendectomy; M-H 5 Mantel-Haenszel.
Figure 6 Forest plot of the OR for reoperation. SILA 5 single-incision laparoscopic appendectomy; CLA 5 conventional laparoscopic appendectomy; M-H 5 Mantel-Haenszel.
Thirty-day morbidity. The incidence of 30-day morbidity was 9.6% and 8.6% in the single-incision and conventional laparoscopic groups, respectively (OR, 1.14; 95% CI, .69 to 1.89; P 5 .60; Fig. 2). No significant heterogeneity among the studies was identified (I2 5 0%), and the likelihood of publication bias was low (Fig. 3). Abdominal abscess. Abdominal abscess developed in 2.7% of the single-incision and 1.3% of the conventional laparoscopy patients (OR, 2.06; 95% CI, .69 to 6.11; P 5
.20; Fig. 4). No heterogeneity existed among the studies (I2 5 0%). Wound infection. Surgical-site infections occurred in 4.0% and 4.8% in the single-incision and conventional laparoscopic groups, respectively (OR, .83; 95% CI, .41 to 1.68; P 5 .60; Fig. 5). No heterogeneity among the studies was found (I2 5 0%). Reoperation rate. Two patients in the conventional laparoscopy group underwent reoperation, whereas none of the
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Figure 7 Forest plot of the OR for conversion. SILA 5 single-incision laparoscopic appendectomy; CLA 5 conventional laparoscopic appendectomy; M-H 5 Mantel-Haenszel.
Figure 8 Forest plot of difference in means for operative time. SILA 5 single-incision laparoscopic appendectomy; CLA 5 conventional laparoscopic appendectomy; IV 5 interval.
patients in the single-incision group required reoperation (OR, .34; 95% CI, .03 to 3.26; P 5 .35; Fig. 6). No heterogeneity among the studies was identified (I2 5 0%). Conversion to open surgery. The conversion rates for the single-incision and conventional laparoscopy groups were 2.4% and .8%, respectively (OR, 2.78; 95% CI, .79 to 9.71; P 5 .11; Fig. 7). There was no evidence of heterogeneity (I2 5 0%).
Duration of surgery. The duration of single-incision surgery was an average of 5.6 minutes longer than that of conventional surgery (46.29 vs 40.73 minutes; WMD, 6.01; 95% CI, 2.26 to 9.76; P , .0001; Fig. 8). No significant heterogeneity among the studies was found (I2 5 0%), and the possibility of publication bias was low (Fig. 9). Hospital stay. The length of hospital stay was similar in the single-incision and conventional laparoscopy groups (48.9 vs 45.1 hours, respectively; WMD, 22.19; 95% CI, 25.05 to .68; P 5 .14; Fig. 10). There was no evidence of heterogeneity. Postoperative pain. No significant differences in visual analogue scale score between the 2 groups were identified (3.04 vs 3.41, respectively; WMD, 2.26; 95% CI, 21.76 to 1.24; P 5 .74; Fig. 11). Significant heterogeneity among the studies existed (I2 5 94%).
Comments
Figure 9 Funnel plot for the outcome measure operative time. MD 5 mean difference.
Data derived from randomized trials of single-incision laparoscopic appendectomy are deemed sufficiently robust to support similar 30-day morbidity compared with conventional laparoscopic surgery. An attempt was made to comparatively evaluate the incidence of postoperative abdominal abscess, but only 2 studies reporting on this
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Figure 10 Forest plot of difference in means for hospital stay. SILA 5 single-incision laparoscopic appendectomy; CLA 5 conventional laparoscopic appendectomy; IV 5 interval.
complication could enter the meta-analytic model.16,18 Although there was a trend toward a higher incidence of abdominal abscess for the single-incision group (2.7% vs 1.3%), this difference did not reach statistical significance. An adequate number of studies reported on the duration of surgery; in these terms, individual differences in means were constantly in favor of conventional laparoscopic surgery. This trend has also been confirmed for single-incision laparoscopic cholecystectomy compared with standard laparoscopy3 and may be associated to technical difficulties due to inadequate triangulation, difficulties manipulating laparoscopic instruments, and difficulty managing intraoperative complications. Furthermore, only 2 studies provided adequate data on postoperative pain, rendering comparative evidence of limited importance. Nevertheless, 4 of the 5 studies providing some data on this outcome measure reported no difference between the study groups. The lower incidence of surgical-site infection is one of the primary advantages of laparoscopic appendectomy over conventional surgery. Strong evidence provided by the present meta-analysis does not support lower wound infection rates for single-incision laparoscopic appendectomy. Relevant data were documented by all trials, but 2 studies with zero incidence of wound infection in both arms could not enter the meta-analytic model. It may thus be suggested that reducing the number of access sites in laparoscopic appendectomy does not result in a reduction of wound infection rates. The incidence of incisional hernia
was reported by 3 studies only,15,17,19 thus providing limited comparative evidence. A recent meta-analysis that compared this complication after single-incision or conventional laparoscopic appendectomy found no significant difference between the 2 approaches.3 Furthermore, because of the low frequency of the need for conversion and reoperation, synthesis of the results was inconclusive regarding these outcome measures. Two patients from the conventional laparoscopy group required reoperation (.5%) compared with none in the single-incision group, whereas the respective rates for conversion to open surgery were .8% and 2.4%. A potential significance of the latter result cannot be estimated by the present meta-analytic approach. Randomized studies of single-incision laparoscopic appendectomy were published exclusively within the past 2 years. The overall methodologic quality was fair, but only 1 trial was blinded to patients and assessors. The increasing interest and the limited evidence on single-incision surgery are expected to be expressed by the publication of further data on this field. It is of specific importance for novel trials to be of adequate quality and to report on a wide range of outcome measures, including postoperative pain, cost, time to resume to oral diet, and time of convalescence. Moreover, because the learning curve may have a significant effect on operative time and surgical outcomes, future randomized trials that adequately report on previous surgeons’ experience with single-incision laparoscopy surgery are essential. Furthermore, to detect potential
Figure 11 Forest plot of difference in means for postoperative pain. SILA 5 single-incision laparoscopic appendectomy; CLA 5 conventional laparoscopic appendectomy; IV 5 interval.
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differences in ORs for abdominal abscess and conversion to open surgery, larger patient populations are required. The best evidence suggests similar overall postoperative morbidity and similar wound infection rates for singleincision laparoscopic appendectomy compared with conventional laparoscopy; however, single-incision surgery requires longer operative time. Meta-analytic synthesis of data on other outcome measures was inconclusive. Further randomized trials in this field are warranted.
References 1. Arezzo A, Scozzari G, Famiglietti F, et al. Is single-incision laparoscopic cholecystectomy safe? Results of a systematic review and meta-analysis. Surg Endosc 2013;27:2293–304. 2. Pisanu A, Reccia I, Porceddu G, et al. Meta-analysis of prospective randomized studies comparing single-incision laparoscopic cholecystectomy (SILC) and conventional multiport laparoscopic cholecystectomy (CMLC). J Gastrointest Surg 2012;16:1790–801. 3. Trastulli S, Cirocchi R, Desiderio J, et al. Systematic review and meta-analysis of randomized clinical trials comparing singleincision versus conventional laparoscopic cholecystectomy. Br J Surg 2013;100:191–208. 4. Joseph M, Phillips MR, Farrell TM, et al. Single incision laparoscopic cholecystectomy is associated with a higher bile duct injury rate: a review and a word of caution. Ann Surg 2012;256:1–6. 5. Ohtani H, Tamamori Y, Arimoto Y, et al. Meta-analysis of the results of randomized controlled trials that compared laparoscopic and open surgery for acute appendicitis. J Gastrointest Surg 2012; 16:1929–39. 6. Woodham BL, Cox MR, Eslick GD. Evidence to support the use of laparoscopic over open appendicectomy for obese individuals: a meta-analysis. Surg Endosc 2012;26:2566–70. 7. Pisanu A, Porceddu G, Reccia I, et al. Meta-analysis of studies comparing single-incision laparoscopic appendectomy and conventional multiport laparoscopic appendectomy. J Surg Res 2012;183: e49–59.
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8. Rehman H, Rao AM, Ahmed I. Single incision versus conventional multi-incision appendicectomy for suspected appendicitis. Cochrane Database Syst Rev 2011;7:CD009022. 9. Liberati A, Altman DG, Tetzlaff J, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. BMJ 2009;339:b2700. 10. DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials 1986;7:177–88. 11. 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. 12. Kye BH, Lee J, Kim W, et al. Comparative study between singleincision and three-port laparoscopic appendectomy: a prospective randomized trial. J Laparoendosc Adv Surg Tech A 2013;23: 431–6. 13. Knott EM, Gasior AC, Holcomb III GW, et al. Impact of body habitus on single-site laparoscopic appendectomy for nonperforated appendicitis: subset analysis from a prospective, randomized trial. J Laparoendosc Adv Surg Tech A 2012;22:404–7. 14. St Peter SD, Adibe OO, Juang D, et al. Single incision versus standard 3-port laparoscopic appendectomy: a prospective randomized trial. Ann Surg 2011;254:586–90. 15. Frutos MD, Abrisqueta J, Lujan J, et al. Randomized prospective study to compare laparoscopic appendectomy versus umbilical singleincision appendectomy. Ann Surg 2013;257:413–8. 16. Lee WS, Choi ST, Lee JN, et al. Single-port laparoscopic appendectomy versus conventional laparoscopic appendectomy: a prospective randomized controlled study. Ann Surg 2013;257:214–8. 17. Sozutek A, Colak T, Dirlik M, et al. A prospective randomized comparison of single-port laparoscopic procedure with open and standard 3-port laparoscopic procedures in the treatment of acute appendicitis. Surg Laparosc Endosc Percutan Tech 2013;23:74–8. 18. Teoh AY, Chiu PW, Wong TC, et al. A double-blinded randomized controlled trial of laparoendoscopic single-site access versus conventional 3-port appendectomy. Ann Surg 2012;256:909–14. 19. Vilallonga R, Barbaros U, Nada A, et al. Single-port transumbilical laparoscopic appendectomy: a preliminary multicentric comparative study in 87 patients with acute appendicitis. Minim Invasive Surg 2012;2012:492409.
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Appendix Combination of search terms Search terms: [any A] AND [B] AND [any C] A. 1. single incision 2. single access 3. single port 4. one access 5. SILS B. laparoscopic C. 1. appendectomy 2. appendicectomy
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