Laparoscopic appendectomy with single port vs conventional access: systematic review and meta-analysis of randomized clinical trials

Background Conventional three-access laparoscopic appendectomy (CLA) is currently the gold standard treatment, however, Single-Port Laparoscopic Appendectomy (SILA) has been proposed as an alternative. The aim of this systematic review/meta-analysis was to evaluate safety and efficacy of SILA compared with conventional approach. Methods Per PRISMA guidelines, we systematically reviewed randomised controlled trials (RCTs) comparing CLA vs SILA for acute appendicitis. The randomised Mantel–Haenszel method was used for the meta-analysis. Statistical data analysis was performed with the Review Manager software and the risk of bias was assessed with the Cochrane "Risk of Bias" assessment tool. Results Twenty-one studies (RCTs) were selected (2646 patients). The operative time was significantly longer in the SILA group (MD = 7,32), confirmed in both paediatric (MD = 9,80), (Q = 1,47) and adult subgroups (MD = 5,92), (Q = 55,85). Overall postoperative morbidity was higher in patients who underwent SILA, but the result was not statistically significant. In SILA group were assessed shorter hospital stays, fewer wound infections and higher conversion rate, but the results were not statistically significant. Meta-analysis was not performed about cosmetics of skin scars and postoperative pain because different scales were used in each study. Conclusions This analysis show that SILA, although associated with fewer postoperative wound infection, has a significantly longer operative time. Furthermore, the risk of postoperative general complications is still present. Further studies will be required to analyse outcomes related to postoperative pain and the cosmetics of the surgical scar.

Acute appendicitis is one of the most common abdominal surgical emergencies [1], and conventional three-access laparoscopic appendectomy (CLA) is currently the gold standard treatment [2].However, an alternative surgical approach, Single-Port Laparoscopic Appendectomy (SILA), has been proposed recently [3,4].SILA aims to improve aesthetics, reduce postoperative pain and hospital stay, and thus lead to a faster return to work and improved quality of life.Potential disadvantages of SILA include loss of triangulation, impaired vision, intra/extra abdominal instrument conflicts, and device cost.
Previous literature reviews analysing the results of low-evidence comparative studies (controlled clinical trials-CCTs) have suggested that the two approaches are comparable but have highlighted the need for analyses of randomised controlled trials (RCTs) to suggest which procedure could be the most appropriate [5][6][7].Therefore, we performed a systematic literature review and meta-analysis of RCTs to evaluate the safety and efficacy of single-incision laparoscopic appendectomy (SILA) compared with conventional laparoscopic appendectomy.

Materials and methods
A systematic literature review was conducted until October 2nd 2022, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Extended author information available on the last page of the article guidelines [8].The research was carried out by analysing the MEDLINE, PubMed, Scopus, and Web of Science databases without language constraints.The registration of protocol was performed on PROSPERO (ID registration CRD42020186856).
Combinations of the following search terms were used: "appendectomy" or "appendectomies, " "single-incision laparoscopic surgery (SILS)", or "single-port laparoscopic surgery", or "single-incision laparoscopic appendectomy", or "conventional 3-port laparoscopic appendectomy" or "conventional laparoscopic surgery" or "multi-incision laparoscopic surgery" or "conventional multiport laparoscopic surgery" or "classic laparoscopic surgery" or "conventional laparoscopic appendectomy" or "single incision" or "single trocar" or "single-port" or "single-port laparoscopic" or "conventional laparoscopic" or "triport laparoscopic" or "one-wound laparoscopic, " and "randomised controlled trial" or "randomised" or "placebo." The "Related articles" function of PubMed was used to expand the research and review all eligible studies' reference lists.A manual search was performed through the Google Scholar database to minimise retrieval bias.The search for ongoing clinical studies was performed on ClinicalTrials.gov.
References of all included studies were selected to identify any studies lost during the initial search and were entered into a dataset.
Studies included in this systematic review consider only randomised controlled trials (RCTs) and non-RCTs that have compared conventional laparoscopic appendectomy vs single-port appendectomy for acute appendicitis.
All titles and abstracts were evaluated to identify articles that could be included in the search.Then the full text of these studies was evaluated, and the following information was extracted: year of publication, inclusion criteria, exclusion criteria, and technologies used in the procedure.
The primary outcomes analysed were the following: overall postoperative complications; operative time and incidence of laparotomic conversions.
Secondary outcomes were identified: surgical wound infections; postoperative pain; length of hospital stays, and the cosmetic appearance of skin scars from trocar access holes.In the analysis of the dichotomous variables, the extracted data were evaluated by Risk Ratio (RR), and in the continuous variables, the data were evaluated by weighted mean differences (WMD) [9].
The randomised Mantel-Haenszel method was used for the meta-analysis.The results obtained were reported in Forest Plot.Higgins index (I 2 ), with its 95% confidence intervals and significant levels of Cochrane Q, were considered as indicators of heterogeneity [10].
Statistical data analysis was performed using the Review Manager meta-analysis software (RevMan version 5.4.1)(Copenhagen: The Nordic Cochrane Center, The Cochrane Collaboration, 2018).
Methodological assessment of the risk of bias was performed with the Cochrane "Risk of Bias" assessment tool for randomised control trials (RCTs) [11].

Systematic review results
The PRISMA flow chart for the systematic review is shown in Fig. 1.
The initial literature search identified 1063 potentially relevant articles.After selecting titles and abstracts based on relevance, the remaining 48 articles were further evaluated for eligibility, and 27 others were excluded.The 21 studies included in this meta-analysis are RCTs.

Characteristics of the studies
The 21 studies enrolled 2646 patients with acute appendicitis who have undergone laparoscopic treatment: 1328 SILA and 1318 CLA.Enrolments took place between 2009 and 2018.Most of the studies were performed in populations from Korea (4 RCTs, comprising a total of 551 patients), the USA (3 RCTs, comprising a total of 485 patients), Spain (3 RCTs, comprising a total of 391 patients) and China (3 RCTs, comprising a total of 339 patients); the remaining studies were conducted in Pakistan (340 patients), Argentina (147 patients), India (100 patients), Scotland (77 patients), Japan (68 patients), Turkey (50 patients), Poland (50 patients) and Egypt (48 patients).Fifteen studies reported surgical experience, but the definitions differed between the included studies.
Thirteen studies reported exclusion criteria such as periappendicular abscess and/or mass, generalised peritonitis, appendicular tumour or phlegmon, and perforated appendix; RCTs' criteria were not significantly different.
The patients' ages were heterogeneous, so we performed a subgroup analysis.The clinical characteristics of the patients enrolled in the included studies are summarised in Table 1.
Division of the mesoappendix and section of the base of the appendix was performed with various techniques and tools.The types of single-port and tools used for SILA also varied.The technical characteristics of the surgeries performed in the included studies are summarised in Table 2.
The major number of studies do not report the calculation of sample size estimation of patients for randomised controlled trials [12][13][14][15][16][17][18][19].In few studies the minimal sample size calculation was generically done on the study [20][21][22][23][24]. Differently, other studies [25][26][27][28] reported the same outcome on which was performed the sample size calculation, respectively post-operative complications and postoperative pain; only one study [29] reported respectively the operative time as primary outcome.In conclusion the overall field is underpowered to detect a difference in complications between the two techniques-likely due to the fact that complications are rare.

Study quality assessment
Methodological quality assessment of the RCTs was performed using the RoB 2 (Revised Cochrane risk of bias tool for randomised trials) [30] (Fig. 2).Overall low risk of bias was reported for 71.4% of the studies (15/21), but "blinding" of participants and healthcare personnel was performed in only 2/21 (9.5%) studies [17,27].In 14.3% (3/21) of the studies [15,18,22], the risk of bias of random sequence generation and allocation was rated as severe, while another 14.3% (3/21) [14,21,31] presented some concerns about the risk of bias due to deviation from intended surgeries.

Postoperative pain
Sixteen studies reported results on postoperative pain, but we did not summarise the results because different scales and assessment times were used (Table 3) [4, 12-29, 31, 33].

The aesthetic appearance of skin scars of trocar access holes
Only nine studies reported results on the cosmetic appearance of skin scars of trocar access holes, but meta-analysis was not performed because different scales were used in each study (Table 4) [14,16,18,19,21,23,25,27,31].

Discussion
This systematic review of the literature pooled the results of 21 RCTs (2646 patients enrolled).It showed that SILA is comparable to CLA in treating acute appendicitis and may have some benefits.
The most important limitation of SILA is reported in the characteristics of thirteen included, studies that reported exclusion criteria as appendicular phlegmon, perforated appendicitis and so on.Very probably this limitation could For this reason, SILA needed an extreme accurate selection of patients: uncomplicated appendicitis associated at mild inflammatory status.In fact, the feasibility of SILA can be very low in complicated appendicitis and it is associated with higher rate risk of conversion to laparotomy and at the impossibility to place an abdominal drainage tube [32].
The only significant finding in this analysis are relates to the longer operative time, which increases significantly for SILA, as observed in most single-incision surgeries.In fact, because of intra/extra abdominal instrument conflicts, SILA is relatively difficult to perform, resulting in a significantly longer operative time than CLA.In some studies, a single surgeon performed the procedures [23,31,33], while other methods involved multiple surgeons.Due to differences in surgical experience, this may have influenced the statistical results.Furthermore, this longer operative time can be the consequence of limited manpower and extra time needed for the preparation and manipulation of the camera holder [34].This longer operative time is associated at higher cost [35] and major postoperative pain for muscular stretching at the single umbilical wound [36].
Data regarding overall morbidity showed fewer cases in the CLA (7,22%) group than in the SILA group (7,94%), an advantage especially evident in paediatric patients.However, they showed no statistically significant difference between SILA and CLA (RR = 1,10, 95% CI 0,83 to 1,46; P = 0,52).In contrast, data analysis regarding abdominal wall morbidity, although equally nonsignificant, suggested a lower incidence of postoperative surgical wound infections in patients who underwent SILA.Therefore, SILA can be considered a safe and effective technique.
Hospital stay was lower in patients who underwent SILA.At the same time, the incidence of laparotomy conversions was lower in CLA than in SILA, but the results were not statistically significant in both cases.This heterogeneity of hospital stay is associated with the different timing of oral intake after appendectomy.Previously, the oral intake starts at return of bowel function evaluated during abdominal examination (bowel sound and passage of flatus); differently in other surgical unit with adopted the ERAS program a soft diet is performed as soon as possible (5-7 h post-surgery) independently from the bowel movement [37].
Data on pain were not summarised because of the heterogeneity of scales and assessment times.Although influenced by the above considerations, the RCTs did not show a significantly better outcome regarding postoperative pain or a reduction in the need for analgesics.The same applies to cosmetics data, which are not homogeneous and have yet to be grouped in a forest plot.Cosmetics were assessed in multiple of our studies through fill-in questionnaires based on subjective judgment and not through international rating scales, making cosmetic appearance an impossible outcome to compare.
The financial cost was not compared in the studies included in our meta-analysis.However, it has been pointed Fig. 6 Surgical wound infections out that SILA can be safely performed with the same tools and costs as CLA [29].High-energy dissection instruments, dedicated angled instruments and commercial single-access port devices were widely used in this study, which, having a high cost, could influence the choice between the two operations.The use of conventional instruments, bipolar coagulation for mesoappendix and limited application of endo stapler for stump transection would significantly lower the cost of the operation.In addition, the solution adopted by Kye et al. [26], Duza et al. [14], Shalaby et al. [12], Mo Kang et al. [21], and Park et al. [31] considers the use of a "homemade" port with a latex surgical glove, which would not affect the budget, unlike commercial single-access ports.
A limitation of the analysis is the need for more data examining the learning curve for SILA.In the studies included in our review, the specification of prior training in SILA was quantified only by Teoh et al. [27] and Lee et al. [28], who considered at least 20 and 10 SILA procedures, respectively, to be necessary to ensure competence in SILA.Frutos et al. [4] and Moriguchi et al. [15] described "previous training in SILA" without further specification, as did Mo Kang et al. [21], which reported only minimal experience in SILA.Golebiewsky et al. [20] and Mori et al. [24] described their experience with both surgical techniques.In an analysis of learning curve, Kim suggested that surgeons can have an adequate surgical skills for SILA after performed 30 appendectomy, furthermore other 90 appendectomy are needed to gain an experienced surgical skills [38].
The present meta-analysis is also limited because the results collected were mainly short-term indicators and needed long-term follow-up results.One of these long-term outcomes is port-site incisional hernia.In fact the literature reported a high rate of incisional hernia rate.In a recent systematic review of literature and meta-analysis performed Fig. 7 Length of hospital stay on single-incision laparoscopic, surgery is associated with a threefold increase in the odds of incisional hernia than conventional laparoscopic surgery (odds ratio 2,83, 95% CI 1,34-5,98, P = 0,006, I2 = 0%) [39], similar results were reported from previous review [40,41].For this reason, recommendation to prevent incisional hernias is commonly performed [42].
Moreover, the results included subjective indices such as pain and aesthetic scores, which patients and evaluators easily influence.

Conclusions
In conclusion, this systematic review and meta-analysis show that Single-Port laparoscopic appendectomy do not report any advantage for the SILA, but there is only significantly longer operative time than CLA.Furthermore, it is not free from the risk of postoperative general complications, prolonged hospital stays, and the need for conversion.Probably, the inferiority of SILA than CLA and the complex learning curve are the reasons for which the SILA is uncommon.[27] VAS (graded from 0 to 100) At 24 h NR 0.253 Villalonga et al. [18] VAS (NR) At 12 h 2.9 ± 0.78 2.8 ± 0.9 0.774 St. Peter et al. [33] NR NR NR NR NR Park et al. [31] VAS (graded from 0 to 10) At 1-2 days NR NR NR Further studies will be required to analyse outcomes related to postoperative pain and the cosmetics of the surgical scar and make cost-benefit assessments.

Table 1
Clinical characteristics of the patients included in the selected trials

Table 2
Technical details of the procedures for single-incision laparoscopic appendectomy (SILA) and conventional three-port laparoscopic appendectomy (CLA)

Table 3
Comparison between different scales of postoperative pain VAS, visual analogue scale; NR, not reported; CLA, conventional three-port laparoscopc appendectomy; SILA, single incision laparoscopic appendectomy

Table 4
Comparison between different scales of postoperative cosmesis NR, not recorded; CLA, conventional three-port laparoscopic appendectomy; SILA, single incision laparoscopic appendectomy