Vol 13 No 02 March-April 2016 2590 REVIEW Laparoendoscopic Single-site Adrenalectomy versus Conventional Laparo- scopic Adrenalectomy: An Updated Meta Analysis Shike Wu,1* Hao Lai,1* Jiangyang Zhao,2* Jiansi Chen,1 Xianwei Mo,1 Hongqun Zuo,1** Yuan Lin1** Purpose: Previous meta-analyses that compared the outcome of laparoendoscopic single-site adrenalectomy (LESSA) and conventional laparoscopic adrenalectomy (CLA) have not shown consistent results. The aim of this meta-analysis was to reassess current evidence regarding the efficacy and safety of LESSA versus CLA. Materials and Methods: A literature search of PubMed, Embase, Medline, and the Cochrane Library was performed to identify eligible articles up until September 2015. Quantitative variables were calculated us- ing the weighted mean differences (WMDs), and qualitative variables were pooled using odds ratios (ORs). Results: Ten retrospective studies, including a total of 704 cases, were identified. Patients in the LESSA group benefitted from shorter length of hospital stay (95% confidence interval [CI]: -1.27 to -0.36, WMD: -0.81, P < .001) and better postoperative pain scores (95% CI: -1.51 to -0.99, WMD: 1.25, P < .001). There was no signif- icant difference between the two techniques in operative time, estimated blood loss, resumption of oral intake, dose of analgesic required, perioperative complications, conversion, transfusion, or pain medications required. Conclusion: Based on current evidence, LESSA appear to be a safe and feasible alternative to CLA with a shorter length of hospital stay and lower postoperative pain scores in certain patients. We await high-quality, double-blind randomized clinical trials with long-term follow-up to confirm and up- date the findings of this analysis; future studies should focus on failure of technique, cosmesis, and cost. Keywords: adrenal glands; surgery; adrenalectomy; methods; laparoscopy; treatment outcome; minimally inva- sive surgical procedures. INTRODUCTION With the advent of laparoscopic surgery in the early 1980s, minimally invasive surgery has continued to evolve. Since Gagner first reported lap- aroscopic adrenalectomy (LA) in 1992,(1) laparoscopic surgery for benign adrenal tumors has become the gold standard for treatment.(2,3) Several studies have shown its advantages compared with open adrenalectomy, such as decreased complications, a shorter postopera- tive length of hospital stay, and reduced costs.(4-7) How- ever, the ‘conventional’ laparoscopic approach requires three or four widely spaced access ports, and remains highly invasive. Recently, with the development of lap- aroscopic techniques and instrumentation, as well as surgical experience, a minimally invasive surgery – so- called single-incision laparoscopic surgery (SILS) – has gained popularity as a method of achieving a “scarless” abdomen through a single incision. In 2005, Hirano and colleagues reported the first experience of a single-inci- sion, retroperitoneoscopic, single-port adrenalectomy. (8) Subsequently, laparoendoscopic single-site adrenal- ectomy (LESSA) has been shown to be feasible for the treatment of benign adrenal tumors.(9-11) To date, many studies have been conducted to determine the advantag- es of surgical outcomes of LESSA versus LA.(12-20) Two meta-analyses comparing conventional laparoscopic adrenalectomy (CLA) and LESSA were reported by Hu and colleagues and Wang and colleagues. in 2012,(21,22) 1 Department of Gastrointestinal Surgery, Affiliated Tumor Hospital of Guangxi Medical University Nanning 530021, Guangxi Autonomous Region, China. 2 Department of Clinical Laboratory, Children's Hospital, Maternal and Child Health Hospital of Guangxi Zhuang Autono- mous Region, Nanning 530003, Guangxi , China. *These authors contributed equally to this work and should be considered as co-first authors. **Correspondence: Department of Gastrointestinal Surgery, Affiliated Tumor Hospital of Guangxi Medical University Nan- ning 530021, Guangxi Autonomous Region, China. Tel: +86 0771 5644230. Fax: +86 0771 5312000.E-mail: hongqunzuo@163.com. Department of Gastrointestinal Surgery, Affiliated Tumor Hospital of Guangxi Medical University Nanning 530021, Guangxi Autonomous Region, China. Tel: +86 0771 5330708. Fax: +86 0771 5312000. E-mail: doctoryuanlin@163.com. Received October 2015 & Accepted February 2016 which summarized and reviewed 171 cases of LESSA compared with 272 cases of CLA(12-20) and showed a longer operative time and lower postoperative visual analog pain score in LESSA, and comparable results for complications, time to oral intake resumption, and esti- mated blood loss between the two groups. More recent publications were not investigated in these previous meta-analyses, which remain controversial.(23-25) Thus, there is a need for an updated meta-analysis to reassess the safety and efficacy of the two procedures and to de- termine whether LESSA is an acceptable alternative to CLA for the treatment of benign adrenal tumors. MATERIALS AND METHODS Literature Search A systematic literature search of the Embase, Cochrane, and PubMed databases was performed to identify stud- ies comparing LESSA with CLA (to September 2015). The following medical subject heading (MeSH) terms and words were used in the search, in all possible com- binations: ‘laparoendoscopic,’ ‘single-site,’ ‘single port,’ ‘single incision,’ ‘single access,’ and ‘adrenalec- tomy.’ A second-level search included a manual search of the reference lists of all the relevant studies, system- atic reviews, and previous meta-analyses to identify po- tentially eligible studies. Inclusion and Exclusion Criteria Titles and abstracts of all identified articles were screened and we included studies that satisfied the fol- lowing criteria: (1) compared LESSA and CLA, (2) LESSA performed using laparoscopic or retroperito- neoscopic techniques through a mono port or a single large port (the operative technique can be described as “laparoscopic,” “single-port,” “single-incision,” “mono port,” “single large port ,” “retroperitoneoscopic,” “conventional laparoscopic,” “3-port laparoscopic” or “4-port laparoscopic”), (3) applied the same approach in the CLA and LESSA group, (4) available in full-text, (5) written in English, and (6) reported at least one of the following outcomes: operative time, length of hospital stay, estimated blood loss (EBL), resumption of oral in- take, postoperative pain scores, perioperative complica- tions, conversion, cosmetic satisfaction score, recovery time, convalescence transfusion and pain medication requirement, dose of analgesic required, and interval to return to work/routine activity. If two studies from the same institution were identified, the most recent or most informative was selected (unless they were reports from clearly different periods or data from overlapping patients could be subtracted). Outcome Measures Outcome variables were considered suitable for anal- ysis if they met the following criteria: (1) continuous outcomes reported as means and standard deviations, and (2) identical variables reported by a minimum of two studies. Outcome variables considered most suita- ble for analysis were as follows: operative time, length of hospital stay, EBL, resumption of oral intake, post- operative pain scores, doses of analgesic required, pe- rioperative complications, conversion, transfusion, and pain medication required. If sufficient data were avail- able, perioperative complications were subdivided into postoperative and intraoperative complications. If units used for the end points were not uniform, we attempted to convert them for ease of analysis. Data Extraction and Quality Assessment Data were extracted from each study by two independ- ent reviewers (Shike Wu and Hao Lai); agreement was achieved through discussion when necessary. We did not use any particular method for estimating standard deviations. The following data were extracted: first au- thor, study period, study design, characteristics of study population, indications for surgery, number of subjects operated on with each technique, and perioperative outcomes. All studies were retrospective comparative studies and none was a randomized clinical trial (RCT). According to The Oxford 2011 Levels of Evidence,(26) the Newcastle-Ottawa Quality Assessment Scale was used to assess the quality of studies.(27) This scale con- tains eight items, categorized into three dimensions, selection, comparability, and outcome. A study can be awarded a maximum of one star for each numbered item within the selection and outcome categories and two stars for comparability. A score of 0–9 (as stars) was al- located to each study: studies with a Newcastle-Ottawa score ≥ 6 were considered to be of high quality. Statistical Analysis Statistical analyses were performed using Stata soft- ware (version 12.0; Stata Corp., College Station, TX, USA). For continuous variables, we calculated weight- ed mean differences (WMDs) with 95% confidence in- tervals (CIs). For dichotomous variables, we used odds ratios (ORs) and a fixed-effects model. We used the χ² test and the I² statistic to assess heterogeneity between studies, with a P value of < .05 indicating statistical sig- nificance and the I² statistic > 50% was considered to represent significant heterogeneity. A random-effects model was used if there was significant heterogeneity. Sensitivity and subgroup analyses were used to explore potential causes of heterogeneity. Subgroup analyses were performed to examine whether results that com- Laparoendoscopic Single-site Adrenalectomy-Wu et al. Review 2591 Vol 13 No 02 March-April 2016 2592 pared LESSA with CLA varied by different approaches (transperitoneal and retroperitoneal). Publication bias was evaluated by a funnel plot. RESULTS In total, 122 studies were identified by the electronic searches; no further study was identified through other sources. Figure 1 depicts a Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow chart for study inclusion and exclusion. After re- moving duplicate results, 116 records remained. Of these, on reviewing the titles and abstract, 97 obviously irrelevant articles were rejected. Thus, 19 relevant arti- cles comparing LESSA and CLA were considered suit- able for the pooled analysis. Nine articles (seven with unavailable data and two repeated studies) were exclud- ed by reading the full-text articles.(19,20,28-34) Finally, 10 studies were included in the analysis.(12-18,23-25) The meth- odological quality of the included studies was relatively high, with a score of six or seven stars: the assessment of the included studies is shown in Figure 2. Study and Patient Characteristics The articles included in the quantitative synthesis were published between 2009 and 2014, with a total of 255 First Author Study Design Study Period Country LESSA LESS CL Number Age (years) BMI (kg/m²) LESSA CLA Procedures Device Device LESSA / CLA LESSA / CLA M / F M / F Jeong, 2009 RA 2001-2009 Korea LESSA Umbilicus through 3 or 4 ports 9 / 17 46.0 / 43.8 NA 4 / 5 11 / 6 a 2-cm incision Walz, 2010 RA 2000-2008 Germany SARA Single-access approach 3 ports 47 / 47 43.3 / 42.2 25.1 ± 3.9 / 25.2 ± 3.9 17 / 30 17 / 30 Tunca, 2012 RA 2006-2010 Turkey SILA Through a 2-cm 3 ports 22 / 74 43.3 ± 10 / 43.4 ± 12.3 NA 4 / 18 29 / 45 umbilical incision Lin, 2012 RA 2006-2011 Taiwan LESSA With a 2.- to 3-cm skin 3 or 4 ports 21 / 28 50.7 (34-74) / 51.7 (25-71) 25.6 / 24.6 12 / 9 14 / 14 incision just beneath the tip of the 12th rib Wang, 2012 RA 2009-2011 China LESSA A 2-3-cm through the NA 13 / 26 47.2 ± 9.31 / 43.9 ± 10.27 24.9 ± 3.10 / 25.1 ± 4.16 8 / 5 10 / 16 umbilicus of 8 patients and a 2-3 cm subcostal incision of 5 patients Shi, 2011 RA 2009 China LESS-ARA A 2.5- to 3-cm transverse skin 3 ports 19 / 38 57.0 / 57.0 29.8 / 29.0 8 / 11 21 / 17 incision made below the lower margin of the 12th rib Kwak, 2011 RA 2008-2009 Korea LAMP At 2 fingerbreadths below the 3 ports 12 / 10 51.08 / 43.70 24.08 ± 4.01 / 26.17 ± 3.11 6 / 6 5 / 5 costal margin at the midclavicular line through a 2.5-cm incision. Hirasawa, 2014 RA 2001-2013 Japan LESSA Through the umbilicus or the side 3 or 4 ports 70 / 140 51.2 ± 11.5 / 50.9 ± 11.5 23.0 ± 3.6 / 23.1 ± 3.6 NA NA of the navel to approach the intraperitoneal space Hora, 2014 RA 2008-2014 Czech LESS AE Quadport + in short pararectal NA 15 / 15 59.3 ± 13.3 / 60.2 ± 11.9 26.9 ± 4.3 / 28.5 ± 2.0 NA NA incision OR in the subcostal region, an additional 3 mm grasper Wen, 2013 RA NA Taiwan LESSRA A 3-cm skin incision below the 3 ports 27 / 54 48.79 ± 1.69 / 49.62 ± 2.39 24.55 ± 6.37 / 25.20 ± 4.43 14 / 13 32 / 22 tip of the 12th rib Table 1. Characteristics of included studies. Abbreviations: RA, retrospective analysis; LESS, laparoendoscopic single-site; CL, conventional laparoscopic; LESSA, laparoendoscopic single-site adrenalectomy; LESSAE or LESS-ARA or LESS RA, laparoendoscopic single-site retroperitoneoscopic adrenalectomy; LAMP, laparoscopic adrenalectomy through mono port; SILA, single-incision laparoscopic adrenalectomy; SARA, single-access retroperitoneoscopic adrenalectomies; CLA, conventional laparoscopic adrenalectomy; BMI, body mass index; M, male; F, female; NA, not available; R, right; L, left. All values are number or mean ± SD or mean. Laparoendoscopic Single-site Adrenalectomy-Wu et al. patients treated with LESSA and 449 patients treated with CLA. The sample size of the trials ranged from 9 to 140. Characteristics of the patients are summarized in Table 1. For LESSA, a commercially available mul- ti-channel port device was used.(15-18,24,25) In one study, a home-made single-port device was inserted at the um- bilicus through a 2-cm incision: a single-layered sterile surgical glove was then used.(13,23) One study used a sin- gle glove or commercially available multi-channel port. (14) The umbilicus or subcostal incision represented the most used access site. For CLA, three or four ports were made. Both transperitoneal and retroperitoneal access approaches were reported. Histopathological data of the adrenal adenomas are summarized in Table 2. Outcome Measurements Operative time All included studies reported operative time;(12-18,23-25) three were not reported as means and standard devi- ations and were excluded.(12,14,15) Subgroup analyses showed no significant difference in the retroperitoneal (RE) group (95% CI: -13.18 to 17.85, WMD: 2.33, P = .768) or the transperitoneal (TR) group (P = .148). The overall pooled estimates also support this finding be- tween the two groups (95% CI: -2.94 to 13.92, WMD: 5.49, P = .202; I² = 64.1%, P = .010 for heterogeneity; Figure 3A). Table 2. Histopathological data of the adrenal adenomas. First Author No. LESSA / CLA FA NFA CS PH HY APA CSD Metastasis AC Myelolipoma MH PCS Others Jeong, 2009 9 / 17 NA 3 / 6 1 / 2 5 / 9 NA NA NA NA NA NA NA NA 1 / 0 Walz, 2010 47 / 47 NA NA 6 / 6 15 / 15 NA NA 20 / 20 NA NA NA NA NA 6 / 6 Tunca, 2012 22 / 74 NA 3 / 17 7 / 18 8 / 26 NA NA NA 0 / 3 0 / 3 NA NA NA 4 / 7 Lin, 2012 21 / 28 11/19 7 / 4 NA 3 / 5 NA NA NA NA NA NA NA NA NA Wang, 2012 13 / 26 NA 6 / 7 2 / 6 0 / 3 5 / 10 NA NA NA NA NA NA NA NA Shi, 2011 19 / 38 NA 5 / 7 4 / 11 3 / 5 7 / 15 NA NA NA NA NA NA NA NA Kwak, 2011 12 / 10 3/5 NA 3 / 1 2 / 0 1 / 4 NA NA 0 / 1 NA 1 / 0 0 / 1 NA NA Hirasawa 2014 70 / 140 NA NA 6 / 36 15 / 24 NA 35 / 67 NA NA NA NA NA NA 14 / 13 Hora, 2014 15 / 15 10/12 NA NA 3 / 2 NA NA NA 2 / 1 NA NA NA NA NA Wen, 2013 27 / 54 NA 11 / 12 4 / 7 0 / 1 NA NA 10 / 30 0 / 1 NA NA NA NA 2 / 3 Abbreviations: No., numbers; FA, functional adenoma; NFA, nonfunctioning adenoma; CS, Cushing’s syndrome; APA, aldosterone-producing adenoma; PH, pheochromocyto- ma; CSD, Conn’s syndrome; AC, adrenal cyst; HY, hyperaldosteronism; MH, medullary hyperplasia; PCS, Pre-Cushing’s syndrome; NA, not available. Figure 1. Flow diagram of the literature search. Figure 2. Quality assessment of included studies with the Newcastle-Ot- tawa scale. Laparoendoscopic Single-site Adrenalectomy-Wu et al. Review 2593 Vol 13 No 02 March-April 2016 2594 Length of Hospital Stay Six studies reported the length of hospital stay.(13,16- 18,23,24) Subgroup analyses showed significant differ- ences in the RE group (95% CI: -1.50 to -0.34, WMD: -0.92, P = .002); however, there was no significant dif- ference in the TR group (95% CI: -1.59 to 0.35, WMD: 0.62, P = .221) The overall pooled estimates showed significant difference between the two groups (95% CI: -1.27 to -0.36, WMD: -0.81, P < .001; I² = 59.0%, P = .032 for heterogeneity; Figure 3B). EBL Five studies reported EBL.(16,18,23-25) Subgroup analyses showed no significant difference in the RE group (95% CI: -4.33 to -37.69, WMD: 16.68, P = .120) or the TR group (P = .341). The overall pooled estimates also sup- ported this finding between the two groups (95% CI: -10.68 to 24.19, WMD: 6.76, P = .448; I² = 0.0%, P = .435 for heterogeneity; Figure 3C). Resumption of Oral Intake Seven studies reported resumption of oral in- take(12-15,18,23,24) of which four included standard mean difference values.(13,18,23,24) Subgroup analyses showed no significant difference in the RE group (95% CI: -0.05 to 0.05, WMD: -0.00, P = .867); however, there was a significant difference in the TR group (95% CI: -0.78 to -0.32, WMD: -0.55, P < .001). The overall pooled estimates showed no significant difference between the two groups (95% CI: -0.47 to 0.12, WMD: -0.17, P = .240; I² = 86.3 %, P < .001 for heterogeneity). Postoperative Pain Scores Two studies were available for analysis.(16,18) Subgroup analyses showed significant differences in the RE group (95% CI: -1.51 to -0.95, WMD: -1.23 P < .001) and the TR group (P < .001). The overall pooled estimates also supported this finding between the two groups (95% CI: -1.51 to -0.99, WMD: -1.25, P < .001; I² = 0.0%, P = .663 for heterogeneity; Figure 3D). Doses of Analgesic Required Two studies reported the doses of analgesic required. (23,24) Subgroup analyses showed no significant differ- ence in the RE group (95% CI: -0.41 to 0.41, WMD: 0.00, P = 1.000) or the TR group (P = .098). The over- all pooled estimates also supported this finding between the two groups (95% CI: -0.44 to 0.10, WMD: -0,17, P = .210; I² = 14.5%, P = .279 for heterogeneity). Pain Medication Requirement Three studies including 183 patients reported pain med- ication requirements.(15,17,18) There were 41 patients who needed pain medication (51.90%) in the LESSA group and 57 (54.81%) in the CLA group. Subgroup analyses showed no significant difference in the RE group (95% CI: 0.65 to 2.83, WMD: 1.36, P = .414) or the TR group Figure 3. A) Forest plot of the comparison of LESSA versus CLA in terms of operative time; B) Forest plot of the comparison of LESSA vs. CLA in terms of length of hospital stay; C) Forest plot of the comparison of LESSA vs. CLA in terms of estimated blood loss (EBL); D) Forest plot of the comparison of LESSA vs. CLA in terms of postoperative pain scores. Abbreviations: LESSA, laparoendoscopic single-site adrenalectomy; CLA, conventional laparoscopic adrenalectomy; EBL, estimated blood loss. Figure 4. A) Forest plot of the comparison of LESSA vs. CLA in terms of perioperative complications; B) Forest plot of the comparison of LESSA vs. CLA in terms of conversion; C) Forest plot of the comparison of LES- SA vs. CLA in terms of transfusion. Abbreviations: LESSA, laparoendoscopic single-site adrenalectomy; CLA, conventional laparoscopic adrenalectomy. Laparoendoscopic Single-site Adrenalectomy-Wu et al. (P = .801). The overall pooled estimates also supported this finding between the two groups (95% CI: 0.16 to 4.88, OR: 0.87, P = .875; I² = 72.2%, P = .027 for het- erogeneity). Perioperative Complications The incidence of perioperative complication was re- ported in seven studies.(12-15,17,18,24) There were 13 com- plications (7.34%) in the LESSA group and 22 (6.54%) in the CLA group. Subgroup analyses showed no sig- nificant difference in the RE group (95% CI: 0.28 to 3.44, WMD: 0.99, P = .985) or the TR (P = .578). The overall pooled estimates also supported this finding (95% CI: 0.58 to 2.39, OR: 1.17, P = .659; I² = 0.0%, P = .719 for heterogeneity; Figure 4A). Conversion Three studies including 330 patients reported con- version events.(12,17,24) The conversion rate was 3.97% (5/126 patients) for LESSA compared with 0.98% (2/202 patients) for CLA. Subgroup analyses showed no significant difference in the RE group (95% CI: 0.51 to 187.87, WMD: 9.83 P = .129) or the TR group (P = .882). The overall pooled estimates also supported this finding between the two groups (95% CI: 0.70 to 13.55, OR: 3.07, P = .139; I² = 0.0%, P = .458 for heterogene- ity; Figure 4B). Transfusion Three studies including 275 patients reported transfu- sion in the TR group only.(12,18,24) There was one (1.09%) transfusion in the LESSA group and three (1.64%) in the CLA group; a pooled analysis showed no significant difference (95% CI: 0.17 to 5.43, OR: 0.96, P = .964; I² = 0.0%, P = .808 for heterogeneity) between the two groups (Figure 4C). Risk of Publication Bias A funnel plot of the studies included in our primary out- come of perioperative complications was prepared to explore publication bias. The scatter-distributed shapes of the funnel plots for operative time and perioperative complications were symmetrical, indicating no evi- dence of publication bias among the included studies (Figures 5A and 5B; other data not shown). Sensitivity Analysis Sensitivity analysis was conducted to assess the effect of study quality. A single study involved in the me- ta-analysis was deleted each time to reflect the influ- ence of each individual data set on the pooled ORs. The corresponding pooled ORs were essentially unaltered, indicating that our results were statistically sound (Figures 5C and 5D; other data not shown). DISCUSSION This meta-analysis of 10 retrospective comparative studies including 704 patients showed that LESSA had similar outcomes to those of CLA, without significant differences in terms of operative time, EBL, doses of analgesic required, perioperative complications, con- version, transfusion, resumption of oral intake, or pain medication requirement. LESSA was also associated with reduced postoperative pain and a shorter length of hospital stay, despite controversies with respect to operative time and length of hospital stay in previous meta-analyses. Indeed, previous meta-analyses demonstrated a signif- icantly increased operating time for SILS.(21,22) Those results were inconsistent with the results of this anal- ysis, which concluded that there was no difference be- tween the two groups. In our meta-analysis, five stud- ies reported a prolonged operating time in the LESSA group,(13,17,18,24,25) but two showed the opposite.(16,23) A sensitivity analysis of the pooled studies showed a con- sistent result. However, different sides of surgery and the various designs of ports (transperitoneal and retro- peritoneal) may have great impacts on operative time. Only one study reported operative time on different sides,(25) so no subgroup analysis on different sides could be conducted. Also, an additional trocar was required Figure 5. A) Funnel plot for operative time; B) Funnel plot for perioper- ative complications; C) Sensitivity analysis for operative time; D) Sensi- tivity analysis for perioperative complications. Laparoendoscopic Single-site Adrenalectomy-Wu et al. Review 2595 Vol 13 No 02 March-April 2016 2596 for liver retraction in three studies,(16,18,25) which may have increased operative time. In addition, this differ- ence in operative time may be due to the learning curve; unfortunately, only one study explicitly described the previous experience of the operating surgeons,(24) so a subgroup analysis could not be perform on this issue. Furthermore, the sample size in each study was differ- ent. All these factors may have contributed to heteroge- neity and influenced the results. Thus, future RCTs are needed to confirm the finding of this study. Considering the similar operative times, which is a surprising result, confirming a clear learning-curve effect in the LESSA treatment group, and the ability of surgeons in using the new devices for LESSA, will likely reduce the technical difficulties.(35) Postoperative pain is another important endpoint. Less pain was expected in the LESSA group for reduced tro- cars. However, the size of the fascial incision needed to accommodate the single-incision port may potentially increase pain, although there was no difference in the numbers of patients demanding pain medication and analgesics between the groups. Only two studies pro- vided adequate data on postoperative pain,(16,18) provid- ing comparative evidence of limited importance. This observation should be regarded with caution because different or unclear postoperative analgesic protocols between groups may have led to bias in postoperative pain score assessment. Additionally, a lack of evaluator and patient blinding may have influenced the results. The shorter length of hospital stay is an apparent ad- vantage of LESSA over CLA, in contrast to a previous meta-analysis.(22) The result is encouraging, because it may reflect faster convalescence and less postoperative pain. In turn, this could decrease hospital costs and may be an important factor for recovery and an earlier return to work. Only one study reported that patients could re- turn to full activities earlier in the LESSA group; more randomized trials are needed to confirm this.(18) The pooled studies showed no difference in EBL be- tween the two groups.(16,18,23-25) Four studies reported the resumption of oral intake, which showed no signif- icant between the groups, although heterogeneity was observed. A study by Wen and colleagues reported a shorter period before resumption of oral intake in the LESSA group;(23) excluding this study from the analysis did not yield different results. Surgical safety was evaluated in terms of perioperative complications, conversion, and transfusion. The com- plication rate is broadly considered as a surrogate for surgical competence. LESSA is technically more dif- ficult to perform and may be associated with increased complication rates. Of the included eight studies, five showed a higher perioperative complication rate in LESSA group,(12,13,15,18,25) although different approaches may have different impacts on perioperative compli- cations. When we divided the surgeries into two ap- proaches, transperitoneal and retroperitoneal, subgroup analyses showed no significant difference between the groups (P = .659), similar to the previous meta-analy- ses.(21,22) However, given the different sample sizes in each included study, this result should be viewed with caution; reduced triangulation, fog evacuation, clash- ing of instruments, and more complex procedures in the LESSA group(36) – and the longer operative time – may also increase perioperative complications. The follow-up was insufficient in most of these studies for estimating late complications. Future randomized tri- als with larger samples and longer-term follow-up are needed to evaluate the rate of complications accurately. Conversion is considered to be a significant factor when counseling patients on the potential risks/benefits of any specific procedure.(37) Technological difficulties may also be associated with conversion. The increasing con- version rate has considerably limited the use of LES- SA, although in the present study, the conversion rate was found to be similar for both techniques. Bleeding requiring transfusion was reported in three studies; the pooled studies showed no difference in transfusion be- tween the two techniques.(12,18,24) Considering the peri- operative complications, high-quality and double-blind RCTs with long-term follow-up are required to assess the safety of the new technique. A previous meta-analysis demonstrated comparable cosmetic satisfaction between the two groups.(22) How- ever, a recent study reported higher cosmetic satisfac- tion among young patients and female patients in the LESSA group.(31) Of the included studies, only one re- ported the outcomes as means and standard deviation,(18) so a meta-analysis of cosmetic satisfaction scores was not conducted. In the included studies, there was no significant differ- ence between the LESSA and CLA groups in terms of basic data such as body mass index (BMI), age, gen- der, or tumor size, suggesting that our analysis may be more reliable than those of the former studies by re- ducing the influence of these confounding factors on the results. Nevertheless, our present meta-analysis had several potential limitations. First, all included studies were retrospective analyses and most had a small sam- ple size. Second, a cost analysis to determine whether this new technique is more expensive could not be con- ducted due to insufficient data from the published re- Laparoendoscopic Single-site Adrenalectomy-Wu et al. ports. Third, heterogeneity was found in operative time, length of hospital stay, resumption of oral intake, and pain medication requirement, which may be attributable to matching criteria, operative techniques, single-port access devices, and different approaches; further stud- ies are required to explore sources of heterogeneity. Finally, the follow-up periods in most reports were in- sufficient; the studies analyzed here provided relatively short-term findings, so long-term outcomes of LESSA compared with CLA are required to confirm the safety and feasibility of this new technique. CONCLUSIONS In conclusion, based on current evidence, LESSA ap- pear to be a safe and feasible alternative to CLA with a shorter length of hospital stay and reduced postopera- tive pain scores in certain patients. We await high-qual- ity, double-blind RCTs with longer-term follow-up to confirm and update the findings of this analysis. Future studies should focus particularly on rates of technical failure, cosmesis, and cost. ACKNOWLEDGMENTS Shike Wu, Hao Lai, and Jiangyang Zhao contributed equally to this work and should be considered as co- first authors. CONFLICT OF INTEREST None declared. REFERENCES 1. Gagner M, Lacroix A, Bolte E. Laparoscopic adrenalectomy in Cushing's syndrome and pheochromocytoma. N Engl J Med. 1992;327:1033. 2. Smith CD, Weber CJ, Amerson JR. Laparoscopic adrenalectomy: new gold standard. World J Surg. 1999;23:389-96. 3. Arslan M, Akin Y, Ates M, et al. Changing surgical approaches for laparoscopic adrenalectomy: single-surgeon data of a 6-year experience. 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