Laparoendoscopic single-site (LESS) vs laparoscopic living-donor nephrectomy: a systematic review and meta-analysis Riccardo Autorino*†, Luis Felipe Brandao*, Bashir Sankari*‡, Homayoun Zargar*, Humberto Laydner*, Oktay Akça*, Marco De Sio†, Vincenzo Mirone§, Shih-Chieh J. Chueh* and Jihad H. Kaouk* *Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH, USA, †Urology Unit, Second University of Naples, §Urology Unit, Federico II University, Naples, Italy, and ‡Department of Surgical Subspecialties, Cleveland Clinic Abu Dhabi, Abu Dhabi, UAE
The aim of this study was to provide a systematic review and meta-analysis of reports comparing laparoendoscopic single-site (LESS) living-donor nephrectomy (LDN) vs standard laparoscopic LDN (LLDN). A systematic review of the literature was performed in September 2013 using PubMed, Scopus, Ovid and The Cochrane library databases. Article selection proceeded according to the search strategy based on Preferred Reporting Items for Systematic Reviews and Meta-analyses criteria. Weighted mean differences (WMDs) were used to measure continuous variables and odds ratios (ORs) to measure categorical ones. Nine publications meeting eligibility criteria were identified, including 461 LESS LDN and 1006 LLDN cases. There were more left-side cases in the LESS LDN group (96.5% vs 88.6%, P < 0.001). Meta-analysis of extractable data showed that LLDN had a shorter operative time (WMD 15.06 min, 95% confidence interval [CI] 4.9–25.1; P = 0.003), without a significant difference in warm ischaemia time (WMD 0.41 min, 95% CI –0.02 to 0.84; P = 0.06). Estimated blood loss was lower for LESS LDN (WMD −22.09 mL, 95% CI –29.5 to –14.6; P < 0.001); however, this difference was not clinically significant. There was a greater likelihood of conversion for
Introduction Living-donor transplantation is established as the optimal treatment for end-stage renal failure [1]. Historically, living-donor nephrectomy (LDN) has been performed as an open technique. However, this is potentially associated with prolonged convalescence, which could be regarded as a disincentive to donation. Thus, over the last two decades, surgical practice has developed with the aim of speeding donor postoperative recovery, while maintaining
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LESS LDN (OR 13.21, 95% CI 4.65–37.53; P < 0.001). Hospital stay was similar (WMD –0.11 days, 95% CI –0.33 to 0.12; P = 0.35), as well as the visual analogue pain score at discharge (WMD –0.31, 95% CI –0.96 to 0.35; P = 0.36), but the analgesic requirement was lower for LESS LDN (WMD –2.58 mg, 95% CI –5.01 to –0.15; P = 0.04). Moreover, there was no difference in the postoperative complication rate (OR 1.00, 95% CI 0.65–1.54; P = 0.99). Renal function of the recipient, as based on creatinine levels at 1 month, showed similar outcomes between groups (WMD 0.10 mg/dL, –0.09 to 0.29; P = 0.29). In conclusion, LESS LDN represents an emerging option for living kidney donation. This procedure offers comparable surgical and early functional outcomes to the conventional LLDN, with a lower analgesic requirement. However, it is more technically challenging than LLDN, as shown by a greater likelihood of conversion. The role of LESS LDN remains to be defined.
Keywords donor nephrectomy, laparoscopic, laparoendoscopic single-site surgery, meta-analysis
transplant quality, from the standard open lumbotomy, through mini-incision muscle-splitting open LDN [2], to minimally invasive techniques, including standard laparoscopy [3], hand-assisted laparoscopy [4], and retroperitoneoscopy [5]. More recently, novel minimally invasive techniques have been introduced in this setting, e.g. laparoendoscopic single-site surgery (LESS) [6], natural orifice transluminal endoscopic surgery (NOTES)-assisted laparoscopy [7,8], mini-laparoscopy [9], and robot-assisted laparoscopy [10]. © 2014 The Authors BJU International © 2014 BJU International | doi:10.1111/bju.12724 Published by John Wiley & Sons Ltd. www.bjui.org
LESS LDN vs conventional laparoscopic LDN
Since its introduction, laparoscopic LDN (LLDN) has been widely implemented, and current evidence suggests that laparoscopic techniques result in less postoperative pain and estimated blood loss (EBL) with a shorter hospital stay, while postoperative graft function is not inferior to that of open LDN [11]. Despite its worldwide adoption for a wide variety of indications [12], the role of LESS in the field of minimally invasive urological surgery remains to be defined and the technique is still far from being regarded as a new standard approach, as novel technological developments are awaited to foster its application [13]. In a recent systematic review and meta-analysis of studies comparing laparoscopic and LESS nephrectomy, including over 1000 cases, Fan et al. [14] showed that LESS patients benefit from less postoperative pain, lower analgesic requirement, shorter hospital stay, faster recovery time, and not surprisingly, a better cosmetic outcome. There were no significant differences in other main surgical outcomes and postoperative renal function. Nevertheless, the authors found that LESS takes more operative time and the procedure carries a greater chance of conversion. Application of LESS to donor nephrectomy poses unique challenges and risks. However, the concept of minimising the skin incision in a healthy (and frequently young) individual is appealing and can be regarded as a potential incentive to organ donation. The aim of the present study was to review systematically the available evidence comparing the outcomes of LESS with those of conventional LLDN.
Materials and Methods Literature Search and Study Selection A systematic review of the literature was performed in September 2013 using PubMed, Scopus, Ovid and The Cochrane Library databases, to identify relevant studies. Three separate searches were done by applying a free-text protocol with the following search terms: ‘single site donor nephrectomy’, ‘LESS donor nephrectomy’ and ‘laparoscopic donor nephrectomy’. Article selection proceeded according to the search strategy based on Preferred Reporting Items for Systematic Reviews and Meta-analyses criteria (PRISMA, www. prismastatement.org) (Fig. 1). Only studies comparing LESS and laparoscopic techniques were included for further screening. In addition, cited references from the selected articles retrieved in the search were assessed for significant papers. Conference abstracts were not included because they were not deemed to be methodologically appropriate.
Study Quality Assessment The level of evidence was rated for each included study according to the criteria provided by the Centre for Evidence-Based Medicine in Oxford, UK (www.cebm.net). The methodological quality of the studies was assessed by using the Newcastle-Ottawa Scale for non-randomised controlled trials (RCTs; consisting of three factors: patient selection, comparability of the study groups, and assessment of outcome; score of 0–9 allocated as stars, with studies achieving six or more stars considered to be of high quality) [15] and the Jadad scale for RCTs (score ranging between 0 and 5, with 0–2 being low, 3–5 high) [16]. Data Extraction and Outcomes of Interest Two reviewers reviewed the full texts of the included studies. Data were extracted from each eligible study. Demographic characteristics were compared including: age, body mass index (BMI), gender and side of procedure. Perioperative outcomes between the two procedures were compared using operative time, EBL, hospital length of stay, analgesic requirements (calculated in terms of morphine equivalents), visual analogue scale of pain at discharge, complication rate, conversion rate (defined as conversion to reduced port laparoscopy, conventional laparoscopy or open surgery), warm ischaemia time (WIT) and postoperative graft function as based on serum creatinine measurement at 1 month. Postoperative complications were graded according to the Clavien-Dindo system [17]. Statistical Analysis A meta-analysis was performed to assess the outcomes of LESS donor nephrectomy when compared with laparoscopy. Odds ratios (ORs) or risk ratios were used for binary variables while the mean differences or weighted mean differences (WMDs) were used for the continuous variables. For studies presenting continuous data as means and ranges, the standard deviations (SD) were calculated using the method described by Hozo et al. [18]. Pooled estimates were calculated with fixed-effect model (Mantel–Haenszel method) [19] if no significant heterogeneity was detected; otherwise, the random effect model (DerSimonian–Laird method) was used [20]. The pooled effects were determined by the Z-test, and a P < 0.05 was considered to indicate statistical significance. The Cochrane chi-square test and inconsistency (I2) were used to evaluate the heterogeneity between all studies. Data analysis was performed using the Review Manager software (RevMan 5.1, Cochrane Collaboration, Oxford, UK). © 2014 The Authors BJU International © 2014 BJU International
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Fig. 1 Preferred reporting items for systematic reviews and meta-analysis flow of study selection.
IDENTIFICATION
Search engines: PubMed, SCOPUS, OVID, THE COCHRANE LIBRARY Search date: 1 September 2013 Search terms: ‘Single Site Donor Nephrectomy’; ‘LESS Donor Nephrectomy’; ‘Laparoscopic Donor Nephrectomy’
ELIGIBILITY
SCREENING
Records after duplicates removed: n=30
Records excluded (n=19): - not specifically related to LDN (n=2) - review articles (n=6) - non-comparative studies (n=11)
Records screened based on title and abstracts: n=29
Records excluded (n=1) comparative data from same institution with overlapping dataset (n=1)
Full-text articles assessed for eligibility: n=10
INCLUDED
Additional records identified through reference lists (n=0)
Studies included in the analysis (n=9)
Results
Surgical Techniques
Description of Included Studies and Quality Assessment
Various surgical techniques have been adopted to perform LESS LDN (Table 1). In most of them, a commercially available multi-channel port was used, whereas in two studies a ‘single-site’ approach was adopted. The umbilicus represented the most used access site. Accessory needle-scopic or mini-laparoscopic ports were used selectively. A flexible-tip scope was preferred by most of the investigators, whereas articulating instruments were not used in five of the studies.
Nine studies were selected for the analysis, including overall 1467 patients who underwent a LDN procedure for kidney transplantation. Of them, 461 (31.5%) were LESS LDN cases and 1006 (68.5%) were conventional LLDN cases. Seven of the included studies were observational retrospective comparative studies. Four of them were observational retrospective and consecutive studies (level of evidence 3a) [21–24], while three of them were observational retrospective non-consecutive comparative studies (level of evidence 3b) [25–27]. Two of the studies were classified as RCTs (level of evidence 2b) [28,29]. The methodological quality of included studies was relatively high, as summarised in Table 1.
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Patient Demographics There were no differences between the LESS LDN and the LLDN group for age [mean (SD) 43.4 (2.71) vs 41.1 (5.65) years; P = 0.27), male gender (34.7% vs 33%; P = 0.30) and BMI [mean (SD) 26.15 (1.89) vs 26.12 (1.54) kg/m2; P = 0.92).
LESS LDN vs conventional laparoscopic LDN
Table 1 Characteristics and quality assessment of the included studies. Study
LOE
Study design
Quality score
Number of patients LESS LDN
Afaneh et al. [22] Andonian et al. [25] Barth et al. [27] Canes et al. [21] Lunsford et al. [23] Ramasamy et al. [24] Stamatakis et al. [26] 3 mm for liver retraction Kurien et al. [28] Richstone et al. [29]
3a 3b 3b 3a 3a 3a 3b
CRS NCR NCR CRS CRS CRS NCR
6 out of 9 ★ 6 out of 9 ★ 5 out of 9 ★ 6 out of 9 ★ 6 out of 9 ★ 6 out of 9 ★ 6 out of 9 ★
2b 2b
RCT RCT
3 out of 5 points 4 out of 5 points
LESS technique
Incision site
Multichannel port
Selective use of one extra port
LLDN
50 6 135 17 10 101 102
50 6 100 17 20 663 111
Single-port Single-site Single-port Single-port Single port Single-port Single-port
Umbilicus Pfannenstiel Umbilicus Umbilicus Umbilicus Umbilicus Umbilicus
Gelpoint None Various* R-port Gelport Gelpoint Gelpoint
No No 2 mm, for retraction 2 mm, for retraction No No 5 mm for dissection,
25 15
25 14
Single-port Single-site
Umbilicus Pfannenstiel
R-port None
3 mm, for retraction No
LOE, level of evidence; CRS, consecutive retrospective study; NCR, non-consecutive retrospective study. Newcastle Ottawa Scale used to assess non-RCTs; Jadad scale to assess RCTs (see methods).*SILS, Gelpoint, Gelport, SSL port, Quadport.
Fig. 2 Forrest plot – analysis of operative time.
Study or Subgroup Afaneh 2011 Andonian 2010 Barth 2013 Canes 2009 Kurien 2011 Lunsford 2011 Ramasamy 2011 Richstone 2013 Stamatakis 2013
Favours [LESS] Mean SD Total 166 28.7 50 142 36 6 216 48 135 269 86 17 172.2 38.4 25 179 9.8 10 156 47.8 101 143 32 15 206 33.8 102
Favours [Laparoscopic] Mean SD Total 129 29.8 50 117 18.3 6 204 36 100 239 54 17 175.8 47.6 25 186.5 34.8 20 148 69 663 128 28 14 181 28.4 111
Total (95% CI) 461 Heterogeneity: Tau2 = 150.46; Chi2 = 30.59, df = 8 (P < 0.001); I2 = 74% Test for overall effect: Z = 2.92 (P = 0.003)
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Weight 14.4% 6.3% 14.7% 3.5% 8.9% 12.0% 14.7% 9.7% 15.7%
Mean Difference IV, Random, 95% CI 37.00 [25.53, 48.47] 25.00 [–7.31, 57.31] 12.00 [1.26, 22.74] 30.00 [–18.27, 78.27] –3.60 [–27.57, 20.37] –7.50 [–23.92, 8.92] 8.00 [–2.70, 18.70] 15.00 [–6.85, 36.85] 25.00 [16.58, 33.42]
100.0%
15.06 [4.96, 25.17]
Mean Difference IV, Random, 95% CI
–100
–50 0 50 100 Favours [LESS] Favours [Laparoscopy]
There were significantly more left-side LDNs in the LESS group (96.5% vs 88.6%, P < 0.001).
groups, but LESS LDN was associated with a lower analgesic requirement (WMD –2.58 mg; 95% CI –5.01 to –0.15; P = 0.04; Fig. 8).
Perioperative Outcomes
There were no significant difference in postoperative complication rates (OR 1.00, 95% CI 0.65–1.54; P = 0.99; Fig. 9). Most of postoperative complications were minor (Clavien grade I or II); 84.2% in the LESS LDN group and 79.8% in the LLDN group.
There was a significant shorter operative time in the LLDN group (WMD 15.06 min, 95% CI 4.96–25.17; P = 0.003; Fig. 2), whereas there was a significant lower EBL in the LESS LDN group (WMD –22.09 mL, 95% CI –29.52 to –14.66; P < 0.001; Fig. 3). There were no significant differences in the WIT (WMD 0.41, 95% CI –0.02 to 0.84; P = 0.06; Fig. 4). There was a significantly higher conversion rate in the LESS LDN group (OR 13.21, 95% CI 4.65–37.53; P < 0.001; Fig. 5). Most of these conversions were to the conventional laparoscopic approach; only one case in the LESS LDN group was converted to open surgery, and no case in the LLDN group was converted to open surgery (all of them were converted to a hand-assisted approach). There were no significant differences in the length of hospital stay (WMD –0.11 days, 95% CI –0.33 to –0.12; P = 0.35; Fig. 6) and visual analogue score for pain at discharge (WMD –0.31, 95% CI –0.96 to –0.35; P = 0.36; Fig. 7) between the
Serum creatinine at the end of the first month of follow-up was similar between groups (WMD 0.10 mg/dL, 95% CI –0.09 to 0.29; P = 0.29; Fig. 10).
Discussion LLDN has become an established alternative to open surgery, with equivalent allograft outcomes, quicker recovery, and superior cosmesis [11]. The present meta-analysis of two RCTs and seven retrospective studies including 1467 patients show that LESS LDN has similar outcomes to those of standard LLDN, without significant differences in terms of WIT, complications, hospital stay, and immediate graft function. Conversely, LESS LDN is associated with a longer operative © 2014 The Authors BJU International © 2014 BJU International
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Fig. 3 Forrest plot – analysis of EBL.
Study or Subgroup Afaneh 2011 Andonian 2010 Barth 2013 Canes 2009 Kurien 2011 Lunsford 2011 Ramasamy 2011 Richstone 2013 Stamatakis 2013
Mean 101 100 77 108 84 50 91.3 139 61.5
LESS SD 85 18.8 64 67 29.2 43.8 106.3 87 32.6
Total 50 6 135 17 25 10 101 15 102
Laparoscopic Mean SD Total 102 113 50 150 50 6 107 121 100 141 65 17 92.4 28.4 25 75 43.8 20 121.9 55 663 146 77 14 85.9 51.5 111
Mean Difference Weight IV, Random, 95% CI –1.00 [–40.19, 38.19] 3.6% 3.0% –50.00 [–92.74, –7.26] 8.1% –30.00 [–56.06, –3.94] 2.8% –33.00 [–77.37, 11.37] –8.40 [–24.37, 7.57] 21.7% –25.00 [–58.25, 8.25] 5.0% 12.3% –30.60 [–51.75, –9.45] –7.00 [–66.71, 52.71] 1.5% 41.9% –24.00 [–35.88, –12.92]
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100.0% –22.09 [–29.52, –14.66]
Total (95% CI) 461 Heterogeneity: Chi2 = 7.21, df = 8 (P = 0.51); I2 = 0% Test for overall effect: Z = 5.83 (P < 0.001)
Mean Difference IV, Random, 95% CI
–100
–50 0 50 100 Favours [LESS] Favours [Laparoscopy]
Fig. 4 Forrest plot – analysis of WIT.
Study or Subgroup Afaneh 2011 Andonian 2010 Barth 2013 Canes 2009 Kurien 2011 Ramasamy 2011 Richstone 2013 Stamatakis 2013
Mean 4 5 2.8 6.1 7.2 3.9 5.3 4.4
LESS SD 0.6 0.8 0.7 2 1.8 0.9 2.3 1.4
Laparoscopic Mean SD Total 4.2 0.8 50 5 0.3 6 2.6 0.5 100 3 0.6 17 5.1 1 25 4 0.8 663 5 1.1 14 5 1.4 111
Total 50 6 135 17 25 101 15 102
Total (95% CI) 451 Heterogeneity: Tau2 = 0.29; Chi2 = 81.96, df = 7 (P < 0.001); I2 = 91% Test for overall effect: Z = 1.87 (P = 0.06)
986
Weight 15.5% 11.7% 16.2% 8.8% 10.5% 16.1% 6.6% 14.7%
Mean Difference IV, Random, 95% CI –0.20 [–0.48, 0.08] 0.00 [–0.68, 0.68] 0.20 [0.05, 0.35] 3.10 [2.11, 4.09] 2.10 [1.29, 2.91] –0.10 [–0.29, 0.09] 0.30 [–1.00, 1.60] –0.60 [–0.98, –0.22]
100.0%
0.41 [–0.02, 0.84]
Mean Difference IV, Random, 95% CI
–4
–2 0 2 4 Favours [LESS] Favours [Laparoscopy]
Fig. 5 Forrest plot – analysis of conversion rate.
Study or Subgroup Afaneh 2011 Andonian 2010 Barth 2013 Canes 2009 Kurien 2011 Lunsford 2011 Ramasamy 2011 Richstone 2013 Stamatakis 2013
LESS Events Total 2 50 0 6 16 135 1 17 2 25 0 10 3 101 2 15 14 102
Laparoscopic Events Total 0 50 0 6 0 100 0 17 0 25 0 20 2 663 0 14 0 111
Total (95% CI) 461 40 Total events 2 Heterogeneity: Chi = 2.57, df = 6 (P = 0.86); I2 = 0% Test for overall effect: Z = 4.85 (P < 0.001)
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15.8% 13.4% 12.7%
Odds Ratio M-H, Fixed, 95% CI 5.21 [0.24, 111.24] Not estimable 27.75 [1.64, 468.40] 3.18 [0.12, 83.76] 5.43 [0.25, 118.96] Not estimable 10.12 [1.67, 61.31] 5.37 [0.24, 122.29] 36.54 [2.15, 620.97]
100.0%
13.21 [4.65, 37.53]
Weight 14.6% 15.5% 14.1% 13.9%
2
time and higher risk of conversion, but it provides a lower analgesic requirement compared with LLDN. The present study represents the first of its kind, as it specifically looks at the outcomes of the LDN procedure, whereas the only available meta-analysis on LESS vs laparoscopy took in consideration a variety of ‘nephrectomy’ procedures [14], each one with specific features, peculiar challenges, and potential risks, and this translates into a more difficult interpretation of the data [30].
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Odds Ratio M-H, Fixed, 95% CI
0.001
0.1 1 10 1000 Favours [LESS] Favours [Laparoscopy]
Regardless of the approach, LDN represents a uniquely challenging procedure, where the surgeon is expected to meet a combination of demanding tasks, including harvesting a quality kidney, achieving excellent transplant allograft outcomes, and maintaining donor safety. In this setting, the application of LESS becomes even more questionable, as intrinsic technical limitations of this approach (lack of triangulation, instrument clashing, poor ergonomy) are recognised, and they necessarily translate into a steep learning curve, limiting its adoption on a large scale. However, the
LESS LDN vs conventional laparoscopic LDN
Fig. 6 Forrest plot – analysis of length of hospital stay.
Study or Subgroup Afaneh 2011 Andonian 2010 Barth 2013 Canes 2009 Kurien 2011 Lunsford 2011 Ramasamy 2011 Richstone 2013 Stamatakis 2013
Mean 2.1 2 2.6 3 3.9 1.7 2.4 2.4 2.2
LESS SD 0.5 0.5 0.9 1.2 0.7 1.3 0.8 1.1 0.7
Total 50 6 135 17 25 10 101 15 102
Laparoscopic Mean SD Total 2.1 0.4 50 2 0.3 6 2.3 0.7 100 3.5 1.2 17 4.5 0.8 25 1.3 1.2 20 2.9 3.5 663 2.1 0.6 14 2.4 0.7 111
Total (95% CI) 461 Heterogeneity: Tau2 = 0.07; Chi2 = 32.01, df = 8 (P < 0.001); I2 = 75% Test for overall effect: Z = 0.94 (P = 0.35)
1006
Weight 16.3% 10.2% 15.8% 5.4% 11.2% 4.2% 13.5% 7.3% 16.1%
Mean Difference IV, Random, 95% CI 0.00 [–0.18, 0.18] 0.00 [–0.47, 0.47] 0.30 [0.10, 0.50] –0.50 [–1.31, 0.31] –0.60 [–1.02, –1.18] 0.40 [–0.56, 1.36] –0.50 [–0.81, –0.19] 0.30 [–0.34, 0.94] –0.20 [–0.39, –0.01]
100.0%
–0.11 [–0.33, 0.12]
Mean Difference IV, Random, 95% CI
–4
–2 0 2 4 Favours [LESS] Favours [Laparoscopy]
Fig. 7 Forrest plot – analysis of visual analogue score for pain at discharge.
Study or Subgroup Afaneh 2011 Andonian 2010 Canes 2009 Kurien 2011 Lunsford 2011 Richstone 2013 Stamatakis 2013
Mean 1.8 1.5 2.7 1.2 2.5 1.2 1
Less SD 1.2 1.9 2.6 0.7 1.3 1.3 1.5
Total 50 6 17 25 10 15 102
Laparoscopic Mean SD Total 1.6 1.2 50 4 1.3 6 1.4 1.6 17 2.1 0.9 25 2 1.3 20 3.1 2.1 14 0.8 1.4 111
Total (95% CI) 225 Heterogeneity: Tau2 = 0.55; Chi2 = 34.93, df = 6 (P < 0.001); I2 = 83% Test for overall effect: Z = 0.91 (P = 0.36)
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Weight 18.5% 7.9% 10.3% 18.7% 14.0% 11.5% 19.1%
Mean Difference IV, Random, 95% CI 0.20 [–0.27, 0.67] –2.50 [–4.34, –0.66] 1.30 [–0.15, 2.75] –0.90 [–1.35, –0.45] 0.50 [–0.49, 1.49] –1.90 [–3.18, –0.62] 0.20 [–0.19, 0.59]
100.0%
–0.31 [–0.96, 0.35]
Mean Difference IV, Random, 95% CI
–4 –2 0 2 4 Favours [LESS] Favours [Laparoscopy]
Fig. 8 Forrest plot – analysis of inpatient analgesic requirements.
Study or Subgroup Afaneh 2011 Andonian 2010 Barth 2013 Canes 2010 Kurien 2011 Lunsford 2011 Ramasamy 2011 Richstone 2013 Stamatakis 2013
Mean 10.2 83 0 100 23.6 20.4 9.9 0 55.7
LESS SD 9.6 33.5 0 62 19.34 16.15 15 0 38.7
Total 50 6 0 17 18 10 101 0 102
Conventional Lap Mean SD Total 14.3 10.5 50 42 14 6 0 0 0 97 58 17 24 14.7 17 25 60.25 20 12.5 22 663 0 0 0 53.3 55.2 111
Total (95% CI) 304 Heterogeneity: Chi2 = 10.04, df = 6 (P = 0.12); I2 = 40% Test for overall effect: Z = 2.08 (P = 0.04)
884
concept of minimising the skin incision in a healthy (and frequently young) individual is appealing and can be regarded as an incentive to organ donation. Gill et al. [6] first reported the successful completion of four single-port transumbilical LDNs. Soon after, the same group reported the first retrospective matched pair comparison of LESS LDN to standard LDN, concluding that the LESS approach may be associated with quicker convalescence and comparable early allograft outcomes [21]. Since then, other groups have reported comparative assessment of the two LDN approaches, with conflicting findings [22–29].
3.6%
Mean Difference IV, Fixed, 95% CI –4.10 [–8.04, –0.16] 41.00 [11.95, 70.05] Not estimable 3.00 [–37.36, 43.36] –0.40 [–11.74, 10.94] –4.40 [–32.84, 23.64] –2.60 [–5.97, 0.77] Not estimable 2.40 [–10.32, 15.12]
100.0%
–2.58 [–5.01, –0.15]
Weight 38.0% 0.7% 0.4% 4.6% 0.7% 52.0%
Mean Difference IV, Fixed, 95% CI
–20
–10 0 10 20 Favours [LESS] Favours [Convent Lap]
When adopting a novel surgical technique, patient safety represents a key factor and this is especially true in the case of a LDN. As a general principle, all eligible laparoscopic-surgery patients may be considered for LESS. At the same time, patient selection with LESS must be more rigorous to minimise the surgical risk. When looking at the overall population of the present analysis, patients were relatively young and not obese, mirroring the current overall pool of patients undergoing LDN [31]. It is a well-established principle that single renal artery left kidneys are preferred by most transplant surgeons due to the © 2014 The Authors BJU International © 2014 BJU International
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Fig. 9 Forrest plot – analysis of postoperative complication rate.
Study or Subgroup Afaneh 2011 Andonian 2010 Barth 2013 Canes 2009 Kurien 2011 Lunsford 2011 Ramasamy 2011 Richstone 2013 Stamatakis 2013
LESS Events Total 4 50 0 6 1 135 2 17 4 25 0 10 8 101 1 15 17 102
Conventional Lap Events Total 5 50 1 6 2 100 0 17 5 25 4 20 47 663 0 14 16 111
Total (95% CI) 461 37 80 Total events 2 Heterogeneity: Chi = 4.65, df = 8 (P = 0.79); I2 = 0% Test for overall effect: Z = 0.01(P = 0.99)
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Weight 11.3% 3.4% 5.6% 1.1% 10.4% 7.3% 28.2% 1.2% 31.5%
Odds Ratio M-H, Fixed, 95% CI 0.78 [0.20, 3.10] 0.28 [0.01, 8.42] 0.37 [0.03, 4.09] 5.65 [0.25, 126.87] 0.76 [0.18, 3.25] 0.17 [0.01, 3.59] 1.13 [0.52, 2.46] 3.00 [0.11, 79.91] 1.19 [0.57, 2.50]
100.0%
1.00 [0.65, 1.54]
Odds Ratio M-H, Fixed, 95% CI
0.005
0.1 1 10 200 Favours [LESS] Favours [Convent Lap]
Fig. 10 Forrest plot – analysis of serum creatinine at the end of the first month of follow-up.
Study or Subgroup Afaneh 2011 Barth 2013 Canes 2009 Stamatakis 2013
Mean 1.4 1.4 1.5 1.5
LESS SD 0.6 0.5 0.5 1.3
Total 50 135 17 102
Laparoscopic Mean SD Total 1.2 0.4 50 1.5 0.5 100 1.3 0.4 17 1.3 0.5 111
Total (95% CI) 304 Heterogeneity: Tau2 = 0.02; Chi2 = 9.38, df = 3 (P = 0.02); I2 = 68% Test for overall effect: Z = 1.06 (P = 0.29)
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Weight 26.8% 32.4% 19.2% 21.6%
Mean Difference IV, Random, 95% CI 0.20 [0.00, 0.40] –0.10 [–0.23, 0.03] 0.20 [–0.10, 0.50] 0.20 [–0.07, 0.47]
100.0%
0.10 [–0.09, 0.29]
longer length of the left renal vein compared with the right renal vein. Not surprisingly, we found an overall higher rate of left-side LDNs in the LESS group (96.5% vs 88.6%, P < 0.001). When taking a closer look at each study, some investigators considered a left-side kidney [21,23,28,29] and a noncomplex vasculature [23,28] as inclusion criteria for LESS, whereas some others did not adopt these criteria, having a broader surgical indication [22,24–27]. As excellent long-term outcomes can be obtained with LDN with right and/or complex vasculature kidneys, unavailability of a single renal artery and/or left kidney should ideally not preclude kidney donation [32]. However, it is wise to selectively use cases with a more favourable anatomy when scrutinising a new technique, and comparing it with a more established one. The present analysis shows an increase of ≈25 min in operating time when LESS LDN is performed as compared with LDN. The finding of a prolonged operating time for LESS is consistently reported by some of the included studies [21,22,24,26], and it can be intuitively explained by the fact that adoption of a novel technique (i.e. LESS) implies a learning curve. On the other hand, absolute operating time is a difficult parameter to compare in the setting of LDN, given expected differences in trainee involvement and co-ordination with the parallel recipient case. Unfortunately, available data do not allow the assessment of a more adequate time-point,
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Mean Difference IV, Random, 95% CI
–2
–1 0 1 2 Favours [LESS] Favours [Laparoscopy]
such as, for example, time to complete renal hilum dissection, as suggested by Stamatakis et al. [26], or time to hilar clamping, as suggested by Barth et al. [27]. Operating time is routinely considered as a parameter to estimate the surgical learning curve. In this regard, Stamatakis et al. [26] observed a little change over the course of their series, suggesting a very shallow learning curve, which they explained by the fact that for a surgeon already experienced with LDN, LESS LDN case number might be a relatively insignificant factor in determining operating time. In the series reported by Barth et al. [27], which represents the largest in terms of sample size, the average operative time to division of the renal artery was similar between the study groups, and initial differences in operative times lost significance after the first 25 cases and equilibrated near the 70th case. Conversely to the report by Fan et al. [14], we found statistically significant lower EBL in the LESS group (WMD –22.09 mL, 95% CI –29.52 to –14.66; P < 0.001). This difference seems not to be clinically significant, and it can also be related to the inevitable inaccuracies in intraoperative measurement. However, Ramasamy et al. [24] found that only EBL predicted overall complications, and for each millilitre of blood loss there was a 0.2% increase in the risk of a complication in their series.
LESS LDN vs conventional laparoscopic LDN
WIT is traditionally recognised as a surrogate measure of surgical quality during LDN [33]. We did not find a significant difference in WIT, despite a trend in favour of multi-port laparoscopy (WMD 0.41 min, 95% CI –0.02 to 0.84; P = 0.06). In their comparative studies, Canes et al. [21] found WIT to be twice as long in the LESS LDN group, and most of this extra time was spent creating an adequate fascial incision, as this site cannot be prepared before extraction. In contrast, Stamatakis et al. [26] were the first to document a statistically significant decrease (0.5 min) in WIT with LESS LDN as compared with LDN. The authors attributed this finding to the use of the GelPOINT™, eliminating the need to complete an incision after transection of the renal vasculature. More clinically relevant than WIT is graft function, which was assessed only in four of the studies by using creatinine levels [21,22,26,27]. Meta-analysis of data showed that 1-month serum creatinine levels were similar between groups (WMD 0.10 mg/dL, 95% CI –0.09 to 0.29; P = 0.29). However, serum creatinine itself is recognised as an insensitive predictor of renal function, especially in the setting of renal transplantation [34]. Although conversion itself cannot be considered a complication, it is nevertheless an important factor when fully counselling patients on the potential risks/benefits of any given procedure [35]. Autorino et al. [36] analysed a multi-institutional dataset of 1163 LESS cases and found an overall conversion rate of 19.7%, including 14.6%, 4% and 1.1% rates of conversion to reduced port laparoscopy (i.e. addition of one extra port), conventional laparoscopy and open surgery, respectively. On multivariable analysis significant factors that increased the likelihood of any type of conversion were oncological surgical indication, pelvic surgery, robotic assistance, high procedure difficulty score, extended operative time and intraoperative complications. In the present study, there was a significantly higher conversion rate in the LESS group (OR 13.21, 95% CI 4.65–37.53; P < 0.001), with most of the conversions being from LESS LDN to the conventional LLDN. The rationale behind the adoption of LESS is mainly based on the potential gain for the patient in terms of lower postoperative pain, shorter hospital stay, and ultimately faster recovery. Length of stay represents an unreliable endpoint in this patient population, as donors may express the desire to remain in the hospital longer because of psychosocial considerations [21]. Unfortunately, a systematic analysis of pain and analgesic use in this setting remains challenging, as this issue has been addressed by the different authors using various methods, different assessment tools, and at different time-points. Moreover, different factors can influence to some extent these variables, including different pain management protocols, patient-specific pain thresholds, and also patient expectations. In their meta-analysis, Fan et al. [14] detected
reduced postoperative pain, and lower analgesic requirement for LESS nephrectomy procedures. Overall, in the present study we found no differences in terms of pain score at discharge, but LESS LDN was associated with a lower inpatient analgesic requirement (WMD –2.58 mg; 95% CI –5.01 to –0.15; P = 0.04). Whether this translates into a significant clinical advantage remains to be seen. The complication rate is broadly considered as another surrogate of surgical competence. Accurate reporting of complications is important for preoperative counselling, and for identifying modifiable risk factors to decrease the complication rate. Greco et al. [37] investigated risk factors for complications in a multi-institutional series of LESS of upper urinary tract disease and found an overall complication rate of 17%. In a larger analysis of LESS including cases for various indications, Autorino et al. [36] reported a 9.4% postoperative overall complication rate, most of them being of low grade. In the present analysis, we did not find any significant difference in terms of postoperative complication rates (OR 1.00, 95% CI 0.65–1.54; P = 0.99) between the two techniques. The overall complication rates for LESS LDN (9.7%) and LLDN (8.4%) compare favourably with a recent analysis of 69 117 LDN cases from the National Inpatient Sample where the procedure-related complication rate for living donors was found to be ≈8% [31]. The present meta-analysis has several potential limitations that should be considered. The main limitation is that most of the studies were retrospective, except for two RCTs, and most had a small sample size. We decided not to include studies from conference abstracts, as they usually do not provide complete information for each endpoint. In addition, the included studies were carried out by surgeons with different backgrounds and applying different techniques. However, all the groups involved in these studies had a solid laparoscopic background. Thus, it might be questionable to extract these findings in different settings and one might argue that LESS may never gain favour as a mainstream urological technique due to current technical difficulties and this is especially true for a high risk/benefit procedure, such as LDN. Finally, the follow-up period was generally short, so long-term outcomes of LESS LDN, especially in terms of graft function, remain to be explored. Moreover, estimated GFR, rather than creatinine levels, represent a more reliable proxy of kidney function. However, it was not possible to do this analysis because of the lack of data. Last, a cost-benefit analysis between LESS LDN and traditional LLDN will also be important in determining the applicability of LESS for this and other applications. Nevertheless, this meta-analysis tries to fill a gap in the current literature on LESS, providing the most up to date information in this area. Moreover, enough data had accumulated to allow an assessment based on meta-analytical methods. Multiple strategies to identify studies, strict criteria of study selection, © 2014 The Authors BJU International © 2014 BJU International
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and standardised evaluation of the methodological quality of the studies have been adopted to provide the best current available evidence.
Conclusions LESS LDN is more technically challenging than its standard LLDN counterpart, as shown by the longer operative time and the greater likelihood of conversion. However, in experienced hands, this procedure can offer comparable surgical and early functional outcomes, and it seems to be associated with lower analgesic requirement. Ultimately, the role of LESS for LDN remains to be defined and, ideally, this novel approach should be compared with standard LLDN in a well-designed, large, prospective, randomised, multi-centre study before gaining wider acceptance.
Conflicts of Interest None disclosed.
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13 Autorino R, Kaouk JH, Stolzenburg JU et al. Current status and future directions of robotic single-site surgery: a systematic review. Eur Urol 2013; 63: 266–80 14 Fan X, Lin T, Xu K et al. Laparoendoscopic single-site nephrectomy compared with conventional laparoscopic nephrectomy: a systematic review and meta-analysis of comparative studies. Eur Urol 2012; 62: 601–12 15 Wells GA, Shea B, O’Connell D et al. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. Ottawa Hospital Research Institute Web site, Available at: http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp. Accessed May 2013 16 Clark HD, Wells GA, Huët C et al. Assessing the quality of randomized trials: 395 reliability of the Jadad scale. Control Clin Trials 1999; 20: 448–52 17 Dindo D, Demartines N, Clavien PA. Classification of surgical complications: 398 a new proposal with evaluation in a cohort of 6336 patients 399 and results of a survey. Ann Surg 2004; 240: 205–13 18 Hozo SP, Djulbegovic B, Hozo I. Estimating the mean and variance from the median, range, and the size of a sample. BMC Med Res Methodol 2005; 5: 13 19 Matel N, Haenszel W. Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst 1959; 22: 719–48 20 DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials 1986; 7: 177–88 21 Canes D, Berger A, Aron M et al. Laparo-endoscopic single site (LESS) versus standard laparoscopic left donor nephrectomy: matched-pair comparison. Eur Urol 2010; 57: 95–101 22 Afaneh C, Aull MJ, Gimenez E et al. Comparison of laparoendoscopic single-site donor nephrectomy and conventional laparoscopic donor nephrectomy: donor and recipient outcomes. Urology 2011; 78: 1332–7 23 Lunsford KE, Harris MT, Nicoll KN et al. Single-site laparoscopic living donor nephrectomy offers comparable perioperative outcomes to conventional laparoscopic living donor nephrectomy at a higher cost. Transplantation 2011; 91: e16–7 24 Ramasamy R, Afaneh C, Katz M et al. Comparison of complications of laparoscopic versus laparoendoscopic single site donor nephrectomy using the modified Clavien grading system. J Urol 2011; 186: 1386–90 25 Andonian S, Rais-Bahrami S, Atalla MA, Herati AS, Richstone L, Kavoussi LR. Laparoendoscopic single-site Pfannenstiel versus standard laparoscopic donor nephrectomy. J Endourol 2010; 24: 429–32 26 Stamatakis L, Mercado MA, Choi JM et al. Comparison of laparoendoscopic single site (LESS) and conventional laparoscopic donor nephrectomy at a single institution. BJU Int 2013; 112: 198–206 27 Barth RN, Phelan MW, Goldschen L et al. Single-port donor nephrectomy provides improved patient satisfaction and equivalent outcomes. Ann Surg 2013; 257: 527–33 28 Kurien A, Rajapurkar S, Sinha L et al. First prize: standard laparoscopic donor nephrectomy versus laparoendoscopic single-site donor nephrectomy: a randomized comparative study. J Endourol 2011; 25: 365–70 29 Richstone L, Rais-Bahrami S, Waingankar N et al. Pfannenstiel laparoendoscopic single-site (LESS) vs conventional multiport laparoscopic live donor nephrectomy: a prospective randomized Controlled trial. BJU Int 2013; 112: 616–22 30 Kaouk JH, Autorino R. Laparoendoscopic single-site surgery (LESS) and nephrectomy: current evidence and future perspectives. Eur Urol 2012; 62: 613–5 31 Schold JD, Goldfarb DA, Buccini LD et al. Comorbidity Burden and Perioperative Complications for Living Kidney Donors in the United States. Clin. J Am Soc Nephrol 2013; 8: 1773–82
LESS LDN vs conventional laparoscopic LDN
32 Chedid MF, Muthu C, Nyberg SL et al. Living donor kidney transplantation using laparoscopically procured multiple renal artery kidneys and right kidneys. J Am Coll Surg 2013; 217: 144–52 33 Hellegering J, Visser J, Kloke HJ et al. Deleterious influence of prolonged warm ischemia in living donor kidney transplantation. Transplant Proc 2012; 44: 1222–6 34 Abouchacra S, Chaaban A, Hakim R et al. Renal biomarkers for assessment of kidney function in renal transplant recipients: how do they compare? Int Urol Nephrol 2012; 44: 1871–6 35 Richstone L, Seideman C, Baldinger L et al. Conversion during laparoscopic surgery: frequency, indications and risk factors. J Urol 2008; 180: 855–9 36 Autorino R, Kaouk JH, Yakoubi R et al. Urological laparoendoscopic single site surgery: multi-institutional analysis of risk factors for conversion and postoperative complications. J Urol 2012; 187: 1989–94
37 Greco F, Cindolo L, Autorino R et al. Laparoendoscopic single-site upper urinary tract surgery: assessmentof postoperative complications and analysis of risk factors. Eur Urol 2012; 61: 510–6
Correspondence: Riccardo Autorino, Center for Laparoscopic and Robotic Surgery, Glickman Urological and Kidney Institute, Cleveland Clinic, 9500 Euclid Avenue/Q-10, Cleveland, OH 44195, USA. e-mail: [email protected]; [email protected] Abbreviations: BMI, body mass index; EBL, estimated blood loss; (L)LDN, (laparoscopic) living-donor nephrectomy; LESS, laparoendoscopic single-site surgery; OR, odds ratio; RCT, randomised controlled trial; VAS, visual analogue score; WIT, warm ischaemia time; WMD, weighted mean difference.
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The aim of this study was to provide a systematic review and meta-analysis of reports comparing laparoendoscopic single-site (LESS) living-donor nephrectomy (LDN) vs standard laparoscopic LDN (LLDN). A systematic review of the literature was performed in September 2013 using PubMed, Scopus, Ovid and The Cochrane library databases. Article selection proceeded according to the search strategy based on Preferred Reporting Items for Systematic Reviews and Meta-analyses criteria. Weighted mean differences (WMDs) were used to measure continuous variables and odds ratios (ORs) to measure categorical ones. Nine publications meeting eligibility criteria were identified, including 461 LESS LDN and 1006 LLDN cases. There were more left-side cases in the LESS LDN group (96.5% vs 88.6%, P < 0.001). Meta-analysis of extractable data showed that LLDN had a shorter operative time (WMD 15.06 min, 95% confidence interval [CI] 4.9–25.1; P = 0.003), without a significant difference in warm ischaemia time (WMD 0.41 min, 95% CI –0.02 to 0.84; P = 0.06). Estimated blood loss was lower for LESS LDN (WMD −22.09 mL, 95% CI –29.5 to –14.6; P < 0.001); however, this difference was not clinically significant. There was a greater likelihood of conversion for
Introduction Living-donor transplantation is established as the optimal treatment for end-stage renal failure [1]. Historically, living-donor nephrectomy (LDN) has been performed as an open technique. However, this is potentially associated with prolonged convalescence, which could be regarded as a disincentive to donation. Thus, over the last two decades, surgical practice has developed with the aim of speeding donor postoperative recovery, while maintaining
BJU Int 2015; 115: 206–215 wileyonlinelibrary.com
LESS LDN (OR 13.21, 95% CI 4.65–37.53; P < 0.001). Hospital stay was similar (WMD –0.11 days, 95% CI –0.33 to 0.12; P = 0.35), as well as the visual analogue pain score at discharge (WMD –0.31, 95% CI –0.96 to 0.35; P = 0.36), but the analgesic requirement was lower for LESS LDN (WMD –2.58 mg, 95% CI –5.01 to –0.15; P = 0.04). Moreover, there was no difference in the postoperative complication rate (OR 1.00, 95% CI 0.65–1.54; P = 0.99). Renal function of the recipient, as based on creatinine levels at 1 month, showed similar outcomes between groups (WMD 0.10 mg/dL, –0.09 to 0.29; P = 0.29). In conclusion, LESS LDN represents an emerging option for living kidney donation. This procedure offers comparable surgical and early functional outcomes to the conventional LLDN, with a lower analgesic requirement. However, it is more technically challenging than LLDN, as shown by a greater likelihood of conversion. The role of LESS LDN remains to be defined.
Keywords donor nephrectomy, laparoscopic, laparoendoscopic single-site surgery, meta-analysis
transplant quality, from the standard open lumbotomy, through mini-incision muscle-splitting open LDN [2], to minimally invasive techniques, including standard laparoscopy [3], hand-assisted laparoscopy [4], and retroperitoneoscopy [5]. More recently, novel minimally invasive techniques have been introduced in this setting, e.g. laparoendoscopic single-site surgery (LESS) [6], natural orifice transluminal endoscopic surgery (NOTES)-assisted laparoscopy [7,8], mini-laparoscopy [9], and robot-assisted laparoscopy [10]. © 2014 The Authors BJU International © 2014 BJU International | doi:10.1111/bju.12724 Published by John Wiley & Sons Ltd. www.bjui.org
LESS LDN vs conventional laparoscopic LDN
Since its introduction, laparoscopic LDN (LLDN) has been widely implemented, and current evidence suggests that laparoscopic techniques result in less postoperative pain and estimated blood loss (EBL) with a shorter hospital stay, while postoperative graft function is not inferior to that of open LDN [11]. Despite its worldwide adoption for a wide variety of indications [12], the role of LESS in the field of minimally invasive urological surgery remains to be defined and the technique is still far from being regarded as a new standard approach, as novel technological developments are awaited to foster its application [13]. In a recent systematic review and meta-analysis of studies comparing laparoscopic and LESS nephrectomy, including over 1000 cases, Fan et al. [14] showed that LESS patients benefit from less postoperative pain, lower analgesic requirement, shorter hospital stay, faster recovery time, and not surprisingly, a better cosmetic outcome. There were no significant differences in other main surgical outcomes and postoperative renal function. Nevertheless, the authors found that LESS takes more operative time and the procedure carries a greater chance of conversion. Application of LESS to donor nephrectomy poses unique challenges and risks. However, the concept of minimising the skin incision in a healthy (and frequently young) individual is appealing and can be regarded as a potential incentive to organ donation. The aim of the present study was to review systematically the available evidence comparing the outcomes of LESS with those of conventional LLDN.
Materials and Methods Literature Search and Study Selection A systematic review of the literature was performed in September 2013 using PubMed, Scopus, Ovid and The Cochrane Library databases, to identify relevant studies. Three separate searches were done by applying a free-text protocol with the following search terms: ‘single site donor nephrectomy’, ‘LESS donor nephrectomy’ and ‘laparoscopic donor nephrectomy’. Article selection proceeded according to the search strategy based on Preferred Reporting Items for Systematic Reviews and Meta-analyses criteria (PRISMA, www. prismastatement.org) (Fig. 1). Only studies comparing LESS and laparoscopic techniques were included for further screening. In addition, cited references from the selected articles retrieved in the search were assessed for significant papers. Conference abstracts were not included because they were not deemed to be methodologically appropriate.
Study Quality Assessment The level of evidence was rated for each included study according to the criteria provided by the Centre for Evidence-Based Medicine in Oxford, UK (www.cebm.net). The methodological quality of the studies was assessed by using the Newcastle-Ottawa Scale for non-randomised controlled trials (RCTs; consisting of three factors: patient selection, comparability of the study groups, and assessment of outcome; score of 0–9 allocated as stars, with studies achieving six or more stars considered to be of high quality) [15] and the Jadad scale for RCTs (score ranging between 0 and 5, with 0–2 being low, 3–5 high) [16]. Data Extraction and Outcomes of Interest Two reviewers reviewed the full texts of the included studies. Data were extracted from each eligible study. Demographic characteristics were compared including: age, body mass index (BMI), gender and side of procedure. Perioperative outcomes between the two procedures were compared using operative time, EBL, hospital length of stay, analgesic requirements (calculated in terms of morphine equivalents), visual analogue scale of pain at discharge, complication rate, conversion rate (defined as conversion to reduced port laparoscopy, conventional laparoscopy or open surgery), warm ischaemia time (WIT) and postoperative graft function as based on serum creatinine measurement at 1 month. Postoperative complications were graded according to the Clavien-Dindo system [17]. Statistical Analysis A meta-analysis was performed to assess the outcomes of LESS donor nephrectomy when compared with laparoscopy. Odds ratios (ORs) or risk ratios were used for binary variables while the mean differences or weighted mean differences (WMDs) were used for the continuous variables. For studies presenting continuous data as means and ranges, the standard deviations (SD) were calculated using the method described by Hozo et al. [18]. Pooled estimates were calculated with fixed-effect model (Mantel–Haenszel method) [19] if no significant heterogeneity was detected; otherwise, the random effect model (DerSimonian–Laird method) was used [20]. The pooled effects were determined by the Z-test, and a P < 0.05 was considered to indicate statistical significance. The Cochrane chi-square test and inconsistency (I2) were used to evaluate the heterogeneity between all studies. Data analysis was performed using the Review Manager software (RevMan 5.1, Cochrane Collaboration, Oxford, UK). © 2014 The Authors BJU International © 2014 BJU International
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Fig. 1 Preferred reporting items for systematic reviews and meta-analysis flow of study selection.
IDENTIFICATION
Search engines: PubMed, SCOPUS, OVID, THE COCHRANE LIBRARY Search date: 1 September 2013 Search terms: ‘Single Site Donor Nephrectomy’; ‘LESS Donor Nephrectomy’; ‘Laparoscopic Donor Nephrectomy’
ELIGIBILITY
SCREENING
Records after duplicates removed: n=30
Records excluded (n=19): - not specifically related to LDN (n=2) - review articles (n=6) - non-comparative studies (n=11)
Records screened based on title and abstracts: n=29
Records excluded (n=1) comparative data from same institution with overlapping dataset (n=1)
Full-text articles assessed for eligibility: n=10
INCLUDED
Additional records identified through reference lists (n=0)
Studies included in the analysis (n=9)
Results
Surgical Techniques
Description of Included Studies and Quality Assessment
Various surgical techniques have been adopted to perform LESS LDN (Table 1). In most of them, a commercially available multi-channel port was used, whereas in two studies a ‘single-site’ approach was adopted. The umbilicus represented the most used access site. Accessory needle-scopic or mini-laparoscopic ports were used selectively. A flexible-tip scope was preferred by most of the investigators, whereas articulating instruments were not used in five of the studies.
Nine studies were selected for the analysis, including overall 1467 patients who underwent a LDN procedure for kidney transplantation. Of them, 461 (31.5%) were LESS LDN cases and 1006 (68.5%) were conventional LLDN cases. Seven of the included studies were observational retrospective comparative studies. Four of them were observational retrospective and consecutive studies (level of evidence 3a) [21–24], while three of them were observational retrospective non-consecutive comparative studies (level of evidence 3b) [25–27]. Two of the studies were classified as RCTs (level of evidence 2b) [28,29]. The methodological quality of included studies was relatively high, as summarised in Table 1.
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Patient Demographics There were no differences between the LESS LDN and the LLDN group for age [mean (SD) 43.4 (2.71) vs 41.1 (5.65) years; P = 0.27), male gender (34.7% vs 33%; P = 0.30) and BMI [mean (SD) 26.15 (1.89) vs 26.12 (1.54) kg/m2; P = 0.92).
LESS LDN vs conventional laparoscopic LDN
Table 1 Characteristics and quality assessment of the included studies. Study
LOE
Study design
Quality score
Number of patients LESS LDN
Afaneh et al. [22] Andonian et al. [25] Barth et al. [27] Canes et al. [21] Lunsford et al. [23] Ramasamy et al. [24] Stamatakis et al. [26] 3 mm for liver retraction Kurien et al. [28] Richstone et al. [29]
3a 3b 3b 3a 3a 3a 3b
CRS NCR NCR CRS CRS CRS NCR
6 out of 9 ★ 6 out of 9 ★ 5 out of 9 ★ 6 out of 9 ★ 6 out of 9 ★ 6 out of 9 ★ 6 out of 9 ★
2b 2b
RCT RCT
3 out of 5 points 4 out of 5 points
LESS technique
Incision site
Multichannel port
Selective use of one extra port
LLDN
50 6 135 17 10 101 102
50 6 100 17 20 663 111
Single-port Single-site Single-port Single-port Single port Single-port Single-port
Umbilicus Pfannenstiel Umbilicus Umbilicus Umbilicus Umbilicus Umbilicus
Gelpoint None Various* R-port Gelport Gelpoint Gelpoint
No No 2 mm, for retraction 2 mm, for retraction No No 5 mm for dissection,
25 15
25 14
Single-port Single-site
Umbilicus Pfannenstiel
R-port None
3 mm, for retraction No
LOE, level of evidence; CRS, consecutive retrospective study; NCR, non-consecutive retrospective study. Newcastle Ottawa Scale used to assess non-RCTs; Jadad scale to assess RCTs (see methods).*SILS, Gelpoint, Gelport, SSL port, Quadport.
Fig. 2 Forrest plot – analysis of operative time.
Study or Subgroup Afaneh 2011 Andonian 2010 Barth 2013 Canes 2009 Kurien 2011 Lunsford 2011 Ramasamy 2011 Richstone 2013 Stamatakis 2013
Favours [LESS] Mean SD Total 166 28.7 50 142 36 6 216 48 135 269 86 17 172.2 38.4 25 179 9.8 10 156 47.8 101 143 32 15 206 33.8 102
Favours [Laparoscopic] Mean SD Total 129 29.8 50 117 18.3 6 204 36 100 239 54 17 175.8 47.6 25 186.5 34.8 20 148 69 663 128 28 14 181 28.4 111
Total (95% CI) 461 Heterogeneity: Tau2 = 150.46; Chi2 = 30.59, df = 8 (P < 0.001); I2 = 74% Test for overall effect: Z = 2.92 (P = 0.003)
1006
Weight 14.4% 6.3% 14.7% 3.5% 8.9% 12.0% 14.7% 9.7% 15.7%
Mean Difference IV, Random, 95% CI 37.00 [25.53, 48.47] 25.00 [–7.31, 57.31] 12.00 [1.26, 22.74] 30.00 [–18.27, 78.27] –3.60 [–27.57, 20.37] –7.50 [–23.92, 8.92] 8.00 [–2.70, 18.70] 15.00 [–6.85, 36.85] 25.00 [16.58, 33.42]
100.0%
15.06 [4.96, 25.17]
Mean Difference IV, Random, 95% CI
–100
–50 0 50 100 Favours [LESS] Favours [Laparoscopy]
There were significantly more left-side LDNs in the LESS group (96.5% vs 88.6%, P < 0.001).
groups, but LESS LDN was associated with a lower analgesic requirement (WMD –2.58 mg; 95% CI –5.01 to –0.15; P = 0.04; Fig. 8).
Perioperative Outcomes
There were no significant difference in postoperative complication rates (OR 1.00, 95% CI 0.65–1.54; P = 0.99; Fig. 9). Most of postoperative complications were minor (Clavien grade I or II); 84.2% in the LESS LDN group and 79.8% in the LLDN group.
There was a significant shorter operative time in the LLDN group (WMD 15.06 min, 95% CI 4.96–25.17; P = 0.003; Fig. 2), whereas there was a significant lower EBL in the LESS LDN group (WMD –22.09 mL, 95% CI –29.52 to –14.66; P < 0.001; Fig. 3). There were no significant differences in the WIT (WMD 0.41, 95% CI –0.02 to 0.84; P = 0.06; Fig. 4). There was a significantly higher conversion rate in the LESS LDN group (OR 13.21, 95% CI 4.65–37.53; P < 0.001; Fig. 5). Most of these conversions were to the conventional laparoscopic approach; only one case in the LESS LDN group was converted to open surgery, and no case in the LLDN group was converted to open surgery (all of them were converted to a hand-assisted approach). There were no significant differences in the length of hospital stay (WMD –0.11 days, 95% CI –0.33 to –0.12; P = 0.35; Fig. 6) and visual analogue score for pain at discharge (WMD –0.31, 95% CI –0.96 to –0.35; P = 0.36; Fig. 7) between the
Serum creatinine at the end of the first month of follow-up was similar between groups (WMD 0.10 mg/dL, 95% CI –0.09 to 0.29; P = 0.29; Fig. 10).
Discussion LLDN has become an established alternative to open surgery, with equivalent allograft outcomes, quicker recovery, and superior cosmesis [11]. The present meta-analysis of two RCTs and seven retrospective studies including 1467 patients show that LESS LDN has similar outcomes to those of standard LLDN, without significant differences in terms of WIT, complications, hospital stay, and immediate graft function. Conversely, LESS LDN is associated with a longer operative © 2014 The Authors BJU International © 2014 BJU International
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Fig. 3 Forrest plot – analysis of EBL.
Study or Subgroup Afaneh 2011 Andonian 2010 Barth 2013 Canes 2009 Kurien 2011 Lunsford 2011 Ramasamy 2011 Richstone 2013 Stamatakis 2013
Mean 101 100 77 108 84 50 91.3 139 61.5
LESS SD 85 18.8 64 67 29.2 43.8 106.3 87 32.6
Total 50 6 135 17 25 10 101 15 102
Laparoscopic Mean SD Total 102 113 50 150 50 6 107 121 100 141 65 17 92.4 28.4 25 75 43.8 20 121.9 55 663 146 77 14 85.9 51.5 111
Mean Difference Weight IV, Random, 95% CI –1.00 [–40.19, 38.19] 3.6% 3.0% –50.00 [–92.74, –7.26] 8.1% –30.00 [–56.06, –3.94] 2.8% –33.00 [–77.37, 11.37] –8.40 [–24.37, 7.57] 21.7% –25.00 [–58.25, 8.25] 5.0% 12.3% –30.60 [–51.75, –9.45] –7.00 [–66.71, 52.71] 1.5% 41.9% –24.00 [–35.88, –12.92]
1006
100.0% –22.09 [–29.52, –14.66]
Total (95% CI) 461 Heterogeneity: Chi2 = 7.21, df = 8 (P = 0.51); I2 = 0% Test for overall effect: Z = 5.83 (P < 0.001)
Mean Difference IV, Random, 95% CI
–100
–50 0 50 100 Favours [LESS] Favours [Laparoscopy]
Fig. 4 Forrest plot – analysis of WIT.
Study or Subgroup Afaneh 2011 Andonian 2010 Barth 2013 Canes 2009 Kurien 2011 Ramasamy 2011 Richstone 2013 Stamatakis 2013
Mean 4 5 2.8 6.1 7.2 3.9 5.3 4.4
LESS SD 0.6 0.8 0.7 2 1.8 0.9 2.3 1.4
Laparoscopic Mean SD Total 4.2 0.8 50 5 0.3 6 2.6 0.5 100 3 0.6 17 5.1 1 25 4 0.8 663 5 1.1 14 5 1.4 111
Total 50 6 135 17 25 101 15 102
Total (95% CI) 451 Heterogeneity: Tau2 = 0.29; Chi2 = 81.96, df = 7 (P < 0.001); I2 = 91% Test for overall effect: Z = 1.87 (P = 0.06)
986
Weight 15.5% 11.7% 16.2% 8.8% 10.5% 16.1% 6.6% 14.7%
Mean Difference IV, Random, 95% CI –0.20 [–0.48, 0.08] 0.00 [–0.68, 0.68] 0.20 [0.05, 0.35] 3.10 [2.11, 4.09] 2.10 [1.29, 2.91] –0.10 [–0.29, 0.09] 0.30 [–1.00, 1.60] –0.60 [–0.98, –0.22]
100.0%
0.41 [–0.02, 0.84]
Mean Difference IV, Random, 95% CI
–4
–2 0 2 4 Favours [LESS] Favours [Laparoscopy]
Fig. 5 Forrest plot – analysis of conversion rate.
Study or Subgroup Afaneh 2011 Andonian 2010 Barth 2013 Canes 2009 Kurien 2011 Lunsford 2011 Ramasamy 2011 Richstone 2013 Stamatakis 2013
LESS Events Total 2 50 0 6 16 135 1 17 2 25 0 10 3 101 2 15 14 102
Laparoscopic Events Total 0 50 0 6 0 100 0 17 0 25 0 20 2 663 0 14 0 111
Total (95% CI) 461 40 Total events 2 Heterogeneity: Chi = 2.57, df = 6 (P = 0.86); I2 = 0% Test for overall effect: Z = 4.85 (P < 0.001)
1006
15.8% 13.4% 12.7%
Odds Ratio M-H, Fixed, 95% CI 5.21 [0.24, 111.24] Not estimable 27.75 [1.64, 468.40] 3.18 [0.12, 83.76] 5.43 [0.25, 118.96] Not estimable 10.12 [1.67, 61.31] 5.37 [0.24, 122.29] 36.54 [2.15, 620.97]
100.0%
13.21 [4.65, 37.53]
Weight 14.6% 15.5% 14.1% 13.9%
2
time and higher risk of conversion, but it provides a lower analgesic requirement compared with LLDN. The present study represents the first of its kind, as it specifically looks at the outcomes of the LDN procedure, whereas the only available meta-analysis on LESS vs laparoscopy took in consideration a variety of ‘nephrectomy’ procedures [14], each one with specific features, peculiar challenges, and potential risks, and this translates into a more difficult interpretation of the data [30].
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Odds Ratio M-H, Fixed, 95% CI
0.001
0.1 1 10 1000 Favours [LESS] Favours [Laparoscopy]
Regardless of the approach, LDN represents a uniquely challenging procedure, where the surgeon is expected to meet a combination of demanding tasks, including harvesting a quality kidney, achieving excellent transplant allograft outcomes, and maintaining donor safety. In this setting, the application of LESS becomes even more questionable, as intrinsic technical limitations of this approach (lack of triangulation, instrument clashing, poor ergonomy) are recognised, and they necessarily translate into a steep learning curve, limiting its adoption on a large scale. However, the
LESS LDN vs conventional laparoscopic LDN
Fig. 6 Forrest plot – analysis of length of hospital stay.
Study or Subgroup Afaneh 2011 Andonian 2010 Barth 2013 Canes 2009 Kurien 2011 Lunsford 2011 Ramasamy 2011 Richstone 2013 Stamatakis 2013
Mean 2.1 2 2.6 3 3.9 1.7 2.4 2.4 2.2
LESS SD 0.5 0.5 0.9 1.2 0.7 1.3 0.8 1.1 0.7
Total 50 6 135 17 25 10 101 15 102
Laparoscopic Mean SD Total 2.1 0.4 50 2 0.3 6 2.3 0.7 100 3.5 1.2 17 4.5 0.8 25 1.3 1.2 20 2.9 3.5 663 2.1 0.6 14 2.4 0.7 111
Total (95% CI) 461 Heterogeneity: Tau2 = 0.07; Chi2 = 32.01, df = 8 (P < 0.001); I2 = 75% Test for overall effect: Z = 0.94 (P = 0.35)
1006
Weight 16.3% 10.2% 15.8% 5.4% 11.2% 4.2% 13.5% 7.3% 16.1%
Mean Difference IV, Random, 95% CI 0.00 [–0.18, 0.18] 0.00 [–0.47, 0.47] 0.30 [0.10, 0.50] –0.50 [–1.31, 0.31] –0.60 [–1.02, –1.18] 0.40 [–0.56, 1.36] –0.50 [–0.81, –0.19] 0.30 [–0.34, 0.94] –0.20 [–0.39, –0.01]
100.0%
–0.11 [–0.33, 0.12]
Mean Difference IV, Random, 95% CI
–4
–2 0 2 4 Favours [LESS] Favours [Laparoscopy]
Fig. 7 Forrest plot – analysis of visual analogue score for pain at discharge.
Study or Subgroup Afaneh 2011 Andonian 2010 Canes 2009 Kurien 2011 Lunsford 2011 Richstone 2013 Stamatakis 2013
Mean 1.8 1.5 2.7 1.2 2.5 1.2 1
Less SD 1.2 1.9 2.6 0.7 1.3 1.3 1.5
Total 50 6 17 25 10 15 102
Laparoscopic Mean SD Total 1.6 1.2 50 4 1.3 6 1.4 1.6 17 2.1 0.9 25 2 1.3 20 3.1 2.1 14 0.8 1.4 111
Total (95% CI) 225 Heterogeneity: Tau2 = 0.55; Chi2 = 34.93, df = 6 (P < 0.001); I2 = 83% Test for overall effect: Z = 0.91 (P = 0.36)
243
Weight 18.5% 7.9% 10.3% 18.7% 14.0% 11.5% 19.1%
Mean Difference IV, Random, 95% CI 0.20 [–0.27, 0.67] –2.50 [–4.34, –0.66] 1.30 [–0.15, 2.75] –0.90 [–1.35, –0.45] 0.50 [–0.49, 1.49] –1.90 [–3.18, –0.62] 0.20 [–0.19, 0.59]
100.0%
–0.31 [–0.96, 0.35]
Mean Difference IV, Random, 95% CI
–4 –2 0 2 4 Favours [LESS] Favours [Laparoscopy]
Fig. 8 Forrest plot – analysis of inpatient analgesic requirements.
Study or Subgroup Afaneh 2011 Andonian 2010 Barth 2013 Canes 2010 Kurien 2011 Lunsford 2011 Ramasamy 2011 Richstone 2013 Stamatakis 2013
Mean 10.2 83 0 100 23.6 20.4 9.9 0 55.7
LESS SD 9.6 33.5 0 62 19.34 16.15 15 0 38.7
Total 50 6 0 17 18 10 101 0 102
Conventional Lap Mean SD Total 14.3 10.5 50 42 14 6 0 0 0 97 58 17 24 14.7 17 25 60.25 20 12.5 22 663 0 0 0 53.3 55.2 111
Total (95% CI) 304 Heterogeneity: Chi2 = 10.04, df = 6 (P = 0.12); I2 = 40% Test for overall effect: Z = 2.08 (P = 0.04)
884
concept of minimising the skin incision in a healthy (and frequently young) individual is appealing and can be regarded as an incentive to organ donation. Gill et al. [6] first reported the successful completion of four single-port transumbilical LDNs. Soon after, the same group reported the first retrospective matched pair comparison of LESS LDN to standard LDN, concluding that the LESS approach may be associated with quicker convalescence and comparable early allograft outcomes [21]. Since then, other groups have reported comparative assessment of the two LDN approaches, with conflicting findings [22–29].
3.6%
Mean Difference IV, Fixed, 95% CI –4.10 [–8.04, –0.16] 41.00 [11.95, 70.05] Not estimable 3.00 [–37.36, 43.36] –0.40 [–11.74, 10.94] –4.40 [–32.84, 23.64] –2.60 [–5.97, 0.77] Not estimable 2.40 [–10.32, 15.12]
100.0%
–2.58 [–5.01, –0.15]
Weight 38.0% 0.7% 0.4% 4.6% 0.7% 52.0%
Mean Difference IV, Fixed, 95% CI
–20
–10 0 10 20 Favours [LESS] Favours [Convent Lap]
When adopting a novel surgical technique, patient safety represents a key factor and this is especially true in the case of a LDN. As a general principle, all eligible laparoscopic-surgery patients may be considered for LESS. At the same time, patient selection with LESS must be more rigorous to minimise the surgical risk. When looking at the overall population of the present analysis, patients were relatively young and not obese, mirroring the current overall pool of patients undergoing LDN [31]. It is a well-established principle that single renal artery left kidneys are preferred by most transplant surgeons due to the © 2014 The Authors BJU International © 2014 BJU International
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Fig. 9 Forrest plot – analysis of postoperative complication rate.
Study or Subgroup Afaneh 2011 Andonian 2010 Barth 2013 Canes 2009 Kurien 2011 Lunsford 2011 Ramasamy 2011 Richstone 2013 Stamatakis 2013
LESS Events Total 4 50 0 6 1 135 2 17 4 25 0 10 8 101 1 15 17 102
Conventional Lap Events Total 5 50 1 6 2 100 0 17 5 25 4 20 47 663 0 14 16 111
Total (95% CI) 461 37 80 Total events 2 Heterogeneity: Chi = 4.65, df = 8 (P = 0.79); I2 = 0% Test for overall effect: Z = 0.01(P = 0.99)
1006
Weight 11.3% 3.4% 5.6% 1.1% 10.4% 7.3% 28.2% 1.2% 31.5%
Odds Ratio M-H, Fixed, 95% CI 0.78 [0.20, 3.10] 0.28 [0.01, 8.42] 0.37 [0.03, 4.09] 5.65 [0.25, 126.87] 0.76 [0.18, 3.25] 0.17 [0.01, 3.59] 1.13 [0.52, 2.46] 3.00 [0.11, 79.91] 1.19 [0.57, 2.50]
100.0%
1.00 [0.65, 1.54]
Odds Ratio M-H, Fixed, 95% CI
0.005
0.1 1 10 200 Favours [LESS] Favours [Convent Lap]
Fig. 10 Forrest plot – analysis of serum creatinine at the end of the first month of follow-up.
Study or Subgroup Afaneh 2011 Barth 2013 Canes 2009 Stamatakis 2013
Mean 1.4 1.4 1.5 1.5
LESS SD 0.6 0.5 0.5 1.3
Total 50 135 17 102
Laparoscopic Mean SD Total 1.2 0.4 50 1.5 0.5 100 1.3 0.4 17 1.3 0.5 111
Total (95% CI) 304 Heterogeneity: Tau2 = 0.02; Chi2 = 9.38, df = 3 (P = 0.02); I2 = 68% Test for overall effect: Z = 1.06 (P = 0.29)
278
Weight 26.8% 32.4% 19.2% 21.6%
Mean Difference IV, Random, 95% CI 0.20 [0.00, 0.40] –0.10 [–0.23, 0.03] 0.20 [–0.10, 0.50] 0.20 [–0.07, 0.47]
100.0%
0.10 [–0.09, 0.29]
longer length of the left renal vein compared with the right renal vein. Not surprisingly, we found an overall higher rate of left-side LDNs in the LESS group (96.5% vs 88.6%, P < 0.001). When taking a closer look at each study, some investigators considered a left-side kidney [21,23,28,29] and a noncomplex vasculature [23,28] as inclusion criteria for LESS, whereas some others did not adopt these criteria, having a broader surgical indication [22,24–27]. As excellent long-term outcomes can be obtained with LDN with right and/or complex vasculature kidneys, unavailability of a single renal artery and/or left kidney should ideally not preclude kidney donation [32]. However, it is wise to selectively use cases with a more favourable anatomy when scrutinising a new technique, and comparing it with a more established one. The present analysis shows an increase of ≈25 min in operating time when LESS LDN is performed as compared with LDN. The finding of a prolonged operating time for LESS is consistently reported by some of the included studies [21,22,24,26], and it can be intuitively explained by the fact that adoption of a novel technique (i.e. LESS) implies a learning curve. On the other hand, absolute operating time is a difficult parameter to compare in the setting of LDN, given expected differences in trainee involvement and co-ordination with the parallel recipient case. Unfortunately, available data do not allow the assessment of a more adequate time-point,
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Mean Difference IV, Random, 95% CI
–2
–1 0 1 2 Favours [LESS] Favours [Laparoscopy]
such as, for example, time to complete renal hilum dissection, as suggested by Stamatakis et al. [26], or time to hilar clamping, as suggested by Barth et al. [27]. Operating time is routinely considered as a parameter to estimate the surgical learning curve. In this regard, Stamatakis et al. [26] observed a little change over the course of their series, suggesting a very shallow learning curve, which they explained by the fact that for a surgeon already experienced with LDN, LESS LDN case number might be a relatively insignificant factor in determining operating time. In the series reported by Barth et al. [27], which represents the largest in terms of sample size, the average operative time to division of the renal artery was similar between the study groups, and initial differences in operative times lost significance after the first 25 cases and equilibrated near the 70th case. Conversely to the report by Fan et al. [14], we found statistically significant lower EBL in the LESS group (WMD –22.09 mL, 95% CI –29.52 to –14.66; P < 0.001). This difference seems not to be clinically significant, and it can also be related to the inevitable inaccuracies in intraoperative measurement. However, Ramasamy et al. [24] found that only EBL predicted overall complications, and for each millilitre of blood loss there was a 0.2% increase in the risk of a complication in their series.
LESS LDN vs conventional laparoscopic LDN
WIT is traditionally recognised as a surrogate measure of surgical quality during LDN [33]. We did not find a significant difference in WIT, despite a trend in favour of multi-port laparoscopy (WMD 0.41 min, 95% CI –0.02 to 0.84; P = 0.06). In their comparative studies, Canes et al. [21] found WIT to be twice as long in the LESS LDN group, and most of this extra time was spent creating an adequate fascial incision, as this site cannot be prepared before extraction. In contrast, Stamatakis et al. [26] were the first to document a statistically significant decrease (0.5 min) in WIT with LESS LDN as compared with LDN. The authors attributed this finding to the use of the GelPOINT™, eliminating the need to complete an incision after transection of the renal vasculature. More clinically relevant than WIT is graft function, which was assessed only in four of the studies by using creatinine levels [21,22,26,27]. Meta-analysis of data showed that 1-month serum creatinine levels were similar between groups (WMD 0.10 mg/dL, 95% CI –0.09 to 0.29; P = 0.29). However, serum creatinine itself is recognised as an insensitive predictor of renal function, especially in the setting of renal transplantation [34]. Although conversion itself cannot be considered a complication, it is nevertheless an important factor when fully counselling patients on the potential risks/benefits of any given procedure [35]. Autorino et al. [36] analysed a multi-institutional dataset of 1163 LESS cases and found an overall conversion rate of 19.7%, including 14.6%, 4% and 1.1% rates of conversion to reduced port laparoscopy (i.e. addition of one extra port), conventional laparoscopy and open surgery, respectively. On multivariable analysis significant factors that increased the likelihood of any type of conversion were oncological surgical indication, pelvic surgery, robotic assistance, high procedure difficulty score, extended operative time and intraoperative complications. In the present study, there was a significantly higher conversion rate in the LESS group (OR 13.21, 95% CI 4.65–37.53; P < 0.001), with most of the conversions being from LESS LDN to the conventional LLDN. The rationale behind the adoption of LESS is mainly based on the potential gain for the patient in terms of lower postoperative pain, shorter hospital stay, and ultimately faster recovery. Length of stay represents an unreliable endpoint in this patient population, as donors may express the desire to remain in the hospital longer because of psychosocial considerations [21]. Unfortunately, a systematic analysis of pain and analgesic use in this setting remains challenging, as this issue has been addressed by the different authors using various methods, different assessment tools, and at different time-points. Moreover, different factors can influence to some extent these variables, including different pain management protocols, patient-specific pain thresholds, and also patient expectations. In their meta-analysis, Fan et al. [14] detected
reduced postoperative pain, and lower analgesic requirement for LESS nephrectomy procedures. Overall, in the present study we found no differences in terms of pain score at discharge, but LESS LDN was associated with a lower inpatient analgesic requirement (WMD –2.58 mg; 95% CI –5.01 to –0.15; P = 0.04). Whether this translates into a significant clinical advantage remains to be seen. The complication rate is broadly considered as another surrogate of surgical competence. Accurate reporting of complications is important for preoperative counselling, and for identifying modifiable risk factors to decrease the complication rate. Greco et al. [37] investigated risk factors for complications in a multi-institutional series of LESS of upper urinary tract disease and found an overall complication rate of 17%. In a larger analysis of LESS including cases for various indications, Autorino et al. [36] reported a 9.4% postoperative overall complication rate, most of them being of low grade. In the present analysis, we did not find any significant difference in terms of postoperative complication rates (OR 1.00, 95% CI 0.65–1.54; P = 0.99) between the two techniques. The overall complication rates for LESS LDN (9.7%) and LLDN (8.4%) compare favourably with a recent analysis of 69 117 LDN cases from the National Inpatient Sample where the procedure-related complication rate for living donors was found to be ≈8% [31]. The present meta-analysis has several potential limitations that should be considered. The main limitation is that most of the studies were retrospective, except for two RCTs, and most had a small sample size. We decided not to include studies from conference abstracts, as they usually do not provide complete information for each endpoint. In addition, the included studies were carried out by surgeons with different backgrounds and applying different techniques. However, all the groups involved in these studies had a solid laparoscopic background. Thus, it might be questionable to extract these findings in different settings and one might argue that LESS may never gain favour as a mainstream urological technique due to current technical difficulties and this is especially true for a high risk/benefit procedure, such as LDN. Finally, the follow-up period was generally short, so long-term outcomes of LESS LDN, especially in terms of graft function, remain to be explored. Moreover, estimated GFR, rather than creatinine levels, represent a more reliable proxy of kidney function. However, it was not possible to do this analysis because of the lack of data. Last, a cost-benefit analysis between LESS LDN and traditional LLDN will also be important in determining the applicability of LESS for this and other applications. Nevertheless, this meta-analysis tries to fill a gap in the current literature on LESS, providing the most up to date information in this area. Moreover, enough data had accumulated to allow an assessment based on meta-analytical methods. Multiple strategies to identify studies, strict criteria of study selection, © 2014 The Authors BJU International © 2014 BJU International
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and standardised evaluation of the methodological quality of the studies have been adopted to provide the best current available evidence.
Conclusions LESS LDN is more technically challenging than its standard LLDN counterpart, as shown by the longer operative time and the greater likelihood of conversion. However, in experienced hands, this procedure can offer comparable surgical and early functional outcomes, and it seems to be associated with lower analgesic requirement. Ultimately, the role of LESS for LDN remains to be defined and, ideally, this novel approach should be compared with standard LLDN in a well-designed, large, prospective, randomised, multi-centre study before gaining wider acceptance.
Conflicts of Interest None disclosed.
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LESS LDN vs conventional laparoscopic LDN
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Correspondence: Riccardo Autorino, Center for Laparoscopic and Robotic Surgery, Glickman Urological and Kidney Institute, Cleveland Clinic, 9500 Euclid Avenue/Q-10, Cleveland, OH 44195, USA. e-mail: [email protected]; [email protected] Abbreviations: BMI, body mass index; EBL, estimated blood loss; (L)LDN, (laparoscopic) living-donor nephrectomy; LESS, laparoendoscopic single-site surgery; OR, odds ratio; RCT, randomised controlled trial; VAS, visual analogue score; WIT, warm ischaemia time; WMD, weighted mean difference.
© 2014 The Authors BJU International © 2014 BJU International
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