Retroperitoneal Versus Transperitoneal Laparoscopic Partial Nephrectomy: A Systematic Review and Meta-analysis△

Jing Fu*, Shan Ye, and Hua-jian Ye

1Department of Urology, Shaoxing Branch, the First Affiliated Hospital of Zhejiang University School of Medicine (Shaoxing Second Hospital), Shaoxing, Zhejiang 312000, China

2Department of Public Health, Tashan Community Health Service Center, Yuecheng District, Shaoxing 312000, Zhejiang, China

Retroperitoneal Versus Transperitoneal Laparoscopic Partial Nephrectomy: A Systematic Review and Meta-analysis△

Jing Fu1*, Shan Ye2, and Hua-jian Ye1

1Department of Urology, Shaoxing Branch, the First Affiliated Hospital of Zhejiang University School of Medicine (Shaoxing Second Hospital), Shaoxing, Zhejiang 312000, China

2Department of Public Health, Tashan Community Health Service Center, Yuecheng District, Shaoxing 312000, Zhejiang, China

retroperitoneal； transperitoneal； laparoscopy； partial nephrectomy；systematic review

Objective To review published literatures comparing the safety and effectiveness of retroperitoneal laparoscopic partial nephrectomy （RLPN） with transperitoneal laparoscopic partial nephrectomy （TLPN） and provide reference for clinical work.

Methods The search strategy was performed to identify relevant papers from the Cochrane Central Register of Controlled Trials， EMBASE， MEDLINE， Google Scholar， China Hospital Knowledge Database，Wangfang Chinese Periodical Database， and VIP Chinese Periodical Database. All papers comparing RLPN with TLPN were included from 2000 to 2015. Two to three reviewers independently screened， evaluated， and extracted the included papers. A Meta-analysis was executed by using Review Manager 5.3 software. The interesting outcomes were tumor size， operating time， estimated blood loss， warm ischaemia time， length of hospital stay， positive margin rate， open conversion rate， overall complication rate， and recurrence rate.

Results The literature search obtained 378 papers， then 10 of them were ultimately met the inclusion criteria and included in the systematic review. Finally， 6 of the 10 papers were included in the Meta-analysis. RLPN had significantly less operating time ［p = 0.01， mean difference （MD）=-33.68， 95% confidence interval （CI） within （-60.35， -7.01）］ and shorter length of hospital stay ［p ＜ 0.0001， MD=-1.47， 95% CI within （-2.18， -0.76）］ than TLPN. Significant differences were not found between RLPN and TLPN in other outcomes.

Conclusions RLPN may be equally safe and be faster than TLPN. Each center can choose a modality according to your own operating habits and experience.

Chin Med Sci J 2015； 30（4）:239-244

P ARTIAL nephrectomy （PN） has become a gold standard treatment for small renal masses.1Compared with radical nephrectomy （RN）， PN is associated with similar oncological outcomes and long-term preservation of renal function.1，2PN can be realized by using open PN （OPN）， laparoscopic PN （LPN）， or robotic-assisted surgery. Compared with OPN， LPN can obtain the same as functional and oncologic outcomes got by OPN， less blood loss， and shorter hospital stay.3，4With advancement in minimally invasive surgery， LPN with retroperitoneal （RLPN） and transperitoneal （TLPN） approaches has obtained worldwide acceptance in experienced centres.4-7RLPN and TLPN approaches have their respective advantages and limitations. By a systematic review and Meta-analysis of related literatures， the safety and effectiveness of the two approaches are compared in order to provide reference for clinical work.

MATERIALS AND METHODS

Literature search

The search strategy was performed to identify relevant papers from the Cochrane Central Register of Controlled Trials， EMBASE， MEDLINE， Google Scholar， China Hospital Knowledge Database， Wangfang Chinese Periodical Database，and VIP Chinese Periodical Database. Language restrictions was not suffered. The search was carried out on February 28， 2O15. The used search terms included "retroperitoneal"，"transperitoneal"， "laparoscopic"， "nephron-sparing surgery"，"partial nephrectomy"， and "heminephrectomy". The references in the retrieved papers and the conference materials were manually searched to identify related papers. The related authors were contacted wherever the papers were unavailable or unclear.

Inclusion criteria

（1） The literature which contained the comparison between RLPN and TLPN was utilized， （2） a randomized controlled trial or the design of a retrospective comparative method was included， and （3） age， gender， race were not constrained.

Exclusion criteria

（1） Literature did not meet the inclusion criteria， （2） if materials were incomplete， then the authors were contacted，but did not reply， and （3） when two similar studies were reported by the same institution and/or authors， the more comprehensive report was selected， and the first author was contacted to clarify the differences.

Quality assessment and data extraction Two reviewers independently screened and assessed the papers that satisfied the inclusion criteria according to the Cochrane Reviewers' Handbook version 5.1.O. Three reviewers independently extracted the related data from them. Disagreements were resolved by all authors' consensus. To compare RLPN with TLPN， the following outcomes were extracted from the included literatures： patient's demographics，tumor size， operating time， estimated blood loss， warm ischaemia time （WIT）， length of hospital stay （LOS），positive margin rate， open conversion rate， overall complication rate， and recurrence rate.

Statistical analysis

This Meta-analysis was executed according to the Cochrane review guidelines. Statistical analysis was completed using Review Manager 5.3 software provided by the Cochrane Collaboration. For dichotomous data， a Mantel-Haenszel chi-square test was used and expressed as the odds ratio（OR） with 95% confidence interval （CI）； while for continuous data， an inverse variance was used and expressed as the mean difference （MD） with 95% CI. In two cases， P＜O.O5 was considered as the statistical significance. Heterogeneity was evaluated by using the chi-square test with the condition P ＜ O.1O and by using the I2test. We used the random-effects model if there was heterogeneity among research results （P＜O.1O， I2＞5O%）. Otherwise， the fixed-effects model was selected. A subgroup analysis was carried out to assess whether the tumor size， the WIT， the positive margin rate， and the complication rate varied between the two cases or not. Although the relational papers were not included in the Meta-analysis， they were included in the systematic review for a general overview. Publication bias was assessed by Begg's funnel plot8and Egger's test.9Begg's funnel plot was asymmetric or Egger's test with P ＜ O.O5 if publication bias existed.

RESULTS

Literature retrieval results

The literature search obtained 378 papers from the year 2OOO until 2O15， then 1O of them ultimately met the inclusion criteria and included in the systematic review.1O-19While 6 of the 1O papers were finally included in the Meta-analysis，11，13，15，16，18，19as shown in Fig. 1. The remaining 4 papers were excluded because their data could not be pooled in the Meta-analysis. Despite our best efforts， we failed to gain the standard deviations of their results. All the papers were retrospective observational papers without randomization. There were 856 patients involved in LPN， while 422 of them were RLPN， and thenthe remaining 434 patients were TLPN. The demographics of the included papers were described in Table 1. The review emphasised on the 6 papers included in the Meta-analysis. Most of the papers were published in the last 5 years， indicating that there was a growing concern.

Meta-analysis results between RLPN and TLPN

From the 6 papers11，13，15，16，18，19， there were not statistical differences between RLPN and TLPN in overall tumor size ［P = O.19， MD =-2.18， 95% CI within （-7.O1， 1.39）］， tumor size of robot-assisted subgroup ［P = O.42， MD =-5.O4， 95% CI within （-17.28， 7.2O）］， and tumor size of no robotassisted subgroup ［P = O.42， MD =-1.92， 95% CI within（-6.64， 2.79）］.

Figure 1. Flowchart of article selection process.

From the five papers，11，13，15，16，18the RLPN group had significantly less operating time than the TLPN group ［P = O.O1， MD = -33.68， 95% CI within （-6O.35， -7.O1）］ （Fig. 2）. When we excluded the robot-assisted study，18the result of Meta-analysis was not changed ［P = O.O4， MD = -31.32，95% CI within （-6O.47， -2.18）］ （Fig. 3）. One paper19reported the result as median （min）： RLPN 12O （95-146.75）vs. TLPN 15O （11O-187.5）. Other four papers1O，12，14，17reported the result as mean without standard deviation［RLPN vs. TLPN （min）］： 21O vs. 324， 133 vs. 125， 83.9（5O-165） vs. 139.3 （9O-19O）， and 148.5 （88-235） vs. 195.3 （1OO-33O）， respectively.

From the six papers11，13，15，16，18，19， there were not statistical differences between RLPN and TLPN in overall WIT ［P = O.14， MD = -5.38， 95% CI within （-12.61，1.85）］， WIT of robot-assisted subgroup ［P = O.O9， MD = -2.75， 95% CI within （-5.96， O.45）］， and WIT of no robot-assisted subgroup ［P = O.18， MD = -7.13， 95% CI within （-17.62， 3.36）］. Three papers1O，14，17reported the result as mean without standard deviation ［RLPN vs. TLPN（min）］： 32.9 vs. 32.5， 22.6（13-37） vs. 24.3（12-45）， and 22.1（O-48） vs. 19.1（O-4O）， respectively.

From the five papers，11，13，15，16，18there was not statistical difference between RLPN and TLPN in estimated blood loss ［P = O.77， MD = -O.85， 95% CI within （-6.58，4.88）］. One paper19reported the result as median （ml）：RLPN 1OO （73.75-212.5） vs. TLPN 15O （1OO-25O）. Other two papers1O，17reported the result as mean without standard deviation ［RLPN vs. TLPN （ml）］： 192 vs. 4O3 and 88 （2O-16OO） vs. 395.1 （2O-31OO）.

From the four papers，11，13，15，16the RLPN group had asignificantly shorter LOS than the TLPN group ［P ＜ O.OOO1，MD = -1.47， 95% CI within （-2.18， -O.76）］ （Fig. 4）. One paper14reported the result as median （d）： RLPN 5 （5-6） vs. TLPN 7 （5.8-8.3）. Three papers1O，12，17reported the result as mean without standard deviation ［RLPN vs. TLPN （d）］：2.3 vs. 3.6， 2.3 （1-6） vs. 2.6 （O.5-5）， and 2.5 （1-5O） vs. 4.6 （1-28）， respectively.

Table 1. Demographics of included studies

From the six papers，11，13，15，16，18，19there were not statistical differences between RLPN and TLPN in overall positive surgical margins ［P = O.87， OR = O.91， 95% CI within （O.3O， 2.77）］， positive surgical margins of robot-assisted subgroup ［P = O.78， OR = 1.32， 95% CI within （O.19， 9.32）］， and positive surgical margins of no robot-assisted subgroup ［P = O.7O， OR = O.76， 95% CI within （O.2O， 2.96）］.

From the six papers11，13，15，16，18，19， there were not statistical differences between RLPN and TLPN in overall complication rate ［P = O.82， OR = 1.O5， 95% CI within（O.67， 1.67）］， complication rate of robot-assisted subgroup［P = O.36， OR = 1.69， 95% CI within （O.55， 5.18）］， and complication rate of no robot-assisted subgroup ［P = O.86，OR = O.96， 95% CI within （O.58， 1.59）］.

There was not statistical difference between the two groups in open conversion rate11，13，15［P = O.71， OR = O.78，95% CI within （O.2O， 2.97）］， or recurrence rate11，15［P = O.51， OR = 1.68， 95% CI within （O.36， 7.91）］.

Publication bias

The funnel plot for tumor size indicated that the research outcome was within the 95% CI and distributed symmetrically （Fig. 5）， and Egger's test was P ＞ O.O5，which are no evidence of publication bias.

Figure 2. Forest plot of operating time （min） for RLPN vs. TLPN in 5 studies. SD：standard deviation； IV：inverse variance； CI： confidence interval.

Figure 3. Forest plot of operating time （min） for RLPN vs. TLPN in 4 studies.

Figure 4. Forest plot of length of hospital stay （d） for RLPN vs. TLPN in 4 studies.

Figure 5. Funnel plot of tumor size analyzed in the Meta-analysis. SE： standard error； MD： mean difference.

DISCUSSION

The systematic review included 1O papers comparing RLPN with TLPN， while 6 of them were performed Metaanalysis. The results found that RLPN had significantly less operating time and shorter LOS. Significant differences were not found between RLPN and TLPN in other outcomes.

Four papers reported less operating time in RLPN.11，13，15，16The four papers also reported shorter LOS in RLPN.11，13，15，16Ng et al11and Choo et al19all reported that TLPN was associated with significantly longer WIT. Cui et al16and Tanaka et al18reported that operating time did not show any significant difference between the two approaches. Although there were differences between RLPN and TLPN，the pooled Meta-analysis found that most of the results were not associated with statistical differences between the two groups， except less operating time and shorter LOS in RLPN.

At present， the essential endoscopic equipment and operative techniques for RLPN and TLPN are almost identical. The transperitoneal path provides a larger working space and familiar anatomic landmarks， but demands mobilization of the bowel to expose the kidney.1OThe disadvantages of the retroperitoneal path include a smaller working space，less anatomic landmarks， the risk of disorientation， and causing inadvertent injury，2Obut it can offer more direct access to the kidney and hilum and avoid bowel mobilization，and thus reduce the operating time. There was also a shorter LOS in RLPN than TLPN. The RLPN can decrease the incidence of intestinal obstruction and make gastrointestinal function recover more quickly by avoiding bowel manipulation and preventing urine and blood from contacting with the bowel.

In addition， 4 papers were excluded in the Metaanalysis due to lack of data. Wright et al1Oreported that RLPN was associated with significantly shorter operating time， less blood loss and shorter LOS than TLPN. Castellan et al12did not find the statistical differences between the two groups. Marszalek et al14reported significantly less operating time and shorter LOS in RLPN. Hughes-Hallett et al17reported that there was a significant reduction in both estimated blood loss and operating time in RLPN.

We would like to emphasize our research limitations. First， patient cohorts in the included papers are small in the Meta-analysis. Only three of the six papers included had more than 1OO patients， and the remaining papers had fewer number of patients.13，16，18These papers might report their initial experiences. However， as the growth of relevant experience， some results of the comparative analysis may change. Second， all the included literature was observational， and the lack of randomization may increase potential selection bias. Third， despite using various search methods， but we can not guarantee that all the papers which meet the inclusion criteria have been searched and included in the systematic review. Finally， heterogeneity among papers was obvious for most of the continuous variables. The possible reasons are as follows. There is significant difference regarding definitions， inclusion and exclusion criteria， operative technique， endoscopic equipment，and measurement of outcomes. It is difficult to match all patient cohorts for their age， body mass index， previous abdominal history， and tumor position. The random-effects model might minimize the effects of heterogeneity， but not eliminate them.

In conclusion， the Meta-analysis of the literature shows that RLPN can shorten the operation time and reduce the LOS. RLPN may be equally safe and be faster than TLPN. Each center can choose a modality according to your own operating habits and experiences. Due to the inherent limitations， further studies need to evaluate the conclusions extracted from the pooled results.

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for publication April 13, 2015.

Tel: 86-75-88055555, E-mail: jingsaox@163.com

△Supported by the Science and Technology Plans of Shaoxing Science and Technology Bureau, China (2010D10014).