Comparison of Laparoscopic and Open Partial Nephrectomy in the Treatment of T1 Renal Tumor:a Systematic Review and Meta-analysis

Objective:Different surgical approaches may bring different treatment results for one disease.We thus determined to gather the current evidence to evaluate the effect of laparoscopic partial nephrecomy(LPN) and open partial nephrectomy(OPN) in the treatment of T1 renal tumor. Methods:We comprehensively researched PubMed,Embase,Google Scholar and Clinicaltrials.gov to nd all referring studies(published between Jan1,2015,and Jan 1,2020 without language restrictions) .We calculated the odds ratios(OR) and standard mean difference(SMD),and analyzed their heterogeneity with RevMan 5.3 software. Results:Six studies were included nally.Comparing open partial nephrectomy, the pooled SMD of operative time was 0.14, (95% condential index CI = [-0.11, 0.38]), the pooled SMD of estimated blood loss was -0.14, (95% CI = [-0.58, 0.31]), the pooled SMD of ischemia time was 0.57, (95% CI = [-0.02, 1.16]), the pooled SMD of length of stay was -0.55, (95% CI = [-1.12, 0.02]),and the pooled OR of positive margin was 1.02, (95% CI = [0.39, 2.68]),the pooled OR of postoperative complications was 0.74,(95% CI = [0.41, 1.36]). Conclusions:LRN had advantages on decreasing postoperative complications rate but the ischemia time of OPN was much shorter.


Introduction
Partial nephrectomy (PN) has become the standard surgical treatment for T1a renal tumors (< 4 cm), and for T1b tumors whenever feasible [1].PN is preferred over radical nephrectomy(RN) for localized T1 renal cell carcinoma,as PN better preserves renal function with comparable oncologic outcomes [2].Furthermore,RN can increase chronic kidney disease and cardiovascular mortality [3].
OPN has been considered as the "gold standard" approach for many years.With the advancement of surgeon's skills and medical equipment,laparoscopic technique has been gradually promoted in the eld of urology.Laparoscopic surgery has the advantages of a small surgical incision, fast postoperative recovery, and small intraoperative blood loss, as well as tumour treatment effectiveness similar to that with open operations [4,5].However,LPN puts higher requirements for surgeon's operating skills and clinical experience.The long learning curve makes LPN available only in large medical centers.
We summarized data for the past ve year on operative time,blood loss volume,ischemia time,length of hospital stay,margin positive rate and postoperative complications rate to compare effects of LPN and OPN on T1 renal tumor patients.We hope it can provide guidance for the clinical application of the surgical approaches.

Search strategy
We comprehensively researched PubMed,Embase,Google Scholar and Clinicaltrials.gov to nd all referring studies,published between Jan1,2015,and Mar 1,2020 without language restrictions.We did the research with key words "T1 renal tumor","partial nephrectomy","laparoscopic","open","LPN","OPN".The systemic reviews and meta-analysis was reported in accordance with the PRISMA guidelines.

Study selection
We searched and read literature matching keywords carefully.Studies were eligible for enrollment only if they met the following criteria:(1)those that conducted LPN versus OPN comparative trials;(2)those whose study subjects were patients at T1 stage;(3)those the data of operative time,blood loss volume,ischemia time,length of hospital stay,margin positive rate and postoperative complications rate were reported.Exclusion criteria were as follows:(1)Patients in the study had signi cant illnesses that could affect the surgery itself;(2)The research data didn't match our target,or recorded data were incomplete and were not suitable for meta-analysis.

Data extraction
Two independent investigators collected literature titles and abstracts,and studies that matched the inclusion criteria were considered as candidates.We extracted the following data from each selected study:study characteristics(authors of the literature,the year of the publication,the study type,basic information of study participants),operative time,blood loss volume,ischemia time,length of hospital stay,margin positive rate and postoperative complications rate.If there was a deviation between the extracted data,the two investigators would discuss and re-extract the relevant data.If there were still differences,it would be referred to a third investigator for judgment.

Data analysis
We calculated pooled estimates of the standard mean differences with 95% con dence intervals in operative time,blood loss volume,ischemia time and length of hospital stay.We calculated pooled estimates of odds ratios with 95% con dence intervals in margin positive rate and postoperative complications rate.We also did I²testing to assess the magnitude of the heterogeneity between studies, with values greater than 50% regarded as being indicative of moderate-to-high heterogeneity [6].We performed sensitivity analysis to the data whose I²>50%.All data were analyzed by Revman(version5.3).

Results
We identi ed 325 studies.After careful selection,6 trials satis ed to the inclusion criteria were included to our study (Fig. 1).All trials were published between 2015 and 2020 (Table 1).Two were prospective studies,one of which was multicenter observational.Four were retrospective studies,one of which wasn't an RCT. Age is exhibited as the median ± IQR The operative time was reported in 4 studies( Fig. 2A).The pooled SMD of theses 4 studies was 0.14 (95% CI = [-0.11, 0.38],P = 0.0005,I²=83%).Considering its high heterogeneity,we used random effect model and performed a sensitivity analysis (Fig. 2B).We found that the main cause of heterogeneity was the study of Luciani 2016.The pooled SMD from these 3 studies was 0.02 (95% CI = [-0.07, 0.11],P = 0.51,I²=0%),which showed no heterogeneity.According to our analysis,there was no signi cant difference(P = 0.63) on operative time between LPN and OPN.

Discussions
PN is the reference standard of care for small renal masses and is preferred over radical nephrectomy because of its equivalent oncological outcomes and superior renal functional preservation [12][13][14].With the prevalence of minimally invasive surgery, LPN becomes common. LPN has several advantages such as accurate tumor dissection, easy intracorporeal suturing, and better perioperative outcomes compared to OPN.In 2003, Gill was the rst to compare the advantages and disadvantages of LPN and OPN in the treatment of renal tumours [15].With the continuous progress of LPN technique,we believe that the data of the past ve years are more representative.
In our study,we compared operative time,blood loss volume,ischemia time,length of hospital stay,margin positive rate and postoperative complications rate.Our results demonstrated that WIT(warm ischemia time) was shorter in OPN compared with LPN,which was consistent with many published studies [15,16].One challenge of LPN is to shorten intraoperative WIT as much as possible, to ensure that postoperative residual kidneys maintain good renal function and to reduce the risk of postoperative acute and chronic renal failure. The consensus in the eld is that a WIT of 25 minutes is the most appropriate in ection point for short-term or long-term renal function damage [17].While a retrospective study by Marszalek et al reported the opposite results and stated that WIT was shorter in LPN compared with OPN [18]. We believe that the reason OPN has a shorter WIT are based on that OPN has lower operational requirements compared with LPN.Theoretically, LPN has very high requirement for microscopic cutting and suture of tumors,although it could be expected that LPN might be bene cial regarding WIT because of pneumoperitoneum.It should be noted that the surgeon's expertise and tumor accessibility are two important factors that may in uence ischemia time [19].
Our study shows that there is no signi cant difference on operative time and estimated blood volume between LPN and OPN.Although we know that LPN has several advantages like reducing bleeding owing to pneumoperitoneum, providing accurate tumor cutting and suturing under magni ed vision, improving patient's postoperative quality through smaller and beautiful surgical incision,and facilitating the coagulation of small vessels [12].According to our analysis,the perioperative success with LPN solely depends on the surgeon's experience.The information of this study comes from different doctors all over the world.Different doctors use different surgical techniques to deal with different patients.This may be the reason that LPN doesn't have advantages in the results of surgical operation.
In our study,we found that LRN had no advantages on length of hospital stay and postoperative positive margin rate.LPN is an advancement in surgical methods.It use a minimally invasive approach to cut the tumor in essence,and there is no change in the surgical method.So,there are not much difference on theses two outcomes,which is also in line with our expectations.
According to our analysis,LPN had advantages on decreasing postoperative complications rate,which is contrary to many published conclusions.In the past,the data trends to that there was no obvious difference between OPN and LPN regarding the postoperative complications rate [20,21].According to our observations,the more stale(out of ve years) data trends to support OPN.The literature in the past three years almost tends to support that LPN has advantages on decreasing postoperative complications rate.We believe that this is due to the development of LPN technique in recent years and the gradually accumulated clinical experience of doctors in large medical institutions.LPN avoids the huge trauma caused by OPN on the patient,and the precise operation under the microscope can avoid damage to adjacent tissues and small blood vessels.Pneumoperitoneum also helps patients avoid gastrointestinal function damage.We believe that LPN can show its full superiority with enough experience.
A limitation of this analysis is that we lack analysis of postoperative oncology and biochemical outcome.After careful data extraction,we found that our statistical literature either lack of relevant data or the data we need were not published under same standards.Second,the sample size is insu cient.There are few relevant literatures in the past ve years and the selection bias is inevitable.Additionally,we were not able to ruled out the effect of surgeon's learning curves on the end results. There was insu cient information on surgeons'experience to perform a sensitivity analysis exploring the impact of the learning curve on end results [22].

Conclusions
Although further studies are needed to con rm that our conclusions are the best clinical applications path,our study clearly lend support to that LRN has advantages on decreasing postoperative complications rate and the ischemia time of OPN was much shorter on T1 renal tumor at this stage.Considering the continuous improvement of surgeon's LPN pro ciency,we can expect that LPN have a long-term development in the future.

Declarations
Acknowledgements None.

Disclaimers
None. It is never been presented/ published before in any form.

Funding
Not applicable.
Availability of data and materials The data used and analyzed in this research can be obtained from the corresponding author with a reasonable request.
Authors' contributions KW is the corresponding author of the article. YMS is the rst author. KW designed the research, interpreted the data, and revised the paper. YMS, ZLZ, KZ, HQS, ZLW, CHL, YLZ, JMG, CL and XYL performed the data extraction. YMS drafted the paper. ZLZ, HTN and KW revised the paper. All authors read and approved the nal manuscript.
Ethics approval and consent to participate All patients in our research provided informed consent before the treatment.
All procedures in this research were performed in accordance with the principles of the Research Ethics Committee of the A liated Hospital of Qingdao University and with the 1964 Helsinki Declaration and its amendments.

Consent for publication
Not applicable.

Figure 1
Study selection process.   The forest plot for the ischemia time between LPN and OPN(A);sensitivity analysis(B).

Figure 5
The forest plot for the length of stay between LPN and OPN. The forest plot for the positive margin rate between LPN and OPN. The forest plot for the postoperative complications rate between LPN and OPN(A);sensitivity analysis(B).