Comparison of Postoperative Complications Between Robotic and Laparoscopic Rectal Cancer Surgery

Objective: Robotic and laparoscopic surgery for rectal cancer have been applied in clinic for decades, nevertheless, which surgical approach has a lower rate of postoperative complications is still inconclusive. Therefore, the aim of this meta-analysis is to compare the postoperative complications between robotic and laparoscopic rectal cancer surgery based on randomized controlled trials. Methods: Randomized controlled trials (until May 2020) which compared robotic and laparoscopic rectal cancer surgery were searched through PubMed, EMbase, Cochrane library, CNKI, Wan Fang databases and CBM. Data regarding sample size, clinical and demographic characteristics, overall postoperative complications, and the incidence of anastomotic leakage (cid:0) incision infection (cid:0) bleeding (cid:0) ileus (cid:0) respiratory complications (cid:0) urinary complications (cid:0) unscheduled reoperation (cid:0) perioperative mortality were extracted. The results were analyzed using RevMan v5.3. Results: Seven randomized controlled trials which included 507 robotic and 516 laparoscopic rectal cancer surgery cases were included. Meta-analysis showed that the overall postoperative complications [Z=1.1 (cid:0) OR=1.18 (cid:0) 95% CI (0.88-1.57), P=0.27], anastomotic leakage [Z=0.96, OR=1.27, 95% CI (0.78-2.08), P=0.34], incision infection [Z=0.18, OR=1.05, 95% CI (0.61-1.79), P=0.86], bleeding [Z=0.19, OR=0.89, 95% CI (0.27-2.97), P=0.0.85], ileus [Z=1.47, OR=0.66, 95% CI (0.38-1.15), P=0.14], respiratory complications [Z=0.84, OR=0.64, 95% CI (0.22-1.82), P=0.40], urinary complications [Z=0.66,


Background
Laparoscopic rectal resection has been widely used for the treatment of rectal cancer because it results in shorter length of hospital stay, less postoperative pain and faster recovery of bowel function when compared with open surgery [1][2][3] . However, laparoscopic technology is associated with some innate limitations, such as a twodimensional view and limited dexterity, which may affect the outcomes of surgery [4,5] .
Since robotic surgery was rst used in rectal disease in 2001 [6] , robotic surgery has gained great popularity around the world. This technique has several advantages over laparoscopic surgery, including an immersive three-dimensional view of the surgical eld, better dexterity capability and a stable camera platform [7] . Surgeons hope that such innovative technology could alleviate some of the maneuverability and visibility challenges that surgeon encounter in the narrow pelvis cavity.
A number of comparative studies have reported the results between robotic and laparoscopic surgery rectal cancer, but it is still unclear which surgical approach has a lower rate of postoperative complications [8][9][10] .Therefore, we conducted this meta-analysis to evaluate the postoperative complications between robotic and laparoscopic rectal cancer surgery based on the randomized controlled trials only.

Search strategy
We conducted this meta-analysis in accordance with the preferred reporting items for systematic reviews and meta-analysis: the PRISMA statement [11] .
The search strategy were according to PICOT framework. P(population): adult population with primary rectal cancer; I(intervention): robotic rectal resection; C(comparison): laparoscopic rectal resection; O(outcomes): postoperative complication; T(type of study design): randomized controlled trial. the following databases were searched PubMed EMbase the Cochrane library CNKI WANFANG databases CBM. A systematic literature search was performed using the combination of medical subject headings (MeSH) and free-text words, the search terms are as follows: rectal neoplasm OR rectal cancer OR rectal carcinoma OR rectal tumor AND robotics OR robotic surgical procedures AND laparoscopy OR laparoscopic surgery AND randomized controlled trial OR prospective.
The last search was performed on April 2020, the search strategy was limited to papers written in English or Chinese language, and the reference lists of the eligible studies were tracked manually for other potentially relevant studies.

Eligibility criteria and study selection
Two independent authors (TB, HZX) screened the articles retrieved from the initial literature, duplicate studies were removed and irrelevant studies were discarded. Two authors further reviewed the eligibility studies independently in abstract form or in full text by assessing if the eligibility criteria were met, Disagreements regarding study selection between the two authors were resolved by discussion and consensus or by consulting a third independent author (LX). Eligibility criteria were predetermined as follows: (1) randomized controlled trials; (2) comparison between robotic and laparoscopic surgery for resection of rectal cancer; (3) postoperative complication were clearly de ned.
Data extraction and quality assessment The following data from the enrolled studies were extracted independently by two authors (TB, HZX): the paper Publication year, country of the study, study design, operative methods, sample size, characteristic of patients (age, gender, body mass index and ASA), clinical outcomes (overall postoperative complications, anastomotic leakage, incision infection, bleeding, ileus, respiratory complications, urinary complications, unscheduled reoperation and perioperative mortality). The quality of included RCTs was evaluated by using the Cochrane collaboration's tool for assessing risk of bias [12] . Discrepancies regarding data extraction between two authors were resolved by discussion with the third author.

Statistical analysis
Review Manager (Revman version 5.3, Copenhagen, Nordic Cochrane Center, Cochrane Collaboration, 2014) was used to perform the meta-analysis. Dichotomous variables were analyzed using the odds ratio (OR) with a 95% CI. Heterogeneity was evaluated by I 2 statistic. If I 2 50% data analysis was performed by using xed effects model, otherwise, a random-effect model was used. P 0.05 was considered statistically signi cant. Publication bias among the included studies was evaluated by funnel plots.

Literature searching
A total of 1593 literatures were identi ed in initial screening, after excluding the duplicated studies, we screened 1183 literature and identi ed 35 eligible studies by scanning the title and abstract. of these 35 studies, we identi ed seven articles that met the inclusion criteria for the nal analysis after full text evaluation [13][14][15][16][17][18][19] . The study selection progress is presented in Fig 1.

Characteristics of included studies
The included studies involved 1023 patients (ranging from 36 to 471 per trial) from ve countries (Korea, China, Egypt, UK, Italy) which contained 507 in the robotic group and 516 in the laparoscopic group. The mean age ranged from 55.1 to 69 years and the male to female ratio was 2.2:1, mean body mass index (BMI) varied from 22 to 25.4 Kg/m 2 , the prevalence of ASA I score varied from 6% to 80%, ASA II from 20% to 64%, ASA III from 0 to 53% and ASA IV from 0 to 2.8%.Characteristics of included studies were summarized in table 1. -

Risk of bias assessment
None included studies were judged as a high risk of bias on all items, seven items were all judged as low risk of bias in two included studies, whereas the remaining studies had one or two items were considered as unclear risk found among studies (I 2 =0%, P=0.55), (Fig 3).  (Fig 10).

Publication bias
A funnel plot was constructed for the overall postoperative complications to assess the publication bias, which showed that the possibility of publication bias was relatively small (Fig 12).

Discussion
With the development of laparoscopic technology, laparoscopic surgery has become a standard surgical procedure for rectal cancer. Compared to open surgery, laparoscopic surgery has the advantage of shorter length of hospital stay, faster recovery after operation, alleviated postoperative pain, and earlier return to normal bowel function [20][21][22] . However, conventional laparoscopic rectal cancer surgery is technically demanding, especially for male and obese patients with narrow pelvis and low rectal cancer. Laparoscopic rectal cancer surgery performed by two dimensional view and long straight instruments shown a higher conversion rate, which undoubtedly lead to increased postoperative complications and worse oncological outcomes [23,24] . Robotic surgery has the advantages to overcome some innate limitations of laparoscopic surgery, including three dimensional magni ed vision, stable camera platform and better dexterity [25] . Although robotic surgery has been applied to the treatment of rectal cancer for decades, whether those advantages of Da Vinci robot can turn into better clinical bene ts , such as lower incidence of postoperative complications, remains debatable. Therefore, we designed this metaanalysis to answer this question. Our results showed that the overall postoperative complications was similar after robotic and laparoscopic rectal cancer resection, and the incidence of anastomotic leakage, incision infection, bleeding, ileus, respiratory complications, urinary complications, unscheduled reoperation and perioperative mortality were also similar between robotic and laparoscopic surgery for rectal cancer resection.
Overall postoperative complications is an important index to measure the safety and feasibility of a surgical procedure, So we further explore the advantages and disadvantages of robotic and laparoscopic surgery from the perspective of postoperative complications. Seven latest RCTs were included in this study including 507 patients undergoing robotic surgery and 516 patients undergoing laparoscopic surgery, and the results of bias risk assessment showed that none included studies were judged as a high risk of bias. the meta-analysis results showed that no signi cant difference in overall postoperative complication between robotic rectal cancer surgery and laparoscopic surgery, which is consistent with previous RCTs and meta-analyses [10,16,26] , Therefore, we conclude that robotic rectal cancer surgery are equally safe and feasible when compared with laparoscopic surgery.
Anastomotic leakage is one of the most important complications after radical resection of rectal cancer. The acute diffuse peritonitis caused by anastomotic leakage is the most serious complication after rectal surgery, which can lead to reoperation, even cause death [27] . In previous study, the incidence of anastomotic leakage is 3.0% to 12.1% in robotic rectal surgery and 2.6% to 6.8% in laparoscopic surgery [13,16] , and the anastomotic leakage usually caused by low anastomotic position, poor blood ow, high tension and local infection [28,29] . In this meta-analysis, the incidence of anastomotic leakage was 7.7%% in robotic group and 6.2% in laparoscopic group, the pooled result shown no signi cant different between two group, which is similar to the results of Prete and Luo's meta-analysis [10,26] . Hence, we conclude that robotic surgery for rectal cancer does not increase the occurrence of anastomotic leakage when compared with laparoscopic surgery.
Urinary complications is one of the parameters to evaluate the protection of pelvic autonomic nerve during operation. Although urinary complications are thought to be caused by multiple factors, iatrogenic damage during surgery is consider to be the main cause, which leads to a great negative impact on the postoperative quality of life [30,31] . Previous studies [15,32] showed that robotic rectal surgery can signi cantly protect pelvic autonomic nerve and reduce the incidence of postoperative urinary complications because of its 10-fold magni cation of surgical eld. But in our meta-analysis, the signi cant difference of the urinary complications between robotic and laparoscopic rectal surgery did not observed. Five included studies reported the results of urinary complications, however, two of included studies did not have clear de nition of urinary complication, and there may be some clinical heterogeneity in the included studies. Therefore, the advantages of robot surgery in protecting pelvic autonomic nerve need further high-quality clinical research to evaluate.
The seven studies included in this meta-analysis incorporated the latest results of prospective randomized controlled trials, especially including the latest results of RCT published by our center in April 2020 [19] . But this current meta-analysis has certain limitation. Firstly, many detail information concerning the gastrointestinal complications, respiratory complications and urinary complications are not mentioned clearly in original studies, which may be one of the reasons for heterogeneity among studies. Secondly, the sample size of some included studies is relatively small, so sensitivity analysis are not available, and the reliability of conclusions is decreased. Finally, difference in learning curve, surgeons' technique and measurement of results may produce some biases that are di cult to avoid and control.

Conclusion
The present study suggests that robotic surgery for rectal cancer has the same incidence of postoperative complications, such as anastomotic leakage, incision infection, bleeding, ileus, respiratory complications and urinary complications, compared with laparoscopic surgery. Further, high quality multicenter RCTs are needed to con rm the advantage of robotic surgery for rectal cancer resection.     Perioperative mortality Figure 12 Funnel plot for overall postoperative complications