Perioperative and long-term functional outcomes of robot-assisted versus open partial nephrectomy: A single-center retrospective study of a Japanese cohort

Objective This study aimed to compare the perioperative and long-term functional outcomes between robot-assisted partial nephrectomy (RAPN) and open partial nephrectomy (OPN) in Japanese patients. Methods We retrospectively analyzed 242 patients who underwent either RAPN or OPN between 2007 and 2017 at our hospital. Propensity score matching was carried out between the two groups at a ratio of 1:1. Perioperative outcomes and postoperative estimated glomerular filtration rates (eGFR) were compared at one and three years of follow-up. Results After propensity score matching, we evaluated 39 patients from each group. The ischemia duration of the RAPN group was significantly shorter than that of the OPN group (18 vs. 24, p < 0.001). Moreover, the estimated blood loss (EBL) was significantly lower in the RAPN group than in the OPN group (50 vs. 174, p < 0.001). However, there were no significant differences in the postoperative eGFR between the two groups at one or three years of follow-up (OPN 54.8 vs. RAPN 61.2, p = 0.109, and OPN 54.8 vs. RAPN 55.5, p = 0.262, respectively). Conclusion RAPN resulted in shorter ischemia durations and lower rates of EBL than did OPN; however, no differences in long-term renal function were observed between RAPN and OPN in our propensity-score matched Japanese cohort.


Introduction
Partial nephrectomy (PN) has been the standard treatment for small renal tumors for some time, as the long-term oncological outcomes and preservation of renal function rival those of radical nephrectomy (RN) [1][2][3]. In terms of the evolution of nephrectomy, open radical nephrectomy (ORN) has been replaced by open PN (OPN) which in turn, paved the way for minimally invasive PN, the latter of which includes both laparoscopic PN (LPN) and robot-assisted PN (RAPN) [4]. Laparoscopic RN (LRN) is a mature technique with a short learning curve that has been widely used by surgeons; moreover, LRN has been associated with fewer perioperative complications than its counterparts [5]. On the other hand, LPN is a challenging procedure with a steep learning curve. Hence, its adoption is limited among urologists [6,7]. Over the past decade, technological evolution and the adoption of robotic surgical platforms has spurred the popularity of RAPN. Large comparative studies and meta-analyses have previously reported the significant advantages of RAPN over LPN [8][9][10].
However, to date, comparisons of outcomes between RAPN and OPN in Japanese patients have not been widely introduced, especially regarding long-term functional outcomes. Therefore, in the present study, we aimed to compare the effects of RAPN on outcomes with those of OPN. The primary aim was to compare the perioperative outcomes of RAPN and OPN, and the secondary aim was to compare the long-term functional outcomes of them, using a propensity-score matched Japanese cohort.

Patient population
In this study, we retrospectively reviewed the clinical data of 242 patients who underwent either RAPN or OPN at Fujita Health University between August 2007 and September 2017, excluding those who had incomplete data, combined surgery, solitary kidney, multiple renal tumors, benign tumors, and metastatic tumors.

Surgery
We discussed the method of RAPN in our previous report [11]. Briefly, the tumor was resected with 2-5 mm of the parenchymal margin. For the inner renorrhaphy layer, the collecting system and large vessels were closed with 3-0 V-Loc sutures, and if needed, parenchymal sutures were made with 2-0 V-Loc. Seven surgeons who completed the da Vinci certification program approved in Japan performed RAPN.
During OPN, ice slush was placed around the kidney. The tumor was excised under cold, ischemic conditions involving clamping of the renal artery, and an adequate surrounding margin of normal renal tissue was retained. Opened calyces and bleeding sites were sutured, and the parenchymal defect was closed with horizontal, interrupted sutures.

Data collection
We recorded the following information preoperatively and at one and three years of follow-up: patient characteristics, including age, gender, and body mass index (BMI); clinical disease characteristics, including tumor side, RENAL score [12], and presence of a hilar tumor; surgical parameters, including operation time, ischemia duration, estimated blood loss (EBL, mL), need for blood transfusion, and presence of complications (Clavien-Dindo) [13]; and renal function findings, including estimated glomerular filtration rate (eGFR, mL/min/1.73 m 2 ) as calculated using the Modification of Diet in Renal Disease equation [14]. All patients underwent preoperative cross-sectional imaging to evaluate location, tumor size, and depth of tumor to assess the RENAL score.
The protocol of this study was approved by the ethics committee of our institution (HM 16-340), and the study was performed in accordance with the ethical standards laid down in the most recent version of the Declaration of Helsinki. The need for informed consent from all patients included in this study was waived because of the retrospective design. The work has been reported in line with the STROCSS criteria [15].

Statistical analyses
Owing to inherent differences in baseline patient and disease characteristics between the RAPN and OPN groups, we used 1:1 propensity score-matched analysis to adjust for imbalances in confounding factors. The propensity scores of each patient were calculated using multivariable logistic regression. Comparisons between the groups were performed using either the chi-square test or Fisher's exact test. All data were analyzed using IBM SPSS Statistics version 23 (SPSS Japan Inc., Tokyo, Japan), and p-values of <0.05 were considered significant in all statistical analyses.

Patients enrolled in the current study
In this study, we selected 242 patients who underwent PN at our hospital between August 2007 and September 2017. After excluding patients who did not fulfill our criteria, a total of 181 patients (OPN: 42, RAPN: 139) were enrolled. A 1:1 propensity score-matched analysis was performed, and 39 patients from each group were evaluated (Fig. 1).

Clinical characteristics of patients
Patient characteristics, including age, sex, BMI, tumor side, preoperative eGFR, RENAL score, and the presence of hilar tumors, were compared between the OPN and RAPN groups both before and after matching. In both cases, no significant differences in factors were observed between the OPN and RAPN groups (Table 1).

Perioperative outcomes
Following propensity matching, we compared the perioperative factors, including operation time, ischemia duration, EBL, need for transfusion, Clavien-Dindo classification ≥3, and postoperative eGFR at both one and three years of follow-up between the OPN and RAPN groups. Although there was no significant difference in the operation time between the two groups (OPN 169 vs. RAPN 175, p = 0.500), the ischemia duration was significantly shorter in the RAPN group than in the OPN group (18 vs. 24, p < 0.001). Moreover, the EBL was significantly lower in the RAPN group than in the OPN group (50 vs. 174, p < 0.001). No significant differences were observed between the OPN and RAPN groups in terms of transfusion and Clavien-Dindo classification (OPN 7.7% vs. RAPN 7.7%, p = 1.00, and OPN 5.1% vs. RAPN 5.1%, p = 1.00, respectively) ( Table 2).

Long-term functional outcomes
With respect to renal function, there were no significant differences in postoperative eGFR between the two groups at either one or three years of follow-up (OPN 54.8, RAPN 61.2, p = 0.109, and OPN 54.8 vs. RAPN 55.5, p = 0.262, respectively) (Fig. 3).
Following 1:1 propensity score matching of the RAPN and OPN groups, 39 Japanese patients from each group were evaluated. Moreover, the ischemia duration of the RAPN group was significantly shorter than that of the OPN group (18 vs. 24, p < 0.001). The OPN procedure can be performed using the cold ischemia technique in order to prevent renal function, whereas RAPN is performed with the warm ischemia technique. Hence, it is unlikely that the difference in ischemia duration between RAPN and OPN affected renal function. Furthermore, Takagi et al. reported that patients undergoing RAPN had a shorter ischemia duration than those undergoing OPN (21 vs. 35 min, p < 0.001), as different ischemia methods were used (warm and cold ischemia in the RAPN and OPN groups, respectively) [24]. However, according to a recent systematic review and meta-analysis of comparative studies comparing perioperative outcomes between RAPN and OPN, the latter had a significantly shorter ischemia duration [29]. These controversial results ultimately depend on the tumor's anatomical complexity and the skill of the surgeon.
Regarding the EBL in the operation, it was significantly less in the RAPN group than in the OPN group (50 vs. 174, p < 0.001). As was the case in our study, Xia et al. demonstrated that the EBL of 2833 patients was significantly lower in patients undergoing RAPN than those undergoing OPN [29].
With respect to long-term renal function, we assessed the postoperative eGFR at one and three years after RAPN. Our study demonstrated that there were no significant differences in the postoperative eGFR at one or three years between the RAPN and OPN groups. This finding was supported by numerous recent studies with similar findings [17,[19][20][21][23][24][25][30][31][32].
This study had some limitations. First, this was a retrospective, single-institution study. Second, in order to adjust for clinical and demographic imbalances, we performed a matched-pair analysis, which resulted in a small number of patients. Third, since several surgeons performed the RAPN and OPN operations, the technical proficiency of Fig. 1. Flowchart of the patients enrolled in the study. We evaluated 242 patients who underwent partial nephrectomy. We included 181 patients in the present study and divided them into groups according to the operation method. Propensity score-matched analysis was performed thereafter.  In conclusion, RAPN and OPN showed similar long-term renal function outcomes in this Japanese cohort. However, a shorter ischemia duration and lower EBL was observed when RAPN was used.

Take-home messages
In the Japanese cohort, RAPN provides similar outcomes of longterm renal function to OPN, however, it appeared to be a valuable alternative to OPN, with the advantages of reduced ischemia time and blood loss.

Source of funding
No specific funding was received for the present analysis.

Ethical approval
The protocol of this study was approved by the ethics committee of our institution (HM 16-340), and the study was performed in accordance with the ethical standards laid down in the most recent version of the Declaration of Helsinki.

Registration of research studies
Name of the registry: Perioperative and long-term functional outcomes of robot-assisted versus open partial nephrectomy: a singlecenter retrospective study of a Japanese cohort Unique Identifying number or registration ID: 7496 Hyperlink to your specific registration (must be publicly accessible and will be checked): performed

Consent
The need for informed consent from all patients included in this study was waived because of the retrospective design.

Provenance and peer review
Not commissioned, externally peer-reviewed.

Guarantor
The Guarantor is Kiyoshi Takahara.

Declaration of competing interest
The authors declare that there are no conflicts of interests.