Abstract
Background/Aim: To analyze the effects of laparoscopic partial nephrectomy (LPN) and robot-assisted partial nephrectomy (RAPN) for the treatment of renal cell carcinoma (RCC) on subsequent split renal function using renal scintigraphy. Patients and Methods: We retrospectively analyzed data from 174 patients who underwent LPN or RAPN by a single surgeon, and assessed their total and split renal function before and 6 months after each procedure. Split renal function was analyzed using 99mTc-2,3 dimercaptosuccinic acid renal imaging and calculated as the total estimated glomerular filtration rate (eGFR) × uptake ratio on the surgical side/uptake ratio on the contralateral side. Results: LPN or RAPN were performed in 51 (29.3%) and 123 (70.7%) participants, respectively. Their median eGFRs before and after surgery were 32.76 and 27.74 ml/min/1.73 m2, respectively, and 70 of them (40.2%) showed a preservation of split eGFR of >90%, which was used to define a successful procedure. Participants who underwent a successful procedure had significantly lower RENAL nephrometry scoring system (RNS) scores and fewer of them had external tumors. Successful procedures were associated with shorter warm ischemia time, were more likely to be RAPN, and less likely to involve parenchymal suturing. Multivariate analysis showed that a low RNS score and parenchymal suturing were significant independent predictors of split renal function following partial nephrectomy (PN). Conclusion: Preoperative RNS score and the use of parenchymal suturing are significantly associated with a preservation of split renal function of >90% in patients who undergo PN for the treatment of RCC.
Partial nephrectomy (PN) is the standard treatment for small renal masses (1), and its objectives are to achieve control of the cancer and the preservation of renal function. The oncological outcomes of PN have been shown to be at least as good as those of radical nephrectomy (RN) (2). In addition, the perioperative outcomes of PN have been shown not to be inferior to those of RN, including with respect to complication rates, hospital costs, and quality of life (3-5). It has also been reported that PN is superior to RN for the long-term preservation of renal function in prospective studies (6). Furthermore, patients with a T1a renal cell carcinoma (RCC) who are treated with PN are at lower risks of cardiovascular disease and non-cancer-related death than those treated with RN (7, 8).
The PN procedure involves renal arterial clamping to reduce blood loss and improve visibility at the excision site. This clamping causes warm ischemia and leads to renal injury (9). Furthermore, it requires the excision of functional nephrons adjacent to the tumor, and thus a loss of normal renal parenchyma. Therefore, PN has a negative impact on renal function and may provoke the development of chronic kidney disease. Thus, the assessment of renal function after PN is very important in patients with RCC.
The procedure involved in PN has progressed from open to minimally invasive surgery, including laparoscopic PN (LPN) and robot-assisted PN (RAPN) (10). According to previous reports, LPN is associated with lower blood loss and shorter hospital stays but longer warm ischemia time (WIT) than OPN, and with no differences in the preservation of renal function or the oncological outcomes (11, 12). However, another study showed that RAPN is associated with shorter hospital stays, shorter WIT, and better preservation of renal function than LPN (13). A comparison of RAPN and OPN showed that the WIT, the change in estimated glomerular filtration rate (eGFR), and the oncological outcomes are similar, whereas RAPN is associated with a lower rate of complications, lower blood loss, and shorter hospital stays than OPN (14). However, because there have been no randomized controlled trials comparing OPN, LPN, and RAPN, it is not clear how the postoperative renal function associated with each compares with that associated with RN. Furthermore, to evaluate the effect of the surgical procedure itself on renal function, it is necessary to evaluate split renal function. 99mTc-2,3 dimercaptosuccinic acid (DMSA) renal imaging is accepted to be the most reliable method of measuring split renal function (15, 16), but although there have been previous studies of postoperative total renal function, split renal function has been assessed in few of these.
In this study, we have assessed the perioperative and postoperative outcomes of LPN and RAPN and analyzed their effects on split renal function using renal scintigraphy.
Patients and Methods
Participants. The study was approved by the Ethics Committee and was performed in accordance with the ethical principles of Declaration of Helsinki. We retrospectively identified 203 patients who had undergone LPN or RAPN for the treatment of a renal tumor, and used the following inclusion criteria: 1. the patient underwent LPN or RAPN, performed by a single surgeon, between November 2012 and November 2020; 2. a surgical record and data were available; and 3. total and split renal function had been assessed before and after surgery (6 months later). Patients who had horseshoe kidney, underwent conversion to open surgery, or underwent conversion to nephrectomy were excluded. One hundred seventy-four patients fulfilled these criteria and were enrolled.
Renal function. Preoperative and postoperative total renal function were evaluated using serum creatinine (sCr) concentration and eGFR, which was calculated for men as 194× sCr-1-094 × age-0.287 and for women as 0.739× the equivalent eGFR for a man. Split renal function was analyzed using 99mTc-DMSA renal imaging as split eGFR=total eGFR× uptake ratio on the surgical side / uptake ratio on the contralateral side. We assessed the split eGFR immediately before and 6 months after surgery and calculated the change in split eGFR.
Perioperative data and surgical procedure. We conducted an exploratory study of the factors associated with the surgery-associated change in renal function. The age; sex; body mass index (BMI); radius, exophytic/endophytic properties, nearness of tumor to the collecting system or sinus in millimeters, anterior/posterior, location relative to polar lines nephrometry scoring system (RNS); and Mayo adhesive probability score (MAP score), assessed using computed tomography (CT), were recorded pre-operatively (17, 18). We also recorded whether the tumor was located externally to the kidney or not, because those located externally are more difficult to fully visualize during PN (Figure 1). The perioperative outcomes recorded were the operative time, WIT, estimated blood loss (EBL), whether the collecting system was opened or not, and whether parenchymal suturing was performed or not.
Location of the tumor that was external or not. An external tumor was defined as being contralateral to the hilum of the kidney.
The surgical approach, either transperitoneal or extraperitoneal, was chosen according to the tumor location. For LPN procedures, four-to-six trocars were used, and for RAPN procedures, the da Vinci Si or Xi surgical system (Intuitive Surgical Inc., Sunnyvale, CA, USA), with four arms and one-to-two trocars, was used. A surgical assistant provided suction and traction, and inserted the tools. The hilar vessels were minimally dissected to permit clamping, then the perirenal fat around the tumor was removed, and laparoscopic ultrasonography was used to confirm the location and shape of the tumor and delineate the appropriate margin for resection. The renal artery was then clamped using a laparoscopic bulldog clamp, excision was performed along the identified line, and the tumor was completely removed from the renal parenchyma. After hemostasis, the opened collecting system and large vessels were repaired using sutures and the clamp on the renal artery was removed. The placement of parenchymal sutures and use of tissue sealants and/or thrombogenic agents were performed at the discretion of the surgeon.
Statistical analysis. Continuous data are presented as median and interquartile range, and categorical data are presented as count and percentage. To compare the characteristics and outcomes of the two groups, the Mann-Whitney U-test and chi-square test were used for continuous and categorical data, respectively. Logistic regression models were used to identify parameters that would predict the preservation of split renal function, and those with p<0.05 on univariate analysis were included in multivariate analysis.
Two-tailed p<0.05 was accepted as indicating statistical significance. Statistical analyses were performed using SPSS Statistics for Windows, version 19.0 (IBM Corp., Armonk, NY, USA).
Results
Participant characteristics. Table I shows the characteristics of the 174 patients who met the inclusion criteria. Their median preoperative and postoperative total eGFRs were 64.25 and 60.26 ml/min/1.73 m2, respectively, and the median preservation of total eGFR was 95.5%. The median preoperative and postoperative split eGFRs were 32.76 and 27.74 ml/min/1.73 m2, respectively, and the median preservation of the split eGFR was 87.4%. A summary of the preoperative evaluation of the difficulty of PN is provided in Table II. The most common RNS values were 6 and 7 points and 11 of the participants had highly complex tumors (≥10 points). Nearly half of the tumors had a high MAP score (≥2) and 62 were located externally to the kidney.
Patient characteristics.
Preoperative parameters describing the surgical difficulty.
Surgical outcomes. A transperitoneal approach or a retroperitoneal approach were used in 110 (63.2%) and 64 (36.8%) participants; and LPN or RAPN was performed in 51 (29.3%) and 123 (70.7%) participants, respectively. The mean operative time was 209 min, the mean EBL was 100 ml, and the mean WIT was 20 min. Renal parenchymal suturing was performed in 124 (71.3%) participants. The pathological finding of 145 (83.3%) of the participants was clear-cell RCC. One patient had a positive surgical margin and another experienced the postoperative complication of pseudo-aneurysm.
Preservation of split renal function. We defined “success” of the procedures as a preservation of the split eGFR of ≥90%. According to this criterion, the procedures were successful in 70 participants (40.2%). A detailed comparison of the participants who underwent successful or unsuccessful procedures is shown in Table III. Success was associated with significantly lower RNS, a lower prevalence of external tumors, and a shorter WIT. Interestingly, many of the participants who experienced success underwent RAPN and did not undergo parenchymal suturing. Logistic regression analysis showed that a low RNS score and parenchymal suturing were significant independent predictors of split renal function following PN.
Comparison of perioperative data for participants who underwent successful or unsuccessful procedures.
Discussion
It is important for PN to achieve the triple goals of negative surgical margin, complication-free recovery, and preservation of function: the so-called “trifecta”. However, negative surgical margins are achieved in most cases, and the incidence of perioperative complications has tended to decrease because of technical advances. Therefore, the achievement of the trifecta requires the targeting of the preservation of renal function. In many previous studies, 1) a WIT of <25 min, or 2) the maintenance of postoperative eGFR at >90% has been used to indicate the preservation of renal function following PN. Several recent studies have shown that prolonged warm ischemia (>25 min) may be associated with irreversible renal injury (19-21). However, others have generated an ischemia threshold of 28 or 30 min (22, 23). Furthermore, the postoperative total eGFR does not reflect the direct effect of surgery alone, because it is affected by contralateral renal function. Therefore, to identify the factors that are associated with the preservation of renal function following surgery, the factors that affect renal function should be characterized.
Many studies have identified factors that affect renal function following PN, and these include age (24), the time to the nadir of eGFR (24), tumor size (24), baseline eGFR (25, 26), loss of nephron volume (25, 27), WIT (26, 27), and type of surgery (26). In the present study, the RNS score, WIT, tumor location, renal parenchymal suturing, and robotic assistance together accounted for the preservation of >90% of split renal function. Furthermore, the RNS score and renal parenchymal suturing were found to be significant independent predictors of the preservation of split renal function. Because the RNS score is an indicator of the difficulty of PN, it is likely to be associated with the preservation of split renal function. In addition, parenchymal suturing may cause injury to renal arterial branches, thereby causing a reduction in peripheral blood flow, leading to irreversible ischemia of the residual renal parenchyma. The primary goal of parenchymal suturing is to ensure hemostasis and the closure of the urinary collecting system. However, because compression of the tumor causes narrowing and reduction in the number of smaller arterioles, hemostasis by parenchymal suturing may not be necessary for tumors that are excised near the tumor capsule (28). The removal of such tumors may not require parenchymal suturing to close the urinary collecting system if this has not been opened. Furthermore, excision near the tumor capsule may contribute to the preservation of most of the non-tumoral parenchyma, thereby assisting with the preservation of renal function. Although case selection is necessary, the avoidance of parenchymal suturing may help preserve split renal function more effectively.
The present study had some limitations. First, it was a retrospective study with a short follow-up period. Therefore, it is impossible to discuss the changes in split renal function that occur over longer periods of time. Second, the data were collected at a single institution and all of the participants were operated on by a single surgeon. Therefore, the results may not be directly translatable to other institutions and surgeons. Third, there is no established standardized target for the preservation of split renal function. In the present study, we defined the appropriate preservation of split renal function as a reduction in split eGFR of <10%, consistent with previous studies (29, 30). However, the findings may help surgeons identify the surgical procedures for LPN and RAPN that are best for the preservation of renal function. To further clarify the factors that contribute to the preservation of renal function, a large prospective clinical study should be conducted.
In conclusion, we have shown that several factors contribute to the preservation of split renal function following LPN and RAPN. Specifically, RNS score, as a preoperative factor, and parenchymal suturing, as an intraoperative factor, are significantly assorted with the preservation of split eGFR at >90%.
Acknowledgements
The Authors thank Mark Cleasby, PhD from Edanz (https://jp.edanz.com/ac) for editing a draft of this manuscript.
Footnotes
Authors’ Contributions
Conception or design of the work: K.O. and T.M.; acquisition of data: K.O., Y.N. and K.M.; analysis or interpretation of data: K.O. and Yasuyoshi Miyata; drafting or revising work: Yasushi Mochizuki, H.N. and K.O.
Conflicts of Interest
The Authors declare that they have no conflicts of interest in relation to this study.
- Received March 9, 2022.
- Revision received April 20, 2022.
- Accepted April 21, 2022.
- Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
