Comparison of Surgical Outcomes Between Resection and Enucleation in Robot-Assisted Laparoscopic Partial Nephrectomy for Renal Tumors According to the Surface-Intermediate-Base Margin Score: A Propensity Score-Matched Study

Abstract

Objective:

To compare the surgical outcomes between resection and enucleation in robot-assisted laparoscopic partial nephrectomy (RAPN) based on the Surface-Intermediate-Base margin score (SIB score).

Patients and Methods:

This study included 282 patients who underwent RAPN between 2014 and 2016. SIB score was macroscopically evaluated immediately after the surgery. We divided the patients into the following two groups: enucleation (SIB score, 1–2) and resection (SIB score, 3–5). To minimize selection bias between the two surgical methods, patient variables were adjusted by 1:1 propensity score matching.

Results:

Of the 282 patients, 48 were assigned to the enucleation group and 234 to the resection group. After matching, 45 patients were included in each group. The mean preoperative estimated glomerular filtration rate (eGFR) was 70 mL/min/1.73 m². The mean tumor size was 32–33 mm. The decrease in eGFR (5.6 vs 12%, p = 0.0365) and total perioperative complication (16% vs 38%, p = 0.0171) were significantly lower in the enucleation group than in the resection group. Estimated blood loss was higher in the enucleation group than in the resection group (129 cc vs 117 cc, p = 0.0088), despite a similar transfusion rate. The postoperative length of hospital stay was shorter in the enucleation group than in the resection group (4.1 vs 5.0 days, p = 0.0288). Operation time and surgical margin status were not significantly different between groups.

Conclusions:

In carefully selected patients, enucleation was associated with more favorable surgical outcomes in the cohort than resection, including improved renal function and a lower complication rate.

Introduction

Partial nephrectomy (PN) is a standard surgical approach for small renal tumors and is listed in several guidelines.^1,2 The purpose of PN is to preserve renal function as much as possible with oncological equivalence to radical nephrectomy and acceptable surgical complications. The most important factor in preserving renal function is the preservation of normal renal parenchyma, given that limited warm ischemia or hypothermal ischemia are applied.

The enucleation technique is an ideal resection method to preserve maximal normal renal parenchyma in cases with a negative surgical margin. A large comparative cohort study demonstrated significantly lower positive surgical margin rates with tumor enucleation (1.4%) than with standard PN (6.9%).³ Moreover, the study emphasized another potential benefit of tumor enucleation, that is, larger branch vessels and the collecting system are avoided by elevating the tumor out of deep sinuses, thereby minimally affecting these critical sutures.³ Previous studies have compared tumor enucleation and standard PN^4
–6; the surgical feasibility of tumor enucleation may be achieved with an appropriate patient selection.

In general, tumor enucleation consists of blunt dissection along a pseudocapsule, yielding a specimen that includes a tumor surrounded by a pseudocapsule with minimal or no parenchyma.⁷ In cases of deep tumors, the pseudocapsule of the area attached to the renal sinus is exposed, while other areas are covered with normal parenchyma. Thus, identifying the surgical technique in such cases, that is, either enucleation or resection, poses a challenge especially considering that a standardized definition of tumor enucleation is lacking. Minervini and colleagues advocated the Surface-Intermediate-Base margin score (SIB score) to standardize the reporting of resection techniques during PN, which reflects the surgical margin status in each part of the resected area.⁸ In our study, we compared the surgical outcomes between tumor enucleation and standard PN based on the SIB score using propensity score matching.

Patients and Methods

Patient population

We obtained study approval from the Institutional Review Board of our hospital. A total of 282 patients who underwent robot-assisted laparoscopic partial nephrectomy (RAPN) between January 2014 and August 2016 participated in this study. The SIB scores were according to a previous study⁸ and determined by macroscopic findings immediately after surgery. Patients were divided into two groups according to their SIB score: the enucleation group (SIB score, 1–2) and the resection group (SIB score, 3–5). Tumor complexity was determined according to the RENAL nephrometry score (RENAL-NS).⁹ The following factors were considered patients' background characteristics to be adjusted by 1:1 propensity score matching to minimize selection bias between the two surgical approaches: age, sex, body mass index, American Society of Anesthesiologists (ASA) score, tumor size, tumor complexity (RENAL-NS score), and preoperative estimated glomerular filtration rate (eGFR). Perioperative surgical outcomes were defined as follows: decrease in eGFR, operation time, warm ischemia time (WIT), estimated blood loss (EBL), transfusion, surgical margin status, perioperative complications, and postoperative length of hospital stay. The Clavien-Dindo classification system¹⁰ was used to classify perioperative complications. Almost all patients underwent enhanced CT to assess for asymptomatic renal artery pseudoaneurysm (RAP).

Surgery

RAPN was performed using the techniques previously described.¹¹ All surgeries were performed by three specific surgeons. In the early period of this study, we intended to resect the tumor with ∼5 mm of normal parenchyma. On the other hand, the enucleation technique was adopted to select patients in the later period of this study. All RAPN procedures were performed under warm ischemia. Renal arteries were clamped with a bulldog clamp in most cases. The renal vein was also clamped when tumors were in close contact with the main branches of the renal vein. After completing the incision, an inner running suture was placed using a barbed suture (15 cm 3-0V-Loc^® 180 with a half-circle 17-mm needle; Covidien, New Haven, CT, USA). After placing the inner suture, the arterial clamp was removed and the absence of arterial bleeding was confirmed. Renorrhaphy was performed using a barbed suture (30 cm 2-0V-Loc^® 180 with a half-circle 37 mm needle; Covidien) and a TachoSil^® bolster was placed in the defect.

Renal function evaluation

All serum creatinine measurements were analyzed at a single clinical reference laboratory, and eGFR values were estimated using the Modification of Diet in Renal Disease two equation recently modified for Japanese patients, as stipulated by the Japanese Society of Nephrology (eGFR = 194 × serum creatinine (mg/dL)^−1.094× age^−0.287 × 0.739 [if female]).¹² Renal function was evaluated <2 months before and 1–3 months after surgery.

Statistical analysis

Continuous variables were analyzed using the Man–Whitney U-test, and categorical variables were analyzed using the χ² test. Multivariate logistic regression analyses were used to calculate the propensity scores. All analyses were performed using JMP 11.2.0 software (SAS Institute, Cary, NC), and p-values less than 0.05 were considered statistically significant.

Results

Table 1 presents a comparison of the patients' background. In the enucleation group (48 patients), 18 patients had a score of 1 and 30 patients a score of 2; in the resection group (234 patients), 43 patients had a score of 3, 45 patients a score 4, and 146 patients a score of 5. Before matching, the patients in the enucleation group had more complex tumors (p < 0.001), a larger tumor size (34 vs 28 mm, p = 0.0017), tumors nearer to the collecting system (p < 0.0001), and more endophytic tumors (p = 0.0058) than those in the resection group. After matching, the mean tumor size was 32–33 mm, and relatively higher complex tumors were distributed in each group (Low: 9%–13%, Intermediate: 62%–73%, High: 18%–24%). The mean preoperative eGFR was 70 mL/min/1.73 m².

Table 1.

Patient Characteristics

	Prematching			Postmatching
	Group 1 (n = 48) ^a	Group 2 (n = 234) ^b	p	Group 1 (n = 45) ^a	Group 2 (n = 45) ^b	p
Age (years), mean (SD)	57 ± 13	58 ± 14	0.8395	57 ± 813	57 ± 16	0.9433
Sex, male, n (%)	30 (63)	172 (74)	0.1234	29 (64)	32 (71)	0.4986
BMI (kg/m2), mean (SD)	24 ± 3.9	24 ± 3.5	0.6373	24 ± 3.8	24 ± 3.2	0.9287
Preop eGFR (mL/min/1.73 m²), mean (SD)	71 ± 16	66 ± 18	0.0842	70 ± 16	70 ± 19	0.9773
ASA score, n (%)
1	11 (23)	52 (22)	0.5009	11 (24)	15 (33)	0.6461
2	36 (75)	167 (71)		33 (73)	29 (64)
3	1 (2)	15 (6)		1 (2)	1 (2)
Tumor complexity, n (%)
Low (4–6)	6 (13)	97 (41)	<0.0001	6 (13)	4 (9)	0.5264
Intermediate (7–9)	28 (58)	117 (50)		28 (62)	33 (73)
High (10–12)	14 (29)	20 (9)		11 (24)	8 (18)
Tumor size (mm), mean (SD)	34 ± 10	28 ± 10	0.0017	33 ± 10	32 ± 11	0.8075
R, n (%)
1	33 (69)	198 (85)	0.0248	33 (73)	32 (71)	0.5538
2	14 (29)	35 (15)		11 (24)	13 (29)
3	1 (2)	1 (0.4)		1 (2)	0
E, n (%)
1	4 (8)	72 (31)	0.0058	4 (9)	2 (4)	0.2080
2	38 (79)	137 (59)		35 (78)	41 (91)
3	6 (13)	25 (11)		6 (13)	2 (4)
N, n (%)
1	2 (4)	94 (40)	<0.0001	2 (4)	2 (4)	0.9557
2	7 (15)	32 (14)		7 (16)	6 (13)
3	39 (81)	108 (46)		36 (80)	37 (82)
L, n (%)
1	14 (29)	95 (40)	0.0488	14 (31)	14 (31)	0.9570
2	7 (15)	52 (22)		7 (16)	8 (18)
3	27 (56)	87 (37)		24 (53)	23 (51)

Group 1: enucleation.

Group 2: resection.

SD = standard deviation; BMI = body mass index; Preop = preoperative; eGFR = estimated glomerular filtration rate; ASA = American Society of Anesthesiologist.

Table 2 shows a comparison of the surgical outcomes between the two groups. After matching, there was a 5.6% decrease in eGFR in the enucleation group and 12% in the resection group, which was significantly different (p = 0.0365). EBL was significantly higher in the enucleation group than in the resection group (129 mL vs 117 mL, p = 0.0088). However, the transfusion rate was 1% in the enucleation group and 2% in the resection group; this difference was not significant (p = 0.5571). Overall perioperative complications were significantly lower in the enucleation group than in the resection group (16% vs 38%, p = 0.0171). The enucleation group included two patients with grade 3 complications, including asymptomatic RAP requiring percutaneous transarterial embolization (TAE). In the resection group, 11 patients had asymptomatic RAP requiring TAE. We hypothesized as to the reason for an incidence rate that was higher than expected in our study. In our institution, patients who are not allergic to dye agents or those with severe renal dysfunction who undergo PN receive enhanced CT on POD3 to screen for asymptomatic RAP as previously reported.^11,13
–15 In addition, most patients prophylactically embolized especially in the early postoperative periods. This might have caused the incidence of asymptomatic RAP to be higher than expected. Patients with the enucleation had shorter hospital stay than those with the resection (4.1 days vs 5.0 days, p = 0.0288). Other outcomes, including operation time, WIT, surgical margin status, and perioperative transfusion rate, were not significantly different between the two groups.

Table 2.

Surgical Outcomes

	Prematching			Postmatching
	Group1 (n = 48) ^a	Group 2 (n = 234) ^b	p	Group1 (n = 45) ^a	Group 2 (n = 45) ^b	p
Preop eGFR (mL/min/1.73 m²), mean (SD)	71 ± 16	66 ± 18	0.0842	70 ± 16	70 ± 19	0.9773
Postop eGFR (mL/min/1.73 m²), mean (SD)	66 ± 914	62 ± 18	0.1361	65 ± 14	62 ± 17	0.2641
Decrease rate in eGFR (%)	6.3 ± 13	7.0 ± 13	0.7239	5.6 ± 13	12 ± 17	0.0365
OT (min), mean (SD)	190 ± 39	180 ± 41	0.1204	189 ± 37	193 ± 43	0.6524
WIT (min), mean (SD)	25 ± 12	18 ± 6.5	0.0002	24 ± 12	20 ± 6.4	0.1562
Console time (min), mean (SD)	140 ± 37	131 ± 35	0.0933	140 ± 36	142 ± 5.7	0.7668
EBL (mL), mean (SD)	124 ± 205	60 ± 159	<0.001	129 ± 211	117 ± 337	0.0088
SM negative, n (%)	47 (98)	233 (99)	0.213	44 (98)	45 (100)	0.3146
Transfusion, n (%)	1 (2)	2 (1)	0.4498	1 (2)	2 (4)	0.5571
Perioperative complications, n (%)
Overall	7 (15)	55 (24)	0.174	7 (16)	17 (38)	0.0171
Clavien 1–2	5 (10)	38 (16)		5 (11)	9 (20)
Clavien 3	2 (4)	24 (10)		2 (4)	8 (18)
PLOS (day), mean (SD)	4.2 ± 1.8	4.8 ± 2.9	0.0033	4.1 ± 1.8	5.0 ± 0.3	0.0288

Group 1: enucleation.

Group 2: resection.

Postop = postoperative; OT = operative time; WIT = warm ischemia time; EBL = estimated blood loss; SM = surgical margin; PLOS = postoperative length of hospital stay.

Discussion

To successfully achieve the goal of PN for renal tumors, preservation of normal parenchyma with limited ischemia time, negative surgical margin, and less perioperative complications are vital. The enucleation technique may be a more ideal surgical method for the preservation of normal parenchyma given the negative surgical margin and lower complication rate. This study demonstrated that enucleation is significantly associated with a better renal functional outcome compared with resection using propensity score matched analyses. However, whether the renal functional benefit resulted from the preservation of the renal parenchyma is uncertain because this study did not include a volumetric study. Blackwell and colleagues addressed functional implications and volume preservation of renal tumor enucleation relative to standard PN using a volumetric analysis that is specific to the operated kidney. They reported that tumor enucleation resulted in the preservation of renal parenchymal mass and surgical precision.⁵ Moreover, preservation of global renal function favored tumor enucleation (96% vs 93%), albeit no statistical difference was found.⁵ Although our study did not analyze surgical precision or parenchymal mass preservation, the enucleation technique could apparently preserve more normal parenchyma.

Surgical margin status is an essential factor to consider in tumor enucleation; several studies have reported on this controversial oncological outcome.^16

–19 This study showed one case of positive surgical margin status in the enucleation group and two cases in the resection group. Several articles addressed this issue and demonstrated that tumor enucleation is not associated with adverse effects on surgical margin status compared with standard PN.^3,4 Instead, tumor enucleation tended to provide a lower positive surgical margin rate compared with standard PN.^3,4 During tumor enucleation, a capsulized tumor is bluntly pealed along the tumor margin from the renal parenchyma, which can be clearly visualized; therefore, the risk of cutting into a tumor capsule by sharp dissection is possibly reduced. Regarding recurrence and survival issues, Minervini and colleagues demonstrated the oncologic equivalence between simple enucleation and standard PN in both progression-free survival and cancer-specific survival with median follow-up periods of 50–55 months.⁴ With appropriate patient selection, the oncological feasibility of tumor enucleation may be achieved. In addition, surgical expertise and sufficient training on the technique will be required to achieve optimal enucleation. Exposing the tumor pseudocapsule without penetrating the tumors and uncovering the tumor surface without rupturing tumors are necessary to ensure optimal oncological outcomes of PN. Performing this procedure optimally requires a certain level of surgical experience and skill.

This study showed a lower incidence of perioperative complications in the enucleation group than in the resection group (p = 0.0171). In addition, the Clavien grade 3 complication, which was asymptomatic RAP requiring TEA, occurred 4% in the enucleation group and 18% in the resection group. In our institution, asymptomatic RAP was routinely screened by enhanced CT on POD3 as reported in previous studies.^11,13
–15 These studies demonstrated that renal sinus exposure was an independent risk factor for asymptomatic RAP¹⁴ and an early unclamp technique might reduce asymptomatic RAP.¹¹ The enucleation technique, which involves pealing the tumor pseudocapsule, enables us to identify vessels feeding into the tumor, which should be clipped or coagulated. Therefore, excessive suturing of the resection bed, which might damage renal artery, is avoided. These factors may result in a lower incidence of asymptomatic RAP when using the enucleation technique. Therefore, we must consider whether asymptomatic RAP should be treated by TAE. It is possible that many asymptomatic RAP naturally disappear. In fact, in the recent period of this study, we observed many cases of asymptomatic RAP that naturally disappeared. Therefore, the incident rate of asymptomatic RAP requiring TAE decreased according to the study era. We were prompt to perform the enucleation technique in relatively recent era, which might account for the difference in the incident rate of asymptomatic RAP requiring TAE.

This study utilized SIB score to define tumor enucleation technique. The concept of this scoring system was firstly described by Minervini and colleagues to standardize the definition of tumor enucleation in PN.⁸ The definition of excision technique was categorized as follows: pure enucleation, hybrid enucleation, pure enucleoresection, hybrid enucleoresection, and resection according to tumor margin status; all these are scored based on the surface, intermediate, and base surgical margins.⁸ Thereafter, they confirmed that the gross scoring reports reflected the thickness of healthy renal margin on microscopic examination.²⁰ The excision methods in our study were divided into two groups according SIB core: enucleation (score, 1–2) and resection (score, 3–5). No patient had a score of 0; 18 patients had a score of 1 (surface score, 1; intermediate score, 0; base score, 0) and 30 patients a score of 2 (surface score, 1; intermediate score, 1; base score, 0). Based on these within-group similarities, the SIB score 1–2 was incorporated into the enucleation group.

Our study has several limitations. First, this study is retrospective in nature, was conducted in a single institution, and included a population of tertiary care patients. Second, the decrease in eGFR of the operated kidney could not be estimated, because pre- and postoperative renal scans were not performed. In addition, because a volumetric study was not included, whether better renal functional outcomes were associated with better surgical precision or normal parenchymal preservation remains to be identified. Third, the selection of the excision methods was dependent on the surgeons (three specific surgeons performed RAPN in this study), and the surgical era. As described in the methods section, the enucleation technique was adopted in the relatively recent period of this study, which might associate with surgical precision including preserving kidney function or incidence of perioperative complications. Fourth, our definition of excision methods, including the enucleation and resection techniques, missed to include the details described in the previous sentence. Fifth, postoperative renal function was measured within 1–3 months after surgery, which was relatively short period to assess renal functional outcome. The strengths of this study include matching of patients' characteristics between the enucleation and resection groups by propensity scoring; thus, the surgical and functional outcomes were well balanced and comparable between the two groups.

Conclusions

This study resulted in better renal functional outcomes in the enucleation group than in the resection group, and despite the longer WIT in the enucleation group, the surgical margin status was similar between the groups in carefully selected patients. Moreover, the SIB scoring method may be an optimal clarification system in defining the excision methods. However, whether enucleation is feasible for challenging tumors, such as cystic tumors, ambiguous pseudocapsule, or locally invasive tumors, remains to be determined. Evaluation of long-term renal functional and oncological outcomes, and more large-scale studies are warranted.

Footnotes

Acknowledgement

We thank Ms. Nobuko Hata for her secretarial work.

Compliance with Ethical Standards

Ethical approval: all procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. IRB approved number: 4223.

Author Disclosure Statement

No competing financial interests exist.

Abbreviations Used

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