Off-Clamp Robot-Assisted Partial Nephrectomy: Is There Something More to Achieve Optimal Trifecta Outcomes?

Abstract

Objectives:

To report trifecta outcomes of our “off-clamp” partial nephrectomy (PN) patients operated without main renal artery and/or any selective/superselective clamping.

Materials and Methods:

Between April 2008 and March 2020, 52 patients received “off-clamp” robot-assisted partial nephrectomy. Postoperative sixth month estimated glomerular filtration rate (eGFR) and eGFR decrease were considered for renal function evaluation. Patients with negative surgical margins, <15% postoperative eGFR decrease and absence of grade ≥2 Clavien–Dindo complications were reported to achieve trifecta outcomes.

Results:

Mean age and body mass index of the patients were 57.51 ± 12.99 years and 27.23 ± 4.35 kg/m², respectively. Mean preoperative hematocrit, serum creatinine, and eGFR were 42.01 ± 3.86%, 0.92 ± 0.28 mg/dL, and 85.26 ± 21.27 mL/min/1.73 m², respectively. Mean tumor size was 30.32 ± 13.64 mm. Mean PADUA and RENAL scores were 7.63 ± 1.46 and 6.21 ± 1.63, respectively. One patient had focal surgical margin positivity. Mean console time and estimated blood loss was 82.11 ± 38.51 minutes and 280.76 ± 278.98 mL, respectively. Complications were observed in two (4%) patients (one Clavien I, one Clavien IIIB). At postoperative sixth month, serum creatinine and eGFR were 0.95 ± 0.32 mg/dL and 83.65 ± 22.44 mL/min/1.73 m², respectively. Eventually seven patients had ≥15% postoperative eGFR decrease, one patient had grade ≥2 complication and one patient had positive surgical margin. Forty-three (83%) patients fulfilled trifecta outcomes.

Conclusion:

Off-clamp PN is important for optimal renal function preservation. Patient selection and additional operative measures along with experience in robotic procedure can contribute achievement of optimal trifecta outcomes.

Introduction

Partial nephrectomy (PN) is deemed treatment of choice for T1 renal tumors.¹ “Trifecta” is a notion to announce PN outcomes. It is composed of negative surgical margins, optimal renal function preservation, and absence of complications in the same patient.²

Preoperative renal function, preserved vascularized renal volume, and ischemia time are main components for renal function recovery.³ Although the first component cannot be surgically modified, the latter two can be. Therefore, different techniques have been described to minimize/eliminate warm ischemia and hence to preserve maximal vascularized renal volume and all are named “zero ischemia.” Approving main renal artery clamping as “on-clamp” and the mainstay for “zero ischemia”; not clamping renal artery; and “off-clamp” PN is thought to be the primary option for “zero ischemia.” However, there are “on-clamp” techniques classified as “zero ischemia.” Selective renal arterial branch/tumor artery clamping, early unclamping, parenchymal clamping are “on-clamp” “zero ischemia” techniques. Targeted flow interruption, radiofrequency, hydro-jet-assisted PN are “off-clamp” “zero ischemia” techniques.^1,4 Simone and colleagues reported the term “minimally ischemic PN” to involve techniques used to achieve “zero ischemia.”⁵

We report trifecta outcomes of our “off-clamp” robot-assisted partial nephrectomy (RAPN) patients operated without main artery or selective/superselective clamping. We also present our attitude for preserving maximum vascularized renal volume together with ideal oncological outcomes and complication rates to achieve optimal trifecta outcomes.

Materials and Methods

Between April 2008 and March 2020, 52 of 267 RAPN patients received “off-clamp” procedure. Data were retrospectively evaluated with approval of Acibadem University Institutional Research Ethics Committee (ATADEK-2020-10/3).

Patients' preoperative demographic data, tumor characteristics, perioperative data, early postoperative complications (within 30 days according to Clavien–Dindo classification) were recorded. Preoperative demographic data included age, gender, body mass index (BMI), American Society of Anesthesiologists (ASA) physical status score, comorbidities, Charlson's comorbidity index (CCI) score, hematocrit (Hct), serum creatinine (Cr), and estimated glomerular filtration rate (eGFR). eGFR was calculated according to 2009 chronic kidney disease (CKD)-EPI (CKD Epidemiology Collaboration) equation.⁶ Tumor characteristics included size, side, PADUA, RENAL scores, histopathology, and surgical margin status. Perioperative data included operative time, estimated blood loss (EBL), transfusion rate, length-of-hospital stay (LOS), drain, urethral catheter removal time, intraoperative complications, and follow-up period.

Patients were evaluated with computed tomography and/or magnetic resonance imaging (MRI) preoperatively. Renal vascular anatomy was investigated. All procedures were performed by a single experienced surgeon with da Vinci Si, Xi Surgical systems transperitoneally. AirSeal^R system was used for insufflation. In all procedures renal pedicle was identified. Tumor borders were delineated with laparoscopic ultrasonography probe. Enucleation was the preferred excision method; when not possible, resection was performed. Peroperative frozen-section analysis (FSA) was performed in case of positive surgical margin (PSM) suspicion. Oxy de cellulose, autolog fibrin, and hemostatic agents were used for hemostasis. Biochemical tests and blood count were performed on postoperative second day.

Complications were documented with Clavien–Dindo system. Follow-up consisted of visits at months 1, 3, and every 3 months thereafter for year 1 and every 6 months for years 2–3, and then annually. Physical examination, biochemical tests, and sonography imaging were performed at each visit and MRI at 12 months and then once a year.

Renal function was evaluated by Cr and eGFR at every visit. For trifecta outcomes, postoperative sixth month eGFR and eGFR decrease were used. CKD upstaging was also evaluated at postoperative sixth month. CKD upstaging was defined as progression to stages III, IV, or V.⁷ Because CKD upstaging alone can conceal the real renal function preservation, eGFR and eGFR decrease were used. Postoperative sixth month data were used to ensure homogeneity. Patients with negative surgical margins, <15% eGFR decrease, and absence of grade ≥2 complications were reported to achieve trifecta outcomes.

Statistical analysis

Mann–Whitney U test was performed to assess the difference of tumor size, PADUA, RENAL score, BMI, ASA, EBL, CCI between the patients with <15%, and ≥15% eGFR decrease. Correlation of EBL, PADUA, and RENAL score with percentage of eGFR decrease was evaluated using Pearson correlation test. After confirmation of correlation between EBL and percentage of eGFR decrease, threshold EBL to differentiate <15% and ≥15% eGFR decrease was searched using two proportions z-test. Pearson correlation test was used to analyze the relationship of PADUA and RENAL score with EBL. After confirmation of correlation between PADUA score, RENAL score, and EBL, threshold PADUA and RENAL scores were searched to discriminate EBL less than and greater than or equal to previously determined threshold for percentage of eGFR decrease using two proportions z-test. Significance of hypertension and diabetes mellitus (DM) between the patients with <15% and ≥15% eGFR decrease was evaluated using two proportions z-test.

Results

Patient characteristics and operative data are given in Table 1. Mean age and BMI were 57.51 ± 12.99 years and 27.23 ± 4.35 kg/m². There were 33 male and 19 female patients. Mean ASA and CCI scores were 1.86 ± 0.59 and 1.58 ± 1.25, respectively. Twenty-eight patients had hypertension (12 with DM and 4 with cardiovascular disease). Two patients had DM. Mean preoperative Hct, Cr, and eGFR were 42.01 ± 3.86%, 0.92 ± 0.28 mg/dL, and 85.26 ± 21.27 mL/min/1.73 m², respectively. Two patients had solitary kidney.

Table 1.

Patient Characteristics and Operative Data

n: 52	Preoperative and demographic data		Tumor characteristics		Periperative data
	Age (years)	57.51 ± 12.99	Size (mm)	30.32 ± 13.64	Operative time (minutes)	82.11 ± 38.51
	Gender	33 M, 19 F	Side	28 R, 24 L	EBL (mL)	280.76 ± 278.98
	BMI (kg/m²)	27.23 ± 4.35	PADUA score	7.63 ± 1.46	Transfusion (n, %)	0 (0%)
	ASA score	1.86 ± 0.59	RENAL score	6.21 ± 1.63	LOS (days)	3.71 ± 1.05
	CCI score	1.58 ± 1.25	Histopathological diagnosis	−39 (75%) RCC−9 (17%) AML−2 (4%) oncocytoma−1 (2%) liposarcoma−1 (2%) leiomyoma	Drain removal period (days)	2.55 ± 1.53
	Hct (%)Cr (mg/dL)	42.01 ± 3.860.92 ± 0.28	PSM (n, %)	1 (2%)	Foley catheter removal period (days)	1.21 ± 0.77
	eGFR (mL/min/1.73 m²)	85.26 ± 21.27			Complications (perop–postoperative 30 days)	2/52 (4%)1 Clavien I1 Clavien IIIB
Follow-up (months)			35.61 ± 21.27

ASA = American Society of Anesthesiologists; AML = angiomyolipoma; BMI = body mass ındex; CCI = Charlson's comorbidity index; Cr = creatinine; EBL = estimated blood loss; eGFR = estimated glomerular filtration rate; Hct = hematocrit; LOS = length-of-hospital stay; PSM = positive surgical margin; RCC = renal cell carcinoma.

Lesions were left sided in 28 patients and right sided in 24. Mean tumor size was 30.32 ± 13.64 mm. Mean PADUA and RENAL scores were 7.63 ± 1.46 and 6.21 ± 1.63. Tumors were polar/centrally located, there was no hilar tumor. FSA was performed in five patients. FSA revealed no surgical margin positivity (SMP), but one patient without FSA had focal SMP. There were 39 renal cell carcinoma, 9 angiomyolipoma, 2 oncocytoma, 1 liposarcoma, and 1 leiomyoma.

Mean console time and EBL was 82.11 ± 38.51 minutes and 280.76 ± 278.98 mL. In three patients pelvicaliceal system was sutured. In all patients oxy de cellulose and in 38 autolog fibrin or hemostatic agents were used.

Mean Hct was 35.93 ± 4.26% on postoperative second day. No patients necessitated transfusion. Mean LOS, drain, and urethral catheter removal time were 3.71 ± 1.05, 2.55 ± 1.53, and 1.21 ± 0.77 days, respectively.

Complications were observed in two patients. One had transcolonic cyst puncture during Veress needle insertion without any further problem (Clavien I). Urinary extravasation was present in one on postoperative day 2 and Double-J stent was inserted (Clavien IIIB). There were no more complications within 30 days. Mean follow-up was 35.61 ± 21.27 months.

Postoperative sixth month Cr and eGFR were 0.95 ± 0.32 mg/dL and 83.65 ± 22.44 mL/min/1.73 m². Pre-postoperative Hct, Cr, and eGFR are given in Table 2. Seven patients had ≥15% eGFR decrease. At postoperative sixth month, two patients in ≥15% eGFR decrease group and two in <15% eGFR decrease group had CKD upstaging.

Table 2.

Comparison of Pre- and Postoperative Renal Function and Hematocrit

n: 52	Preoperative	Postoperative	p-Value^a
Creatinine (ng/dL) (mean ± SD)	0.92 ± 0.28	0.95 ± 0.32 (Postop sixth month)	4.4E-1^b
eGFR (mL/min/1.73 m²) (mean ± SD)	85.26 ± 21.27	83.65 ± 22.44 (Postop sixth month)	6.4E-1^b
Hct (%) (mean ± SD)	42.01 ± 3.86	35.93 ± 4.26 (Postop second day)	6.14E-10^c

Wilcoxon signed-rank test.

Nonsignificant.

Significant.

SD = standard deviation.

Eventually seven patients had ≥15% eGFR decrease, one grade ≥2 complication, and one PSM. These nine (17%) patients could not fulfill trifecta outcomes (Table 3).

Table 3.

“Trifecta” Outcomes

n = 52	Preop–Postop eGFR difference		Complications (Clavien–Dindo)		SM
	<15% decrease (n)	45/52	<Grade 2 (n)	1/52	(−) (n)	51/52
	≥15% decrease (n)	7/52	≥Grade 2 (n)	1/52	(+) (n)	1/52
Non-trifecta	7		1		1
Trifecta (n, %)	43/52 (83%)

SM = surgical margin.

EBL was significantly more in ≥15% eGFR decrease group compared with <15% eGFR decrease group (p = 2.72E-2, two-tailed Mann–Whitney U-test). Mean and median EBL were 578.57 ± 388.21 mL and 650 (50–1000) mL and 234.44 ± 231.00 mL and 150 (20–1000) mL in the patients with ≥15% and <15% eGFR decrease, respectively. There was no any other significant difference regarding tumor size, PADUA score, RENAL score, BMI, ASA, and CCI. The boxplot of EBL in two groups are given in Figure 1.

There was a significant correlation between EBL and eGFR decrease (r = 0.32, p = 2.20E-2; Pearson). Significance was obtained for EBL = 650 mL (p = 9.96E-4). There was no significant correlation between PADUA and RENAL scores and age of %eGFR decrease.

PADUA and RENAL scores were significantly correlated with EBL (r = 0.37, p = 6.40E-3; r = 0.41, p = 2.31E-3; Pearson; respectively). PADUA score 9 (p = 2.99E-2) and RENAL score 6 (p = 1.51E-2) were found to be thresholds to differentiate high (≥650 mL) and low (<650 mL) EBL patients.

Presence of hypertension and DM did not reveal a difference between the patients with <15% and ≥15% eGFR decrease.

Discussion

The term “Trifecta” intends to standardization of reporting PN outcomes. Trifecta criteria are negative surgical margins, optimal renal function preservation, and absence of complications in the same patient.² In our series nine patients could not fulfill trifecta criteria. Seven did not have optimal renal function preservation, one had PSM, and another had grade ≥2 complication. Zargar et al. reported trifecta and optimal perioperative results in RAPN (1185 patients) and laparoscopic PN (646 patients) patients.⁸ Trifecta was defined as negative surgical margin, zero complications, and warm ischemia ≤25 minutes. Optimal outcome was defined as trifecta achievement with 90% eGFR preservation and no CKD upstaging. Trifecta and optimal outcome rate were 70% and 38.5% for RAPN. Our trifecta rate is good, but although off-clamp, most important factor aggravating trifecta outcomes was renal function preservation.

Preoperative renal function, preserved vascularized renal volume, and ischemia time are reported to be vital for renal function recovery.³ In our series, mean preoperative Cr and eGFR were 0.92 ± 0.28 mg/dL and 85.26 ± 21.27 mL/min/1.73 m². Hypertension and DM did not reveal a difference between the patients with <15% and ≥15% eGFR decrease. This can be related to optimal preoperative control of hypertension and DM. Because preservation of vascularized renal volume and ischemia time are surgically modifiable, off-clamp RAPN, without assignment of oncological outcomes and operation safety, was preferred.

In a review by Cacciamani and colleagues,¹ nine studies comparing on- and off-clamp RAPN (896 patients) were evaluated. Off-clamp group had shorter operative time and higher EBL, but there was no difference regarding transfusion rates. Shorter operative time was reported to be likely owing to less complex tumors and surgeon experience. In our cohort, mean console time and EBL was 82.11 ± 38.51 minutes and 280.76 ± 278.98 mL, respectively. No patients necessitated transfusion. RENAL score was low-medium (6.21 ± 1.63) and all patients were operated by a single expert surgeon.

In the Cacciamani and colleagues's review,¹ renal function outcomes were in favor of off-clamp group and assessed by eGFR and percentage of eGFR change. We had seven patients with suboptimal renal function preservation. At postoperative sixth month, two patients in ≥15% eGFR decrease group and two in <15% eGFR decrease group had CKD upstaging. If CKD upstaging was used for renal function evaluation, four patients would have suboptimal renal function preservation.

Cacciamani et al. reported similar complication and PSM rates in off- and on-clamp RAPN patients.¹ Our preferred excision technique is enucleation and when not feasible, resection. In case of PSM suspicion, FSA was performed. The patient with positive margin had focal positivity and because there was no doubt of PSM, the patient did not undergo FSA. Cacciamani and associates reported PSM rate as 4.7% in the off-clamp and 5.7% in the on-clamp group.¹ Our 2% PSM rate is consistent and even better.

In another study, EBL of 886 RAPN patients in matched off- and on-clamp cohorts were evaluated. All procedures were performed by experienced surgeons. EBL was higher in off-clamp patients (228 vs 157 mL, p = 0.009).⁹ Abdel Raheem et al. reported >400 mL EBL to be a predictor of CKD upstaging.¹⁰ In addition, in our series, EBL was significantly higher in ≥15% eGFR decrease group. Significant threshold EBL was 650 mL (p = 9.96E-4). In 62 off-clamp RAPN patients, Abdel Raheem and associates¹⁰ declared cut-off tumor size of 3.2 cm and PADUA score of 9 to be thresholds for EBL >400 mL. In addition, their subanalysis of PADUA components showed tumors invading the pelvicaliceal system to be a risk factor for EBL >400 mL.

In our series, there was no correlation between PADUA and RENAL scores and percentage of eGFR decrease. However, PADUA and RENAL scores were significantly correlated with EBL (r = 0.37, p = 6.40E-3; r = 0.41, p = 2.31E-3; Pearson; respectively). PADUA score 9 (p = 2.99E-2) and RENAL score 6 (p = 1.51E-2) were found to be thresholds to differentiate high- and low-EBL patients. Mean EBL of 280.76 ± 278.98 mL, mean PADUA and RENAL scores of 7.63 ± 1.46 and 6.21 ± 1.63 contributed to our trifecta results.

Regarding complexity, Minervini et al. classified renal tumors as low, intermediate, and high according to PADUA and RENAL scores.¹¹ Low-complexity tumors had PADUA score 6–7 and RENAL score 4–6; intermediate complexity tumors had PADUA score 8–9 and RENAL score 7–9; and high complexity tumors had PADUA score 10–14 and RENAL score 10–12. In our series, tumor complexity was low-intermediate. Tumor borders were delineated with laparoscopic ultrasonography probe. This enabled a precise dissection and low EBL. Pelvicaliceal system was opened in three patients. These along with optimal tumor size and low-intermediate PADUA and RENAL scores contributed our trifecta results.

There is more about EBL and renal function recovery. Hakimi et al. evaluated proportional eGFR change of the operated kidney with pre- and postoperative renal scintigraphy in 73 patients and found higher EBL to have negative impact on postoperative renal function.¹² Surgical factors affecting recovery of renal function after PN in 141 patients were evaluated.¹³ In multivariate analysis, decreased renal function at postoperative first day and sixth month was reported to be significantly predicted only by change in early postoperative Hct level. Higher reduction in hemoglobin (Hb) is reported to reduce oxygenation of renal tubules. Hb decrease can be a messenger of bleeding and can result in reduction of renal perfusion pressure.¹⁰ Oxy de cellulose in all our patients and hemostatic agents when deemed necessary were used to minimize postoperative bleeding.

Transfusion after cardiac procedure was reported to be a risk factor for postoperative acute kidney injury.¹⁴ There is evidence about red blood cell changes during storage and transfusion especially after 14 days storage may cause renal and multiorgan failure.¹⁵ None of our patients necessitated transfusion. We had optimal renal function preservation along with low EBL and zero transfusion rate.

Minervini et al. reported impact of excision technique on perioperative outcomes and surgical margins on 507 patients.¹¹ Excision technique was enucleation in 266 patients, enucleoresection in 150, and resection in 91. Acute kidney injury rate was significantly higher after enucleoresection compared with enucleation. Clavien–Dindo grade 2 complications were significantly more after enucleoresection than after enucleation and resection. SMP was significantly higher after enucleoresection compared with enucleation and resection. Trifecta rate after enucleoresection was significantly lower than after enucleation (54.7% vs 69.8%, p = 0.002) and resection (54.7% vs 69.2%, p = 0.025).

In our cohort, enucleation was preferred. If enucleation was not possible, resection was performed. Because precise excision without compromising oncological principles and optimal renal function preservation is of paramount importance, enucleoresection was not preferred. This preference contributed to our results.

Annino evaluated AirSeal during RAPN.¹⁶ Fifty-five patients operated with standard insufflator were compared with 67 patients operated with AirSeal. Importance of constant intra-abdominal pressure allowing decline in venous bleeding and optimal suction capability to provide a clean surgical field with Airseal system were emphasized. All our patients were operated with AirSeal. This enabled us to perform a precise operation contributing to trifecta outcomes.

There are shortcomings of this study. It is retrospective with small patient number. All patients were operated by an expert surgeon. Our trifecta outcomes may not be replicated by other centers with limited experience. However, our attitude for preserving maximum vascularized renal volume together with ideal oncological outcomes and complication rates can be a reference to obtain favorable outcomes.

Conclusion

“Off-clamp” PN is important for renal function preservation. Patient selection, reducing blood loss, tumor excision technique, and appropriate operative devices along with experience can contribute to achievement of optimal trifecta outcomes.

Footnotes

Author Disclosure Statement

No competing financial interests exist.

Funding Information

No funding was received.

Abbreviations Used

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