Comparison of Perioperative, Functional, and Oncologic Outcomes of Open vs. Robot-Assisted Off-Clamp Partial Nephrectomy: A Propensity Scored Match Analysis.

Off-clamp partial nephrectomy represents one of the latest developments in nephron-sparing surgery, with the goal of preserving renal function and reducing ischemia time. The aim of this study was to evaluate and compare the functional, oncologic, and perioperative outcomes between off-clamp robot-assisted partial nephrectomy (off-C RAPN) and off-clamp open partial nephrectomy (off-C OPN) through a propensity score-matched (PSM) analysis. A 1:1 PSM analysis was used to balance variables potentially affecting postoperative outcomes. To report surgical quality, 1 year trifecta was used. Univariable Cox regression analysis was performed to identify predictors of trifecta achievement. The Kaplan-Meier method was used to compare cancer-specific survival (CSS), overall survival (OS), disease-free survival (DFS), and metastasis-free survival (MFS) probabilities between groups. Overall, 542 patients were included. After PSM analysis, two homogeneous cohorts of 147 patients were obtained. The off-C RAPN cohort experienced shorter length of stay (LoS) (3.4 days vs. 5.4 days; p < 0.001), increased likelihoods of achieving 1 year trifecta (89.8% vs. 80.3%; p = 0.03), lower postoperative Clavien-Dindo ≤ 2 complications (1.3% vs. 18.3%, p < 0.001), and lower postoperative transfusion rates (3.4% vs. 12.2%, p = 0.008). At univariable analysis, the surgical approach (off-C RAPN vs. off-C OPN, OR 2.22, 95% CI 1.09-4.46, p = 0.02) was the only predictor of 1 year trifecta achievement. At Kaplan-Meier analysis, no differences were observed between the two groups in terms of OS (log-rank p = 0.451), CSS (log-rank p = 0.476), DFS (log-rank p = 0.678), and MFS (log-rank p = 0.226). Comparing RAPN and OPN in a purely off-clamp scenario, the minimally invasive approach proved to be a feasible and safe surgical approach, with a significantly lower LoS and minor rate of postoperative complications and transfusions as a result of improved surgical quality expressed by higher 1 year trifecta achievement.

The role of warm ischemia time on functional outcomes after robotic partial nephrectomy: a radionuclide renal scan study from the clock randomized trial.

PURPOSE: To evaluate the relationship between warm ischemia time (WIT) duration and renal function after robot-assisted partial nephrectomy (RAPN). METHODS: The CLOCK trial is a phase 3 randomized controlled trial comparing on- vs off-clamp RAPN. All patients underwent pre- and postoperative renal scintigraphy. Six-month absolute variation of eGFR (AV-GFR), rate of relative variation in eGFR over 25% (RV-GFR > 25), absolute variation of split renal function (SRF) at scintigraphy (AV-SRF). The relationships WIT/outcomes were assessed by correlation graphs and then modeled by uni- and multivariable regression. RESULTS: 324 patients were included (206 on-clamp, 118 off-clamp RAPN). Correlation graphs showed a threshold on WIT equal to 10 min. The differences in outcome measures between cases with WIT < vs ≥ 10 min were: AV-GFR - 3.7 vs - 7.5 ml/min (p < 0.001); AV-SRF - 1% vs - 3.6% (p < 0.001); RV-GFR > 25 9.3% vs 17.8% (p = 0.008). Multivariable models found that AV-GFR was related to WIT ≥ 10 min (regression coefficient [RC] - 0.52, p = 0.019), age (RC - 0.35, p = 0.001) and baseline eGFR (RC - 0.30, p < 0.001); RV-GFR > 25 to WIT ≥ 10 min (odds ratio [OR] 1.11, p = 0.007) and acute kidney injury defined as > 50% increase in serum creatinine (OR 19.7, p = 0.009); AV-SRF to WIT ≥ 10 min (RC - 0.30, p = 0.018), baseline SRF (RC - 0.76, p < 0.001) and RENAL score (RC - 0.60. p = 0.028). The main limitation was that the CLOCK trial was designed on a different endpoint and therefore the present analysis could be underpowered. CONCLUSIONS: Up to 10 min WIT had no consequences on functional outcomes. Above the 10-min threshold, a statistically significant, but clinically negligible impact was found.

Feasibility of Microwave Scissors-Based Off-Clamp Laparoscopic Partial Nephrectomy in a Porcine Model.

OBJECTIVES: To assess the feasibility of off-clamp laparoscopic partial nephrectomy using microwave scissors. METHODS: We performed transperitoneal laparoscopic partial nephrectomy, without hilar clamping or renorrhaphy, using only microwave scissors for renal resection in a porcine model. For each kidney, 2 types of procedures were performed: a middle pole resection excising an area of 2-cm diameter and approximately 1-cm depth and a lower pole resection at the level of the lower polar line. The renal calyces exposed during renal resection were sealed and transected using microwave scissors. After 3 days of follow-up, the pigs were reoperated to inspect for postoperative complications. Euthanasia was performed to collect the remaining kidneys for histopathological examination. RESULTS: Ten procedures were successfully performed, without hilar clamping or suturing of the renal calyces and parenchyma, in 5 kidneys from 3 pigs. The median resecting time, blood loss, and lateral thermal injury were 23.2 min, 47.1 mL, and 6.8 mm in the middle pole resection, and were 15.1 min, 26.5 mL, and 6.9 mm in the lower pole resection, respectively. No complications were noted during reoperation, such as postoperative hemorrhage and major urine leakage. Extravasation occurred in 2 middle pole resections and 3 lower pole resections during retrograde pyelogram. Hematoxylin and eosin staining revealed thermal injury characterized by tissue microwave fixation in the near zone and acute coagulative necrosis in the intermediate zone. CONCLUSIONS: Microwave scissors-based off-clamp laparoscopic partial nephrectomy is feasible in pigs and can be used for clinical applications.

Is off-clamp robot-assisted partial nephrectomy beneficial for renal function? Data from the CLOCK trial.

OBJECTIVES: To compare the functional outcomes of on- vs off-clamp robot-assisted partial nephrectomy (RAPN) within a randomized controlled trial (RCT). MATERIALS AND METHODS: The CLOCK study (CLamp vs Off Clamp the Kidney during robotic partial nephrectomy; NCT02287987) is a multicentre RCT including patients with normal baseline function, two kidneys and masses with RENAL scores ≤ 10. Pre- and postoperative renal scintigraphy was prescribed. Renal defatting and hilum isolation were required in both study arms; in the on-clamp arm, ischaemia was imposed until the completion of medullary renorraphy, while in the off-clamp condition it was not allowed throughout the procedure. The primary endpoint was 6-month absolute variation in estimated glomerular filtration rate (AV-GFR); secondary endpoints were: 12, 18 and 24-month AV-GFR; 6-month estimated glomerular filtration rate variation >25% rate (RV-GFR >25); and absolute variation in ipsilateral split renal function (AV-SRF). The planned sample size was 102 + 102 cases, after taking account crossover of cases to the alternate study arm; a 1:1 randomization was performed. AV-GFR and AV-SRF were compared using analysis of covariation, and RV-GFR >25 was assessed using multivariable logistic regression. Intention-to-treat (ITT) and per-protocol analyses (PP) were performed. RESULTS: A total of 160 and 164 patients were randomly assigned to on- and off-clamp RAPN, respectively; crossover was observed in 14% and 43% of the on- and off-clamp arms, respectively. We were unable to find any statistically significant difference between on- vs off-clamp with regard to the primary endpoint (ITT: 6-month AV-GFR -6.2 vs -5.1 mL/min, mean difference 0.2 mL/min, 95% confidence interval [CI] -3.1 to 3.4 [P = 0.8]; PP: 6-month AV-GFR -6.8 vs -4.2 mL/min, mean difference 1.6 mL/min, 95% CI -2.3 to 5.5 [P = 0.7]) or with regard to the secondary endpoints. The median warm ischaemia time was 14 vs 15 min in the ITT analysis and 14 vs 0 min in the PP analysis. CONCLUSION: In patients with regular baseline function and two kidneys, we found no evidence of differences in functional outcomes for on- vs off-clamp RAPN.

Expanding the limits of nephron-sparing surgery: Surgical technique and mid-term outcomes of purely off-clamp robotic partial nephrectomy for totally endophytic renal tumors.

OBJECTIVES: To report surgical technique, perioperative, oncological, and mid-term functional outcomes in a single-center purely off-clamp robotic partial nephrectomy series for totally endophytic masses. METHODS: A retrospective analysis of a prospectively collected, institutional review board-approved renal cancer database was carried out to include patients with a totally endophytic renal tumor treated with off-clamp robotic partial nephrectomy between January 2013 and December 2020 at our center. Our database was queried to identify cases that had been assigned 3 points for the "E" domain of the R.E.N.A.L. nephrometry score and 3 points for the "exophytic rate" domain of the PADUA (Preoperative Aspects and Dimensions Used for an Anatomical) nephrometry score. Preoperative indocyanine green renal mass marking was performed in 33 patients, in whom the tumor was vascularized by a specific feeding artery. Surgical steps, perioperative, oncological and functional data were reported. RESULTS: Fifty-six consecutive patients with totally endophytic renal masses were treated. The median tumor diameter was 3 cm, and median PADUA and R.E.N.A.L. scores were both 10. The median operative time was 82 min. Low-grade Clavien complications occurred in two patients (3.6%) and high-grade Clavien complications were observed in four patients (7.1%). Positive surgical margins were detected in one patient; 2-year recurrence-free, cancer-specific, and overall survival rates were 100%, 100%, and 98.2%, respectively. At a median follow-up of 24 months, new onset of chronic kidney disease stage 3b occurred in one patient. At last follow-up, the median estimated glomerular filtration rate was 77 mL/min, with a median estimated glomerular filtration rate percent decrease of 5.5%. Trifecta was achieved in 91% of patients. CONCLUSIONS: Purely off-clamp robotic partial nephrectomy is a feasible and safe surgical approach, even in totally endophytic renal tumors, providing a favorable perioperative complications rate, excellent oncological outcomes, and negligible impact on renal function at mid-term follow-up. Indocyanine green preoperative marking of endophytic renal tumors represents a useful tool for rapid intraoperative identification of the mass, real-time control of resection margins, and a more precise dissection.

Assessment of surgical outcomes of off-clamp open partial nephrectomy without renorrhaphy for ≥T1b renal tumours.

PURPOSE: To assess the surgical outcomes of off-clamp open partial nephrectomy without renorrhaphy. In the era of robot-assisted surgeries, open partial nephrectomy remains a surgical option for ≥ T1b renal tumours. Although the necessity of renal pedicle clamping and renorrhaphy in open partial nephrectomy for larger tumours remains to be discussed, reports on this issue are rare. METHODS: Twenty-seven open partial nephrectomies for ≥ T1b renal tumours were performed without renal pedicle clamping or renorrhaphy. A soft coagulation system was used to control bleeding from the resection bed. Surgical results, complications, and predictors of perioperative estimated glomerular filtration rate (eGFR) preservation at 1 month and 3 months after surgery were analysed. RESULTS: The median estimated volume of blood loss was 420 mL. The rates of perioperative eGFR preservation were 88.9 and 87.3% at 1 and 3 months after surgery, respectively. Tumour size was an independent predictor of perioperative eGFR preservation at 1 month after surgery, whereas age and exophytic/endophytic properties of the tumour were independent predictors of perioperative eGFR preservation at 3 months after surgery. CONCLUSION: Open partial nephrectomy without renal pedicle clamping or renorrhaphy could be safely performed for ≥ T1b renal tumours, even when tumours were entirely endophytic and located close to the renal pedicle. Mild perioperative eGFR reduction was observed. Although surgical indications should be carefully considered in these cases, off-clamp open partial nephrectomy without renorrhaphy is a feasible procedure for patients with ≥ T1b renal tumours.

Safety of on- vs off-clamp robotic partial nephrectomy: per-protocol analysis from the data of the CLOCK randomized trial.

PURPOSE: To compare the safety of on- vs off-clamp robotic partial nephrectomy (RAPN). METHODS: 302 patients with RENAL masses ≤ 10 were randomized to undergo on-clamp (150) vs off-clamp (152) RAPN (CLOCK trial-ClinicalTrials.gov NCT02287987) at seven institutions by one experienced surgeon per institution. Intra-operative data, complications, and positive surgical margins were compared. RESULTS: Due to a relevant rate of shift from the assigned treatment, the per-protocol analysis only was considered and the data from 129 on-clamp vs 91 off-clamp RAPNs analyzed. Tumor size (off-clamp vs on-clamp, 2.2 vs 3.0 cm, p < 0.001) and RENAL score (5 vs 6, p < 0.001) significantly differed. At univariate analysis, no differences were found regarding intra-operative estimated blood loss (off- vs on-clamp, 100 vs 100 ml, p = 0.7), post-operative complications rate (19% vs 26%, p = 0.2), post-operative anemia (Hb decrease > 2.5 g/dl 26% vs 27%, p = 0.9; transfusion rate 3.4% vs 6.3%, p = 0.5; re-intervention due to bleeding 1.1% vs 4%, p = 0.4), acute kidney injury (4% vs 6%, p = 0.8), and positive surgical margins (3.5% vs 8.2%, p = 0.1). At multivariate analysis accounting for tumor diameter and complexity, considering the on-clamp group as the reference category, a significant difference was noted in the off-clamp group exclusively for blood loss (OR 0.3, 95% CI 0.09-0.52, p = 0.008). CONCLUSIONS: The on-clamp and off-clamp approaches for RAPN showed a comparable safety profile.

On-clamp versus off-clamp partial nephrectomy: Propensity score-matched comparison of long-term functional outcomes.

OBJECTIVES: To compare long-term functional outcomes of off-clamp or on-clamp partial nephrectomy patients of two high-volume centers with cT1-2/N0 M0 renal tumors and baseline estimated glomerular filtration rate >60 mL/min. METHODS: A 3:1 propensity score-matched analysis was used to select two homogeneous cohorts to compare off-clamp versus on-clamp partial nephrectomy. Joinpoint regression analysis was used to compare the 2-8-year probabilities of estimated glomerular filtration rate modifications in both selected cohorts. The Kaplan-Meier method assessed the risk of developing a stage ≥3b chronic kidney disease during follow up. Multivariable analyses aimed to identify predictors of renal function deterioration. Perioperative complications and oncological outcomes were compared. RESULTS: Overall, 1073 patients were included (588 on-clamp and 485 off-clamp). After applying the propensity score-matched analysis, the two cohorts of 157 on-clamp and 472 off-clamp patients did not differ for all covariates, except for warm ischemia time and last estimated glomerular filtration rate. At joinpoint analysis, the off-clamp group showed higher probabilities of maintaining an unmodified estimated glomerular filtration rate (P = 0.02). The probability of developing a stage ≥3b chronic kidney disease was significantly higher (P < 0.001) in the on-clamp cohort. At multivariable analysis, estimated glomerular filtration rate at discharge and off-clamp approach were independent predictors of improved functional outcomes. Perioperative complications were comparable among the two cohorts (P = 0.67). There were not any statistically significant differences in terms of cancer-specific survival (P = 0.26) and overall survival (P = 0.18). CONCLUSIONS: Off-clamp partial nephrectomy seems to offer a higher probability of maintaining 100% estimated glomerular filtration rate after surgery. In our cohort, patients undergoing on-clamp partial nephrectomy presented a 7.3-fold increased risk of developing a severe chronic kidney disease during follow up.

Off-clamp partial nephrectomy has a positive impact on short- and long-term renal function: a systematic review and meta-analysis.

BACKGROUND: Ongoing efforts are focused on shortening ischemia intervals as much as possible during partial nephrectomy to preserve renal function. Off-clamp partial nephrectomy (off-PN) has been a common strategy for to avoid ischemia in small renal tumors. Although studies comparing the advantages between off-PN with conventional on-clamp partial nephrectomy (on-PN) have been reported, the impact on short- and especially long-term renal function of the two surgical methods has not been discussed seriously and remained unclear. Our purpose is to evaluate the impact on short- (within postoperative 3 months) and long-term (postoperative 6 months or longer) renal function of off-PN compared with that of on-PN. METHODS: We comprehensively searched databases, including PubMed, EMBASE, and the Cochrane Library, without restrictions on language or region. A systematic review and cumulative meta-analysis of the included studies were performed to assess the impact of the two techniques on short- and long-term renal function. RESULTS: A total of 23 retrospective studies and 2 prospective cohort studies were included. The pooled postoperative short-term decrease of estimated glomerular filtration rate (eGFR) was significantly less in the off-PN group (weighted mean difference [WMD]: 4.81 ml/min/1.73 m2; 95% confidence interval [CI]: 3.53 to 6.08; p < 0.00001). The short-term increase in creatinine (Cr) level in the on-PN group was also significant (WMD: - 0.05 mg/dl; 95%CI: - 0.09 to - 0.00; p = 0.04). Significant differences between groups was observed for the long-term change and percent (%) change of eGFR (p = 0.04 and p < 0.00001, respectively) but not for long-term Cr change (p = 0.40). The postoperative short-term eGFR and Cr levels, but not the postoperative long-term eGFR, differed significantly between the two groups. The pooled odds ratios for acute renal failure and postoperative progress to chronic kidney disease (stage≥3) in the off-PN group were found to be 0.25 (p = 0.003) and 0.73 (p = 0.34), respectively, compared with the on-PN group. CONCLUSIONS: Off-PN exerts a positive impact on the short- and long-term renal function compared with conventional on-PN. Given the inherent limitations of our included studies, large-volume and well-designed RCTS with extensive follow up are needed to confirm and update the conclusion of this analysis.

The Impact of Arterial Clamping Technique in Robot-Assisted Partial Nephrectomy on Renal Function and Surgical Outcomes: Six-Year Experience at Siriraj Hospital, Thailand.

INTRODUCTION: Robot-assisted partial nephrectomy (RAPN) with different arterial clamping techniques has increasingly been performed to avoid ischemic injury to nephron. However, postoperative renal function remains controversial. We determine the impact of each renal arterial clamping on surgical and renal outcomes after RAPN. MATERIALS AND METHODS: Patients who underwent RAPN at Siriraj Hospital from 2010 to 2016 were retrospectively reviewed and stratified into 3 cohorts: main-clamp (MAC), selective-clamp, and off-clamp. RESULTS: Main, selective, and off-clamping were performed in 27, 38, and 12, respectively. Median tumor size and Radius, Exophytic or endophytic, Nearness to collecting system or sinus, Anterior or posterior, and Location relative to polar lines (RENAL) score were 3 cm and 7, respectively. Longer operative time was observed in MAC (p = 0.002) although estimated blood loss, transfusion rate, and complication were comparable. Warm ischemia time was not different between cohorts. However, number of patients with prolonged ischemia time in MAC were greater (p ≤ 0.01). All margins were negative. Median postoperative and latest glomerular filtration rate reduction were 3.8 and 5.3 mL/min/1.73 m2, respectively without significant difference between cohorts. On multivariable analysis, hypertension independently associated with reduced renal function preserved (p = 0.03). Median follow-up was 18 months. CONCLUSIONS: Our study is the first to report surgical and renal functional outcomes after RAPN in Southeast-Asian population. Based on our experience, clamping techniques does not impact on renal functions and complication rate was low even in small-volume center.