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.

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.

Efficacy and safety of intravesical fibrin glue instillation for management of patients with refractory hemorrhagic cystitis: 12-months results. A promising therapy for hemorrhagic cystitis.

OBJECTIVES: Fibrin glue (FG) endo-vesical application seems to be a promising therapy for hemorrhagic cystitis (HC). We aimed to evaluate efficacy and safety of FG instillation in patients with HC. METHODS: Patients with HC not responsive to conventional treatments (bladder irrigation, catheterization, blood transfusions, hyperhydration and endoscopic coagulation) were treated with FG endo-vesical instillation (April 2017- December 2018). FG was prepared from 120 mL of patient blood with the Vivostat® system. After standard cystoscopy, bladder was insufflated with carbon dioxide (CO2) according to bladder compliance and autologous FG was applied to bladder wall and bleeding sites. RESULTS: Ten patients included with grade 2 or higher HC secondary to bone marrow graft for hematological diseases (30%) or to actinic cystitis caused by prostate cancer radiotherapy (RT) (70%). The median HC onset time after RT was 4.8 (IQR 3.9- 6.3) years and 35 (IQR 27.5-62.5) days after hematopoietic stem cell transplantation (HSCT). Five patients had a complete response after one treatment, three patients had clinical response (grade < 2 hematuria, amelioration of symptoms), one of them required catheterization and bladder irrigation. One patient required a second instillation of FG achieving a clinical response. No adverse events related to the procedure were recorded, however one patient died for causes not related to the procedure. Median Interstitial Cystitis Symptoms Index was 13.0 (IQR 11.0-15.0) pre-operatively and 4.0 (IQR 2.0-5.0) post-operatively. CONCLUSIONS: Our study showed that, even in hematological patients, autologous FG instillation maybe a safe, repeatable and effective treatment modality in patients with refractory HC.

Conservative treatment of upper urinary tract carcinoma in patients with imperative indications.

BACKGROUND: To report our experience for endoscopic treatment of upper urinary tract carcinoma (UTUC) in patients with imperative indications for management. METHODS: Retrospective data were collected for all patients who underwent endoscopic management of UTUC for imperative situations, from September 2013 to January 2019. Comorbidity was determined by using the age-adjusted Charlson Comorbidity Index (CCI). The primary endpoint of the study was overall survival (OS). Secondary outcomes were recurrence-free survival (RFS) rates, complication rates and global renal function. RESULTS: A total of 29 patients were enrolled in the study. The median age was 69.0 (IQR 63.0-79.0) years and the median CCI was 6 (IQR 4-8). Overall, 137 endoscopic procedures were performed; 117 (85.4%) had no complication. Clavien-Dindo grade III and IV complications were 3 (2.2%) and 1 (0.7%) respectively. The median follow-up of 23 months (IQR 14-35). During the follow-up, 2 (6.9%) patients died for cause not related to cancer. Recurrence of UTUC occurred in 18 patients (61.1%). The 24-month OS was 96.4±3.5% and the 24-month RFS was 31.7±9.4%. Lower RFS rates were found in high grade tumor patients (22.2±13.9%) compared to low grade tumor patients (35.6±12.3%) (P=0.237). There was statistical difference in creatinine and eGFR values when comparing baseline to last follow-up (P=0.018 and P=0.005, respectively). CONCLUSIONS: Endoscopic management of UTUC in patients with imperative indications appears to be a reasonable alternative to nephroureterectomy. However, stringent endoscopic follow-up is necessary due to the high risk of disease recurrence.

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.

Multicenter Analysis of Postoperative Complications in Octogenarians After Radical Cystectomy and Ureterocutaneostomy: The Role of the Frailty Index.

BACKGROUND: The purpose of this study was to assess patient frailty as a risk factor for radical cystectomy (RC) complications. MATERIALS AND METHODS: We performed an analysis of prospectively collected data of consecutive patients 80 years of age or older who underwent RC and ureterocutaneostomy in 6 primary care European urology centers. Frailty was measured using a simplified frailty index (sFI) with a 5-item score including: (1) diabetes mellitus; (2) functional status; (3) chronic obstructive pulmonary disease; (4) congestive cardiac failure; and (5) hypertension, with a maximum 5-item score meaning high level of frailty. Within 90 days surgical complications were scored according to the Clavien Classification System (CCS). sFI ≥3 was considered as poor frailty status. Clinical and pathological variables were analyzed as predictors of severe complications (CCS ≥3). RESULTS: One hundred seventeen patients were enrolled. Most patients reported an sFI score of 2 and 3, respectively, 31/117 (26.5%) and 45/117 patients (38.5%). CCS ≥3 occurred in 17/117 patients (14.5%). Patients with sFI ≥3 were significantly older than patients with sFI <3 (median age, 85 years [interquartile range (IQR), 82-86] versus 82 years [IQR, 80-84]; P = .001). Most CCS ≥3 scores occurred in patients with sFI ≥3: 13 (11.1%) versus 4 (3.4%; P = .02). No significative differences were detected in terms of length of hospital stay, pathological stage, and postoperative bowel canalization when related to sFI. sFI ≥3 was an independent risk factor of CCS ≥3 in univariate and multivariate analysis (respectively, odds ratio [OR], 3.81 [95% confidence interval (CI), 1.16-12.5; P = .02] and OR, 3.1 [95% CI, 0.7-13.7; P = .01]). Body mass index, age, American Society of Anesthesiologists score ≥3, and pathological stage were not related to CCS ≥3. CONCLUSION: RC appears feasible in elderly patients with an sFI <3. In cases of sFI ≥3, this choice should be carefully valued, discussed, and possibly avoided because of a higher risk of complications.

Predictors of the Transition from Off to On Clamp Approach during Ongoing Robotic Partial Nephrectomy: Data from the CLOCK Randomized Clinical Trial.

PURPOSE: We sought to identify predictive factors of the transition from off clamp to on clamp robotic partial nephrectomy following an intraoperative decision. MATERIALS AND METHODS: In the multicenter, randomized, prospective CLOCK (CLamp vs Off Clamp the Kidney during robotic partial nephrectomy) trial 152 and 149 of the 301 patients with a localized renal mass were assigned to undergo off clamp and on clamp robotic partial nephrectomy, respectively. Surgery was done at a total of 7 referral institutions by 1 surgeon per institution. A localized renal mass was defined as having a R.E.N.A.L. (radius, exophytic/endophytic, nearness to collecting system or sinus, anterior/posterior, location relative to polar lines, hilar) score less than 10. Surgeons had similar experience with at least 100 previous robotic partial nephrectomies. All patients underwent a preoperative and a 6-month renal scan. The current study deals with one of the secondary end points of the trial, comparing cases finalized as clampless (off robotic partial nephrectomy group) with those which were converted (shift robotic partial nephrectomy group). RESULTS: Of the 152 patients randomized to off clamp 61 (40%) were shifted to clamp with a median ischemia time of 15 minutes. In the shift robotic partial nephrectomy group the masses were larger (3.5 vs 2.2 cm) and more complex (R.E.N.A.L. score 7 vs 6). A significant association with transition was found for tumor diameter (OR 1.4) and the R.E.N.A.L. score continuously (OR 1.4) and when recoded in groups, including 4-no risk (referent OR 1), 5-6-low risk (OR 1.8), 7-8-intermediate risk (OR 3.6) and 9 or greater-high risk (OR 6.6). The shift robotic partial nephrectomy group had longer operative time, higher blood loss and increased performance of 2-layer renorrhaphy. No significant differences were noted in postoperative complications or renal function after 6 months. CONCLUSIONS: The transition from off to on clamp robotic partial nephrectomy is associated with renal mass diameter and complexity. Under the specific conditions of the current trial no harm was related to this decision.

Monocenter Experience with 532 Nm-Laser Photoselective-Vaporization of the Prostate by GreenLight XPS™ Laser: Is It Really an Endourological Joker Card?

INTRODUCTION: In our study, we reported on our monocenter experience with GreenLight (GL) Xcelerated Performance System (XPS)™ /MoXy™ laser fiber (American Medical Systems Inc., Minnetonka, Minnesota), examining its efficacy, safety, and its ability to effectively treat lower urinary tract symptoms (LUTS) in benign prostate obstruction (BPO). We also explored and compared the three different endoscopic approaches used for GL treatment of benign prostatic hyperplasia (BPH), standard photovaporization (PVP), anatomical PVP, and GreenLight XPS™ enucleation of the prostate. MATERIALS AND METHODS: Between February 2013 and April 2017, 140 patients, with an average age of 67.7 years (range 47-85), were treated using the XPS™/MoXy™ system in a single-operative urologic center. The data were retrospectively analyzed with an assessment of the main intra- and postoperative outcomes at three, six, 12, and 18 months comparing both subjective (international prostate symptom score [IPSS]) and objective (uroflow [Qmax] parameters and prostate volume) parameters to the preoperative data. Patients underwent standard PVP, anatomical PVP, or prostate photo-selective en-bloc enucleation (PEBE) according to surgeon preferences. RESULTS: Median prostate volume (MPV) and prostate-specific antigen (PSA) were 69cc and 3.24 ng/dl, respectively. An indwelling catheter, at the time of surgery, was observed in 15% of men. Median operative-laser time and energy applied were 56.4 minutes, 26.5 minutes, and 245813 kJ. Outpatient surgery was feasible with median length of stay at 48 hours. Significant improvement in IPSS and Qmax are observed at all endpoints. No significant intraoperative complications were reported. When stratifying postoperative complications according to the Cavien-Dindo classification, only two cases of high-degree emerged (grades III-IV). CONCLUSION: Our data confirm that in treating men with symptomatic benign prostate disease, the GreenLight XPS™/MoXy™ laser fiber is safe and able to achieve challenging results in terms of clinical outcomes and prostate volume reduction. Balance between functional outcomes and complications was great without statistically significant differences, in terms of outcomes, between the different surgical techniques.

Trifecta and Pentafecta Rates After Robotic Assisted Partial Nephrectomy: Comparative Study of Patients with Renal Masses <4 and ≥4 cm.

OBJECTIVES: Robotic-assisted partial nephrectomy (RAPN) is preferred to radical nephrectomy because it guarantees superior functional outcomes in patients with small renal masses (RMs). Only a few studies so far have evaluated the feasibility of RAPN for the treatment of RM ≥4 cm. The aim of this study is to evaluate the safety and feasibility of RAPN based on a comparison of trifecta and pentafecta rates for RMs ≥4 cm. MATERIAL AND METHODS: We retrospectively analyzed prospectively collected data from an institutional database of patients undergoing RAPN from September 2013 to November 2016. Demographic and perioperative data were collected and statistically analyzed. Pentafecta is defined as achievement of trifecta (negative surgical margins, no postoperative complications, and warm ischemia time ≤25 minutes) with the addition of two other variables, namely, over 90% estimated glomerular filtration rate preservation and no chronic kidney disease stage progression 1 year after surgery. RESULTS: Overall, 123 patients underwent RAPN. Of those, 38 (30.9%) had RMs ≥4 cm. Trifecta was achieved in 72.9% of patients with RMs <4 cm and in 44.7% of those with ≥4 cm, whereas pentafecta was achieved by 23.5% of patients with RMs <4 cm and by 10.5% of those with RMs ≥4 cm. No significant predictive factors were found in connection with trifecta, whereas only one was found in connection with pentafecta, namely, age (odds ratio: 0.91; 95% confidence interval 0.85-0.98; P = .01). CONCLUSIONS: RAPN may be considered a feasible and safe surgical approach ensuring good functional outcome even for patients with RMs ≥4 cm. Pentafecta rates after RAPN were comparable between RMs <4 and ≥4 cm in diameter.