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.

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.

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.

The Use of Haemostatic Agents and Sealants for the Prevention of Lymphocele After Urological Surgery: A Review of the Literature.

BACKGROUND: Despite the continuous technological innovation in urological surgery procedures, lymphocele represents one of the major and more frequent complications both in tumour and transplant surgery. Haemostatic agents have been used hypothesizing a beneficial effect on the prevention of lymphoceles. We aimed to review the published literature to establish whether haemostatic agents and sealants are an effective option for lymphocele prevention following urological procedure. MATERIALS AND METHODS: An extensive PubMed search was performed including the following keywords: "lymphocele", "lymphocele prevention", "fibrin glue", "collagen patch", "fibrin patch", and "haemostatic material". The search, which collected data until January 2000, was restricted to the full text available articles in the English language and human studies. RESULTS: Our research identified 64 articles, among these only four fulfilled the inclusion criteria. A total of 133 patients underwent surgery and were treated with haemostatic agents and/or sealants to reduce the lymphoceles formation. The mean age was 56.1 years. A negligible variability in study design and in results and complication reporting is common. The 6.45% of patients treated with haemostatic biomaterials developed lymphocele. The rate difference of lymphoceles formation and recurrence between patient groups treated with sealant than in the controls groups is small (6.45% vs 6.88%). CONCLUSIONS: The evidences presented in the examined studies are only preliminary and insufficient to draw significant conclusions. A major, multicentre, randomized controlled trial is strongly needed.

Giant renal artery aneurysm: A case report.

A case of a 12 cm giant renal artery aneurysm (RAA) in an 59-year-old woman is reported. The patient was referred to our hospital for flank pain and spot hematuria. Ultrasonography (US) revealed some wide lacunar areas in her right kidney and a thin cortex. Three-dimensional computed tomography (3D-CT) revealed a giant right renal arteriovenous malformation (AVM). AngioCT scan showed a pervious right renal artery. The cavities of the right kidney were dilated and the parenchyma was markedly reduced. Two months later the patient underwent an open resection of the aneurysm and a right nephrectomy. She had an uneventful recovery and a healthy status (last follow-up: 9 month). In this particular case, a safe approach is the transabdominal approach since the aneurysm was very large, friable, and located on the right side. This report confirms the opportunity of a planned nephrectomy once there is adequate renal reserve in the opposite kidney using a midline approach.

The Clinical Use of the Neutrophil to Lymphocyte Ratio (NLR) in Urothelial Cancer: A Systematic Review.

The neutrophil to lymphocyte ratio (NLR) is an inflammatory index that has been considered as a potential prognostic factor in human cancer. The aim of this study was to evaluate the available evidence regarding the NLR as a prognostic value in patients affected by urothelial cancer. This literature review, including papers on NLR in urothelial cancers, was done on PubMed/Medline and Cochrane libraries in November 2015. The selection of the articles followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses process. Twenty-three of 99 articles fulfilled all the inclusion criteria, including data on 6240 patients affected by urothelial cancers. Overall, cancer-specific, and recurrence-free survival were evaluated as the main oncological outcomes. There was significant heterogeneity among studies, and the majority of studies were of poor quality. Overall, NLR was considered as a prognostic marker in 87.5%, 80%, and 60% of the studies on upper tract urothelial cancer, urothelial bladder cancer, and metastatic and advanced disease, respectively. The NLR cut-off value ranged between 2 and 5. A high NLR was associated with worse overall, cancer-specific, and recurrence-free survival. NLR is a widely available, easy-to-collect, costless, prognostic marker in urothelial cancers. Its clinical use still remains under investigation, especially for the need for cut-off values, particularly in different subsets of patients.

Magnetic resonance spectroscopic imaging 3T and prostate cancer: correlation with transperineal ultrasound guided prostate biopsy.

OBJECTIVES: The aim of our study was to correlate the results obtained by 3T Magnetic Resonance Spectroscopic Imaging (MRSI3T) with those obtained by histological examination of samples of the trans-perineal ultrasound-guided prostate biopsy (TPUS-B). METHODS: 34 patients were enrolled in the study. All patients had a clinical suspicion of cancer due to increased PSA and/or positive digital rectal examination. Patients were subjected to an MRSI 3T examination and subsequently to TPUS-B. RESULTS: Of the 22 (22/34) patients who presented abnormalities MRSI at 3T, 9 had a histological diagnosis of Prostate adenocarcinoma. Of the remaining 13 patients, 6 were found to be histologically positive for Benign Prostatic Hypertrophy and 7 Chronic Interstitial Inflammation or High Grade Prostatic Intraepithelial Neoplasia. 12 (12/34) patients found to have no peripheral alterations in their prostate on 3T MRSI, none were positive for ADK or inflammation on histology. The sensitivity, specificity, positive predictive value and negative predictive value were 100%, 48%, 40% and 100% respectively. DISCUSSION: In this study, we correlated the values obtained from 3T MRSI with the results of histologically examined prostate biopsies. Our work shows that 72.8% of the voxels in which there was a change in ratio of Cit/(Cho + Cr), corresponded to areas of prostate tissue disease. Of these, 73.2% were positive for ADK and 26.8% for CII or HG PIN. In literature, it is noted that PCa can be distinguished from areas of benign tissue, in the peripheral zone, on the basis of the values of the ratio Cit/(Cho + Cr) (17), although some benign conditions, such as prostatitis or PINHG, can alter these values (18-19). CONCLUSIONS: In conclusion, the use of MRSI 3T before performing prostate biopsies may represent a valid aid for the urologist in the diagnosis of PCa, allowing them to avoid unnecessary prostate biopsies that may be negative. Furthermore, it would also be possible to reduce the total number of biopsies, thus decreasing patient exposure to the unnecessary risks associated with biopsy.