The Mayo Adhesive Probability score can help predict intra- and postoperative complications in patients undergoing laparoscopic donor nephrectomy.

PURPOSE: Living donor nephrectomy is a high-stake procedure involving healthy individuals, therefore every effort should be made to define each patient's individualized risk and improve potential donors' information. The aim of this study was to evaluate the interest of the Mayo adhesive probability (MAP) score, an imaging-based score initially designed to estimate the risk of adherent perinephric fat in partial nephrectomy, to predict intra- and postoperative complications of living donor nephrectomy. MATERIALS AND METHODS: We retrospectively reviewed the imaging, clinical, and follow-up data of 452 kidney donors who underwent laparoscopic donor nephrectomy in two academic centers. RESULTS: Imaging and follow-up data were available for 307 kidney donors, among which 44 (14%) had a high MAP score (≥ 3). Intraoperative difficulties were encountered in 50 patients (16%), including difficult dissection (n = 35) and bleeding (n = 17). Conversion to open surgery was required for 13 patients (4.2%). On multivariate analysis, a MAP score ≥ 3 was significantly associated with the risk of intraoperative difficulty [OR 14.12 (5.58-35.7), p < 0.001] or conversion to open surgery [OR 18.96 (3.42-105.14), p = 0.0042]. Postoperative complications were noted in 99 patients (32%), including 12 patients (3.9%) with Clavien-Dindo grade III-IV complications. On multivariate analysis, a high MAP score was also associated with the risk of postoperative complications [OR 2.55 (1.20-5.40), p = 0.01]. CONCLUSIONS: In this retrospective bicentric study, a high MAP score was associated with the risk of intra- and postoperative complications of laparoscopic donor nephrectomy. The MAP score appears of interest in the living donor evaluation process to help improve donors' information and outcomes.

Aortic bypass surgery for asymptomatic patients awaiting a kidney transplant: A word of caution.

INTRODUCTION: In the presence of severe aorto-iliac calcification, aortic bypass surgery can be mandatory to allow kidney transplantation. The aim of our study was to evaluate the safety and outcomes of this strategy among asymptomatic patients. MATERIALS AND METHODS: We retrospectively reviewed the files of all patients that had undergone vascular bypass surgery prior to kidney transplantation between November 2004 and March 2016. All patients undergoing aortic bypass surgery prior to kidney transplantation without any vascular-related symptoms were included. RESULTS: Twenty-one asymptomatic patients were included. Ten patients (48%) have not received a kidney transplant. Four patients died before kidney transplantation, including 2 deaths related to the bypass surgery (9.5%). Early post-operative morbidity involved 11 cases. Eleven patients (52%) were transplanted. Transplanted patients were significantly younger (median age 60 [56-61] vs 67 [60-72] years, P = .04) at the time of bypass and were less frequently treated for coronary heart disease (9% vs 50%, P = .06). CONCLUSION: Aortic bypass surgery performed prior to kidney transplantation among asymptomatic patients has significant mortality and morbidity rates. When transplantation is possible, the results are satisfying. Larger studies are required to define the selection criteria, such as age and coronary heart disease.

Super-selective robot-assisted partial nephrectomy using near-infrared flurorescence versus early-unclamping of the renal artery: results of a prospective matched-pair analysis.

INTRODUCTION: Super-selective clamping of tumor-specific segmental arteries was developed to eliminate ischemia of the remnant kidney while limiting hemorrhage during partial nephrectomy. The objective is to evaluate the benefice of super-selective clamping on renal functional outcome, compared to early-unclamping of the renal artery. MATERIALS AND METHODS: From March 2015 to July 2016, data from 30 patients undergoing super-selective robot-assisted PN (RAPN) for a solitary tumor by a single surgeon were prospectively collected. Tumor devascularization was assessed using indocyanine green near-infrared fluorescence. A matched-pair analysis with a retrospective cohort undergoing early-unclamping was conducted, adjusting on tumor complexity and preoperative eGFR. Perioperative, oncologic and functional outcomes using DMSA-renal scintigraphy were assessed. Multivariate analysis was performed to identify predictors of postoperative renal function and de novo chronic kidney disease (CKD). RESULTS: Super-selective RAPN was successful in 23/30 patients (76.7%), 5 requiring secondary main artery clamping due to persistent tumor fluorescence. Matched-pair analysis showed similar operating time, blood loss, positives margins and complication rates. Super-selective clamping was associated with an improved eGFR variation at discharge (p=0.002), 1-month (p=0.01) and 6-month post-op (-2%vs-16% p=0.001). It also led to a better relative function on scintigraphy (46%vs40% p=0.04) and homolateral eGFR (p=0.04), and fewer upstaging to CKD stage ≥3 (p=0.03). On multivariate analysis, super-selective clamping was a predictor of postoperative renal function. CONCLUSION: Super-selective RAPN leads to an improved preservation of renal function and a reduced risk of de novo CKD stage≥3, while keeping the benefit of main artery clamping on perioperative outcomes.

Immortal Time-Bias-Corrected Survival of Highly Sensitized Patients and HLA-desensitized Kidney Transplant Recipients.

INTRODUCTION: In the setting of kidney transplantation (KT), we assessed the efficacy of desensitization and compared the survival of desensitized patients (HLA-incompatible KT) with similarly sensitized patients receiving HLA-compatible KT or sensitized patients still on a waiting list after adjusting for the usually unaccounted immortal time bias. METHODS: All patients in a French KT center on the waiting list between August 1994 and December 2019 with a high level of sensitization (panel-reactive antibodies [PRAs] ≥80%) were included. The primary outcome was all-cause mortality. A time-varying covariate Cox survival model was used to account for the immortal time bias. A landmark analysis was used as a sensitivity analysis. RESULTS: During the study period, 326 patients with high PRAs were followed, among which 147 (45%) remained on the waiting list at the time of last follow-up and 179 benefited from a KT. Thirty-six patients were desensitized, of which 30 received a kidney transplant, including eight deceased kidney donors. There were no differences in mortality rates between desensitized KT patients, nondesensitized KT patients, and waitlisted patients after adjusting for immortal time bias (hazard ratio [HR] = 0.48, P = 0.22). Death-censored graft survival was similar between desensitized and nondesensitized KT patients (HR = 0.92, P = 0.88 adjusting for donor age >65 years, donor status, and time on the waiting list). Mean estimated glomerular filtration rate at 1 year post-KT was similar for desensitized KT patients (53.3 ± 21 vs. 53.6 ± 21 ml/min per 1.73 m2 for nondesensitized patients; P = 0.95). CONCLUSIONS: HLA-desensitization was effective for highly sensitized patients and gave access to KT without detrimental effects on patient or graft survival rates.

Cooperative Blockade of CK2 and ATM Kinases Drives Apoptosis in VHL-Deficient Renal Carcinoma Cells through ROS Overproduction.

Kinase-targeted agents demonstrate antitumor activity in advanced metastatic clear cell renal cell carcinoma (ccRCC), which remains largely incurable. Integration of genomic approaches through small-molecules and genetically based high-throughput screening holds the promise of improved discovery of candidate targets for cancer therapy. The 786-O cell line represents a model for most ccRCC that have a loss of functional pVHL (von Hippel-Lindau). A multiplexed assay was used to study the cellular fitness of a panel of engineered ccRCC isogenic 786-O VHL- cell lines in response to a collection of targeted cancer therapeutics including kinase inhibitors, allowing the interrogation of over 2880 drug-gene pairs. Among diverse patterns of drug sensitivities, investigation of the mechanistic effect of one selected drug combination on tumor spheroids and ex vivo renal tumor slice cultures showed that VHL-defective ccRCC cells were more vulnerable to the combined inhibition of the CK2 and ATM kinases than wild-type VHL cells. Importantly, we found that HIF-2α acts as a key mediator that potentiates the response to combined CK2/ATM inhibition by triggering ROS-dependent apoptosis. Importantly, our findings reveal a selective killing of VHL-deficient renal carcinoma cells and provide a rationale for a mechanism-based use of combined CK2/ATM inhibitors for improved patient care in metastatic VHL-ccRCC.

Ex-Vivo Treatment of Tumor Tissue Slices as a Predictive Preclinical Method to Evaluate Targeted Therapies for Patients with Renal Carcinoma.

Clear cell renal cell carcinoma (ccRCC) is the third type of urologic cancer. At time of diagnosis, 30% of cases are metastatic with no effect of chemotherapy or radiotherapy. Current targeted therapies lead to a high rate of relapse and resistance after a short-term response. Thus, a major hurdle in the development and use of new treatments for ccRCC is the lack of good pre-clinical models that can accurately predict the efficacy of new drugs and allow the stratification of patients into the correct treatment regime. Here, we describe different 3D cultures models of ccRCC, emphasizing the feasibility and the advantage of ex-vivo treatment of fresh, surgically resected human tumor slice cultures of ccRCC as a robust preclinical model for identifying patient response to specific therapeutics. Moreover, this model based on precision-cut tissue slices enables histopathology measurements as tumor architecture is retained, including the spatial relationship between the tumor and tumor-infiltrating lymphocytes and the stromal components. Our data suggest that acute treatment of tumor tissue slices could represent a benchmark of further exploration as a companion diagnostic tool in ccRCC treatment and a model to develop new therapeutic drugs.

Transrectal ultrasound-guided prostate biopsies vs. magnetic resonance imaging ultrasound fusion targeted biopsies: Who are the best candidates?

INTRODUCTION: The aim of this study was to compare the results of ultrasound-guided prostate biopsies (US-PB) and magnetic resonance imaging-ultrasound fusion biopsies (MRI-PB) in two contemporary cohorts and to describe the parameters orienting the choice of technique. METHODS: Two contemporary cohorts of patients undergoing US-PB or MR-PB using the Urostation® (Koelis, Grenoble, France) between November 2010 and July 2015 were analyzed retrospectively. Patients with metastatic cancer or recurrence after treatment, saturation biopsies, and US-PB performed after a negative MRI were excluded. Comparison of populations, biopsy results, and clinical and biological parameters guiding the choice of technique were studied on multivariate analysis (logistic regression) taking into account the following confounding factors: age, prostate-specific antigen (PSA) rate, prostatic volume, number of previous biopsies, and abnormal digital rectal examination. RESULTS: One hundred fourteen patients were included in the US-PB group and 118 in the MR-PB group. Prostate cancer was diagnosed among 65 patients in the US-PB group (detection rate 57.0%) and 70 patients in the MR-PB group (detection rate 59.3%) (odds ratio [OR] 3.00; 95% confidence interval [CI] 1.52-6.17; p=0.002). Among the cancers diagnosed in the MR-PB group, 21 were diagnosed by the two targeted biopsy cores only (15.5%). Patients undergoing MR-PB were significantly younger (p=0.0005), with a higher number of previous biopsy sessions (p<10-7) and larger prostate volume (p=0.001). PSA rate alone (p=0.23) and digital rectal examination (p=0.48) did not significantly interfere with the choice of a technique. CONCLUSIONS: Younger patients with larger prostates and prior negative biopsy were more likely to be offered the MR-PB technique. On multivariate analysis, the detection rate was higher in the MR-PB group.

Super-selective robot-assisted partial nephrectomy using near-infrared flurorescence versus early-unclamping of the renal artery: results of a prospective matched-pair analysis

ABSTRACT Introduction Super-selective clamping of tumor-specific segmental arteries was developed to eliminate ischemia of the remnant kidney while limiting hemorrhage during partial nephrectomy. The objective is to evaluate the benefice of super-selective clamping on renal functional outcome, compared to early-unclamping of the renal artery. Materials and Methods From March 2015 to July 2016, data from 30 patients undergoing super-selective robot-assisted PN (RAPN) for a solitary tumor by a single surgeon were prospectively collected. Tumor devascularization was assessed using indocyanine green near-infrared fluorescence. A matched-pair analysis with a retrospective cohort undergoing early-unclamping was conducted, adjusting on tumor complexity and preoperative eGFR. Perioperative, oncologic and functional outcomes using DMSA-renal scintigraphy were assessed. Multivariate analysis was performed to identify predictors of postoperative renal function and de novo chronic kidney disease (CKD). Results Super-selective RAPN was successful in 23/30 patients (76.7%), 5 requiring secondary main artery clamping due to persistent tumor fluorescence. Matched-pair analysis showed similar operating time, blood loss, positives margins and complication rates. Super-selective clamping was associated with an improved eGFR variation at discharge (p=0.002), 1-month (p=0.01) and 6-month post-op (-2%vs-16% p=0.001). It also led to a better relative function on scintigraphy (46%vs40% p=0.04) and homolateral eGFR (p=0.04), and fewer upstaging to CKD stage ≥3 (p=0.03). On multivariate analysis, super-selective clamping was a predictor of postoperative renal function. Conclusion Super-selective RAPN leads to an improved preservation of renal function and a reduced risk of de novo CKD stage≥3, while keeping the benefit of main artery clamping on perioperative outcomes.