Primary implantation of an artificial urinary sphincter using the perineal and penoscrotal approaches: Functional results and assessment of reoperative procedures.

INTRODUCTION: Artificial urinary sphincter (AUS) is the standard treatment for severe stress urinary incontinence in men. While the perineal access is considered the gold standard, some authors have proposed penoscrotal AUS in order to facilitate the procedure. The main objective of our study was to evaluate the duration of survival without revision surgery (SSRC) according to the surgical approach for primary implantation. MATERIAL AND METHODS: Data from 1179 patients implanted in France between 1991 and 2020 with an AMS 800 AUS were retrospectively analyzed. A total of 762 men were implanted perineally (VP) and 417 penoscrotally (VPS). RESULTS: Median follow-up was 20 vs. 25months respectively. The groups were equivalent overall, apart from the use of anticoagulants (11% VP vs. 6.3% VPS P=0.014). In our population, 54% patients were considered as "dry" in the case of VPS vs. 42% for VP. There was no significant difference in terms of survival time without reoperation, revision, replacement or explantation. In univariate and multivariate analysis, age over 70years was predictive of more reinterventions, whereas the use of a 4.5cm cuff was protective, with hazard ratios of 1.42 (P=0.001) and 0.78 (P=0.04), respectively. CONCLUSION: The penoscrotal approach does not appear to be associated with more complications, has good functional results and no significant difference in reoperation-free survival. A prospective multicenter non-inferiority study could be of interest to confirm our findings.

Nephrometry scores to predict oncological outcomes following partial nephrectomy (UroCCR Study 70).

PURPOSE: Partial nephrectomy (PN) for large or complex renal tumors can be difficult and associated with a higher risk of recurrence than radical nephrectomy. We aim to evaluate the clinical useful of nephrometry scores for predicting oncological outcomes in a large cohort of patients who underwent PN for renal cell carcinomas. METHODS: Our analysis included patients who underwent PN for renal cell carcinoma in 21 French academic centers (2010-2020). RENAL, PADUA, and SPARE scores were calculated based on preoperative imaging. Uni- and multivariate cox models were performed to identify predictors of recurrence-free survival and overall survival. The area under the curve (AUC) was used to identify models with the highest discrimination. Decision curve analyses (DCAs) determined the net benefit associated with their use. RESULTS: A total of 1927 patients were analyzed with a median follow-up of 32 months (14-45). RENAL score (p = 0.01), age (p = 0.002), histological type (p = 0.001), high nuclear grade (p = 0.001), necrotic component (p < 0.001), and positive margins (p = 0.005) were significantly related to recurrence in multivariate analyses. The discriminative performance of the 3 radiological scores was modest (65, 63, and 63%, respectively). All 3 scores showed good calibration, which, however, deteriorated with time. Decision curve analysis of the three models for the prediction of overall and recurrence-free survival was similar for all three scores and of limited clinical relevance. CONCLUSION: The association between nephrometry scores and oncological outcomes after NP is very weak. The use of these scores for predicting oncological outcomes in routine practice is therefore of limited clinical value.

Decipher Score predicts prostate specific antigen persistence after prostatectomy.

BACKGROUND: The aim of this study was to evaluate genomic risk of patients with persistent prostate specific antigen (PSA) using mRNA expression analysis and a validated prognostic genomic-risk classifier. METHODS: Monocentric retrospective study including all patients who underwent radical prostatectomy (RP) by one surgeon and Decipher Test from October 2013 to December 2018. PSA persistent population was defined as all patients with two consecutive PSA>0.1 ng/mL at follow-up after the surgery. Neurovascular Structure-adjacent Frozen-section Examination (NeuroSAFE) was performed intraoperatively for research of positive surgical margins. Multivariate analysis was performed for persistent PSA (pPSA) predictors. A specific localized, organ-confined, and negative margins sub-population with PSA persistence was compared to a similar sub-population without PSA persistence for genomic differential expression analyses. RESULTS: A total of 564 patients were included and 61 of them had pPSA. Preoperative PSA was higher in the PSA persistent group (11.6 [6.4, 21.2] vs. 6.2 [4.7, 9.2] P=0.00010), as well as PSA density (PSAd) (0.3 [0.2, 0.5] vs. 0.2 [0.1, 0.3] P=0.0001). Postoperative characteristics, Gleason Score, and positive surgical margins were significantly higher in the PSA persistent population. 31 patients had pPSA in our specific subpopulation and were compared to 217 patients with no pPSA. On multivariate analysis, only Decipher Score (OR=5.64 [1.28; 24.89], P=0.022) and preoperative PSA (OR=1.06, [1.02; 1.09], P=0.001) were significant predictors for PSA persistence. We found two genes to be significantly upregulated with a 2.5-fold change in our specific subpopulation (SERPINB11 and PDE11A). CONCLUSIONS: We found unique genomic features of patients with pPSA, whilst confirming previous clinical findings that this condition behaves to a worse prognosis. Given this high genomic risk, further imaging studies should be performed to select patients for early treatment intensification.

Clinical trial protocol for P-NeLoP: a randomized controlled trial comparing the feasibility and outcomes of robot-assisted partial nephrectomy with low insufflation pressure using AirSeal versus standard insufflation pressure (UroCCR no. 85 study).

Robot-assisted partial nephrectomy (RAPN) is the standard of care for small, localized kidney tumors. This surgery is conducted within a short hospital stay and can even be performed as outpatient surgery in selected patients. In order to allow early rehabilitation of patients, an optimal control of postoperative pain is necessary. High-pressure pneumoperitoneum during surgery seems to be the source of significant pain during the first hours postoperatively. Our study is a prospective, randomized, multicenter, controlled study which aims to compare post-operative pain at 24 h between patients undergoing RAPN at low insufflation pressure (7 mmHg) and those operated on at standard pressure (12 mmHg) using the AirSeal system.This trial is registered in the US National Library of Medicine Trial Registry (NCT number: NCT05404685).

Efficacy, Safety, and Reoperation-free Survival of Artificial Urinary Sphincter in Non-neurological Male Patients over 75 Years of Age.

Background: Artificial urinary sphincter (AUS) is a gold standard treatment in male stress urinary incontinence but remains poorly used in elderly patients. Objective: To assess the efficacy, safety, and reoperation-free survival of AUS implantation in male patients over 75 yr of age. Design setting and participants: We retrospectively reviewed the charts of all 1233 non-neurological male AUS implantations between 2005 and 2020 at 13 French centers. We compared 330 patients ≥75 yr old (GROUP75+) with 903 patients <75 yr old (GROUP75-) at the time of AUS implantation. Outcome measurements and statistical analysis: Our primary endpoint was social continence at 3 mo defined as the use of one or fewer pad daily. We used Kaplan-Meier analyses to assess reoperation-free survival. We sought factors of erosion using logistic regression. Results and limitations: Early postoperative continence was comparable in both groups (74.4% vs 80.1%, p = 0.114). We observed a higher rate of postoperative complications in GROUP75+ (18.8% vs 12.6%, p = 0.014), but the complications were more frequently of low grade in GROUP75+ (p = 0.025). The overall reoperation-free survival was similar (p = 0.076) after a median follow-up of 2 yr. However, patients in GROUP75+ had poorer explantation-free survival (p < 0.0001). A history of radiotherapy was a predictive factor of erosion (odds ratio [OR] = 5.31, p < 0.01), but age was not (OR = 1.08, p = 0.87). Unfortunately, our dataset did not include a systematic geriatric evaluation. Conclusions: AUS in elderly patients appears to be an effective option to treat stress urinary incontinence. However, we observed more postoperative complications and explantations, although age was not associated with the onset of erosion. A prospective study is required to determine whether a geriatric evaluation would be an effective strategy to select patients before surgery. Patient summary: In this study, we looked at outcomes of artificial urinary sphincter in elderly men in a large population. We found satisfying efficacy but slightly more postoperative complications and device infections.

Minimally invasive nephron-sparing treatments for T1 renal cell cancer in patients over 75 years: a comparison of outcomes after robot-assisted partial nephrectomy and percutaneous ablation.

PURPOSE: To compare the oncological and perioperative outcomes of robot-assisted partial nephrectomy (RPN) and percutaneous thermal ablation (PTA) for treatment of T1 renal cell cancer (RCC) in patients older than 75 years. MATERIALS AND METHODS: Retrospective national multicenter study included all patients older than 75 years treated for a T1 RCC by RPN or PTA between January 2010 and January 2021. Patients' characteristics, tumor data, and perioperative and oncological outcomes were compared. RESULTS: A total of 205 patients for 209 procedures (143 RPN and 66 PTA) were included. In the PTA group, patients were older (80.4 ± 3.7 vs. 79 ± 3.7 years (p = 0.01)); frailer (ASA score (2.43 ± 0.6 vs. 2.17 ± 0.6 (p < 0.01)); and more frequently had a history of kidney surgery (16.7% [11/66] vs. 5.6% [8/143] (p = 0.01)) than in the RPN group. Tumors were larger in the RPN group (2.7 ± 0.7 vs. 3.2 ± 0.9 cm (p < 0.01)). Operation time, length of hospital stay, and increase of creatinine serum level were higher in RPN (respectively 92.1 ± 42.7 vs. 150.7 ± 61.3 min (p < 0.01); 1.7 ± 1.4 vs. 4.2 ± 3.4 days (p < 0.01); 1.9 ± 19.3% vs. 10.1 ± 23.7 (p = 0.03)). Disease-free survival and time to progression were similar (respectively, HR 2.2; 95% CI 0.88-5.5; p = 0.09; HR 2.1; 95% CI 0.86-5.2; p = 0.1). Overall survival was shorter for PTA that disappeared after Cox adjusting model (HR 3.3; 95% CI 0.87-12.72; p = 0.08). CONCLUSION: Similar oncological outcomes are observed after PTA and RPN for T1 RCC in elderly patients. CLINICAL RELEVANCE STATEMENT: Robot-assisted partial nephrectomy and percutaneous thermal ablation have similar oncological outcomes for T1a kidney cancer in patients over 75 years; however, operative time, decrease in renal function, and length of hospital stay were lower with ablation. KEY POINTS: • After adjusting model for age and ASA score, similar oncological outcomes are observed after percutaneous thermal ablation and robot-assisted partial nephrectomy for T1 renal cell cancer in elderly patients. • Operation time, length of hospital stay, and increase of creatinine serum level were higher in the robot-assisted partial nephrectomy group.

Association between Expression of Connective Tissue Genes and Prostate Cancer Growth and Progression.

To find an association between genomic features of connective tissue and pejorative clinical outcomes on radical prostatectomy specimens. We performed a retrospective analysis of patients who underwent radical prostatectomy and underwent a Decipher transcriptomic test for localized prostate cancer in our institution (n = 695). The expression results of selected connective tissue genes were analyzed after multiple t tests, revealing significant differences in the transcriptomic expression (over- or under-expression). We investigated the association between transcript results and clinical features such as extra-capsular extension (ECE), clinically significant cancer, lymph node (LN) invasion and early biochemical recurrence (eBCR), defined as earlier than 3 years after surgery). The Cancer Genome Atlas (TCGA) was used to evaluate the prognostic role of genes on progression-free survival (PFS) and overall survival (OS). Out of 528 patients, we found that 189 had ECE and 27 had LN invasion. The Decipher score was higher in patients with ECE, LN invasion, and eBCR. Our gene selection microarray analysis showed an overexpression in both ECE and LN invasion, and in clinically significant cancer for COL1A1, COL1A2, COL3A1, LUM, VCAN, FN1, AEBP1, ASPN, TIMP1, TIMP3, BGN, and underexpression in FMOD and FLNA. In the TCGA population, overexpression of these genes was correlated with worse PFS. Significant co-occurrence of these genes was observed. When presenting overexpression of our gene selection, the 5-year PFS rate was 53% vs. 68% (p = 0.0315). Transcriptomic overexpression of connective tissue genes correlated to worse clinical features, such as ECE, clinically significant cancer and BCR, identifying the potential prognostic value of the gene signature of the connective tissue in prostate cancer. TCGAp cohort analysis showed a worse PFS in case of overexpression of the connective tissue genes.

Value of multiphoton microscopy in uro-oncology: a narrative review.

Background and Objective: Multi-photon microscopy (MPM) is a 3-dimension fluorescence imaging technique that combines the excitation of two low-energy photons, enabling less photo-bleaching and deeper penetration of the imaged tissue. Two signals are detected, autofluorescence (AF), from natural intracellular fluorophores [such as nicotinamide adenine dinucleotide phosphate (NADP) and flavine adenine dinucleotide (FAD) transformation], and second harmonic generation (SHG), a physical property of the laser enhancing non-centrosymmetric structures such as collagen fibers. MPM can give both visual and quantitative information of a fresh tissue (without the need of processing, cutting or staining the tissue), aiding in the progress towards optimizing a real-time imaging device. The objective of this review is to show the value and benefits of the use of MPM in uro-oncology. Methods: A structured literature review was performed using PubMed and Web of Sciences, including all articles with the following keywords: "multiphoton microscopy", "two-photon microscopy", "non-linear microscopy", "second harmonic generation", "urology", "prostate", "bladder", "kidney", "upper tract", "oncology", "surgical margins", "frozen section". Articles were reviewed to summarize the use of this tool in performing biopsies, assessing surgical margins, staging and grading complementary tool, and real-time imaging. Key Content and Findings: A total of 476 articles were identified with these keywords, and later screened for inclusion. We finally included 47 publications that were relevant to our topic. The advantages of this technique have led to its application in the management of several cancers, allowing cellular description as well as quantitative measurements of AF or SHG and their correlation with clinical outcomes. Conclusions: MPM has shown great improvement in providing a real time assessment of fresh tissue, giving oncologic diagnosis, performing in vivo imaging and quantitative analysis of the tissue as well as increasing precision of the diagnosis. This nonlinear optical technique has the potential of guiding both biopsy and surgery, as well as helping the surgeon with interesting additional tissue information intra-operatively.

Machine-learning approach for prediction of pT3a upstaging and outcomes of localized renal cell carcinoma (UroCCR-15).

OBJECTIVES: To assess the impact of pathological upstaging from clinically localized to locally advanced pT3a on survival in patients with renal cell carcinoma (RCC), as well as the oncological safety of various surgical approaches in this setting, and to develop a machine-learning-based, contemporary, clinically relevant model for individual preoperative prediction of pT3a upstaging. MATERIALS AND METHODS: Clinical data from patients treated with either partial nephrectomy (PN) or radical nephrectomy (RN) for cT1/cT2a RCC from 2000 to 2019, included in the French multi-institutional kidney cancer database UroCCR, were retrospectively analysed. Seven machine-learning algorithms were applied to the cohort after a training/testing split to develop a predictive model for upstaging to pT3a. Survival curves for disease-free survival (DFS) and overall survival (OS) rates were compared between PN and RN after G-computation for pT3a tumours. RESULTS: A total of 4395 patients were included, among whom 667 patients (15%, 337 PN and 330 RN) had a pT3a-upstaged RCC. The UroCCR-15 predictive model presented an area under the receiver-operating characteristic curve of 0.77. Survival analysis after adjustment for confounders showed no difference in DFS or OS for PN vs RN in pT3a tumours (DFS: hazard ratio [HR] 1.08, P = 0.7; OS: HR 1.03, P > 0.9). CONCLUSIONS: Our study shows that machine-learning technology can play a useful role in the evaluation and prognosis of upstaged RCC. In the context of incidental upstaging, PN does not compromise oncological outcomes, even for large tumour sizes.

Evaluation of oncological outcomes of robotic partial nephrectomy according to the type of hilar control approach (On-clamp vs Off-clamp), a multicentric study of the French network of research on kidney cancer-UROCCR 58-NCT03293563.

PURPOSE: To compare off-clamp vs on-clamp robotic partial nephrectomy (RPN) for renal cell carcinoma (RCC) in terms of oncological outcomes, and to assess the impact of surgical experience (SE). METHODS: We extracted data of a contemporary cohort of 1359 patients from the prospectively maintained database of the French national network of research on kidney cancer (UROCCR). The primary objective was to assess the positive surgical margin (PSM) rate. We also evaluated the oncological outcomes regardless of the surgical experience (SE) by dividing patients into three groups of SE as a secondary endpoints. SE was defined by the caseload of RPN per surgeon per year. For the continuous variables, we used Mann-Whitney and Student tests. We assessed survival analysis according to hilar control approach by Kaplan-Meier curves with log rank tests. A logistic regression multivariate analysis was used to evaluate the independent factors of PSM. RESULTS: Outcomes of 224 off-clamp RPN for RCC were compared to 1135 on-clamp RPN. PSM rate was not statistically different, with 5.6% in the off-clamp group, and 11% in the on-clamp group (p = 0.1). When assessing survival analysis for overall survival (OS), local recurrence-free survival (LR), and metastasis-free survival (MFS) according to hilar clamping approach, there were no statistically significant differences between the two groups with p value log rank = 0.2, 0.8, 0.1, respectively. In multivariate analysis assessing SE, hilar control approach, hospital volume (HV), RENAL score, gender, Age, ECOG, EBL, BMI, and indication of NSS, age at surgery was associated with PSM (odds ratio [OR] 1.03 (95% CI 1.00-1.04), 0.02), whereas SE, HV, and type of hilar control approach were not predictive factors of PSM. CONCLUSION: Hilar control approach seems to have no impact on PSM of RPN for RCC. Our findings were consistent with randomized trials.

Positive surgical margin's impact on short-term oncological prognosis after robot-assisted partial nephrectomy (MARGINS study: UroCCR no 96).

The oncological impact of positive surgical margins (PSM) after robot-assisted partial nephrectomy (RAPN) is still under debate. We compared PSM and Negative Surgical Margins (NSM) in terms of recurrence-free survival (RFS), metastasis-free survival (MFS) and overall survival (OS) after RAPN, and we identified predictive factors of PSM. Multi-institutional study using the UroCCR database, which prospectively included 2166 RAPN between April 2010 and February 2021 (CNIL DR 2013-206; NCT03293563). Two groups were retrospectively compared: PSM versus NSM. Prognostic factors were assessed using Kaplan-Meyer curves with log-Rank test, cox hazard proportional risk model and logistic regression after univariate comparison. 136 patients had PSM (6.3%) and 2030 (93.7%) had NSM. During a median follow-up of 19 (9-36) months after RAPN, 160 (7.4%) recurrences were reported. Kaplan-Meier curves and analysis suggested that RFS, MFS and OS were not affected by a PSM (p = 0.68; 0.71; 0.88, respectively). In multivariate analysis predictors of PSM were a lower RENAL score (p = 0.001), longer warm ischemia time (WIT) (p = 0.003) and Chromophobe Renal Cell Carcinoma (chrRCC) (p = 0.043). This study found no impact of PSM on RFS, MFS or OS, and predictors of PSM were the RENAL score, WIT and chrRCC.

Impact of Renal Cell Carcinoma Histological Variants on Recurrence After Partial Nephrectomy: A Multi-Institutional, Prospective Study (UROCCR Study 82).

BACKGROUND: The prognostic impact of renal cell carcinoma (RCC) morphotype remains unclear in patients who undergo partial nephrectomy (PN). Our objective was to determine the risk factors for recurrence after PN, including RCC morphotype. METHODS: Patients with RCC who had undergone PN were extracted from the prospective, national French database, UroCCR. Patients with genetic predisposition, bilateral or multiple tumours, and those who had undergone secondary totalization were excluded. Primary endpoint was 5-year, recurrence-free survival (RFS), and secondary endpoint was overall survival (OS). Risk factors for recurrence were assessed by multivariable Cox regression analysis. RESULTS: Overall, 2,767 patients were included (70% male; median age: 61 years [interquartile range (IQR) 51-69]). Most (71.5%) of the PN procedures were robot-assisted. Overall, 2,573 (93.0%) patients were recurrence free, and 74 died (2.7%). Five-year RFS was 84.9% (IQR 82.4-87.4). A significant difference in RFS was observed between RCC morphotypes (p < 0.001). Surgical margins (hazard ratio [HR] = 2.0 [95% confidence interval (CI): 1.3-3.2], p < 0.01), pT stage >1 (HR = 2.6 [95% CI: 1.8-3.7], p < 0.01]) and Fuhrmann grade >2 (HR = 1.9 [95% CI: 1.4-2.6], p < 0.001) were risk factors for recurrence, whereas chromophobe subtype was a protective factor (HR = 0.08 [95% CI: 0.01-0.6], p = 0.02). Five-year OS was 94.0% [92.4-95.7], and there were no significant differences between RCC subgroups (p = 0.06). The main study limitation was its design (multicentre national database), which may be responsible for declarative bias. CONCLUSIONS: Chromophobe morphotype was significantly associated with better RFS in RCC patients who underwent PN. Conversely, pT stage, Fuhrman group and positive surgical margins were risk factors for recurrence.

Low T Cell Responsiveness in the Early Phase of COVID-19 Associates with Progression to Severe Pneumonia in Kidney Transplant Recipients.

Kidney transplant (KT) recipients are at increased risk of developing severe forms of COVID-19. Little is known about the immunological mechanisms underlying disease severity in these patients receiving T-cell targeting immunosuppressive drugs. We investigated the relationship between T cell responsiveness at the beginning of the infection and the risk of subsequent progression to respiratory failure. We performed a multicentric prospective study in KT recipients with a positive RT-PCR COVID-19 test and only mild symptoms at inclusion. Blood samples were collected at baseline in a cell culture system containing T cell stimuli. We assessed T cell responsiveness by computing the ratio between the levels of Th1, Th2, Th17 and Treg cytokines produced after polyclonal stimulation and the number of blood lymphocytes. We then used an unsupervised classification approach to stratify patients into low and high T cell responders and a penalized logistic regression to evaluate the association between T cell responsiveness and progression to severe pneumonia. Forty-five patients were included. All patients who progressed to severe pneumonia (24.4%, n = 11) were low T cell responders at baseline (p = 0.01). In multivariate analysis, low T cell responsiveness at baseline was the main risk factor for subsequent progression to severe pneumonia. This study provides novel insights into the mechanisms underlying COVID-19 severity in organ transplant recipients and data of interest to clinicians managing immunosuppressive drugs in these patients.

Early Efficacy and Safety Outcomes of Artificial Urinary Sphincter for Stress Urinary Incontinence Following Radical Prostatectomy or Benign Prostatic Obstruction Surgery: Results of a Large Multicentric Study.

BACKGROUND: Artificial urinary sphincter (AUS) is the gold standard for the management of moderate to severe stress urinary incontinence (SUI) in the male population. While outcomes of this device in postprostatectomy incontinence (PPI) are widely described, those obtained for incontinence after benign prostatic obstruction (BPO) surgery remains poorly explored. OBJECTIVE: To compare continence outcomes after AUS implantation in a PPI population with those obtained in men incontinent after BPO surgery. DESIGN, SETTING, AND PARTICIPANTS: A retrospective review of all cases of AUS implantation between 2005 and 2020 in 16 different French centers was conducted. Only patients with primary implantation whose indication was moderate to severe SUI after prostatectomy or BPO surgery were included (excluding those with a history of radiation therapy, brachytherapy, cystectomy, high-intensity focused ultrasound therapy, or neurogenic disease). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was the rate of social continence (zero or one pad per day) at 3 mo. Complications were also noted within 90 d of implantation. RESULTS AND LIMITATIONS: A total of 417 patients were included in the PPI group and 50 in the BPO surgery group. Social continence rates at 3 mo were similar between the groups (79% vs 72%, p = 0.701). Complication rate was significantly higher in the BPO group (8% vs 18%, p = 0.044). The same was found for the Clavien-Dindo type 2 complication rate (20.6% vs 44.4%, p = 0.026). The retrospective nature and lack of precise definition of incontinence are the main limitations of this study. CONCLUSIONS: This multicentric study strengthens the position of AUS as gold standard for SUI after radical prostatectomy. Comparable efficacy results were found for incontinence after BPO surgery, with nevertheless a higher rate of complications. PATIENT SUMMARY: Artificial urinary sphincter represents the gold standard for the treatment of moderate to severe stress urinary incontinence. Efficacy results are comparable between postprostatectomy incontinence and incontinence after benign prostatic obstruction surgery.

Cancer-associated fibroblasts in renal cell carcinoma: implication in prognosis and resistance to anti-angiogenic therapy.

OBJECTIVES: To investigate the role of cancer-associated fibroblasts (CAFs) in clear cell renal cell carcinoma (ccRCC) with respect to tumour aggressiveness, metastasis development, and resistance to anti-angiogenic therapy (vascular endothelial growth factor receptor-tyrosine kinase inhibitors [VEGFR-TKI]). PATIENTS AND METHODS: Our study involved tissue samples from three distinct and independent cohorts of patients with ccRCC. The presence of CAFs and tumour lymphangiogenesis was investigated, respectively, by transcriptional signatures and then correlated with tumour development and prognosis. The effect of these CAFs on tumour cell migration and VEGFR-TKI resistance was analysed on co-cultures of ccRCC cells with CAFs. RESULTS: Results from our cohorts and from in silico investigations showed that VEGFR-TKI significantly increase the number of CAFs in tumours. In the same populations of patients with ccRCC, the proportion of intra-tumoral CAFs correlated to shorter disease-free and overall survival. The presence of CAFs was also correlated with lymphangiogenesis and lymph node metastasis. CAFs increased the migration and decreased the VEGFR-TKI-dependent cytotoxic effect of tumour cells. CONCLUSIONS: Our results show that VEGFR-TKI promote the development of CAFs, and CAFs favour tumour aggressiveness, metastatic dissemination, and resistance to treatment in ccRCC. CAFs could represent a new therapeutic target to fight resistance to treatment of ccRCC. Targeting CAF and immunotherapies combination are emerging as efficient treatments in many types of solid tumours. Our results highlight their relevance in ccRCC.

Long-term survival benefit from dual kidney transplantation using kidneys from donors with very extended criteria-a French cohort between 2002 and 2014.

BACKGROUND: This national multicentre retrospective cohort study aimed to assess the long-term outcomes of dual kidney transplantation (DKT) and compare them with those obtained from single kidney transplantation (SKT). METHODS: Our first analysis concerned all first transplants performed between May 2002 and December 2014, from marginal donors, defined as brain death donors older than 65 years, with an estimated glomerular filtration rate (eGFR) lower than 90 mL/min/1.73 m2. The second analysis was restricted to transplants adequately allocated according to the French DKT program based on donor eGFR: DKT for eGFR between 30 and 60, SKT for eGFR between 60 and 90 mL/min/1.73 m2. Recipients younger than 65 years or with a panel-reactive antibody percentage ≥25% were excluded. RESULTS: The first analysis included 461 DKT and 1131 SKT. DKT donors were significantly older (77.6 versus 74 years), had a more frequent history of hypertension and a lower eGFR (55.1 versus 63.6 mL/min/1.73 m2). While primary nonfunction and delayed graft function did not differ between SKT and DKT, 1-year eGFR was lower in SKT recipients (39 versus 49 mL/min/1.73 m2, P < 0.001). Graft survival was significantly better in DKT, even after adjustment for recipient and donor risk factors. Nevertheless, patient survival did not differ between these groups. The second analysis included 293 DKT and 687 SKT adequately allocated with donor eGFR and displayed similar results but with a smaller benefit in terms of graft survival. CONCLUSIONS: In a context of organ shortage, DKT is a good option for optimizing the use of kidneys from very expanded criteria donors.

Is night-time surgical procedure for renal graft at higher risk than during the day? A single center study cohort of 179 patients.

INTRODUCTION: Various surgical centers tend to postpone a kidney transplantation (KT) to the following morning than to operate at night-time. The objective of our study was to assess whether there was any difference between daytime and night-time renal transplantation in our institution. METHOD: This study is a retrospective monocentric study including all the KTs that were performed between 2012 and 2013 by transplant expert surgeons in our institution. Clavien-Dindo (CD) complications were classified according to 7 variables going from 1 to 5. Time before postgraft diuresis and delayed graft function (DGF) were also analyzed. Two groups of patients were formed according to threshold value of incision time (6.30 p.m.). Data comparison were performed using the Kruskal-Wallis nonparametric test. RESULTS: A total of 179 patients were included. Median follow-up was 24 months. Cold ischemia time was longer in the night-time transplantation (1082 vs. 807 min, p < .001), but rewarming time was shorter (47.24 vs. 52.15 min, p = .628). No statistically significant differences were observed between the two groups using the Kruskal-Wallis method for CD complications (Qobs: 0.076; p = .735). CD complications proportion was similar, with a majority of grade II complications (72.7% daytime group vs. 75.4% night-time group (p = .735). DGF (19 patients for daytime group vs. 13 patients for night-time group, p = .359) and time before postgraft diuresis (4.65 days daytime group vs. 5.27 days night-time group, p = .422) were similar between both groups. Multivariate analysis did not show significant predictors of CD complications Grade 3 and more. CONCLUSION: Night-time renal transplantation did not induce more postoperative CD complications than diurnal procedures in our cohort, challenging the false preconceptions that allow surgical teams to delay this surgery.

Plasmatic osteopontin and vascular access dysfunction in hemodialysis patients: a cross-sectional, case-control study (The OSMOSIS Study).

BACKGROUND AND AIMS: Despite close follow-up of patients with native arteriovenous fistulas (AVFs), up to 10% experience thrombosis each year. The OSMOSIS Study (Osteopontin as a Marker of Stenosis) tested the hypothesis that the systemic osteopontin level, a pro-inflammatory mediator related to vascular remodelling and intimal hyperplasia, increases in AVF stenosis, and may be used in clinical surveillance. METHODS: Our cross-sectional study compared the level of plasmatic osteopontin (pOPN) between patients with a well-functioning AVF (control group) and patients who required revision of their AVF due to stenosis (stenosis group). Blood samples were collected before dialysis (control group) or before intervention (stenosis group) from the AVF arm, and from the opposite arm as a within-subject control. pOPN level was measured by enzyme-linked immunosorbent assay. RESULTS: A total of 76 patients were included in the study. Baseline characteristics were similar between the groups (mean age, 70 years; men, 63%; AVF duration, 39 months), apart from prevalence of type 2 diabetes (T2D) (control group, 33%; stenosis group, 57%; p = 0.04). pOPN levels were similar between the AVF arm and the contralateral arm (551 ± 42 ng/mL vs. 521 ± 41 ng/mL, respectively, p = 0.11, paired t-test). Patients in the stenosis group displayed a higher pOPN level than patients in the control group (650.2 ± 59.8 ng/mL vs. 460.5 ± 61.2, respectively, p = 0.03; two-way ANOVA). T2D was not identified as an associated factor in a multivariate analysis (p = 0.50). CONCLUSIONS: The level of pOPN in hemodialysis patients was associated with the presence of AVF stenosis requiring intervention. Thus, its potential as a diagnostic biomarker should be assessed in a vascular access surveillance program.