Prognostic value of programmed death ligand-1 and programmed death-1 expression in patients with upper tract urothelial carcinoma.

OBJECTIVE: To evaluate the prognostic value of programmed death ligand-1 (PD-L1) and programmed death-1 (PD-1) expression in patients with upper tract urothelial carcinoma (UTUC). PATIENTS AND METHODS: A retrospective multicentre study was conducted in 283 patients with UTUC treated with radical nephroureterectomy (RNU) between 2000 and 2015 at 10 French hospitals. Immunohistochemistry analyses were performed using 2 mm-core tissue microarrays with NAT105® and 28.8® antibodies at a 5% cut-off for positivity on tumour cells and tumour-infiltrating lymphocytes to evaluate PD-L1 and PD-1 expression, respectively. Multivariable Cox regression models were used to determine the independent predictors of recurrence-free (RFS), cancer-specific (CSS) and overall survival (OS). RESULTS: Overall, 63 (22.3%) and 220 (77.7%) patients with UTUC had PD-L1-positive and -negative disease, respectively, while 91 (32.2%) and 192 (67.8%) had PD-1-positive and -negative disease, respectively. Patients who expressed PD-L1 or PD-1 were more likely to have pathological tumour stage ≥pT2 (68.3% vs 49.5%, P = 0.009; and 69.2% vs 46.4%, P < 0.001, respectively) and high-grade (90.5% vs 70.0%, P = 0.001; and 91.2% vs 66.7%, P < 0.001, respectively) disease with lymphovascular invasion (52.4% vs 17.3%, P < 0.001; and 39.6% vs 18.2%, P < 0.001, respectively) as compared to those who did not. In multivariable Cox regression analysis adjusting for each other, PD-L1 and PD-1 expression were significantly associated with decreased RFS (hazard ratio [HR] 1.83, 95% confidence interval [CI] 1.09-3.08, P = 0.023; and HR 1.59, 95% CI 1.01-2.54, P = 0.049; respectively), CSS (HR 2.73, 95% CI 1.48-5.04, P = 0.001; and HR 1.96, 95% CI 1.12-3.45, P = 0.019; respectively) and OS (HR 2.08, 95% CI 1.23-3.53, P = 0.006; and HR 1.71, 95% CI 1.05-2.78, P = 0.031; respectively). In addition, multivariable Cox regression analyses evaluating the four-tier combination of PD-L1 and PD-1 expression showed that only PD-L1/PD-1-positive patients (n = 38 [13.4%]) had significantly decreased RFS (HR 3.07, 95% CI 1.70-5.52; P < 0.001), CSS (HR 5.23, 95% CI 2.62-10.43; P < 0.001) and OS (HR 3.82, 95% CI 2.13-6.85; P < 0.001) as compared to those with PD-L1/PD-1-negative disease (n = 167 [59.0%]). CONCLUSIONS: We observed that PD-L1 and PD-1 expression were both associated with adverse pathological features that translated into an independent and cumulative adverse prognostic value in UTUC patients treated with RNU.

Who Is at Risk of Death after Renal Trauma? An Analysis of Thirty-Day Mortality after 1,799 Cases of Renal Trauma.

INTRODUCTION: The aim of the study was to report the 30-day mortality (30DM) after renal trauma and identify the risk factors associated with death. METHODS: The TRAUMAFUF project was a retrospective multi-institutional study including all patients with renal trauma admitted to 17 French hospitals between 2005 and 2015. The included population focused on patients of all age groups who underwent renal trauma during the study period. The primary outcome was death within 30 days following trauma. The multivariate logistic regression model with a stepwise backward elimination was used to identify predictive factors of 30DM. RESULTS: Data on 1,799 renal trauma were recorded over the 10-year period. There were 59 deaths within 30 days of renal trauma, conferring a 30DM rate of 3.27%. Renal trauma was directly involved in 5 deaths (8.5% of all deaths, 0.3% of all renal trauma). Multivariate stepwise logistic regression analysis revealed that age >40 years (odds ratio [OR] 2.18; 95% confidence interval [CI]: 1.20-3.99; p = 0.01), hemodynamic instability (OR 4.67; 95% CI: 2.49-9; p < 0.001), anemia (OR 3.89; 95% CI: 1.94-8.37; p < 0.001), bilateral renal trauma (OR 6.77; 95% CI: 2.83-15.61; p < 0.001), arterial contrast extravasation (OR 2.09; 95% CI: 1.09-3.96; p = 0.02), and concomitant visceral and bone injuries (OR 6.57; 95% CI: 2.41-23.14; p < 0.001) were independent predictors of 30DM. CONCLUSION: Our large multi-institutional study supports that the 30DM of 3.27% after renal trauma is due to the high degree of associated injuries and was rarely a consequence of renal trauma alone. Age >40 years, hemodynamic instability, anemia, bilateral renal trauma, arterial contrast extravasation, and concomitant visceral and bone lesions were predictors of death. These results can help clinicians to identify high-risk patients.

Observation vs. early drainage for grade IV blunt renal trauma: a multicenter study.

INTRODUCTION: The aim of this study was to compare observation and early drainage by ureteral stenting in patients with blunt renal trauma and urinary extravasation. MATERIALS AND METHODS: A retrospective national multicenter study was performed including all patients admitted for renal trauma at 17 hospitals between 2005 and 2015. Patients presenting with a urinary extravasation on initial imaging were considered for inclusion. Patients were divided in two groups according to the initial approach: observation vs. early drainage by ureteral stent (within 48 h after admission). The primary endpoint was the persistence of urinary extravasation on follow-up imaging. RESULTS: Out of 1799 patients with renal trauma, 238 were included in the analysis (57 in the early drainage and 181 in the observation group). In the early drainage group, 29 patients had persistent urinary extravasation vs. 77 in the observation group (50.9% vs. 42.5%; p value = 0.27). The rates of secondary upper urinary tract drainage did not differ significantly between the early drainage group (26.4%) and the observation group (16%) (p = 0.14). There were no statistically significant differences between the two groups in terms of secondary nephrectomy (0% vs. 2.8%; p = 0.34), and death from trauma (0% vs. 1.8%; p = 0.99). In multivariate analysis, early drainage remained not statistically associated with persistence of urinary extravasation on follow-up imaging (OR = 1.35; p = 0.36) CONCLUSION: In this multicenter cohort, observation was not different from early drainage in terms of persistent urinary extravasation after grade IV blunt renal trauma. Further randomized controlled prospective trials are needed to confirm these findings.

Early discharge in selected patients with low-grade renal trauma.

INTRODUCTION: The aim of this study was to assess whether early discharge could be non-inferior to inpatient management in selected patients with low-grade renal trauma (AAST grades 1-3). MATERIALS AND METHODS: A retrospective national multicenter study was conducted including all patients who presented with renal trauma at 17 hospitals between 2005 and 2015. Exclusion criteria were iatrogenic and AAST grades 4 and 5 trauma, non-conservative initial management, Hb < 10 g/dl or transfusion within the first 24 h, and patients with concomitant injuries. Patients were divided into two groups according to the length of hospital stay: ≤ 48 h (early discharge), and > 48 h (inpatient). The primary outcome was "Intervention" defined as any interventional procedure needed within the first 30 days. A Stabilized Inverse Probability of Treatment Weighting (SIPTW) propensity score based binary response model was used to estimate risk difference. RESULTS: Out of 1764 patients with renal trauma, 311 were included in the analysis (44 in the early discharge and 267 in the inpatient group). In the early discharge group, only one patient required an intervention within the first 30 days vs. 10 in the inpatient group (3.7% vs. 5.2%; p = 0.99). Adjusted analysis using SIPTW propensity score showed a risk difference of - 2.8% [- 9.3% to + 3.7%] of "interventions" between the two groups meeting the non-inferiority criteria. CONCLUSION: In a highly selected cohort, early discharge management of low-grade renal trauma was not associated with an increased risk of early "intervention" compared to inpatient management. Further prospective randomized controlled trials are needed to confirm these findings.

External validation of a nomogram for identification of pathologically favorable disease in intermediate risk prostate cancer patients.

OBJECTIVE: To establish an external validation of the new nomogram from Gandaglia et al which provides estimates of the probability of pathological favorable disease in pre-operatively defined intermediate-risk PCa. PATIENTS AND METHODS: Overall, 2928 intermediate-risk PCa patients according to the D'Amico classification undergoing RP and bilateral lymph node dissection in seven academic centres between 2000 and 2011. Pathologically favorable PCa was defined as low-grade organ-confined disease. The Receiver Operating Characteristic (ROC) curve was obtained to quantify the overall accuracy (Area Under the Curve, AUC) of the model to predict specimen-confined (SC) disease. Calibration curve was then constructed to illustrate the relationship between the risk-estimates obtained by the model and the observed proportion of SC disease. Kaplan-Meier method was used for PSA recurrence-free survival (PSA-RFS) assessment. RESULTS: Median age was 68 years. 10.6% patients finally presented pathologically favorable disease characteristics at RP. A higher PSAD (OR = 0.01; 95%CI = 0.00-0.04; P < 0.0001) and percentage of positive cores (OR = 0.97; 95%CI = 0.96-0.98; P < 0.0001) were associated with a reduced probability of favorable disease at RP in multivariate analysis. ROC curve analysis showed strongest accuracy of the model (AUC = 0.82; 95%CI = 0.79-0.84). Favorable PCa had a significantly better PSA recurrence-free survival rates as compared to unfavorable PCa after RP (94.2% vs 74.4% at 4 years, P < 0.0001). CONCLUSIONS: This external validation of the Gandaglia nomogram shows relevant accuracy with one out of ten patients in this intermediate risk PCa group with pathologically proven organ-confined disease. This validated risk calculator can help physician to distinguish favorable intermediate risk PCa that can be treated by conservative approach or safer nerve-sparing surgery.

Impact of Hospital Volume on the Outcomes of Renal Trauma Management.

BACKGROUND: Some health care systems have set up referral trauma centers to centralize expertise to improve trauma management. There is scant and controversial evidence regarding the impact of provider's volume on the outcomes of trauma management. OBJECTIVE: To evaluate the impact of hospital volume on the outcomes of renal trauma management in a European health care system. DESIGN SETTING AND PARTICIPANTS: A retrospective multicenter study, including all patients admitted for renal trauma in 17 French hospitals between 2005 and 2015, was conducted. INTERVENTION: Nephrectomy, angioembolization, or nonoperative management. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Four quartiles according to the caseload per year: low volume (eight or fewer per year), moderate volume (nine to 13 per year), high volume (14-25/yr), and very high volume (≥26/yr). The primary endpoint was failure of nonoperative management defined as any interventional radiology or surgical procedure needed within the first 30 d after admission. RESULTS AND LIMITATIONS: Of 1771 patients with renal trauma, 1704 were included. Nonoperative management was more prevalent in the very-high- and low-volume centers (p = 0.02). In a univariate analysis, very high hospital volume was associated with a lower risk of nonoperative management failure than low (odds ratio [OR] = 0.54; p = 0.05) and moderate (OR = 0.48; p = 0.02) hospital volume. There were fewer nephrectomies in the high- and very-high-volume groups (p = 0.003). In a multivariate analysis, very high volume remained associated with a lower risk of nonoperative management failure than low (OR = 0.48; p = 0.04) and moderate (OR = 0.42; p = 0.01) volume. Study limitations include all the shortcomings inherent to its retrospective multicenter design. CONCLUSIONS: In this multicenter study, management of renal trauma varied according to hospital volume. There were lower rates of nephrectomy and failure of nonoperative management in very-high-volume centers. These results raise the question of centralizing the management of renal trauma, which is currently not the case in our health care system. PATIENT SUMMARY: In this study, management of renal trauma varied according to hospital volume. Very-high-volume centers had lower rates of nephrectomy and failure of nonoperative management.

Factors Predictive of Selective Angioembolization Failure for Moderate- to High-grade Renal Trauma: A French Multi-institutional Study.

BACKGROUND: Angiography with selective angioembolization (SAE) is safe and effective in addressing bleeding in patients with renal trauma. However, there are no validated criteria to predict SAE efficacy. OBJECTIVE: To evaluate factors predictive of SAE failure after moderate- to high-grade renal trauma. DESIGN, SETTING, AND PARTICIPANTS: TRAUMAFUF was a retrospective multi-institutional study including all patients who underwent upfront SAE for renal trauma in 17 French hospitals between 2005 and 2015. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was SAE efficacy, defined as the absence of repeat SAE, salvage nephrectomy, and/or death for each patient. RESULTS AND LIMITATIONS: Out of 1770 consecutive patients with renal trauma, 170 (9.6%) with moderate- to high-grade renal trauma underwent SAE. Overall upfront SAE was successful in 131 patients (77%) and failed in 39 patients: six patients died after the embolization, ten underwent repeat SAE, 22 underwent open nephrectomy, and one underwent open surgical exploration. In multivariate logistic regression analysis, gross hematuria (odds ratio [OR] 3.16, 95% confidence interval [CI] 1.29-8.49; p=0.015), hemodynamic instability (OR 3.29, 95% CI 1.37-8.22; p=0.009), grade V trauma (OR 2.86, 95% CI 1.06-7.72; p=0.036), and urinary extravasation (OR 3.49, 95% CI 1.42-8.83; p=0.007) were predictors of SAE failure. The success rate was 64.7% (22/34) for patients with grade V trauma and 59.6% (31/52) for those with hemodynamic instability. The study was limited by its retrospective design and the lack of a control group managed with either surgery or surveillance. CONCLUSIONS: We found that gross hematuria, hemodynamic instability, grade V trauma, and urinary extravasation were significant predictors of SAE failure. However, success rates in these subgroups remained relatively high, suggesting that SAE might be appropriate for those patients as well. PATIENT SUMMARY: Selective angioembolization (SAE) is a useful alternative to nephrectomy to address bleeding in patients with renal trauma. Currently, there are no validated criteria to predict SAE efficacy. We found that gross hematuria, hemodynamic instability, grade V trauma, and urinary extravasation were significant predictors of SAE failure.

Benign Prostatic Hyperplasia Endoscopic Surgical Procedures in Kidney Transplant Recipients: A Comparison Between Holmium Laser Enucleation of the Prostate, GreenLight Photoselective Vaporization of the Prostate, and Transurethral Resection of the Prostate.

Purpose: The main objective of this multicentric retrospective pilot study was to evaluate the 1-year follow-up safety (i.e., minor [Clavien-Dindo I-II] and major [Clavien-Dindo ≥III] complications) of holmium laser enucleation of the prostate (HoLEP), GreenLight photoselective vaporization of the prostate (GL PVP), and transurethral resection of the prostate (TURP) performed after kidney transplantation (KT). The secondary objectives were to evaluate the efficacy and to assess the impact of these procedures on graft function. Materials and Methods: We retrospectively included all KT recipients who underwent a HoLEP or GL PVP or TURP for benign prostatic hyperplasia (BPH) in three French university centers. Results: From January 2013 to April 2018, 60 BPH endoscopic surgical procedures in KT recipients were performed: 17 HoLEP (HoLEP group), 9 GL PVP (GL PVP group), and 34 TURP (TURP group). Age, body mass index, preoperative serum creatinine, preoperative International Prostatic Symptom Score, preoperative Qmax, preoperative prostate-specific antigen, medical history of acute urinary retention (AUR), urinary tract infection (UTI), and indwelling urethral catheter were similar in all study groups. Mean preoperative prostate volume was higher in HoLEP group. The rate of overall postoperative complications was statistically higher in the HoLEP group (11/17 [64.7%] vs 1/9 [11.1%] vs 12/34 [35.3%] in HoLEP group, GL PVP group, and TURP group, respectively, p = 0.02), with higher rate of long-term UTI and AUR. Qmax improved in all groups after operation. Delta postoperative month 12-preoperative serum creatinine was similar in the all groups. Conclusions: Although our study is underpowered, the rate of postoperative complications is higher with HoLEP procedure, in comparison with GL PVP, for the treatment of BPH after KT. One-year efficacy is similar in HoLEP, GL PVP, and TURP groups. Further prospective randomized controlled trials are needed to confirm our results.

Comparison of the Comprehensive Complication Index and Clavien-Dindo systems in predicting perioperative outcomes following radical nephroureterectomy.

BACKGROUND: Complications can occur following radical nephroureterectomy (RNU) in 20-40% of patients. The Comprehensive Complication Index (CCI) is an alternative grading system to the Clavien-Dindo (CD) grading system that aggregates all complications experienced by a patient on a continuous (as opposed to categorical) scale. We investigate whether the cumulative nature of CCI renders it superior to CD in predicting perioperative course after RNU. METHODS: The records of 596 patents who underwent RNU at 7 academic medical centers from 2005 to 2015 were reviewed. Complications occurring within 30 days of RNU were annotated using both the CD and CCI classification systems. Logistic regression was used to determine associations between CD and CCI with perioperative covariates as well as measures of convalescence [hospital length of stay (LOS) and readmission]. RESULTS: A total of 377 men and 219 women with a median age of 71, BMI of 27, and Charlson comorbidity score of 4 were included. Over half underwent a minimally invasive RNU. Median LOS following RNU was 6.0 days (range, 1-37 days) and readmission within 30-days occurred in 45 (8%) patients. Overall, 136 patients (23%) experienced a post-operative complication with 91 having a single complication and 45 with multiple (range, 2-6); 44 (7%) patients had Clavien III or greater complications, and the median CCI for those patients experiencing a complication was 20.9 (range, 8.7-100). Both the upper quartile of CCI (≥75th %) and major CD complications were associated with higher baseline Charlson score, ECOG ≥2, and CKD stage ≥ III (all P<0.05). However, only the upper quartile of CCI was associated with LOS (8.9 vs. 5.4 days, P<0.01) and hospital readmission (OR 3.2, 95% CI: 1.9-5.6, P=0.02) after RNU. CONCLUSIONS: The CD and CCI classification systems both are associated with similar baseline and perioperative characteristics for RNU patients. However, the cumulative nature of the CCI allows for superior prediction of postoperative course after RNU including LOS and readmission.