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.

Transcutaneous tibial nerve stimulation: 2 years follow-up outcomes in the management of anticholinergic refractory overactive bladder.

PURPOSE: To evaluate long-term use, efficacy and tolerability of transcutaneous tibial nerve stimulation (TTNS) in the treatment of refractory overactive bladder (OAB). METHODS: We performed a prospective observational study and included all patients treated in a single center for OAB persisting after first-line anticholinergic treatment, with ≥ 24 months follow-up. The protocol consisted of daily stimulation at home. The primary outcome was treatment persistence. Amelioration was defined as an improvement in urinary symptom profile (USP) score. RESULTS: We assessed 84 consecutive patients. After a mean follow-up of 39.3 months and a mean treatment use of 8.3 months, almost two-thirds of patients (71.8%) had discontinued TTNS. Treatment continuation was > 12 months for 28 patients (33.3%) and > 18 months for 16 patients (19%). TTNS was successful following 3 months of treatment in 60 (71%) patients. Mean USP score stayed significantly lower than baseline until 12 months of treatment, but was not significant anymore after 18 months. Discontinuation therapy reasons were a lack of sufficient symptom relief for 59 (70%) patients, compliance difficulty for 5 (6%) patients and becoming asymptomatic for 6 (8%) patients. No serious adverse events occurred. CONCLUSIONS: The present study confirms the utility of TTNS as a treatment option for patients with resistant OAB. In the long-term use, few patients continued with therapy, mostly because of a decreased effectiveness with time.

How Did We Obtain Complete Remission in Patients Who Had Metastatic Renal Cancer in the Era of Targeted Therapies?

BACKGROUND: The management of metastatic renal cell carcinoma (mRCC) has been transformed by the use of targeted therapies, ablative therapies and improved surgical techniques. The objective of this study was to identify therapeutic strategies that resulted in complete remission (CR) and to assess survival of patients in CR. METHODS: In a prospective database, we included all patients treated for mRCC at a university hospital between 2007 and 2015. CR was defined as the absence of metastasis after a full-body computed tomographic scan. RESULTS: We treated 77 patients with mRCC and experienced a CR in 22 (29 %) patients. Patients in CR had, respectively, synchronous and metachronous metastases in 7 (32 %) and 15 (68 %) cases and unique and multiple metastases in 4 (18 %) and 18 (82 %) cases. All patients were treated with cytoreductive nephrectomy and 21 (96 %) had metastasectomy or percutaneous ablation of their metastases. One patient had a CR after systemic treatment with sunitinib. After a median (range) follow-up since metastatic diagnosis of 35 (1-89) months, 12 patients (55 %) had disease recurrence. The median (range) duration of CR before recurrence was 14 (1-39) months. After recurrence, a new CR was obtained in 7 patients (58 %). At the end of follow-up, 16 patients (73 %) were still in CR, 5 (23 %) were undergoing medical treatment, and 1 patient died during the postoperative course. CONCLUSIONS: In the era of targeted-therapies, CRs were obtained with multimodal treatment of metastatic kidney cancer. All patients in CR had a nephrectomy and almost all of them had multiple metastasectomies.

Comparison of 1800 Robotic and Open Partial Nephrectomies for Renal Tumors.

BACKGROUND: Only a few studies have compared the outcomes of robotic partial nephrectomy (RPN) and open partial nephrectomy (OPN). This study aimed to compare perioperative and oncologic outcomes of RPN and OPN. METHODS: The data of all patients who underwent partial nephrectomy from 2006 to 2014 in six academic departments of urology were retrospectively collected. Perioperative outcomes were compared between OPN and RPN patients. Cancer-specific survival (CSS) and recurrence-free survival (RFS) were estimated using the Kaplan-Meier method and compared using the log-rank test. RESULTS: The study included 1800 patients: 937 who underwent RPN and 863 who underwent OPN. The patients in the robotic group had smaller tumors (33.1 vs. 39.9 mm; p < 0.001) but comparable RENAL scores (6.8 vs. 6.7; p = 0.37). The complication rate was higher in the OPN group (28.6 vs. 18 %; p < 0.001). The OPN patients had greater estimated blood loss (359.5 vs. 275 ml; p < 0.001) and more frequent hemorrhagic complications (12.1 vs. 6.9 %; p < 0.001). The robotic approach was associated with a shorter warm ischemia time (WIT 15.7 vs. 18.6 min; p < 0.001) and a shorter hospital of stay (4.7 vs. 10.1 days; p < 0.001). In the propensity score-weighted analysis, the inverse probability of treatment weighting adjusted odds ratio for the risk of complication after OPN versus RPN was 2.11 (95 % confidence interval, 1.53-2.91; p < 0.001). After a median postoperative follow-up period of 13 months for OPN and 39 months for RPN (p < 0.001), CSS and RFS were similar in the two groups. In the multivariate analysis, RPN showed an impact on the occurrence of a complication but had no effect on WIT or RFS. CONCLUSION: In this study, RPN was less morbid than OPN, with lower complications, less blood loss, and a shorter hospital of stay. The intermediate-term oncologic outcomes were similar in the two groups.

Posterior Spinal Cord Syndrome after Flexible Ureteroscopy for Kidney Stones.

A 49-year-old woman was treated for right kidney stones using flexible ureteroscopy and laser lithotripsy. She was readmitted 2 weeks after the treatment with complaints of walking difficulties. On neurologic examination, it was found that she had a bilateral proprioceptive dysfunction. Spinal MRI revealed an intramedullary lesion at the T10-T11 level consistent with an intramedullary cavernoma. The final diagnosis was a spinal compression consecutive to the cavernoma bleeding associated with the prolonged lithotomy position. Symptoms have not been reversible and the patient continued to have walking difficulties. We report for the first time a major complication that arises as a result of using flexible ureteroscopy for treating kidney stones.

Double-J ureteral stent under local anesthesia for women.

INTRODUCTION: Ureteral stent placement is a key urologic procedure used to manage ureteral obstructions. It is usually performed under general anesthesia (GA) with its inherent risks. The objective was to evaluate safety, feasibility and tolerance of ureteral stent placement under local anesthesia (LA) in women. MATERIALS AND METHODS: From January 2010 to January 2013, we prospectively and consecutively reviewed all female patients who had an urgent retrograde ureteral stent placement under LA. Only primary stent placements were included in the study. Pain was assessed after surgery by Visual Analog Scale (VAS) and pain and comfort assessment during stent placement were reported. We compared outcomes and tolerance with patients under general anesthesia (GA) matched by age and operatives indications during the same period. RESULTS: We included 36 patients (18 under LA and 18 under GA) with a mean age of 59.4 +/- 22.4 years. The mean operative time was 24.4 +/- 12.9 min and 18.8 +/- 6.5 min in LA group and GA group (p = 0.110), respectively. One patient needed GA due to a poor tolerance. The mean perioperative VAS scores under LA and GA were 5.89 +/-2.95 and 2.06 +/- 2.67 (p < 0.0001), respectively. There were no intraoperative complications in either group. The procedure was painful for 16 (88.8%) patients from the LA group and 9 (50%) patients would not accept to undergo this intervention under LA again. CONCLUSION: Ureteral stent placement under LA in women can be performed safely and effectively. However, this procedure is painful and should be proposed only to selected cases.

Do Failure of Posterior Tibial Nerve Stimulation Precludes to Use Sacral Neuromodulation in Patient With Overactive Bladder?

PURPOSE: To evaluate the outcomes of sacral neuromodulation (SNM) after failure of transcutaneous posterior tibial nerve stimulation (TPTNS) in patients with overactive bladder (OAB). METHODS: A retrospective study was conducted in 3 university hospitals and included all patients with OAB and treated with SNM after TPTNS had been tried between October 2008 and May 2018. The primary endpoint was the proportion of definitive SNM device implantation in patients with 50% objective and/or subjective improvement after a test period (stage 1). The secondary outcomes of interest were changes of the number of diurnal voids and nocturia episodes per 24 hours between the end of TPTNS and the end of stage 1. RESULTS: Overall, 28 of the 43 patients included achieved at least 50% objective and/or subjective improvement during stage 1 and underwent an Interstim II implantation (65.1%). The mean daytime frequency decreased significantly from 10.3/day at the end of TPTNS to 7.8 diurnal voids/day at the end of SNM stage 1 (P=0.01). The mean number of nocturia episodes decreased from 2.5/night at the end of TPTNS to 2.1/night at the end of stage 1, but this did not reach statistical significance (P=0.18). There was no other parameter significantly associated with response to SNM. CONCLUSION: SNM might improve OAB symptoms in most patients who experienced no or poor efficacy with TPTNS. History of failed TPTNS should not preclude the use of SNM in OAB patients.

Primary female epispadias: Perineal approach or Kelly repair?

OBJECTIVES: Primary female epispadias encompasses a spectrum of disease, presenting with a variable degree of incontinence. We hypothesized that although perineal urethrocervicoplasty can be a successful first-line procedure in patients with normal bladder, a more radical reconstruction was necessary to achieve continence in cases lying at the most severe end of the spectrum. Our aim was to assess the results of a surgical management using perineal approach in girls with normal bladder capacity, and Kelly radical soft-tissue mobilization (RSTM) in patients with inadequate bladder, based on the assumption that bladder capacity (BC) is a reliable marker of epispadias severity. STUDY DESIGN: Prospective inclusion of incontinent girls with female epispadias referred to a single institution. Patients with normal BC were treated with perineal urethrocervicoplasty (PUCP, group 1). Patients with small bladder underwent RSTM (group 2). Follow-up was at 1, 3, 6, and 12 months postoperatively, then annually, including physical examination, renal ultrasound at each visit, continence status, and estimation of functional/maximal BC. The main study outcome was continence status at the age of 5 years or later, if postoperative follow-up was >12 months. RESULTS: From 2006 to 2017, 16 consecutive children were prospectively included in this study, at a median age of 39 months (5-102 months). Seven girls were included in group 1 and underwent PUCP; at the last follow-up, five out of seven were dry by day (4/5 day and night), although three out of five required bladder-neck injection after perineal reconstruction due to stress incontinence. Two patients with persistent incontinence and absence of BC increase after PUCP subsequently underwent RSTM. Eleven patients with low BC (56% [10-94%] of expected BC) were included in group 2 (9 without prior surgery, 2 after PUCP failure). Among the eight evaluable patients, eight out of eight achieved diurnal continence, and 3/8 were fully continent. One girl with obstructive micturition required clean intermittent catheterization. DISCUSSION: The traditional approach of female epispadias based on staged reconstruction (urethroplasty followed by bladder-neck reconstruction) raised concerns regarding the risk of non-physiological obstructive micturition. The perineal approach was suggested as an alternative, with reported diurnal continence rates of 60-80%, but less than 50% of nocturnal continence, presumably in relation with limited bladder capacity. In cases selected within the most severe end of the epispadias spectrum, the Kelly RSTM seems to offer excellent continence rates. CONCLUSION: A tailored approach to female epispadias, based on perineal reconstruction in favorable cases, and radical soft-tissue mobilization in severe cases, seems to yield good continence outcomes in the long term.

Functional characterization of the 12p12.1 renal cancer-susceptibility locus implicates BHLHE41.

Genome-wide association studies have identified multiple renal cell carcinoma (RCC) susceptibility loci. Here, we use regional imputation and bioinformatics analysis of the 12p12.1 locus to identify the single-nucleotide polymorphism (SNP) rs7132434 as a potential functional variant. Luciferase assays demonstrate allele-specific regulatory activity and, together with data from electromobility shift assays, suggest allele-specific differences at rs7132434 for AP-1 transcription factor binding. In an analysis of The Cancer Genome Atlas data, SNPs highly correlated with rs7132434 show allele-specific differences in BHLHE41 expression (trend P value=6.3 × 10(-7)). Cells overexpressing BHLHE41 produce larger mouse xenograft tumours, while RNA-seq analysis reveals that constitutively increased BHLHE41 induces expression of IL-11. We conclude that the RCC risk allele at 12p12.1 maps to rs7132434, a functional variant in an enhancer that upregulates BHLHE41 expression which, in turn, induces IL-11, a member of the IL-6 cytokine family.