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BackgroundWith growing interest in focal therapy (FT) of prostate cancer (PCa) there is an increasing armamentarium of treatment modalities including high-intensity focused ultrasound (HIFU), cryotherapy, focal laser ablation (FLA), irreversible electroporation (IRE), vascular targeted photodynamic therapy (VTP), focal brachytherapy (FBT) and stereotactic ablative radiotherapy (SABR). Currently there are no clear recommendations as to which of these technologies are appropriate for individual patient characteristics. Our intention was to review the literature for special aspects of the different technologies that might be of advantage depending on individual patient and tumour characteristics.MethodsThe current literature on FT was screened for the following factors: morbidity, repeatability, tumour risk category, tumour location, tumour size and prostate volume and anatomical issues. The ESUT expert panel arrived at consensus regarding a position statement on a structured pathway for available FT technologies based on a combination of the literature and expert opinion.ResultsSide effects were low across different studies and FT modalities with urinary continence rates of 90–100% and erectile dysfunction between 5 and 52%. Short to medium cancer control based on post-treatment biopsies were variable between ablative modalities. Expert consensus suggested that posterior lesions are better amenable to FT using HIFU. Cryotherapy provides best possible outcomes for anterior tumours. Apical lesions, when treated with FBT, may yield the least urethral morbidity.ConclusionsFurther prospective trials are required to assess medium to long term disease control of different ablative modalities for FT. Amongst different available FT modalities our ESUT expert consensus suggests that some may be better for diffe`rent tumour locations. Tumour risk, tumour size, tumour location, and prostate volume are all important factors to consider and might aid in designing future FT trials.

Cellular senescence is a state of cell cycle arrest induced by repetitive cell mitoses or different stresses, which is implicated in various physiological or pathological processes. The beneficial or adverse effects of senescent cells depend on their transitory or persistent state. Transient senescence has major beneficial roles promoting successful post-injury repair and inhibiting malignant transformation. On the other hand, persistent accumulation of senescent cells has been associated with chronic diseases and age-related illnesses like renal/urinary tract disorders. The deleterious effects of persistent senescent cells have been related, in part, to their senescence-associated secretory phenotype (SASP) characterized by the release of a variety of factors responsible for chronic inflammation, extracellular matrix adverse remodeling, and fibrosis. Recently, an increase in senescent cell burden has been reported in renal, prostate, and bladder disorders. In this review, we will summarize the molecular mechanisms of senescence and their implication in renal and urinary tract diseases. We will also discuss the differential impacts of transient versus persistent status of cellular senescence, as well as the therapeutic potential of senescent cell targeting in these diseases.

Sphingosine kinase-1 (SphK1) is an oncogenic lipid kinase notably involved in response to anticancer therapies in prostate cancer. Androgens regulate prostate cancer cell proliferation, and androgen deprivation therapy is the standard of care in the management of patients with advanced disease. Here, we explored the role of SphK1 in the regulation of androgen-dependent prostate cancer cell growth and survival. Short-term androgen removal induced a rapid and transient SphK1 inhibition associated with a reduced cell growth in vitro and in vivo, an event that was not observed in the hormono-insensitive PC-3 cells. Supporting the critical role of SphK1 inhibition in the rapid effect of androgen depletion, its overexpression could impair the cell growth decrease. Similarly, the addition of dihydrotestosterone (DHT) to androgen-deprived LNCaP cells re-established cell proliferation, through an androgen receptor/PI3K/Akt dependent stimulation of SphK1, and inhibition of SphK1 could markedly impede the effects of DHT. Conversely, long-term removal of androgen support in LNCaP and C4-2B cells resulted in a progressive increase in SphK1 expression and activity throughout the progression to androgen-independence state, which was characterized by the acquisition of a neuroendocrine (NE)-like cell phenotype. Importantly, inhibition of the PI3K/Akt pathway--by negatively impacting SphK1 activity--could prevent NE differentiation in both cell models, an event that could be mimicked by SphK1 inhibitors. Fascinatingly, the reversability of the NE phenotype by exposure to normal medium was linked with a pronounced inhibition of SphK1 activity. We report the first evidence that androgen deprivation induces a differential effect on SphK1 activity in hormone-sensitive prostate cancer cell models. These results also suggest that SphK1 activation upon chronic androgen deprivation may serve as a compensatory mechanism allowing prostate cancer cells to survive in androgen-depleted environment, giving support to its inhibition as a potential therapeutic strategy to delay/prevent the transition to androgen-independent prostate cancer.

Introduction Through a cross-sectional survey, we tried to assess whether practices of urologists and radiation oncologists are uniform when faced with similar clinical situations. Materials and Methods A self-administered questionnaire was mailed to all French urologists and radiation oncologists. Respondents were asked about their practices through 11 case scenarios. The scenarios cover most of localized prostate cancer situations and were gradually organized depending on prostate cancer progression risk and the age of the patient. The eight first scenarios address the situation of treatment-naive patients, and the last cases were about the management of patients after radical prostatectomy. Physicians were asked to choose a treatment modality for each case. The responses were first stratified according to the intention to treat: either curative-intent treatment or palliative. The curative-treatment modality chosen were afterward assessed. The responses to clinical scenarios were compared between the two specialties. Results Concerning the intention to treat, practice patterns were overall consistent except in one case. Indeed, a higher rate of radiation oncologists prefer curative-intent treatment for intermediate-risk prostate cancer in aged patients: 57.4 versus 14.6 % ( p  < 0.001). Each medical specialist prefers the treatment that he himself delivers ( p  < 0.005). For intermediate-risk prostate cancer in 65-year-old patient: 96.5 % of urologists chose radical prostatectomy versus 37.7 % of radiation oncologists ( p  < 0.001). Fewer urologists (almost 14 %) compared to radiation oncologists (47.5 %) would prescribe adjuvant treatment after radical prostatectomy for T3a R0 prostate cancer with post-operative PSA undetectable ( p  < 0.001). Conclusion Significant differences were found in therapeutic approach between the two main specialties that deal with localized prostate cancer.

Purpose To assess clinical and urodynamic efficacy of the first and repeated intradetrusor injections of abobotulinum toxin A (Dysport ® , Ipsen ® , France) in patients with neurogenic detrusor overactivity (NDO) refractory to anticholinergic treatment. Methods A single-center retrospective study was conducted in 81 consecutive patients who had never received any botulinum toxin intradetrusor injections. They were treated with at least one 750 U intradetrusor injection of abobotulinum toxin A. All patients performed clean intermittent self-catheterization (CIC) before injections. Success was defined as a combination of no incontinence episode, a number of catheterization <8 reported in a 3-day bladder diary and the lack of detrusor overactivity. Results Six weeks after the first injection, the success rate was 64.2 %. The proportion of continent patients was 80.2 %, the mean number of CIC per 24 h reduced (−3.55, p  < 0.0001) and the mean catheterization volume increased (+237.3 ml, p  < 0.0001). Regarding urodynamics, mean maximum cystometric capacity and mean volume at the first uninhibited contraction increased (+132.7 ml, p  < 0.0001 and +180 ml, p  < 0.0001, respectively) and mean maximum bladder pressure decreased significantly (−21.5 cm H 2 O, p  < 0.0001). Mean reinjection number was 3.9 and mean interval between reinjection was 8.8 ± 3 months. The clinical efficacy rate after each reinjection (up to fourteen) was at least 86.7 %. Out of 55 patients who underwent repeated injections, secondary resistance was noted in 2 (3.6 %). Conclusion The results of the present study are in favor of a long-term safety and efficacy of abobotulinum toxin A 750 U for NDO.

Objective Kidney transplantation from a living donor nephrectomy (LDN) is the best treatment for end-stage renal disease, but decrease in donor renal function is often revealed. The aim of this study was to evaluate the association between preoperative factors and postoperative estimated glomerular filtration rate (eGFR) and test a predictive model to estimate postoperative eGFR, 1 year after LDN. Patients and methods We reviewed 226 records of consecutive patients who underwent laparoscopic live donor nephrectomy between 2006 and 2014 in a single tertiary center. Of these, complete data on 202 patients were analyzed. A training (2/3 of the whole population) and a validation set (1/3) were randomized. A multivariate regression model was used to identify predictors and a formula to estimate of 1-year postoperative eGFR in the training set, using the CKD-EPI formula. Then, the formula was subjected to internal validation using the validation set using receiver operating characteristic (ROC) curves. Results Two hundred and two LLDN were evaluated with a mean preoperative eGFR of 94.1 ± 15.5 ml/min/1.73 m 2 and postoperative eGFR of 64.6 ± 14.5 ml/min/1.73 m 2 ( p  < 0.0001). In multivariable analysis, age and preoperative eGFR were independent predictors of postoperative eGFR in the training set. A formula to estimate postoperative eGFR was generated with Pearson r  = 0.70 in the training cohort and 0.65 in the validation cohort (both p  < 0.0001). Area under the ROC curve of the formula was 0.89 in the training cohort and 0.83 in the validation cohort (both p  < 0.0001). Conclusions Preoperative eGFR and age are predictors of postoperative eGFR after LDN. The internally validated predictive model of postoperative eGFR developed could be an accurate tool to improve the selection of LDN candidates.

Purpose To evaluate and compare perioperative outcomes in patients undergoing either transperitoneal (TP) or retroperitoneal (RP) laparoscopic nephrectomy for autosomal dominant polycystic kidney disease (ADPKD). Methods All patients with ADPKD who underwent unilateral laparoscopic nephrectomy between 2000 and 2012 in two academic departments were retrospectively included. The perioperative parameters were compared between the TP and RP groups. Results A total of 82 patients were included, 43 patients in the TP group and 39 in the RP group. The patients’ characteristics were similar between TP set and RP set, except for the time from dialysis onset to nephrectomy ( p  = 0.02). Complication rates (25.6 vs 33.3 %, p  = 0.44), transfusion rates (11.6 vs 20.5 %, p  = 0.27) and conversion to open surgery (4.6 vs 7.7 %, p  = 0.56) were similar between the TP and RP groups, respectively. Operative time was shorter for TP procedures (171.6 vs 210.5 min, p  = 0.002), but there was no difference between the two approaches after 20 surgeries ( p  = 0.06). Patients in TP group had a shorter length of hospital stay (5.3 ± 1.9 vs 7.2 ± 2.5 days, p  = 0.002). However, there was a trend towards shorter return of bowel function in the RP group (2.1 ± 0.9 vs 2.4 ± 0.8 days, p  = 0.09). Conclusion TP and RP laparoscopic nephrectomies provide good outcomes in patients with ADPKD. The choice of a TP route could decrease the length of hospital stay and the operative time during the beginning of the learning curve period.

ABSTRACT Purpose The present study assessed the incidence and histopathological features of incidentally diagnosed prostate cancer (PCa) in specimens from radical cystoprostatectomy (RCP) for bladder cancer. The patient outcomes also were evaluated. Methods We retrospectively reviewed the histopathological features and survival data of 4,299 male patients who underwent a RCP for bladder cancer at 25 French centers between January 1996 and June 2012. No patients had preoperative clinical or biological suspicion of PCa. Results Among the 4,299 RCP specimens, PCa was diagnosed in 931 patients (21.7 %). Most tumors (90.1 %) were organ-confined (pT2), whereas 9.9 % of them were diagnosed at a locally advanced stage (≥pT3). Gleason score was <6 in 129 cases (13.9 %), 6 in 575 cases (61.7 %), 7 (3 + 4) in 149 cases (16.0 %), 7 (4 + 3) in 38 cases (4.1 %), and >7 in 40 cases (4.3 %). After a median follow-up of 25.5 months (interquartile range 14.2–47.4), 35.4 % of patients had bladder cancer recurrence and 23.8 % died of bladder cancer. Only 16 patients (1.9 %) experienced PCa biochemical recurrence during follow-up, and no preoperative predictive factor was identified. No patients died from PCa. Conclusions The rate of incidentally diagnosed PCa in RCP specimens was 21.7 %. The majority of these PCas were organ-confined. PCa recurrence occurred in only 1.9 % of cases during follow-up.

Background Varicocele is a condition characterized by dilated, tortuous veins within the pampiniform venous plexus of the scrotal sac. Presence of varicocele is associated with an increased risk of alteration of semen parameters. The objective of this study was to compare the current standard in varicocele treatment procedures: sub-inguinal microscopic ligation to percutaneous embolization in terms of semen parameters improvement, fertility, and morbidity at the university hospital of Toulouse (France). Seventy six patients with clinical varicocele, alteration of semen parameters and infertility, underwent either procedure (microsurgery in 49 case performed by a single surgeon and embolization in 27 cases) and were prospectively analyzed. Outcome measures were: semen parameters, spontaneous pregnancies, pain, side effects, recovery time and overall satisfaction. All patients were contacted in January 2015 in order to determine reproductive events. Results Preoperatively, there was no difference in clinical and biological items between the two groups. Postoperatively, on the overall population, there was a significant improvement of sperm concentration at 3, 6, 9 and 12 months ( p  = <0.001, <0.001, 0.012, 0.018) and sperm motility at 6 months ( p  = 0.002). The sperm concentration was higher at 6 months in the percutaneous embolization group (13.42, vs. 8.1×10 6 /ml; p  = 0.043). With a median follow-up of 4 years, 27 pregnancies occurred (spontaneous pregnancy rate of 35.5%). There was no significant difference between procedures on the sperm quality, pregnancy rate, and the overall satisfaction. Patients undergoing percutaneous embolization reported a faster recovery time ( p  = 0.002) and less postoperative pain ( p  = 0.007). Conclusion Our study shows that percutaneous embolization seems to be an equivalent alternative to sub-inguinal microscopic ligation in term of sperm quality improvement, pregnancy rate, and overall satisfaction with a slight advantage on post-operative morbidity.

Purpose To assess the postsurgical survival of patients with urothelial carcinoma of the bladder with pT0 tumor at pathologic examination of cystectomy specimens. Methods A multi-institutional, retrospective database was analyzed with data from 4758 radical cystectomy (RC) patients who underwent RC without neoadjuvant chemotherapy and who were diagnosed with pT0 on the basis of the pathologic specimen. Survival curves were estimated. A multivariate Cox model was used to evaluate the association between prognosis factors and disease recurrence or survival. Results Overall, 258 patients (5.4%) were included in the study. The median age was 64 years. At last resection, 171 tumors were invasive (at least pT2), and 87 were not. Median follow-up was 51 months. At multivariate analysis, initial location of the tumor and absence of lymphadenectomy were associated with tumor recurrence ( P  = 0.03 and P  = 0.005, respectively) and specific mortality ( P  = 0.005 and 0.001, respectively). The main limitation of the study is its retrospective design, which is due to the rarity of this situation. Cancer-specific and recurrence-free survival rates were 89 and 85%, respectively, at 5 years and 82 and 80%, respectively, at 10 years. Conclusions Despite acceptable oncological outcomes, patients with a pT0 tumor at the time of RC are still at risk of recurrence and progression and should not be considered to be entirely cured. In this population, stringent follow-up according to current recommendations should be effective.