Integrated molecular and pharmacological characterization of patient-derived xenografts from bladder and ureteral cancers identifies new potential therapies.

Background: Muscle-invasive bladder cancer (MIBC) and upper urinary tract urothelial carcinoma (UTUC) are molecularly heterogeneous. Despite chemotherapies, immunotherapies, or anti-fibroblast growth factor receptor (FGFR) treatments, these tumors are still of a poor outcome. Our objective was to develop a bank of patient-derived xenografts (PDXs) recapitulating the molecular heterogeneity of MIBC and UTUC, to facilitate the preclinical identification of therapies. Methods: Fresh tumors were obtained from patients and subcutaneously engrafted into immune-compromised mice. Patient tumors and matched PDXs were compared regarding histopathology, transcriptomic (microarrays), and genomic profiles [targeted Next-Generation Sequencing (NGS)]. Several PDXs were treated with chemotherapy (cisplatin/gemcitabine) or targeted therapies [FGFR and epidermal growth factor (EGFR) inhibitors]. Results: A total of 31 PDXs were established from 1 non-MIBC, 25 MIBC, and 5 upper urinary tract tumors, including 28 urothelial (UC) and 3 squamous cell carcinomas (SCCs). Integrated genomic and transcriptomic profiling identified the PDXs of three different consensus molecular subtypes [basal/squamous (Ba/Sq), luminal papillary, and luminal unstable] and included FGFR3-mutated PDXs. High histological and genomic concordance was found between matched patient tumor/PDX. Discordance in molecular subtypes, such as a Ba/Sq patient tumor giving rise to a luminal papillary PDX, was observed (n=5) at molecular and histological levels. Ten models were treated with cisplatin-based chemotherapy, and we did not observe any association between subtypes and the response. Of the three Ba/Sq models treated with anti-EGFR therapy, two models were sensitive, and one model, of the sarcomatoid variant, was resistant. The treatment of three FGFR3-mutant PDXs with combined FGFR/EGFR inhibitors was more efficient than anti-FGFR3 treatment alone. Conclusions: We developed preclinical PDX models that recapitulate the molecular heterogeneity of MIBCs and UTUC, including actionable mutations, which will represent an essential tool in therapy development. The pharmacological characterization of the PDXs suggested that the upper urinary tract and MIBCs, not only UC but also SCC, with similar molecular characteristics could benefit from the same treatments including anti-FGFR for FGFR3-mutated tumors and anti-EGFR for basal ones and showed a benefit for combined FGFR/EGFR inhibition in FGFR3-mutant PDXs, compared to FGFR inhibition alone.

Available evidence on HIFU for focal treatment of prostate cancer: a systematic review

ABSTRACT Purpose: Prostate cancer (PCa) is the second most common oncologic disease among men. Radical treatment with curative intent provides good oncological results for PCa survivors, although definitive therapy is associated with significant number of serious side-effects. In modern-era of medicine tissue-sparing techniques, such as focal HIFU, have been proposed for PCa patients in order to provide cancer control equivalent to the standard-of-care procedures while reducing morbidities and complications. The aim of this systematic review was to summarise the available evidence about focal HIFU therapy as a primary treatment for localized PCa. Material and methods: We conducted a comprehensive literature review of focal HIFU therapy in the MEDLINE database (PROSPERO: CRD42021235581). Articles published in the English language between 2010 and 2020 with more than 50 patients were included. Results: Clinically significant in-field recurrence and out-of-field progression were detected to 22% and 29% PCa patients, respectively. Higher ISUP grade group, more positive cores at biopsy and bilateral disease were identified as the main risk factors for disease recurrence. The most common strategy for recurrence management was definitive therapy. Six months after focal HIFU therapy 98% of patients were totally continent and 80% of patients retained sufficient erections for sexual intercourse. The majority of complications presented in the early postoperative period and were classified as low-grade. Conclusions: This review highlights that focal HIFU therapy appears to be a safe procedure, while short-term cancer control rate is encouraging. Though, second-line treatment or active surveillance seems to be necessary in a significant number of patients.

Available evidence on HIFU for focal treatment of prostate cancer: a systematic review.

PURPOSE: Prostate cancer (PCa) is the second most common oncologic disease among men. Radical treatment with curative intent provides good oncological results for PCa survivors, although definitive therapy is associated with significant number of serious side-effects. In modern-era of medicine tissue-sparing techniques, such as focal HIFU, have been proposed for PCa patients in order to provide cancer control equivalent to the standard-of-care procedures while reducing morbidities and complications. The aim of this systematic review was to summarise the available evidence about focal HIFU therapy as a primary treatment for localized PCa. MATERIAL AND METHODS: We conducted a comprehensive literature review of focal HIFU therapy in the MEDLINE database (PROSPERO: CRD42021235581). Articles published in the English language between 2010 and 2020 with more than 50 patients were included. RESULTS: Clinically significant in-field recurrence and out-of-field progression were detected to 22% and 29% PCa patients, respectively. Higher ISUP grade group, more positive cores at biopsy and bilateral disease were identified as the main risk factors for disease recurrence. The most common strategy for recurrence management was definitive therapy. Six months after focal HIFU therapy 98% of patients were totally continent and 80% of patients retained sufficient erections for sexual intercourse. The majority of complications presented in the early postoperative period and were classified as low-grade. CONCLUSIONS: This review highlights that focal HIFU therapy appears to be a safe procedure, while short-term cancer control rate is encouraging. Though, second-line treatment or active surveillance seems to be necessary in a significant number of patients.

Cellular Senescence in Renal and Urinary Tract Disorders.

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.

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.

Which technology to select for primary focal treatment of prostate cancer?-European Section of Urotechnology (ESUT) position statement.

BACKGROUND: With 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. METHODS: The 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. RESULTS: Side 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. CONCLUSIONS: Further 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.

Focal Treatment for Unilateral Prostate Cancer Using High-Intensity Focal Ultrasound: A Comprehensive Study of Pooled Data.

BACKGROUND: Focal therapy for prostate cancer (PCa) remains experimental. Aim of the current study is to review available evidence and perform a pooled analysis exploring oncologic and functional results of high intensity focus ultrasound (HIFU) focal therapy for the treatment of unilateral PCa. METHODS: The National Library of Medicine Database was searched for relevant articles. A wide search was performed, including the combination of following words: "HIFU," "prostate," "cancer," and "focal." Overall, 167 articles were reviewed. Of these, seven articles were identified and eligible for the pooled analysis. Data on HIFU hemiablation or focal prostate ablation, oncologic and functional results were pooled from these seven studies that included 366 men with unilateral PCa. RESULTS: In the 366 analyzed cases, mean age was 67 years (95% confidence interval 66-69), and mean preoperative prostate-specific antigen was 6.4 ng/cc (5.5-7.4). Three studies included PCa up to Gleason 7 (3 + 4), three studies did include also Gleason 7 (4 + 3), whereas one study had no limitation in terms of Gleason score. Regarding early complications, low-grade Clavien-Dindo I-II were reported in 26% (16-37), whereas high-grade Clavien-Dindo ≥III were found in 3.8% (0-8.6). Analyzing oncologic outcomes mean follow-up was 26 months (23-31): at one year after HIFU, negative biopsy rate for clinically significant PCa was 87% (79-96), whereas salvage treatment-free survival rate was 92% (85-98). Regarding functional outcomes, reported potency rates were 74% (64-84), and continence 96% (91-100), although definitions of potency and continence were not homogenous across studies. CONCLUSIONS: This pooled analysis of the results of focal HIFU treatment of PCa shows promising oncologic and functional outcomes. Well-selected patients may be candidates for such a conservative partial treatment of the gland. Well-designed trials are awaited to compare HIFU focal treatment with current standard of care.

Subinguinal microsurgical varicocelectomy vs. percutaneous embolization in infertile men: Prospective comparison of reproductive and functional outcomes.

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. 8.1×106/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.

CONTEXTE: La varicocèle est une affection caractérisée par une dilatation et tortuosité des veines du plexus veineux pampiniforme du sac scrotal. La présence de varicocèle est associée à un risque accru d'altération des paramètres du sperme. Cette étude vise à comparer la norme actuelle des procédures de traitement par varicocèle: la ligature microscopique sous-inguinale à l'embolisation percutanée en termes d'amélioration des paramètres spermatiques, de fertilité et de morbidité dans l'hôpital universitaire de Toulouse(France). Soixante-seize patients atteints de varicocèle clinique, d'altération des paramètres spermatiques et d'infertilité ont subi une intervention (microchirurgie dans 49 cas réalisées par un seul urologue et embolisation dans 27 cas) et ont fait l'objet d'une analyse prospective. Les données étudiées sont les suivantes: paramètres du sperme, grossesses spontanées, douleur, effets secondaires, temps de récupération et satisfaction globale. Tous les patients ont été contactés en janvier 2015 afin de déterminer les grossesses spontanées. RÉSULTATS: En préopératoire, il n'existait aucune différence sur les items cliniques et biologiques entre les deux groupes. Sur la population globale, on observe une amélioration significative de la concentration spermatique à 3, 6, 9 et 12 mois (p = <0,001, <0,001, 0,012, 0,018) et de la motilité à 6 mois (p = 0,002). La concentration de spermatozoïdes était plus élevée à 6 mois dans le groupe d'embolisation percutané (13,42 vs 8,09; p = 0,043). Avec un suivi médian de 4 ans, 27 grossesses sont survenues (taux de grossesse spontanée de 35.5%). Il n'y avait pas de différence significative entre les procédures sur la qualité du sperme, le taux de grossesse et la satisfaction globale. Les patients traités par embolisation percutanée ont rapporté un temps de récupération plus rapide (p = 0,002) et moins de douleur postopératoire (p = 0,007). CONCLUSION: Notre étude montre que l'embolisation percutanée semble être une alternative équivalente à la ligature microscopique sous-inguinale en terme d'amélioration de la qualité du sperme, du taux de grossesse et de la satisfaction globale avec un léger avantage sur la morbidité post-opératoire.

Predictive model of 1-year postoperative renal function after living donor nephrectomy.

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 m2 and postoperative eGFR of 64.6 ± 14.5 ml/min/1.73 m2 (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.

Assessment of a program to encourage the multidisciplinary management of urinary disorders in multiple sclerosis.

AIMS: Urinary disorders (UD) secondary to multiple sclerosis (MS) are common and can be responsible for complications. Since 2004, we organized in our region their management through a neuro-urological activity and a care network that established and distributed an algorithm for screening and first line care. The objective was to assess the effects of this organization on the management of UD and its impact for patients. METHODS: Between January 2004 and December 2009, 328 patients were seen in neuro-urological consultation. The data of a group of 168 patients consulting during the deployment of our organization (before January 2007: group 1) were compared to those of 160 patients taken when the organization was well established (from January 2007: group 2). In parallel, the modification of the prescription rate of the first-line examination patients was evaluated. RESULTS: The two groups were significantly different concerning age, duration of MS, EDSS score (Group 1 vs. Group 2 respectively 51.6 ± 12.6 vs. 48 ± 11.8 years, P = 0.008; 19 ± 9.7 vs. 13.8 ± 10.5 years, P < 0.0001; 5.8 ±2.0 vs. 5.1 ± 2.1, P = 0.008). The occurrence of urinary complications in group 1 was more frequent than in group 2 (66.3% vs. 40%, P < 0.0001). The rate of first-line examinations rose from 1/16 patient seen in January 2006 to 9/12 patients in January 2008. CONCLUSION: The multidisciplinary management of UD in MS led to patients being cared for sooner in the evolution of MS, with fewer complications and to an improvement in the rate of prescription of first-line examinations. Neurourol. Urodynam. 36:706-709, 2017. © 2016 Wiley Periodicals, Inc.

Focal High Intensity Focused Ultrasound of Unilateral Localized Prostate Cancer: A Prospective Multicentric Hemiablation Study of 111 Patients.

BACKGROUND: Up to a third of patients with localized prostate cancer have unilateral disease that may be suitable for partial treatment with hemiablation. OBJECTIVE: To evaluate the ability of high intensity focused ultrasound (HIFU) to achieve local control of the tumor in patients with unilateral localized prostate cancer. DESIGN, SETTING, AND PARTICIPANTS: The French Urological Association initiated a prospective IDEAL multi-institutional study (2009-2015), to evaluate HIFU-hemiablation as a primary treatment. INTERVENTION: Multiparametric magnetic resonance imaging and biopsy were used for unilateral cancer diagnosis and control, and HIFU-hemiablation. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Primary: absence of clinically significant cancer (CSC) on control biopsy at 1 yr (CSC: Gleason score ≥ 7 or cancer core length>3mm regardless of grade or > 2 positive cores). Secondary: presence of any cancer on biopsy, biochemical response, radical treatment free survival, adverse events, continence (no pad), erectile function (International Index of Erectile Function-5 ≥ 16), and quality of life (European Organization for Research and Treatment of Cancer QLQ-C28) questionnaires. RESULTS AND LIMITATIONS: One hundred and eleven patients were treated (mean age: 64.8 yr [standard deviation 6.2]; mean prostate-specific antigen: 6.2 ng/ml [standard deviation 2.6]; 68% low risk, 32% intermediate risk). Of the 101 patients with control biopsy, 96 (95%) and 94 (93%) had no CSC in the treated and contralateral lobes, respectively. Mean prostate-specific antigen at 2 yr was 2.3 ng/ml (standard deviation 1.7). The radical treatment-free survival rate at 2 years was 89% (radical treatments: six radical prostatectomies, three radiotherapies, and two HIFU). Adverse events were Grade 3 in 13%. At 12 mo continence and erectile functions were preserved in 97% and 78%. No significant decrease in quality of life score was observed at 12 mo. One limitation is the number of low-risk patients included in this study. CONCLUSIONS: At 1 yr, HIFU-hemiablation was efficient with 95% absence of clinically significant cancer associated with low morbidity and preservation of quality of life. Radical treatment-free survival rate was 89% at 2 yr. PATIENT SUMMARY: This report shows that high intensity focused ultrasound half-gland treatment of unilateral prostate cancer provides promising results with high cancer control and low morbidity.

Intradetrusor injections of onabotulinum toxin A (Botox®) 300 U or 200 U versus abobotulinum toxin A (Dysport®) 750 U in the management of neurogenic detrusor overactivity: A case control study.

AIMS: To compare the outcomes of the first intradetrusor injections of abobotulinum toxin 750 U and onabotulinum toxin 200 and 300 U in patients with neurogenic detrusor overactivity (NDO). METHODS: A retrospective case-control study was conducted including 211 NDO patients treated in three consecutives eras with onabotulinum toxin 300 U (2004-2006; 80 patients), abobotulinum toxin 750 U (2007-2011; 78 patients) or onabotulinum toxin 200 U (2011-2014; 53 patients). Urodynamic and clinical parameters were compared between groups. The primary endpoint was the rates of success defined as the combination of urgency, urinary incontinence, and detrusor overactivity resolution. RESULTS: When comparing abobotulinum toxin to onabotulinum toxin any doses (200 or 300 U; n = 133), success rates were similar (65.4% vs. 55.6%; P = 0.16). Patients treated with abobotulinum toxin 750 U had higher success rate (65.4% vs. 41.5%; P = 0.007) compared to those who received onabotulinum toxin 200 U. In contrast, there were similar success rates in abobotulinum toxin 750 U and onabotulinum toxin 300 U groups (65.4% vs. 65%; P = 0.91) but with a trend towards longer interval between the first and the second injection in the onabotulinum toxin 300 U group (12.4 vs. 9.3 months; P = 0.09). CONCLUSIONS: Intradetrusor injections of abobotulinum toxin 750 U for NDO provided better outcomes than injections of onabotulinum toxin 200 U. Success rates of abobotulinum toxin 750 U and onabotulinum toxin 300 U were similar but interval between injections tended to be longer with onabotulinum toxin 300 U. Neurourol. Urodynam. 36:734-739, 2017. © 2016 Wiley Periodicals, Inc.

Efficacy and safety of the first and repeated intradetrusor injections of abobotulinum toxin A 750 U for treating neurological detrusor overactivity.

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 H2O, 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.

Laparoscopic nephrectomy for polycystic kidney: comparison of the transperitoneal and retroperitoneal approaches.

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.

Preliminary results of botulinum toxin A switch after first detrusor injection failure as a treatment of neurogenic detrusor overactivity.

AIMS: To assess the results of onabotulinum toxin detrusor injections when abobotulinum toxin detrusor injection failed. METHODS: Twenty-six patients, 15 women and 11 men, mean age 40.8 ± 12.7 years old, in whom a first injection of 750 U abobotulinum toxin in 20 sites failed in treating neurogenic detrusor overactivity, received onabotulinum toxin 300 U detrusor injections in 30 sites. Neurologic conditions were spinal cord injury in 14 cases, multiple sclerosis in nine, myelomeningocele in two and myelitis in one. Mean time between the two injections was 5.6 ± 1.4 months. Before and 6 weeks after each injection, patients carried out a 3-day bladder diary and had urodynamics. The success was defined as the combination of a clean intermittent self-catheterization number under 8 per 24 hr, urgency, urinary incontinence and detrusor overactivity relief. RESULTS: Out of 26 patients, the second injection was successful in 15 (57.7%). While the first injection of 750 U abobotulinum toxin had no impact at all, after 300 U onabotulinum toxin injection, the number of clean intermittent self-catheterization decreased significantly (11.3 ± 2.1 vs. 6.4 ± 1.9, P = 0.01), 17/26 (65.4%) patients achieved continence, urgency was relieved in 18/26 (69.2%) and detrusor overactivity in 15/26 (57.7%). CONCLUSIONS: In case of failure after a first detrusor injection of abobotulinum toxin, switching for onabotulinum toxin is efficient. Further investigations should be performed to assess whether the replacement of onabotulinum toxin by abobotulinum toxin provides the same results.

Sphingosine Kinase 1 urothelial expression is increased in patients with neurogenic detrusor overactivity

Objectives: To evaluate the expression of sphingosine kinase 1 (SPK1) in the bladder wall in patients with neurogenic lower urinary tract dysfunction and its association with clinical, urodynamic and pathological features. Materials and Methods: The expression of SPK1 was studied in bladder wall specimens obtained from cystectomy using immunohistochemistry in ten patients with spinal cord injury (n=8) or multiple sclerosis (n=2) with urodynamically proven neuropathic bladder dysfunction, and in controls (n=5). Inflammation and fibrosis were analysed with histological criteria and SPK1 expression was determined by individual immunohistochemical staining. Results: Significant increased SPK1 urothelial immunoreactivity was shown in patients compared to control group (p=0.03). By contrast, SPK1 immunoreactivity in patients was significantly decreased in the sub-urothelium, muscles and nerves, p=0.02; 0.01 and 0.003, respectively. Patients with neurogenic detrusor overactivity (NDO) had higher SPK1 urothelium expression than those without any DO (p=0.04). Conclusions: SPK1 is expressed in the human bladder wall, specifically the urothelium, in bladder specimens from patients with NDO. The role of SPK1 in the pathophysiology of NDO needs further elucidation.

Failure of botulinum toxin injection for neurogenic detrusor overactivity: Switch of toxin versus second injection of the same toxin.

OBJECTIVES: To evaluate the efficacy of a second injection of the same toxin versus switching to a different botulinum toxin A after failure of a first detrusor injection in patients with neurogenic detrusor overactivity. METHODS: The charts of all patients who underwent detrusor injections of botulinum toxin A (either abobotulinumtoxinA or onabotulinumtoxinA) for the management of neurogenic detrusor overactivity at a single institution were retrospectively reviewed. Patients in whom a first detrusor injection had failed were included in the present study. They were managed by a second injection of the same toxin at the same dosage or by a new detrusor injection using a different botulinum toxin A. Success was defined as a resolution of urgency, urinary incontinence and detrusor overactivity in a patient self-catheterizing seven times or less per 24 h. RESULTS: A total of 58 patients were included for analysis. A toxin switch was carried out in 29 patients, whereas the other 29 patients received a reinjection of the same toxin at the same dose. The success rate was higher in patients who received a toxin switch (51.7% vs. 24.1%, P = 0.03). Patients treated with a switch from abobotulinumtoxinA to onabotulinumtoxinA and those treated with a switch from onabotulinumtoxinA to abobotulinumtoxinA had similar success rates (52.9% vs. 50%, P = 0.88). CONCLUSION: After failure of a first detrusor injection of botulinum toxin for neurogenic detrusor overactivity, a switch to a different toxin seems to be more effective than a second injection of the same toxin. The replacement of onabotulinumtoxin by abobotulinumtoxin or the reverse provides similar results.

The Cumulated Stone Diameter: A Limited Tool for Stone Burden Estimation.

OBJECTIVE: To compare the performance of the main methods used to estimate stone burden in order to improve and standardize preoperative evaluation of stone disease. METHODS: From January 2012 to June 2013, a series of consecutive retrograde intrarenal stone surgery was prospectively evaluated at a single institute. All patients had a pre- and postoperative CT scan. The stone burden was estimated using 3 methods: the cumulative stone diameter (M1), Ackermann's formula (M2), and the sphere formula (M3). The predictive value of the postoperative stone-free status of these methods was then compared. RESULTS: Overall (n = 142), the stone-free rate was 64%. The three methods (M1, M2, and M3) were all predictive of stone-free status for stones <20 mm (P = .0076, .018, and .016, respectively). However, only M2 and M3 were significant for stones >20 mm (P = .0024 and .023). Using receiver operating characteristic curves, we found that areas under the curve were 0.73, 0.70, and 0.71 for stones below 20 mm and 0.53, 0.74, and 0.74 for stones above 20 mm for M1, M2, and M3, respectively. In multivariate analysis, M1 and M3 were both found to be independently associated with the stone-free status in the whole series (P <.001 and .011, respectively). However, for stones above 20 mm, only M3 was significant (P = .020). CONCLUSION: Evaluation of the stone burden is an important predictor of the outcome of retrograde intrarenal stone surgery. For stones below 20 mm, all the three methods approximate stone burden correctly; however, for the stones above 20 mm, calculation of volume is recommended.