Phase II open-label study investigating apalutamide in patients with biochemical progression after radical prostatectomy.

Apalutamide, a competent inhibitor of the androgen receptor, has shown promising clinical efficacy results for patients with advanced prostate cancer. Here, we describe the rationale and design for the SAVE trial, a multi-center, Phase II study, wherein 202 men with biochemical progression after radical prostatectomy are randomly assigned 1:1 to apalutamide plus salvage radiotherapy (SRT) or androgen-deprivation therapy with an luteinizing hormone-releasing hormone agonist or antagonist plus SRT. The primary objective is to compare sexual function between the two treatment arms based on the expanded prostate cancer index-26 sexual domain score at nine months after start of hormonal treatment. The key secondary objectives are to assess quality of life, to evaluate the safety profile and the short-term efficacy of apalutamide in combination with SRT. ClinicalTrials.gov identifier: NCT03899077.

Mucinous cystadenocarcinoma in the renal pelvis: primary or secondary? Case report and literature review.

INTRODUCTION: Cystic lesions in the renal pelvis may cause a diagnostic dilemma. These lesions may be benign or (pre)malignant and primary of secondary. CASE REPORT: A 65-year-old woman presents with a complex cystic mass in the lower pole of the left kidney measuring approximately 16 cm in size and classified as Bosniak type 2F with minimally thickened septa and thick calcifications on non-contrast-enhanced computed tomography. The histopathological findings are consistent with a mucinous cystadenocarcinoma in the renal pelvis. Given the absence of a primary focus and based on clinical and radiological examination, the diagnosis of a primary renal neoplasm is preferred. DISCUSSION: A review of the literature is performed to evaluate the histological differential diagnosis and confirm the diagnosis. Epidemiology with an overview of available similar cases since 2009, as well as etiological factors, treatment and prognosis was reviewed. CONCLUSION: Primary renal mucinous cystadenocarcinoma is an exceedingly rare tumor. Histopathology still remains the gold standard for the diagnosis of this tumor. Because of the rarity, secondary involvement from more common sites, such as ovary and gastrointestinal tract, should be thoroughly excluded.

A prospective randomized controlled multicentre trial comparing intravesical DMSO and chondroïtin sulphate 2% for painful bladder syndrome/interstitial cystitis.

OBJECTIVE: To compare effectiveness of intravesical chondroïtin sulphate (CS) 2% and dimethyl sulphoxide (DMSO) 50% in patients with painful bladder syndrome/interstitial cystitis (PBS/IC). MATERIALS AND METHODS: Patients were randomized to receive either 6 weekly instillations of CS 2% or 50% DMSO. Primary endpoint was difference in proportion of patients achieving score 6 (moderately improved) or 7 (markedly improved) in both groups using the Global Response Assessment (GRA) scale. Secondary parameters were mean 24-hours frequency and nocturia on a 3-day micturition dairy, changes from baseline in O'Leary-Sant questionnaire score and visual analog scale (VAS) for suprapubic pain. RESULTS: Thirty-six patients were the intention to treat population (22 in CS and 14 in DMSO group). In DMSO group, 57% withdrew consent and only 6 concluded the trial. Major reasons were pain during and after instillation, intolerable garlic odor and lack of efficacy. In CS group, 27% withdrew consent. Compared with DMSO group, more patients in CS group (72.7% vs. 14%) reported moderate or marked improvement (P=0.002, 95% CI 0.05-0.72) and achieved a reduction in VAS scores (20% vs. 8.3%). CS group performed significantly better in pain reduction (-1.2 vs. -0.6) and nocturia (-2.4 vs. -0.7) and better in total O'Leary reduction (-9.8 vs. -7.2). CS was better tolerated. The trial was stopped due to high number of drop-outs with DMSO. CONCLUSIONS: Intravesical CS 2% is viable treatment for PBS/IC with minimal side effects. DMSO should be used with caution and with active monitoring of side effects. More randomized controlled studies on intravesical treatments are needed.

Obstetric fistula in a district hospital in DR Congo: Fistula still occur despite access to caesarean section.

OBJECTIVE: To study the profile of classification, etiology, and the relation between initial classification, and the results of vesicovaginal fistula surgery in a district hospital in DR Congo. METHODS: This study was based on the analysis of all consecutive patients being treated for VVF in Kisantu between November 2006 and November 2012. The fistula was classified according to the classification of Waaldijk. The location of VVF and degree of fibrosis were noted. Post-operatively, the first examination of patients took place a few days after catheter removal and subsequent review 2-3 months later. Statistical analysis was done in Graphpad Prism 6. RESULTS: Among 146 patients with VVF, 117 had a primary fistula. The majority of fistula was type I (56%) followed by type III (21%). The majority underwent a caesarean section (63.4%). The mean duration of labor was 30.7 hr. Delay in getting a caesarean in time was due to difficulties in reaching the hospital in 55%. Overall, the closure rate after the first surgical treatment was 65%. The continence rate of the patients with a successful closure was 63%. CONCLUSION: VVF can occur after caesarean section because of the prolonged labor that already causes ischemia and necrosis of the bladder wall and vesicovaginal septum before or while the caesarean section is being performed. Access to general hospitals and the management of the pregnant women needs to be improved. Despite a reasonable closure rate of 65%, post-fistula incontinence remains an important clinical problem.

Nutritional Supplement With Fermented Soy in Men With an Elevated Risk of Prostate Cancer and Negative Prostate Biopsies: General and Oncological Results From the Prospective PRAECAP Trial.

OBJECTIVE: To investigate the effect of a dietary supplement containing fermented soy on PSA, IPSS, changes in prostate volume and prostate cancer (PCa) development after a 6-month challenge in men at increased risk of PCa and negative previous biopsies. MATERIALS AND METHODS: Patients with an elevated risk of PCa, defined by either 1 of the following criteria: PSA >3 ng/mL, suspect lesion at digital rectal examination (DRE), suspect lesion at transrectal ultrasound (TRUS)/magnetic resonance imaging (MRI) and previous negative prostate biopsies (at least 8 cores) within 12 months before inclusion. Statistical analysis was carried out using a non-parametric 1-sided paired Wilcoxon rank sum test, chi-square test, and Fisher's exact test. RESULTS: In this trial, 94 patients were eligible for analysis. A PSA response was detected in 81% of the cases. In 25.8% (24/93) of patients, a decrease of at least 3 points on the IPSS was observed. The median prostate volume did not statistically change after 6 months (P = .908). Patients with PSA modulation required fewer investigations and had fewer positive biopsies (P <.001) and significantly fewer ISUP ≥3 lesions (P = .02). CONCLUSION: We observed a significantly lower PSA level after a 6-month challenge with a fermented soy-containing supplement, and an effect on IPSS in a subset of patients. Prescribing a fermented soy supplement in patients with an increased PCa risk could lead to a better selection of patients at real increased risk of having occult PCa.

E. coli bacterial meningitis after transrectal prostate biopsy under antibiotic prophylaxis: a case report and literature review.

Prostate biopsy, a frequently performed procedure, is not harmless. In rare cases, life-threatening complications occur. We document a potential lethal bacterial meningitis after transrectal biopsy. In addition to our overview of all previously documented cases, we highlight the evidence of prevention of infectious complications when performing a prostate biopsy.

Single incision mini-sling versus a transobutaror sling: a comparative study on MiniArc and Monarc slings.

INTRODUCTION AND HYPOTHESIS: A retrospective, dual-center, cohort study on the single incision MiniArc sling and the transobturator Monarc sling in the treatment of stress urinary incontinence is presented. We hypothesized that both systems would perform equally well. METHODS: One hundred thirty-one (MiniArc n = 75, Monarc n = 56) consecutive patients were evaluated. Evaluation was performed by cough stress test (CST), daily pad use, IIQ-7, UDI-6, and a 0-5 visual analog scale for quality of life. The 1-year data are presented. RESULTS: Six weeks after surgery, 91% of the patients in both populations had a negative CST. At 1 year, 85% of the MiniArc group and 89% of the Monarc group (p = 0.60) maintained a negative CST. QoL, symptom scores, and number of pads improved significantly and were comparable in both groups. Complication rates were similar. CONCLUSIONS: These results suggest that MiniArc sling and Monarc sling are equally effective in the treatment of stress incontinence at 1 year follow-up.

Kidney Stone Dissolution Therapy in Phosphate Stones: A Case Report.

Background: Phosphate stones can be divided into struvite (7%), apatite (20%), and brushite stones (2%). They often present as large staghorn calculi and, therefore, can be challenging to treat. Moreover, it is crucial to obtain a stone-free patient to prevent recurrence. Therefore, local chemolysis can be an interesting tool when complete surgical removal of the stone is impossible or as an adjuvant treatment for residual stone fragments after surgery. Case Presentation: We present a case of an 84-year old Caucasian man in whom local chemolysis therapy with a citric acid solution resulted in a rapid reduction of the stone load, making less invasive therapy possible. Conclusion: We describe the procedure, (dis)advantages, and possible indications for local chemolysis.

Hypovolemic Shock Caused by Massive Renal Hematoma After a Third Consecutive Extracorporeal Shockwave Lithotripsy Session: A Case Report.

Extracorporeal shockwave lithotripsy (SWL) is a commonly used technique for treating urinary calculi. Although noninvasive, highly effective, and widely accepted, SWL is not without complications. Next to fragmenting the calculi, the surrounding tissue is damaged, which can result in renal hematoma, a well-described complication. In most cases, the collateral tissue damage is mild and resolves with conservative treatment. However, rarely, severe complications may arise. Here we present a case of a 46-year-old male who developed a massive hematoma, both subcapsular and retroperitoneal, after a third consecutive SWL session, resulting in hypovolemic shock. Different probable causes are proposed, of which one cause, the length of the interval between SWL sessions, is not yet studied properly. Probably, short intervals keep the damaged tissue from healing sufficiently, as proposed in our case. Possibly, life-threatening situations can be avoided if more evidence-based guidelines are available.

A prospective randomized controlled multicentre trial comparing intravesical DMSO and chondroïtin sulphate 2% for painful bladder syndrome/interstitial cystitis

ABSTRACT Objective To compare effectiveness of intravesical chondroïtin sulphate (CS) 2% and dimethyl sulphoxide (DMSO) 50% in patients with painful bladder syndrome/interstitial cystitis (PBS/IC). Materials and methods Patients were randomized to receive either 6 weekly instillations of CS 2% or 50% DMSO. Primary endpoint was difference in proportion of patients achieving score 6 (moderately improved) or 7 (markedly improved) in both groups using the Global Response Assessment (GRA) scale. Secondary parameters were mean 24-hours frequency and nocturia on a 3-day micturition dairy, changes from baseline in O’Leary-Sant questionnaire score and visual analog scale (VAS) for suprapubic pain. Results Thirty-six patients were the intention to treat population (22 in CS and 14 in DMSO group). In DMSO group, 57% withdrew consent and only 6 concluded the trial. Major reasons were pain during and after instillation, intolerable garlic odor and lack of efficacy. In CS group, 27% withdrew consent. Compared with DMSO group, more patients in CS group (72.7% vs. 14%) reported moderate or marked improvement (P=0.002, 95% CI 0.05-0.72) and achieved a reduction in VAS scores (20% vs. 8.3%). CS group performed significantly better in pain reduction (-1.2 vs. -0.6) and nocturia (-2.4 vs. -0.7) and better in total O’Leary reduction (-9.8 vs. -7.2). CS was better tolerated. The trial was stopped due to high number of drop-outs with DMSO. Conclusions Intravesical CS 2% is viable treatment for PBS/IC with minimal side effects. DMSO should be used with caution and with active monitoring of side effects. More randomized controlled studies on intravesical treatments are needed.

The presence of Fowler's syndrome predicts successful long-term outcome of sacral nerve stimulation in women with urinary retention.

OBJECTIVES: Sacral nerve stimulation (SNS) is an effective treatment for women with urinary retention. Some women present specific electromyography abnormalities of the external urethral sphincter (Fowler's syndrome). The aim of this study was to evaluate whether Fowler's syndrome and psychologic preimplant screening could be predictive factors for long-term success of SNS in women with urinary retention. METHODS: All patients underwent electrophysiologic and urodynamic studies and voiding charts. A validated psychologic screening questionnaire was used. Women with successful temporary stimulation, received a definitive implant (Interstim Medtronic). They were followed prospectively every 6 months. Failure was defined as recurrent retention needing intermittent or permanent catheterisation. RESULTS: Sixty-two women were implanted, 30 with Fowler's syndrome, 32 with idiopathic retention. In those with Fowler's syndrome, 26.6% screened positive for somatisation, as did 43.8% in the idiopathic group (not significant [ns]). Screening for depression was positive in 30% and 18.8%, respectively (ns). There was no correlation with outcome. Twenty-eight patients failed: 9 with Fowler's syndromes, 19 without (p=0.04). Kaplan-Meier analysis showed that patients with Fowler's syndrome benefitted significantly longer from SNS (log-rank test, p=0.005). CONCLUSIONS: The presence of Fowler's syndrome is a positive predictive factor for SNS in female urinary retention. Idiopathic urinary retention patients can benefit as well, but the success might be less predictable. Preimplant psychologic screening, using the Patient Health Questionnaire, does not correlate with long-term outcome of SNS in this population.

Autonomous contractile activity in the isolated rat bladder is modulated by a TRPV1 dependent mechanism.

AIMS: Resiniferatoxin (RTX), a vanilloid compound and agonist of the transient receptor potential channel 1 (TRPV1), is known for its beneficial effects on neurogenic detrusor overactivity. The mainstream rationale for its use is the desensitization of TRPV1 on sensory bladder afferents. However, recent findings showed that TRPV1 is present in other cell types in the bladder. To eliminate the effects of RTX on spinal and central neural circuits, we investigated autonomous contractility in normal and neurogenic rat bladders after treatment with RTX. METHODS: Female Wistar rats were made paraplegic at vertebral level T8-T9. Animals were intravesically pre-treated with vehicle (ethanol 5%) or RTX (100 nM) and sacrificed after 72 hr. Each bladder was excised and placed in a heated organ bath, where intravesical pressures were measured. Effects on contractile parameters of intravesical volume load, the non-selective muscarinic receptor agonist carbachol (CA) and electrical stimulation (ES) of nerves were studied in both groups. RESULTS: In RTX-treated normal bladders we found shorter contractions with higher amplitude than in control bladders (P < 0.05). In RTX-treated neurogenic bladders the amplitude and duration of autonomous contractions were increased compared with controls (P < 0.05). Furthermore RTX induced an increased response to CA and to ES (P < 0.05). CONCLUSIONS: RTX significantly affected the properties of autonomous bladder contractile activity. This provides evidence for local effects of RTX on bladder contractile activity, which are not mediated by afferent neural pathways and which may contribute to the beneficial effects on detrusor overactivity. TRPV1 and TRPV1(+) cells seem to play an important role in (autonomous) bladder contractility.

Comparison study of autonomous activity in bladders from normal and paraplegic rats.

AIM: To identify differences in the pattern of pressure generated by isolated bladders from normal and paraplegic rats. MATERIALS AND METHODS: Nine female Wister rats were made paraplegic by spinal cord transsection at the vertebral level T8-T9 and sacrificed between D21 and D28. A further group (n = 9) was used as a control group. Each bladder was excised and placed in an organ bath where intravesical pressures were measured. Pressure changes were divided in two well-defined groups: macro-transients and spikes. The effects of intravesical volume load and muscarinic (M) agonists were studied. RESULTS: We demonstrated a higher frequency, a longer duration, and a higher variance of duration in macro-transients in the neurogenic group. Intravesical volume load influenced the amplitude and frequency of macro-transients in both groups similarly. The effects of the muscarinic (M(2))-selective agonist arecaïdine were different in neurogenic bladder; the effects of the non-selective muscarinic (M)-agonist carbachol were similar in both groups. CONCLUSION: We showed that the pattern of autonomous activity was significantly different between normal and neurogenic rat bladders. We also found evidence for alterations in the muscarinic response of isolated neurogenic rat bladders. This model offers an exciting new research tool to evaluate the detrusor activity in neurogenic and normal conditions.

Gastrointestinal stromal tumor of the prostate.

We present a unique case of an atypical prostate tumor in a 49-year-old man with acute urinary retention. Digital rectal examination revealed a large prostate with a parenchymal mass on the left side. Radiologic imaging showed a 14.2 x 9.6 x 14.0-cm prostatic mass and multiple liver metastases. A pathologic diagnosis of a prostatic gastrointestinal stromal tumor was made and was confirmed by molecular analysis. Therapy consisted of a tyrosine kinase inhibitor, resulting in prostate mass reduction. After 100 weeks, the patient was in good physical condition with a continuing partial response with a reduced mass volume and liver nodules.

Topography of the vanilloid receptor in the human bladder: more than just the nerve fibers.

PURPOSE: We determined the presence and distribution of vanilloid receptor-1 in the human bladder and confirmed or rejected previous findings of other groups that used indirect methods or vanilloid receptor-1 antibodies made by immunizing experimental animals. Also, we tested the reproducibility of results using commercially available antibodies against the N-terminus and C-terminus of the vanilloid receptor. MATERIALS AND METHODS: A total of 11 normal bladder tissue samples were obtained from cystectomy specimens and fresh frozen processed. Specimens were studied by immunohistochemistry and confocal laser microscopy using 3 vanilloid receptor-1 antibodies. Immunohistochemical co-localization studies for neurofilament, neuronal nitric oxide synthase and nerve growth factor were performed. RESULTS: Our results confirm the presence of vanilloid receptor-1 on nonmyelinated and myelinated nerve fibers. There was vanilloid receptor-1 immunoreactivity on smooth muscle cells but different sensitivities for the antibodies. There was immunoreactivity on interstitial cells located in the suburothelium and intermuscular septa of the muscularis. There was co-localization of neuronal nitric oxide synthase with interstitial cells but not with neurofilament. No co-localization was found for nerve growth factor and vanilloid receptor-1. CONCLUSIONS: Vanilloid receptor-1 is located on small unmyelinated and myelinated nerve fibers. In addition, vanilloid receptor-1 is also present on interstitial cells in the suburothelium. There is smooth muscle cell immunoreactivity but a difference in antibodies raised against the C-terminus and N-terminus. These data suggest that the current hypothesis about the mechanism of action of vanilloids is through blocking the afferent reflex arc must be revised and the function of interstitial cells deserves further attention.

Identification of kit positive cells in the human urinary tract.

PURPOSE: Analogous to interstitial cells of Cajal in the bowel, functional important networks of interstitial cells could have a role in the complex mechanism of central and peripheral control of urinary tract function. Recently various reports mentioned the presence of interstitial cells in different parts of the urinary tract and in different species. Since important differences among species exist, we performed immunohistochemistry on fresh frozen human tissue to study the presence of interstitial cells in the human urinary tract. MATERIALS AND METHODS: A total of 65 tissue pieces from all levels of the urinary tract were obtained from 44 patients treated at our institution. Tissue was processed for immunohistochemistry immediately after removal. We performed immunohistochemistry for kit, connexin 43 and VRL1/TRPV2. RESULTS: Interstitial cells immunopositive for all 3 antibodies were seen beneath the urothelium and between smooth muscle cells in all tissue pieces with slight topographical differences. CONCLUSIONS: Together with morphological and functional data from other experiments these morphological data suggest that, as in the bowel, networks of interstitial cells might have an important role in the physiology and pathology of the urinary tract. They could be involved in pacemaking or have an integrating role through the modulation of neurotransmission and conduction of electrical impulses. Functional experiments are the next step to study these hypotheses.