Urodynamic efficacy of fesoterodine for the treatment of neurogenic detrusor overactivity and/or low compliance bladder.

OBJECTIVE: To examine the urodynamic effects of fesoterodine on neurogenic detrusor overactivity and/or low compliance bladder. METHODS: A total of 77 patients (52 men, 25 women; aged 61.6 ± 20.3 years) were given fesoterodine 4-8 mg/day and prospectively followed for 12 weeks. The primary end-point variable was change in the maximum cystometric capacity on urodynamic study. The secondary end-point was to assess the number of patients whose neurogenic detrusor overactivity disappeared, and the changes in the urodynamic parameters, lower urinary tract symptoms questionnaires and the 3-day frequency volume chart parameters after the treatment. RESULTS: A total of 13 patients (16.9%) withdrew because of adverse events (dry mouth or blurred vision), and four patients dropped out for unknown reasons. Finally, 60 patients completed the study. Bladder capacity at first desire to void, maximum cystometric capacity and bladder compliance increased by 29.2 mL, 79.9 mL and 22.2 mL/cm H2 O, respectively, showed statistical significance (P = 0.026, P < 0.001 and P < 0.001). Neurogenic detrusor overactivity disappeared in 12 of 51 patients (23.5%), and a significant increase was observed in bladder capacity at first involuntary contraction (P < 0.001), and a significant decrease was observed in maximum detrusor contraction (P < 0.001). In patients with low compliance bladder (with detrusor underactivity without neurogenic detrusor overactivity; n = 9), maximum cystometric capacity and bladder compliance increased significantly (P = 0.003 and P = 0.006, respectively). Overactive bladder symptom score, International Consultation on Incontinence Questionnaire-Short Form, most items of King's Health Questionnaire, and the number of urgency episodes and leaks in a day decreased significantly after treatment. CONCLUSIONS: Fesoterodine seems to be a valid treatment option for neurogenic detrusor overactivity and/or low compliance bladder in neurogenic bladder patients.

Development of novel nomograms to predict renal functional outcomes after laparoscopic adrenalectomy in patients with primary aldosteronism.

PURPOSE: Most patients with primary aldosteronism (PA) show a significant decrease in kidney function after surgery. Glomerular hyperfiltration peculiar to PA can mask mild renal failure before surgery. The aim of this retrospective study was to investigate postoperative renal functional outcomes in PA patients from different viewpoints and to develop novel nomograms that can predict renal functional outcomes in PA patients after surgery. METHODS: 130 Japanese PA patients treated by unilateral laparoscopic adrenalectomy were retrospectively surveyed. Pre- and postoperative changes of estimated glomerular filtration rates (eGFRs) and the distribution of eGFR classification were compared. Furthermore, predictors of the following renal functional outcomes were investigated: (I) the percentage decrease >25% in eGFR and (II) the presence of new-onset eGFR <45 ml/min/1.73 m2. Finally, two nomograms that predicted postoperative renal functional outcomes were developed and internally validated. RESULTS: At 6 months, the average decrease in eGFR was 16.7 mL/min/1.73 m2 (corresponding percent decrease: 19.7%). Upstaging of eGFR classification was observed in 54.6% of patients. Age, potassium, plasma aldosterone concentration, and initial eGFR were incorporated into a nomogram predicting a >25% postoperative decrease in eGFR. Duration of hypertension and initial eGFR were incorporated into a nomogram predicting new-onset eGFR <45 ml/min/1.73 m2. The value of the area under the receiver operating characteristics curve for each nomogram was 0.82 and 0.74, respectively. CONCLUSION: The first nomograms that can predict postoperative renal outcomes in PA patients were developed. They will help clinicians calculate the probability of renal dysfunction in PA patients after laparoscopic adrenalectomy.

Hypertension Cure Following Laparoscopic Adrenalectomy for Hyperaldosteronism is not Universal: Trends Over Two Decades.

BACKGROUND: Laparoscopic adrenalectomy has been established as a standard surgical method for unilateral primary aldosteronism. Meanwhile, the background characteristics of the patients undergoing adrenalectomy have changed over the last 20 years. The aim of this study was to investigate the changes in hypertension cure rates after laparoscopic adrenalectomy during the last two decades. METHODS: This retrospective clinical study included 176 patients who underwent unilateral laparoscopic adrenalectomy for primary aldosteronism from 1995 to 2015. The patients were divided into two groups by decade. The patients' baseline characteristics and the hypertension cure rates were compared between the two groups. Additionally, the values were re-examined based on predictive model predicting postoperative hypertension cure. RESULTS: The hypertension cure rate decreased significantly from 51.8 to 31.1%. The following variables were significantly different between the two groups: age, sex, body mass index, history of diabetes mellitus, preoperative systolic and diastolic blood pressures, potassium level, and plasma renin activity. CONCLUSIONS: This study showed that the number of patients with unfavorable conditions for hypertension cure after adrenalectomy has recently increased. The treatment goal for primary aldosteronism is not only to cure the hypertension but also to prevent organ disorders due to inappropriate aldosterone levels. Therefore, we recommend laparoscopic adrenalectomy for unilateral primary aldosteronism, even if hypertension is not always cured postoperatively. However, clinicians need to fully explain the postoperative hypertension outcomes to primary aldosteronism patients.

Expression profile of urothelial transcription factors in bladder biopsies with interstitial cystitis.

OBJECTIVES: To characterize interstitial cystitis pathology based on the expression profile of urothelial tissue-specific master transcription factors. METHODS: Bladder carcinoma cell lines derived from the urothelial stem cells (epithelial or mesenchymal) were used to identify candidate urothelial master transcription factors. Gene expression was measured with quantitative reverse transcription polymerase chain reaction. From the initial screening of 170 transcription factors (human homologs of Drosophila segmentation genes and known master transcription factors from a database), 28 transcription factors were selected. Subsequently, messenger ribonucleic acid from bladder biopsies of interstitial cystitis patients was purified, and gene expression levels of known urothelial marker genes and candidate master transcription factors were measured. Multivariate expression data were analyzed with spss software. RESULTS: Factor analysis decomposed the expression profile into four axes: principal axis 1 included retinoic acid receptors and 17 candidate master transcription factors. Principal axis 2 included KRT5 and five candidates. Principal axis 3 included transcription factor TP63 and two candidates. Principal axis 4 included SHH and two candidates. Principal component analysis segregated biopsies from Hunner's lesion in the principal component 1 (retinoic acid)/principal component 2 (SOX13)/principal component 3 (TP63) space. CONCLUSIONS: Urothelial master transcription factors could serve as novel diagnostic markers and potentially explain the molecular pathology of interstitial cystitis.

Risk of New-Onset Dyslipidemia After Laparoscopic Adrenalectomy in Patients with Primary Aldosteronism.

BACKGROUND: Many patients with primary aldosteronism (PA) show a significant decline in kidney function after adrenalectomy. Thus, PA patients who undergo surgery are at greater risk of both postoperative renal damage and new-onset metabolic events associated with renal insufficiency. The aim of this study was to explore postoperative changes in serum lipid levels and to identify risk factors associated with postoperative new-onset dyslipidemia in PA patients. METHODS: The records of 57 Japanese patients who underwent unilateral laparoscopic adrenalectomy for PA were retrospectively surveyed. Clinical and biochemical data were evaluated at baseline and 12 months after surgery. Preoperative and postoperative estimated glomerular filtration (eGFR) and serum lipid profile, including triglycerides, high-density lipoprotein (HDL)-cholesterol and low-density lipoprotein (LDL)-cholesterol levels, were compared. Furthermore, uni- and multivariate analyses were performed to determine the predictors for postoperative new-onset dyslipidemia. RESULTS: A significant decrease in eGFR and deterioration of serum lipid levels was identified postoperatively in most patients. Of the 39 patients without pre-existing dyslipidemia, 18 developed new-onset dyslipidemia postoperatively. Multivariate analysis identified preoperative lower eGFR and higher body mass index as independent predictors for new-onset dyslipidemia after surgery. On univariate analyses, additional factors associated with new-onset dyslipidemia included older age, male sex, higher LDL-cholesterol, and higher LDL/HDL ratio. CONCLUSIONS: PA patients had a higher risk of postoperative new-onset or progressive dyslipidemia. Clinicians should pay attention to not only follow-up of renal impairment but also total management of new-onset metabolic events associated with renal insufficiency in PA patients.

Potential of Cranberry Jelly to Prevent Urinary Stone Formation After Cutaneous Ureterostomy: A Case Report.

One complication of cutaneous ureterostomy is urinary stone formation, which may lead to recurrent pyelonephritis. Frequent catheter changes and the prophylactic administration of antibiotics are commonly used to prevent stone formation. Cranberry products have been reported to inhibit stone formation in indwelling urethral catheters. We herein examined the inhibitory effects of a cranberry product on stone formation in a case of catheter occlusion due to stone formation after cutaneous ureterostomy. The results obtained indicate the potential of cranberry products to prevent stone formation after cutaneous ureterostomy requiring catheter placement.

Transrectal ultrasound vector projectile imaging for time-resolved visualization of flow dynamics in the male urethra: A clinical pilot study.

BACKGROUND: Quantitative and comprehensive visualization of urinary flow dynamics in the urethra is crucial for investigating patient-specific mechanisms of lower urinary tract symptoms (LUTS). Although some methods can evaluate the global properties of the urethra, it is critical to assess the local information, such as the location of the responsible lesion and its interactions with urinary flow in relation to LUTS. This approach is vital for enhancing personalized and focal treatments. However, there is a lack of such diagnostic tools that can directly observe how the urethral shape and motion impact urinary flow in the urethra. PURPOSE: This study aimed to develop a novel transrectal ultrasound imaging modality based on the contrast-enhanced urodynamic vector projectile imaging (CE-UroVPI) framework and validate its clinical applicability for visualizing time-resolved flow dynamics in the urethra. METHODS: A new CE-UroVPI system was developed using a research-purpose ultrasound platform and a custom transrectal linear probe, and an imaging protocol for acquiring urodynamic echo data in male patients was designed. Thirty-four male patients with LUTS participated in this study. CE-UroVPI was performed to acquire ultrasound echo signals from the participant's urethra and urinary flow at various voiding phases (initiation, maintenance, and terminal). The ultrasound datasets were processed with custom software to visualize urinary flow dynamics and urethra tissue deformation. RESULTS: The transrectal CE-UroVPI system successfully visualized the time-resolved multidirectional urinary flow dynamics in the prostatic urethra during the initiation, maintenance, and terminal phases of voiding in 17 patients at a frame rate of 1250 fps. The maximum flow speed measured in this study was 2.5 m/s. In addition, when the urethra had an obstruction or an irregular partial deformation, the devised imaging modality visualized complex flow patterns, such as vortices and flow jets around the lesion. CONCLUSIONS: Our study findings demonstrate that the transrectal CE-UroVPI system developed in this study can effectively image fluid-structural interactions in the urethra. This new diagnostic technology has the potential to facilitate quantitative and precise assessments of urethral voiding functions and aid in the improvement of focal and effective treatments for patients with LUTS.

Efficacy of Transcutaneous Tibial Nerve Stimulation With Silver Spike Point® Electrodes for Refractory Overactive Bladder: A Single-Arm Study.

Background Tibial nerve stimulation therapy is a treatment option for an overactive bladder. A surface electrode called a Silver Spike Point® electrode, which does not directly puncture the skin as in transcutaneous tibial nerve stimulation, but is expected to exert the same therapeutic effect as percutaneous tibial nerve stimulation, was developed. This study investigated the efficacy and safety of tibial nerve stimulation with Silver Spike Point® electrodes for refractory overactive bladder. Methodology This was a six-week, single-arm, prospective study on the efficacy and safety of transcutaneous tibial nerve stimulation for patients with refractory overactive bladder. Each treatment lasted 30 minutes and was performed twice a week. The stimulation sites of the tibial nerve were the Sanyinjiao point (SP6) and Zhaohai point (KI6) in both legs. The primary endpoint was the change in the total overactive bladder symptom score. Results In total, 29 patients (20 males and nine females: 64.86 ± 17.98 years old) were included in this study. Two women dropped out; one because of an adverse event and the other as requested. Therefore, 27 patients completed the study. The total overactive bladder symptom and International Consultation on Incontinence Questionnaire-Short Form scores significantly decreased by 2.22 and 2.39 points, respectively (p < 0.01 each). In the frequency volume chart, the numbers of urgency episodes and leaks in 24 hours significantly decreased by 1.53 and 0.44, respectively (p = 0.02 each). Conclusions Transcutaneous tibial nerve stimulation therapy using Silver Spike Point® electrodes was useful for patients with refractory overactive bladder and, thus, has potential as a new treatment option for refractory overactive bladder.

The Efficacy of Compression Stockings on Patients With Nocturia: A Single-Arm Pilot Study.

OBJECTIVES:  Behavioral treatment for nocturia includes wearing compression stockings. However, a reading of the cited literature for evidence shows that there is not enough research data to support this recommendation, and it is controversial. The present study aimed to investigate and supplement evidence on the effects of wearing compression stockings during the daytime in patients with nocturia. METHODS: This was a single-arm prospective study to investigate the effects of compression stockings on nocturia for four weeks. Patients were asked to record a frequency-volume chart and complete various questionnaires at baseline and after four weeks, and also provide feedback on treatment satisfaction. The primary endpoint was a change in night-time frequency in the frequency-volume chart from the baseline to the end of treatment. RESULTS: Thirty-four patients (19 men and 15 women; age: 72.3 ± 12.6 years) were included. Two patients dropped out because of pain associated with wearing compression stockings and one due to a refusal to wear compression stockings every day. Therefore 31 patients were analyzed. In the frequency-volume chart, night-time and 24-hour frequencies significantly decreased by 0.5 and 1.1 episodes, respectively (P = 0.004 and P = 0.035, respectively). The hours of undisturbed sleep significantly increased by 0.8 h (P = 0.013). No significant differences were observed in nocturnal or 24-h urine volumes, the number of urgency or urinary incontinence episodes, the mean or maximum voided volume, the nocturnal polyuria index, or the first night-time voided volume. The total overactive bladder symptom score significantly decreased (P = 0.006). Significant reductions were also observed in all overactive bladder symptom score subscores, except for the daytime frequency score. CONCLUSION: The present results suggest the effectiveness of wearing compression stockings during the day was satisfactory in most patients with nocturia, and the treatment was safely continued in patients who experienced no pain when wearing the stockings. Based on the results of this study, we believe that it is worth considering as a treatment for nocturia.

Effects of magnetic stimulation on urodynamic stress incontinence refractory to pelvic floor muscle training in a randomized sham-controlled study.

OBJECTIVE: The aim of the present study was to evaluate the effect of magnetic stimulation on urodynamic stress incontinence refractory to pelvic floor muscle training in a randomized sham-controlled study. METHODS: Female patients with urodynamic stress incontinence who had not been cured by pelvic floor muscle training were randomly assigned at a ratio of 2 : 1 to either active treatment or sham treatment for 10 weeks. The randomization was made using magnetic cards for individuals indicating active or sham stimulation. The primary endpoint was changes in the number of incontinence episodes/week, with secondary endpoints of the degree of incontinence (in g/day; determined using the pad test), the total score on the International Consultation on Incontinence Questionnaire - Short Form (ICIQ-SF), the ICIQ quality of life (QOL) score, and the abdominal leak point pressure (ALPP) on urodynamic study. RESULTS: Although 39 patients were enrolled in the study, 9 dropped out, leaving a total patients for analysis (18 in the active treatment group, 12 in the sham treatment group). The number of incontinence episodes/week, the degree of incontinence, total ICIQ-SF score, ICIQ-QOL score, and ALPP were significantly improved after active treatment compared with baseline (all P < .05), but did not change significantly after sham treatment. There was a significant intergroup difference with regard to changes from baseline in the ICIQ-SF and ALPP in favor of the active treatment group (P < .05). There were no significant differences in any other parameters between the 2 groups. Treatment-related adverse events were not found in both groups. CONCLUSION: Magnetic stimulation was effective in treating urodynamic stress incontinence.

Abiraterone acetate withdrawal syndrome: Speculations on the underlying mechanisms.

A 72-year-old man initially presented with lumbar and right chest pain, but was later found out to also have an elevated prostate-specific antigen (PSA) level at 2,000.0 ng/ml. Further evaluation disclosed metastatic prostate cancer involving the bones and lymph nodes. The patient was initially treated with combined androgen blockade (CAB) with leuprolide acetate and bicalutamide. After 6 months of CAB, the patient's PSA level began to rise from the nadir (85.1 ng/ml) to 113.3 ng/ml. Bicalutamide was withdrawn in anticipation of anti-androgen withdrawal syndrome and the PSA level declined temporally. However, it increased up to 517.0 ng/ml thereafter. Consequently, a year after CAB, abiraterone acetate (AA) was initiated at a standard dose of 1,000 mg daily in combination with 10 mg of prednisolone. PSA rapidly decreased to the nadir of 20.1 ng/ml thereafter. The PSA level remained stable until 2 years after AA administration. However, he decided to reduce the dose of AA to half of the standard dose (500 mg daily). Contrary to our expectations, the serum PSA level promptly decreased to a nadir of 8.1 ng/ml. Thereafter, the PSA level remained stable until 3 years and 9 months after AA administration. Subsequently, the patient stopped taking AA and prednisolone. However, to our surprise, the patient's serum PSA level decreased further to <1.0 ng/ml after AA discontinuation. His PSA remained <1.0 ng/ml without clinical or radiological progression for 1 year after AA withdrawal. Recently, it was reported that cessation of AA is associated with AA withdrawal syndrome in metastatic castration-resistant prostate cancer, defined as a PSA decrease after AA discontinuation, mimicking anti-androgen withdrawal syndrome. In the present study, explanations of the mechanisms underlying this phenomenon were explored, including mutant AR activation by alternative ligands.