Characteristics of uroflowmetry patterns in men with detrusor underactivity revealed by artificial intelligence.

OBJECTIVES: To elucidate the characteristics of uroflowmetry (UFM) observed in men with detrusor underactivity (DU) using our developed artificial intelligence (AI) diagnostic algorithm to distinguish between DU and bladder outlet obstruction (BOO). METHODS: Subjective and objective parameters, including four UFM parameters (first peak flow rate, time to first peak, gradient to first peak, and the ratio of first peak flow rate to maximum flow rate [Qmax ]) selected by analyzing the judgment basis of the AI diagnostic system, were compared in 266 treatment-naive men with lower urinary tract symptoms (LUTS). Patients were divided into the DU (70; 26.32%) and non-DU (196; 73.68%) groups, and the UFM parameters for predicting the presence of DU were determined by multivariate analysis and receiver operating characteristic (ROC) curve analysis. Detrusor underactivity was defined as a bladder contractility index <100 and a BOO index <40. RESULTS: Most parameters on the first peak flow of UFM were significantly lower in the DU group. On multivariate analysis, lower first peak flow rate and lower ratio of first peak flow rate to Qmax were significant parameters to predict DU. In the ROC analysis, the ratio of the first peak flow rate to Qmax showed the highest area under the curve (0.848) and yielded sensitivities of 76% and specificities of 83% for DU diagnosis, with cutoff values of 0.8. CONCLUSIONS: Parameters on the first peak flow of UFM, especially the ratio of the first peak flow rate to Qmax , can diagnose DU with high accuracy in men with LUTS.

Effects of human Muse cells on bladder inflammation, overactivity, and nociception in a chemically induced Hunner-type interstitial cystitis-like rat model.

INTRODUCTION AND HYPOTHESIS: We investigated the effects of locally administered human multilineage-differentiating stress enduring (Muse) cells, nontumorigenic pluripotent-like endogenous stem cells, on bladder tissues, function, and nociceptive behavior in a chemically induced Hunner-type interstitial cystitis (HIC)-like rat model without immunosuppressant. METHODS: Chemical cystitis was induced by intravesical instillation of 0.2 N hydrochloride (HCl) for 15 min in female F344 rats. SSEA-3+ Muse cells, SSEA-3- non-Muse cells or Hanks' balanced salt solution (HBSS; vehicle) were injected into the anterior and posterior bladder wall at each 1×104 cells/10 µl 6 h after HCl application. The sham group received HBSS without HCl instillation. Urinary frequency was assessed using metabolic cages, cystometrograms, nociceptive behavior, and histological analysis of the bladder and L6 spinal cord. RESULTS: Increases in urinary frequency and decreases in bladder capacity compared with the sham group were observed in the vehicle and non-Muse groups, but not in the Muse group, at 1 week. Significant increases in nociceptive behavior compared with the sham group and the expression of TNFα in the bladder and c-Fos in the bilateral dorsal horns of L6 spinal cord were also observed in the vehicle and non-Muse groups, whereas these changes were not seen in the Muse group at 1 week. Histological analysis exhibited a higher proportion of injected Muse cells remaining in the urothelial basal layer and lamina propria of the bladder than non-Muse cells until 4 weeks. CONCLUSIONS: Muse cell therapy could be a promising modality for treating HIC.

Impairment of accessory nerves around major pelvic ganglion leading to overflow urinary incontinence in rats.

AIMS: To investigate the relationship between lower urinary tract function and the accessory nerve (ACN) arising from the major pelvic ganglion (MPG). METHODS: Ten-week-old male Wistar/ST rats were randomly divided into eight groups according to the type of treatment (sham or bilateral accessory nerve injury [BACNI]) and the duration of observation (3 days, 1 week, 2 weeks, or 4 weeks: Sham-3d, Sham-1w, Sham-2w, Sham-4w, BACNI-3d, BACNI-1w, BACNI-2ws, and BACNI-4w. BACNI was induced in the following manner: the ACN was crushed for 1 min (2 mm away from the MPG) using reverse-action tweezers. The same procedure was performed on both sides. On the last day of each observation period, the bladder function was measured by awake cystometry, and histological evaluation was performed. RESULTS: All rats in the Sham groups micturated normally. In the BACNI-3d and BACNI-1w groups, all rats showed symptoms of overflow urinary incontinence (OUI). This OUI improved gradually over time. The bladder's size in the BACNI group was significantly larger than that in the Sham group (p < .01). In addition, fibrosis was observed in the subserosa of the bladder of rats in BACNI groups. CONCLUSION: The BACNI model rats exhibited OUI, suggesting that ACN is involved in the lower urinary tract function. It might be possible that ACN controls the function of either the bladder, the urethra, or both.

Filtrated Adipose Tissue-Derived Mesenchymal Stem Cell Lysate Ameliorates Experimental Acute Colitis in Mice.

BACKGROUND: Inflammatory bowel disease (IBD) is a chronic, persistent, and intractable enteritis; however, an effective treatment strategy is yet to be established. Mesenchymal stem cells (MSCs) and their paracrine factors exhibit anti-inflammatory actions and have been proposed as a new therapeutic candidate for IBD treatment, although the efficacy of MSC lysate on enteritis is unclear. AIMS: Here, we examined the efficacy and appropriate regimen of filtrated murine adipose-derived mesenchymal stem cell lysate (FADSTL) in an acute colitis mouse model as a novel cell-free MSC therapy. METHODS: To confirm the clinical effects of FADSTL, survival rate, body weight, and disease activity index (DAI) were investigated in the DSS-induced colitis mouse model. Further, differences in efficacy with dosing frequency were assessed to optimize the proper regimen. Colon length, histological findings, gene expression of inflammatory mediators and tight junction proteins in colon tissues, and anti-apoptotic effects were also compared in 3-day continuous FADSTL administration and PBS groups. RESULTS: Three-day continuous FADSTL administration significantly improved weight loss and DAI score compared to those in the PBS-treated group, whereas the effect was not observed with single administration. Additionally, colon shortening and histological inflammation were suppressed in the FADSTL-treated group. Further, this treatment decreased gene expression of inflammatory mediators, maintained expression of tight junction proteins in the colon, and showed anti-apoptotic effects. CONCLUSIONS: FADSTL effects were dependent on its administration frequency, suggesting the requirement of continuous FADSTL administration. FADSTL improved colitis by maintaining the intestinal barrier function through its anti-inflammatory and anti-apoptotic actions.

Development of an artificial intelligence diagnostic system for lower urinary tract dysfunction in men.

OBJECTIVES: To establish an artificial intelligence diagnostic system for lower urinary tract function in men with lower urinary tract symptoms using only uroflowmetry data and to evaluate its usefulness. METHODS: Uroflowmetry data of 256 treatment-naive men with detrusor underactivity, bladder outlet obstruction, or detrusor underactivity + bladder outlet obstruction were used for artificial intelligence learning and validation using neural networks. An optimal artificial intelligence diagnostic model was established using 10-fold stratified cross-validation and data augmentation. Correlations of bladder contractility index and bladder outlet obstruction index values for the artificial intelligence system and pressure flow study values were examined using Spearman's correlation coefficients. Additionally, diagnostic accuracy was compared between the established artificial intelligence system and trained urologists with uroflowmetry data of 25 additional patients by χ2 -tests. Detrusor underactivity was defined as bladder contractility index ≤100 and bladder outlet obstruction index ≤40, bladder outlet obstruction was defined as bladder contractility index >100 and bladder outlet obstruction index >40, and detrusor underactivity + bladder outlet obstruction was defined as bladder contractility index ≤100 and bladder outlet obstruction index >40. RESULTS: The artificial intelligence system's estimated bladder contractility index and bladder outlet obstruction index values showed significant positive correlations with pressure flow study values (bladder contractility index: r = 0.60, P < 0.001; bladder outlet obstruction index: r = 0.46, P < 0.001). The artificial intelligence system's detrusor underactivity diagnosis had a sensitivity and specificity of 79.7% and 88.7%, respectively, and those for bladder outlet obstruction diagnosis were 76.8% and 84.7%, respectively. The artificial intelligence system's average diagnostic accuracy was 84%, which was significantly higher than that of urologists (56%). CONCLUSIONS: Our artificial intelligence diagnostic system developed using the uroflowmetry waveform distinguished between detrusor underactivity and bladder outlet obstruction with high sensitivity and specificity in men with lower urinary tract symptoms.

Biological characterization of adipose-derived regenerative cells used for the treatment of stress urinary incontinence.

OBJECTIVE: To assess the characteristics of adipose-derived regenerative cells, and provide supportive data explaining the mechanism of efficacy observed for the use of these cells in the treatment of stress urinary incontinence. METHODS: Adipose tissues were harvested by abdominal liposuction from healthy donors and patients with stress urinary incontinence. Adipose-derived regenerative cells were isolated from tissues using the Celution system, and assessed for their characteristics and ability to differentiate into smooth muscle cells. RESULTS: Adipose-derived regenerative cells isolated by the Celution system developed into fibroblastic colonies. Flow cytometric analysis of adipose-derived stem cell markers showed that adipose-derived regenerative cells were positive for CD34 and CD44, and negative for CD31. Immunofluorescence staining after differentiation showed that colony-forming cells were positive for alpha-smooth muscle actin, calponin and desmin, which are smooth muscle cell markers. A cytokine release assay showed that adherent cells secreted cytokines associated with angiogenesis, including vascular endothelial growth factor-A, angiopoietin-2 and placental growth factor. CONCLUSIONS: Adipose-derived regenerative cells collected by the Celution system might have clonogenic capacity and an angiogenetic function. These properties might contribute to the mechanisms through which regenerative cell therapy by periurethral injection of autologous adipose-derived regenerative cells ameliorates stress urinary incontinence.

The effect of mirabegron on bladder blood flow in a rat model of bladder outlet obstruction.

PURPOSE: To evaluate the effects of mirabegron on bladder blood flow in a rat model of bladder outlet obstruction (BOO). METHODS: Adult female Sprague-Dawley rats were divided into three groups based on whether they underwent a sham operation (sham group) or an operation to establish partial BOO (BOO and BOO + mirabegron groups). The BOO + mirabegron group was treated with mirabegron (0.3 mg/kg/h, subcutaneously) for 14 days. Subsequently, we performed continuous cystometry, bladder blood flow measurements with a 2D laser blood flow imager, hematoxylin-eosin staining of the bladder tissue, and malondialdehyde (MDA) measurements in the bladder tissue. RESULTS: Cystometry revealed significantly higher peak pressure, more residual urine volume, and lower voiding efficiency in the BOO and BOO + mirabegron groups than in the sham group. The BOO + mirabegron group had significantly fewer non-voiding contractions (NVCs) than the BOO group, while the latter had more frequent NVCs than the sham group. The BOO and BOO + mirabegron groups had significantly decreased bladder blood flow than the sham group, whereas the BOO + mirabegron group showed significantly increased bladder blood flow than the BOO group. The bladder tissue in the BOO group contained more hypertrophic detrusor muscle compared to the sham group, while mirabegron treatment suppressed detrusor hypertrophy. The MDA levels were significantly higher in the BOO group than in the BOO + mirabegron and sham groups. CONCLUSION: Mirabegron treatment significantly improved BOO-induced bladder dysfunction through the amelioration of bladder blood flow.

Pre-treatment serum testosterone level can be a useful factor to predict the improvement in bladder outlet obstruction by tadalafil for male patients with lower urinary tract symptoms induced by benign prostatic obstruction.

INTRODUCTION: To investigate possible pre-treatment factors related to the therapeutic effect of tadalafil on bladder outlet obstruction (BOO). MATERIALS AND METHODS: Eighty untreated outpatients with lower urinary tract symptoms (LUTS) due to BOO received 5 mg tadalafil daily for 12 months. Subjective symptoms and objective findings were evaluated before and 12 months after treatment. At 12 months, the patients were divided into two groups according to an improvement grade in BOO index (BOOI). Patient characteristics including age, serum total testosterone level (TT), PSA, and prostate volume, and subjective and objective parameters on LUTS were set as candidates of pre-treatment factors, and the parameters that influenced the improvement of BOO were statistically analysed. RESULTS: A total of 69 patients with mean age of 69.8 years and mean prostate volume of 48.8 mL were included. Subjective symptoms and BOOI were significantly ameliorated after 12 months. In terms of an improvement of BOOI, 30 patients (43.5%) showed insignificant improvement in BOO, whereas 39 patients (56.5%) exhibited excellent improvement. Comparison of pre-treatment factors between the groups showed that TT was the only independent predictor related to the improvement in BOO. The improvement of BOO was significantly better in patients with higher TT. CONCLUSIONS: Pre-treatment TT was considered to be a useful predictor of therapeutic effects of tadalafil for BOO.

Regenerative treatment for male stress urinary incontinence by periurethral injection of adipose-derived regenerative cells: Outcome of the ADRESU study.

OBJECTIVES: To report the outcome of the ADRESU study, a multicenter, single-arm, investigator-initiated clinical trial to confirm the efficacy and safety of regenerative treatment for male patients with stress urinary incontinence. METHODS: The participants were male patients with mild-to-moderate stress urinary incontinence persisting for >1 year after prostatectomy. Autologous adipose-derived regenerative cells were isolated using the Celution system from adipose tissue obtained by liposuction. Adipose-derived regenerative cells and mixture of adipose-derived regenerative cells with adipose tissue were transurethrally injected into the rhabdosphincter and submucosal space of the urethra, respectively. The primary end-point was the proportion of patients with improvement of the urine leakage volume at 52 weeks (or last visit within 52 weeks). Improvement of leakage volume was defined as a decrease from baseline >50% by the 24-h pad test. A total of 10 secondary end-points were set. RESULTS: A total of 45 patients satisfying the eligibility criteria were enrolled. The primary end-point was met; the proportion of patients with improvement in leakage volume at 52 weeks was 37.2% (95% confidence interval 23.0-53.3%). No serious adverse events with causal relationships to the adipose-derived regenerative cells were encountered. There was a progressive improvement in secondary end-points. In the King's Health Questionnaire, improvement of quality of life scores showed greater improvement in responders, as compared with non-responders. CONCLUSIONS: Findings from the ADRESU study suggest the efficacy and safety of regenerative treatment for male patients with mild-to-moderate stress urinary incontinence.

The influence of the presence of intraductal carcinoma of the prostate on the grade group system's prognostic performance.

BACKGROUND: Although the presence of intraductal carcinoma of the prostate (IDC-P) influences biochemical failure in radical prostatectomy patients, no data are available regarding the impact of its integration into the classification grade group system. Thus, the aim of this study was to enhance the utility of the grade group system by integrating the presence of IDC-P. METHODS: This study was a retrospective evaluation of 1019 patients with prostate cancer who underwent radical prostatectomy between 2005 and 2013 without neoadjuvant or adjuvant therapy. The data on age, prostate-specific antigen (PSA) level at diagnosis, pathological T stage (pT), presence of Gleason pattern 5 (GP5), presence of IDC-P, and surgical margin status were analyzed to predict PSA recurrence after prostatectomy. RESULTS: The median patient age was 67 (range, 45-80) years and the median initial PSA level was 6.8 (range, 0.4-82) ng/mL. The median follow-up period was 82 (range, 0.7-148) months. IDC-P was detected in 157 patients (15.4%). Among these patients, the increase in the positive rate of IDC-P correlated with tumor upgrading. The grade groups (GGs) were as follows: GG1 without IDC-P, 16.0% (n = 163); GG2 without IDC-P, 46.1% (n = 470); GG3 without IDC-P, 15.7% (n = 160); GG4 without IDC-P, 2.6% (n = 27); GG5 without IDC-P, 4.1% (n = 42); any GG with IDC-P, 15.4% [n = 157; GG 2 (n = 29); GG3 (n = 60); GG4 (n = 13); GG5 (n = 55)]. Any grade Group with IDC-P showed significantly worse prognosis than any other group without IDC-P (P < 0.0001). In a multivariate analysis, integration of the IDC-P into the Grade Groups, the PSA level at diagnosis, and the surgical margin status were significant prognostic predictors (P < 0.0001, < 0.0001 and < 0.0001, respectively). CONCLUSIONS: Integrating the presence of IDC-P into the grade group system will result in more accurate predictions of patient outcome.

Integrating tertiary Gleason pattern 5 into the ISUP grading system improves prediction of biochemical recurrence in radical prostatectomy patients.

Although the presence of tertiary Gleason pattern 5 is reportedly related to unfavorable prostate cancer characteristics, few data are available regarding the effects of tertiary Gleason pattern 5 on the new ISUP (International Society of Urological Pathology) grading system in radical prostatectomy patients. In this study, we evaluated the effect of tertiary Gleason pattern 5 on biochemical recurrence following radical prostatectomy in patients with prostate cancer. We retrospectively evaluated 1000 patients with prostate cancer who underwent radical prostatectomy. The ISUP Grades were as follows: Grade 1, 16.3%; Grade 2, 48.1% (with tertiary Gleason pattern 5, 8.0% and without tertiary Gleason pattern 5, 40.1%); Grade 3, 21.9% (with tertiary Gleason pattern 5, 9.1% and without tertiary Gleason pattern 5, 12.8%); Grade 4, 3.9%; and Grade 5, 9.8%. Biochemical recurrence-free survival differed significantly among the five groups (Grade 1-5) (P < 0.0001). Grade 2 with tertiary Gleason pattern 5 had a significantly worse prognosis than Grade 2 without tertiary Gleason pattern 5. Similarly, Grade 3 with tertiary Gleason pattern 5 demonstrated a significantly worse prognosis than Grade 3 without tertiary Gleason pattern 5. When Grade 2 and Grade 3 were divided with or without tertiary Gleason pattern 5, the survival curves differed significantly among Grade 1, Grade 2 without tertiary Gleason pattern 5, Grade 2 with tertiary Gleason pattern 5, Grade 3 without tertiary Gleason pattern 5, Grade 3 with tertiary Gleason pattern 5, and Grade 4 (P < 0.0001) (hazard ratios: 1, 1.14, 1.86, 2.23, 3.53, and 6.30). In a multivariate analysis, integrating tertiary Gleason pattern 5 into the ISUP Grade, PSA, and surgical margin status significantly predicted biochemical recurrence (P < 0.0001). Integrating tertiary Gleason pattern 5 into the ISUP grading system will improve the accuracy of patient outcome prediction following radical prostatectomy in patients with prostate cancer.

Objective impacts of tadalafil on storage and voiding function in male patients with benign prostatic hyperplasia: 1-year outcomes from a prospective urodynamic study.

PURPOSE: To investigate the 1-year effects of tadalafil on storage and voiding function in patients with lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (LUTS/BPH) based on a urodynamic study. METHODS: In a one-armed, prospective study, 105 untreated outpatients with LUTS/BPH received 5 mg tadalafil every day for 12 months. Subjective symptoms and objective findings on voiding and storage functions, obtained through urodynamic studies that included cystometry and pressure flow study, were evaluated before, at 3 months, and at 12 months of treatment. RESULTS: The analysis included 94 patients with a mean age of 70.7 years and a mean prostate volume of 44.5 mL. Subjective symptom parameters of LUTS were significantly ameliorated after 3 months, and progressively improved until study conclusion. Similarly, monitoring of storage and voiding functions revealed significant improvements after 3 months that continued to improve until 12 months. In 49 patients who revealed detrusor overactivity during cystometry at the baseline assessment, uninhibited detrusor contractions disappeared in 15 (30.6%) patients after 3 months (p = 0.02), and in 22 (44.9%) after 12 months (p < 0.001). Mean maximum flow rate significantly increased by 2.9 mL/s during the 12-month treatment (p < 0.001), whereas mean bladder outlet obstruction index significantly decreased from 59.5 at baseline to 45.7 at 3 months (p = 0.001), and to 42.9 at 12 months (p < 0.001). CONCLUSIONS: Tadalafil significantly improved storage and voiding functions, along with LUTS, in patients with LUTS/BPH during a 1-year treatment.

Investigation of the relationship between bladder function and sarcopenia using pressure flow studies in elderly male patients.

AIMS: Although detrusor underactivity is often encountered in elderly patients, the etiology remains unclear. We have hypothesized that sarcopenia was associated with impaired bladder contractility. Therefore, we have evaluated the relationship between bladder contractility and clinical parameters including sarcopenia markers in elderly male patients. METHODS: This retrospective, single-centre study included male patients over 65 years of age who underwent a pressure flow study (PFS). We excluded patients with any previous medical histories that could affect bladder function, currently on urinary medication, and with no available data of abdominal CT scan. The psoas muscle area (PMA) (cm2 /m2 ) was measured as a surrogate for psoas muscle mass on computed tomography. PMA, serum CRP, and albumin are known as sarcopenia markers. Correlation and multiple regression analyses were performed to evaluate the association of bladder contractility index (BCI) with the following parameters: age, body mass index (BMI), prostate volume, bladder outlet obstruction index (BOOI), serum C-reactive protein (CRP), serum albumin, and PMA. RESULTS: Out of 558 male patients identified in our PFS database, 119 patients were enrolled. In the correlation analysis, age, prostate volume, serum albumin, BOOI, and PMA significantly correlated with BCI. However, no significant correlation of BCI with CRP or BMI was observed. Multiple linear regression analysis showed that serum albumin, BOOI, and PMA were significantly associated with BCI. CONCLUSIONS: We have demonstrated that serum albumin and PMA were significantly positively associated with detrusor contractility. It is possible that sarcopenia is associated with impaired detrusor contractility.

Comparison in the efficacy of fesoterodine or mirabegron add-on therapy to silodosin for patients with benign prostatic hyperplasia complicated by overactive bladder: A randomized, prospective trial using urodynamic studies.

AIMS: To compare the efficacy of fesoterodine or mirabegron add-on therapy for persistent overactive bladder (OAB) symptoms despite silodosin monotherapy in men with lower urinary tract symptoms suggestive of benign prostatic hyperplasia, in both subjective and objective aspects. METHODS: A total of 120 patients with persistent OAB symptoms despite silodosin monotherapy were randomized to receive add-on therapy with fesoterodine (4 mg/day) or mirabegron (50 mg/day) for 12 weeks. At week 12, changes from baseline in patients' subjective symptoms and voiding/storage functions, as assessed using the International Prostate Symptom Score (IPSS), OAB symptom score (OABSS), and urodynamic studies, were compared between the groups. RESULTS: The final analysis included 50 and 52 patients in the fesoterodine and mirabegron groups, respectively. Although the IPSS and OABSS significantly improved in both groups, the fesoterodine (vs mirabegron) group showed significantly greater improvements in the OABSS-total (-2.8 vs -1.5, P = 0.004), IPSS-QOL (-1.5 vs -1.1, P = 0.04), and OABSS-urgency score (-1.5 vs -0.9, P = 0.008) at 12 weeks. Regarding storage functions, although both groups showed significant improvements, the fesoterodine group demonstrated greater improvements in the detrusor overactivity alleviation rate (52.6% vs 28.9%, P = 0.03). Voiding functions did not deteriorate in either group at 12 weeks; no significant inter-group differences were observed. Post-void residual urine significantly increased by 16 mL only in the fesoterodine group. CONCLUSION: Add-on therapy of fesoterodine to silodosin was more effective than adding mirabegron to silodosin for improving OAB symptoms and storage functions, without deteriorating voiding symptoms or functions.

Urodynamic analysis of the impact of diabetes mellitus on bladder function.

OBJECTIVES: To analyze sequential changes of diabetic cystopathy based on urodynamic data in patients with diabetes mellitus. METHODS: Participants included male diabetes patients who underwent a pressure flow study at Nagoya University Graduate School of Medicine, Nagoya, Japan, from April 2005 to October 2016. Patients with a previous history of lower urinary tract dysfunction were excluded. Bladder dysfunction was categorized into four urodynamic patterns: (i) normal; (ii) detrusor overactivity with normal detrusor contractility; (iii) detrusor hyperreflexia/impaired contractility; and (iv) detrusor underactivity. The urodynamic patterns were evaluated according to the presence of diabetic retinopathy and nephropathy, which was correlated to diabetes mellitus duration. Furthermore, the association of clinical factors with voiding function, as well as sensory function, was investigated. RESULTS: A total of 57 patients were enrolled. Detrusor overactivity with normal detrusor contractility patterns was seen only in cases with neither diabetic retinopathy nor diabetic nephropathy, whereas the prevalence of detrusor hyperreflexia/impaired contractility pattern was highest in cases with diabetic retinopathy. Detrusor underactivity pattern was found with the highest frequency in cases with both diabetic retinopathy and diabetic nephropathy. On multivariate analysis, the existence of diabetic retinopathy was only significantly correlated with bladder contractility index. Furthermore, multivariate analysis showed that first desire volume and maximum cystometric capacity were significantly positively correlated with post-void residual urine volume, and also negatively correlated with voiding efficiency independent of bladder contractility index. CONCLUSIONS: Diabetes patients have diverse progressive bladder dysfunction according to the diabetes stage. An optimal screening program is necessary to detect and manage diabetic cystopathy at an early stage.

Treatment of male stress urinary incontinence using autologous adipose-derived regenerative cells: Long-term efficacy and safety.

OBJECTIVES: To investigate the long-term efficacy and safety of periurethral injection of autologous adipose-derived regenerative cells for the treatment of post-prostatectomy stress urinary incontinence. METHODS: A total of 13 patients with persistent stress urinary incontinence after prostate surgery (radical prostatectomy, 10 patients; holmium laser enucleation of the prostate, three patients) underwent periurethral injection of adipose-derived regenerative cells and were followed up for >4 years. A 24-h pad test was carried out for four consecutive days in each evaluation period, and changes in the mean daily leakage volume during the 4 days from baseline to 60 months after treatment were evaluated. RESULTS: The mean follow-up period was 69 months (range 55-72 months). The mean leakage volume/24 h in all patients changed from 260.7 g to 152.7 g. Urinary incontinence progressively improved up to 12 months after treatment in 10 patients, who maintained improvement up to the final assessment, with the mean daily leakage volume decreasing from 281.5 g to 119.0 g (reduction rate 57.7%). The other three patients showed no improvement at 1 year and at the final assessment. After the perioperative period, significant adverse events or prostate-specific antigen increase were not observed during long-term follow up. CONCLUSIONS: The present findings suggest that periurethral injection of autologous adipose-derived regenerative cells is a safe and feasible treatment modality with long-term efficacy for patients with male stress urinary incontinence caused by urethral sphincter deficiency.

Role of microglia in the spinal cord in colon-to-bladder neural crosstalk in a rat model of colitis.

AIMS: We investigated whether spinal cord microglia are involved in colon-to-bladder neural crosstalk in a rat model of colitis. METHODS: Adult female SD rats were divided into A) control, B) colitis, and C) colitis + minocycline groups. Experimental colitis was induced by administering 50% trinitrobenzene sulfonic acid into the distal colon in the colitis group and the minocycline group. Minocycline, a microglial inhibitor, was continuously infused into the intrathecal space in the minocycline group. The following investigations were performed on day 7: (1) continuous cystometry (CMG) in an awake condition; (2) nociceptive behavior observation induced by intravesical instillation of resiniferatoxin; (3) toluidine blue staining in the bladder; (4) Immunofluorescence staining for the microglial marker, CD11b, in L6 spinal cord sections; and (5) quantitative RT-PCR to investigate interleukin-1ß (IL-1ß), chemokine ligand 3 (CCL3), and brain-derived neurotrophic factor (BDNF) gene expression in the L6 spinal cord. RESULTS: In comparison with the control group, the colitis group showed significant increases in (1) micturition frequency during cystometry; (2) resiniferatoxin-induced freezing behavior (bladder pain); (3) the number of total and degranulated mast cells in the bladder; (4) the number of microglia in the L6 spinal cord, and (5) the expression of IL-1ß, CCL3, and BDNF mRNA in the L6 spinal cord. Moreover, intrathecal administration of minocycline alleviated these pathophysiological findings caused by experimental colitis. CONCLUSIONS: Spinal microglia may play an important role in colitis-induced bladder overactivity and enhanced bladder pain sensitivity in colitis rats.

Bladder wall injection of mesenchymal stem cells ameliorates bladder inflammation, overactivity, and nociception in a chemically induced interstitial cystitis-like rat model.

INTRODUCTION AND HYPOTHESIS: We investigated the effects of bladder wall injection of mesenchymal stem cells (MSCs) on bladder tissues, function, and nociceptive behavior in a chemically induced interstitial cystitis-like rat model. METHODS: Chemical cystitis of female rats was induced by intravesical instillation of 0.1 N hydrochloride (HCl) once a week for 2 weeks. Bladders were harvested 1, 2, 3, and 4 weeks after the second application for histological examination. Adipose-derived MSCs (HCl + MSCs) or phosphate-buffered saline (HCl + PBS) was injected into the bladder wall at the time of the second application of HCl. Histological examination, nociceptive behavior, and cystometrograms were evaluated 2 weeks after the injection compared with controls, which received instillation and injection of PBS into the bladder (sham + PBS). RESULTS: The number of mast cells and expression of tumor necrosis factor-α (TNF-α) and transforming growth factor-ß (TGF-ß) were significantly increased at 1 and 2 weeks, and expression of collagen fibers was significantly increased from 2-4 weeks after the second application of HCl. Significantly increased nociceptive behavior, number of mast cells, expression of TNF-α, TGF-ß, and collagen fibers were observed in HCl + PBS compared with sham + PBS, whereas these changes were significantly decreased in HCl + MSCs compared with HCl + PBS. In addition, bladder capacity and voiding threshold pressures were significantly decreased in HCl + PBS but not in HCl + MSCs compared with sham + PBS. CONCLUSIONS: The results suggest that bladder injection of MSCs ameliorates inflammation and fibrosis in bladder tissues, bladder overactivity, and nociception in a rat model of chemically induced cystitis.

Comparison of inflammatory urine markers in patients with interstitial cystitis and overactive bladder.

INTRODUCTION AND HYPOTHESIS: Chronic inflammatory conditions seem to be a shared characteristic in patients with interstitial cystitis (IC) and overactive bladder (OAB). Thus, we measured 40 inflammatory urine markers in IC patients with or without Hunner's lesions (HIC and NHIC respectively) and OAB patients. METHODS: Urine was collected from consecutive HIC patients, NHIC patients, and age and gender-matched OAB patients with no history of IC, recurrent urinary tract infection or bladder cancer. The diagnosis of IC was based on the Asian IC guideline criteria. A representative 40 inflammatory growth factors, cytokines, and chemokines in urine were measured using a MILLIPLEX immunoassay kit. Statistical differences in these markers among the groups were determined by nonparametric ANOVA followed by multiple comparison test. The diagnostic efficiency of these markers was measured using receiver operating characteristic analysis. RESULTS: Vascular endothelial growth factor (VEGF), interleukin-1α (IL-1α), IL-6, and chemokines including CCL2, CCL5, CXCL1, CXCL8, and CXCL10 were significantly increased in HIC (n = 30) and NHIC (n = 30) patients compared with OAB (n = 28) patients. The significant increases in CXCL8 and CXCL10 were also found in HIC patients compared with NHIC patients. However, there were no significant differences in the other urine markers among the groups. Area under the curves for VEGF, CXCL10, CXCL8, IL-1α, CCL5, CCL2, IL-6, and CXCL1 to detect IC in these patients were 0.87, 0.86, 0.81, 0.80, 0.80, 0.71, 0.66, and 0.50 respectively. CONCLUSIONS: The increases in angiogenesis-associated proteins such as VEGF and CXCL10 may be pathophysiologically important for the development of IC.

Effects of tadalafil on storage and voiding function in patients with male lower urinary tract symptoms suggestive of benign prostatic hyperplasia: A urodynamic-based study.

OBJECTIVE: To investigate the effects of tadalafil on storage and voiding function in treatment-naïve patients with lower urinary tract symptoms suggestive of benign prostatic hyperplasia, based on a urodynamic study. METHODS: This was an open-labeled, single-center, prospective study. A total of 80 untreated outpatients with lower urinary tract symptoms suggestive of benign prostatic hyperplasia received tadalafil 5 mg/day for 12 weeks. Subjective symptoms and objective findings on voiding and storage function obtained through urodynamic studies, including cystometry and pressure flow study, were evaluated before and after treatment. RESULTS: A total of 71 patients with a mean age of 70.2 years and a mean prostate volume of 45.6 mL were included in the analysis. In the International Prostate Symptom Score and Overactive Bladder Symptom Score, mean total scores significantly improved from 18.2 to 13.4 (P < 0.001) and 6.5 to 4.7 (P < 0.001), respectively, after treatment. Mean maximum bladder capacity significantly increased by approximately 35 mL (P < 0.001). Detrusor overactivity disappeared in 15 (39.5%) of 38 patients with detrusor overactivity at baseline (P < 0.001). Mean maximum flow rate on pressure flow study significantly increased from 7.1 to 9.1 mL/s (P < 0.001) and mean bladder outlet obstruction index significantly decreased from 61.3 to 47.1 (P < 0.001). CONCLUSIONS: Treatment with tadalafil 5 mg once daily effectively relieves lower urinary tract symptoms based on objective improvement of storage and voiding function, such as detrusor overactivity and bladder outlet obstruction, in patients with lower urinary tract symptoms suggestive of benign prostatic hyperplasia.