Efficiency of HoLEP in patients with detrusor underactivity and renal dysfunction secondary to BPO.

PURPOSE: The purpose of this study was to assess the bladder and renal functional outcomes of holmium laser enucleation of the prostate (HoLEP) in patients with benign prostatic obstruction (BPO) complicated by detrusor underactivity (DU) and secondary renal dysfunction. METHODS: Thirty-one patients were included in this prospective study. Eligible patients had urinary retention, a bladder outlet obstruction index (BOOI) greater than 40, a bladder contractility index (BCI) less than 100, abnormal renal function at the initial diagnosis (serum creatinine > 132 µmol/L) and a renal pelvis anteroposterior diameter (PRAPD) > 1.5 cm bilaterally. All patients underwent HoLEP in a routine manner and were evaluated preoperatively and at 1, 3 and 6 months after surgery. The baseline characteristics of the patients, perioperative data, postoperative outcomes and complications were assessed. RESULTS: Significant improvement was observed in the international prostate symptom score (IPSS), quality of life (QoL) score, maximal urinary flow rate (Qmax), post-void residual volume (PVR), Scr and RPAPD at the 6-month follow-up. Bladder wall thickness (BWT) exhibited a decreasing trend but did not significantly differ from the preoperative values. No grade 3 or higher adverse events occurred, and grade 3 and lower complications were treated conservatively. Three patients required reinsertion of indwelling catheters, and they were able to void spontaneously after two weeks of catheterisation training and medication treatment. CONCLUSION: HoLEP is an effective treatment for men with BPO accompanied by DU and consequent renal function impairment. Patients are able to regain spontaneous voiding. Both bladder and renal functions were preserved and improved.

Association of detrusor underactivity with aging and metabolic syndrome: suggestions from animal models.

Detrusor underactivity, a condition in which the bladder muscle does not contract strongly or long enough to empty the bladder completely or within the normal time frame, is a common cause of lower urinary tract symptoms in older individuals of both sexes. Although aging is a known risk factor for detrusor underactivity, its pathophysiological mechanisms are not fully understood. Therefore, establishing animal models that closely mimic the pathophysiology of detrusor underactivity in humans is necessary to elucidate these mechanisms. Metabolic syndrome is a cluster of several risk factors, including obesity, hyperlipidemia, hyperglycemia, and hypertension, which are associated with the development of diabetes, cardiovascular disease, and lower urinary tract dysfunction in both sexes. Notably, bladder dysfunction resulting from detrusor underactivity is observed at an earlier age in animal models with diabetes mellitus than in those without. Recently, detrusor underactivity-like phenotypes have been observed at a relatively early age in animal models with metabolic syndrome, involving obesity, hyperlipidemia, and hypertension, compared with those without. Therefore, this review introduces the association of detrusor underactivity with aging and metabolic syndrome, as well as possible pathophysiological mechanisms for detrusor underactivity from reports of various animal models. Notably, metabolic syndrome may accelerate the onset of age-related detrusor underactivity, and further analysis of old animal models with metabolic syndrome may help elucidate the pathogenesis of detrusor underactivity in humans.

Pirfenidone improves voiding function by suppressing bladder fibrosis in underactive bladder rats.

Underactive bladder (UAB), characterized by a complex set of symptoms with few treatment options, can significantly reduce the quality of life of affected people. UAB is characterized by hyperplasia and fibrosis of the bladder wall as well as decreased bladder compliance. Pirfenidone is a powerful anti-fibrotic agent that inhibits the progression of fibrosis in people with idiopathic pulmonary fibrosis. In the current study, we evaluated the efficacy of pirfenidone in the treatment of bladder fibrosis in a UAB rat model. UAB was induced by crushing damage to nerve bundles in the major pelvic ganglion. Forty-two days after surgery, 1 mL distilled water containing pirfenidone (100, 300, or 500 mg/kg) was orally administered once every 2 days for a total of 10 times for 20 days to the rats in the pirfenidone-treated groups. Crushing damage to the nerve bundles caused voiding dysfunction, resulting in increased bladder weight and the level of fibrous related factors in the bladder, leading to UAB symptoms. Pirfenidone treatment improved urinary function, increased bladder weight and suppressed the expression of fibrosis factors. The results of this experiment suggest that pirfenidone can be used to ameliorate difficult-to-treat urological conditions such as bladder fibrosis. Therefore, pirfenidone treatment can be considered an option to improve voiding function in patient with incurable UAB.

Summary Paper on Underactive Bladder from the European Association of Urology Guidelines on Non-neurogenic Male Lower Urinary Tract Symptoms.

BACKGROUND AND OBJECTIVE: The European Association of Urology (EAU) Guidelines Panel on non-neurogenic male lower urinary tract symptoms (LUTS) aimed to develop a new subchapter on underactive bladder (UAB) in non-neurogenic men to inform health care providers of current best evidence and practice. Here, we present a summary of the UAB subchapter that is incorporated into the 2024 version of the EAU guidelines on non-neurogenic male LUTS. METHODS: A systematic literature search was conducted from 2002 to 2022, and articles with the highest certainty evidence were selected. A strength rating has been provided for each recommendation according to the EAU Guideline Office methodology. KEY FINDINGS AND LIMITATIONS: Detrusor underactivity (DU) is a urodynamic diagnosis defined as a contraction of reduced strength and/or duration, resulting in prolonged bladder emptying and/or failure to achieve complete bladder emptying within a normal time span. UAB is a terminology that should be reserved for describing symptoms and clinical features related to DU. Invasive urodynamics is the only widely accepted method for diagnosing DU. In patients with persistently elevated postvoid residual (ie, >300 ml), intermittent catheterization is indicated and preferred to indwelling catheters. Alpha-adrenergic blockers are recommended before more invasive techniques, but the level of evidence is low. In men with DU and concomitant benign prostatic obstruction (BPO), benign prostatic surgery should be considered only after appropriate counseling. In men with DU and no BPO, a test phase of sacral neuromodulation may be considered. CONCLUSIONS AND CLINICAL IMPLICATIONS: The current text represents a summary of the new subchapter on UAB. For more detailed information, refer to the full-text version available on the EAU website (https://uroweb.org/guidelines/management-of-non-neurogenic-male-luts).

Is detrusor overactivity with detrusor underactivity limited to the elderly?

OBJECTIVE: Detrusor overactivity with detrusor underactivity (DO-DU) is classically described in frail institutionalized elderly patients, but we have also observed this diagnosis in younger populations. This research aims to identify the differences between two age groups of DO-DU patients. MATERIALS AND METHODS: This study included DO-DU patients from a single center from 2012 to 2023. Patients were divided into two groups: the "Younger" group (aged less than 70 years) and the "Older" group (aged 70 years or older). We separately compared demographics, the number of risk factors considered to affect bladder function, clinical presentations, and urodynamic findings between these two groups in each gender. RESULTS: There were 210 patients included in the analysis, with 50.48% in the younger group and 49.52% in the older group. The median ages of males and females in the younger group were 57 and 62 years, whereas the median ages of males and females in the older group were 76.5 and 76 years. Multiple sclerosis exhibited statistically significant prevalence in the younger patients (7.7% vs. 0%, p = 0.03 in males and 19.9% vs. 4.6% in females). While diabetes mellitus (DM) was more prevalent in the older males (20.0% vs. 4.6%, p = 0.01), transabdominal hysterectomy was more common in the younger females (46.3% vs. 25%, p = 0.04). 69.8% of the younger group and 71.2% of the older group have at least one risk factor that impact their bladder function. There was no statistically significant difference between the two groups across various risk factor categories. The older males reported a higher incidence of urgency (78.3% vs. 58.5%, p = 0.02) and urge incontinence (61.7% vs. 32.3%, p < 0.01), while the younger females reported a higher incidence of straining during voiding on history (46.3% vs. 20.5%, p = 0.01). The younger males exhibited a greater volume of strong desire to void (385 vs. 300 mL, p = 0.01), maximal cystometric capacity (410 vs. 300 mL, p < 0.01), and a lower highest detrusor overactivity (DO) pressure (37 vs. 50.5 cmH2O, p = 0.02). The younger group had a higher postvoid residual (170 vs. 85 mL in males, p < 0.01 and 180 vs. 120 mL in females, p = 0.02). The voiding efficiency was lower in younger females (40% vs. 60%, p = 0.02). In both ages, the ICS detrusor contraction index and projected isovolumetric pressure 1 were similar. However, without considering risk factors, the older males had the highest DO pressure (57 vs. 29 cmH2O, p < 0.01), and the younger males had a higher voiding pressure (PdetQmax) than the older males (28 vs. 20 cmH2O, p = 0.02). CONCLUSION: DO-DU is not exclusive to elderly patients. It can also be diagnosed in individuals with risk factors regardless of age; therefore, clinicians need a high degree of suspicion, especially in patients who have risk factor(s) for DO and DU. A notable clinical differentiation is that older males diagnosed with DO-DU have a higher incidence of urgency and urge urinary incontinence, while younger females have a higher incidence of straining.

Effect of detrusor underactivity on surgical outcomes of holmium laser enucleation of the prostate.

OBJECTIVE: To evaluate the effect of detrusor underactivity (DUA) on the postoperative outcomes of holmium laser enucleation of the prostate (HoLEP) in patients with benign prostatic hyperplasia (BPH). PATIENTS AND METHODS: Patients with BPH who underwent HoLEP between January 2018 and December 2022 were enrolled in this prospective database study. Patients were divided into DUA (bladder contractility index [BCI] <100) and non-DUA (BCI ≥100) groups. Objective (maximum urinary flow rate [Qmax], post-void residual urine volume [PVR]) and subjective outcomes (International Prostate Symptom Score [IPSS], Overactive Bladder Symptom Score [OABSS], satisfaction with treatment question [STQ], overall response assessment [ORA], and willingness to undergo surgery question [WUSQ]) were compared between the two groups before surgery, and at 3 and 6 months after HoLEP. RESULTS: A total of 689 patients, with a mean (standard deviation [SD]) age of 69.8 (7.1) years, were enrolled. The mean (SD) BCI in the non-DUA (325 [47.2%]) and DUA (364 [52.8%]) groups was 123.4 (21.4) and 78.6 (14.2), respectively. Both objective (Qmax and PVR) and subjective (IPSS, IPSS-quality of life, and OABSS) outcomes after surgery significantly improved in both groups. The Qmax was lower in the DUA than in the non-DUA group postoperatively. At 6 months postoperatively, the total IPSS was higher in the DUA than in the non-DUA group. There were no significant differences in surgical complications between the two groups. Responses to the STQ, ORA, and WUSQ at 6 months postoperatively demonstrated that the patients were satisfied with the surgery (90.5% in the DUA group; 95.2% in the non-DUA group), their symptoms improved with surgery (95.9% in the DUA group; 100.0% in the non-DUA group), and they were willing to undergo surgery again (95.9% in the DUA group; 97.9% in the non-DUA group). There were no significant differences in the responses to the STQ and WUSQ between the two groups. CONCLUSION: Our midterm results demonstrated that patients with BPH and DUA showed minimal differences in clinical outcomes after HoLEP compared to those without DUA. The overall satisfaction was high in the DUA group.

Association between frailty and detrusor overactivity with detrusor underactivity in older women.

PURPOSE: While detrusor overactivity (DO) with detrusor underactivity (DU) (DO-DU) has been described as typical of aging, the pathogenesis of DO-DU is highly multifactorial, and often thought to involve medical conditions beyond the urinary tract. We aimed to explore potential associations between idiopathic DO-DU and frailty in older women after accounting for age. METHODS: The design of the study is a cross-sectional single-center study, in an outpatient urodynamic unit specializing in geriatrics. Participants are consecutive female patients aged ≥65 years without contributory neurological conditions or bladder outlet obstruction who completed a comprehensive geriatric assessment followed by urodynamic evaluation from 2015 to 2019. Participants were categorized as having DO, DU, combined DO-DU, or a negative study. Multinomial logistic regression analysis was used to assess the relationship between urodynamic outcomes and frailty, as quantified using the Frailty index (FI). RESULTS: Ninety-five patients were included (median age 78 [interquartile range: 70-83] years), among whom 29% had combined DO-DU. The median FI score was 0.27 (0.2-0.32) (5-12). A higher FI was associated with significantly greater age-adjusted odds of DO-DU when either DU or subjects with a negative urodynamic assessment were used as the reference group. Age was not significantly associated with DO-DU across all multivariable analyses. CONCLUSION: A higher FI was associated with an increased likelihood of DO-DU, which could not be attributed to the effect of age alone. The pathogenesis of DO-DU is likely more complex than chronological aging in and of itself and merits further study.

How do we make progress in phenotyping patients with LUT such as OAB and underactive detrusor, including using urine markers and microbiome data, in order to personalize therapy? ICI-RS 2023: Part 1.

INTRODUCTION: Overactive bladder (OAB) and Underactive bladder (UAB) could be associated with metabolic syndrome, affective disorders, sex hormone deficiency, changes in urinary microbiota, functional gastrointestinal disorders, or autonomic nervous system dysfunction. OBJECTIVES: The aim of this Think Tank was to provide a guide on how to investigate OAB and/or detrusor underactivity (DU) patients to better clarify the underlying pathophysiology and possibly personalize the treatment. METHODS: A compendium of discussion based on the current evidence related to phenotyping patients with OAB or DU investigating metabolic, neurogical, psychological and gastrointestinal aspects with the aim to personalize the treatment. RESULTS AND CONCLUSIONS: The article emphasizes the critical significance of adopting a comprehensive yet tailored approach to phenotyping patients with lower urinary tract symptoms, such as OAB and UAB. The intricate interplay between the lower urinary tract and various factors, metabolic, neurological, psychological, and gastrointestinal can define unique LUT profiles, enabling personalized therapies to replace the one-size-fits-all approach.

How do we make progress in phenotyping patients with lower urinary tract such as overactive bladder and underactive detrusor, including using urine markers and microbiome data, to personalize therapy? ICI-RS 2023-Part 2.

INTRODUCTION: Overactive bladder (OAB) and underactive bladder (UAB) could be associated with metabolic syndrome, affective disorders, sex hormone deficiency, changes in urinary microbiota, functional gastrointestinal disorders, or autonomic nervous system dysfunction. OBJECTIVES: The aim of this Think Tank was to provide a guide on how to investigate OAB and/or detrusor underactivity (DU) patients to better clarify the underlying pathophysiology and possibly personalize the treatment. METHODS: A compendium of discussion based on the current evidence related to phenotyping patients with OAB or DU using urodynamic tests, functional neuro-imaging, urinary markers, and microbiome. RESULTS AND CONCLUSIONS: The article emphasizes the critical significance of adopting a comprehensive yet tailored approach to phenotyping patients with lower urinary tract (LUT) symptoms, such as OAB and UAB. The intricate interplay between the LUT and various factors, metabolic, neurological, psychological, and gastrointestinal can define unique LUT profiles, enabling personalized therapies to replace the one-size-fits-all approach.

Can we predict whether a man with acute or chronic urinary retention will void after bladder outflow resistance reduction surgery? ICI-RS 2023.

AIMS: To address the predictive factors of a successful voiding after bladder outflow resistance reduction surgery (BORRS) in men presenting with acute or chronic urinary retention (UR). METHODS: A think tank (TT) of ICI-RS was gathered in 2023, Bristol, UK, to discuss several aspects of the problem, such as the pathophysiology of UR, the clinical and urodynamic evaluation of men with UR and whether it is possible to predict which men will be able to successfully void after treatment with contemporary surgical options. RESULTS: The TT agreed that successful voiding after BORRS depends on several factors but that a strong recommendation cannot be made regarding preoperative evaluation and whether there are predictive factors of success because of the heterogeneity of patients and methodology in published trials. The diagnosis of obstruction in men with UR may be challenging when there is apparent reduced detrusor contraction during urodynamic studies. Even in the absence of bladder contractility there is documentation of such cases that have voided adequately after BORRS. Still, detrusor underactivity and inadequate relief of prostatic obstruction are the main causes of an unsuccessful voiding after BORRS. Conventional resection and enucleation methods remain the most successful surgeries in relieving UR in men, whereas the efficacy of minimally invasive surgical treatments needs to be assessed further. CONCLUSION: Research is needed to understand the pathophysiology of UR and the predictors of successful voiding after different types of BORRS in men with UR.

Therapeutic outcome of active management in male patients with detrusor underactivity based on clinical diagnosis and videourodynamic classification.

Detrusor underactivity (DU) could be resulted from many different etiologies. Patients with DU might have reduced bladder sensation, low detrusor contractility, and large post-void residual volume. This study analyzed therapeutic outcome of active management for male DU patients, based on clinical and urodynamic characteristics. Male DU patients aged > 18 years old were retrospectively reviewed from the videourodynamic study (VUDS) records in recent 10 years. The patients' demographics, VUDS results, treatment modalities, and treatment outcome were analyzed. The treatment outcomes were compared among patients with different DU subgroups, clinical diagnosis and treatment modalities. Patients with voiding efficiency of > 66.7% were considered having a successful treatment outcome. For comparison, 30 men with normal VUDS finding served as the control arm. Most of the DU patients had reduced bladder sensation. The reduced bladder sensation is closely associated with low detrusor contractility. After active treatment, a successful outcome was achieved in 68.4% of patients after bladder outlet surgery, 59.1% after urethral botulinum toxin A injection, and 57.6% after medical treatment, but only 18.2% after conservative treatment. A successful treatment outcome was achieved in patients with an intact detrusor contractility, either low (69.2%) or normal voiding pressure (81.8%), and in patients with a normal or increased bladder sensation (78.1%). However, patients with detrusor acontractile (41.3%) or absent bladder sensation (17.9%) had less favorable treatment outcome after any kind of urological management. This study revealed that active management can effectively improve voiding efficiency in patients with DU. The normal bladder sensation, presence of adequate detrusor contractility, and bladder outlet narrowing during VUDS provide effective treatment strategy for DU patients. Among all management, BOO surgery provides the best treatment outcome.

Age is associated with reduced urethral pressure and afferent activity in rat.

Age-related changes in the lower urinary tract (LUT) can affect the coordination of reflexes and increase the incidence of bladder disorders in elderly. This study examines the age-related loss of urethral signaling capability by measuring the afferent activity directly. We find that less urethral pressure develops in response to fluid flow in old rats compared to young rats and that pressure and flow evoke less urethral afferent activation. These findings are consistent with our previous study demonstrating that the urethra-to-bladder reflex, which is required for efficient voiding, becomes weaker with age. We measured the pudendal afferent response in young (4-7 months) and old (18-24 months) rats to fluid flow in the urethra across a range of flow rates. We used paraffin embedding and hematoxylin and eosin staining to quantify age-related changes in the sensory branch of the pudendal nerve. Urethral afferent signaling in response to the same urethral flow rates was weaker in older animals. That is, the sensitivity of urethra afferents to flow decreased with age, and higher flow rates were required in older animals to recruit urethra afferents. There was also a reduction in the myelin thickness of pudendal afferents in old rats, which is a possible contributing factor to the sensory activity. Furthermore, the same flow rates evoked less pressure in the urethras of old animals, indicating there is an age-related change of the urethral tissue that reduces the pressure stimulus to which these afferents respond. These results help characterize the underlying changes in LUT system with age.

Correlations between bladder wall thickness and clinical manifestations in female patients with detrusor underactivity and detrusor overactivity-with-detrusor underactivity.

BACKGROUND: Among female patients with lower urinary tract symptoms, detrusor underactivity (DU), and detrusor overactivity-with-detrusor underactivity (DO-DU) are two common diagnoses. Here, we investigated the correlations between bladder wall thickness (BWT) and clinical manifestations of the two diagnoses. METHODS: From 2011 to 2016, female patients with DU or DO-DU, diagnosed at our institute, were recruited. We analyzed their urodynamic parameters and collected three questionnaires (IPSS, UDI-6, OABSS). Using transabdominal sonography, the BWT was recorded. DU was defined as follows: maximum free flow rate (Qmax) ≤ 15 cc/s; detrusor pressure at maximum flow (PdetQmax) ≤ 20 cmH2O; bladder capacity > 150 cc. DO-DU was defined as follows: Qmax ≤ 15 cc/s; PdetQmax ≤ 20 cmH2O; bladder capacity ≤ 150 cc. The BWTs of the two groups were compared using the Mann-Whitney U test; the correlations among the BWTs and the results of three questionnaires were analyzed using Spearman's rank correlation coefficient. RESULTS: Forty-eight female patients with DU and 13 with DO-DU were recruited. Demographic data revealed no differences between the two groups. The mean BWT of the DO-DU patients was significantly larger than that of the DU patients (4.11 vs 3.42 mm; p = 0.001). In the DO-DU group, a high correlation existed between the BWT and some of the UDI-6 items (urgency incontinence: r = 0.831, p = 0.006; incontinence related to activity: r = 0.884, p = 0.002; small amounts of leakage: r = 0.809, p = 0.008). The BWT of the DO-DU patients also exhibited a moderate correlation with the urgency incontinence from the OABSS questionnaire (r = 0.679; p = 0.044). No correlations existed between the BWT of the DU patients and any of the data from the three questionnaires. CONCLUSION: The BWT in the DO-DU patients was significantly thicker than that in the DU patients. The DO-DU patients with thicker bladder walls also had higher UDI-6 scores for both urgency and urgency incontinence.

Aging-related severe hypertension induces detrusor underactivity in rats.

AIMS: Aging is an obvious risk factor for detrusor underactivity. We investigated the effects of aging on bladder function in spontaneously hypertensive rats. MAIN METHODS: Male spontaneously hypertensive rats and Wistar Kyoto rats (used as normotensive controls) at the ages of 18, 36, 54, or 72 weeks were used. Bladder weight, blood pressure, bladder blood flow, and urodynamic and renal parameters were measured. Additionally, detrusor thickness and renal histology were evaluated. KEY FINDINGS: In spontaneously hypertensive rats, significant increases were observed in bladder weight/body weight ratio, blood pressure, detrusor thickness, intercontraction interval, urine output, serum creatinine, and renal glomerular and tubular scores, and decreases in bladder blood flow and urine osmolality at 72 weeks as compared to those at 18 weeks. In spontaneously hypertensive rats, significant increases were observed in single voided volume, post voiding residual urine volume, and bladder capacity, with decrease in voiding efficiency were observed at 54 or 72 weeks than at 18 weeks. However, there were no significant differences in blood pressure, urodynamic and renal parameters, detrusor thickness and renal histology among Wistar Kyoto rats of different ages. SIGNIFICANCE: In spontaneously hypertensive rats, aging induces significant increases in blood pressure, single voided volume, post voiding residual urine volume, intercontraction intervals and urine output, and decreases in voiding efficiency and bladder blood flow indicative of detrusor underactivity. Aging-related severe hypertension could induce voiding dysfunction such as detrusor underactivity via severe bladder ischemia and polyuria. Aged spontaneously hypertensive rats may be useful animal models for detrusor underactivity.

Detrusor underactivity causes neurogenic voiding dysfunction in a rat bilateral accessory nerve-injury model.

We aimed to investigate detrusor function in a previously developed rat neurogenic voiding dysfunction model that we have developed previously. We performed sham or bilateral accessory nerve injury (BACNI) surgeries on ten-week-old male Wistar/ST rats. One week after surgery, we evaluated detrusor contractility in the bladder using isometric tension and mRNA expression assays. Cholinergic contraction was attenuated in the injury model, whereas carbachol-evoked contraction was enhanced, and mRNA expression of the cholinergic receptor increased. These findings suggest that there was a reduction in neurotransmitter release causing detrusor underactivity.

Superficial peroneal neuromodulation of persistent bladder underactivity induced by prolonged pudendal afferent nerve stimulation in cats.

The purpose of this study is to determine whether superficial peroneal nerve stimulation (SPNS) can reverse persistent bladder underactivity induced by prolonged pudendal nerve stimulation (PNS). In 16 α-chloralose-anesthetized cats, PNS and SPNS were applied by nerve cuff electrodes. Skin surface electrodes were also used for SPNS. Bladder underactivity consisting of a significant increase in bladder capacity to 157.8 ± 10.9% of control and a significant reduction in bladder contraction amplitude to 56.0 ± 5.0% of control was induced by repetitive (4-16 times) application of 30-min PNS. SPNS (1 Hz, 0.2 ms) at 1.5-2 times threshold intensity (T) for inducing posterior thigh muscle contractions was applied either continuously (SPNSc) or intermittently (SPNSi) during a cystometrogram (CMG) to determine whether the stimulation can reverse the PNS-induced bladder underactivity. SPNSc or SPNSi applied by nerve cuff electrodes during the prolonged PNS inhibition significantly reduced bladder capacity to 124.4 ± 10.7% and 132.4 ± 14.2% of control, respectively, and increased contraction amplitude to 85.3 ± 6.2% and 75.8 ± 4.7%, respectively. Transcutaneous SPNSc and SPNSi also significantly reduced bladder capacity and increased contraction amplitude. Additional PNS applied during the bladder underactivity further increased bladder capacity, whereas SPNSc applied simultaneously with the PNS reversed the increase in bladder capacity. This study indicates that a noninvasive superficial peroneal neuromodulation therapy might be developed to treat bladder underactivity caused by abnormal pudendal nerve somatic afferent activation that is hypothesized to occur in patients with Fowler's syndrome.

Therapeutic effect of Low intensity Extracorporeal Shock Wave Therapy (Li-ESWT) on diabetic bladder dysfunction in a rat model.

Objectives: Low intensity extracorporeal shock wave therapy (Li-ESWT) has proven to be effective and safe for the treatment of various urological disorders including erectile dysfunction and chronic pelvic pain syndrome. In this study, we elucidated the therapeutic effect and possible mechanisms of Li-ESWT on diabetic bladder dysfunction (DBD) in a rat model. Materials and Methods: In all, thirty-two female Sprague-Dawley rats were divided into three groups: normal control (NC), diabetes mellitus (DM) control, and DM Li-ESWT. The two DM groups were given high fat diets for one month, followed by 2 intraperitoneal injections of streptozotocin (STZ) 30 mg/kg separated by one week. Body weight and fasting blood glucose were monitored every week. Only rats with fasting blood glucose 140 mg/dL or more were considered diabetic and used in the subsequent portions of the study. The Li-ESWTs were applied toward the pelvis of the rats twice a week for 4 weeks with energy flux density (EFD) 0.02 mJ/mm2, 500 shocks, at 3Hz. All rats underwent plasma insulin tolerance test, conscious cystometry, leak-point pressure (LPP) assessment, and immunohistochemical studies. Results: DM groups had significantly lower insulin sensitivity and higher body weight. Conscious cystometry also revealed voiding dysfunctions. In the DM Li-ESWT group, the rats had significantly improved voiding functions that were reflected in longer micturition intervals and higher LPP compared to DM control. Immunofluorescence in DM control groups showed increased tyrosine hydroxylase (TH) expression and decreased neuronal nitric oxide synthase (nNOS) expression in the longitudinal urethral smooth muscles. Besides, rats had dilations and deformities of suburothelium capillary network of the bladder, revealing the deterioration of the nerve function of the urethra and destruction of the vascularization of the bladder. However, the DM Li-ESWT group exhibited recovery of the nerve expression of the urethra and vascularization of bladder. Conclusions: Li-ESWT ameliorates the bladder dysfunction and urinary continence in the DBD rat model, reflected in restoration of the nerve expression of the urethra and the vascularization of the bladder. Non-invasive Li-ESWT could be an alternative therapeutic option for DBD.