Clinical, Translational, and Basic Research and Novel Therapy on Functional Bladder Diseases and Lower Urinary Tract Dysfunctions

Topic Information

Dear Colleagues,

Recently, the diagnosis and treatment of functional urology have attracted great attention in urology, gynecology, and neurology. Although functional bladder diseases and lower urinary tract symptoms (LUTS) do not usually immediately affect general health, LUTS have been found to have a great impact on mental health and quality of life. Clinically, these bladder diseases and bladder outlet dysfunction result in storage and emptying symptoms. There is a wide spectrum of overlap between bladder and bladder outlet diseases—for example, patients with an overactive bladder or interstitial cystitis may have bladder storage symptoms and voiding dysfunction, and bladder hypersensitivity could result in a dysfunctional voiding. Male patients with bladder outlet obstruction may also have overactive bladder symptoms in addition to voiding difficulty. Furthermore, bladder dysfunction in patients with spinal cord injury may influence upper urinary tract health and recurrent urinary tract infection. Lower urinary tract dysfunction (LUTD) might also be an early neurological sign of central nervous system disease, such as cerebral ischemia, Parkinson’s disease, or early dementia. Conducting urodynamic and electrophysiology studies enables us to understand the etiology and physiology of LUTD. Using urine protein analysis, it is possible to diagnose different LUTDs and identify the pathophysiology of bladder or bladder outlet diseases. These clinical and research advances have brought the treatment of bladder diseases and LUTD to a new era. The diagnosis of LUTD is not only predicated on examining clinical symptoms and images but also on urodynamics, electrophysiology, and perhaps in the future, urine biomarkers analysis. The treatment of functional LUTD may include medicines, injecting agents, and surgical intervention.

This Topic welcomes articles from clinical, translational, and basic research on any bladder diseases and LUTD, such as male or female bladder outlet obstruction, interstitial cystitis, overactive bladder syndrome, detrusor underactivity, neurogenic lower urinary tract dysfunction due to spinal cord injury, or central nervous diseases. With the collection of these articles, we hope to further advance functional urology.

Prof. Dr. Hann-Chorng Kuo
Dr. Yao-Chi Chuang
Dr. Chun-Hou Liao
Topic Editors

Keywords

Participating Journals

Journal Name	Impact Factor	CiteScore	Launched Year	First Decision (median)	APC
Biomedicines biomedicines	3.9	5.2	2013	14.6 Days	CHF 2600	Submit
Diseases diseases	2.9	0.8	2013	21.4 Days	CHF 1800	Submit
Journal of Clinical Medicine jcm	3.0	5.7	2012	16 Days	CHF 2600	Submit
Journal of Personalized Medicine jpm	-	4.1	2011	17.4 Days	CHF 2600	Submit
Uro uro	-	-	2021	27.9 Days	CHF 1000	Submit
Reports reports	0.8	-	2018	18.6 Days	CHF 1400	Submit

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Published Papers (6 papers)

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11 pages, 490 KiB  

Open AccessArticle

Patient-Reported Urinary Symptom Progression After Bacillus Calmette–Guerin Therapy for Bladder Cancer

by Zorawar Singh, Ananth Punyala, Christina Sze, Naeem Bhojani, Kevin C. Zorn, Dean Elterman and Bilal Chughtai

Uro 2025, 5(1), 4; https://doi.org/10.3390/uro5010004 - 28 Feb 2025

Viewed by 412

Abstract

Background/Objectives: Lower urinary tract symptoms (LUTs) are commonly reported complications of intravesical Bacillus Calmette–Guerin (BCG) instillation for non-muscle invasive bladder cancer; however, there is limited characterization of the severity of the symptoms. We aim to explore the progression of LUTs with BCG treatment [...] Read more.

Background/Objectives: Lower urinary tract symptoms (LUTs) are commonly reported complications of intravesical Bacillus Calmette–Guerin (BCG) instillation for non-muscle invasive bladder cancer; however, there is limited characterization of the severity of the symptoms. We aim to explore the progression of LUTs with BCG treatment for bladder cancer. Methods: Patients were given the Overactive Bladder Questionnaire Short Form (OAB-q SF) to complete prior to their weekly BCG instillation during their primary six-week induction course. Mean symptom scores were compared for weeks 2 through 6 to baseline scores (week 1) utilizing two-sample tests. Subgroup analysis was conducted to identify cohorts at increased risk for urinary symptom progression. Simple linear regression was performed to determine the change in mean symptom scores over time. Results: A total of 60 patients completed the full six-week induction course and completed the required questionaries. Intravesical BCG administration was associated with no significant change in scores across either the symptom bothers or HFQL surveys, which were taken independently or in aggregate. No statistically significant differences in symptom scores were found between subgroups created based on demographic variables, tumor characteristics, or clinical presentation. Conclusions: Although intravesical BCG may cause acute urinary symptoms, it does not seem to impact a patient’s baseline urinary symptom profile. This is important when counseling patients about the perceived chronic urinary symptom risk associated with BCG treatment. Full article

(This article belongs to the Topic Clinical, Translational, and Basic Research and Novel Therapy on Functional Bladder Diseases and Lower Urinary Tract Dysfunctions)

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16 pages, 1598 KiB  

Open AccessArticle

Clustering of Urinary Biomarkers to Identify Interstitial Cystitis Subtypes and Different Clinical Characteristics and Treatment Outcomes

by Jing-Hui Tian, Chung-You Tsai, Wan-Ru Yu, Yuan-Hong Jiang, Jia-Fong Jhang and Hann-Chorng Kuo

Biomedicines 2025, 13(2), 369; https://doi.org/10.3390/biomedicines13020369 - 5 Feb 2025

Viewed by 747

Abstract

Purpose: Interstitial cystitis/bladder pain syndrome (IC/BPS) is mysterious and difficult to diagnose without cystoscopic hydrodistention. This study aimed to explore non-invasive and highly reliable urine biomarkers to identify Hunner’s IC (HIC) and different non-Hunner’s IC (NHIC) subtypes. Methods: In total, 422 women with [...] Read more.

Purpose: Interstitial cystitis/bladder pain syndrome (IC/BPS) is mysterious and difficult to diagnose without cystoscopic hydrodistention. This study aimed to explore non-invasive and highly reliable urine biomarkers to identify Hunner’s IC (HIC) and different non-Hunner’s IC (NHIC) subtypes. Methods: In total, 422 women with and without clinically diagnosed IC/BPS (n = 376 and 46, respectively) were retrospectively enrolled. Patients were diagnosed with HIC or NHIC by cystoscopic hydrodistention under anesthesia. Then, the maximal bladder capacity (MBC) and glomerulation grade were determined. Thirteen urine inflammatory cytokines, chemokines, and oxidative stress biomarkers based on the previously reported predictors of IC/BPS were assayed using commercial microsphere kits. The dataset was randomly divided into training (70%) and test (30%) sets for model construction and validation using logistic regression and stepwise variable selection techniques. To construct the predictive models, univariate analysis was performed to evaluate the discriminative power of each urinary biomarker, measured by the area under the curve (AUC). Biomarkers with AUC values < 0.6 were excluded from further modeling. Multivariate logistic regression was then employed, with variables selected through stepwise forward selection based on log-likelihood criteria. For dichotomization, cutoff values were determined using quartile ranges from the control group. The final model’s performance was assessed using AUC, accuracy, sensitivity, and specificity in both training and test sets. Results: By setting the screening criterion to AUC ≥ 0.60, the potential urinary biomarkers for identifying IC/BPS cases were eotaxin, monocyte chemoattractant protein-1, tumor necrosis factor-alpha (TNF-α), 8-hydroxy-2′-deoxyguanosine (8-OHdG), and 8-isoprostane. Those for identifying HIC from the IC/BPS cohort were interleukin (IL)-6, IL-8, interferon γ-inducible protein 10 (IP-10), and regulated on activation, normal T-cell expressed and secreted (RANTES). A diagnostic algorithm using a cluster of urinary biomarkers included TNF-α ≥ 0.95 pg/mL or 8-OHDG ≥ 22.34 pg/mL and 8-isoprastane ≥ 22.34 pg/mL for identifying IC/BPS from the overall cohort; for identifying HIC from the IC/BPS cohort, the urinary IP-10 ≥ 3.74 pg/mL or IP-10 ≥ 19.94 pg/mL was added. Conclusions: Using a cluster of urinary biomarkers such as TNF-α or 8-OHdG and 8-isoprostane can identify IC/BPS from a study cohort, and adding the urinary IP-10 can distinguish HIC from IC/BPS cases. Full article

(This article belongs to the Topic Clinical, Translational, and Basic Research and Novel Therapy on Functional Bladder Diseases and Lower Urinary Tract Dysfunctions)

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11 pages, 231 KiB  

Open AccessArticle

Prediction of Bladder Outlet Obstruction in Male Patients with Lower Urinary Tract Symptoms Based on Symptom Scores and Noninvasive Office-Based Diagnostic Tools

by Min-Ching Liu, Yuan-Hong Jiang and Hann-Chorng Kuo

Biomedicines 2025, 13(2), 301; https://doi.org/10.3390/biomedicines13020301 - 26 Jan 2025

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Abstract

Purpose: The purpose of this study was to investigate the predictive values of combining symptom scores, prostatic parameters, uroflowmetry parameters, intravesical prostatic protrusion, and prostatic urethral angle for the establishment of a bladder outlet obstruction (BOO) risk score for diagnosing BOO in men [...] Read more.

Purpose: The purpose of this study was to investigate the predictive values of combining symptom scores, prostatic parameters, uroflowmetry parameters, intravesical prostatic protrusion, and prostatic urethral angle for the establishment of a bladder outlet obstruction (BOO) risk score for diagnosing BOO in men with lower urinary tract symptoms. Materials and Methods: A total of 355 men with lower urinary tract symptoms were enrolled and divided into a training set (N = 285) and validation set (N = 70). Videourodynamic studies were used to diagnose lower urinary tract dysfunction subtypes, which were subdivided into a non-BOO and BOO group, which included bladder neck dysfunction and benign prostate obstruction. The parameters were categorized as 0, 1, 2, or 3 according to their cutoff value regarding the specificity of predicting BOO. The BOO risk score was constructed by summing scores of seven variables of symptoms and prostate and uroflowmetry parameters. The area under the curve (AUC) was used to select appropriate cutoff values for predicting lower urinary tract dysfunctions. Results: Among the 355 men examined, 234 (65.9%) had BOO, including 136 (38.3%) with bladder neck dysfunction and 98 (27.6%) with benign prostate obstruction. Other lower urinary tract dysfunctions included detrusor overactivity in 37 patients (10.4%), dysfunctional voiding in 28 patients (7.9%), poor relaxation of the external sphincter in 26 patients (7.3%), detrusor underactivity in 14 patients (3.9%), stable bladder in 9 patients (2.5%), and a hypersensitive bladder in 7 patients (2%). With the summation of the BOO risk scores from each variable, a BOO risk score of ≥10 could yield a sensitivity of 0.822 and specificity of 0.656 for benign prostate obstruction in the training set [AUC = 0.800 (0.741–0.859)] and a sensitivity of 0.80 and specificity of 0.64 in the validation set [AUC = 0.813 (0.701–0.925)]. Conclusions: With office-based diagnostic tools, including symptom scores and uroflowmetry and prostate parameters, a BOO risk score was established. A BOO risk score of ≥10 can predict the presence of benign prostate obstruction in >80% of men with lower urinary tract symptoms refractory to initial medication. Full article

(This article belongs to the Topic Clinical, Translational, and Basic Research and Novel Therapy on Functional Bladder Diseases and Lower Urinary Tract Dysfunctions)

15 pages, 285 KiB  

Open AccessReview

Posterior Urethral Valves and Fertility: Insight on Paternity Rates and Seminal Parameters

by Marcello Della Corte, Simona Gerocarni Nappo, Antonio Aversa, Sandro La Vignera, Francesco Porpiglia, Cristian Fiori and Nicola Mondaini

Diseases 2025, 13(1), 21; https://doi.org/10.3390/diseases13010021 - 17 Jan 2025

Viewed by 694

Abstract

Background: Posterior urethral valves (PUVs) represent the most common cause of male congenital lower urinary tract obstruction, often responsible for renal dysplasia and chronic renal failure. Despite recent improvements in patients’ outcomes thanks to prenatal ultrasound early diagnosis, PUVs can still impact sexual [...] Read more.

Background: Posterior urethral valves (PUVs) represent the most common cause of male congenital lower urinary tract obstruction, often responsible for renal dysplasia and chronic renal failure. Despite recent improvements in patients’ outcomes thanks to prenatal ultrasound early diagnosis, PUVs can still impact sexual function and fertility. This study aims to review the available evidence on fertility in PUV patients, examining paternity rates and semen parameters. Methods: A review was conducted of the PubMed, Cochrane, Scopus, and Embase databases. Studies focusing on fertility and paternity outcomes in PUV patients were selected, including case reports, case series, and retrospective and prospective studies. Results: A total of 15 studies met the inclusion criteria. The review revealed that PUV patients often exhibit compromised semen parameters, including low sperm count, reduced motility, and abnormal morphology, as well as alterations in seminal plasma. PUV diagnoses are common in adults exhibiting infertility and ejaculation disorders, suggesting PUVs cannot be considered only a pediatric disease. Paternity rates among PUV patients were rarely reported in extenso, hampering the correct assessment of the overall medium paternity rate and its comparison with that of healthy individuals. Lastly, seminal parameters were assessed in a minimal cohort of patients, therefore, they could not be considered representative. Conclusions: Fertility and seminal parameters in PUV patients represent an under-investigated area. PUVs can variably and non-univocally affect fatherhood, and they may be associated with compromised semen quality. Early intervention and long-term follow-up are essential to address potential fertility issues. Future research should focus on developing targeted strategies to preserve and enhance fertility in this patient population. Full article

(This article belongs to the Topic Clinical, Translational, and Basic Research and Novel Therapy on Functional Bladder Diseases and Lower Urinary Tract Dysfunctions)

12 pages, 242 KiB  

Open AccessArticle

Clinical Comorbidities and Videourodynamic Characteristics of Dysfunctional Voiding in Women

by Cheng-Ling Lee, Yuan-Hong Jiang, Jia-Fong Jhang, Tien-Lin Chang, Jing-Hui Tian and Hann-Chorng Kuo

Biomedicines 2025, 13(1), 199; https://doi.org/10.3390/biomedicines13010199 - 15 Jan 2025

Viewed by 648

Abstract

Purpose: The current study aimed to investigate the clinical comorbidities and urodynamic characteristics of a large cohort of women with dysfunctional voiding (DV) validated on a videourodynamic study (VUDS). Methods: Women who presented with VUDS-confirmed DV from 1998 to 2022 were retrospectively analyzed. [...] Read more.

Purpose: The current study aimed to investigate the clinical comorbidities and urodynamic characteristics of a large cohort of women with dysfunctional voiding (DV) validated on a videourodynamic study (VUDS). Methods: Women who presented with VUDS-confirmed DV from 1998 to 2022 were retrospectively analyzed. Data on clinical symptoms, VUDS findings, and medical comorbidities including medical illness and previous surgical history were recorded and examined. Patients with DV were subgrouped according to age, presence of medical comorbidity, and different urodynamic parameters. The urodynamic parameters and treatment outcomes among the different subgroups were examined. Results: In total, 216 women were retrospectively analyzed. Among them, 188 (88.3%) presented with storage symptoms and 130 (61.0%) with voiding symptoms. Regarding outcomes, 48 (22.2%) patients had successful treatment outcomes; 76 (35.2%), improved outcomes; and 92 (42.6%), failed outcomes. Then, 150 (69.0%) patients presented with urodynamic DO. Patients with terminal DO experienced a significantly higher incidence of hypertension (56.8%), diabetes mellitus (37.9%), and latent central nervous system diseases (38.9%) than those with non-DO or phasic DO. Patients with phasic DO had a significantly higher detrusor pressure (Pdet) and bladder outlet obstruction index than those with non-DO and terminal DO. Patients with hypertension or those with a Pdet ≥ 35 cmH₂O had high rates of successful treatment outcomes. Conclusions: DV is significantly associated with older age and a higher incidence of central nervous system diseases, hypertension, and diabetes mellitus in women. Patients with phasic DO had a high Pdet and BOO, and patients with hypertension or those with Pdet ≥35 cm H₂O who received urethral sphincter treatment had a better treatment outcome. Full article

(This article belongs to the Topic Clinical, Translational, and Basic Research and Novel Therapy on Functional Bladder Diseases and Lower Urinary Tract Dysfunctions)

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11 pages, 842 KiB  

Open AccessArticle

Lower Urinary Tract Dysfunction Among Patients Undergoing Surgery for Deep Infiltrating Endometriosis: A Prospective Cohort Study

by Anna-Sophie Villiger, Diana Hoehn, Giovanni Ruggeri, Cloé Vaineau, Konstantinos Nirgianakis, Sara Imboden, Annette Kuhn and Michael David Mueller

J. Clin. Med. 2024, 13(23), 7367; https://doi.org/10.3390/jcm13237367 - 3 Dec 2024

Viewed by 915

Abstract

Background/Objectives: Postsurgical lower urinary tract dysfunction (LUTD) is a common problem following deep infiltrating endometriosis (DIE) resection. The condition may be caused either by surgically induced damage to the bladder innervation or by pre-existing endometriosis-associated nerve damage. The aim of this study [...] Read more.

Background/Objectives: Postsurgical lower urinary tract dysfunction (LUTD) is a common problem following deep infiltrating endometriosis (DIE) resection. The condition may be caused either by surgically induced damage to the bladder innervation or by pre-existing endometriosis-associated nerve damage. The aim of this study is to evaluate the efficacy of preoperative and postoperative multichannel urodynamic testing (UD) in identifying pre-existing or surgically induced LUTD among patients with DIE. Methods: Women with suspected DIE and planned surgical resection of DIE at the Department of Obstetrics and Gynecology at the University Hospital of Bern from September 2015 to October 2022 were invited to participate in this prospective cohort study. UD was performed before and 6 weeks after surgery. The primary outcome was the maximum flow rate (uroflow), an indicator of LUTD. Secondary outcomes were further urodynamic observations of cystometry and pressure flow studies, lower urinary tract symptoms (LUTS) as assessed by the International Prostate Symptom Score (IPSS), and pain as assessed by the visual analog scale (VAS). Results: A total of 51 patients requiring surgery for DIE were enrolled in this study. All patients underwent surgical excision of the DIE. The cohort demonstrated a uroflow of 22.1 mL/s prior to surgery, which decreased postoperatively to 21.5 mL/s (p = 0.56, 95%CI −1.5–2.71). The mean bladder contractility index (BCI) exhibited a notable decline from 130.4 preoperatively to 116.6 postoperatively (p = 0.046, 95%CI 0.23–27.27). Significant improvements were observed in the prevalence of dysmenorrhea, abdominal pain, dyspareunia, and dyschezia following surgical intervention (p = <0.001). The IPSS score was within the lower moderate range both pre- and postoperatively (mean 8.37 vs. 8.51, p = 0.893, 95%CI −2.35–2.05). Subgroup analysis identified previous endometriosis surgery as a significant preoperative risk factor for elevated post-void residual (43.6 mL, p = 0.026, 95%CI 13.89–73.37). The postoperative post-void residual increased among participants with DIE on the rectum to 54.39 mL (p = 0.078, 95%CI 24.06–84.71). Participants who underwent hysterectomy exhibited a significantly decreased uroflow (16.4 mL/s, p = 0.014, 95%CI 12–20) and BCI (75.1, p = 0.036, 95%CI 34.9–115.38). Conclusions: Nerve-respecting laparoscopy for DIE may alter bladder function. UD is not advisable before surgery, but the measurement may detect patients with LUTD. Full article

(This article belongs to the Topic Clinical, Translational, and Basic Research and Novel Therapy on Functional Bladder Diseases and Lower Urinary Tract Dysfunctions)

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