Publications by authors named "Hann-Chorng Kuo"

293 Publications

Therapeutic efficacy of biofeedback pelvic floor muscle exercise in women with dysfunctional voiding.

Sci Rep 2021 Jul 2;11(1):13757. Epub 2021 Jul 2.

Department of Urology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, and Tzu Chi University, No. 707, Chung-Yang Rd., Sec. 3, Hualien, Taiwan, ROC.

Dysfunctional voiding (DV), a voiding dysfunction due to hyperactivity of the external urethral sphincter or pelvic floor muscles leading involuntary intermittent contractions during voiding, is not uncommon in neurologically normal women with lower urinary tract symptoms (LUTS). We aimed to investigate the therapeutic efficacy of biofeedback pelvic floor muscle training (PFMT) in female patients with DV and to identify the therapeutic efficacy. Thirty-one patients diagnosed with DV. All participates completed the 3-month biofeedback PFMT program, which was conducted by one experienced physiotherapist. At 3 months after treatment, the assessment of treatment outcomes included global response assessment (GRA), and the changes of clinical symptoms, quality of life index, and uroflowmetry parameters. 25 (80.6%) patients had successful outcomes (GRA ≥ 2), and clinical symptoms and quality of life index significantly improved after PFMT. Additionally, uroflowmetry parameters including maximum flow rate, voided volume, voiding efficiency, total bladder capacity, voiding time, and time to maximum flow rate significantly improved after PFMT treatment. Patients with the history of recurrent urinary tract infection in recent 1 year were found to have unsatisfied therapeutic outcomes. In conclusion, biofeedback PFMT is effective in female patients with DV with significant improvements in clinical symptoms, quality of life, and uroflowmetry parameters. The history of urinary tract infection in recent 1 year is a negative predictor of successful outcome.
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http://dx.doi.org/10.1038/s41598-021-93283-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8253800PMC
July 2021

Therapeutic Efficacy of Urethral Sphincteric Botulinum Toxin Injections for Female Sphincter Dysfunctions and a Search for Predictive Factors.

Toxins (Basel) 2021 06 2;13(6). Epub 2021 Jun 2.

Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan.

External urethral sphincter (EUS) dysfunction is a common, bothersome female voiding dysfunction. This study aims to analyze the characteristics of different types of female EUS dysfunction, as well as to determine the outcome predictors of sphincteric botulinum toxin A (BoNT-A) injection. Women receiving sphincteric BoNT-A injections for refractory EUS dysfunction were retrospectively reviewed. A comparison of the baseline clinical, urodynamic parameters and the treatment responses were made for patients with different EUS dysfunctions. A total of 106 females were included. Significantly increased detrusor overactivity, detrusor contracting pressure and the bladder outlet obstruction index with decreased urge sensation were noted in patients diagnosed with dysfunctional voiding or detrusor sphincter dyssynergia comparing to those diagnosed with poor relaxation of the external urethral sphincter. The average subjective improvement rate was 67% for the injection. The therapeutic effect was not affected by the type of EUS dysfunction. The multivariate analysis revealed that bladder neck narrowing and catheterization history were predictive of negative outcomes. There is a distinct urodynamic presentation for each type of female EUS dysfunction. Sphincteric BoNT-A injection provides a good therapeutic outcome for refractory EUS dysfunction. A narrowing bladder neck and a history of catheterization suggest poor therapeutic outcomes.
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http://dx.doi.org/10.3390/toxins13060398DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8226632PMC
June 2021

Novel Applications of Non-Invasive Intravesical Botulinum Toxin a Delivery in the Treatment of Functional Bladder Disorders.

Toxins (Basel) 2021 05 18;13(5). Epub 2021 May 18.

Department of Urology, Buddhist Tzu Chi General Hospital, 707 Chung-Yang Road, Section 3, Hualien 970, Taiwan.

Although intravesical botulinum toxin type A (BoNT-A) injection for functional bladder disorders is effective, the injection-related problems-such as bladder pain and urinary tract infection-make the procedure invasive and inconvenient. Several vehicles have recently been developed to deliver BoNT-A without injection, thereby making the treatment less or non-invasive. Laboratory evidence revealed that liposome can carry BoNT-A across the uroepithelium and act on sub-urothelial nerve endings. A randomized placebo controlled study revealed that intravesical administration of liposome-encapsulated BoNT-A and TC-3 hydrogel embedded BoNT-A can improve urinary frequency, urgency, and reduce incontinence in patients with overactive bladders. A single-arm prospective study also revealed that intravesical administration of TC-3 hydrogel embedded BoNT-A can relieve bladder pain in patients with interstitial cystitis/bladder pain syndrome (IC/BPS). We recently administered suprapubic energy shock wave (ESW) after BoNT-A intravesical administration in six patients with IC/BPS. Although pain reduction and symptom improvement were not significant, immunochemical staining showed cleaved synaptosome-associated protein 25 in the bladder after the procedure. This suggests that ESW can promote passage of BoNT-A across the uroepithelium. In conclusion, using vehicles to intra-vesically deliver BoNT-A for functional bladder disorders is promising. Further studies are necessary to confirm the efficacy and explore novel applications.
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http://dx.doi.org/10.3390/toxins13050359DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8157602PMC
May 2021

Therapeutic Effects of Urethral Sphincter Botulinum Toxin A Injection on Dysfunctional Voiding with Different Videourodynamic Characteristics in Non-Neurogenic Women.

Toxins (Basel) 2021 05 19;13(5). Epub 2021 May 19.

Department of Urology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Tzu Chi University, Hualien 970, Taiwan.

Although female dysfunctional voiding (DV) is common in urological practice, it is difficult to treat. This study evaluated the therapeutic efficacy of urethral botulinum toxin A (BoNT-A) on non-neurogenic female DV. Based on the videourodynamic study (VUDS), the DV was classified into three subgroups according to the obstructive site. A successful treatment outcome was defined as an improvement of voiding efficiency by 10% and reported global response assessment by ≥1. The study compared therapeutic efficacy, baseline urodynamic parameters, and changes in urodynamic parameters between the treatment success and failure groups and among three DV subgroups. Predictive factors for successful treatment were also investigated. A total of 81 women with DV were categorized into three groups: 55 (67.9%) had mid-urethral DV, 19 (23.5%) had distal urethral DV, and 7 (8.6%) had combined BN dysfunction and mid-urethral DV after BN transurethral incision. The treatment outcome was successful for 55 (67.9%) patients and failed for 26 (32.1%). Successfully treated patients had a significant decrease of detrusor pressure, post-void residual volume, and bladder outlet obstruction index, as well as an increase in voiding efficiency at follow-up versus the treatment failure group. The logistic regression of urodynamic parameters and clinical variables revealed that a greater volume of first sensation of filling predicts a successful BoNT-A treatment outcome ( = 0.047). The urethral BoNT-A injection is effective in treating non-neurogenic women with DV, with a success rate of 67.9%. The videourodynamic characteristics of DV may differ among patients but does not affect the treatment outcome.
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http://dx.doi.org/10.3390/toxins13050362DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8159094PMC
May 2021

Voiding dysfunctions in patients with non-Hunner's ulcer interstitial cystitis/bladder pain syndrome do not affect long-term treatment outcome.

Int J Clin Pract 2021 May 17:e14372. Epub 2021 May 17.

Department of Urology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, and Tzu Chi University, Hualien, Taiwan.

Purpose: The role of urodynamic study in the diagnosis and prognostication of interstitial cystitis/bladder pain syndrome (IC/BPS) is still controversial. This study evaluated the correlation of the baseline voiding dysfunctions and long-term treatment outcome in patients with non-Hunner's ulcer IC (NHIC).

Materials And Methods: A total of 211 NHIC patients were enrolled. All patients underwent videourodynamic (VUDS) examination at baseline to identify their voiding conditions and received subsequent treatments. The primary endpoint was Global Response Assessment (GRA) at the interview. Secondary endpoints included O'Leary-Sant symptom score (OSS), Visual Analogue Scale (VAS) for pain and the rate of IC symptom flare-up.

Results: The mean age was 56.8 ± 12.8 years, and mean duration of IC was 16.0 ± 9.9 years. At baseline, 83 (39.3%) patients had a voiding dysfunction and 132 (62.7%) had 1 to 3 co-morbidities. The duration, co-morbidities, treatments, changes in OSS and VAS, maximum bladder capacity (MBC), glomerulations, GRA and flare-up rate showed no significant difference among different subgroups. When we divided patients by their storage and voiding conditions, patients with non-hypersensitivity bladder (HSB) (n = 32) had significantly greater MBC (P = .002) whereas those with HSB with (n = 76) or without (n = 103) voiding dysfunction had higher glomerulation (P = .021). When we analysed voiding dysfunction subgroups by GRA, patients with a GRA of ≥2 had a significantly shorter duration of disease (13.9 ± 8.6 years, P = .021). There were also significant associations between GRA and the changes of OSS (P < .001) and VAS (P < .001).

Conclusions: VUDS can disclose voiding dysfunction in 39.3% of NHIC patients. With adequate therapy, the voiding dysfunctions in NHIC patients do not affect long-term treatment outcome.
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http://dx.doi.org/10.1111/ijcp.14372DOI Listing
May 2021

Decreased urothelial cytoskeleton and cell proliferation protein expression suggest interstitial cystitis/bladder pain syndrome patients with Hunner's lesion and grade 3 glomerulation might be different from other types of patients.

Int J Urol 2021 May 8. Epub 2021 May 8.

Department of Urology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Tzu Chi University, Hualien, Taiwan.

Objectives: To explore the expression of cytoskeletal and cell proliferation proteins in urothelial cells of patients diagnosed with various clinical subtypes of interstitial cystitis/bladder pain syndrome.

Methods: Biopsy specimens from 85 interstitial cystitis/bladder pain syndrome patients were classified according to findings on cystoscopy. Cytokeratins and cell proliferation proteins detected in the specimens were evaluated with immunofluorescence staining and quantified with western blotting. A total of 22 patients diagnosed with pure stress urinary incontinence were enrolled as controls.

Results: Interstitial cystitis/bladder pain syndrome patients with Hunner's lesion and with grade 3 glomerulation hemorrhage had smaller bladder capacities than the other interstitial cystitis/bladder pain syndrome patients without Hunner's lesion. Diminished expression of CK14, CK20, cell proliferation protein tumor protein 63, sonic hedgehog, and fibroblast growth factor receptors 3 and 4, and increased expression of CK5 and BCL2-associated X protein were observed in biopsy specimens from patients with Hunner's lesion compared with those from patients without Hunner's lesion and controls. In the patients with grade 3 glomerulation hemorrhage, lower expression levels of urothelial CK20, tumor protein 63 and fibroblast growth factor receptor 4, and lower expression of CK5 and BCL2-associated X protein were detected compared with other types of NHIC.

Conclusion: A diminished expression of proliferation proteins tumor protein 63 and the mature urothelium marker CK20, and increased expression of the immature marker CK5 in specimens from both Hunner's lesion and grade 3 glomerulation hemorrhage patients can be observed. The urothelium of patients with interstitial cystitis/bladder pain syndrome might be in a state of persistent or chronic injury that could relate to the limited expression of cell proliferation proteins.
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http://dx.doi.org/10.1111/iju.14585DOI Listing
May 2021

Adding mirabegron after intravesical onabotulinumtoxinA injection improves therapeutic effects in patients with refractory overactive bladder.

Low Urin Tract Symptoms 2021 May 6. Epub 2021 May 6.

Department of Urology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, and Buddhist Tzu Chi University, Hualien, Taiwan.

Objectives: To investigate whether adding an anticholinergic or beta-3 agonist can improve the therapeutic effect of intravesical onabotuliumtoxinA injection in patients with refractory overactive bladder (OAB).

Methods: Ninety OAB patients who received an intravesical 100-U onabotulinumtoxinA injection 1 month previously were consecutively invited into a prospective, randomized, open-label study. They were randomly adding on solifenacin 5 mg daily (QD) (30 patients), mirabegron 50 mg QD (31 patients), or no medication (29 patients, control). All enrolled patients completed a 3-day voiding diary, Overactive Bladder Symptom Score (OABSS) and Urgency Severity Scale (USS) questionnaires, Global Response Assessment (GRA) scale, and uroflowmetry at baseline (1 month after intravesical onabotulinumtoxinA injection) and 3-, 6-, 9-, and 12-month follow-up. The primary end point was the effective therapeutic outcome defined as no OAB wet during the 12-month period. The secondary end point included changes of GRA, OABSS, and the parameters of the voiding diary at 3 months.

Results: The baseline data were comparable among the three groups. The percentage of OAB wet in the mirabegron-added-on group was significantly less than that in the solifenacin-added-on and onabotulinumtoxinA-only groups at four different time points (P = .02). At 3 months, the changes of GRA, OABSS, USS, urge urinary incontinence, frequency, nocturia episodes, and functional bladder capacity in the mirabegron-added-on group were significantly greater than those in the other groups. No serious adverse events were reported.

Conclusions: Adding mirabegron could increase the therapeutic effects, mainly on OAB symptoms and GRA scale, after intravesical onabotulinumtoxinA injection in refractory OAB patients.
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http://dx.doi.org/10.1111/luts.12384DOI Listing
May 2021

Will repeated botulinum toxin A improve detrusor overactivity and bladder compliance in patients with chronic spinal cord injury?

Tzu Chi Med J 2021 Apr-Jun;33(2):101-107. Epub 2020 Jul 29.

Department of Urology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and Tzu Chi University, Hualien, Taiwan.

Chronic spinal cord injury (SCI) can induce neurogenic detrusor overactivity (NDO), leading to urinary incontinence and renal damage due to low bladder compliance and high detrusor pressure during the storage and voiding of urine. In 2011, Botox (onabotulinumtoxinA, botulinum neurotoxin serotype A [BoNT-A]) was approved by the Food and Drug Administration for the treatment of NDO. Intradetrusor injection of BoNT-A has been shown to have clinical utility for the treatment of urinary incontinence, with consequent improvements in quality of life for patients. In the past 20 years, this treatment has been shown to be an effective treatment for patients with SCI refractory to antimuscarinic medication. The present review focused on publications in MEDLINE/PubMed relating to botulinum toxin to evaluate the treatment outcomes of repeated injection of BoNT-A, the mechanisms of action, results of clinical and urodynamic studies, and adverse effects.
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http://dx.doi.org/10.4103/tcmj.tcmj_77_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8059473PMC
July 2020

A novel management for postprostatectomy urinary incontinence: platelet-rich plasma urethral sphincter injection.

Sci Rep 2021 Mar 8;11(1):5371. Epub 2021 Mar 8.

Department of Urology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and Tzu Chi University, Hualien, Taiwan, ROC.

Platelet-rich plasma (PRP) is the most innovative blood-derived product used in regenerative medicine. We aimed to investigate the therapeutic efficacy of PRP urethral sphincter injection for the management of postprostatectomy incontinence (PPI). In total, 28 PPI patients with a mean age of 71.8 ± 8.9 years were prospectively enrolled. They received four PRP urethral sphincter injections each month. The clinical outcomes were assessed 3 months after the fourth injection as posttreatment Global Response Assessment (GRA) score, the newly designed visual analogue scale of stress urinary incontinence (VAS of SUI), and in urodynamic parameters. After injections, the posttreatment median GRA with quartiles was 2.0 (1.0, 2.0). Overall, six (21.4%) patients achieved complete continence and pad-free status, 20 (71.4%) achieved successful outcome (GRA score ≥ 2), and 26 (92.9%) showed clinical improvement (GRA score ≥ 1). The VAS of SUI significantly improved from 6.5 (5.0, 8.0) to 3.5 (2.0-5.8) (p < 0.001) as well as abdominal leak point pressure, from 57.5 (50.0, 115.0) to 126.0 (68.3, 150.0), (p = 0.004). After repeated PRP urethral sphincter injections, the SUI severity reduced significantly with high success rates. There was no major adverse event, except three patients with mild hematuria and micturition pain. In conclusion, PRP urethral sphincter injection is safe and effective as a novel management of PPI.
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http://dx.doi.org/10.1038/s41598-021-84923-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7940644PMC
March 2021

Smaller bladder capacity and stronger bladder contractility in patients with ketamine cystitis are associated with elevated TRPV1 and TRPV4.

Sci Rep 2021 Mar 4;11(1):5200. Epub 2021 Mar 4.

Department of Urology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and Tzu Chi University, 707, Sec. 3, Chung Yang Rd., Hualien, 970, Taiwan.

Stronger contractility and smaller bladder capacity are common symptoms in ketamine cystitis (KC). This study investigates the association between expression levels of transient receptor potential cation channel subfamily V (TRPV) proteins and the clinical characteristics of KC. Bladder tissues were obtained from 24 patients with KC and four asymptomatic control subjects. Video urodynamic parameters were obtained before surgical procedures. The TRPV proteins were investigated by immunoblotting, immunofluorescence staining, and immunohistochemistry. The Pearson test was used to associate the expression levels of TRPV proteins with clinical characteristics of KC. The expression level of TRPV1 and TRPV4 was significantly higher in the severe KC bladders than in mild KC or control bladders. The TRPV1 proteins were localized in all urothelial cell layers, and TRPV4 was located in the basal cells and lamina propria. The expression of TRPV1 was negatively associated with maximal bladder capacity (r = - 0.66, P = 0.01). The expression of TRPV4 was positively associated with the velocity of detrusor pressure rise to the maximum flow rate (r = 0.53, P = 0.01). These observations suggest smaller bladder capacity and stronger contractility in KC are associated with an elevated expression of TRPV1 and TRPV4, respectively.
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http://dx.doi.org/10.1038/s41598-021-84734-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7933333PMC
March 2021

High percentage of neurologic deficits in the electrophysiology study of the lower urinary tract in patients with detrusor underactivity and chronic urinary retention.

Neurourol Urodyn 2021 03 1;40(3):883-890. Epub 2021 Mar 1.

Department of Urology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and Tzu Chi University, Hualien, Taiwan.

Objectives: Both detrusor underactivity (DU) and bladder outlet obstruction are the common causes of chronic urinary retention. Some novel treatment approaches focus on modulating micturition reflex and external urethral sphincter (EUS) function. This study used electrophysiologic (EP) studies to investigate the micturition reflex and EUS conditions of chronic urinary retention patients.

Methods: Sixty patients with urodynamic DU and chronic urinary retention were studied using (1) bulbocavernous reflex (BCR) by electric stimulation, (2) electromyography (EMG) of the EUS, and (3) nerve conduction velocity (NCV) studies of the pudendal nerve. The EP findings were analyzed in DU patients with different etiologies.

Results: The BCR was positive in 41.7% of patients. In EMG studies, denervation, reinnervation, and reduced recruitment of the EUS were observed in 21.7%, 71.7%, and 88.3% patients, respectively. Decreased amplitude of pudendal nerve conduction in NCV studies was noted in 73.3% of patients. Patients with sacral neuropathy had a lower BCR positive rate (p = 0.001), a nonsignificant but higher denervation rate (p = 0.059) in EMG studies, and a higher rate of decreased amplitude in NCV (p = 0.011) than those without sacral neuropathy. Excluding patients with sacral neuropathy or diabetes mellitus, a high percentage of neurologic deficits was still detected in EP studies.

Conclusions: Chronic urinary retention patients with urodynamic DU not only have bladder dysfunction, but also potential neuropathy in the sacral reflexes, pudendal nerve, or urethral sphincter innervation. The neurologic deficits explored in EP studies may affect the decision-making around the therapy to restore the voiding function in DU.
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http://dx.doi.org/10.1002/nau.24644DOI Listing
March 2021

Recurrent urinary tract infection in women and overactive bladder - Is there a relationship?

Tzu Chi Med J 2021 Jan-Mar;33(1):13-21. Epub 2020 Jun 29.

Department of Urology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and Tzu Chi University, Hualien, Taiwan.

Overactive bladder (OAB) in women has similar symptomatology with other common urologic diseases such as recurrent urinary tract infection (UTI). Recent evidence showed that chronic low-grade bacterial bladder colonization might exacerbate OAB symptoms and could be the etiology of recurrent UTI. The high prevalence of lower urinary tract dysfunction is associated with OAB. Women with urgency urinary incontinence refractory to antimuscarinic therapy had more bacteria and a more diverse urinary microbiome. The bacterial reside in the superficial urothelial cells to form intracellular bacterial community and outbreak when the host innate immunity is low. Women with recurrent UTI are found to have highly prevalent voiding dysfunction and detrusor overactivity. These functional abnormalities will further damage the urothelial barrier integrity and create vulnerable to uropathogen invasion. The defective urinary microbiota is less common in women with recurrent UTI, suggesting that the normal flora in the urine might inhibit uropathogen growth and invasion. The defective urothelial barrier function, deficient basal proliferation, and deficient maturation might be owing to chronic suburothelial inflammation, resulting in activation of sensory nerves (causing OAB) and failure elimination of intracellular bacterial communities (causing recurrent UTI). Precision diagnosis and multidisciplinary treatment of the underlying pathophysiology of OAB and recurrent UTI is necessary.
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http://dx.doi.org/10.4103/tcmj.tcmj_38_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7821830PMC
June 2020

Therapeutic Efficacy of Urethral Sphincter Injections of Platelet-Rich Plasma for the Treatment of Stress Urinary Incontinence due to Intrinsic Sphincter Deficiency: A Proof-of-Concept Clinical Trial.

Int Neurourol J 2021 Mar 19;25(1):51-58. Epub 2021 Jan 19.

Department of Urology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Tzu Chi University, Hualien, Taiwan.

Purpose: The aim of this study was to investigate the efficacy of autologous platelet-rich plasma (PRP) in the treatment of stress urinary incontinence (SUI) due to intrinsic sphincter deficiency (ISD) refractory to medical treatment.

Methods: Thirty-five patients with SUI due to urodynamically proven ISD were prospectively enrolled. Five milliliters of PRP (2.5-5 times the platelet concentration in peripheral blood) was injected into the external sphincter at 5 sites; all patients received 4 injections at monthly intervals. The primary end-point was the change in SUI severity as assessed by a visual analogue scale (VAS of SUI). The secondary-endpoints were the Global Response Assessment score and changes in urodynamic parameters from baseline to 3 months after treatment.

Results: The mean age of patients was 68.7±12 years; the median duration of SUI was 4 years. Five patients had neurogenic SUI, while 30 had nonneurogenic SUI (21 with postprostatectomy incontinence, 6 with previous radical cystectomy, and 3 with other etiologies). Complete dryness was achieved in 7 patients (20.0%) while moderate improvement was observed in 14 (40.0%). The mean VAS of SUI score decreased significantly from 6.57±1.89 to 3.77±2.41 after treatment. The abdominal leak point pressure (ALPP) increased significantly from 98.3±55.8 to 157.3±79.3 cm H2O. There was no increase of ALPP in neurogenic SUI and less increase of ALPP in patients with failed treatment outcomes. No perioperative adverse events or severe complications occurred.

Conclusion: Urethral PRP injection is safe and effective in increasing urethral resistance and improving SUI. PRP could be an alternative treatment modality for male and female patients with moderate SUI due to nonneurogenic causes.
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http://dx.doi.org/10.5213/inj.2040272.136DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8022168PMC
March 2021

Predictors of further anti-incontinence interventions or transvaginal urethrolysis after a pubovaginal sling procedure in women with and without neurologic disorders.

J Formos Med Assoc 2021 Jul 16;120(7):1464-1477. Epub 2021 Jan 16.

Department of Urology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and Tzu Chi University, Hualien, Taiwan. Electronic address:

Background/purpose: The impact of neurologic disorders on the clinical outcome of suburethral sling procedures has seldom been studied. Our aim is to elucidate factors predicting further anti-incontinence interventions or transvaginal urethrolysis after a re-adjustable pubovaginal sling procedure (PVS), especially in patients with neurologic disorders.

Methods: Medical records of all consecutive women who underwent re-adjustable PVS for stress urinary incontinence (SUI) were reviewed.

Results: A total of 589 women were enrolled, 152 (25.8%) women were found to have persistent or recurrent SUI after surgery, and 39 (6.6%) women underwent further anti-incontinence interventions. Postoperative voiding dysfunction was found in 46 (7.8%) women, and 23 women (3.9%) underwent transvaginal urethrolysis. Low body mass index (hazard ratio = 0.92) and low functional bladder capacity (dL, hazard ratio = 0.83) were factors predicting the presence of persistent/recurrent SUI. However, the presence of spinal cord disorder (hazard ratio = 8.91) and a history of prior surgery for pelvic organ prolapse (hazard ratio = 2.51) were factors predicting further anti-incontinence interventions. A high post-void residual volume (PVR, dL, hazard ratio = 1.52) and preoperative bladder outlet obstruction (BOO, hazard ratio = 5.39) were factors predicting postoperative voiding dysfunction. Similarly, a high PVR (dL, hazard ratio = 1.50) and preoperative BOO (hazard ratio = 5.38) were factors predicting transvaginal urethrolysis. A PVR >1.51 dL was an optimal cut-off value for predicting transvaginal urethrolysis.

Conclusion: The presence of spinal cord disorder and prior surgery for pelvic organ prolapse were predictors of further anti-incontinence interventions after re-adjustable PVS. In addition, a large PVR and preoperative BOO were predictors of transvaginal urethrolysis after re-adjustable PVS.
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http://dx.doi.org/10.1016/j.jfma.2020.12.029DOI Listing
July 2021

Urine biomarkers in ESSIC type 2 interstitial cystitis/bladder pain syndrome and overactive bladder with developing a novel diagnostic algorithm.

Sci Rep 2021 01 13;11(1):914. Epub 2021 Jan 13.

Department of Urology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and Tzu Chi University, 707, Section 3, Chung Yang Road, Hualien, Taiwan.

This study aimed to investigate the diagnostic values of urine cytokines in interstitial cystitis/bladder pain syndrome (IC/BPS) and overactive bladder (OAB) patients, and to develop a novel diagnostic algorithm. Urine samples were collected from 40 IC/BPS, 40 OAB patients, and 30 controls. Commercially available multiplex immunoassays were used to analyze 31 targeted cytokines. Urine cytokine profiles were significantly different among study groups and controls. MIP-1β showed the highest sensitivity (92.2%) for identifying diseased study patients from controls. The cytokines with high diagnostic values for distinguishing between IC and OAB included IL-10, RANTES, eotaxin, CXCL10, IL-12p70, NGF, IL-6, IL-17A, MCP-1, and IL-1RA. The diagnostic algorithm was subsequently developed according to the diagnostic values obtained. MIP-1β was selected for the initial screening test to diagnose diseased patients and controls with diagnostic rates of 81.6% and 68.4%, respectively. As confirmation tests for IC/BPS, the diagnostic rates of eotaxin, CXCL10, and RANTES were 73.3%, 72.7%, and 69.7%, respectively. As the confirmation test for OAB, the diagnostic rate of IL-10 was 60%. Urine cytokine profiles of IC/BPS and OAB patients differed from those of controls and might be useful as biomarkers for diagnosis. A novel pilot diagnostic algorithm was developed based on these profiles.
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http://dx.doi.org/10.1038/s41598-020-80131-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7806856PMC
January 2021

Cystoscopic hydrodistention characteristics provide clinical and long-term prognostic features of interstitial cystitis after treatment.

Sci Rep 2021 01 11;11(1):455. Epub 2021 Jan 11.

Department of Urology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and Tzu Chi University, 707, Section 3, Chung-Yang Road, Hualien, Taiwan.

To evaluate the correlations of clinical symptoms, urodynamic parameters, and long-term treatment outcomes with different findings of cystoscopic hydrodistention (HD) in patients with interstitial cystitis/bladder pain syndrome (IC/BPS). This retrospective analysis of 486 patients with IC/BPS investigated baseline clinical symptoms, disease duration, medical comorbidities, urodynamic findings, cystoscopic characteristics [including maximal bladder capacity (MBC) and the presence of glomerulations and Hunner's lesions], and outcomes according to the five IC/BPS HD subtypes based on the glomerulation grade, MBC, and the presence of Hunner's lesions. Receiver operation characteristic analysis identified an optimal cutoff value of MBC ≥ 760 ml as a predictor of satisfactory outcomes. Glomerulation grade and MBC were significantly correlated (r =  - 0.403, P < 0.001), and both were significantly associated with IC Symptom Index scores. The rate of satisfactory outcomes was better for the patients with low glomerulation grade and MBC ≥ 760 ml (64.2%), and significantly worse for those with Hunner's lesions (36.8%); no significant differences were noted among the other groups. The results suggested that IC/BPS patients can be classified into the following three distinct subgroups: (1) those with low glomerulation grade and MBC ≥ 760 ml; (2) those with low glomerulation grade and MBC < 760 ml, or with high glomerulation grade regardless of MBC; and (3) those with Hunner's lesions. The results showed that three IC/BPS subgroups had distinct bladder characteristics and treatment outcomes. The patients with high MBC and low glomerulation grade after HD had more medical comorbidities but a significantly higher rate of satisfactory treatment outcome.IRB: 105-25-B.
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http://dx.doi.org/10.1038/s41598-020-80252-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7801576PMC
January 2021

Frontiers in the Clinical Applications of Botulinum Toxin A as Treatment for Neurogenic Lower Urinary Tract Dysfunction.

Int Neurourol J 2020 Dec 31;24(4):301-312. Epub 2020 Dec 31.

Department of Urology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Tzu Chi University, Hualien, Taiwan.

Patients with neurogenic lower urinary tract dysfunction (NLUTD) experience urinary incontinence with or without difficult urination, which might promote recurrent urinary tract infection (UTI) and exacerbate upper urinary tract function. Nonetheless, appropriate bladder management has been shown to reduce urological complications and improve quality of life. In addition to pharmacological therapy and surgical intervention, botulinum toxin A (BoNT-A) has been widely utilized in NLUTD. The therapeutic efficacy of detrusor BoNT-A injections for neurogenic detrusor overactivity due to spinal cord injury (SCI), multiple sclerosis, or other central nervous system lesions, such as cerebrovascular accident, Parkinson disease, early dementia, and pediatric NLUTD due to myelomeningocele, has been well established, with repeated BoNT-A injections every 6 to 9 months being necessary to maintain its therapeutic effects. Urethral BoNT-A injection can decrease urethral sphincter resistance and facilitate efficient voiding in patients with NLUTD who wish to preserve self-voiding. Detrusor BoNT-A injection can also decrease the occurrence of autonomic dysreflexia in patients with SCI, even after failed augmentation enterocystoplasty, with additional benefits including reduced UTI episodes and preserved renal function with repeated injections. However, this treatment does have some side effects. Complete informed consent for BoNT-A injection therapy with full disclosure of its potential complications should therefore be obtained before this procedure is undertaken.
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http://dx.doi.org/10.5213/inj.2040354.177DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7788334PMC
December 2020

Urothelial health after platelet-rich plasma injection in intractable recurrent urinary tract infection: Improved cell proliferation, cytoskeleton, and barrier function protein expression.

Low Urin Tract Symptoms 2021 Apr 16;13(2):271-278. Epub 2020 Nov 16.

Department of Urology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and Tzu Chi University, Hualien, Taiwan.

Objective: This clinical study used autologous intravesical platelet-rich plasma (PRP) injections to treat patients with recurrent urinary tract infection (rUTI). Changes in urothelial proliferation, cytoskeleton, and barrier function protein expression after treatment were investigated.

Materials: All patients underwent 4-monthly intravesical PRP injections with 1-year follow-up. Successful treatment was defined as ≤2 UTI episodes within the preceding 1 year. Bladder biopsies were performed at the first and fourth PRP injection, and specimens were investigated by Western blot for the proteins sonic hedgehog (Shh), CD34, cytokeratin 5 (CK5), CK14, CK20, zonula occludens-1 (ZO-1), E-cadherin, inflammatory proteins tryptase and p38, apoptotic protein BAX (BCL2-associated X protein) and caspase-3, functional proteins M2 (muscarinic receptor 2) and M3, and beta-adrenoceptor-3, with glyceraldehyde phosphate dehydrogenase used as normalizing protein for quantification.

Results: The study enrolled 22 patients with rUTI and 17 controls, with successful outcome in 14 of 22 (63.6%) patients. Compared with controls, Western blot quantification results showed that rUTI patients had lower CD34, CK20, M3, and ZO-1, but higher CK5, BAX, and caspase-3 at baseline. The reduced CD34, CK20, M2, and M3 expressions at baseline were significantly increased after repeat PRP injections. Patients with a successful outcome had significant increase of CD34, Shh, CK20, M2, and M3 expressions after PRP injections.

Conclusion: Intravesical PRP repeat injections improve the urothelial cell proliferation and increase the CK 20 expression in umbrella cells. PRP repeat injections have a beneficial effect on bladder urothelium-associated changes in rUTI. Thus, PRP injection may restore urothelial health and prevent UTI recurrence in intractable rUTI.
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http://dx.doi.org/10.1111/luts.12364DOI Listing
April 2021

Deficits of urothelial cell proliferation, cytoskeleton, and barrier function protein expressions in patients with recurrent and persistent urinary tract infections.

Low Urin Tract Symptoms 2021 Apr 1;13(2):203-209. Epub 2020 Nov 1.

Department of Urology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and Tzu Chi University, Hualien, Taiwan.

Objectives: Recurrent urinary tract infection (rUTI) is a common infectious disease in women. This study investigated the urothelial cell proliferation, the cytoskeleton, barrier proteins, and inflammatory protein expression in women with rUTIs.

Methods: Female patients with recurrent or persistent UTIs were recruited. Bladder mucosal specimens were investigated by Western blot and immunohistochemical staining for the urothelial cytoskeleton proteins cytokeratin 5 (CK5), CK14, and CK20; proteins involved in cellular proliferation, including CD34, sonic hedgehog (SHH), and tumor protein 63 (TP63); barrier proteins zonula occludens 1 (ZO-1) and E-cadherin; inflammatory proteins p38 and tryptase; and proapoptotic proteins Bcl2-associated agonist of cell death protein (BAD), Bcl2-associated X protein (BAX), and caspase-3. Women with stress urinary incontinence without bladder symptoms served as controls. Bladder specimens from 18 recurrent UTI patients with rUTIs and 12 persistent UTIs, and 17 controls were analyzed, and protein expressions were compared between the three groups.

Results: Cell proliferation protein expression for CD34, SHH, and TP63 was significantly lower in the urothelium of patients with rUTIs than in controls. Expression of CK5 increased, whereas CK20 decreased significantly in rUTIs compared with those of controls. Apoptotic proteins BAD, BAX, and caspase-3 were significantly higher in patients with rUTIs. However, barrier proteins ZO-1 and E-cadherin, and tryptase were not significantly lower in patients with rUTIs.

Conclusion: Deficits in expression of proteins involved in urothelial cell proliferation, cytoskeleton, and barrier function were noted in patients with rUTIs. These urothelial deficits may be due to deficient proliferation and differentiation resulting in inadequate urothelial barrier function and further in rUTIs.
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http://dx.doi.org/10.1111/luts.12351DOI Listing
April 2021

Will detrusor acontractility recover after medical or surgical treatment? A longitudinal long-term urodynamic follow-up.

Neurourol Urodyn 2021 01 14;40(1):228-236. Epub 2020 Oct 14.

Department of Urology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and Tzu Chi University, Hualien, Taiwan.

Aims: Patients with urinary retention due to detrusor acontractility (DA) might regain voiding efficiency (VE) after treatment. This study investigated the long-term outcomes and predictors of recovery following treatment.

Methods: A total of 32 patients with DA were retrospectively identified and enrolled. DA was defined by P .Q  = 0 cmH O and postvoid residual (PVR) > 300 ml determined through videourodynamic study (VUDS). All patients received medical or surgical treatment and were followed up for at least 3 months, during which repeat VUDS was conducted. Detrusor contractility recovery was confirmed when patients were able to void with a P .Q  ≥ 10 cmH O after treatment.

Results: Our patients comprised 22 women and 10 men (mean age, 73.2 ± 9.7 years; mean follow-up duration, 1.6 ± 1.8 [0.3-7.4] years). Follow-up VUDS revealed that 14 (43.9%) patients recovered from detrusor contractility, with five patients recovering within 1 year and nine after 1 year. P .Q , voided volume, PVR, maximum flow rate, and VE significantly improved in both the recovery and nonrecovery groups. The recovery group had significantly better VE (p = .039) and significantly lower bladder compliance (74.2 ± 83.2 vs. 119 ± 82.6; p = .007) than the nonrecovery group. Receiver operating characteristic (ROC) analysis revealed an optimum bladder compliance cutoff value of <80 ml/cmH O for predicting detrusor contractility recovery with an area under the ROC curve of 0.780.

Conclusions: Among the included patients with DA, 43.9% had detrusor contractility recovery after treatment, with bladder compliance of <80 ml/cmH O predicting bladder function recovery.
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http://dx.doi.org/10.1002/nau.24540DOI Listing
January 2021

Repeated intravesical injections of platelet-rich plasma improve symptoms and alter urinary functional proteins in patients with refractory interstitial cystitis.

Sci Rep 2020 09 16;10(1):15218. Epub 2020 Sep 16.

Department of Urology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, and Tzu Chi University, Hualien, Taiwan.

Repeated intravesical injections of autologous platelet-rich plasma (PRP) have been shown to improve symptoms in patients with interstitial cystitis/bladder pain syndrome (IC/BPS); however, there is a paucity of objective evidence of the effectiveness of this therapy. In this study, we investigated the changes in urinary markers after PRP treatment. Forty patients with IC/BPS who were refractory to conventional therapy received four injections of PRP at monthly intervals; 10 mL PRP solution with 2.5 times the peripheral blood platelet concentration was used. Urine levels of thirteen functional proteins, growth factors, and cytokines were assessed at baseline and at the 4th PRP injection. The clinical parameters included visual analog scale (VAS) pain score, daily urinary frequency, nocturia episodes, functional bladder capacity, and global response assessment (GRA). The GRA and symptom score significantly decreased post-treatment. In patients with GRA ≥ 2, the success rates at 1 month and at 3 months after the 4th PRP injection were 70.6% and 76.7%, respectively. The VAS pain score, frequency, and nocturia showed a significant decrease (all p < 0.05). Urinary levels of nerve growth factor, matrix metalloproteinase-13, and vascular endothelial growth factor significantly decreased post-treatment (p = 0.043, p = 0.02, and p = 0.000, respectively); platelet-derived growth factor-AB showed a significant increase (p = 0.004) at the 4th PRP treatment compared with baseline. In this study, repeated intravesical PRP injections provided significant symptom improvement in IC/BPS patients with concomitant changes in the related biomarker levels.Trial registration: ClinicalTrial.gov: NCT03104361; IRB: TCGH 105-48-A.
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http://dx.doi.org/10.1038/s41598-020-72292-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7495440PMC
September 2020

Clinical Relevance of Bladder Histopathological Findings and Their Impact on Treatment Outcomes among Patients with Interstitial Cystitis/Bladder Pain Syndrome: An Investigation of the European Society for the Study of Interstitial Cystitis Histopathological Classification.

J Urol 2021 Jan 28;205(1):226-235. Epub 2020 Aug 28.

Department of Urology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, and Tzu Chi University, Hualien, Taiwan.

Purpose: We investigate the clinical significance of European Society for the Study of Interstitial Cystitis (ESSIC) bladder histopathological classification and its impact on treatment outcomes among patients with interstitial cystitis/bladder pain syndrome.

Materials And Methods: Bladder biopsy specimens obtained from severe, treatment refractory interstitial cystitis/bladder pain syndrome cases were analyzed by a single pathologist blinded to clinical data. Inflammatory cell infiltration and urothelium denudation, eosinophil infiltration, plasma cell infiltration, lamina propria hemorrhage and granulation in specimens were evaluated separately. Patients with at least 1 histopathological finding were classified as ESSIC type C, with the rest being classified as ESSIC type A. Current overall treatment outcomes were determined via telephone interview.

Results: Bladder specimens were obtained from 352 patients with interstitial cystitis/bladder pain syndrome. Bladder inflammation, urothelium denudation, eosinophil and plasma cell infiltration, lamina propria hemorrhage and granulation were present in 69.6%, 44.6%, 9.1%, 15.3%, 4.8% and 5.1% of the bladder specimens, respectively. Approximately 78.7% of the patients included were ESSIC type C and had a smaller cystometric bladder capacity and higher bladder pain compared to ESSIC type A. Although individual histopathological findings were not associated with treatment outcome, a higher proportion of ESSIC type A patients had worse, unchanged or less than 25% improvement outcomes compared to ESSIC type C (43.1% vs 25.8%, p=0.025).

Conclusions: Bladder histopathological findings were associated with clinical parameters and differences in patient reported treatment outcomes. Accordingly, patients with interstitial cystitis/bladder pain syndrome who had no remarkable bladder histopathological findings had less favorable treatment outcomes compared to those who did.
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http://dx.doi.org/10.1097/JU.0000000000001334DOI Listing
January 2021

A double-blind, randomized, placebo-controlled, parallel study to evaluate the efficacy and safety of imidafenacin in patients with overactive bladder in Taiwan.

Low Urin Tract Symptoms 2021 Jan 25;13(1):108-117. Epub 2020 Aug 25.

Department of Urology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, and Tzu Chi University, Hualien, Taiwan.

Objective: This study evaluated the efficacy and safety of imidafenacin 0.1 mg twice daily vs placebo for Taiwanese patients with overactive bladder (OAB) after a 12-week oral administration.

Methods: This randomized, double-blind, placebo-controlled, two-arm, parallel-group, prospective study enrolled 118 patients across 11 study sites in Taiwan. Subjects were randomized to imidafenacin or placebo in a 2:1 ratio and entered the 12-week treatment period. At the subsequent visits, efficacy outcome measures and safety assessments were collected for analysis. The primary efficacy outcome was the change in the mean number of micturitions per day. Secondary endpoints included mean changes from baseline in urgency episodes and urge incontinence episodes per day and mean volume voided per micturition. Safety outcomes were also collected and compared between groups.

Results: A total of 78 and 40 patients were allocated to the imidafenacin and placebo groups, respectively. Among them, 100 patients (imidafenacin, 65 and placebo, 35) completed the trial. Compared with placebo, imidafenacin was significantly better at reducing the number of micturitions per day (-1.29 ± 2.23 vs -0.46 ± 3.49, P = .0171) and reducing the mean number of urge incontinence episodes (-0.15 ± 0.52 vs 0.04 ± 0.50, P = .0386) at week 12. Adverse events were reported in 35 subjects (44.9%) and 16 (40%) in the imidafenacin and placebo groups, including constipation (n = 3, 4), dry mouth (n = 11, 2), and urinary tract infection (n = 7, 4), respectively. One patient in the imidafenacin group had mild dysuria.

Conclusion: Imidafenacin demonstrated efficacy and safety in the treatment of OAB in Taiwanese patients.
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http://dx.doi.org/10.1111/luts.12341DOI Listing
January 2021

Botulinum toxin A injection in the treatment of chronic pelvic pain with hypertonic pelvic floor in women: Treatment techniques and results.

Low Urin Tract Symptoms 2021 Jan 12;13(1):5-12. Epub 2020 Jul 12.

Department of Urology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and Tzu Chi University, Hualien, Taiwan.

Chronic pelvic pain (CPP) is an extremely bothersome condition which leads to major effects in women's everyday life. In addition to visceral sources of pain, pelvic floor dysfunction including myofascial pain and spasm on the pelvic floor muscles causing hypertonicity are causes often overlooked. Injecting botulinum toxin type A (BoNT-A) into hypertonic pelvic floor muscles may aid the relaxation of pelvic floor musculature. The muscles that are injected in CPP treatment include the obturator internus, levator ani (pubococcygeus, iliococcygeus, and puborectalis), and coccygeus. Generally, injections can be performed tolerably with safety under conscious sedation combined with local anesthesia. Most practitioners perform BoNT-A injection of pelvic floor muscles using anatomical landmarks identified by manual palpation only. For the precise location of injection sites, some needle guidance techniques were proposed, including electromyography, electrical stimulation, ultrasound, fluoroscopy, and/or computed tomography. Side effects of BoNT-A injection in CPP are rare and self-limiting. Because of the reversible nature of BoNT-A, reinjection appears to be necessary. Increasing proof points out that BoNT-A is a promising treatment option for CPP in women. We conducted a review of published literature in Pubmed, using chronic pelvic pain in women, hypertonic pelvic floor, and botulinum toxin as the keywords. This article aims to summarize the treatment techniques and results of BoNT-A injection for hypertonic pelvic floor in women with chronic pelvic pain.
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http://dx.doi.org/10.1111/luts.12334DOI Listing
January 2021

Obstructive patterns in videourodynamic studies predict responses of female dysfunctional voiding treated with or without urethral botulinum toxin injection: a long-term follow-up study.

Int Urogynecol J 2020 Dec 18;31(12):2557-2564. Epub 2020 Jun 18.

Department of Urology, Buddhist Tzu Chi General Hospital and Tzu Chi University, 707, Sec. 3, Chung-Yang Rd., Hualien, Taiwan.

Introduction And Hypothesis: We report long-term changes in VUDS profiles of women with dysfunctional voiding and investigate potential predictors for treatment response.

Methods: Women with dysfunctional voiding and available VUDS data between November 1997 and June 2018 were enrolled for retrospective analysis. The patients were all treated with medication first. In refractory patients, urethral botulinum toxin was provided as an additional option. The primary outcome was the change of VUDS parameters between baseline and follow-up studies. The secondary outcomes were baseline parameters and clinical factors that were associated with the BOOI response (> 10 points of BOOI reduction).

Results: A total of 195 women with DV were included in this study. The mean age was 54.5 years old. Sixty patients received urethral botulinum toxin injection. For all patients, Pdet decreased from 47.2 to 36.8 cm HO (p < 0.0001), and BOOI decreased from 26.4 to 17.7 (p = 0.0001). Patients with urethral injection had significantly smaller Qmax, voided volume, and voiding efficiency (VE) and significantly larger PVR and BOOI at baseline, indicating a severer obstruction in this group. The overall BOOI response rate was 44% (85/195). A higher baseline BOOI was associated with the BOOI response in multivariate analysis.

Conclusions: In this long-term study of women with dysfunctional voiding, medical treatment with or without urethral botulinum toxin injection both resulted in reduction of Pdet and BOOI. A more prominent obstructive profile at baseline VUDS study was associated with a higher rate of BOOI response at follow-up study.
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http://dx.doi.org/10.1007/s00192-020-04333-1DOI Listing
December 2020

Botulinum Toxin Paves the Way for the Treatment of Functional Lower Urinary Tract Dysfunction.

Authors:
Hann-Chorng Kuo

Toxins (Basel) 2020 06 14;12(6). Epub 2020 Jun 14.

Department of Urology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, and Tzu Chi University, Hualien 970, Taiwan.

Botulinum toxin A (BoNT-A) is a potent protein that can selectively modulate neurotransmission from nerve endings, resulting in the blocking of neurotransmitter releases and causing muscular paralysis [...].
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http://dx.doi.org/10.3390/toxins12060394DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7354673PMC
June 2020

Female bladder neck dysfunction-A video-urodynamic diagnosis among women with voiding dysfunction.

Low Urin Tract Symptoms 2020 Sep 8;12(3):278-284. Epub 2020 Jun 8.

Department of Urology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, and Tzu Chi University, Hualien, Taiwan.

Objective: To investigate bladder neck dysfunction (BND) in women with voiding dysfunction by video-urodynamic study (VUDS) and to examine the therapeutic results of different BND subtypes.

Materials And Methods: We retrospectively reviewed consecutive women who had undergone VUDS for investigation of voiding dysfunction at our institution. The diagnosis of BND was made based on a nonfunneling bladder neck with or without high voiding detrusor pressure. Patients diagnosed as BND were retrieved, and the urodynamic parameters were compared with patients with dysfunctional voiding (DV) and other bladder outlet obstructions (BOO).

Results: Among 810 women with bladder outlet dysfunction, BND was noted in 100 (12.3%), poor pelvic floor relaxation in 336 (41.5%), DV in 325 (40.1%), cystocele in 19 (2%), and urethral stricture in 30 (4%). Compared with the normal tracing group, BND patients had a significantly smaller volume of bladder filling sensation (included first sensation of filling, full sensation and cystometric bladder capaicity) and a greater BOO index (BOOI) (all P < .05). Detrusor overactivity was noted in 46 (46%) BND patients. These urodynamic parameters in BND were not significantly different from patients with DV or other BOO. High-pressure BND had a greater BOOI, but low-pressure BND had a lower voiding efficiency. Both alpha-blocker therapy and transurethral incision of the bladder neck improved uroflow parameters in BND patients.

Conclusions: BND includes 12.3% of women with bladder outlet dysfunction. High-pressure BND can cause anatomical BOO, whereas low-pressure BND is likely to affect micturition through inhibiting detrusor contractility. VUDS is the mainstay diagnostic tool to diagnose BND in women.
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http://dx.doi.org/10.1111/luts.12318DOI Listing
September 2020

Pain reduction realized with extracorporeal shock wave therapy for the treatment of symptoms associated with interstitial cystitis/bladder pain syndrome-A prospective, multicenter, randomized, double-blind, placebo-controlled study.

Neurourol Urodyn 2020 06 11;39(5):1505-1514. Epub 2020 May 11.

Department of Urology, Hualien Tzu Chi General Hospital, Tzu Chi Medical Foundation, Buddhist Tzu Chi University, Hualien, Taiwan.

Aims: Extracorporeal shock wave therapy (ESWT) inhibited bladder inflammation and pain in preclinical studies. We assessed ESWT for the treatment of refractory interstitial cystitis/bladder pain syndrome (IC/BPS).

Methods: This double-blind, randomized, placebo-controlled physician-initiated study enrolled 54 patients with IC/BPS. The patients were assigned to ESWT (N = 24; 2000 shocks, frequency of 3 Hz, and maximum total energy flow density 0.25 mJ/mm ) once a week for 4 weeks at suprapubic bladder area or placebo (N = 25; shock wave setting without energy transmission). The primary endpoint was the average changes in O'Leary-Sant symptom scores (OSS) between baseline and 4 weeks after treatment. Secondary endpoints included visual analog scale (VAS, 0-10) for pain, the average changes of variables in a 3-day voiding diary, and global response assessment of patient satisfaction.

Results: At 4 weeks posttreatment, both groups were associated with a statistically significant decrease in OSS and VAS pain scale. However, there were no difference in mean change between ESWT vs placebo groups. A significantly higher proportion of patients on ESWT responded as improved in the VAS ≥ 3 vs placebo (P = .035). At 12 weeks posttreatment, improvement in the VAS ≥ 3 was 57.1% vs 19.0% (ESWT vs placebo; P = .011). The finding was associated with an improvement in frequency - 1.0 ± 2.3 vs 0.7 ± 3.2 (ESWT vs placebo; P = .065). No significant adverse events were found in either group.

Conclusions: A reduction in pain was discovered in this trial assessing ESWT in patients with IC/BPS but OSS, which was the primary outcome parameter, was not improved.
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http://dx.doi.org/10.1002/nau.24382DOI Listing
June 2020

Clinical guidelines for interstitial cystitis/bladder pain syndrome.

Int J Urol 2020 Jul 14;27(7):578-589. Epub 2020 Apr 14.

Department of Urology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

The clinical guidelines for interstitial cystitis and related symptomatic conditions were revised by updating our previous guidelines. The current guidelines define interstitial cystitis/bladder pain syndrome as a condition with chronic pelvic pain, pressure or discomfort perceived to be related to the urinary bladder accompanied by other urinary symptoms, such as persistent urge to void or urinary frequency in the absence of confusable diseases. The characteristic symptom complex is collectively referred as hypersensitive bladder symptoms. Interstitial cystitis/bladder pain syndrome is divided into Hunner-type interstitial cystitis and bladder pain syndrome; Hunner-type interstitial cystitis and bladder pain syndrome represent interstitial cystitis/bladder pain syndrome with Hunner lesions and interstitial cystitis/bladder pain syndrome without Hunner lesions, respectively. So-called non-Hunner-type interstitial cystitis featured by glomerulations or bladder bleeding after distension is included in bladder pain syndrome. The symptoms are virtually indistinguishable between Hunner-type interstitial cystitis and bladder pain syndrome; however, Hunner-type interstitial cystitis and bladder pain syndrome should be considered as a separate entity of disorder. Histopathology totally differs between Hunner-type interstitial cystitis and bladder pain syndrome; Hunner-type interstitial cystitis is associated with severe inflammation of the urinary bladder accompanied by lymphoplasmacytic infiltration and urothelial denudation, whereas bladder pain syndrome shows little pathological changes in the bladder. Pathophysiology would also differ between Hunner-type interstitial cystitis and bladder pain syndrome, involving interaction of multiple factors, such as inflammation, autoimmunity, infection, exogenous substances, urothelial dysfunction, neural hyperactivity and extrabladder disorders. The patients should be treated differently based on the diagnosis of Hunner-type interstitial cystitis or bladder pain syndrome, which requires cystoscopy to determine the presence or absence Hunner lesions. Clinical studies are to be designed to analyze outcomes separately for Hunner-type interstitial cystitis and bladder pain syndrome.
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http://dx.doi.org/10.1111/iju.14234DOI Listing
July 2020

Urine cytokines as biomarkers for diagnosing interstitial cystitis/bladder pain syndrome and mapping its clinical characteristics.

Am J Physiol Renal Physiol 2020 06 13;318(6):F1391-F1399. Epub 2020 Apr 13.

Department of Urology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and Tzu Chi University, Hualien, Taiwan.

The objective of the present study was to investigate the diagnostic values of urine cytokines in patients with interstitial cystitis/bladder pain syndrome (IC/BPS) and to identify their correlations with clinical characteristics. Urine samples were collected from 127 patients with IC/BPS [European Society for the Study of Interstitial Cystitis (ESSIC) types 1 and 2] and 28 controls. Commercially available multiplex immunoassays (MILLIPLEX map kits) were used to analyze 31 targeted cytokines. Cytokine levels between patients with IC/BPS and controls were analyzed using ANOVA. Receiver-operating characteristic curves of each cytokine to distinguish IC/BPS from controls were generated for calculation of the area under the curve. Patients with IC/BPS had urine cytokine profiles that differed from those of controls. Between patients with ESSIC type 1 and 2 IC/BPS, urine cytokine profiles were also different. Among cytokines with high diagnostic values (i.e., area under the curve > 0.7) with respect to distinguish patients with ESSIC type 2 IC/BPS from controls, regulated upon activation, normal T cell expressed and presumably secreted (RANTES), macrophage inflammatory protein (MIP)-1β, and IL-8 were of higher sensitivity, whereas macrophage chemoattractant protein (MCP)-1, chemokine (C-X-C motif) ligand 10 (CXCL10), and eotaxin-1 were of higher specificity. In multivariate logistic regression models controlling for age, sex, body mass index, and diabetes mellitus, the urine cytokines with high diagnostic values (MCP-1, RANTES, CXCL10, IL-7, and eotaxin-1) remained statistically significant in differentiating IC/BPS and controls. MCP-1, CXCL10, eotaxin-1, and RANTES were positively correlated with glomerulation grade and negatively correlated with maximal bladder capacity. In conclusion, patients with IC/BPS had urine cytokine profiles that clearly differed from those of controls. Urine cytokines might be useful as biomarkers for diagnosing IC/BPS and mapping its clinical characteristics.
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http://dx.doi.org/10.1152/ajprenal.00051.2020DOI Listing
June 2020
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