A Randomized, Double-Blind, Placebo-Controlled, Bridging Study to Evaluate the Efficacy and Safety of Vibegron in Treating Korean Patients With Overactive Bladder / 대한배뇨장애요실금학회지

Purpose@#Vibegron, a novel, potent β3 agonist, has been approved for clinical use in overactive bladder (OAB) treatment in Japan and the Unites States. We performed a bridging study to investigate the efficacy and safety of a daily 50-mg vibegron (code name JLP-2002) dose in Korean patients with OAB. @*Methods@#A multicenter, randomized, double-blind, placebo-controlled study was conducted from September 2020 to August 2021. Adult patients with OAB with a symptom duration of more than 6 months entered a 2-week placebo run-in phase. Eligibility was assessed at the end of this phase and selected patients entered a double-blind treatment phase after 1:1 randomization to either the placebo or vibegron (50 mg) group. The study drug was administered once daily for 12 weeks and follow-up visits were scheduled at weeks 4, 8, and 12. The primary endpoint was the change in mean daily micturition at the end of treatment. The secondary endpoints included changes in OAB symptoms (daily micturition, nocturia, urgency, urgency incontinence, and incontinence episodes, and mean voided volume per micturition) and safety. A constrained longitudinal data model was used for statistical analysis. @*Results@#Patients who took daily vibegron had significant improvements over the placebo group in both primary and secondary endpoints, except for daily nocturia episodes. The proportions of patients with normalized micturition and resolution of urgency incontinence and incontinence episodes were significantly higher in vibegron group than in the placebo. Vibegron also improved the patients’ quality of life with higher satisfaction rates. The incidence of adverse events in the vibegron and placebo groups was similar with no serious, unexpected adverse drug reactions. No abnormality in electrocardiographs was observed as well as no significant increase in postvoid residual volume. @*Conclusions@#Once daily vibegron (50 mg) for 12 weeks was effective, safe, and well-tolerated in Korean patients with OAB.

Efficacy and Safety of DA-8010, a Novel M3 Antagonist, in Patients With Overactive Bladder: A Randomized, Double-Blind Phase 2 Study / 대한배뇨장애요실금학회지

Purpose@#DA-8010 is a novel muscarinic M3 receptor antagonist with significant selectivity for bladder over salivary gland in preclinical studies. We evaluated the clinical efficacy and safety of DA-8010 in overactive bladder (OAB) patients. @*Methods@#This phase 2, randomized, double-blind, parallel-group, active reference- and placebo-controlled trial was conducted at 12 centers in South Korea (NCT03566134). Patients aged ≥19 years with OAB symptoms for ≥3 months were enrolled. Three hundred six patients (30.07% male) were randomized to 12 weeks of treatment among 4 groups; 2 experimental groups (DA-8010 2.5 or 5 mg), an active reference group (solifenacin 5 mg), and a placebo group. The change from the baseline of (=∆) 24-hour frequency at 12 weeks (primary endpoint), episodes of urgency, overall/urgency urinary incontinence, average/ maximum voided volume, nocturia, and patients’ subjective responses were analyzed. @*Results@#In the full analysis set, the mean (standard deviation) [median] values for ∆ 24-hour frequency at 12 weeks were -1.01 (2.44) [-1.33] for placebo, -1.22 (2.05) [-1.33] for DA-8010 2.5 mg, and -1.67 (2.25) [-1.67] for DA-8010 5 mg; DA-8010 5 mg showed a significant decrease compared with placebo (P=0.0413). At 4 and 8 weeks, both DA-8010 2.5 mg (P=0.0391 at 4 weeks, P=0.0335 at 8 weeks) and DA-8010 5 mg (P=0.0001 at 4 weeks, P=0.0210 at 8 weeks) showed significant decrease in ∆ 24-hour frequency compared with placebo. DA-8010 5 mg achieved a significant decrease in ∆ number of urgency episodes, compared with placebo at 4 (P=0.0278) and 8 (P=0.0092) weeks. Adverse drug reactions (ADRs) were observed in 3.95% of placebo, 6.67% of DA-8010 2.5 mg, 18.42% of DA-8010 5 mg, and 17.33% of solifenacin 5 mg groups. No serious ADRs were observed in any patient. @*Conclusions@#Both DA-8010 2.5 mg and 5 mg showed therapeutic efficacy for OAB without serious ADRs. Therefore, both dosages of DA-8010 can advance to a subsequent large-scale phase 3 trial.

Pathophysiology and Management of Long-term Complications After Transvaginal Urethral Diverticulectomy / 대한배뇨장애요실금학회지

Female urethral diverticulum (UD) is a rare and benign condition that presents as an epithelium-lined outpouching of the urethra. It has various symptoms, of which incontinence in the form of postmicturition dribble is the most common. The gold standard for the diagnosis of UD is magnetic resonance imaging, and the treatment of choice is transvaginal diverticulectomy. Despite the high success rate of transvaginal diverticulectomy, postoperative complications such as de novo stress urinary incontinence (SUI), recurrence, urethrovaginal fistula, recurrent urinary tract infections, newly-onset urgency, and urethral stricture can occur. De novo SUI is thought to result from weakening of the anatomical support of the urethra and bladder neck or damage to the urethral sphincter mechanism during diverticulectomy. It can be managed conservatively or may require surgical treatment such as a pubovaginal sling, Burch colposuspension, or urethral bulking agent injection. Concomitant SUI can be managed by concurrent or staged anti-incontinence surgery. Recurrent UD may be a newly formed diverticulum or the result of a remnant diverticulum from the previous diverticulectomy. In cases of recurrent UD requiring surgical repair, placing a rectus fascia pubovaginal sling may be an effective method to improve the surgical outcome. Urethrovaginal fistula is a rare, but devastating complication after urethral diverticulectomy; applying a Martius flap during fistula repair may improve the likelihood of a successful result. Malignancies in UD are rarely reported, and anterior pelvic exenteration is the recommended management in such cases.

Pathophysiology and Management of Long-term Complications After Transvaginal Urethral Diverticulectomy / 대한배뇨장애요실금학회지

Female urethral diverticulum (UD) is a rare and benign condition that presents as an epithelium-lined outpouching of the urethra. It has various symptoms, of which incontinence in the form of postmicturition dribble is the most common. The gold standard for the diagnosis of UD is magnetic resonance imaging, and the treatment of choice is transvaginal diverticulectomy. Despite the high success rate of transvaginal diverticulectomy, postoperative complications such as de novo stress urinary incontinence (SUI), recurrence, urethrovaginal fistula, recurrent urinary tract infections, newly-onset urgency, and urethral stricture can occur. De novo SUI is thought to result from weakening of the anatomical support of the urethra and bladder neck or damage to the urethral sphincter mechanism during diverticulectomy. It can be managed conservatively or may require surgical treatment such as a pubovaginal sling, Burch colposuspension, or urethral bulking agent injection. Concomitant SUI can be managed by concurrent or staged anti-incontinence surgery. Recurrent UD may be a newly formed diverticulum or the result of a remnant diverticulum from the previous diverticulectomy. In cases of recurrent UD requiring surgical repair, placing a rectus fascia pubovaginal sling may be an effective method to improve the surgical outcome. Urethrovaginal fistula is a rare, but devastating complication after urethral diverticulectomy; applying a Martius flap during fistula repair may improve the likelihood of a successful result. Malignancies in UD are rarely reported, and anterior pelvic exenteration is the recommended management in such cases.

Reconstruction of Penile and Long Urethral Defect Using a Groin Flap

Urethral reconstruction is a problematic issue, thus its management can be challenging. Different methods using various materials were introduced for urethral reconstruction. The authors have made some changes in the groin flap surgery, affording more successful urethral reconstruction for defects of long urethra and penile soft tissue. A 45-year-old male requested both functional and cosmetic reconstruction of his defected penis, caused by an iatrogenic urethral injury and chronic infection following removal of paraffin self-injected on the penile shaft. The defect affected the full length of the penile urethra, corpus spongiosum, and prepuce. A groin flap was designed, measuring 28×10 cm. The most distal flap was utilized for the construction of the luminal surface of the neourethra; relaxed length measuring 8 cm, and the lumen wide enough. Competent external meatus and neourethra was confirmed by retrograde cystogram and the patient voided with sufficient urine caliber up to 2 years follow-up. This operative technique has advantages. Donor sites have non-hair bearing skin for the neourethra and minimal or almost not-recognizable donor site morbidity. After surgery, the patient was relieved from voiding difficulties combined with psychological stress. The author would like to introduce a unique approach for the urethral and ventral phalloplasty using the groin flap.

Evaluation of holmium laser for transurethral deroofing of severe and multiloculated prostatic abscesses

PURPOSE: Our objective was to evaluate the use of a holmium laser for transurethral deroofing of a prostatic abscess in patients with severe and multiloculated prostatic abscesses. MATERIALS AND METHODS: From January 2011 to April 2014, eight patients who were diagnosed with prostatic abscesses and who underwent transurethral holmium laser deroofing at Pusan National University Hospital were retrospectively reviewed. RESULTS: Multiloculated or multifocal abscess cavities were found on the preoperative computed tomography (CT) scan in all eight patients. All patients who underwent transurethral holmium laser deroofing of a prostatic abscess had successful outcomes, without the need for secondary surgery. Of the eight patients, seven underwent holmium laser enucleation of the prostate (HoLEP) for the removal of residual adenoma. Markedly reduced multiloculated abscess cavities were found in the follow-up CT in all patients. No prostatic abscess recurrence was found. Transient stress urinary incontinence was observed in three patients. The stress urinary incontinence subsided within 3 weeks in two patients and improved with conservative management within 2 months in the remaining patient. CONCLUSIONS: Transurethral holmium laser deroofing of prostatic abscesses ensures successful drainage of the entire abscess cavity. Because we resolved the predisposing conditions of prostatic abscess, such as bladder outlet obstruction and prostatic calcification, by simultaneously conducting HoLEP, there was no recurrence of the prostatic abscesses after surgery. We recommend our method in patients requiring transurethral drainage.

Laparoscopic Removal of a Broken Sewing Needle in a Patient with Irritative Bladder Symptoms / 대한배뇨장애요실금학회지

A foreign body near the bladder is rare. Although foreign bodies in the bladder can be easily found and removed by endoscopic transurethral removal, extravesical foreign bodies may require the use of an open or laparoscopic procedure. Here, we report a case of a patient complaining of frequency and urgency in whom an extravesical sewing needle was successfully removed by a laparoscopic approach. A 4.5 cm rusty sewing needle was found between the bladder and the left external iliac vessels and was removed through a 5 mm trocar port by use of endo forceps with no complications.

Survival Rates and Related Factors in Men with Hormone-Refractory Prostate Cancer

PURPOSE: We evaluated survival rate in patients with hormone-refractory prostate cancer (HRPC) and the clinical factors that influenced survival rate and time. MATERIALS AND METHODS: The medical records of 96 patients who had HRPC and were not treated with chemotherapy from 2000 to 2008 were reviewed. We evaluated the survival rates at the 1st, 3rd, and 5th year by using Kaplan-Meier survival curves. We also evaluated survival differences according to clinical variables (clinical T stage, Gleason score, nadir prostate-specific antigen [PSA], PSA doubling time, and PSA velocity) by using the log-rank test and the relations between survival rates and these variables by using Cox proportional hazards models. RESULTS: The mean age of the patients was 67.8+/-7.5 years and the mean follow-up period was 23.3+/-13.7 months. Cancer-specific survival rates at the 1st, 3rd, and 5th year were 57.8%, 16.8%, and 10.1%, respectively, and survival differences were significantly related to nadir PSA (p=0.002) and PSA velocity (p=0.019). In the univariate analysis, nadir PSA (p=0.004) and PSA velocity (p=0.024) were related to survival rate, but only nadir PSA remained as a significant variable for survival rate in patients with HRPC in the multivariate analysis (p=0.044). CONCLUSIONS: Cancer-specific survival rates in patients with HRPC at the 1st, 3rd, and 5th year were 57.8%, 16.8%, and 10.1%, respectively, and they were related to nadir PSA. These results may be useful in determining a therapeutic approach in patients with HRPC.

Effect of a Prolyl 4-hydroxylase Inhibitor on Bladder Fibrosis in a Rat Model of Partial Bladder Outlet Obstruction / 대한비뇨기과학회지

PURPOSE: This study was performed to investigate prolyl 4-hydroxylase (P4H) expression changes and an inhibitor-mediated effect on bladder fibrosis in rats with partial bladder outlet obstruction(PBOO). MATERIALS AND METHODS: Twenty female Sprague-Dawley rats were divided into four groups. Group A(n=5) consisted of rats with PBOO treated with 2mg/kg P4H inhibitor, group B(n=5) consisted of rats with PBOO treated with 20mg/kg P4H inhibitor, group C(n=5) consisted of rats with PBOO treated with normal saline and group D(n=5) consisted of normal control animals. After PBOO for two weeks in the A, B, and C group rats, each amount of inhibitor was administered orally once a day for two weeks. After a total of four weeks, the bladders from all of the group rats were removed and evaluated. RESULTS: The muscle thickness calculated from Masson's trichrome staining was 0.85+/-0.22mm, 1.06+/-0.15mm, 1.19+/-0.30 and 0.49+/-0.10mm for group A, B, C, and D rats, respectively. The overall P4H expression was 65.7+/-15.2%, 13.4+/-8.4%, 73.8+/-15.5% and 10.0+/-10.0% for group A, B, C, and D rats, respectively. The overall collagen I protein expression was 16.9+/-18.0%, 17.0+/-24.1%, 30.5+/-13.4% and 8.8+/-8.7% for group A, B, C, and D rats, respectively. The overall collagen III protein expression was 9.6+/-4.2%, 8.8+/-2.9%, 12.5+/-10.6% and 7.5+/-3.5% for group A, B, C, and D rats, respectively. These results showed that PBOO led to increased muscle thickness and to an increased expression of P4H, collagen I and III protein, as compared with the group D control animals. Muscle thickness and expression of P4H, collagen I and III protein was decreased in rats treated with the P4H inhibitor-treated groups decreased as compared with rats in group C (saline-treated animals). The ratio of collagen I/III was 1.8, 1.9, 2.4 and 1.2 in group A, B, C, and D rats, respectively. CONCLUSIONS:Our results suggest that the P4H inhibitor may be potentially utilized to reduce bladder fibrosis caused by PBOO.

Outcomes of the Transobturator Tape Procedure for Elderly Women above 60 Years Old with Stress Urinary Incontinence

PUROPOSE: This study was aimed at evaluating the clinical efficacy, satisfaction and complication of patients with transobturator tape (TOT) operation for the elderly women suffering with stress urinary incontinence (SUI). MATERIAL AND METHODS: 58 women with stress urinary incontinence who underwent TOT procedure between March 2004 and June 2006 were included in this study. To assess whether outcome was influenced by the patient's age, the patients were divided into two age groups: women aged 60 years and older (n=22) and women aged less than 60 years (n=36). Preoperatively, the patients were evaluated with history taking, a physical examination, a one-hour pad test, uroflowmetry and urodynamic study. The procedure was carried out using a previously established method under local anesthesia. The post-operative symptoms and patient satisfaction were assessed by questionnaire. RESULTS: There was no significant difference between the 2 groups in terms of the success rate: cure (71.4% vs. 78.2%, p=0.746), improved (19.1% vs. 9.3%, p=0.415), and same as preoperation (9.5% vs. 12.5%, p=1.000) for above 60 years old women and less than 60 years old women, respectively. In addition, the patient satisfaction rate was not different significantly between 2 groups. De novo urge symptoms were observed in 2 women aged 60 years and older. The intraoperative complications were not found. CONCLUSIONS: TOT procedure in elderly women with SUI offers high success rate and satisfaction for operation. TOT should play a significant role in treating them, due to its safety and availability. However, we do not know how long the improvement of voiding symptoms will last, and so additional longer term follow-up should be done.

Therapeutic Effect of Rebamipide in Infertile Men with Oxidative Stress / 대한비뇨기과학회지

PURPOSE: This study was performed to investigate whether rebamipide is useful in the treatment of male infertility due to oxidative damage. MATERIALS AND METHODS: 50 infertile males with elevated reactive oxygen species (ROS) in their semen were enrolled. All patients were given an oral daily dose of 900mg rebamipide for at least 3 months. The concentrations of rebamipide and ROS, and the levels of lipid peroxidation, sperm motility, vitality and fertilizing capacity were measured by a high-performance liquid chromatography (HPLC) fluorescent method, chemiluminescence, the thiobarbituric acid method, a computer assisted semen analyzer, eosin-nigrosin staining and hypo-osmotic swelling test, respectively. Additionally, the clinical outcomes, including pregnancy and delivery, were observed at the gynecology outpatient and IVF clinics. RESULTS: The rebamipide concentration in semen after medication was 220.77+/-327.84ng/ml (SD), with a large deviation, but this was higher than the level found in the serum, which was 126+/-76ng/ml (SD). The levels of seminal ROS and lipid peroxidation were significantly decreased according to the duration of treatment (p<0.05). The sperm vitality and fertilizing capacity were also significantly improved at 2-3 months post treatment (p<0.05). Out of the 41 cases with trial pregnancies, 20 (48.8%) became pregnant, consisting of childbirth, miscarriage or ongoing in 17, 2 and 1 case, respectively. Side effects were observed in only 1 case (2%) with self-limits. CONCLUSIONS: These results suggest that rebamipide is an effective free radical scavenger, which may be useful as an oral antioxidant in patients with male infertility due to oxidative damage caused by high tissue affinity to the male accessory organ, antioxidant effect and the improving effect of seminal parameters.

Free radical scavenger effect of rebamipide in sperm processing and cryopreservation / 亚洲男科学杂志(英文版)

<p><b>AIM</b>To study the effect of rebamipide added to semen samples and cryoprotectant on reactive oxygen species (ROS) production.</p><p><b>METHODS</b>Semen samples from 30 fertile and healthy volunteers were collected by masturbation after 2 days approximately 3 days of abstinence. After liquefaction, the specimens were diluted with sperm wash media to a uniform density of 20 x 10(6)/mL. Rebamipide was added to semen samples and cryoprotectant to a final concentration of 10 micromol/L, 30 micromol/L, 100 micromol/L or 300 micromol/L. Specimens were incubated at 37 degree C in a 0.5 % CO(2) incubator for 1 h or cryopreserved at -196 degree C LN(2) for 3 days. The sperm motility and viability and the levels of ROS and lipid peroxidation of sperm membrance were assessed before and after incubation and cryopreservation by means of computer assisted semen analyzer, eosin-nigrosin stain, chemiluminescence and thiobarbituric acid assay, respectively.</p><p><b>RESULTS</b>The sperm motility was significantly increased after incubation with 100 micromol/L and 300 micromol/L rebamipide (P<0.05). After cryopreservation, the sperm motility was significantly decreased in all concentrations (P<0.05), but the decrease was less with 100 micromol/L and 300 micromol/L rebamipide than that with other concentrations. The sperm viability showed no significant difference before and after incubation (P>0.05). The levels of ROS and lipid peroxidation in semen were significantly decreased in proportion to the concentrations of rebamipide both after incubation and cryopreservation (P<0.05).</p><p><b>CONCLUSION</b>Rebamipide is an effective free radical scavenger in semen in vitro.</p>

Malignant Rhabdoid Tumor of Kidney in Infant / 대한비뇨기과학회지

A malignant rhabdoid tumor of the kidney, an uncommon renal tumor of children, is one of the most lethal neoplasms in early life. It was considered to be a sarcomatous variant of Wilms' tumor; however, further studies of its histological and clinical characteristics have proven it to be a distinct entity. We report a case of malignant rhabdoid tumor of the kidney in a 3-month-old girl, with a left abdominal palpable mass that had developed over the previous month. A left radical nephrectomy, with a regional lymph node biopsy, and 4 cycles of adjuvant chemotherapy, was performed. On the 45th postoperative day, multiple metastasises in liver, contralateral kidney and left upper lobe of lung were found. The patient expired 2 months after the operation.

Outcome of Tubularized Incised Plate (TIP) Urethroplasty for Hypospadias Reoperation / 대한비뇨기과학회지

PURPOSE: We evaluated the outcomes of a tubularized incised plate (TIP) urethroplasty on reoperative hypospadias repairs. MATERIALS AND METHODS: A total of 17 reoperative hypospadias repairs were performed. We retrospectively reviewed the medical records of all patients, which included the level of meatus, technique of repair, age at surgery and complications. The mean patient age and number of prior repairs were 6.3 years and 1.6 times, respectively. Before the reoperation the level of meatus was the anterior type in 2, the middle type in 7 and the posterior type in 8 patients. RESULTS: The follow-up periods ranged from 1 to 35 months (average 18.5 months). The success rates, according to the type of hypospadias, were 2/2 (100%) in the anterior type, 4/7 (57.1%) in the middle type and 6/8 (75%) in the posterior type (70.6% overall success rate). The patients had undergone TIP repairs (5), Denis-Brown-Crawford flaps (2), Thiersch-Duplay tubes (2), Mathieu repairs (1), onlay island flaps (1), transverse prepubital island flaps (TPIF) (1), a TPIF and Mathieu repair (1) and Flip-flaps (1), with an unknown (3) as the primary procedures. An urethrocutaneous fistula occurred in 3 patients, and 1 each of meatal stenosis and a glans repair breakdown also occurred (29.4% overall complication rate). Fistula repairs were successfully performed 7, 9 and 10 months later in the 3 patients. The patient with meatal stenosis was treated with simple dilatation. CONCLUSIONS: This preliminary experience provides further proof of the versatility of TIP urethroplasty, showing its potential use following a reoperative hypospadias repair.