Investigative and Clinical Urology最新文献

Purpose: Mirabegron, the first-in-class beta-3 agonist, is the mainstay medication for overactive bladder (OAB). The aim of this study was to investigate the efficacy and safety of generic drugs of mirabegron (Mirabek^®) in adults diagnosed with OAB through a multicenter, prospective, non-interventional observational study.

Materials and methods: Adult patients with OAB prescribed Mirabek^® SR Tab. 50 mg for the first time were recruited from hospitals between September 2021 and September 2022. Participants underwent baseline registration followed by two follow-ups at 4- and 8-week intervals. Data on demographics, medical history, OAB symptoms, vital signs, medication administration, and adverse events were collected.

Results: Among 1,714 patients, Mirabek^® SR Tab. 50 mg effectively improved OAB symptoms over an 8-week treatment period, with significant differences in symptom improvement between baseline and both 4- and 8-week time points as well as between 4 weeks and 8 weeks. The incidence rate of adverse events was 0.70%; most cases were mild with no severe reactions.

Conclusions: This study demonstrated that Mirabek^®, a generic drug of betmiga, is an effective and safe treatment option for adults with OAB. Furthermore, the introduction of generic drug reduced the costs of prescription drugs and expanded the opportunity for many patients to access mirabegron.

Purpose: To investigate the therapeutic potential of eliminating insulin-like growth factor-binding protein 5 (IGFBP5) expression in improving erectile function in mice with cavernous nerve injury (CNI)-induced erectile dysfunction (ED).

Materials and methods: Eight-week-old male C57BL/6 mice were divided into four groups: a sham-operated group and three CNI-induced ED groups. The CNI-induced ED groups were treated with intracavernous injections 3 days before the CNI procedure. These injections included phosphate-buffered saline, scrambled control short hairpin RNA (shRNA), or shRNA targeting mouse IGFBP5 lentiviral particles. One week after CNI, erectile function was evaluated and the penile tissue was then harvested for histological examination and western blot analysis. Additionally, the major pelvic ganglia (MPG) and dorsal root ganglia (DRG) were cultured for ex vivo neurite outgrowth assays.

Results: Following CNI, IGFBP5 expression in the cavernous tissues significantly increased, reaching its peak at day 7. First, ablation of IGFBP5 expression promotes neurite sprouting in MPG and DRG when exposed to lipopolysaccharide. Second, ablating IGFBP5 expression in CNI-induced ED mice improved erectile function, likely owing to increased neurovascular contents, including endothelial cells, pericytes, and neuronal processes. Third, ablating IGFBP5 expression in CNI-induced ED mice promoted neurovascular regeneration by increasing cell proliferation, reducing apoptosis, and decreasing Reactive oxygen species production. Finally, western blot analysis demonstrated that IGFBP5 ablation attenuated the JNK/c-Jun signaling pathway, activated the PI3K/AKT signaling pathway, and increased vascular endothelial growth factor and neurotrophic factor expression.

Conclusions: Ablating IGFBP5 expression enhanced neurovascular regeneration and ultimately improved erectile function in CNI-induced ED mice.

Purpose: Recurrent cystitis, particularly common in women, substantially diminishes patient quality of life and represents a major clinical practice and public health burden. Increasing development of resistance to antibiotics has encouraged the search for alternative treatments. The benefits of a food supplement associating two Lactobacillus strains with proanthocyanidin A-rich cranberry and cinnamon extracts were evaluated in 80 women with a history of cystitis recurrence.

Materials and methods: Post-inclusion recurrence frequency was compared between women taking the investigated supplement daily for 6 months and non-supplemented women, based on patient-completed Acute Cystitis Symptom Score (ACSS) questionnaires.

Results: Two-thirds (64.9%) of supplemented women experienced no further episodes of cystitis during the first 6 months of the study compared to only one-third (31.6%) of non-supplemented women (p=0.004), the difference between the two groups being significant from 3 months onward. ACSS scores revealed significantly fewer and less severe urinary symptoms in supplemented women, as well as a significantly reduced impact of these symptoms on quality of life (p<0.0001).

Conclusions: The results shown by extensive data on women suffering from recurrent cystitis, collected over 8 months, indicate that taking the tested supplement daily for 6 months can provide significant benefits in terms of recurrence frequency, symptoms, and quality of life. The study is registered on the ClinicalTrials.gov site under the identifier NCT04987164.

Purpose: Developmentally regulated GTP-binding protein 2 (DRG2) regulates microtubule dynamics and G2/M arrest during docetaxel treatment. Poly ADP-ribose polymerase (PARP) acts as an important repair system for DNA damage caused by docetaxel treatment. This study investigated whether DRG2 expression affects response to PARP inhibitors (olaparib) using prostate cancer cell lines PC3, DU145, LNCaP-FGC, and LNCaP-LN3.

Materials and methods: The cell viability and DRG2 expression levels were assessed using colorimetric-based cell viability assay and western blot. Cells were transfected with DRG2 siRNA, and pcDNA6/V5-DRG2 was used to overexpress DRG2. Flow cytometry was applied for cell cycle assay and apoptosis analysis using the Annexing V cell death assay.

Results: The expression of DRG2 was highest in LNCaP-LN3 and lowest in DU145 cells. Expressions of p53 in PC3, DU145, and the two LNCaP cell lines were null-type, high-expression, and medium-expression, respectively. In PC3 (DRG2 high, p53 null) cells, docetaxel increased G2/M arrest without apoptosis; however, subsequent treatment with olaparib promoted apoptosis. In DU145 and LNCaP-FGC (DRG2 low), docetaxel increased sub-G1 but not G2/M arrest and induced apoptosis, whereas olaparib had no additional effect. In LNCaP-LN3 (DRG2 high, p53 wild-type), docetaxel increased sub-G1 and G2/M arrest, furthermore olaparib enhanced cell death. Docetaxel and olaparib combination treatment had a slight effect on DRG2 knockdown PC3, but increased apoptosis in DRG2-overexpressed DU145 cells.

Conclusions: DRG2 and p53 expressions play an important role in prostate cancer cell lines treated with docetaxel, and DRG2 levels can predict the response to PARP inhibitors.

Purpose: Although the mechanism underlying interstitial cystitis/bladder pain syndrome (IC/BPS) remains unclear, oxidative stress is suggested to be implicated in IC/BPS development. Sea buckthorn (SB; Hippophae rhamnoides L.) contains several compounds with antioxidant properties. In addition, intravesical application of hydrochloric acid (HCl) in rats induces histological changes similar to those observed in humans with IC. Therefore, the aim of this study was to evaluate the anti-inflammatory effects of SB in an HCl-induced rat cystitis model.

Materials and methods: Twenty 8-week-old female Sprague-Dawley rats were instilled with HCl in their bladders to create an IC/BPS model. The model rats were divided into three groups and orally administrated distilled water (control, n=4), concentrated SB (n=8), or pentosan polysulfate (PPS, n=8) daily. Pathologic inflammation grade (H&E staining), number of mast cells per square millimeter (toluidine blue staining), fibrotic changes (Masson's trichrome staining), and apoptosis (terminal deoxynucleotidyl transferase dUTP nick end labeling staining) of bladder tissue samples were compared among the groups.

Results: Compared to the control group, the SB and PPS groups showed reduced edema (5.25±0.96 vs. 2.25±0.46 vs. 2.50±0.54, p=0.004, p=0.005, respectively), number of mast cells (12.5±3.6 vs. 6.8±1.9 vs. 6.6±1.8, p=0.010, p=0.002, respectively), ratio of fibrotic submucosal tissue (63.9%±7.0% vs. 43.6%±9.9% vs. 40.5%±5.2%, p<0.001, p<0.001, respectively), and ratio of apoptotic nucleus (40.7%±11.7% vs. 7.7%±6.5% vs. 5.1%±4.9%, p<0.001, p<0.001, respectively).

Conclusions: SB exhibited anti-inflammatory effects comparable to those of PPS in the HCl-induced chemical cystitis model.

Purpose: This study aims to develop and implement an economic evaluation using a micro-costing approach to provide a precise and transparent analysis of the direct costs of cystoscopic procedures in Korean hospitals. The study seeks to identify key cost components and evaluate whether current reimbursement rates accurately reflect these direct costs.

Materials and methods: Significant variations in cost items were identified across different studies. An economic evaluation was conducted using a micro-costing methodology for the cost analysis of cystoscopic procedures, developed through literature review, data collection from studies, and expert consultations.

Results: Gangnam Severance Hospital (GSH) performed 2,188 cystoscopic procedures, including 1,847 cystoscopies and 341 JJ stent removals, with average costs of $100.8 and $110.6, respectively. At National Health Insurance Service Ilsan Hospital (NHIMC), 1,463 procedures were performed, including 1,167 cystoscopies and 296 JJ stent removals, with average costs of $119.2 and $125.3. Cystoscopy costs at GSH were driven by reprocessing ($45.8, 45.4%) and equipment ($33.1, 32.9%), while NHIMC's were $52.5 (44.0%) for equipment and $48.7 (40.8%) for reprocessing. Both hospitals incurred financial losses, with NHIS (National Health Insurance Service) covering only about 71.7% and 60.6% of costs for cystoscopy, and 71.0% and 62.7% for JJ stent removal.

Conclusions: The significant discrepancy between HIRA (Health Insurance Review & Assessment Service)'s estimated costs and those identified here suggests that current fees for cystoscopic procedures may be underestimated and require reassessment. Given the results, reevaluating these rates is essential to ensure fair compensation for healthcare providers and to deliver optimal patient care.

Purpose: To create a computer-aided prediction (CAP) system to predict Wilms tumor (WT) responsiveness to preoperative chemotherapy (PC) using pre-therapy contrast-enhanced computed tomography (CECT).

Materials and methods: A single-center database was reviewed for children <18 years diagnosed with WT and received PC between 2001 and 2021. Patients were excluded if pre- and post-PC CECT were not retrievable. According to the Response Evaluation Criteria in Solid Tumors criteria, volumetric response was considered favorable if PC resulted in ≥30% tumor volume reduction. Histological response was considered favorable if post-nephrectomy specimens had ≥66% necrosis. Four steps were used to create the prediction model: tumor delineation; extraction of shape, texture and functionality-based features; integration of the extracted features and selection of the prediction model with the highest diagnostic performance. K-fold cross-validation allowed the presentation of all data in the training and testing phases.

Results: A total of 63 tumors in 54 patients were used to train and test the prediction model. Patients were treated with 4-8 weeks of vincristine/actinomycin-D combination. Favorable volumetric and histologic responses were achieved in 46 tumors (73.0%) and 38 tumors (60.3%), respectively. Among machine learning classifiers, support vector machine had the best diagnostic performance with an accuracy, sensitivity, and specificity of 95.24%, 95.65%, and 94.12% for volumetric and 84.13%, 89.47%, 88% for histologic response prediction.

Conclusions: Based on pre-therapy CECT, CAP systems can help identify WT that are less likely to respond to PC with excellent accuracy. These tumors can be offered upfront surgery, avoiding the cons of PC.

Purpose: To describe the incidence and mortality of upper tract urothelial carcinoma (UTUC) from 2002-2020 using data from the Korean National Health Insurance Service, which contains data from the entire Korean population.

Materials and methods: Reimbursement records for 43,255 patients diagnosed with primary UTUC (according to the International Classification of Disease 10th revision code C65 and C66) between 2002-2020 were retrieved. The study period was split into four: period I (2002-2005), period II (2006-2010), period III (2011-2015), and period IV (2016-2020). Trends were quantified by calculating the annual percentage change (APC). Mortality data were obtained from the Statistics Korea.

Results: From 2002-2020, the incidence of UTUC in Korea increased gradually from 9.34 to 11.40 per 100,000 person-years. Although there was a male predominance, the male to female ratio did not change significantly over time; however, age at the time of diagnosis, the comorbidity index, and the proportion of patients undergoing open/laparoscopic surgery increased significantly over time. There was a modest improvement in 5-year survival (both all cause- and cancer-specific) over the study period. Multivariate analysis identified age at diagnosis, sex, the comorbidity index, and open/laparoscopic surgery as being associated with survival.

Conclusions: Between 2002 and 2020, the incidence of UTUC in Korea showed a general upward trend; however, survival outcomes have improved. These representative datasets from the Korean population might provide crucial information that enables clinicians to better understand of the epidemiology of UTUC in Korea.

The global increase in urolithiasis prevalence has led to a shift towards minimally invasive procedures, such as retrograde intrarenal surgery, supported by advancements in laser technologies for lithotripsy. Pulsed lasers, particularly the holmium YAG and the newer thulium fiber laser, have significantly transformed the management of upper urinary tract stones. However, the use of high-power lasers in these procedures introduces risks of heat-related injury. Laser lithotripsy works through photothermal and photomechanical effects to fragment stones, but up to 96% of the laser energy is converted into heat, increasing the risk of thermal damage to the surrounding urothelial mucosa. Studies show that even at low-power settings, intrarenal temperatures can exceed the threshold for cellular injury, particularly in confined spaces like the ureter. This narrative review explores strategies to mitigate thermal injury, including optimizing laser settings, improving irrigation flow rates, and incorporating novel methods such as cold irrigation, controlling outflow resistance, and using suction. Understanding these approaches is crucial to enhancing patient safety during high-power laser lithotripsy procedures.

Purpose: To evaluate the feasibility of robot-assisted ureteral reconstruction as a minimally invasive alternative to open surgery for managing ureteric complications in transplanted kidneys.

Materials and methods: From January 2020 to December 2023, robot-assisted ureteral reconstruction was performed on fifteen kidney transplant patients with vesicoureteral reflux (VUR) or ureteral stricture who had previously failed endoscopic treatments.

Results: Twelve females and three males, with a mean age of 48.6±6.6 years, were included in the study. Nine patients (60.0%) underwent surgery due to VUR (grade III or higher) of the transplanted kidney, and six patients (40.0%) had transplanted ureteral strictures. Postoperative voiding cystourethrogram (VCUG) was performed at 3.2±1.6 months. Seven patients (77.8%) became VUR-free, while two patients (22.2%) had VUR regression from grade IV to I. All six patients who underwent reconstruction due to anastomosis site stricture became stenosis-free without the need for an indwelling ureteral catheter. In cases where the ureter was too short for reimplantation, a Boari flap or end-to-end anastomosis with the native ureter was performed. The mean hospital stay was 5.9±4.5 days. The urethral catheter was removed after 15.1±5.4 days, and the ureteral catheter was removed after 4.9±1.5 weeks. The mean follow-up period was 23.9±6.8 months, with no additional interventions required after surgery. No complications above Clavien-Dindo grade I were recorded.

Conclusions: Robotic ureteral reconstruction is technically feasible and offers an effective, minimally invasive treatment for ureteric complications in kidney transplant patients, serving as an alternative to open surgery.