Effects of ß3 Agonists and Anticholinergic Drugs on Defecation in Patients With Overactive Bladder.

BACKGROUND/AIM: In clinical practice, constipation is one of the most frequent adverse events caused by drugs for overactive bladder (OAB). The occurrence of constipation greatly deteriorates the patient's quality of life. The aim of the study was to evaluate and compare the effects of three commonly used ß3 agonists and anticholinergic drugs on the defecation status in patients with OAB. PATIENTS AND METHODS: We retrospectively reviewed the defecation status in patients who received mirabegron, solifenacin, or fesoterodine for OAB. We evaluated changes in the (a) urological parameters using the OAB symptom score (OABSS) and (b) defecation status using the Bristol Stool Form Scale (BSFS) and constipation scoring system (CSS) following 12 weeks of drug administration. RESULTS: We analyzed data from 165 patients (mirabegron=56, fesoterodine=52, and solifenacin=57). The solifenacin group showed a significant decrease in BSFS (from 3.2±1.0 at baseline to 2.3±12 post-treatment) and an increase in hardened stools (p<0.001). Elimination worsened as assessed by almost all items, and the total modified CSS scores worsened significantly from 4.8±2.6 points at baseline to 8.O±4.8 points after 12 weeks of solifenacin treatment (p<0.001). The mirabegron group showed no changes in any of the CSS items. In the fesoterodine group, the CSS scores for "completeness" and "assistance" increased significantly after treatment (p<0.001 and p=0.013, respectively). CONCLUSION: All three drugs were effective for OAB. Mirabegron had almost no effect on constipation; fesoterodine, an anticholinergic drug, also had hardly any effect on defecation.

Pathological Significance and Prognostic Role of WWC1 in Upper Urinary Tract Urothelial Cancer.

BACKGROUND/AIM: WW and C2 domain-containing 1 (WWC1) protein is a suppressor of malignancies. However, there is no information on the pathological significance of WWC1 in upper urinary tract cancer (UTUC). PATIENTS AND METHODS: In this study, WWC1 immunoreactivity was investigated in 152 non-metastatic UTUC samples. The relationships between WWC1 expression and grade, pT stage, proliferative index (using an antibody to Ki-67), and the immunohistochemical expression of matrix metalloproteinase (MMP)-2 and -9 were evaluated. RESULTS: WWC1 expression was negatively associated with tumor grade and pT stage (p<0.001). Positive expression of WWC1 was a better predictor of the UTUC recurrence and subsequent metastasis, and the multivariate analysis showed that WWC1 expression was a significant predictor of subsequent metastasis (hazard ratio=0.29, p=0.020). WWC1 expression inversely correlated with the proliferative index (odds ratio=2.59, p=0.023) and expression of MMP9 (odds ratio=2.19, p=0.040) but not with MMP2 expression, by multivariate analyses. CONCLUSION: WWC1 expression was negatively associated with malignant aggressiveness via the suppression of cancer cell proliferation and MMP9 expression in patients with UTUC. This suggests WWC1 to be a useful predictor and novel therapeutic target in patients with UTUC.

Oral administration of E-type prostanoid (EP) 1 receptor antagonist suppresses carcinogenesis and development of prostate cancer via upregulation of apoptosis in an animal model.

Prostaglandin E2 plays an important role in carcinogenesis and malignant potential of prostate cancer (PC) cells by binding to its specific receptors, E-type prostanoid (EP) receptors. However, anti-carcinogenic effects of the EP receptor antagonist are unclear. In this study, we used a mouse model of PC. The mice were provided standard feed (control) or feed containing the EP1 receptor antagonist and were sacrificed at 10, 15, 30, and 52 weeks of age. Apoptosis was evaluated by immunohistochemical analysis using a cleaved caspase-3 assay. The incidence of cancer in the experimental group was significantly lower than that in the control group at 15, 30, and 52 weeks of age. The percentage of poorly differentiated PC cells was significantly lower in the experimental group than in the control group at 30 and 52 weeks of age. The percentage of apoptotic cells in the experimental group was significantly higher than that in the control group at 15, 30, and 52 weeks of age. These findings indicate that feeding with the addition of EP1 receptor antagonist delayed PC progression via the upregulation of apoptosis. We suggest that the EP1 receptor antagonist may be a novel chemopreventive agent for PC.

Pathological Roles of Prostaglandin E2-specific E-type Prostanoid Receptors in Hormone-sensitive and Castration-resistant Prostate Cancer.

BACKGROUND/AIM: Prostaglandin (PG) E2 mediates malignant aggressiveness by binding to four specific E-type prostanoid receptors (EP1R - 4R). This study aimed to clarify the pathological significance of EPRs in hormone-sensitive prostate cancer (HSPC) and castration-resistant prostate cancer (CRPC). MATERIALS AND METHODS: EP1R - 4R expression was examined in 102 HSPC and 27 CRPC specimens. The relationships between their expression and proliferation index (PI), apoptotic index (AI), and vascular endothelial growth factor (VEGF)-A expression were analyzed. RESULTS: EP4R expression in CRPC was significantly higher compared to that in HSPC, even in advanced disease (T3/4, N1, and/or M1). EP4R expression was significantly correlated with PI, AI, and VEGF-A expression in CRPC. Such significant relationships were not detected between EP1R - 3R and CRPC. CONCLUSION: EP4R expression in CRPC was significantly higher than that in HSPC and was associated with cancer cell proliferation, apoptosis, and pro-angiogenetic potential.

Rare case of penile fracture caused by an injury to the crus penis: Delayed repair using the transperineal approach.

INTRODUCTION: Penile fracture is a rare urologic emergency, and its surgical treatment is selected based on the damaged site of the penile corpus cavernosum. Penile fractures at the site of the crus penis are quite rare, and there is controversy regarding the preferred method of surgical repair. CASE PRESENTATION: A 25-year-old Asian man was injured when rolling over in bed. Magnetic resonance imaging showed a tear in the left crus of the penis with a hematoma. Delayed surgery was successfully performed using the transperineal approach. He did not experience pain, dysuria, or erectile dysfunction postoperatively. CONCLUSION: Delayed surgical repair using transperineal approach may be useful for penile fractures associated with penile crus injuries.