Association between the presence of bacteria in prostate tissue and histopathology in biopsies from men not complaining of lower urinary tract symptoms

Objective: To investigate the presence of bacteria in prostate tissue, and relationships between the bacteria and histopathological findings. Methods: Samples were collected from prostate biopsy patients with no obvious lower urinary tract symptoms (LUTS). Detection and identification of bacterial species in the prostate tissues were performed with PCR for 16SrDNA and DNA sequencing. Histopathology was also evaluated. LUTS and lower urinary tract function were assessed by questionnaires, uroflowmetry, and ultrasonography. Results: DNA was extracted from 97 prostate biopsies, with 5 bacterial species detected among samples from 7 patients (7.2%). The stroma-to-gland ratio in the prostate tissues from patients with bacteria was lower than in those without bacteria (p < 0.01). Glandular epithelial hyperplasia was also identified in the prostates harboring bacteria. International Prostate Symptom Score (IPSS), IPSS-quality of life (IPSS-QOL), Overactive Bladder Symptom Score (OABSS), maximum flow rate, urine volume by uroflowmetry, and post-voided residual urine were not significantly different when comparing patients with and without bacteria in their prostate samples. Conclusions: The present study demonstrated that 7.2% of men without obvious LUTS had bacteria in their prostate tissues. The presence of such bacteria might induce glandular hyperplasia and contribute to pathological changes in the early stages of benign prostate enlargement before affecting LUTS

<span style="font-variant: small-caps">l</span>-Theanine Protects Bladder Function by Suppressing Chronic Sympathetic Hyperactivity in Spontaneously Hypertensive Rat

Chronic sympathetic hyperactivity is known to affect metabolism and cause various organ damage including bladder dysfunction. In this study, we evaluated whether l-theanine, a major amino acid found in green tea, ameliorates bladder dysfunction induced by chronic sympathetic hyperactivity as a dietary component for daily consumption. Spontaneously hypertensive rats (SHRs), as an animal model of bladder dysfunction, were divided into SHR–water and SHR–theanine groups. After 6 weeks of oral administration, the sympathetic nervous system, bladder function, and oxidative stress of bladder tissue were evaluated. The mean blood pressure, serum noradrenaline level, and media-to-lumen ratio of small arteries in the suburothelium were significantly lower in the SHR–theanine than in the SHR–water group. Micturition interval was significantly longer, and bladder capacity was significantly higher in the SHR–theanine than in the SHR–water group. Bladder strip contractility was also higher in the SHR–theanine than in the SHR–water group. Western blotting of bladder showed that expression of malondialdehyde was significantly lower in the SHR–theanine than in the SHR–water group. These results suggested that orally administered l-theanine may contribute at least partly to the prevention of bladder dysfunctions by inhibiting chronic sympathetic hyperactivity and protecting bladder contractility

Role of puboperinealis and rectourethralis muscles as a urethral support system to maintain urinary continence after robot-assisted radical prostatectomy

Abstract The present study investigated the role of a urethral support system to maintain urinary continence after robot-assisted radical prostatectomy (RARP), with a focus on pelvic floor muscles, such as the puboperinealis muscle (PPM) and rectourethralis muscle (RUM). Finally, 323 patients who underwent RARP were analyzed in this study. All patients performed a one-hour pad test 1, 3, 6, 9, and 12 months after RARP to assess urinary incontinence and MRI before and 9 months after RARP to evaluate the pelvic anatomical structure. The preoperative cross-sectional area of PPM (2.21 ± 0.69 cm2) was significantly reduced by 19% after RARP (1.79 ± 0.60 cm2; p < 0.01). Positive correlations were observed between the amount of urinary leakage according to the 1-h pad test 1, 3, 6, 9, and 12 months after RARP and the change in the cross-sectional area of PPM by RARP (p < 0.01, < 0.001, < 0.001, < 0.001, and < 0.001, respectively). A positive correlation was also noted between the amount of urinary leakage 6 and 12 months after RARP and the preoperative RUM diameter (p < 0.05). The amount of urinary leakage 1, 3, 6, 9, and 12 months after RARP negatively correlated with the change in the antero-posterior diameter of the membranous urethra (MU diameter) from the static to dynamic phases during the Valsalva maneuver by cine MRI. Furthermore, the change in the MU diameter negatively correlated with the change in the cross-sectional area of PPM (p < 0.05). PPM and RUM play significant roles as a supportive mechanism to maintain urinary continence by functioning as a urethral support

Involvement of Mast-Cell-Tryptase- and Protease-Activated Receptor 2—Mediated Signaling and Urothelial Barrier Dysfunction with Reduced Uroplakin II Expression in Bladder Hyperactivity Induced by Chronic Bladder Ischemia in the Rat

We aimed to investigate the relationship between mast cell (MC) infiltration into the bladder with urothelial barrier dysfunction and bladder hyperactivity in a chronic bladder ischemia (CBI) rat model. We compared CBI rats (CBI group; n = 10) with normal rats (control group; n = 10). We measured the expression of mast cell tryptase (MCT) and protease-activated receptor 2 (PAR2), which are correlated with C fiber activation via MCT, and Uroplakins (UP Ia, Ib, II and III), which are critical to urothelial barrier function, via Western blotting. The effects of FSLLRY-NH2, a PAR2 antagonist, administered intravenously, on the bladder function of CBI rats were evaluated with a cystometrogram. In the CBI group, the MC number in the bladder was significantly greater (p = 0.03), and the expression of MCT (p = 0.02) and PAR2 (p = 0.02) was significantly increased compared to that of the control group. The 10 μg/kg FSLLRY-NH2 injection significantly increased the micturition interval of CBI rats (p = 0.03). The percentage of UP-II-positive cells on the urothelium with immunohistochemical staining was significantly lower in the CBI group than in the control group (p < 0.01). Chronic ischemia induces urothelial barrier dysfunction via impairing UP II, consequently inducing MC infiltration into the bladder wall and increased PAR2 expression. PAR2 activation by MCT may contribute to bladder hyperactivity

Evaluation of testicular stiffness in boys with unilateral cryptorchidism after orchiopexy by ultrasound strain elastography

Purpose: We assessed the stiffness of unilateral undescended testes after orchiopexy, examining its value in tracking histopathological changes and fertility potential during postoperative follow-up. Additionally, we explored the optimal timing for surgery based on testicular stiffness. Patients and Methods: Thirty-six boys who had been diagnosed with unilateral undescended testis and treated with orchiopexy were included in the study. Testicular stiffness was evaluated several times over respective follow-up periods by ultrasound strain elastography after orchiopexy. The strain ratios were measured as the ratios of the elasticities of the descended testis to those of the operated testes. The patients were divided into two groups based on the age at which they underwent orchiopexy:under < 2 years (Group A) and ≥ 2 years (Group B). Results: The mean strain ratios were 0.90 ± 0.32 and 0.92 ± 0.20 in Groups A and B, respectively. In Group A, the strain ratio was constant regardless of postoperative months (r = 0.01, p = 0.99); however, in Group B, it tended to increase with postoperative months (r = 0.42, p = 0.07). Conclusions: Evaluation of testicular stiffness may be useful for the estimation of histopathological changes and fertility potential in boys with unilateral undescended testes at follow-up appointments after orchiopexy. Our data indicate that performing orchiopexy as early as possible may be recommended to avoid testicular damage

Comprehensive approach for post-prostatectomy incontinence in the era of robot-assisted radical prostatectomy

Robot-assisted radical prostatectomy (RARP) has enabled steady and stable surgical procedures due to both meticulous maneuvers and magnified, clear, 3-dimensional vision. Therefore, better surgical outcomes have been expected with RARP than with other surgical modalities. However, even in the RARP era, post-prostatectomy incontinence has a relatively high incidence as a bothersome complication. To overcome post-prostatectomy incontinence, it goes without saying that meticulous surgical procedures and creative surgical procedures, i.e., "Preservation", "Reconstruction", and "Reinforcement" of the anatomical structures of the pelvis, are most important. In addition, medication and appropriate pad usage might sometimes be helpful for patients with post-prostatectomy incontinence. However, patients who have 1) BMI > 26 kg/m(2), 2) prostate volume > 70 mL, 3) eGFR 2 have a tendency to develop post-prostatectomy incontinence despite undergoing the same surgical procedures. It is important for patients who have a high risk for post-prostatectomy incontinence to be given information about delayed recovery of post-prostatectomy incontinence. Thus, not only the surgical procedures, but also a comprehensive approach, as mentioned above, are important for post-prostatectomy incontinence

Interleukin-6 induces drug resistance in renal cell carcinoma

Metastatic renal cell carcinoma (mRCC) is a tumor entity with poor prognosis due to limited therapy options. Tyrosine kinase inhibitors (TKIs), the novel targeted agents have been used for the treatment of mRCC and have shown efficacy. Interferon (IFN)-α is also one of the most frequently used agents in immunotherapy. However, drug resistance needs to be overcome to achieve a sufficiently positive effect. Interleukin-6 (IL-6), which induce suppressor of cytokine signaling-3 (SOCS3) expression, is one of the factors associated with poor prognosis of patients with renal cell carcinoma (RCC). To analyze the influence of IL-6 in drug resistance of RCC, anti-IL-6 receptor antibody was used in combination with IFN or TKIs. The SOCS3 mRNA expression level was significantly increased by IFN-α stimulation in 786-O RCC cells which were resistant to IFN, but not in ACHN cells that were sensitive to IFN. The overexpression of SOCS3 by gene transfection in ACHN significantly inhibited the growth-inhibitory effect of IFN-α. An in vivo study demonstrated that co-administration of SOCS3-targeted siRNA promoted INF-α-induced cell death and growth suppression in 786-O cell xenograft. SOCS3 could be a key component in the resistance to interferon treatment of renal cell carcinoma. Because SOCS3 is rapidly up-regulated by IL-6 and a negative regulator of cytokine signaling, IL-6 expression on RCC cells was also analyzed and the 786-O cells showed the high level of IL-6 mRNA expression under the condition of interferon stimulation. IL-6R antibody, tocilizumab, significantly suppressed cell proliferation in 786-O cells by interferon stimulation accompanied with phosphorylation of STAT1 and inhibited SOCS3 expression. The in vivo effects of combination therapy with tocilizumab and interferon showed significant suppression of 786-O tumor growth in a xenograft model. We also hypothesized that TKI resistance and IL-6 secretion are causally connected. And we found that 786-O RCC cells secrete high IL-6 levels after low dose stimulation with the TKIs sorafenib, sunitinib and pazopanib, inducing activation of AKT-mTOR pathway, NFκB, HIF-2α and VEGF expression. Tocilizumab neutralizes the AKT-mTOR pathway activation and results in reduced proliferation. A combination therapy with tocilizumab and TKI suppresses 786-O tumor growth and inhibits angiogenesis in vivo more efficient than TKI alone. Our findings suggest that IL-6 could induce drug resistance on RCC, and combination therapy of IL-6R inhibitors and IFN/TKIs may represent a novel therapeutic approach for RCC treatment