The activated complement pathway in the fibrous process of benign prostatic hyperplasia.

BACKGROUND: To elucidate the changes in activated complement pathway in the fibrous process of benign prostatic hyperplasia (BPH), we analyzed the correlation between complement component expression and histological types of fibrosis using human BPH tissue. METHODS: Fifty-six histological BPH patients who underwent prostate needle biopsy at our institution (mean age 68.6 ± 6.5 years), divided into two histological groups, fibromuscular and fibrous, were compared. Inflammatory cell infiltration in BPH tissue was evaluated by immunohistochemical staining using CD45, with complement expression analysis performed using C3, factor B, and C5b-9 antibody, and the occupancy ratio of the stained region was calculated. Further, correlation between the histological types of fibrous components in BPH tissue and lower urinary tract symptoms questionnaires was analyzed. RESULTS: Twenty-seven (48.2%) and 29 (51.8%) cases were classified in the fibromuscular and fibrous groups, respectively. The proportion of CD45-positive cells in BPH tissue was significantly higher in the fibromuscular group. In complement component analysis, factor B did not significantly differ between groups, while C3 (fibromuscular group; 10.7 ± 8.2%, fibrous group; 16.4 ± 12.7%) and C5b-9 (fibromuscular group; 15.9 ± 6.2%, fibrous group; 17.6 ± 9.2%) were significantly higher in the fibrous group (p = 0.04, p = 0.04, respectively). International Prostate Symptom Score Q5 subscore, indicating slow stream, was significantly higher in the fibrous group (p = 0.04). CONCLUSIONS: In fibrous BPH with abundant fibrosis, the late complement pathway in addition to alternative pathway was activated compared to fibromuscular BPH. These results suggested that the alternative and late complement pathways were involved in the histological fibrous process of BPH.

Unilateral adrenalectomy for a drug-resistant bilateral primary aldosteronism with heart failure: pathophysiology and surgical indication.

BACKGROUND: Patients with bilateral primary aldosteronism (PA) generally are treated with antihypertensive drugs, but optimal treatment for patients with complications due to refractory hypertension has not been established. In this report, we present a case with bilateral PA who presented with persistent hypertension, despite treatment with 6 drugs, and left-dominant heart failure, which was improved after unilateral adrenalectomy. CASE PRESENTATION: A 61-year-old man was admitted to our hospital because of severe left-dominant heart failure. His heart rhythm was atrial fibrillation and the left ventricle was diffusely hypertrophic and hypokinetic. Coronary arteries were normal on coronary arteriogram. Primary aldosteronism was suspected based on severe hypokalemia (2.5 mEq/L) and plasma aldosterone concentration (PAC; 1,410 pg/mL). Although computed tomography (CT) showed a single left cortical nodule, adrenal vein sampling (AVS) indicated bilateral PA. Early in the case, heart failure and hyperkalemia in this patient were improved by treatment with a combination of 6 antihypertensive drugs (spironolactone 25 mg/day, eplerenone 100 mg/day, azosemide 60 mg/day, tolvaptan 7.5 mg/day, enalapril 5 mg/day, and bisoprolol fumarate 10 mg/day); however, heart failure relapsed after four months of treatment. We hypothesized that hypertension caused by excess aldosterone was inducing the patient's heart failure. In order to reduce aldosterone secretory tissue, a laparoscopic adrenalectomy was performed for the left adrenal gland, given the higher level of aldosterone from the left gland compared to the right. Following surgery, the patient's heart failure was successfully controlled despite the persistence of high PAC. Treatment with anti-hypertensive medications was reduced to two drugs (eplerenone 100 mg/day and bisoprolol fumarate 10 mg/day). In order to elucidate the mechanism of drug resistance, immunohistochemistry (IHC) and real time-polymerase chain reaction (RT-PCR) assays were performed to assess the expression of steroidogenic factor 1 (SF-1), a regulator of steroid synthesis in adrenal tissue. IHC and RT-PCR demonstrated that the expression of SF-1 in this patient (at both the protein and mRNA levels) was higher than that observed in unilateral PA cases that showed good responsivity to drug treatment. CONCLUSIONS: Unilateral adrenalectomy to reduce aldosterone secretory tissue may be useful for patients with drug-refractory, bilateral PA. Elevated expression of SF-1 may be involved in drug resistance in PA.

Mechanism of Androgen-Independent Stromal Proliferation in Benign Prostatic Hyperplasia.

Benign prostatic hyperplasia (BPH) is a chronic proliferative disease showing stromal-dominant proliferation. However, the detailed proliferation mechanism has remained unclear. Although aging and androgen have been reported as definitive risk factors for BPH, recent studies have focused on the involvement of androgen-independent factors. Androgen-independent factors include ischemia, oxidative stress, metabolic syndrome, infection, autoimmune reactions, and inflammation, with inflammation in BPH tissues playing a central role in the BPH proliferative process. Inflammation in BPH tissues by various factors finally leads to tissue remodeling and stromal proliferation through the wound healing process of the prostate. To elucidate the proliferative mechanism of BPH, a study using whole-genome gene expression analysis in a stromal-dominant BPH rat model was performed and showed that immune response-related pathways and complement classical pathways are activated. Furthermore, expression analysis using this BPH rat model showed that the autoimmune reaction triggered complement pathway activation in the proliferative process of BPH. BPH is a multifactorial disease, and understanding the role of androgen-independent factors including immune responses contributes to elucidating the pathogenesis of BPH. Androgen-independent factors may lead to new therapeutic targets for BPH, and further development of this research is expected.

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.

Insights into the development of a new index, vesical adaptation response to diuresis, for understanding lower urinary tract dysfunction.

OBJECTIVES: To clarify how vesical adaptation response, the homeostatic system that constantly changes voided volume to adapt to diuresis, is involved in male lower urinary tract symptoms and bladder storage function. METHODS: We included male patients older than 65 years with lower urinary tract symptoms. Vesical adaptation response to diuresis was defined as a positive correlation between urine output rate and voided volume on 3-day sensory-related frequency volume charts. Patients were divided into two groups according to the presence or absence of vesical adaptation response to diuresis, and characteristics were compared between groups. RESULTS: Ninety-four male patients were finally analyzed. Vesical adaptation response to diuresis was found in 48 patients (51%) and was lacking in 46 patients (49%). Patients without vesical adaptation response to diuresis were significantly more often diagnosed with overactive bladder (P = 0.04). After adjusting for confounders, absence of vesical adaptation response to diuresis was significantly associated with overactive bladder (adjusted odds ratio 3.76, 95% confidence interval 1.34-10.55; P = 0.01) and benign prostatic enlargement (adjusted odds ratio 1.04, 95% confidence interval 1.01-1.07; P = 0.02). CONCLUSIONS: The absence of vesical adaptation response to diuresis, characterized by decreased voided volume during a diuretic phase, can be interpreted as a form of bladder storage dysfunction. Assessment of vesical adaptation response to diuresis may provide a new index of bladder storage function and contribute to a better understanding of the pathophysiology underlying bladder storage dysfunction in patients with lower urinary tract symptoms.

Efficacy of the opened legs position for protecting against postoperative rhabdomyolysis after robot-assisted radical prostatectomy: A propensity score-matched analysis of perioperative outcomes.

OBJECTIVES: The aim of the present study was to clarify the relationships of intraoperative surgical position with the incidence of postoperative rhabdomyolysis and with postoperative renal function to safely perform robot-assisted radical prostatectomy. METHODS: The participants in the present study were 276 consecutive patients who underwent robot-assisted radical prostatectomy at our institutions between 2013 and 2020; 130 cases were performed in the opened legs position and 146 cases in the lithotomy position with a steep 23°-25° head-down position. Rhabdomyolysis was defined as creatine kinase values greater than 1000 IU/L. Propensity score matching including age, body mass index, the presence of comorbidities, preoperative creatine kinase, preoperative estimated glomerular filtration rate, and prostate-specific antigen was performed, resulting in a matched cohort of 146 patients (opened legs position group n = 73; lithotomy position group n = 73). RESULTS: After propensity score matching, creatine kinase values on the first day after surgery were significantly lower in the opened legs position group than in the lithotomy position group (opened legs position group: lithotomy position group = 246.9 ± 114.9 IU/L: 558.2 ± 114.9 IU/L, P = 0.034). There were significantly fewer patients diagnosed with postoperative rhabdomyolysis in the opened legs position group (opened legs position group: lithotomy position group = 0% (0/73): 9.6% (7/73), P < 0.001). In addition, fluid replacement volume was significantly less in the opened legs position group (opened legs position group: lithotomy position group = 5747 ± 180 mL: 6349 ± 0176 mL, P = 0.018). CONCLUSIONS: To prevent rhabdomyolysis after surgery, robot-assisted radical prostatectomy should be performed in the opened legs position.

Upregulation of glucocorticoid receptor-mediated glucose transporter 4 in enzalutamide-resistant prostate cancer.

Enzalutamide (Enz) is a second-generation androgen receptor (AR) antagonist for castration-resistant prostate cancer (CRPC) therapy, and it prolongs survival time in these patients. However, during Enz treatment, CRPC patients usually acquire resistance to Enz and often show cross-resistance to other AR signaling inhibitors. Although glucocorticoid receptor (GR) is involved in this resistance, the role of GR has not yet been clarified. Here, we report that chronic Enz treatment induced GR-mediated glucose transporter 4 (GLUT4) upregulation, and that upregulation was associated with resistance to Enz and other AR signaling inhibitors. Additionally, inhibition of GLUT4 suppressed cell proliferation in Enz-resistant prostate cancer cells, which recovered from Enz resistance and cross-resistance without changes in GR expression. Thus, a combination of Enz and a GLUT4 inhibitor could be useful in Enz-resistant CRPC patients.

The effect of ß3-adrenoceptor gene polymorphisms on lower urinary tract function in males.

PURPOSE: To clarify the role of Trp64Arg polymorphisms of the gene encoding the ß3-adrenoceptor for lower urinary tract function in males, the present study investigated the association between the Trp64Arg polymorphisms and lower urinary tract symptoms (LUTS) and function. METHODS: This prospective observational study included patients who underwent robot-assisted radical prostatectomy. Before surgery, blood samples were collected, and analyses of ß3-adrenoceptor gene polymorphism were performed using the real-time polymerase chain reaction. The present cohort was divided into patients with wild type (Trp64Trp) and with variant type (Trp64Arg + Arg64Arg), and LUTS and lower urinary tract function before surgery were compared between them. RESULTS: Wild type was found in 247 patients, with variant type in 129. There were no significant differences in LUTS between the two groups. Residual urine volume (PVR) (wild type: variant type = 47 ± 53 mL: 58 ± 77 mL, P = 0.04) and voiding time on uroflowmetry (wild type: variant type = 29 ± 15 s: 33 ± 17 s, P = 0.04) were significantly increased in the variant type. CONCLUSION: The Trp64Arg variant of the ß3-adrenoceptor gene significantly increased PVR and voiding time in men. However, it was not significantly associated with the emergence of LUTS. Thus, since the effect of ß3-adrenoceptor gene polymorphisms on the genitourinary organs might be weak, whether men possess the Trp64Arg variant of the ß3-adrenoceptor gene might not critically affect urinary quality of life, but modestly affect the lower urinary tract function.

Prevalence and predictors of postoperative detrusor underactivity after robot-assisted radical prostatectomy: A prospective observational study.

OBJECTIVES: To identify the prevalence and predictors of postoperative detrusor underactivity during the early postoperative period after robot-assisted radical prostatectomy. METHODS: We carried out a prospective observational study of 64 patients scheduled for robot-assisted radical prostatectomy using urodynamic study before and 1 month after robot-assisted radical prostatectomy. Detrusor underactivity was defined as maximum flow rate ≤15 mL/s and detrusor pressure at maximum flow rate ≤25 cmH2 O during voiding. Incidences of pre- and postoperative detrusor underactivity were assessed, and predictors of postoperative detrusor underactivity were determined using uni- and multivariate logistic regression analyses. Factors comprised patient characteristics (age, prostate weight etc.), operative factors (surgical duration, nerve sparing etc.) and preoperative urodynamic study parameters (maximum flow rate, bladder contractile index etc.). RESULTS: Pre- and postoperative detrusor underactivity at 1 month after robot-assisted radical prostatectomy were detected in one patient (1.6%) and 24 patients (37.5%), respectively. Univariate analysis selected preoperative maximum flow rate (P = 0.02), detrusor pressure at maximum flow rate (P = 0.04) and bladder contractile index (P < 0.01) as predictors of postoperative detrusor underactivity (odds ratio 0.83, 0.97 and 0.94, respectively). On multivariate analyses, only preoperative bladder contractile index was associated with postoperative detrusor underactivity (P < 0.01; odds ratio 0.94). A cut-off of 102.8 offered optimal accuracy in receiver operating characteristic analysis. Patient characteristics and operative factors were not significantly associated with postoperative detrusor underactivity. CONCLUSIONS: A comparatively high prevalence of postoperative detrusor underactivity is observed in patients at 1 month after robot-assisted radical prostatectomy. Patients with preoperative low bladder contractile index have a higher probability of developing early postoperative detrusor underactivity after robot-assisted radical prostatectomy.

Perioperative Detection of Circulating Tumor Cells in Radical or Partial Nephrectomy for Renal Cell Carcinoma.

BACKGROUND: The current study was conducted to clarify the frequency of systemic circulating tumor cells (CTCs) appearing after surgery for renal cell carcinoma and to evaluate the differences in postoperative CTCs between different surgical procedures. METHODS: This prospective, cohort study included 60 consecutive patients who underwent laparoscopic radical nephrectomy (RN) (n = 22), laparoscopic partial nephrectomy (PN) (n = 19), open RN (n = 8), or open PN (n = 11). In this study CTCs were measured by the FISHMAN-R system, and CTCs drawn from a peripheral artery were collected just before and immediately after surgery. The number of pre- and postoperative CTCs and the perioperative changes in CTCs were measured for each surgical method. RESULTS: Six patients were excluded from the current analyses. Preoperative CTCs did not differ significantly by surgical approach (laparoscopic RN: 3.4 ± 4.2; laparoscopic PN: 3.4 ± 4.1; open RN: 7.7 ± 6.8; open PN: 6.0 ± 7.6; P = 0.19). Open RN resulted in a significantly greater number of postoperative CTCs (laparoscopic RN: 4.8 ± 3.7; laparoscopic PN: 7.9 ± 9.1; open RN: 22.5 ± 26.3; open PN: 6.4 ± 6.3; P < 0.001) and perioperative changes in CTCs (laparoscopic RN: 1.3 ± 5.3; laparoscopic PN: 4.5 ± 9.6; open RN: 14.7 ± 25.0; open PN: 0.4 ± 6.3; P < 0.001). No significant differences in these were observed among the three groups except in the open RN group. In the multivariate analysis, the surgical approach was significantly correlated with the number of postoperative CTCs (P = 0.016) and the perioperative change in CTCs (P = 0.01). CONCLUSIONS: This proof-of-concept study indicated that after surgery, more cancer cells can be expelled into the bloodstream, especially after open RN. Sufficient and careful follow-up assessment for the emergence of distant metastases is needed for patients undergoing open RN.

Morphological change and characteristics of myofibroblasts during the growth process of benign prostatic hyperplasia.

OBJECTIVES: To clarify the morphological change and characteristics of myofibroblast during the growth process of benign prostatic hyperplasia. METHODS: This study examined the characteristics of myofibroblasts during the growth process of the prostate in the stromal component-dominant benign prostatic hyperplasia rat model. Transforming growth factor-ß1 and insulin-like growth factor-binding protein 3 expression were evaluated by western blotting (n = 6). We used double immunohistochemical staining to evaluate the number of myofibroblasts positive for α-smooth muscle actin and vimentin in benign prostatic hyperplasia tissues. Expression and histological analyses of the benign prostatic hyperplasia were also carried out in rats at 2, 3 and 8 weeks after urogenital sinus implantation (n = 6). To evaluate the fine morphological characteristics of myofibroblasts in human benign prostatic hyperplasia tissues, electron microscopy analysis was additionally carried out. RESULTS: There was a significant upregulation of the transforming growth factor-ß1 and insulin-like growth factor-binding protein 3 expression in benign prostatic hyperplasia (P < 0.05). There was a significant increase in the number of myofibroblasts in benign prostatic hyperplasia (P < 0.05) compared with normal prostate, with these abundantly located in the stromal area. The transforming growth factor-ß1 and insulin-like growth factor-binding protein 3 expression and number of myofibroblasts showed a time-dependent increase (P < 0.05), with growth factor expressions preceding the myofibroblast increase. Electron microscopy confirmed that the myofibroblast progenitor cells, which possess abundant stress fibers, were predominantly located around fibrous areas in human benign prostatic hyperplasia. CONCLUSIONS: Differentiation into myofibroblasts induced by transforming growth factor-ß1 and insulin-like growth factor-binding protein 3 actively occurs during the growth process of benign prostatic hyperplasia. Myofibroblast progenitor cells seem to be associated with prostatic fibrosis in human benign prostatic hyperplasia.

The association between local arteriosclerosis of the prostatic arteries and chronic inflammation in human benign prostatic enlargement.

BACKGROUND: To elucidate the pathogenesis of benign prostatic enlargement (BPE) in humans due to chronic inflammation caused by arteriosclerosis, the relationships between prostate size and the degree of chronic inflammation induced by local arteriosclerosis were investigated. METHODS: The present cohort included 50 subjects who underwent robot-assisted radical prostatectomy (RARP) in a prospective study. The presence or absence of local arteriosclerosis in the prostatic arteries removed during RARP was evaluated by microscopic assessment. Chronic inflammation in the prostate was judged according to both the density and the extent of inflammatory cells. The expression of lectin-like oxidized-low density lipoprotein receptor-1 (LOX-1) and the infiltration of macrophages in the prostate, which are high in arteriosclerosis, were investigated by immunohistochemistry. RESULTS: Local arteriosclerosis was observed in 28% (14/50). Prostate size and the inflammation score were significantly increased in the presence of arteriosclerosis (P = 0.006, P < 0.001, respectively). There was also a significant increase of LOX-1 in the epithelial and stromal cells of the prostate in the presence of arteriosclerosis (all, P < 0.001). Concerning the presence of macrophages, subjects with arteriosclerosis had significantly more positive expression of ionized calcium-binding adapter molecule-1 (IBA-1), a marker of macrophages, than subjects without arteriosclerosis (P < 0.001). CONCLUSIONS: In human surgical specimens, chronic inflammation owing to local arteriosclerosis of the prostatic arteries was significantly related to prostatic enlargement. Given the immunohistochemical analyses, the putative pathogenesis for this relationship is that LOX-1 induces macrophage infiltration, leading to BPE.

Single Nucleotide Polymorphisms of HAAO and IRX6 Genes as Risk Factors for Hypospadias.

PURPOSE: We evaluated the association of hypospadias and 17 susceptibility loci previously identified by a European genome-wide association study in a cohort of Japanese patients. We also examined the expression of candidate genes in male mouse embryos to determine the possible underlying mechanisms of this disease. MATERIALS AND METHODS: We enrolled 169 Japanese patients (mean age at surgery 3.7 years) who underwent repair of hypospadias. Genotyping of 17 single nucleotide polymorphisms was performed using a multiplex polymerase chain reaction invader assay. We also performed in situ hybridization to determine whether candidate genes were expressed in the male genital tubercle during embryonic development of the external genitalia in mice. RESULTS: Single nucleotide polymorphism rs3816183 of HAAO was significantly associated with susceptibility to hypospadias in general (p = 0.0019) and to anterior/middle hypospadias (p = 0.0283) and posterior hypospadias (p = 0.0226), while single nucleotide polymorphism rs6499755 of IRX6 showed an association with susceptibility to anterior/middle hypospadias (p = 0.0472). In mouse embryos there was no significant upregulation of Haao expression in the developing male external genitalia. Irx3 and Irx5, which are linked to Irx6 within the IrxB cluster, were expressed in the mesenchyme remote from the urethral plate epithelium during the critical embryonic period for masculinization. Irx6 was expressed in the ectodermal epithelium, demonstrating prominent dorsal ectodermal expression without expression in the ventral ectoderm adjacent to the urethral plate during the same period. CONCLUSIONS: Genetic variations of HAAO and IRX6 influence susceptibility to hypospadias in the Japanese population. Further research is needed to clarify the mechanism by which variations in these genes contribute to the pathogenesis of hypospadias.

Usefulness of a novel classification based on perioperative changes of membranous urethral length using hierarchical cluster analysis of urinary incontinence and overactive bladder symptoms after robot-assisted radical prostatectomy: A prospective observational study.

AIMS: The aim of the present study was to construct a novel classification based on perioperative changes of membranous urethral length (MUL) using hierarchical cluster analysis to predict urinary incontinence (UI) and overactive bladder (OAB) symptoms after robot-assisted radical prostatectomy (RARP). METHODS: A total of 299 patients who underwent RARP with complete pre and postoperative MUL data were included in the present study. Hierarchical cluster analysis was performed to identify the groups with similar perioperative MUL and prostate size. UI and OAB symptoms after RARP were evaluated in each cluster for 12 months after RARP. RESULTS: Four groups were identified by the cluster analysis of these factors: preservation of MUL type (cluster 1, n = 92); standard type (cluster 2, n = 137); large prostate type (cluster 3, n = 23); and loss of MUL type (cluster 4, n = 47). Although there was significantly more UI in clusters 3 and 4 than in clusters 1 and 2 up to 3 months after RARP, UI improvement was the most delayed in cluster 3. Improvement of OAB symptoms was also most delayed in cluster 3. Urinary quality of life (QOL) was significantly worse in cluster 4 than in clusters 1 and 2. CONCLUSIONS: Cluster analysis successfully classified patients after RARP into four characteristic groups based on perioperative MUL. Recovery from UI and OAB symptoms and urinary QOL after RARP were significantly different among these groups. This classification based on cluster analysis might be useful to predict recovery from UI and OAB symptoms when following QOL after RARP.

Atherosclerosis as a predictor of transient exacerbation of overactive bladder symptoms after robot-assisted laparoscopic radical prostatectomy.

OBJECTIVES: To assess whether atherosclerosis is involved in the development of overactive bladder and the function of lower urinary tract after robot-assisted radical prostatectomy. METHODS: The present cohort consisted of 80 consecutive participants. The preoperative cardio-ankle vascular index was used to evaluate the presence of atherosclerosis. The present cohort was split into two groups, the atherosclerotic group, whose cardio-ankle vascular index was ≥9.0, and the control group, whose index was <9.0. The overactive bladder symptom score and lower urinary tract function were compared for 12 months after surgery. RESULTS: The total score of the questionnaire was significantly higher at 6 and 9 months after surgery in the atherosclerosis group (P = 0.04, P = 0.03, respectively). Both the urgency and urgency incontinence subscores of the questionnaire showed a parallel tendency to that of the total score after surgery. At 3 months after surgery, there was a significant increase in the prevalence of de novo overactive bladder in the atherosclerosis group (P = 0.04). At 9 and 12 months after surgery, there was a significant decrease of voided volume in the atherosclerotic group (P < 0.01, P = 0.04, respectively). CONCLUSIONS: Atherosclerosis delays the improvement in both overactive bladder symptoms and storage function postoperatively, and it is involved in the transient increase in the prevalence of de novo overactive bladder. Atherosclerosis might be a predictor of the development of overactive bladder after robot-assisted radical prostatectomy.

The association between local atherosclerosis of the prostatic artery and benign prostatic enlargement in humans: Putative mechanism of chronic ischemia for prostatic enlargement.

BACKGROUND: To investigate the possible pathogenesis of the benign prostatic enlargement (BPE) induced by local atherosclerosis, the association between local atherosclerosis and prostatic enlargement was investigated, and molecular biological analyses were performed using human prostatectomy specimens. METHODS: A total of 69 consecutive patients who underwent robot-assisted radical prostatectomy (RARP) participated in this prospective study. To evaluate actual local atherosclerosis, prostatic arteries were removed during RARP. Microscopic assessment of local atherosclerosis was classified as one of three degrees of narrowing (minimal, moderate, and severe) according to the degree of obstruction of the inner cavity of the prostatic artery. The expressions of several mediators related to chronic ischemia and cell proliferation of the prostate were investigated by immunohistochemistry. RESULTS: The median age of the present cohort was 68 (range: 55-75) years. Although there was no relationship between local atherosclerosis and lower urinary symptoms evaluated by questionnaires, local atherosclerosis was significantly more severe in patients who had a history of treatment for benign prostatic hyperplasia (P = 0.02). Prostate size was significantly larger in the severe local atherosclerosis group than in the minimal and moderate local atherosclerosis groups (P < 0.001 and P = 0.03, respectively). Thepositive expression rates of hypoxia-inducible factor (HIF)-1α, malondialdehyde (MDA), transforming growth factor (TGF)-ß1 , and basic fibroblast growth factor (bFGF) in the prostate were significantly higher in patients with local atherosclerosis than in patients without local atherosclerosis (all P < 0.01, respectively). CONCLUSIONS: In human surgical specimens, there is evidence that local atherosclerosis of the prostatic artery is significantly associated with prostate size. Given the molecular evidence provided in this study, the putative mechanism for this relationship is that chronic ischemia induced upregulation of oxidative stress pathways, leading to BPE.

The impact of nerve-sparing robot-assisted radical prostatectomy on lower urinary tract function: Prospective assessment of patient-reported outcomes and frequency volume charts.

AIMS: To elucidate the effects of a nerve-sparing (NS) procedure on lower urinary tract symptoms (LUTS) and urinary function after robot-assisted radical prostatectomy (RARP), the associations between the NS procedure and LUTS and urinary function were investigated. METHODS: The participants in this study were 200 consecutive patients who underwent RARP. These patients were categorized into unilateral and bilateral NS groups and the non-NS group. The International Prostate Symptom Score (IPSS), quality of life (QOL) index, frequency-volume chart, uroflowmetry, 1-h pad test, and the 5-item International Index of Erectile Function (IIEF-5) questionnaire were evaluated before and after RARP. RESULTS: The total IPSS score was significantly lower in the unilateral (P = 0.03) and bilateral NS groups (P = 0.03) than in the non-NS group after RARP. Diurnal maximum voided volume (MVV) values were significantly greater in the bilateral NS group than in the non-NS group after RARP (P = 0.002). Nocturnal frequency was significantly decreased in the unilateral NS group than in the non-NS group after RARP (3 months P = 0.01, 12 months P = 0.01). Erectile function was significantly better in both the unilateral NS group (P < 0.0001) and the bilateral NS group (P = 0.02) than in the non-NS group 12 months after RARP. CONCLUSIONS: The NS procedure in RARP has the possibility to improve not only erectile function, but also LUTS, owing to both the increase of MVV and the decrease of nocturia. Therefore, the NS procedure is also recommended from the viewpoint of early improvement of LUTS and lower urinary tract dysfunction after RARP.

Effects of barbed suture during robot-assisted radical prostatectomy on postoperative tissue damage and longitudinal changes in lower urinary tract outcome.

OBJECTIVE: To compare the postoperative tissue damage and longitudinal changes in functional and patient-reported outcomes after vesicourethral anastomosis with barbed suture and nonbarbed suture in robot-assisted laparoscopic radical prostatectomy (RARP). MATERIALS AND METHODS: This was a prospective cohort study involving 88 consecutive patients who underwent RARP. These patients were categorized into the barbed suture group (n = 50) and the nonbarbed suture group (n = 38). Urethral and periurethral damages determined by magnetic resonance imaging at nine months after RARP were compared using generalized linear models. The International Prostate Symptom Score (IPSS), quality of life (QOL) index, uroflowmetry, and the 1-h pad test were measured at baseline and at 1, 3, 6, 9, and 12 months after RARP. The findings were analyzed using mixed-effects models. Confounding was adjusted for using propensity score covariate adjustment. RESULTS: The likelihood of having Grade 2/3 urethral and periurethral damages was greater in the barbed suture group than in the nonbarbed suture group (adjusted risk ratios: 2.98 and 3.85, respectively). IPSS, QOL index, and urinary leakage transiently increased at one month after RARP in both groups. QOL index was higher in the barbed suture group than in the nonbarbed suture group at 1, 9, and 12 months (P = 0.023, P = 0.025, and P = 0.011, respectively). The barbed suture group had significantly more cases of urinary incontinence than the nonbarbed suture group at 3 months (P = 0.041). Other outcomes were comparable between the two groups at all time points. CONCLUSIONS: This cohort study showed that, after RARP, barbed sutures during VUA induced more severe tissue damage as determined by MRI and greater transient aggravation of QOL and continence function than nonbarbed sutures. The present findings suggest that using nonbarbed sutures during VUA may facilitate earlier acquisition of urinary QOL and urinary continence.

Infrarenal high intra-abdominal testis: fusion of T2-weighted and diffusion-weighted magnetic resonance images and pathological findings.

BACKGROUND: Several recent reports have demonstrated that the preoperative sensitivity and accuracy of identifying and locating non-palpable testes increases with the use of conventional MRI, in addition to diffusion-weighted imaging (DWI). Therefore, pre-operative prediction of the presence and location of testes using imaging techniques may guide management of intra-abdominal testis. Fowler-Stephens orchiopexy is effective for treating patients with intra-abdominal testis; however, long-term testicular function after this procedure has not been clarified. We present a case of a high intra-abdominal testis located below the kidney, and discuss the usefulness of fusion view with T2-weighted and DWI images to make a diagnosis of high intra-abdominal testis and the pathological findings to predict future fertility potential. CASE PRESENTATION: A 10-month-old boy was referred to the urology department for the management of non-palpable testis. We employed not only conventional MRI, but also DWI, to improve the diagnostic accuracy of non-palpable testes by MRI examination. The high-intensity mass-like structure below the kidney on the T2-weighted image and the markedly high signal intensity mass on the DWI image completely matched, which suggested that the mass below the kidney was the right testis. The patient underwent diagnostic and therapeutic laparoscopy. A testis was found under the ascending colon, 1 cm below the right kidney. We performed 2-stage Fowler-Stephens orchiopexy. The testis could be delivered to the scrotum without any tension. We examined expression patterns of the stem cell marker, undifferentiated embryonic cell transcription factor 1 (UTF1) in the testicular biopsy sample, and demonstrated that the UTF1-positive Ad spermatogonia / negative Ad spermatogonia ratio was lower in this patient than in boys his age with descended and inguinal undescended testes, indicating that spermatogonial stem cell activity may decrease remarkably in this boy. CONCLUSIONS: Fusion view with T2-weighted and DWI images may be a useful diagnostic modality for high intra-abdominal testes. Fowler-Stephens orchiopexy may provide blood supply to the testis but that might not be enough to achieve spermatogenesis.

Case of possible multiple system atrophy with a characteristic imaging finding of open bladder neck during storage phase as an initial sign.

Multiple system atrophy is a neurodegenerative disease that affects autonomic and motor systems. Patients with multiple system atrophy usually experience lower urinary tract symptoms, which sometimes appear as an initial symptom before the emergence of the generalized symptoms. An open bladder neck during the filling phase on video urodynamic study is one characteristic imaging finding after the diagnosis of multiple system atrophy, but has not previously been reported at an early phase of the disease. We report a case in which an open bladder neck was observed on several imaging modalities before generalized symptoms emerged. Because occult neurogenic bladder might exist in patients whose lower urinary tract symptoms are resistant to pharmacotherapy, we report this case to raise awareness of the importance of sufficient imaging evaluations. An open bladder neck might be an important imaging finding for diagnosing multiple system atrophy, irrespective of the presence of generalized symptoms. This finding could help avoid false diagnosis and unnecessary treatment.