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.

Association between nocturnal polyuria and 24-h blood pressure fluctuations in males with lower urinary tract symptoms: A multicenter prospective study.

OBJECTIVES: Nocturnal polyuria (NP) is one of the causes of nocturia that impairs quality of life. It is necessary to consider that NP is latent when the initial treatment for nocturia is unsatisfactory. Therefore, it is important to establish a treatment for NP based on the pathophysiology. We have previously reported the relationship between NP and fluctuation in blood pressure. The present study aimed to investigate the association between NP and 24-h blood pressure fluctuations in a multicenter prospective study. METHODS: This study included male patients with lower urinary tract symptoms. We categorized the patients into the nonnocturnal polyuria (non-NP) group (≤0.33) and the NP group (>0.33) based on the nocturnal polyuria index from the frequency volume chart. We measured the 24-h diurnal blood pressure and compared the two groups. RESULTS: Among 90 patients, 46 in the non-NP group and 44 in the NP group were included. There was no significant difference in the systolic and diastolic blood pressure during waking time between the two groups; however, the degree of systolic blood pressure reduction during sleep time in the NP group was significantly less than that in the non-NP group (p = 0.039). In the multivariate analysis, systolic BP during sleep was significantly associated with NP (OR 0.970, p = 0.028). CONCLUSION: NP is associated with inadequate nocturnal blood pressure reduction in males, suggesting that reduction in nocturnal blood pressure may lead to improvement in nocturia.

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.

Preoperative prognostic model for localized and locally advanced renal cell carcinoma: Michinoku Japan Urological Cancer Study Group.

BACKGROUND: The Modified International Metastatic Renal Cell Carcinoma Dataset Consortium model (mIMDC) is a preoperative prognostic model for pT3cN0M0 renal cell carcinoma (RCC). This study aimed to validate the mIMDC and to construct a new model in a localized and locally advanced RCC (LLRCC). METHODS: A database was established (the Michinoku Japan Urological Cancer Study Group database) consisting of 79 patients who were clinically diagnosed with LLRCC (cT3b/c/4NanyM0) and underwent radical nephrectomy from December 2007 to May 2018. Using univariable and multivariable analyses, we retrospectively analyzed disease-free survival (DFS) and overall survival (OS) in this database, constructed a new prognostic model according to these results, and estimated the model fit using c-index on the new and mIMDC models. RESULTS: Independent poorer prognostic factors for both DFS and OS include the following: ≥ 1 Eastern Cooperative Oncology Group performance status, 2.0 mg/dL C-reactive protein, and > upper normal limit of white blood cell count. The median DFS in the favorable (no factor), intermediate (one factor), and poor-risk group (two or three factors) was 76.1, 14.3, and 4.0 months, respectively (P < 0.001). The 3-year OS in the favorable, intermediate, and poor-risk group were 92%, 44%, and 0%, respectively (P < 0.001). The c-indices of the new and mIMDC models were 0.67 and 0.60 for DFS (P = 0.060) and 0.74 and 0.63 for OS (P = 0.012), respectively. CONCLUSION: The new preoperative prognostic model in LLRCC can be used in patient care and clinical trials.

The "GU-GU-RU" project to eliminate discrimination related to the health effects of the Fukushima nuclear accident.

BACKGROUND: Although 12 years have passed since Great East Japan Earthquake and following Fukushima nuclear accident, approximately 40% of Japanese citizen still believe that the current radiation exposure in Fukushima residents will likely/ very likely to cause genetic effects of radiation. This incorrect understanding could continue unexpected discrimination and prejudice towards those from Fukushima now and in the future. In order to provide updated knowledge and eliminate rumors related to radiation, Japanese Ministry of the Environment has launched "GU-GU-RU" project in 2021 with consisting of five sections. OBJECTIVE: (1) To discuss the objectives and effects of the "GU-GU-RU" project (results after the first year), (2) to present administrative measures that may be effective in the long-term to prevent unjustified discrimination and prejudice, and (3) to eliminate rumors in the event of future large-scale disasters, including radiation disasters. METHODS: We showed the contents of each sections carried out under the project and observed the result of first-year activities in each section. RESULTS: Among the programs, the "Radiation College" has steadily produced positive results, with nearly 1,300 students participating and 50 students sharing their thoughts and ideas. In addition, the project has adopted strategies such as creating and broadcasting a TV program and collaborations with manga, which are expected to have a significant impact on society. CONCLUSIONS: Compared to previous efforts on disseminating information related to health effect of radiation exposure, the "GU-GU-RU" project has taken a different approach in providing primary data of radiation and its health effects, which could become a better understanding of health effects of radiation for the general public, in order to eliminate rumors that may lead unjustified discrimination and prejudice.

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.

Significance of upfront cytoreductive nephrectomy stratified by IMDC risk for metastatic renal cell carcinoma in targeted therapy era - a multi-institutional retrospective study.

BACKGROUND: This retrospective multicenter study aimed to evaluate the survival benefit of upfront cytoreductive nephrectomy (CN) in metastatic renal cell carcinoma (RCC) patients stratified by International Metastatic RCC Database Consortium (IMDC) risk criteria. METHODS: We reviewed the medical records in the Michinoku Database between 2008 and 2019. Patients who received upfront CN, systemic therapy without CN (no CN) and CN after drug therapy (deferred CN) were analyzed. To exclude selection bias due to patient characteristics, baseline clinical data were adjusted by inverse probability of treatment weighting (IPTW). Overall survival (OS) was compared between upfront CN and non-upfront CN (no CN plus deferred CN). Associations between time-varying covariates including systemic therapies and OS stratified by IMDC risk criteria were analyzed by IPTW-adjusted Cox regression method. RESULTS: Of 259 patients who fulfilled the selection criteria, 107 were classified in upfront CN and 152 in non-upfront CN group. After IPTW-adjusted analysis, upfront CN showed survival benefit compared to non-upfront CN in patients with IMDC intermediate risk (median OS: 52.5 versus 31.3 months, p < 0.01) and in patients with IMDC poor risk (27.2 versus 11.4 months, p < 0.01). In IPTW-adjusted Cox regression analysis of time-varying covariates, upfront CN was independently associated with OS benefit in patients with IMDC intermediate risk (hazard ratio 0.52, 95% confidence interval 0.29-0.93, p = 0.03) and in patients with IMDC poor risk (0.26, 0.11-0.59, p < 0.01). CONCLUSIONS: Upfront CN may confer survival benefit in RCC patients with IMDC intermediate and poor risk.

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 Firmicutes/Bacteroidetes ratio of the human gut microbiota is associated with prostate enlargement.

BACKGROUND: The pathophysiology of the prostate enlargement underlying lower urinary tract symptoms is unknown. Meanwhile, the gut microbiota can contribute to various host conditions. We hypothesized that the gut microbiota plays a role in prostate enlargement. METHODS: We included 128 patients who underwent prostate biopsies at our hospitals between December 2018 and March 2020, excluding those who had used antibiotics within the past 6 months and those who were diagnosed with prostate cancer of cT3 or higher. Patients with prostate volumes ≥30 ml were defined as the prostate-enlargement (PE) group; those with prostate volumes <30 ml were defined as the non-PE group. Their gut microbiotas were analyzed via 16S rRNA metagenomic analyses of rectal swab samples and were compared between the groups. RESULTS: The PE group included 66 patients; the non-PE group included 62 patients. Age, body mass index, and prostate-specific antigen levels did not significantly differ between the groups. Linear discriminant analysis effect size analysis indicated a higher proportion of Firmicutes and Actinobacteria in the PE group and a higher proportion of Bacteroidetes in the non-PE group. The Firmicutes/Bacteroidetes (F/B) ratio was significantly higher in the PE group than in the non-PE group (2.21 ± 0.39 vs. 1.61 ± 0.40, p = 0.015). CONCLUSION: The F/B ratio of the gut microbiota was associated with prostate enlargement. Although the detailed mechanisms are unclear, the gut microbiota might affect prostate enlargement.

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.

Prognosis of Japanese metastatic renal cell carcinoma patients in the targeted therapy era.

BACKGROUND: The aims of this study were to investigate prognosis and validate prognostic models [Memorial Sloan-Kettering Cancer Center (MSKCC), International Metastatic Renal Cell Carcinoma Data Consortium (IMDC), and Japanese metastatic renal cancer (JMRC) models] in the targeted therapy era in Japanese patients with metastatic renal cell carcinoma. METHODS: We retrospectively analyzed 692 patients who were diagnosed with mRCC from January 2008 to August 2018 in the Michinoku Japan Urological Cancer Study Group database. Nivolumab as sequential therapy was widely used. Other immune checkpoint inhibitors were excluded from this study. RESULTS: The median overall survival (95% confident interval) in all, MSKCC favorable, intermediate, and poor risk patients was 41.0 months (33.9-46.8), not reached (63.5 to not estimable), 46.8 months (37.1-52.9), and 10.4 months (8.9-14.4), respectively. The median overall survival (95% confident interval) in IMDC favorable, intermediate, and poor risk patients was not reached (61.6 to not estimable), 47.4 months (41.4-56.5), and 11.5 (9.9-16.3), respectively. The c-index of the MSKCC, IMDC, and JMRC models calculated at mRCC diagnosis was 0.680, 0.689, and 0.700, respectively. No statistical differences were found in the c-index among the models. CONCLUSION: While the real-world overall survival in Japanese patients with mRCC in the targeted therapy era improved compared to that previously reported in the cytokine era, there was no clear difference in the survival of poor risk patients between these eras. There were no differences in the superiority among the models.

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.

Impact of cytoreductive nephrectomy in patients with primary metastatic renal cell carcinoma receiving systemic tyrosine kinase inhibitor therapy: A multicenter retrospective study.

OBJECTIVES: To compare overall survival between patients with metastatic renal cell carcinoma treated by cytoreductive nephrectomy and those not treated by cytoreductive nephrectomy. METHODS: We retrospectively evaluated 278 patients with metastatic renal cell carcinoma treated with first-line tyrosine kinase inhibitors between January 2008 and November 2019. Patients were divided into two groups: a cytoreductive nephrectomy group (immediate or deferred cytoreductive nephrectomy) and a group who received systemic tyrosine kinase inhibitor therapies alone without cytoreductive nephrectomy (control group). Overall survival comparisons were made in all patients in the control versus the cytoreductive nephrectomy group, the control versus the immediate cytoreductive nephrectomy group, the control versus the deferred cytoreductive nephrectomy group, and the deferred cytoreductive nephrectomy versus the immediate cytoreductive nephrectomy group. Analyses were weighted using the propensity score-based inverse probability of treatment weighting method to adjust for group imbalances. RESULTS: The median (range) age of the patients was 65 (59-73) years. Of the 278 patients, 132 and 146 were in the control group and the cytoreductive nephrectomy (immediate, n = 107 and deferred, n = 39) group, respectively. A significant difference was noted between the control and cytoreductive nephrectomy groups in age, clinical stage, International Metastatic Renal Cell Carcinoma Database Consortium risk factors, and the number of metastatic sites. Inverse probability of treatment weighting-adjusted Cox regression analysis showed a significant difference in overall survival between the control and the cytoreductive nephrectomy groups and between the control and the immediate or deferred cytoreductive nephrectomy groups. However, there was no significant difference in overall survival between the immediate and the deferred cytoreductive nephrectomy groups. CONCLUSIONS: Our findings suggest that metastatic renal cell carcinoma patients undergoing cytoreductive nephrectomy are more likely to have longer overall survival than those who receive tyrosine kinase inhibitor therapy only.

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.

Pediatric congenital hydronephrosis (ureteropelvic junction obstruction): Medical management guide.

The prevalence of asymptomatic hydronephrosis, now detected by ultrasonography, has increased. However, definitive management guidelines for the management of congenital hydronephrosis have not been established. The Japanese Society of Pediatric Urology created a "medical management guide" based on new findings for physicians practicing pediatric urology. We developed a medical management guide focused on congenital hydronephrosis caused by ureteropelvic junction obstruction. This medical management guide consists of the definition, pathophysiology, epidemiology, diagnosis, classification, treatment using a clinical management algorithm of hydronephrosis and the long-term course of the disease. The aim of hydronephrosis management is to determine whether surgery should be carried out to avoid renal dysfunction, as there is a possibility for improvement without intervention. Ultrasonography is essential to make treatment decisions. Management is determined by a comprehensive assessment, including the degree of hydronephrosis, anterior-posterior diameter of the renal pelvis and, if necessary, a nuclear medicine evaluation of the status of urine drainage and renal function.

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.