Synthetic retinoid-mediated preconditioning of cancer-associated fibroblasts and macrophages improves cancer response to immune checkpoint blockade.

BACKGROUND: The proliferation of cancer-associated fibroblasts (CAFs) hampers drug delivery and anti-tumor immunity, inducing tumor resistance to immune checkpoint blockade (ICB) therapy. However, it has remained a challenge to develop therapeutics that specifically target or modulate CAFs. METHODS: We investigated the involvement of Meflin+ cancer-restraining CAFs (rCAFs) in ICB efficacy in patients with clear cell renal cell carcinoma (ccRCC) and urothelial carcinoma (UC). We examined the effects of Am80 (a synthetic retinoid) administration on CAF phenotype, the tumor immune microenvironment, and ICB efficacy in cancer mouse models. RESULTS: High infiltration of Meflin+ CAFs correlated with ICB efficacy in patients with ccRCC and UC. Meflin+ CAF induction by Am80 administration improved ICB efficacy in the mouse models of cancer. Am80 exerted this effect when administered prior to, but not concomitant with, ICB therapy in wild-type but not Meflin-deficient mice. Am80-mediated induction of Meflin+ CAFs was associated with increases in antibody delivery and M1-like tumor-associated macrophage (TAM) infiltration. Finally, we showed the role of Chemerin produced from CAFs after Am80 administration in the induction of M1-like TAMs. CONCLUSION: Our data suggested that Am80 administration prior to ICB therapy increases the number of Meflin+ rCAFs and ICB efficacy by inducing changes in TAM phenotype.

Novel clinical diagnostic criteria based on noninvasive examination findings to predict the presence of urodynamic detrusor underactivity in men.

AIMS: To investigate the usefulness of novel clinical diagnostic criteria based on noninvasive examination findings to diagnose urodynamic detrusor underactivity (DU) in men. METHODS: We developed clinical diagnostic criteria to predict the presence of urodynamic DU in men as follows: (a) bladder voiding efficiency <70% on uroflowmetry, (b) existence of "sawtooth and interrupted waveforms" on uroflowmetry, and (c) ultrasonography-documented intravesical prostatic protrusion <10 mm. We analyzed the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of these clinical criteria for diagnosing urodynamic DU in men aged 50 years or above with lower urinary tract symptoms who underwent urodynamic studies. RESULTS: Of the 314 men analyzed (mean age, 72.4 years; mean detrusor contraction index [DCI], 98.8; and mean bladder outlet obstruction index [BOOI], 43.9), 89 men met this clinical DU diagnostic criteria. Of these, 79 men (88.8%) had urodynamic DU (DCI < 100 and BOOI < 40), nine (10.1%) had DU + BOO (DCI < 100 and BOOI ≥ 40), and one (1.1%) had normal voiding functions. None of the men with urodynamic BOO (DCI ≥ 100 and BOOI ≥ 40) met the clinical DU diagnostic criteria. The sensitivity, specificity, PPV, and NPV of these clinical diagnostic criteria for urodynamic DU were 69.3%, 95.0%, 88.8%, and 84.4%, respectively. CONCLUSION: The proposed clinical DU diagnostic criteria showed a high PPV (88.8%) for diagnosing urodynamic DU. None of the patients with BOO met the clinical diagnostic criteria for DU. These clinical DU diagnostic criteria may be useful in identifying men with urodynamic DU in clinical practice.

Recent insights on the clinical, pathological, and molecular features of intraductal carcinoma of the prostate.

Intraductal carcinoma of the prostate, a unique histopathologic entity that is often observed (especially in advanced prostate cancer), is characterized by the proliferation of malignant cells within normal acini or ducts surrounded by a basement membrane. Intraductal carcinoma of the prostate is almost invariably associated with an adjacent high-grade carcinoma and is occasionally observed as an isolated subtype. Intraductal carcinoma of the prostate has been demonstrated to be an independent poor prognostic factor for all stages of cancer, whether localized, de novo metastatic, or castration-resistant. It also has a characteristic genetic profile, including high genomic instability. Recognizing and differentiating it from other pathologies is therefore important in patient management, and morphological diagnostic criteria for intraductal carcinoma of the prostate have been established. This review summarizes and outlines the clinical and pathological features, differential diagnosis, molecular aspects, and management of intraductal carcinoma of the prostate, as described in previous studies. We also present a discussion and future perspectives regarding intraductal carcinoma of the prostate.

Clinical utility of intraductal carcinoma of the prostate in treatment selection for metastatic hormone-sensitive prostate cancer.

BACKGROUND: In recent years, the usefulness of androgen receptor axis-targeted agents (ARATs) such as abiraterone, enzalutamide, and apalutamide for the upfront treatment of metastatic hormone-sensitive prostate cancer (mHSPC) has been demonstrated. However, it remains unclear which patients would truly benefit from these treatments. Furthermore, intraductal carcinoma of the prostate (IDC-P) is a known poor prognostic factor in patients with prostate cancer. We investigated the association between the presence of IDC-P and response to therapy in patients with mHSPC. METHODS: This retrospective analysis included 318 patients with mHSPC who received treatment at Nagoya University and its 12 affiliated institutions between 2014 and 2021. Their biopsy specimens were evaluated for the presence of IDC-P. The patients were classified according to their first-line treatment into the ARAT (n = 100, receiving a combination of androgen-deprivation therapy [ADT] and ARAT) or conventional therapy (n = 218, receiving ADT with or without standard antiandrogen agents) group. We compared the overall survival (OS) and second progression-free survival (PFS2) between the ARAT and conventional groups according to the presence of IDC-P to evaluate whether presence of IDC-P predicts the response to each treatment. PFS2 was defined as the period from mHSPC diagnosis to disease progression on second-line treatment or death. Propensity score matching with one-to-one nearest-neighbor matching was used to minimize the potential effects of selection bias and confounding factors. The clinicopathological variables of the patients were well-balanced after propensity score matching. RESULTS: Most patients in the ARAT (79%) and conventional therapy (71%) groups were ICD-P positive. In the propensity score-matched cohort, the OS and PFS2 of IDC-P-positive patients were significantly longer in the ARAT group than in the conventional group (OS: hazard ratio [HR], 0.36; p = 0.047; PFS2: HR, 0.30; p < 0.001). In contrast, no difference in OS and PFS2 was observed between the ARAT and conventional groups in IDC-P-negative patients (OS: HR, 1.09; p = 0.920; PFS2: HR, 0.40; p = 0.264). CONCLUSIONS: The findings highlight a high prevalence of IDC-P among patients with mHSPC and suggest that IDC-P positivity may be a reliable indicator that ARAT should be implemented as first-line treatment.

Adiponectin can be a good predictor of urodynamic detrusor underactivity: a prospective study in men with lower urinary tract symptoms.

PURPOSE: To investigate whether circulating adiponectin, which is considered a possible marker of anti-atherogenic effects, is a useful predictor of bladder function, especially detrusor underactivity (DU), in men with lower urinary tract symptoms (LUTS). METHODS: A total of 130 treatment-naïve men with non-neurogenic LUTS were prospectively stratified into two groups (the DU and non-DU groups) based on the presence or absence of DU, where DU is defined as a bladder contractility index < 100 and bladder outlet obstruction index (BOOI) < 40. The impact of serum adiponectin levels on urodynamic function, including DU, was assessed using univariate, binomial logistic regression, and receiver operating characteristic (ROC) curve analyses. RESULTS: In total, data from 118 men were analyzed; 39 (33.0%) had DU (DU group) and 79 (67.0%) did not have DU (non-DU group). The median serum adiponectin in the DU group was significantly lower than in the non-DU group (6.2 vs 12.6 µg/mL, p < 0.001). In the binomial logistic regression analysis, lower adiponectin, smaller intravesical prostatic protrusion, and lower bladder voiding efficiency were significant factors related to DU. In the ROC analyses, serum adiponectin had the highest area under the curve value for DU diagnosis (0.849). Additionally, a cutoff value of 7.9 µg/mL for serum adiponectin level was identified for DU, which yielded a sensitivity and specificity of 79% and 90%, respectively. CONCLUSIONS: The serum adiponectin level was significantly associated with bladder function and may be a useful marker for predicting DU in men with LUTS.

Two types of detrusor underactivity in men with nonneurogenic lower urinary tract symptoms.

AIMS: To clarify the clinical features of men with nonneurogenic detrusor underactivity (DU) by focusing on storage dysfunction (SD). METHODS: We retrospectively reviewed the clinical and urodynamic data of men with nonneurogenic DU. Patients were divided into two groups according to the presence or absence of SD, such as detrusor overactivity (DO) and reduced bladder compliance (BC). Patient characteristics, lower urinary tract symptoms (LUTS), and urodynamic parameters were compared. DU was defined as bladder contractility index (BCI) ≤ 100 and bladder outlet obstruction index (BOOI) ≤ 40. RESULTS: Of 212 men with DU, 123 (58.0%) had concomitant SD (SD + DU group), and 89 (42.0%) had only DU (DU-only group). Age, prostate volume, and severity of storage symptoms were significantly higher in the SD + DU group. Particularly, >80% of men in the SD + DU group met the diagnostic criteria for overactive bladder in Japan, which was significantly higher than the 26% of men in the DU-only group. The frequency of urinary urgency incontinence (UUI) was also significantly higher in the SD + DU group (65% vs. 12% in DU-only group). In contrast, voiding symptoms, including straining, were more severe in the DU-only group. Regarding the urodynamic parameters, compared to the DU-only group, bladder capacity was significantly smaller and BOOI and BCI were significantly higher in the SD + DU group. However, there was no significant difference in the maximum flow rate and bladder voiding efficiency. CONCLUSIONS: Approximately 60% of men with DU had SD, such as DO and/or reduced BC, whereas the remaining 40% had increased bladder capacity without an increase in detrusor pressure during the storage phase. There were significant differences in the storage and voiding symptoms between the groups. It is important to divide patients with DU based on SD to accurately clarify the clinical picture of DU.

Characteristics of uroflowmetry patterns in men with detrusor underactivity revealed by artificial intelligence.

OBJECTIVES: To elucidate the characteristics of uroflowmetry (UFM) observed in men with detrusor underactivity (DU) using our developed artificial intelligence (AI) diagnostic algorithm to distinguish between DU and bladder outlet obstruction (BOO). METHODS: Subjective and objective parameters, including four UFM parameters (first peak flow rate, time to first peak, gradient to first peak, and the ratio of first peak flow rate to maximum flow rate [Qmax ]) selected by analyzing the judgment basis of the AI diagnostic system, were compared in 266 treatment-naive men with lower urinary tract symptoms (LUTS). Patients were divided into the DU (70; 26.32%) and non-DU (196; 73.68%) groups, and the UFM parameters for predicting the presence of DU were determined by multivariate analysis and receiver operating characteristic (ROC) curve analysis. Detrusor underactivity was defined as a bladder contractility index <100 and a BOO index <40. RESULTS: Most parameters on the first peak flow of UFM were significantly lower in the DU group. On multivariate analysis, lower first peak flow rate and lower ratio of first peak flow rate to Qmax were significant parameters to predict DU. In the ROC analysis, the ratio of the first peak flow rate to Qmax showed the highest area under the curve (0.848) and yielded sensitivities of 76% and specificities of 83% for DU diagnosis, with cutoff values of 0.8. CONCLUSIONS: Parameters on the first peak flow of UFM, especially the ratio of the first peak flow rate to Qmax , can diagnose DU with high accuracy in men with LUTS.

Impact of the coronavirus disease 2019 pandemic on the number of undergoing radical nephroureterectomy and postoperative adjuvant systematic therapy for upper tract urothelial carcinomas in Japan: A multicenter retrospective study.

OBJECTIVES: The coronavirus disease 2019 pandemic has affected cancer management worldwide. For upper tract urothelial carcinomas, delays in treatments are not recommended even during the pandemic. We investigated the impact of the pandemic on patients with these carcinomas who underwent radical nephroureterectomy (RNU) and adjuvant systematic therapy before and after COVID-19 spread in Japan. METHODS: This multicenter retrospective study included 304 patients who underwent RNU for upper tract urothelial carcinomas between May 1, 2019, and December 31, 2021, in Aichi, Japan. The patients were categorized into three groups based on whether they underwent surgery in the prepandemic (before infection spread in Japan), early pandemic (between confirmation of the first case and vaccination initiation), and late pandemic (after the start of vaccination in Japan) phases. The patient characteristics, diagnostic methods, pathological findings, and postoperative therapy were compared among the three phases. RESULTS: Overall, 74, 152, and 78 patients underwent RNU in the prepandemic, early pandemic, and late pandemic phases, respectively. The number of patients who underwent preoperative ureteroscopy decreased significantly from the prepandemic phase to the late pandemic phase due to pandemic-related restrictions (p = 0.016). There was no difference in the time to the first visit or pathological findings. Among patients classified as high-risk according to existing clinical trials, the proportion receiving adjuvant systematic therapy after RNU decreased significantly from 52.3% to 19% (p = 0.003). CONCLUSIONS: There was no difference in the pathological findings. The number of patients receiving appropriate adjuvant systematic therapy decreased during the pandemic.

Peritoneal Expression of Membrane Complement Regulators Is Decreased in Peritoneal Dialysis Patients with Infected Peritonitis.

In peritoneal dialysis (PD) patients, fungi and Pseudomonas aeruginosa are considered important causative microorganisms for peritonitis with poor prognosis. Our objective was to explore expressions of membrane complement (C) regulators (CRegs) and tissue injuries in the peritoneum of patients with PD-related peritonitis, including fungal and Pseudomonas aeruginosa peritonitis. In peritoneal biopsy tissues obtained at PD catheter removal, we investigated the severity of peritonitis-associated peritoneal injuries and the expression of CRegs, CD46, CD55, and CD59 against peritoneal tissues without any episode of peritonitis. In addition, we evaluated peritoneal injuries among fungal and Pseudomonas aeruginosa-peritonitis (P1) and Gram-positive bacterial peritonitis (P2). We also observed deposition of C activation products such as activated C and C5b-9 and measured sC5b-9 in the PD fluid of patients. As a result, the severity of peritoneal injuries correlated inversely with the expression of peritoneal CRegs. Peritoneal CReg expression in peritonitis was significantly reduced compared to no peritonitis. Peritoneal injuries were more severe in P1 than in P2. CReg expression was further decreased and C5b-9 further increased in P1 than in P2. In conclusion, severe peritoneal injuries due to fungal and Pseudomonas aeruginosa-peritonitis decreased CReg expression and increased deposition of activated C3 and C5b-9 in the peritoneum, suggesting that peritonitis, particularly fungal and Pseudomonas aeruginosa-peritonitis, might induce susceptibility to further peritoneal injuries due to excessive C activation.

Urodynamic risk factors of asymptomatic bacteriuria in men with non-neurogenic lower urinary tract symptoms.

PURPOSE: To investigate the prevalence of asymptomatic bacteriuria (ASB) in middle-aged and older men with non-neurogenic lower urinary tract symptoms (LUTS) and clarify urodynamic factors related to the presence of ASB. METHODS: We retrospectively reviewed the clinical data of men with LUTS who underwent urine culture examination, LUTS severity assessment, and urodynamic studies. The patients were allocated into two groups (the ASB + LUTS and LUTS-only) according to presence or absence of ASB. The patients' characteristics and urodynamic factors related to the development of ASB were assessed using univariate, binomial logistic regression, and receiver-operating characteristic (ROC) curve analyses. RESULTS: Of 440 men, 93 (21.1%) had ASB. Parameters related to voiding functions, such as maximum flow rate, post-void residual urine volume, bladder voiding efficiency (BVE), and bladder contractility index (BCI), were significantly reduced in the ASB + LUTS group, while bladder outlet obstruction index was not different between the groups. Binomial logistic regression analysis showed that the presence of diabetes, lower BCI, and lower BVE were significantly associated with the presence of ASB. In addition, ROC analysis identified 55% as the optimal cutoff value of BVE for the presence of ASB, with a sensitivity of 84% and specificity of 83%. CONCLUSIONS: ASB was found in > 20% of men with non-neurogenic LUTS and was associated with decreased bladder contractility and decreased BVE. BVE could predict presence of ASB with high sensitivity and specificity.

Clinical features and urodynamic findings in elderly men with chronic prostatitis.

OBJECTIVES: To investigate the complication rate of chronic prostatitis/chronic pelvic pain syndrome in men with lower urinary tract symptoms, and to clarify their clinical features and urodynamic findings. METHODS: We retrospectively reviewed the clinical data of treatment-naïve men with lower urinary tract symptoms. Patients were divided into two groups (chronic prostatitis/chronic pelvic pain syndrome + lower urinary tract symptoms and lower urinary tract symptoms only) according to the presence or absence of chronic prostatitis/chronic pelvic pain syndrome, and the patient characteristics as well as the parameters of lower urinary tract symptoms and lower urinary tract function assessed by urodynamics were compared. The diagnostic criteria for chronic prostatitis/chronic pelvic pain syndrome included a complaint of pelvic pain for ≥3 months, National Institutes of Health Chronic Prostatitis Symptom Index pain subscore ≥4, and negative culture of a urine specimen collected after prostate massage. RESULTS: Out of 386 men, 123 (31.9%) had chronic prostatitis/chronic pelvic pain syndrome. Parameters of lower urinary tract symptoms and National Institutes of Health Chronic Prostatitis Symptom Index scores were significantly higher in the chronic prostatitis/chronic pelvic pain syndrome + lower urinary tract symptoms group. Although there were no significant intergroup differences in voiding parameters such as maximum flow rate and bladder outlet obstruction index, storage functions such as the incidence of detrusor overactivity and bladder compliance were significantly reduced in the chronic prostatitis/chronic pelvic pain syndrome + lower urinary tract symptoms group. The multivariable regression analysis revealed that a low serum total testosterone level (<3.5 ng/mL), complications of hyperlipidemia, and presence of overactive bladder and detrusor overactivity were significantly associated with the development of chronic prostatitis/chronic pelvic pain syndrome. CONCLUSIONS: Chronic prostatitis causes a significant decrease in storage function, such as an increase in detrusor overactivity. Additionally, low serum testosterone levels and hyperlipidemia were found to be significantly associated with the development of chronic prostatitis/chronic pelvic pain syndrome in men with lower urinary tract symptoms.

A small pilot study to evaluate the accuracy and feasibility of a novel automated voiding diary device for recording urine output measurements.

AIMS: Recording a voiding diary can be bothersome for patients and is sometimes inaccurate and unhygienic. This study aimed to develop and assess the accuracy and convenience of a novel device that automatically records the voiding diary by measuring pre- and post-void body weight. METHODS: We used this novel device for seven healthy volunteers and ten hospitalized patients. The examinees got on the device before and after voiding and the device recorded the voiding diary automatically. The examinees also manually recorded a voiding diary by collecting their urine in a cup and measuring its volume and weight. We examined the correlation between the traditional and the automated voiding diary to confirm the accuracy of voiding measurements using this device. Additionally, we investigated which measurement method was preferred by the participants. RESULTS: In the healthy volunteers group, there was a strong correlation between the voided urine weight recorded by the device and voided urine weight measured manually by the examinee (R2 = 0.9935). In the patients group, there was a strong (R2 = 0.9117) but lower correlation than that of the volunteers group, with an error of ±25 g 62% of the time, and ±50 g 82% of the time, respectively. All of the healthy volunteers and seven of the ten patients preferred using the automated voiding diary. CONCLUSIONS: This novel device recorded a reasonably accurate voiding diary for everyday clinical practice.

Urodynamic evaluation before and after to RARP to identify pre and intraoperative factors affecting postoperative continence.

AIMS: To investigate factors contributing to pre and postoperative urethral function in male patients who underwent robot-assisted radical prostatectomy (RARP) using the urethral pressure profile (UPP). METHODS: Study A A total of 313 patients who underwent RARP between April 2013 and March 2015 were prospectively investigated. UPP was performed preoperatively in all patients. Correlation and multiple regression analyses were performed to investigate predictive factors for low preoperative maximum urethral closure pressure (MUCP). Study B To validate the predictive factors for low preoperative MUCP obtained in Study A, 755 patients who underwent RARP between May 2010 and October 2017 were retrospectively examined. Relationships between the time to pad-free status and the following factors were investigated: number of predictive factors, nerve-sparing surgery, and vesicourethral anastomosis (VUA) methods (barbed vs. nonbarbed suture). RESULTS: Study A A total of 187 patients were enrolled. Multivariate analysis revealed that older age, large prostate volume, low erectile function domain scores in International Index Erectile Function 15, and use of calcium channel blockers were significantly associated with low preoperative MUCP. Study B A total of 515 patients were included. Cox proportional hazard regression showed that the number of predictive factors and VUA method were significantly associated with the time to pad-free status. CONCLUSIONS: Our study demonstrated that older age, larger prostate volume, poor erectile function, and calcium channel blocker use could be predictive markers for recovery from postprostatectomy urinary incontinence.

Grade group 2 (10% ≥ GP4) patients have very similar malignant potential with grade group 1 patients, given the risk of intraductal carcinoma of the prostate.

BACKGROUND: It has been argued that grade group 2 (GG2) with a low Gleason pattern 4 (GP4) proportion should be an indication for active surveillance (AS) of prostate cancer (PCa). However, the cut-off GP4 proportion for AS remains unclear. Here, we evaluated the effect of GP4 proportion and IDC-P on cancer recurrence following radical prostatectomy (RP) in GG1 and GG2 patients, and identified candidates for AS. METHODS: We retrospectively evaluated 646 patients with PCa who underwent RP between 2005 and 2014, and whose specimens were of GG1 or GG2 status. RESULTS: The GGs were as follows: GG1, 25.2% (n = 163); GG2 (5% ≥ GP4), 11.4% (n = 74); GG2 (5% < GP4 ≤ 10%), 25.9% (n = 167); and GG2 (20% ≤ GP4), 37.5% (n = 242). IDC-P was detected in 26 patients (4%), i.e., in 2/167 GG2 (5% < GP4 ≤ 10%; 1%) cases and 24/242 GG2 (20% ≤ GP4; 10%) cases. GG2 patients with IDC-P exhibited a significantly poorer prognosis than did those without IDC-P (P < 0.0001), as did GG2 (20% ≤ GP4) patients without IDC-P (P < 0.05). The GG2 (5% ≥ GP4) and (5% < GP4 ≤ 10%) groups exhibited prognoses similar to those of the GG1 patients. In multivariate analysis, GG2 (20% ≤ GP4) without IDC-P, the presence of IDC-P, and the prostate-specific antigen level at diagnosis significantly predicted prognosis (P < 0.05, < 0.0001, and < 0.0001, respectively). CONCLUSION: Our findings suggest that GG2 (GP4 ≤ 10%) patients could be indicated for AS, similar to GG1 patients, given the risk of IDC-P tumors.

Daily urine loss immediately after urethral catheter removal may be an effective predictor of long-term urinary incontinence following robot-assisted laparoscopic radical prostatectomy.

PURPOSE: Some patients who undergo robot-assisted laparoscopic radical prostatectomy (RARP) continue to experience long-term urinary incontinence (UI). This study aimed to evaluate easily obtainable factors that can predict long-term UI following RARP. MATERIALS AND METHODS: A total of 315 patients who underwent RARP for localised prostatic cancer were analysed. We separated the patients into two groups, namely, the Continence group and the Incontinence group, according to the presence or absence of UI at 12 months after surgery, and we compared the patients' characteristics and operative data to identify clinical signs associated with long-term UI. Additionally, correlations between these factors and postoperative urethral function were evaluated. Urinary continence was defined as both the use of 0 pads/per day and <2 g of urine lost using the 24-hours pad weight test. RESULTS: Of 315 patients, 250 (79.4%) achieved urinary continence and 65 (20.6%) had long-term UI. Age, storage-related lower urinary tract symptoms before surgery, nerve-sparing surgery and the 24-hours urine loss immediately after urethral catheter removal significantly affected long-term UI after RARP. Multivariate logistic regression analyses revealed that the 24-hours urine loss after catheter removal was a significant predictor of long-term UI. Receiver operating characteristic curve analysis identified a urine loss of 330 g/d as the optimal cut-off value, which yielded 92% sensitivity and 84% specificity, and it showed significant correlations with postoperative urethral function and the time to recover urinary continence. CONCLUSION: The 24-hours urine loss immediately after urethral catheter removal may be the most reliable and useful predictor of long-term UI following RARP.

Effects of tadalafil versus silodosin on voiding function in male patients with non-neurogenic detrusor underactivity: A comparative study using propensity score matching.

OBJECTIVES: To investigate and compare the effects of tadalafil and silodosin on lower urinary tract symptoms and voiding functions in men with non-neurogenic detrusor underactivity. METHODS: A total of 126 treatment-naive men with lower urinary tract symptoms diagnosed as non-neurogenic detrusor underactivity received tadalafil (5 mg/day) or silodosin (8 mg/day) for 12 months. After propensity score matching, parameter changes from before administration to 12 months since treatment initiation were assessed based on subjective symptoms and urodynamic findings, including bladder contractility index and maximum urinary flow rate, and were compared between the tadalafil treatment group and the silodosin group. Detrusor underactivity was defined as bladder contractility index <100 and bladder outlet obstruction index <40. RESULTS: After propensity score matching, the final analysis included 48 patients each in the tadalafil and silodosin groups. No significant differences in prostate volume, subjective symptoms or urodynamic parameters were detected between the groups at baseline. Compared with baseline, significant improvements in subjective symptoms and storage and voiding functions were observed at month 12 in both groups. Maximum urinary flow rate significantly improved by 1.7 mL/s in the silodosin group and by 3.0 mL/s in the tadalafil group. In addition, the mean bladder contractility index increased from 80.0 to 86.1 in the silodosin group and from 77.9 to 97.6 in the tadalafil group. Improvements in maximum urinary flow rate and bladder contractility index were significantly superior in the tadalafil group. CONCLUSIONS: Both tadalafil and silodosin significantly improve lower urinary tract symptoms and voiding function in patients with non-neurogenic detrusor underactivity. Furthermore, tadalafil is more effective than silodosin in improving bladder contractility index and maximum urinary flow rate.

Development of an artificial intelligence diagnostic system for lower urinary tract dysfunction in men.

OBJECTIVES: To establish an artificial intelligence diagnostic system for lower urinary tract function in men with lower urinary tract symptoms using only uroflowmetry data and to evaluate its usefulness. METHODS: Uroflowmetry data of 256 treatment-naive men with detrusor underactivity, bladder outlet obstruction, or detrusor underactivity + bladder outlet obstruction were used for artificial intelligence learning and validation using neural networks. An optimal artificial intelligence diagnostic model was established using 10-fold stratified cross-validation and data augmentation. Correlations of bladder contractility index and bladder outlet obstruction index values for the artificial intelligence system and pressure flow study values were examined using Spearman's correlation coefficients. Additionally, diagnostic accuracy was compared between the established artificial intelligence system and trained urologists with uroflowmetry data of 25 additional patients by χ2 -tests. Detrusor underactivity was defined as bladder contractility index ≤100 and bladder outlet obstruction index ≤40, bladder outlet obstruction was defined as bladder contractility index >100 and bladder outlet obstruction index >40, and detrusor underactivity + bladder outlet obstruction was defined as bladder contractility index ≤100 and bladder outlet obstruction index >40. RESULTS: The artificial intelligence system's estimated bladder contractility index and bladder outlet obstruction index values showed significant positive correlations with pressure flow study values (bladder contractility index: r = 0.60, P < 0.001; bladder outlet obstruction index: r = 0.46, P < 0.001). The artificial intelligence system's detrusor underactivity diagnosis had a sensitivity and specificity of 79.7% and 88.7%, respectively, and those for bladder outlet obstruction diagnosis were 76.8% and 84.7%, respectively. The artificial intelligence system's average diagnostic accuracy was 84%, which was significantly higher than that of urologists (56%). CONCLUSIONS: Our artificial intelligence diagnostic system developed using the uroflowmetry waveform distinguished between detrusor underactivity and bladder outlet obstruction with high sensitivity and specificity in men with lower urinary tract symptoms.

The clinical benefit of sequential therapy with androgen receptor axis-targeted agents alone in patients with castration-resistant prostate cancer: A propensity score-matched comparison study.

BACKGROUND: The optimal sequential therapy for castration-resistant prostate cancer (CRPC) remains unknown. In recent years, some doubts have emerged regarding the clinical benefit of sequential therapy with androgen receptor axis-targeted agents (ART) such as abiraterone (ABI) or enzalutamide (ENZ) for patients with CRPC. We compared the effect of ART-to-ART (AA) sequential therapy after castration resistance with that of docetaxel (DTX)-combined sequential therapy (ART to DTX or DTX to ART) in patients with CRPC. METHODS: We retrospectively identified and analyzed the data of 315 patients with CRPC treated in our seven affiliated institutions between 2009 and 2019. All patients received either DTX or ART (ABI or ENZ) as the first- or second-line therapy after castration resistance. We compared the overall survival (OS) and the second progression-free survival (PFS2), calculated from the initiation of first-line therapy after castration resistance, between the AA sequence group and the DTX-combined sequence group. PFS2 was defined as the period from the start of first-line treatment after castration resistance to progression on second-line treatment. To minimize selection bias from possible confounders, we performed propensity score matching using one-to-one nearest neighbor matching without replacement. RESULTS: Overall, 106 and 209 patients were administered the AA sequential therapy and DTX-combined sequential therapy, respectively. The clinicopathological variables of patients were well balanced after propensity score matching, and there were no significant differences between the two groups. In the propensity score-matched cohort, OS was not significantly different between the two groups (median, 37.9 vs. 45.4 months; hazard ratio [HR], 1.10; 95% confidence interval [CI], 0.68-1.79; p = .701), while PFS2 was significantly shorter in the AA group than in the DTX-combined group (median, 12.9 vs. 21.6 months; HR, 1.70; 95% CI, 1.16-2.48; p = .007). CONCLUSIONS: Certain patients with CRPC can benefit from ART-to-ART sequential therapy in a daily clinical setting.

Response of intraductal carcinoma of the prostate to androgen deprivation therapy predicts prostate cancer prognosis in radical prostatectomy patients.

BACKGROUND: Intraductal carcinoma of the prostate (IDC-P) has a poor prognosis and is thought to be completely resistant to current therapies, including androgen deprivation therapy (ADT). However, to date, there are no data showing direct evidence of such resistance. METHODS: We retrospectively evaluated 145 patients with high-risk prostate cancer who underwent radical prostatectomy (RP) with neoadjuvant ADT between 1991 and 2005. All patient data were collected from slides prepared from needle biopsy (NB) samples of prostate tissue and RP specimens. Data were analyzed in terms of serum level of prostate specific antigen (PSA), Gleason score of NB samples, clinical T stage, the positive cancer core rate, maximum cancer extension rate, presence of Gleason pattern 5, and presence of IDC-P in both NB samples and RP specimens. RESULTS: The median initial PSA was 33.2 ng/mL (range, 2.4-296 ng/mL), and the median follow-up period was 109 months (range, 11-257 months). The preoperative median ADT period was 4 months (range, 1-20 months). IDC-P was present in 53 patients (37%) in NB samples and 65 (45%) in RP. The patients were divided into three groups based on the presence or absence of IDC-P in NB/RP samples (IDC-P-negative at biopsy: 92 cases, IDC-P-positive at biopsy with IDC-P disappearance: 15 cases, and IDC-P-positive at biopsy with IDC-P persistence: 38 cases). Overall, 28% of IDC-P-positive cases in NB samples showed the disappearance of IDC-P at RP. IDC-P persistence cases showed the poorest prognosis, while IDC-P disappearance cases had a similar prognosis to that of IDC-P-negative at biopsy cases in terms of disease-free survival, cancer-specific survival, and overall survival (P = .0018, P = .0087, and P = .0034, respectively). CONCLUSIONS: Some cases with IDC-P responded to ADT and demonstrated favorable clinical outcomes similar to those of cases without IDC-P. These findings indicate that cases with IDC-P are heterogeneous.

The effect of mirabegron on bladder blood flow in a rat model of bladder outlet obstruction.

PURPOSE: To evaluate the effects of mirabegron on bladder blood flow in a rat model of bladder outlet obstruction (BOO). METHODS: Adult female Sprague-Dawley rats were divided into three groups based on whether they underwent a sham operation (sham group) or an operation to establish partial BOO (BOO and BOO + mirabegron groups). The BOO + mirabegron group was treated with mirabegron (0.3 mg/kg/h, subcutaneously) for 14 days. Subsequently, we performed continuous cystometry, bladder blood flow measurements with a 2D laser blood flow imager, hematoxylin-eosin staining of the bladder tissue, and malondialdehyde (MDA) measurements in the bladder tissue. RESULTS: Cystometry revealed significantly higher peak pressure, more residual urine volume, and lower voiding efficiency in the BOO and BOO + mirabegron groups than in the sham group. The BOO + mirabegron group had significantly fewer non-voiding contractions (NVCs) than the BOO group, while the latter had more frequent NVCs than the sham group. The BOO and BOO + mirabegron groups had significantly decreased bladder blood flow than the sham group, whereas the BOO + mirabegron group showed significantly increased bladder blood flow than the BOO group. The bladder tissue in the BOO group contained more hypertrophic detrusor muscle compared to the sham group, while mirabegron treatment suppressed detrusor hypertrophy. The MDA levels were significantly higher in the BOO group than in the BOO + mirabegron and sham groups. CONCLUSION: Mirabegron treatment significantly improved BOO-induced bladder dysfunction through the amelioration of bladder blood flow.