CHARGE syndrome with both primary and secondary hypogonadism.

Introduction: CHARGE syndrome is a rare disorder that causes congenital abnormalities in multiple organs, including secondary hypogonadism. We report, herein, a unique case of CHARGE syndrome with both primary and secondary hypogonadism and discuss the possible causes and pathogenesis in this patient. Case presentation: A 15-year-old boy with delayed secondary sexual characteristics and non-palpable testes was referred to our hospital. Physical examination and detection of a chromodomain-helicase-deoxyribonucleic acid-binding protein 7 gene mutation confirmed CHARGE syndrome. Hormone stimulation tests suggested both primary and secondary hypogonadism. Laparoscopic bilateral orchiectomy was performed because of decreased testosterone production and atrophy in both testes. Pathological examination of the testes revealed maturation arrest, germ cell neoplasm in situ, and decreased expression of steroid synthase. Conclusion: This appears to be the first report of CHARGE syndrome with both primary and secondary hypogonadism demonstrated in endocrinological and histological examinations.

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.

PSMA Targeted Molecular Imaging and Radioligand Therapy for Prostate Cancer: Optimal Patient and Treatment Issues.

Theranostics (therapy + diagnosis) targeting prostate-specific membrane antigen (PSMA) is an emerging therapeutic modality that could alter treatment strategies for prostate cancer. Although PSMA-targeted radioligand therapy (PSMA-RLT) has a highly therapeutic effect on PSMA-positive tumor tissue, the efficacy of PSMA-RLT depends on PSMA expression. Moreover, predictors of treatment response other than PSMA expression are under investigation. Therefore, the optimal patient population for PSMA-RLT remains unclear. This review provides an overview of the current status of theranostics for prostate cancer, focusing on PSMA ligands. In addition, we summarize various findings regarding the efficacy and problems of PSMA-RLT and discuss the optimal patient for PSMA-RLT.

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

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

SMARCB1-deficient basal cell carcinoma of the prostate controlled using radiation therapy.

Introduction: Basal cell carcinoma of the prostate is rare, with no established treatment for its recurrence or metastasis. We report a case involving basal cell carcinoma of the prostate controlled using radiotherapy. Case presentation: A 57-year-old man complained of perineal pain. Although his prostate-specific antigen was 0.657 ng/mL, a digital rectal examination revealed his prostate was stone hard. Prostate needle biopsy showed basal cell carcinoma of the prostate. The patient then underwent radical prostatectomy. Local recurrence and sacral bone metastasis appeared 2 months after surgery. OncoGuide™ NCC Oncopanel System showed deletion of SMARCB1; however no recommended treatment was identified. Thus, we decided to perform radiotherapy, which reduced all lesions. Conclusion: Basal cell carcinoma of the prostate may have a poor prognosis with recurrence or metastasis, hence evaluation of prognostic factors is important. In this case, the genomic profiling test suggested that SMARCB1 deletion may be a prognostic factor associated with disease progression.

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.

Concurrent Reduced Expression of Contiguous PKD1, TSC2 and NTHL1 Leading to Kidney Diseases and Multiple Diverse Renal Cancers.

BACKGROUND/AIM: Several cases of concurrent reduction of expression of polycystin 1 (PKD1) and Tuberous Sclerosis Complex 2 (TSC2) that are contiguous in chromosome 16p13 have been previously reported. This study newly addresses the concurrent reduction of expression of PKD1, TSC2 and NTHL1, which is adjacent to TSC2 and is a tumor suppressor gene. MATERIALS AND METHODS: We investigated the mRNA expression levels of PKD1, TSC2, PKD2, TSC1 and NTHL1 in blood and renal cell carcinoma (RCC) tissues in a proband with autosomal dominant polycystic kidney disease (ADPKD), tuberous sclerosis complex (TSC) and multiple pathologically diverse RCCs, including clear cell, papillary and chromophobe types. Additionally, we investigated germline variants in blood using whole exome sequencing (WES) in the proband and her four siblings. RESULTS: mRNA expression levels of PKD1, TSC2 and NTHL1 were reduced in the proband's blood and RCCs, compared with control groups. WES identified one novel variant with amino acid changes in the PKD1 exon in the three subjects with ADPKD, including the proband. Moreover, two variants in the TSC2 intron specific to the proband were also identified. CONCLUSION: In this study, we report a novel pathogenic variant in the PKD1 exon which likely led to ADPKD, and two variants in the TSC2 intron, which might have led to reduction in the expression of both TSC2 and NTHL1, consequently leading to TSC and multiple pathologically diverse RCCs.

Successful management of pelvic recurrence of MSI-High endometrial cancer by total pelvic exenteration followed by administration of pembrolizumab:A case report.

Surgery can be curative treatment for pelvic locoregional recurrence of endometrial cancer; however, a cure is contingent on complete resection. Here, we report the case of a patient in whom recurrent endometrial tumor remained in the pelvis after resection; long-term control was achieved with postoperative administration of pembrolizumab.The patient had recurrent endometrial cancer of stage IA and was treated with chemotherapy and radiation, but tumor persisted in the pelvic cavity. We therefore attempted total pelvic exenteration, but the tumor was adherent to the pelvic wall and complete resection could not be achieved. However, postoperative administration of pembrolizumab controlled the residual tumor for more than two years without regrowth. We believe that since the resected tumor was MSI-High, the residual tumor responded well to pembrolizumab. It is not known whether cytoreductive surgery contributes to a long-term response to pembrolizumab, but at least in our patient, pembrolizumab appeared to be a very effective drug therapy for MSI-High endometrial cancer that was refractory to chemotherapy and radiotherapy.

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

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

Low Risk of Venous Thromboembolism After Robot-assisted Radical Prostatectomy Through Systemic Image Assessment: A Prospective Study.

BACKGROUND/AIM: The aim of the study was to evaluate the risk of venous thromboembolism (VTE) after robot-assisted radical prostatectomy (RARP) and discuss whether a uniform prophylaxis for VTE after radical prostatectomy is also suitable for robotic surgery. On this context, we investigated the incidence and risk factors of VTE, including asymptomatic events, after RARP compared to transurethral resection of bladder tumor (TUR-BT). PATIENTS AND METHODS: The participants were 209 patients with localized prostate cancer who underwent RARP, and 93 patients who underwent TUR-BT as controls. The incidence and risk factors of VTE, including deep vein thrombosis and pulmonary embolism, were systemically investigated seven days after surgery using contrast-enhanced computed tomography. RESULTS: Of the 209 RARP patients, 5.7% (12/209) patients had VTE. All events were asymptomatic and the incidence of VTE was not significantly different between the two surgeries (p=0.90). In multivariate analyses, neoadjuvant androgen deprivation therapy (ADT) (p=0.006), D-dimer value on postoperative day 1 (p=0.001) and lymphocele formation (p=0.043) were significantly associated with VTE after RARP. CONCLUSION: The risk of VTE after RARP might not be so high and uniform prophylaxis might not be suitable for RARP because it might be the same as that after transurethral resection for bladder tumors. However, neoadjuvant ADT, high D-dimer levels after surgery and lymphocele formation should be noted as risk factors of VTE after RARP.

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.

Impacts of Neoadjuvant Hormonal Therapy Prior to Robot-Assisted Radical Prostatectomy on Postoperative Hormonal- and Sexual-Related Quality of Life - Assessment by Patient-Reported Questionnaire.

PURPOSE: Neoadjuvant hormonal therapy (HT) before radical prostatectomy (RP) is not recommended by current guidelines in terms of oncological outcomes. Despite this, neoadjuvant HT is sometimes conducted before RP for a small proportion of patients in clinical practice. This study evaluated the impacts of neoadjuvant HT on hormonal- and sexual-related quality of life (QOL) among patients who underwent robot-assisted RP (RARP). MATERIALS AND METHODS: Participants comprised 470 patients divided into a non-neoadjuvant HT group (n = 408) and a neoadjuvant HT group (n = 62). Hormonal- and sexual-related QOL were measured using the Expanded Prostate Cancer Index Composite (EPIC) questionnaire. RESULTS: Hormonal summary scores at 6 and 9 months, function scores before and 3, 6, and 9 months and bother score at 6 months after RARP were significantly lower in the neoadjuvant HT group than in the non-neoadjuvant HT group. Sexual function scores were decreased in the neoadjuvant HT group compared to the non-neoadjuvant HT group before and 6 months after RARP. In the neoadjuvant HT group, sexual function at 3 months after RARP was significantly worse in patients with >5 months of neoadjuvant HT than in patients with ≤5 months of neoadjuvant HT. Conversely, sexual bother at 3 months after RARP was significantly worse in patients with ≤5 months of neoadjuvant HT than in patients with >5 months of neoadjuvant HT. CONCLUSION: Vintage neoadjuvant HT prior to RARP should not be recommended due to not only oncological outcomes, but also the impacts on postoperative hormonal- and sexual-related QOL.

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.

l-Theanine Protects Bladder Function by Suppressing Chronic Sympathetic Hyperactivity in Spontaneously Hypertensive Rat.

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

Usefulness of the mayo adhesive probability score as a predictive factor for renal function deterioration after partial nephrectomy: a retrospective case-control study.

PURPOSE: Whether the Mayo adhesive probability score, an index of the perinephric fat environment, could be a predictive factor for renal function deterioration after partial nephrectomy was investigated. METHODS: A retrospective case-control study of 78 patients who underwent laparoscopic partial nephrectomy was performed. An estimated glomerular filtration rate preservation rate at ≤ 90% at 3 months after surgery was defined as postoperative renal function deterioration. These patients were divided into two groups (non-deterioration and deterioration groups). Patient factors including Mayo adhesive probability scores (both tumor and unaffected sides) and surgical factors were evaluated to identify the predictors for postoperative renal function deterioration. The statistical analysis used univariate and multivariate logistic regression analyses. RESULTS: Thirty-seven (47.4%) patients had postoperative renal function deterioration after partial nephrectomy. Univariate analysis identified Mayo adhesive probability score on the unaffected side (p = 0.02), and warm ischemia time (p < 0.01) as predictors of postoperative renal function deterioration. On multivariate analyses, Mayo adhesive probability score on the unaffected side (odds ratio: 1.38 [1.05-1.79], p = 0.02) and warm ischemia time (odds ratio: 1.04 [1.01-1.07], p < 0.01) were significantly associated with postoperative renal function deterioration as same as univariate analysis. On receive operating characteristic curve analysis, Mayo adhesive probability score on the unaffected side (cutoff value 1.5; p = 0.02) and warm ischemia time (cutoff value 26.5 min; p = 0.01) were significant predictors of renal function deterioration 3 month after surgery. CONCLUSION: The Mayo adhesive probability score on the unaffected side and warm ischemia time are useful predictors for renal function deterioration after partial nephrectomy. TRIAL REGISTRATION NUMBER: 2019-249, January 21st, 2019, retrospectively registered.

Association Between Surgical Stress and Biochemical Recurrence After Robotic Radical Prostatectomy.

BACKGROUND AND OBJECTIVES: This study was conducted to identify whether surgical stress during the peri-operative period of robot-assisted radical prostatectomy might affect biochemical recurrence in patients with positive surgical margins. METHODS: Participants in the present study were 324 consecutive patients with localized prostate cancer who underwent robot-assisted radical prostatectomy between February 2013 and June 2018. Positive surgical margins were diagnosed in 61 of them. Patients with positive surgical margins were divided into those with (n = 19) and those without (n = 42) biochemical recurrence. Lymph node dissection, estimated blood loss, inhalation anesthetic volume, and surgical duration were evaluated as indicators of surgical stress. White blood cell count, C-reactive protein, body temperature, and usage of analgesics were postoperatively evaluated as surrogate markers of surgical stress. The associations between factors, including patients' characteristics and pathological features, and biochemical recurrence were investigated. RESULTS: In univariate analyses, surgical duration (P = 0.004), D'Amico risk class (P = 0.002), Gleason score (P = 0.022) and the number of positive cores in prostate biopsy (P = 0.009) were statistically significantly associated with biochemical recurrence. In multivariate analyses, only surgical duration was significantly associated with biochemical recurrence (P = 0.042), at a cut-off value of surgical duration of 228.5 minutes. CONCLUSIONS: Prolonged surgical duration is associated with biochemical recurrence in patients with positive surgical margins. Thus, surgical duration should be limited as much as possible to reduce surgical stress, which might cause biochemical recurrence.

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.

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.

Tetrahydrobiopterin prevents chronic ischemia-related lower urinary tract dysfunction through the maintenance of nitric oxide bioavailability.

This study aimed to investigate the influence of chronic ischemia on nitric oxide biosynthesis in the bladder and the effect of administering tetrahydrobiopterin (BH4), a cofactor for endothelial nitric oxide synthase (eNOS), on chronic ischemia-related lower urinary tract dysfunction (LUTD). This study divided male Sprague-Dawley rats into Control, chronic bladder ischemia (CBI) and CBI with oral BH4 supplementation (CBI/BH4) groups. In the CBI group, bladder capacity and bladder muscle strip contractility were significantly lower, and arterial wall was significantly thicker than in Controls. Significant improvements were seen in bladder capacity, muscle strip contractility and arterial wall thickening in the CBI/BH4 group as compared with the CBI group. Western blot analysis of bladder showed expressions of eNOS (p = 0.043), HIF-1α (p < 0.01) and dihydrofolate reductase (DHFR) (p < 0.01), which could regenerate BH4, were significantly higher in the CBI group than in Controls. In the CBI/BH4 group, HIF-1α (p = 0.012) and DHFR expressions (p = 0.018) were significantly decreased compared with the CBI group. Our results suggest that chronic ischemia increases eNOS and DHFR in the bladder to prevent atherosclerosis progression. However, DHFR could not synthesize sufficient BH4 relative to the increased eNOS, resulting in LUTD. BH4 supplementation protects lower urinary tract function by promoting eNOS activity.