Randomized controlled study of the efficacy and safety of continuous saline bladder irrigation after transurethral resection for the treatment of non-muscle-invasive bladder cancer.

OBJECTIVE: To evaluate the efficacy and safety of continuous saline bladder irrigation (CSBI) after transurethral resection of bladder tumour (TURBT) in patients with low- to intermediate-risk non-muscle invasive bladder cancer (NMIBC). PATIENTS AND METHODS: In this prospective randomized study, 250 patients with primary low- to intermediate-risk tumours were enrolled. Patients were randomly allocated to receive CSBI (2 000 mL/h for the first 1 h, then 1 000 mL/h for 2 h, followed by 500 mL/h for 15 h) or a single immediate instillation of mitomycin C (MMC) after TURBT. The primary endpoint was recurrence-free survival, and secondary endpoints were progression-free survival and adverse events. RESULTS: A total of 227 patients (114 in the CSBI group and 113 in MMC group) remained for analysis after exclusion criteria had been applied. The median follow-up period was 37 months. No significant differences in patient characteristics were observed between the groups. The 5-year recurrence-free rates for CSBI and MMC were 62.6% (95% confidence interval [CI] 0.49-0.73) and 70.4% (95% CI 0.59-0.78), respectively. Kaplan-Meier analysis of recurrence-free survival did not show any significant differences between the groups (log-rank test P = 0.53). Furthermore, there were no significant differences between the groups in terms of tumour progression rate and the median time to first recurrence. The incidence of adverse events was significantly lower in the CSBI group. CONCLUSIONS: The results show that CSBI after TURBT may be a treatment option for patients with low- to intermediate-risk NMIBC in terms of its prophylactic effect and safety.

Predictive Factors for Extracapsular Extension of Prostate Cancer to Select the Candidates for Nerve-sparing Radical Prostatectomy.

Nerve-sparing radical prostatectomy (NSRP) for prostate cancer (PC) enables better postoperative recovery of continence and potency but may increase the risk of positive surgical margins. This study aimed to investigate preoperative predictive factors for extracapsular extension (ECE) of PC to select patients for NSRP. We retrospectively evaluated 288 patients with PC (576 lobes) diagnosed with 12-core transrectal ultrasound-guided biopsy and magnetic resonance imaging (MRI) who underwent laparoscopic or robot-assisted radical prostatectomy at our institution. Surgical specimens and preoperative parameters (prostate-specific antigen, prostate volume, biopsy and MRI findings, preoperative therapy) were analyzed. Of 576 prostate lobes, the incidence Ipsilateral ECE was identified in 97 (16.8%) lobes. The higher number of unilateral positive biopsy cores, the highest Gleason score 8 or more and positive unilateral findings on MRI are significant higher in prostate sides with ECE in univariate analysis. In multivariate analysis, positive unilateral MRI findings (odds ratio [OR], 2.86; p < 0.001) and unilateral biopsy positive core ≥ 3 (OR, 3.73; p < 0.001) were independent predictors of unilateral ECE. The detection rate of unilateral ECE in those cases with two factors (side-specific positive biopsy core 2 or less and side-specific MRI findings negative) was 7.1% (19/269). Patients with fewer unilateral positive biopsy cores and negative unilateral MRI findings might be good candidates for NSRP.

Simple and reliable predictive factor for early recovery of urinary continence after non-nerve-sparing robot-assisted laparoscopic radical prostatectomy.

Post-prostatectomy urinary incontinence is one of the greatest concerns for both patients and urologists. The aim of this study is to elucidate simple and reliable factors contributing to early recovery of urinary continence (UC) and to develop a prediction model for early continence recovery after robot-assisted laparoscopic non-nerve-sparing radical prostatectomy (non-NS RARP). A retrospective analysis of 212 consecutive patients who underwent non-NS RARP by a single surgeon was carried out. Early recovery of urinary continence was defined as using no pads or one security pad per day within 1 month. Preoperative membranous urethral length (MUL) was measured on MRI, and the urinary continence at the standing position (UCSP) after removal of the catheter was examined during cystourethrography 6 days after surgery. Multivariable analysis was performed to detect predictive and postoperative factors associated with early recovery of urinary continence. The early continence recovery rate was 56.1%. Multivariable analysis revealed that MUL ≥ 13 mm, UCSP, and age ≤ 67 were the independent factors for early continence recovery. Early recovery rates were 97.1% for good risk, 76.3% for intermediate risk, and 28.4% for poor risk when divided into three risk groups by the sum score of three independent factors. Preoperative MUL, UCSP, and age are independent predictors of early recovery of UC in non-NS RARP, and our simple prediction model with the combination of the three factors could be a useful tool in clinical practice.

Neonatal adrenal hemorrhage presenting as an acute scrotum: A case report on the rare presentation of right adrenal hemorrhage and contralateral left scrotal hematoma.

Introduction: Acute swelling and discoloration of the scrotum in a newborn is a rare condition and can have several causes such as testicular torsion, trauma, inguinal hernia, hydrocele, or adrenal hemorrhage. Case presentation: We report a neonate of adrenal hemorrhage presenting clinically as the acute scrotum. Definitive diagnosis was defined by ultrasonography and computed tomography scan, and the conservative management was successfully performed. Conclusion: Adrenal hemorrhage should be considered as one of the causes of acute scrotum in newborns. The abdominal ultrasonography, as well as the scrotal ultrasonography, should be performed routinely to achieve a definitive diagnosis to avoid unnecessary invasive procedures.

Usefulness of Biparametric Magnetic Resonance Imaging Combined With Prostate Specific Antigen Density in Pre-biopsy Detection of Clinically Insignificant Prostate Cancer.

BACKGROUND/AIM: The aim of this study was to identify simple and reliable factors to detect clinically insignificant prostate cancer (PC) for avoiding immediate prostate biopsies using biparametric magnetic resonance imaging (MRI), which consists of T2-weighted and diffusion-weighted imaging. PATIENTS AND METHODS: We retrospectively evaluated 427 men with suspected PC, who underwent biparametric MRI and standard 12-core transrectal prostate biopsy. MRI and prostate specific antigen density (PSAD) were analysed. To evaluate the combination of the two parameters, patients were divided into three groups (Group A: MRI negative and PSAD <0.23, Group B: MRI positive or PSAD ≥0.23, Group C: MRI positive and PSAD ≥0.23). A grade of ≥2 was defined as clinically significant PC. RESULTS: Clinically significant PC was detected in 46.5% of men with positive MRI findings, and 60.0% of men with PSAD ≥0.23. When combining MRI and PSAD, detection rates of clinically significant PC were 10.0%, 28.4% and 65.3% in group A, B and, C, respectively. CONCLUSION: Negative biparametric MRI findings with PSAD <0.23 might be a reliable evidence for avoiding immediate prostate biopsies.

Impact of noninvasive down-staging after transurethral resection of bladder tumor plus systemic chemotherapy on bladder-sparing strategy in patients with muscle-invasive bladder cancer.

OBJECTIVE: To identify the optimal selection criteria for bladder sparing strategy with transurethral resection of bladder tumor (TURBT) and systemic chemotherapy in patients with muscle-invasive bladder cancer (MIBC). METHODS: We conducted a retrospective cohort study in 71 patients with MIBC (T2-4aN0M0) who desire to bladder preservation received neoadjuvant chemotherapy (NAC) after maximal TURBT, followed by clinical restaging and second-TURBT. Fifty-eight of 71 patients with no residual tumor on the second-TURBT were placed on conservative management for bladder sparing (BS). Noninvasive down-staging (NID) was defined as cT0/Ta/Tis/T1N0 at first-TURBT after NAC and no residual tumor on second-TURBT. Overall survival (OS) and cystectomy-free survival (CFS) were assessed according to the response of NAC in the BS group by using Kaplan-Meier methods. Cox proportional hazards regression model was used to identify independent variables predicting OS. RESULTS: At a median follow-up of 40 months 5-year OS and CFS in patients with NID and non-NID were 89.1% versus 20.8% and 84.8% versus 16.7%, respectively. Multivariate analysis showed that the ≥3 cycles of NAC (hazard ratio [HR] 0.14, 95% confidential index [CI] 0.03-0.7; P = 0.017) and achievement of NID (HR 0.11, 95% CI 0.03-0.46, P = 0.002) favorably associated with OS. CONCLUSIONS: Patients who achieved NID might be optimal candidates for the bladder sparing strategy with maximum TURBT plus NAC followed by second-TURBT.

Lactobacillus paragasseri as a novel causative pathogen of cavernosal abscess.

Most cases of cavernosal abscesses result from the progression of sexually transmitted diseases (STDs) commonly caused by Neisseria gonorrhoeae; however, cavernosal abscesses without STDs are rare events. Herein, we describe the first case report of a Lactobacillus paragasseri cavernosal abscess. A 63-year-old man with diabetes and a history of foreign object insertion into the urethra one year prior presented with high-grade fever and slight local pain. The patient was diagnosed with L. paragasseri cavernosal abscess based on computed tomography and microbial biochemical examinations in addition to matrix-assisted laser desorption ionization (MALDI) and 16S rRNA sequencing from blood and pus cultures. The patient was successfully treated with a surgical procedure and appropriate antimicrobials. Hence, L. paragasseri, a commensal bacterium of the gastrointestinal or genitourinary tract, can cause cavernosal abscesses. Notably, L. paragasseri is difficult to distinguish from L. gasseri using MALDI or 16S rRNA sequencing without microbial biochemical examinations owing to morphological similarities. Therefore, special attention should be paid, clinically and microbiologically, to the potential of L. paragasseri cavernosal abscess in clinical settings.

Prognostic Effect of Preoperative Psoas Muscle Hounsfield Unit at Radical Cystectomy for Bladder Cancer.

Radical cystectomy (RC) is the standard treatment for patients with advanced bladder cancer. Since RC is a highly invasive procedure, the surgical indications in an aging society must be carefully judged. In recent years, the concept of "frailty" has been attracting attention as a term used to describe fragility due to aging. We focused on the psoas muscle Hounsfield unit (PMHU) and analyzed its appropriateness as a prognostic factor together with other clinical factors in patients after RC. We retrospectively analyzed the preoperative prognostic factors in 177 patients with bladder cancer who underwent RC between 2008 and 2020. Preoperative non-contrast computed tomography axial image at the third lumbar vertebral level was used to measure the mean Hounsfield unit (HU) and cross-sectional area (mm2) of the psoas muscle. Univariate analysis showed significant differences in age, sex, clinical T stage, and PMHU. In multivariate analysis using the Cox proportional hazards model, age (hazard ratio (HR) = 1.734), sex (HR = 2.116), cT stage (HR = 1.665), and PMHU (HR = 1.758) were significant predictors for overall survival. Furthermore, using these four predictors, it was possible to stratify the prognosis of patients after RC. Finally, PMHU was useful as a simple and significant preoperative factor that correlated with prognosis after RC.

Successful management of a fistula between an external iliac artery and an ileal conduit with endovascular embolization and vascular bypass.

INTRODUCTION: Fistula formation between an ileac artery and an ileal conduit after radical cystectomy is a rare complication. CASE PRESENTATION: A 72-year-old woman underwent laparoscopic radical cystectomy with ileal conduit. After surgery, leakage of ileal-ureteral anastomosis with infection was observed. Five months after surgery, sudden bleeding from the ileal conduit occurred that stopped spontaneously. Contrast-enhanced computed tomography suggested a pseudo aneurysm of the right external iliac artery in contact with the ileal conduit. A fistula between the artery and ileal conduit was suspected. She underwent embolization of the common iliac artery and femorofemoral bypass. She had a good clinical course and no sign of hematuria over 6 months of follow-up. CONCLUSION: An episode of warning hemorrhage from the urostomy is an important sign of fistula, and endovascular treatment is a feasible approach to treat this condition.

A Combination of Findings Obtained from Pre- and Postoperative Imaging Predict Recovery of Urinary Continence After Non-nerve-sparing Laparoscopic Radical Prostatectomy.

BACKGROUND/AIM: The aim of the study was to identify the reliable predictor for early recovery of urinary continence (UC) after non-nerve-sparing laparoscopic radical prostatectomy (NNS-LRP) according to the findings of pre- and postoperative imaging. MATERIALS AND METHODS: A retrospective analysis of 215 patients who underwent NNS-LRP was carried out. Early recovery of UC was defined as using no pads or one security pad per day within 3 months. Preoperative membranous urethral length (MUL) measured on MRI and postoperative bladder neck angle (BNA) identified by cystography were analyzed to evaluate the relationship with recovery of UC. Patients were divided into three groups based on MUL and BNA (Group A: MUL ≥12.1 mm and BNA ≥103°, Group B: either MUL ≥12.1 mm or BNA ≥103°, Group C: MUL <12.1 mm and BNA <103°. RESULTS: Early recovery rates were 80.3% in patients with MUL ≥12.1 mm, 37.5% in patients with MLU<12.1 (p<0.001), and 77.8% in patients with BNA ≥103°, 50% in patients with BNA <103°(p<0.001). In the combination of the two parameters, early recovery rates were 90.4%, 58%, and 36.1% in group A, B and C respectively (p<0.001). Kaplan-Meier curve of the time to recovery of UC showed significant differences among the three groups (log rank test: p<0.001). CONCLUSION: A combination of preoperative MUL and postoperative BNA was the reliable predictor of recovery of UC after NNS-LRP. Longer MUL with wider BNA is significantly and positively associated with an early recovery of UC.

The role of continuous saline bladder irrigation after transurethral resection in patients with high-grade non-muscle-invasive bladder cancer.

OBJECTIVE: To compare the efficacy and safety of continuous saline bladder irrigation (CSBI) to a single immediate instillation of chemotherapy after transurethral resection of bladder tumor (TURBT) in patients with high grade primary non-muscle invasive bladder cancer (HG-NMIBC). MATERIALS AND METHODS: This study retrospectively reviewed 250 patients with primary NMIBC who were enrolled in a prospective randomized trial of CSBI vs single instillation of mitomycin C (SI-MMC) immediately after TURBT. Results of histopathology were re-reviewed using the World Health Organization (WHO) 2004/2016 classification. Of the 250 patients, 151 HG-NMIBC patients (78 in the CSBI group and 73 in the SI-MMC group) were evaluated according to the recurrence and progression rates and adverse events. RESULTS: The median follow-up period was 58 months. No significant differences for patients' characteristics were observed between the CSBI group and SI-MMC group. There was no statistically significant difference between the CSBI group and SI-MMC. group regarding recurrence rates of 12, 18 and 24 months (25.6% vs 23.3%、28.5% vs 23.3% and 32.1% vs 28.8%, respectively), time to first recurrence (12.6 ± 11 vs 12.4 ± 10.1 months) and progression rate (8.9% vs 8.2%). The incidence of adverse events was significantly lower in the C.S.B.I. group. CONCLUSION: The difference of recurrence and progression rate between CSBI and SI-MMC after TURBT was not statistically significant in HG-NMIBC, although a larger study is necessary to prove its equivalence or non-inferiority. CSBI after TURBT is easy to administer with a reduced risk of adverse events, and may be a treatment choice for patients with HG-NMIBC.

A G/A polymorphism in the androgen response element 1 of prostate-specific antigen gene correlates with the response to androgen deprivation therapy in Japanese population.

Prostate-specific antigen (PSA) gene expression is regulated by androgen receptor (AR) through androgen response elements (AREs) in the promoter region of the PSA gene. A single nucleotide polymorphism with guanine (G) to adenine (A) substitution is identified at position -158 in the ARE of the PSA gene. The purpose of this study was to investigate the allelic differences in the PSA promoter activity in vitro and the relation to several clinical factors of prostate cancer patients in the Japanese population. No significant differences of promoter activity in luciferase assay and binding activity of androgen receptor were noted between the two alleles in vitro. The PSA -158 G/A polymorphism was determined by PCR amplification and restriction digestion assays in 101 organ-confined prostate cancer (PC) patients who underwent radical prostatectomy and 52 controls with benign prostatic hyperplasia. The results revealed that homozygosity for the A allele in Japanese is less common (only 8.5%) than in ethnic populations. There were no significant differences in serum PSA value at the time of diagnosis, differentiation of cancer, pathological stage, cancer volume or ratio of serum PSA/ cancer volume. However, cancer volume after neoadjuvant endocrine therapy was significantly smaller in GG genotype than in AA + AG genotypes. Our data indicate that the PSA -158 G/A polymorphism has no effect on the PSA promoter activity in vitro and no association with the serum PSA level in Japanese men, however suggest that the patients with GG genotype of ARE1 may be more sensitive to androgen ablation therapy. Taken together, the ARE1 polymorphism in the PSA gene promoter may be one of the biomarkers for response to androgen deprivation therapy.

Efficacy of Ethinylestradiol Re-challenge for Metastatic Castration-resistant Prostate Cancer.

BACKGROUND: There has recently been renewed interest in the use of estrogens as a treatment strategy for castration-resistant prostate cancer (CRPC). The purpose of this study was to evaluate the feasibility and efficacy of ethinylestradiol re-challenge (re-EE) in the management of CRPC. PATIENTS AND METHODS: Patients with metastatic CRPC who received re-EE after disease progression on prior EE and other therapy were retrospectively reviewed for prostate-specific antigen (PSA) response, PSA progression-free survival (P-PFS) and adverse events. RESULTS: Thirty-six re-EE treatments were performed for 20 patients. PSA response to the initial EE treatment was observed in 14 (70%) patients. PSA response to re-EE was 33.3% in 36 re-EE treatments. The median P-PFS for patients treated with initial and re-EE was 7 months and 4 months, respectively. Interestingly, PSA response to re-EE was observed even in non-responders to initial EE, and those treated with multiple re-EE. No patients developed cardiovascular or thromboembolic events. CONCLUSION: Re-EE may be safely repeated several times and can lead to a prolonged disease control in selected patients. Re-challenge with EE appears to be a reasonable option worth considering for patients with metastatic CRPC.

Down-regulation of Skp2 is correlated with p27-associated cell cycle arrest induced by phenylacetate in human prostate cancer cells.

We have demonstrated that phenylacetate (PA)induced cell cycle arrest in human prostate cancer is mediated by increase of p27. In this study, we further investigated the mechanism of PA-induced p27 expression in prostate cancer cells (LNCaP, androgen-independent LNCaP [AIDL] and PC-3). A striking decrease in Skp2 mRNA and protein expression and reciprocal increase in p27 protein level were observed in three PA-treated prostate cancer cells. Interestingly, reduction of phospho-Akt and up-regulation of p27 mRNA levels were observed only in PC-3 cells. No significant differences were found in phospho-Akt and p27 mRNA levels in LNCaP and AIDL. In vitro ubiquitination assay showed a decreased p27 ubquitination in PA-treated prostate cancer cells. Our results suggest that PA attenuated Skp2 expression, thereby inhibiting ubiquitination and promoting p27 accumulation in all three prostate cancer cell lines. Therapeutic strategies designed to reduce Skp2 may clinically play an important role in the treatment of both androgen-sensitive and hormone-refractory prostate cancer.

Papillary adenocarcinoma of the renal pelvis and ureter producing carcinoembryonic antigen, carbohydrate antigen 19-9 and carbohydrate antigen 125.

We report a case of advanced renal pelvis and ureter adenocarcinoma producing carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9) and carbohydrate antigen 125 (CA125). A 72-year-old woman was diagnosed with right renal pelvic and ureter tumor with para-aortic lymph node swelling. Biopsy of the ureteral mass revealed papillary adenocarcinoma. Serum levels of CEA, CA19-9 and CA125 were extremely elevated. The patient was successfully treated with paclitaxel/carboplatin chemotherapy followed by surgery.