Bladder cancer immunomodulatory effects of intravesical Nitazoxanide, Rapamycin, Thalidomide and Bacillus Calmette-Guérin (BCG).

PURPOSE: To understand the effect of Nitazoxanide (NTZ), Rapamycin, Thalidomide, alone and in combination with BCG on bladder cancer (BC) histopathology and programmed death-ligand 1 (PD-L1) and anti-cytotoxic T lymphocyte antigen 4 (CTLA4) expression. METHODS: Female Fisher-344 rats underwent intravesical N-methyl-N-nitrosourea (MNU) followed by weekly intravesical treatment with saline (controls, n = 10), BCG (n = 10), NTZ (n = 8), BCG plus NTZ (n = 8), Rapamycin (n = 10) BCG plus Rapamycin (n = 10), Thalidomide (n = 10), and BCG plus Thalidomide (n = 10), and euthanized after 8 weeks and their bladders were investigated for BC and PD-L1 and CTLA4 expression. RESULTS: Rapamicyn alone and in combination with BCG had the lowest number of bladder neoplasias in the histopathology exam (1/10). Neoplastic lesions were found in 4/10 BCG recipients, 5/10 Thalidomide recipients, 4/10 Thalidomide plus BCG recipients, 5/8 NTZ and 3/8 NTZ plus BCG recipients. Adding NTZ to BCG increased the expression of PD-L1 and adding Rapamycin or Thalidomide decreased PD-L1 and CTLA4 expression compared to BCG alone. Rapamycin alone significantly increased CTLA4 and slightly increased PD-L1 expression but its combination with BCG significantly decreased both markers. Thalidomide had a similar effect; however, it was only slightly different from the control and BCG alone groups. CONCLUSION: Intravesical BCG combination treatment seems to effectively prevent BC development in an immunecompetent clinically relevant animal model, introducing Thalidomide, Nitazoxanide, and specially Rapamycin as candidates in the intravesical immunotherapy advancement. Our study contributes in understanding the mechanism of cancer immunotherapy.

Incontinence after laparoscopic radical prostatectomy: a reverse systematic review

ABSTRACT Purpose: To report the prevalence of the definitions used to identify post-prostatectomy incontinence (PPI) after laparoscopic radical prostatectomy (LRP), and to compare the rates of PPI over time under different criteria. Materials and Methods: In the period from January 1, 2000, until December 31, 2017, we used a recently described methodology to perform evidence acquisition called reverse systematic review (RSR). The continence definition and rates were evaluated and compared at 1, 3, 6, 12, and >18 months post-operative. Moreover, the RSR showed the "natural history" of PPI after LRP. Results: We identified 353 review articles in the systematized search, 137 studies about PPI were selected for data collection, and finally were included 203 reports (nr) with 51.436 patients. The most used criterion of continence was No pad (nr=121; 59.6%), the second one was Safety pad (nr=57; 28.1%). A statistically significant difference between continence criteria was identified only at >18 months (p=0.044). From 2013 until the end of our analysis, the Safety pad and Others became the most reported. Conclusion: RSR revealed the "natural history" of PPI after the LRP technique, and showed that through time the Safety pad concept was mainly used. However, paradoxically, we demonstrated that the two most utilized criteria, Safety pad and No pad, had similar PPI outcomes. Further effort should be made to standardize the PPI denomination to evaluate, compare and discuss the urinary post-operatory function.

Testosterone kinetics on hypogonadal men under clomiphene.

OBJECTIVE: To evaluate total testosterone (TT) kinetics and its predictors 6 months after the discontinuation of clomiphene citrate (CC) in patients with hypogonadism. MATERIALS AND METHODS: Consecutive patients with normal testicles and male hypogonadism defined by TT < 300 ng/dl in the presence of signs or symptoms according to the previous consensus were prospectively evaluated in a urologic outpatient clinic by TT levels at baseline (T0), after a daily dose of 50 mg CC for 40 days (T1), and after the washout period of 6 months of CC discontinuation (T2). RESULTS: Among 75 patients, mean age 56.8 years, testosterone at T1 > 300 ng/dl was achieved by 69 (92%), 450-600 ng/dl by 32 (42.6%), and > 600 ng/dl by 27 (36.0%). 18 subjects (24%) maintained asymptomatic and TT levels over 300 ng/dl at T2. Age negatively related to testosterone response and T1 response > 810 ng/dl predicts a median gain of 166.5 ng/dl at 6 months of CC discontinuation. CONCLUSIONS: CC is a compelling option to treat male hypogonadism, although a chronic treatment is needed in most patients. About one in every four patients respond to a CC short trial to "reboot" the physiology. Further understanding of TT kinetics in these patients in the long term is warranted.

Incontinence after laparoscopic radical prostatectomy: a reverse systematic review.

PURPOSE: To report the prevalence of the definitions used to identify post-prostatectomy incontinence (PPI) after laparoscopic radical prostatectomy (LRP), and to compare the rates of PPI over time under different criteria. MATERIALS AND METHODS: In the period from January 1, 2000, until December 31, 2017, we used a recently described methodology to perform evidence acquisition called reverse systematic review (RSR). The continence definition and rates were evaluated and compared at 1, 3, 6, 12, and >18 months post-operative. Moreover, the RSR showed the "natural history" of PPI after LRP. RESULTS: We identified 353 review articles in the systematized search, 137 studies about PPI were selected for data collection, and finally were included 203 reports (nr) with 51.436 patients. The most used criterion of continence was No pad (nr=121; 59.6%), the second one was Safety pad (nr=57; 28.1%). A statistically significant difference between continence criteria was identified only at >18 months (p=0.044). From 2013 until the end of our analysis, the Safety pad and Others became the most reported. CONCLUSION: RSR revealed the "natural history" of PPI after the LRP technique, and showed that through time the Safety pad concept was mainly used. However, paradoxically, we demonstrated that the two most utilized criteria, Safety pad and No pad, had similar PPI outcomes. Further effort should be made to standardize the PPI denomination to evaluate, compare and discuss the urinary post-operatory function.

Differential Diagnosis of Azoospermia in Men with Infertility.

The differential diagnosis between obstructive and nonobstructive azoospermia is the first step in the clinical management of azoospermic patients with infertility. It includes a detailed medical history and physical examination, semen analysis, hormonal assessment, genetic tests, and imaging studies. A testicular biopsy is reserved for the cases of doubt, mainly in patients whose history, physical examination, and endocrine analysis are inconclusive. The latter should be combined with sperm extraction for possible sperm cryopreservation. We present a detailed analysis on how to make the azoospermia differential diagnosis and discuss three clinical cases where the differential diagnosis was challenging. A coordinated effort involving reproductive urologists/andrologists, geneticists, pathologists, and embryologists will offer the best diagnostic path for men with azoospermia.

Moreau Strain Bacillus Calmette-Guérin Low Versus Standard Dose in the Treatment of High-Grade T1 Bladder Cancer: A Retrospective Observational Cohort Study.

PURPOSE: To evaluate recurrence, progression, and cancer-specific mortality of high-grade T1 non-muscle-invasive bladder cancer by assessing receipt of a low dose of the underexplored bacillus Calmette-Guérin (BCG) Moreau strain in a retrospective observational cohort study. PATIENTS AND METHODS: From January 2006 to December 2015, a total of 219 consecutive patients with high-grade T1 non-muscle-invasive bladder cancer received half-dose (40 mg; n = 109) or standard-dose (80 mg; n = 110) BCG Moreau strain after transurethral resection of the bladder. BCG therapy was initiated 2 or 3 weeks after transurethral resection of the bladder using the following protocol: 6 weekly doses, 12 monthly, 4 once every 3 months, and 2 once every 6 months, with a total of 24 doses. RESULTS: Comparing the half-dose and standard-dose treatment groups, in a median follow-up of 74.6 months, recurrence (n = 51, 46.8% vs. n = 60, 54.5%, P = .28), progression (n = 18, 16.5% vs. n = 16, 14.5%, P = .69), and disease-specific mortality (n = 9, 8.3% vs. n = 5, 4.5%, P = .26) were not significantly different on Kaplan-Meier curves and log-rank test, respectively. Charlson comorbidity index was an independent predictor of death from disease (hazard ratio = 1.341; 95% confidence interval, 1.033-1.740; P = .0274); no predictor of recurrence or progression was identified. Treatment intolerance occurred in 1 (0.9%) versus 6 (5.4%) patients (P = .12), respectively. No hospital admission or systemic BCG toxicity was reported. CONCLUSION: To our knowledge, this is the largest low-dose Moreau BCG strain study in high-grade T1 scenario. A half dose of BCG Moreau strain might be safe and effective in terms of tumor control, progression, or cancer-specific mortality with a low complication rate, which is central to the worldwide scenario of BCG shortage, and can help regulatory agencies approve efficient daughter BCG strains.

Prognostic impact of non-adherence to follow-up cystoscopy in non-muscle-invasive bladder cancer (NMIBC).

PURPOSE: To evaluate the underexplored context of cystoscopy adherent versus non-adherent patients in the follow-up of urothelial high-risk non-muscle-invasive bladder cancer (NMIBC). METHODS: We performed a retrospective study (2005-2016) that evaluated patients´ demographical characteristics, histopathological data, recurrence, progression and cancer-specific mortality between adherent and non-adherents patients in the first 3 years of a proposed cystoscopy protocol. RESULTS: Among the 198 included patients, comparing cystoscopy non-adherent (n = 36, 18%) and adherent patients (n = 162, 82%), there was no demographic or histopathological differences; the rates of disease recurrence, progression and cancer-specific mortality were 15 (41.7%) versus 68 (42.2%), p = 0.58; 12 (33.3%) versus 28 (17.9%), p = 0.014 and 4 (11.1%) versus 19 (11.7%), p = 0.98, respectively. Cystoscopy non-adherence was associated with an inferior number of urinary cytology (p < 0.001) and 2.33 HR for cancer progression, p = 0.014, (95% CI 1.18-4.59). CONCLUSIONS: Non-adherence to follow-up cystoscopy in NMIBC is associated with more than twice progression risk. Future studies are needed to confirm our results and correlate cystoscopy non-adherence to other covariates.