GFP Transfection Alters Protein Expression Patterns in Prostate Cancer Cells: A Proteomic Study.

PURPOSE: Green Fluorescent Protein is widely used as a cellular marker tool, but its potential influence on cells has been questioned. Although the potential off-target effects of GFP on tumor cells have been studied to some extent, the findings at the molecular level are insufficient to explain the effect of GFP expression on the tumorigenic capacity of cancer cells. Here, we aimed to investigate the effect of GFP expression on the tumorigenicity of PC3 prostate cancer cells. METHODS: Using GFP-expressing and wild-type PC-3 cells, xenograft models were generated in athymic BALB/C mice. To identify differentially expressed proteins, the change in cells proteome was investigated by label-free quantification with nano-high performance liquid chromatography to tandem mass spectrometry (nHPLC-MS/MS). Proteins that showed significantly altered expression levels were evaluated using the bioinformatics tools. RESULTS: Unlike the wild-type PC-3 cells, GFP-expressing cells failed to develop tumor. Comparative proteome analysis of GFP-expressing cells with WT PC-3 cells revealed a total of 216 differentially regulated proteins, of which 98 were upregulated and 117 were downregulated. CONCLUSION: Upon GFP expression, differential changes in several pathways including the immune system, translational machinery, energy metabolism, elements of cytoskeletal and VEGF signaling pathway were observed. Therefore, care should be taken into account to prevent reporting deceitful mechanisms generated from studies utilizing GFP.

Therapeutic Effects of AF219 on Interstitial Cystitis/Bladder Pain Syndrome Induced by Cyclophosphamide or Water Avoidance Stress in Rats.

INTRODUCTION AND HYPOTHESIS: To evaluate the effect of AF219, a P2X3 receptor antagonist, in animal models of interstitial cystitis/bladder pain syndrome (IC/BPS) induced by cyclophosphamide (CYP) or water avoidance stress (WAS). METHODS: Thirty-two adult female Wistar albino rats were used in each IC/BPS model. Assessment of nociception and anxiety and severity of inflammation in the bladder were assessed by behavioral experiments and histopathological examinations respectively. The contraction responses of the bladder were evaluated in vitro and protein levels of P2X3, P2X7, Trk-A, TRPV1, and TRPA1 were analyzed by Western blot. RESULTS: The IC/BPS groups had shorter response times to noxious stimuli, exhibited more anxiety-like behavior, had higher inflammation-based histological scores, and showed greater increased contraction responses to carbachol, adenosine triphosphate, and electrical field stimulation in in vitro bladder strips than controls for both models (p < 0.05). The improvements in behavioral and bladder contraction responses and inflammation scores in the IC/BPS + AF219 groups were similar to control findings (p > 0.05). Exposure to WAS or CYP increased P2X3 expression in the bladder compared with the controls (p < 0.05). Apart from TRPA1, the levels of P2X7, Trk-A, and TRPV1 were also higher in the IC/BPS groups than in the controls (p < 0.05). No significant differences were observed between IC/BPS + AF219 and controls regarding P2X3, P2X7, Trk-A, and TRPV1 in the WAS model (p > 0.05). Moreover, P2X3 and P2X7 levels were significantly lower in IC/BPS + AF219 than in the AF219-untreated WAS model (p < 0.05). CONCLUSIONS: These findings suggest that P2X3 receptors play a significant role in bladder functional responses, nociception, and also the pathogenesis of IC/BPS. AF219 may be a promising therapeutic strategy for IC/BPS. Comparing AF219 with current IC/BPS treatment agents in future studies may yield valuable insights into its efficacy.

Is Psoas Muscle Mass Associated with Failure of Ureteral Access Sheath Insertion and Complications from Retrograde Intrarenal Surgery? A Case-Control Study from RIRSearch group.

Objective: To investigate the association between psoas muscle mass (PMM) and failure of ureteral access sheath (UAS) insertion and complications from retrograde intrarenal surgery (RIRS). Materials and Methods: A multicenter retrospective case-control study was conducted that included patients who underwent RIRS despite failure of UAS insertion (Cohort 1) and confounder-matched control patients who underwent RIRS after successful UAS insertion (Cohort 2). For morphometric analysis of PMM, ipsilateral psoas muscle areas (iPMAs) were measured using the coreslicer.com webkit. After comparing demographic, clinical, and complication rates and iPMAs between cohorts, gender-specific median iPMAs were also determined to further subdivide patients in each cohort as either low iPMAs or high iPMAs. Thereafter, patients were also compared in terms of RIRS complications. Results: Cohort 1 included 86 patients whereas Cohort 2 consisted of 124 matched cases. The median (interquartile range) iPMAs were similar between the cohorts: Cohort 1, 11.05 (6.82-14.44) cm2 versus 11.12 (6.97-13.69) cm2 for Cohort 2 (P ˃ .05). There was a significant inverse relationship between iPMAs with age (r = -0.222) and Charlson comorbidity index (r = -0.180) for all patients (P ˂ .05). Perioperative and postoperative complication rates were 8.1% and 16.3% for Cohort 1 and 6.5% and 21% for Cohort 2, respectively. The complication rates were not statistically different between patients with high iPMAs and those with low iPMAs, in male or female patients (P > .05). Conclusions: These results show that failure of UAS was not associated with PMM. Furthermore, since the complication rates were similar between patients with high PMM and low PMM, RIRS may be a reliable treatment choice for sarcopenic patients as well as in nonsarcopenic patients.

Does neo-adjuvant chemotherapy improve the negative effect of lymphovascular invasion in survival after radical cystectomy?

PURPOSE: There is a lack of studies in the literature to evaluate the impact of the specific benefit of the use of neo-adjuvant chemotherapy (NAC) on the negative effect of lymphovascular invasion (LVI) on prognosis. We aimed to evaluate the survival differences of patients according to the presence of LVI with and without administration of NAC before radical cystectomy (RC). MATERIALS AND METHODS: We retrospectively evaluated data of the patients who underwent RC with pelvic lymphadenectomy and urinary diversion for bladder cancer recorded in the bladder cancer database of the Turkish Uro-oncology Association between 2007 and 2021. Patient demographics, follow-up time and overall survival (OS) were noted. RESULTS: A total of 633 subjects included in the analyses. Median follow-up time was 24 months (IQR 12-54). Five years OS of the whole cohort was 55.1%. This was 54.7% and 59.9% in NAC- and NAC+ groups (P = 0.683), respectively. It was also 35.7% and 65.7% in LVI+ and LVI- patients (P < 0.0001), respectively. There was a significant difference between LVI+ and LVI- patients (33.2% vs. 68.2%, P < 0.0001) in NAC- group, but similar 5-year OS was found (53.2% vs. 64.5%, P = 0.552) in NAC+ group. In multivariable analyses, female gender, pN stages, presence of variant histology and LVI were significant independent predictive factors for OS in the whole cohort and in the NAC- group. However, gender association, pN stages and LVI lost significance in NAC+ group. CONCLUSION: Presence of LVI significantly reduced OS, and the NAC treatment improved the negative effects of LVI on OS. Our findings encourage the use of NAC before RC.

Immediately repaired penile fractures: age is the only predictor of postoperative long-term functional outcomes.

Background: Penile fractures can lead to many functional complications, especially erectile dysfunction (ED). Few studies have evaluated the factors that predict late complications of an immediately repaired penile fracture. Aim: To identify the potential predictors of long-term poor functional outcomes following immediate surgical intervention for penile fractures. Methods: Sixty-eight consecutive patients with suspected penile fracture between 2003 and 2022 were retrospectively reviewed. Functional outcomes, postoperative complications, and follow-up duration were obtained from the records of follow-up visits. Age at presentation, location and length of the tunical tear, the presence of urethral rupture, and time to surgery were all analyzed as potential risk factors for postoperative functional outcomes. Outcomes: Postoperative erectile function and intercourse satisfaction were measured by the IIEF-5 (the 5-item version of the International Index of Erectile Function). Penile curvature, a palpable nodule, and paresthesia/numbness were detected by physical examination. Uroflowmetry was used to assess urinary flow in patients who underwent urethral repair. Results: Fifty-eight patients were analyzed. The mean ± SD age was 38.1 ± 10.4 years; the median follow-up was 79.0 months (range, 13-180); the median time to surgery was 9.8 hours (4-30); and the median tunical tear length was 15.5 mm (4-40). Urethral rupture was observed in 8 patients (13.8%). In univariable analyses, urethral rupture was associated with postoperative complications (P = .034). In addition, age at presentation and tunical tear size were significantly associated with postoperative complications and ED (P < .05). However, in multivariable analyses, only age at presentation significantly predicted postoperative complications and ED (P = .004 and P = .037). Clinical Implications: Age at presentation is the most important factor determining the prognosis of immediate surgical repair of the penile fracture, which aids in predicting potential complications and discussing them with patients prior to surgical intervention and during the follow-up period. Strengths and Limitations: The study's retrospective design is an important limitation. Furthermore, there were no data on an IIEF-5 outcome measuring preoperative erectile function. Conclusion: These results revealed an association between (1) urethral rupture, longer tunical tears, and older age and (2) the development of late complications. The remarkable finding of this study was that age at presentation was the only significant predictor of functional complications based on multivariable analyses. This relationship also remained robust in tests evaluating the covariance of the effects of aging on ED.

The prognostic value of expressions of STAT3, PD-L1, and PD-L2 in Ta/T1 urothelial carcinoma before and after BCG treatment.

INTRODUCTION: Nonmuscle invasive bladder cancers (NMIBC) are common tumors diagnosed in older individuals and men (median age: 69 years). Immunotherapy is a treatment option in cases resistant to Bacillus-Calmette-Guerin (BCG) therapy. We aimed to evaluate the prognostic role of programmed-cell-death ligand (PD-L)-1 (PD-L1), PD-L2, and signal transducer and activator of transcription 3 (STAT3) expressions, which are closely related to immune mechanisms, in the response to BCG treatment of NMIBC. METHODS: The data of patients at the Ta and T1 stages of the cancer without muscularis propria invasion, who were treated with intravesical BCG therapy between 2017 and 2022 were retrospectively analyzed. Immunohistochemical staining for PD-L1, PD-L2, and STAT3 was performed on transurethral resection materials. RESULTS: The mean age of 59 patients was 66.5 ±7.7 and 83.9% were male. The percentage of patients with complete response to BCG treatment was 66.1% and that of BCG refractory patients was 33.9%. Demographic and clinical data did not differ significantly according to BCG treatment response (P> 0.05). The proportion of patients with tumor-infiltrating lymphocytes (TILs) ≥20% were 9.7% among those with Ta-stage tumors and 46.4% among those with T1-stage tumors (P = 0.0014). The percentages of tumor cell scoring (TCS), immune cell scoring (ICS), combined scoring (CS), and expression levels of PD-L1, PD-L2, and H-score of STAT3 did not differ significantly according to tumor stage and treatment response (P > 0.05). However, the median ICS and CS for PD-L1 and median H-score for STAT3 were significantly higher among patients in T1 stage compared to those in Ta stage (P = 0.0487, 0.0462, 0.0112, respectively). Among BCG refractory patients, median STAT3 of patients in T1 stage was significantly higher than those at stage Ta (P = 0.0356) and the rate of TILs was ≥20% in only 3 patients in T1 stage (P = 0.031). Among all patients, significant positive correlation was found between TCS for PD-L1 and H-score for STAT3 (P = 0.0302); and between ICS for PD-L1 and TCS for PD-L2 (P = 0.0053) and TILs ratio (P < 0.0001). Among BCG-refractory cases, pretreatment and post-treatment TCS for PD-L2 and H-scores for STAT3 were significantly correlated (P = 0.0361 and 0.0021, respectively). CONCLUSIONS: The success of BCG treatment in NMIBC was not related to PD-L1, PD-L2, and STAT3 expression status, but PD-L1 expression was correlated with both PD-L2 and STAT3 as well as TILs rate, but this correlation was lost after BCG treatment.

Retrograde Intrarenal Surgery Learning Curves of Urology Residents Supervised by an Experienced Endourologist: An RIRSearch Study.

INTRODUCTION: Although retrograde intrarenal surgery (RIRS) is being performed with increasing frequency, there are only a limited number of studies about the learning curve (LC). This study aimed to analyze the LC of RIRS for five surgeons who underwent the same training. MATERIALS AND METHODS: The data of the 410 patients who underwent RIRS between April 2017 and 2022 in a single institution, which were performed consecutively by five surgeons, were analyzed. All 50 cases performed by each surgeon were included and numbered consecutively and separately, according to the date of the operation. The combined stone-free rate (SFR) was calculated for each surgeon's cases in the same row, and the LCs were created using moving average and cumulative sum (CUSUM) analyses. Separate multivariable analyses identified each period's (LC vs. beyond) characteristics. RESULTS: The LCs from the combined SFRs reached a plateau after approximately 50 cases for both the CUSUM and the moving average. The effect of stone burden on SFR was more evident in the first 50 cases compared to subsequent cases in the multivariable analyses (p = 0.001 and p = 0.047, respectively). Case order and stone density were independent factors in the first 50 cases (OR: 1.02 [95% CI 1.00-1.04], p = 0.04 and OR: 0.99 [95% CI 0.99-1.00], p = 0.04) but not significant in subsequent cases (OR: 0.97 [95% CI 0.94-1.00], p = 0.1 and OR: 1.00 [95% CI 0.99-1.00], p = 0.7, respectively). Compared to single locations except the lower calyx, the unfavorable effect of the multiple-stone localization on SFR grew in strength after the 50th case (OR: 0.42 [95% CI 0.23-0.78], p = 0.01 and OR: 0.20 [95% CI 0.09-0.46], p < 0.001, respectively). CONCLUSIONS: This is the first study reporting on the RIRS LCs of urology residents. While stone burden, density, and multiple-stone localization were the factors determining SFR in the learning period, after completing the LC, the effect of stone burden weakened and multiple-stone localization became stronger.

Evaluation of comprehensive complication index versus Clavien-Dindo classification in prediction of overall survival after radical cystectomy.

PURPOSE: We aimed to evaluate the benefits of Comprehensive Complication Index (CCI) compared with the Clavien-Dindo Classification (CDC) in the reporting of radical cystectomy (RC) complications. MATERIALS AND METHODS: We retrospectively analyzed post-operative complications of 251 consecutive RC patients between 2009 and 2021. Patient demographics and causes of mortality were noted. Oncologic outcomes included the recurrence, time to recurrence, cause of all deaths, and time to death. Each complication was graded with CDC and, corresponding and cumulative CCI calculated for each patient. RESULTS: A total of 211 patients are included. Median patient age and follow-up time were 65 (IQR 60-70) years and 20 (IQR 9 - 53) months, respectively. The five-year recurrence and death rates were 39.3% (83/211) and 59.7% (126/211), respectively. Post-operative 521 complications were recorded. Patients with experienced any complication were 69.6% (147/211) and 45.0% (95/211) had > 1 complications. Thirty (14.2%) patients ended up with a cumulative CCI score that corresponded to a higher CDC grade. Severe complications calculated with CDC increased from 18.5% to 19.9% (p < 0.001) with cumulative CCI. Female gender, positive lymph node, and positive surgical margin, presence of severe CDC complication, and CCI score were significant independent predictive factors for overall survival (OS). The contribution of CCI to the multivariable model was 1.8% higher than CDC. CONCLUSIONS: Cumulative morbidity reporting improved with the use of CCI compared to CDC. Both CDC and CCI are significant predictive factors for OS independent of oncologic predictive factors. Reporting the cumulative burden of complications with CCI is more predictive on oncologic survival than reporting complications with CDC.

Reporting perioperative complications of radical cystectomy: the influence of using standard methodology based on ICARUS and EAU quality criteria.

PURPOSE: We aimed to evaluate perioperative complications of radical cystectomy (RC) by using standardized methodology. Additionally, we identified independent risk factors associated with perioperative complications. MATERIALS AND METHODS: We retrospectively analyzed 30-day and 90-day perioperative complications of 211 consecutive RC patients. The intraoperative and postoperative complications were defined according to Clavien-Dindo classification (CDC) and reported based on the ICARUS criteria, Martin, and EAU quality criteria. Age-adjusted Charlson comorbidity index (ACCI), systemic inflammatory response index (SIRI), body mass index (BMI) ≥ 25 kg/m2, and neoadjuvant chemotherapy (NAC) were also evaluated. Multivariable regression models according to severe (CDC ≥ IIIb grade) complications were tested. RESULTS: Overall, 88.6% (187/211) patients experienced at least one intraoperative complication. Bleeding during cystectomy was the most common complication observed (81.5% [172/211]). Severe intraoperative complications (EAUiaiC grade > 2) were recorded in 8 patients. Overall, 521 postoperative complications were recorded. Overall, 69.6% of the patients experienced complications. Thirty-nine patients suffered from most severe (CDC ≥ IIIb grade) complications. ACCI (OR: 1.492 [1.144-1.947], p = 0.003), SIRI (OR: 1.279 [1.029-1.575], p = 0.031), BMI (OR: 3.62 [1.58-8.29], p = 0.002), and NAC (OR: 0.342 [0.133-0.880], p = 0.025) were significant independent predictive factors for 90-day most severe complications (CDC ≥ IIIb grade). CONCLUSIONS: RC complications were reported within a standardized manner, concordant with the ICARUS and Martin criteria and EAU guideline recommendations. Complication reporting seems to be improved with the use of standard methodology. Our results showed that ACCI, SIRI, and BMI ≥ 25 kg/m2 and the absence of NAC were significant predictive factors for most severe complications.

The systemic inflammation response index: An independent predictive factor for survival outcomes of bladder cancer stronger than other inflammatory markers.

PURPOSE: We aimed to evaluate the prognostic value of the preoperative systemic inflammation response index (SIRI) to predict the outcomes after open radical cystectomy (RC). MATERIALS AND METHODS: We conducted a retrospective analysis of the institutional cystectomy database and identified 241 consecutive RC patients. Patient demographics and oncologic outcomes were noted. We calculated the SIRI as previously described (NeutrophilxMonocytes/Lymphocytes), based on the blood-tests at the day before surgery and a minimum >30-day later. RESULTS: Median follow-up time was 20 months (interquartile range 9-52). Two, 3 and 5 years recurrence free (RFS) and overall survival (OS) rates were 60.6%, 57.1%, 48.9%, and 54.7%, 47.0%, 37.2%, respectively. Patients with preoperative SIRI >1.91 had significantly higher recurrence rates (P < 0.001) and lower OS (P < 0.001). For internal validation, we evaluated postoperative SIRI >1.91 (repeatability testing), and again found significantly higher recurrence rates (P < 0.001) and lower OS (P = 0.004). Persistently high SIRI increased the recurrence and death risk 5.79 and 2.87 fold, respectively. SIRI was also a significant independent predictive factor for RFS and OS in the multivariable cox regression analyses (P < 0.05). SIRI improved the discriminative ability of the models 1.5% to 4.2% and this was quite higher than other inflammatory markers (NLR, MLR, PLR, SII) in all models. CONCLUSIONS: Patients with SIRI >1.91 had significantly higher recurrence and lower OS rates. The cut-off value is validated internally. SIRI is an independent predictive factor for RFS and OS. The contribution of SIRI in the cox models is higher than other inflammatory markers.

Oncological and functional outcomes of patients who underwent open partial nephrectomy for kidney tumor.

OBJECTIVE: To report long-term functional and oncological outcomes of OPN Methods: We enrolled 182 patients who underwent consecutive OPN with a diagnosis of kidney tumor in our clinic between April 2002 and February 2020 and were selected from our prospective OPN database. Preoperative demographic and clinical characteristics, intraoperative and pathological results, and patients' postoperative functional and oncological follow-up data were retrospectively analyzed. Overall survival (OS) and disease- free survival (DFS) were evaluated using Kaplan-Meier survival analysis. The time-dependent variation between preoperative and postoperative functional results was statistically analyzed and presented in a graph. RESULTS AND LIMITATIONS: The mean age was 54.4 ± 10.8 yr, and the median age-adjusted Charlson comorbidity index (ACCI) was 1 (interquartile range [IQR] 0-1). The mean tumor size was 3.1 ± 1.2 cm, and the median RENAL score was 6 (IQR 5-8). The most common malign histopathological subtype was clear cell carcinoma with 76.6%, and five cases (3.4%) had positive surgical margins (PSMs). The most common surgical techniques were the retroperitoneal approach (98.9%) and cold ischemia (88.5%). Estimated glomerular filtration rate (eGFR) preservation was 92% (80.8-99.3, IQR), which translates to 32% chronic kidney disease (CKD) upstaging. Acute kidney injury (AKI) was detected in 27 (14.8%) patients according to RIFLE criteria. The intraoperative complication rate was 5.5%, and the postoperative overall complication rate (Clavien-Dindo 1-5) was 30.2%. Major complications (Clavien-Dindo 3-5) were observed in 13 (7.1%) patients. The median oncological follow-up was 42 mo (21.3- 84.6, IQR), and the 5- and 10-yr OS were 90.1% and 78.6%, 5 and 10-yr DFS were 99.4% and 92.1%, respectively. No local recurrence was observed in 5 (3.4%) patients with PSMs; only one had distant metastasis in the 8th postoperative month. The retrospective design, the small number of patients who underwent PN based on mandatory indication, and one type of surgical approach may limit the generalizability of our findings. CONCLUSIONS: This study confirms excellent long-term oncologic and functional outcomes after OPN in a cohort of patients selected from a single institution. In light of the information provided by the literature and our study, our recommendation is to push the limits of PN under every technically feasible condition in the treatment of kidney tumors to protect the kidney reserve and achieve near-perfect oncological results.

The Impact of COVID-19 Pandemic on Urological Emergencies, 8 Months Results of a Multicenter Retrospective Study From Turkey.

Objectives: We aimed to reveal the change of urological emergencies during the COVID-19 pandemic compared to the same period of the previous year. Methods: The number of admissions to the emergency department (ED), admissions to the urology outpatient clinic, emergency urological consultations, and urological and emergency urological surgeries during the periods April-November-2019 and April-November-2020 were recorded. The data of the COVID-19 period were compared with the previous year. Results: While the number of admissions to the urological outpatient clinic was 160,447 during the COVID period, it was 351,809 during the non-COVID period. The number of admissions to the ED decreased from 3.2 million to 2.4. The number of admissions to the urology outpatient clinic significantly decreased by 54% during the pandemic (p=0.001). Percutaneous cystostomy performed due to acute urinary obstruction decreased by 27.96%, double J stent, nephrostomy decreased by 16.61%, and ureterorenoscopy decreased by 12.26%. Urogenital trauma also decreased. On the contrary, surgical procedures performed due to penile fracture, gross hematuria, Fournier gangrene, and testicular torsion increased. Conclusion: During the COVID-19 pandemic, a significant decrease was observed in non-COVID patients' admissions to the emergency and urology department, and in urologic surgeries.

The pelvic anatomic index is an independent predictor for the difficulty of radical prostatectomy.

OBJECTIVES: The aim of the study was to investigate whether a novel simple measurement of pelvic anatomy, the pelvic anatomical index (PAI), which is obtained from simple physical examination, was predictive for potential difficulty and adverse outcome in radical prostatectomy. MATERIALS AND METHODS: Available data from 73 consecutive radical prostatectomy patients were analyzed. The distances between umbilicus and cranial edge of the symphysis pubis (USPD) and between root of the penis and umbilicus (PUD) were measured. PAI was obtained using the formula (PUD/USPD) × body mass index (BMI). Indicators of surgical difficulty assessed were operation time (OT), dorsal vein bleeding (DVB), total blood loss (TBL), and surgical margin (SM) status. Patients with below-median values of the OT, DVB, TBL, and had negative SM were grouped as favorable surgery (n = 18). RESULTS: Median OT, DVB, and TBL were 215 (IQR: 187.5-240) min, 380 (IQR: 200-500) cc, and 1000 (IQR: 700-1300) cc, respectively. Both PAI and BMI were significantly correlated with TBL, DVB, and OT (p < 0.05, for all). PAI and BMI significantly associated with favorable surgery (p = 0,006 and p = 0.048, respectively). However, only PAI was an independent predictor of favorable surgery in multivariable logistic regression analysis. A PAI 36 kg/m2 was determined as the threshold value for favorable surgery with 83.3% sensitivity and 60% specificity. CONCLUSION: PAI significantly correlated with almost all surgical parameters and was a significant independent predictor of favorable surgery. PAI can enable the physician to select and discuss individualized treatment options for patients during preoperative planning.

Does routine intraoperative Double J stent insertion avoid urine leakage after open partial nephrectomy?

OBJECTIVE: To evaluate the impact of Double J stent (DJS) insertion during open partial nephrectomy (OPN) on postoperative prolonged urinary leakage. MATERIALS AND METHODS: A retrospective study was made in consecutive cases of OPN performed between 2002 and 2020 for localized kidney tumors at our tertiary center. Urinary leakage was defined as drainage > 72 hours after surgery by biochemical analysis consistent with urine or radiographic evidence of urine leakage. The patients were divided into two groups according to intraoperative DJS placement, and compared regarding clinicopathologic characteristics, perioperative and postoperative outcomes. Univariate and multivariate logistic regression analyses were performed to determine the factors associated with urinary leakage after the operation. RESULTS: Review of records identified 182 patients who were included in the study. In 73 (40%) patients PN was performed without insertion of a DJS. Thus, 109 (60%) of patients had a DJS inserted. Apart from higher preoperative eGFR values among patients with DJS (96.6 vs. 94.3 mL/min/1.73 m²; p = 0.03), demographic characteristics were similar between groups. The two groups were not different regarding perioperative, postoperative and clinicopathologic outcomes. Patients with DJS had longer ischemia times (31 vs. 23 min; p = 0.02) and longer length of stay (6 vs. 5 days; p = 0.04). Urinary leakage was seen in 7.6% (n = 14) of all patients and it did not differ according to DJS placement (DJS+ 9.2 vs. DJS- 5.5%; p = 0.41). On multivariate analysis, the tumor nearness to the collecting system was the sole independently significant factor (p = 0.04) predicting postoperative urine leak. CONCLUSIONS: Routine intraoperative DJS insertion during OPN does not appear to reduce the probability of postoperative urine leak.

Minimal invasive management of bladder neck contracture using Allium round posterior stent: the long-term results.

BACKGROUND: The purpose of this study was to assess the long-term clinical efficacy of temporary, Allium round posterior stent (RPS) used for treatment of recurrent bladder neck contracture (BNC). METHODS: Records of 42 patients with recurrent BNC who underwent Allium RPS placement after bladder neck incision, between 2009 and 2019, were analyzed. After stent removal, the success criteria for Allium RPS treatment were defined as: no evidence of stricture on urethrogram or endoscopy; more than 12 ml/sec of urinary peak flow; and no recurrent urinary tract infections. Based on clinical success, patients were divided into two groups and compared. Clinical success was evaluated with particular regard to stent indwelling time and contracture etiology. RESULTS: The mean ± standard deviation age, stricture length, and indwelling time were 66.7 ± 9 years, 2.4 ± 1.4 cm, and 7.7 ± 2.2 months, respectively. Median (range) follow-up was 59 (8-73) months. The etiologies of BNC in this cohort were 57.1% retropubic radical prostatectomy; and 42.9% transurethral resection of prostate. Overall clinical success was achieved in 64.3% and the success rates did not differ by etiology. The success rates were 54.2% and 77.8% (P = 0.118) for retropubic radical prostatectomy and transurethral resection of prostate, respectively. Longer indwelling time (8-14 vs 3-7, months) was significantly associated with clinical success (78.3% vs 47.4%, P = 0.040). CONCLUSION: Our data suggest that better clinical success was associated with longer indwelling time for stent in BNC treatment. In BNC management, Allium RPS treatment may be considered since its clinical efficacy is acceptable and tolerable.

Buried penis in adults as a complication of circumcision: Surgical management and long-term outcomes.

We aimed to evaluate the feasibility and long-term functional outcomes of surgical correction of adult buried penis patients due to complications of childhood circumcision. A retrospective analysis was performed for patients who underwent treatment for buried penis between 1997 and 2019. An autologous split-thickness skin graft (STSG) was used. Surgical management steps included circumcision, resection of the bands between the corpora and other tissues, harvesting of STSG from femoral region and graft application. Surgical and functional outcomes were the primary end points. Thirteen patients were included with a mean age of 22.4 years and median body mass index 27. Patients had similar symptoms, including sexual dysfunction, inadequate penile length, impossible penetration and decreased quality of life. No early post-operative complication was seen. During a median of 44-month follow-up, post-operative long-term complications were seen in 4 (30%) patients: decreased graft sensation (n = 2); graft contracture five months after surgery (n = 1); and retarded ejaculation (n = 1). Patients' post-operative three-month International Index of Erectile Function (IIEF) score and sexual satisfaction score (SSS) significantly increased compared with patients' pre-operative scores (IIEF; 22.8 vs. 14.1, p = .03, SSS; 8.7 vs. 3.2, p < .01). Buried penis is a rare but challenging condition. Patients had excellent graft acceptance with successful functional outcomes.

Prognostic value of immunological profile based on CD8+ and FoxP3+ T lymphocytes in the peritumoral and intratumoral subsites for renal cell carcinoma.

PURPOSE: We aimed to assess an "Immunological Profile (IP)" including CD8+ and FoxP3+ T lymphocytes for renal cell carcinoma (RCC) to evaluate its effects on tumor pathological characteristics, disease progression, and survival. METHODS: Adjacent normal and intratumoral specimens from 42 patients who had undergone radical nephrectomy for RCC were analyzed for counts of CD8+ and FoxP3+ T lymphocytes by immunohistochemistry. Tissue from both sites were evaluated and scored separately according to low (0) or high (1) expression of CD8 and FoxP3. A total score (min: 0, max: 4) was assigned to each patient. Thereafter, patients were divided into two groups for clinicopathologic and survival stratification based on score (IPWeak 0-2; and IPStrong 3-4). Survival curves were constructed using the Kaplan-Meier method, and a multivariable Cox regression model was used for overall survival (OS) and progression-free survival (PFS). RESULTS: The mean follow-up was 54.73 ± 21.34 months. Poor RCC characteristics including pT3-T4, tumor necrosis, lymphovascular invasion, lymph node involvement, and larger tumor size were significantly more common in the IPWeak patients compared to IPStrong (p < 0.05). Kaplan-Meier analysis showed that IPWeak patients had worse OS (62.5 vs. 100%; p = 0.006) and PFS (50 vs. 94.4%; p = 0.002) compared to IPStrong patients. In multivariable analysis, IPWeak (HR 8.64; 95% CI 1.09-68.05, p = 0.042) and high tumor node metastasis stage (HR 45.33; 95% CI 4.69-437.68, p < 0.001) were significant independent predictors of poor PFS. CONCLUSION: Assessment of IP including CD8+ and FoxP3+ T lymphocytes in adjacent normal and intratumoral sites in RCC may serve as a good predictive marker for PFS.

Comparision effects of solifenacin, darifenacin, propiverine on ocular parameters in eyes: A prospective study

ABSTRACT Objective To evaluate the effects of solifenacin, darifenacin, and propiverine on nasal-, subfoveal-, temporal choroidal thicknesses (NCT, SFCT, TCT), intraocular pressure (IOP) and pupil diameter (PD). Materials and Methods Patients with overactive bladder (OAB) diagnosed according to The International Continence Society were administered with solifenacin, darifenacin or propiverine on a daily basis between November 2017 and May 2018. NCT, SFCT, TCT, IOP, and PD of these patients were measured and compared as initial, fourth and twelfth weeks. Results A total of 165 patients (330 eyes) with OAB were evaluated. Solifenacin (n=140) significantly reduced IOP from 17.30±2.72 mmHg to 16.67±2.56 mmHg (p=0.006) and 16.57±2.41 mmHg (p=0.002), at the fourth and twelfth weeks, respectively. Darifenacin (n=110) significantly reduced NCT from 258.70±23.96 μm to 257.51±22.66 μm (p=0.002) and 255.36±19.69 μm (p=0.038), at the fourth and twelfth weeks, respectively. Propiverine (n=80) significantly increased PD from 4.04±0.48 mm to 4.08±0.44 mm (p=0.009) and 4.09±0.45 mm (p=0.001), at the fourth and twelfth weeks, respectively. Conclusion These findings can help to decide appropriate anticholinergic drug choice in OAB patients. We finally suggest further well-designed randomized prospective studies with a larger population to evaluate the anticholinergic-related complications in eyes.

Histopathologic and molecular comparative analyses of intravesical Aurora kinase-A inhibitor Alisertib with bacillus Calmette-Guérin on precancerous lesions of bladder in a rat model.

PURPOSE: Recent studies have shown that Aurora-A expression is associated with bladder cancer initiation and progression. In this study, the effects of intravesical Aurora-A inhibitor Alisertib (ALS) and bacillus Calmette-Guérin (BCG) were compared on bladder carcinogenesis. METHODS: Two mg N-Methyl-N-nitrosourea was administered intravesically to forty of Wistar-albino rats every other week for 8 weeks. At week 10, rats were divided into four groups (10/group): No-treatment (vehicle), ALS-alone, BCG-alone, and ALS + BCG. The intravesical treatment of ALS, BCG, and ALS plus BCG was performed once a week for 6 weeks. At week 16, bladders were collected for immunohistopathological and Western blot analysis. The cell cycle regulators p53, p21, Aurora-A, phosphorylated Aurora-A (p-Aurora-A), and apoptotic marker cleavage of poly [ADP-ribose] polymerase (c-PARP) were determined by Western blot. RESULTS: Histopathologically relatively healthy urothelium was observed in ALS + BCG group (87.5%) compared to the ALS-alone (50%) and the BCG-alone (50%) groups. The lowest expression of p21 and p53 was detected in the BCG-alone, while the highest level of expression was evident in no-treatment group. The ALS treatment alone caused a slight decrease in Aurora-A while there was a dramatic decrease in p-Aurora-A in comparison to no-treatment group. In overall combined treatment with ALS + BCG significantly increased c-PARP compared to all mono-treatments, and decreased all cell cycle parameters compared to no-treatment group. CONCLUSIONS: Although intravesical ALS treatment has similar antiproliferative effects like BCG, ALS + BCG combined treatment led to a best histopathologic and apoptotic response. Consequently, BCG combined with Aurora-A inhibition may provide a new intravesical treatment modality in the prevention of bladder carcinogenesis.

Monitoring the response of urothelial precancerous lesions to Bacillus Calmette-Guerin at the proteome level in an in vivo rat model.

Intravesical Bacillus Calmette-Guerin (BCG) is the best treatment modality for progression of non-muscle invasive bladder cancer. We aimed to monitor changes at the proteome level to identify putative protein biomarkers associated with the response of urothelial precancerous lesions to intravesical BCG treatment. The rats were divided into three groups (n = 10/group): control, non-treated, and BCG-treated groups. The non-treated and BCG-treated groups received N-methyl-N-nitrosourea intravesically. BCG Tice-strain was instilled into bladder in BCG-treated group. At the endpoint of experiment, all surviving rat bladders were collected and equally divided into two portions vertically from dome to neck. Half of each bladder was assessed immunohistopathologically and the other half was used for 2D-based comparative proteomic analysis. Differentially expressed proteins were validated by Western blot analysis. Precancerous lesions of bladder cancer were more common in non-treated group (77.8%) than in BCG-treated group (50%) and the control group (0%). Greater than twofold changes occurred in the expression of a number of proteins. Among them, Rab-GDIß, aldehyde dehydrogenase 2 (ALDH2) and 14-3-3 zeta/delta were important since they were previously reported to be associated with cancer and their expression levels were found to be lower in BCG-treated group in comparison to the non-treated group. ALDH2 and 14-3-3 zeta/delta were also found to be highly expressed in the non-treated group compared to the control group. The down-regulation of these proteins and Rab-GDIß was achieved with BCG; this result indicates that they may be used as putative biomarkers for monitoring changes in bladder carcinogenesis in response to BCG immunotherapy.