Elevated levels of MMP12 sourced from macrophages are associated with poor prognosis in urothelial bladder cancer.

BACKGROUND: Urothelial bladder cancer is most frequently diagnosed at the non-muscle-invasive stage (NMIBC). However, recurrences and interventions for intermediate and high-risk NMIBC patients impact the quality of life. Biomarkers for patient stratification could help to avoid unnecessary interventions whilst indicating aggressive measures when required. METHODS: In this study, immuno-oncology focused, multiplexed proximity extension assays were utilised to analyse plasma (n = 90) and urine (n = 40) samples from 90 newly-diagnosed and treatment-naïve bladder cancer patients. Public single-cell RNA-sequencing and microarray data from patient tumour tissues and murine OH-BBN-induced urothelial carcinomas were also explored to further corroborate the proteomic findings. RESULTS: Plasma from muscle-invasive, urothelial bladder cancer patients displayed higher levels of MMP7 (p = 0.028) and CCL23 (p = 0.03) compared to NMIBC patients, whereas urine displayed higher levels of CD27 (p = 0.044) and CD40 (p = 0.04) in the NMIBC group by two-sided Wilcoxon rank-sum tests. Random forest survival and multivariable regression analyses identified increased MMP12 plasma levels as an independent marker (p < 0.001) associated with shorter overall survival (HR = 1.8, p < 0.001, 95% CI:1.3-2.5); this finding was validated in an independent patient OLINK cohort, but could not be established using a transcriptomic microarray dataset. Single-cell transcriptomics analyses indicated tumour-infiltrating macrophages as a putative source of MMP12. CONCLUSIONS: The measurable levels of tumour-localised, immune-cell-derived MMP12 in blood suggest MMP12 as an important biomarker that could complement histopathology-based risk stratification. As MMP12 stems from infiltrating immune cells rather than the tumor cells themselves, analyses performed on tissue biopsy material risk a biased selection of biomarkers produced by the tumour, while ignoring the surrounding microenvironment.

Upper urinary tract and urethral recurrences following radical cystectomy: review of risk factors and outcomes between centres with different follow-up protocols.

PURPOSE: To examine which patient-related and tumour-related characteristics predict upper urinary tract recurrence (UUTR) and urethral recurrence (UR) of bladder cancer post-radical cystectomy (RC). Secondary objective is to evaluate whether or not recurrence patterns are similar between two centres with different post-RC follow-up (F/U) protocols. METHODS: A retrospective cohort study of 574 consecutive patients undergoing radical cystectomy for urothelial carcinoma of the bladder at two tertiary centres was performed. Clinicopathological factors associated with bladder cancer recurrence and patient-related outcomes, including time to recurrence and death, were collected. Risk factors for recurrences were examined using univariate and multivariable regression analyses. Likelihood of recurrence, time to recurrence, and survival were compared. RESULTS: There was a 3.7 % risk of UUTR (21/574) and a 3.6 % risk of UR (18/503) for the combined cohort at a median F/U of 45 months. When controlling for the effects of all variables modelled, female gender was a significant risk factor for UUT recurrence (OR 3.2, 95 % CI 1.0-9.5, p = 0.03) and prostatic urethral involvement was a significant risk factor for urethral recurrence (OR 7.8, 95 % CI 2.2-27.6, p = 0.001). UUTR were similar (p = 0.82) between Turku (8/205) and Toronto (12/369). Urethral recurrences trended (p = 0.06) towards being more common in Turku (9/151, 6.0 %) versus Toronto (9/352, 2.6 %), but no difference in overall survival was demonstrated between sites. CONCLUSION: The frequency of UUT and urethral recurrences post-cystectomy is relatively low and remained stable for the past 15 years. The ideal F/U protocol to maximize patient-survival remains unknown.

Treatment of bacillus Calmette-Guerin refractory non-muscle invasive bladder cancer.

Treatment options for patients with non-muscle invasive bladder cancer (NMIBC) refractory to intravesical bacillus Calmette-Guerin (BCG) therapy is reviewed in this article based on the recent published literature. Although intravesical BCG is the best bladder sparing treatment option for NMIBC to prevent recurrence and progression, about 1/3 of cases are refractory to this treatment. At this point radical cystectomy is the standard treatment of choice. If this option is not feasible, intravesical chemotherapy with docetaxel or gemcitabine, the combination of BCG and interferon (INF)-a or device-assisted intravesical strategies, such as mitomycin-EMDA or chemohyperthermia are some of the candidates for further treatment.

Does patient age affect survival after radical cystectomy?

UNLABELLED: What's known on the subject? and What does the study add? Elderly patients have more years to compound comorbidities and it has previously been shown that comorbidity is an important predictor of overall survival in patients with bladder cancer, including those treated with radical cystectomy (RC). Other studies have also demonstrated higher stage at diagnosis, higher rate of upstaging on final pathology and a longer delay to definitive therapy for older patients. Because of these findings, elderly patients are being offered RC less often than younger patients. Whether or not this practice is justified has come under recent scrutiny and there has been much conflicting data in the literature. While some studies have shown worse outcomes for elderly patients, others have shown similar results for both elderly and younger patients. Large population-based databases have recently been used to try to determine whether age effects outcome after RC but their conclusions may not be as generalizable as ours for several reasons: billing code data was used to build patient cohorts, patients were generally recipients of Medicare, lack of pathological review, and lack of available and accurate clinical data. Our series is unique in that it comprises a large group of patients from two major tertiary care academic institutions using a very robust dataset. Pathological specimens were reviewed by dedicated genitourinary pathologists, including those recovered from peripheral hospitals. Our sample size is one of the largest single- or multi-institutional studies. OBJECTIVE: • To analyse the impact of patient age on survival after radical cystectomy (RC). PATIENTS AND METHODS: • After ethics review board approval, two databases of patients with bladder cancer (BC) undergoing RC at the University Heath Network, Toronto, Canada (1992-2008) and the University of Turku, Turku, Finland (1986-2005) were retrospectively analysed. • A total of 605 patients who underwent this procedure between June 1985 and March 2010 were included. • Patients were divided into four age groups: ≤ 59, 60-69, 70-79 and ≥ 80 years. • Demographic, clinical and pathological data were compared, as well as recurrence-free survival (RFS), disease-specific survival (DSS) and overall survival (OAS) rates. RESULTS: • Compared with younger patients (age ≤ 79 years), elderly patients (age ≥ 80 years) had higher American Society of Anesthesiologists scores (P < 0.001), a greater number of lymph nodes removed during surgical dissection (P < 0.001), and underwent less adjuvant treatment (P < 0.001). • Choice of urinary diversion differed among the groups, with ileal conduit being used for all patients ≥ 80 years (P < 0.001). • No differences were noted between age groups with respect to RFS (P= 0.3), DSS (P= 0.4) or OAS (P= 0.4). CONCLUSION: • Although RC is an operation with significant morbidity, it is a viable treatment option for carefully selected elderly patients. Senior patients (≥ 80 years) should not be denied RC if they are deemed fit to undergo surgery. • Senior adults do not suffer from adverse histopathological features as compared with younger patients.

Upstaging of urothelial cancer at the time of radical cystectomy: factors associated with upstaging and its effect on outcome.

UNLABELLED: What's known on the subject? and What does the study add? The reported discordance between staging on transurethral bladder resection and on radical cystectomy pathology in the literature ranges from 20 to 80%.Correct staging in bladder cancer has direct implications for its management. The upstaging from organ-confined (OC) to non-organ-confined (nOC) disease has been reported in 40% of cases. Lymphovascular invasion (LVI) is a factor known to be associated with poor clinical outcome. Pathological upstaging was observed in our cohort in 40% of cases and most cases (80%) were upstaged from OC to nOC disease. During the study period the frequency of upstaging observed increased. We found LVI (hazard ratio [HR]= 5.07, 95% CI = 3.0-8.3, P < 0.001) and any histological variant variant (HR = 2.77, 95% CI = 1.6-4.8, P < 0.001) to be strong independent predictors of upstaging. Patients with clinical T2 bladder cancer found with upstaging at the time of radical cystectomy had a poorer outcome than patients with no upstaging. Identification of patients at high risk of upstaging at radical cystectomy is key to improving their management and outcome. OBJECTIVES: To analyse the details of bladder cancer (BC) staging in a large combined radical cystectomy (RC) database from two academic centres. To study rate and time trends, as well as risk factors for upstaging, especially clinical factors associated with staging errors after RC. PATIENTS AND METHODS: Characteristics of patients undergoing RC at University Health Network, Toronto, Canada (1992-2010) and University of Turku, Turku, Finland (1986-2005) were analysed. RESULTS: Among 602 patients undergoing RC, 306 (51%) had a discordance in clinical and pathological stages. Upstaging occurred in 240 (40%) patients and 192 (32%) patients were upstaged from organ-confined (OC) to non-organ-confined (nOC) disease. During the study period, upstaging became more common in both centres. In multivariate analyses, T2 disease at initial presentation (P= 0.001, odds ratio [OR]= 2.62, 95% confidence interval [CI]: 1.44-4.77), high grade disease (P= 0.01, OR = 2.85, 95% CI: 1.21-6.7), lymphovascular invasion (LVI) (P < 0.001, OR = 5.17, 95% CI: 3.48-7.68), female gender (P= 0.038, OR = 0.6, 95% CI: 0.38-0.97, and histological variants (P < 0.001, OR = 2.77, 95% CI: 1.6-4.8) were associated with a risk of upstaging from OC to nOC disease. Upstaged patients had worse survival rates than patients with correct staging. This was especially significant among patients with carcinoma invading bladder muscle before undergoing RC (16% vs 46% 10-year disease-specific mortality, P < 0.001). CONCLUSIONS: Upstaging is a common problem and unfortunately no improvements have been observed during the last two decades. LVI and the presence of histological variants are strong predictors of upstaging at the time of RC. Pathologists should be encouraged to report LVI and any histological variant at the time of TURBT.

The Evaluation of the Relation between Bladder Cancer and Oxidative Stress Using NRF-2/KEAP-1 Pathway, Zinc and Copper Levels.

PURPOSE: It has been shown that the Copper and Zinc contribute to the structure of the antioxidant enzymes. In addition NRF-2 and KEAP-1 complex have powerful effect on the intracellular organization of the antioxidants. We evaluated the relation of Copper, Zinc, NRF-2 and KEAP-1 complex regarding to the oxidative stress with tumor stage - grade in patients with bladder cancer. MATERIALS AND METHODS: A total of 52 patients (32 bladder cancer and 20 control group) were included to the study. The demographic properties of groups were identical. Serum NRF-2, KEAP-1, Cu and Zn levels were compared by ELISA method between the groups and tissue NRF-2, KEAP-1, Cu and Zn levels were evaluated also by ELISA method at cancer patients.

Combination of biomarkers for neoadjuvant systemic chemotherapy before cystectomy in patients with urinary bladder cancer.

Clinical utility of cisplatin based neoadjuvant chemotherapy (NAC) prior to radical cystectomy is limited because of lack of tools that can guide for a better patient selection. We aim to explore if a combination of biomarkers is superior to a single marker. Pretreatment tumor specimens and clinical data from two randomized trials including 250 patients with T2-T4 urothelial bladder cancer, were used. The information on the expressions on tumor tissue of four biomarkers; CCTα, emmprin, survivin, and BCL-2, detected by immunohistochemistry in our previous studies, was used. Cox proportional hazard models, including treatment-by-biomarker interaction terms, were used to assess the predictive value of the biomarkers for efficacy of NAC on overall survival. CCTα provided predictive information about the efficacy of NAC (interaction P=0.009). None of the other biomarkers provided statistically significant information additional to CCTα. The adjusted hazard ratio for NAC treated versus no-NAC was 0.42 (95% CI: 0.27-0.64) for patients with negative CCTα expression, when adding information about emmprin it decreased to 0.33 (95% CI: 0.19-0.56) for patients with both negative CCTα and emmprin. This corresponds to a decrease in number needed to treat from 4 to 3 patients. The combination of CCTα with survivin or BCL-2 yielded similar results. In a group of patients with muscle invasive bladder cancer a combination of two biomarkers might improve the possibility to identify patients most likely to benefit from the use of NAC. Further studies designed to have sufficient power to detect an interaction effect are needed.

The presence of transurethral cystometry catheter and type of stress test affect the measurement of abdominal leak point pressure (ALPP) in women with stress urinary incontinence (SUI).

AIMS: Abdominal leak point pressure (ALPP) measurements in female SUI may show variability because of the variations in measurement protocols. The aim of this study is to investigate the effect of cystometry catheter on ALPP measurement and compare the sensitivity of Valsalva and cough maneuvers in demonstrating urinary leakage in women complaining of SUI. METHODS: In this prospective study, 194 female patients complaining of SUI underwent urodynamic studies using a 8-fr urethral cystometry and 10-fr rectal catheter. At the cystometric capacity, Valsalva and then cough ALPP was measured in semi-supine position. The same procedure was repeated after removing the cystometry catheter. The results were analyzed with Chi-square and student's t-test where appropriate. RESULTS: In the whole study group, more patients lost urine when coughing than with Valsalva (122 vs. 93, P = 0.0013). One hundred thirty-seven (71%) women revealed a positive stress test both with and without catheter where the presence of the catheter was associated with significantly higher cough and Valsalva ALPP. In this subgroup of 137 patients, cough-induced ALPP values were significantly higher than Valsalva ALPP. Another 29 (15%) women leaked only after the removal of the catheter. Urine leakage could not be demonstrated in the rest of 28 patients (14%) with any maneuver even without catheter in the semi-supine position. CONCLUSION: Cough-induced stress test is significantly more sensitive than Valsalva to demonstrate urinary leakage. Cystometry catheter significantly increases cough and Valsalva ALPP whereas stress test can be false negative due obstructive effect of cystometry catheter in a group of patients. Stress test may be negative in the semi-supine position in about 14% of women complaining of SUI.

Is Bcl-2 a predictive marker of neoadjuvant chemotherapy response in patients with urothelial bladder cancer undergoing radical cystectomy?

Background: Response to neoadjuvant cisplatin treatment in bladder cancer has been linked to expression of Bcl-2 protein by cancer cells. The objective of this study was to test Bcl-2 as a predictive marker of neoadjuvant cisplatin chemotherapy response in a patient cohort from randomized cystectomy trials. Methods: Tumor samples were taken from 247 patients with T2-T4 bladder cancer enrolled in two randomized trials comparing cystectomy with or without neoadjuvant chemotherapy. Tissue microarrays from pre-intervention transurethral resection specimens were assessed for Bcl-2 protein status by immunohistochemistry. Extension of staining above 10% was regarded as positive. Downstaging and survival ratios in relation to Bcl-2 immunoreactivity and neoadjuvant chemotherapy utilization were calculated using the log rank test and multivariate Cox proportional hazards regression analyses. Results: Bcl-2 expression was positive in 38% and negative in 62% of the 236 evaluable patients. Bcl-2 negative patients receiving neoadjuvant chemotherapy had a significant increase in survival (p = 0.009), while Bcl-2 positive patients showed no difference (p = 0.4). However, the interaction variable between neoadjuvant chemotherapy and biomarker status was not significant (p = 0.38). When the prognostic value was assessed in the no-chemotherapy group, 5-year overall survival times were significantly better among Bcl-2 positive patients than among Bcl-2 negative patients (42 months vs 33 months, p = 0.04), but again Bcl-2 status did not remain independent when other factors were adjusted. Also, in a multivariate analysis with all patients, Bcl-2 was not significant. Conclusions: Bcl-2 status is not an independent predictor of neoadjuvant cisplatin chemotherapy response and is not prognostic in muscle-invasive bladder cancer.

Choline-phosphate cytidylyltransferase-α as a possible predictor of survival and response to cisplatin neoadjuvant chemotherapy in urothelial cancer of the bladder.

OBJECTIVES: The aim of this study was to test choline-phosphate cytidylyltransferase-α (CCT-α) protein as a biomarker for neoadjuvant cisplatin chemotherapy response in a bladder tumor setting. MATERIALS AND METHODS: A total of 238 patients with T2-T4 bladder cancer enrolled into two prior randomized trials comparing neoadjuvant cisplatin-based chemotherapy (NAC) plus cystectomy with cystectomy only (no-NAC) were used as discovery and validation cohorts. Protein expression was determined with immunohistochemistry and assessed with Histo (H)-scoring. RESULTS: In the discovery cohort, comprising 61 patients, the survival ratio after NAC treatment for CCT-α-negative patients was significantly increased (p = 0.001) while there was no survival advantage in the CCT-α-positive patient group. Similarly, in the validation cohort with 177 patients, NAC treatment improved survival only in the CCT-α-negative group (p = 0.006). Although there was a tendency for a good NAC response with negative CCT-α status, the interaction variable between biomarker and treatment was not significant (p = 0.24). In the cystectomy-only group, patients with positive CCT-α expression had a better survival than CCT-α-negative patients. This prognostic effect of CCT-α expression remained significant after adjusting for well-known prognostic factors in a multivariate analysis. In a pooled database of both patient data sets, multivariate analyses showed CCT-α status as an independent factor for overall survival (p = 0.018; hazard ratio = 1.80, 95% confidence interval 1.11-2.93). CONCLUSION: CCT-α status was not predictive of outcome of NAC response; however, in the control group with cystectomy only it was found to have prognostic value.

The Comparison of the Effects of Nebivolol and Metoprolol on Erectile Dysfunction in the Cases with Coronary Artery Bypass Surgery.

PURPOSE: Beta-blocker use is common in the cases with coronary artery bypass surgery. According to the literature, beta-blockers have positive effects but may cause erectile dysfunction (ED). The most commonly used beta-blockers in ischemic cardiac disease are nebivolol and metoprolol. In our clinic, we aimed to compare the effects of nebivolol and metoprolol succinate on ED in the sexually active cases with coronary artery bypass surgery. METHODS: In our clinic, a total of 119 patients with coronary artery bypass surgery were included in the study. International Index of Erectile Function (IIEF-5) Test was used to evaluate whether the patients had ED and to grade the cases. RESULTS: No significant difference was found in terms of anti-ischemic efficacy between metoprolol succinate and nebivolol in the postoperative period; however, the incidence of any grade ED was %85.96 in Group 1, %83.87 in Group 2. This difference was considered as statistically significant (p = 0.036). CONCLUSION: Beta-blocker use increases the risk of ED in cases with ischemic cardiac disease. We suggest that the complaints of ED could be less frequent with nebivolol use in sexually active cases with ischemic cardiac disease.

Mannitol has a protective effect on testicular torsion: An experimental rat model.

OBJECTIVE: Testicular torsion is an emergency condition that causes testicular injury. Any treatment opportunity reducing the destructive effect of testicular torsion is important for the future life of patients. In this experimental study we investigated the protective effect of mannitol on ischemia-reperfusion (I/R) injury in a rat testes torsion model. METHOD: In total, 32 male Sprague Dawley rats were included. Four experimental groups included eight rats each. Group A was a sham group in which the right testis was brought out through a scrotal incision and then replaced in the scrotum without torsion. In Group B, the right testis was torsioned, by rotating 720° clockwise and fixed to the scrotum with no treatment. In Group C, the same testicular torsion process was performed with saline infusion just after testicular torsion. In group D, mannitol infusion was used just after testicular torsion. Testicles were detorsioned after 3 h and left inside for more than 2 h before orchiectomy. Histopathological, immunohistochemical, and biochemical analyses were performed. RESULTS: Testicular architecture was disturbed significantly in the torsion groups without mannitol infusion. However, testicular tissue structure was significantly better in the mannitol-treated group, demonstrating a protective effect. Similar findings were also shown for the proliferating cell nuclear antigen (PCNA) index and antioxidant activity; both were higher in the mannitol group than in the no-treatment and saline groups (p < 0.01). The apoptotic index was also significantly lower in the mannitol-treated group compared with the no treatment and saline groups (p < 0.01). CONCLUSIONS: The seminiferous tubule structure in testicular torsion without mannitol treatment was significantly disturbed, whereas the structural disruption was considerably less in the mannitol group. Mannitol treatment also decreased reactive oxygen radical levels significantly and was able to decrease apoptosis. These results were consistent with other organ model studies that evaluated the protective effects of mannitol treatment in I/R injury. Mannitol infusion had a protective effect against I/R injury in testicular torsion in rats. This experimental study may guide clinicians to evaluate the effectiveness of mannitol in human testicular torsion.

The histomorphological findings of kidneys after application of high dose and high-energy shock wave lithotripsy.

INTRODUCTION: In this animal study, we reviewed the histomorphological findings in rabbit kidneys after a high number of high-energy shock wave applications and observed if there were any cumulative effects after repeated sessions. MATERIAL AND METHODS: We formed 2 groups, each consisting of 8 rabbits. Group 1 received 1 session and group 2 received 3 sessions of ESWL with a 7 day interval between sessions, consisting of 3500 beats to the left kidney and 5500 beats to the right kidney per session. The specimens of kidneys were examined histomorphologically after bilateral nephrectomy was performed. For statistical analysis, 4 groups of specimens were formed. The first and second groups received 1 session, 3500 and 5500 beats, respectively. The third and fourth groups received 3 sessions, at 3500 and 5500 beats per each session, respectively. The sections were evaluated under a light microscope to determine subcapsular thickening; subcapsular, intratubular and parenchymal hemorrhage; subcapsular, intersitital, perivascular and proximal ureteral fibrosis; paranchymal necrosis; tubular epithelial vacuolization; tubular atrophy; glomerular destruction and calcification. RESULTS: In histopathological examinations capsular thickening, subcapsular hematoma, tubuloepithelial vacuolisation, glomerular destruction, parenchymal hemorrhage, interstitial fibrosis, and perivascular fibrosis were observed in all groups. In statistical analysis, on the basis of perivascular fibrosis and tubular atrophy, there was a beats per session dependent increase of both. CONCLUSIONS: The detrimental effects from ESWL are dose dependent but not cumulative for up to 3 sessions. Histopathological experimental animal studies will aid in understanding local and maybe, by means of these local effects, systemic effects.

Effect of voiding position on uroflowmetric parameters in healthy and obstructed male patients.

PURPOSE: Uroflowmetry is frequently used and simple urodynamic test, but it may be affected by various factors. Voiding position is one of the factors that can change the results. We tried to compare the uroflowmetric parameters in sitting and standing positions during urination. MATERIAL AND METHODS: A total of 198 patients were enrolled to the study. All patients underwent an uroflowmetry in standing and sitting position at late afternoon (2-4 PM) of two corresponding days with a gravimetric uroflowmeter (Uroscan, Aymed, Turkey). A transabdominal ultrasonography was used to evaluate post voiding residue (PVR). All uroflowmetric parameters and PVR were compared with paired t test or Wilcoxon signed rank test. RESULTS: The median age of study population was 58.0 (36-69) years. There was no statistically significant difference at voided volume of patients in standing and sitting position as it was 271.5 ± 81.8 mL and 274.8 ± 82.4 mL, respectively (P = .505). Mean maximum flow rate (Qmax) during urination at standing position was 15.3 ± 6.7 mL/s while it was 15.0 ± 7.0 mL/s at sitting position (P = .29). Mean average flow rate in standing position was 8.60 ± 4.0 mL/s and 8.25 ± 3.8 mL/s in sitting position (P = .054). There was a statistically significant difference between the median post-voiding residues in standing and sitting urination which was 29.5 (0-257) mL in standing and 47.5 (2-209) mL in sitting position (P < .0001). Other uroflowmetric parameters (time to maximum flow and voiding time) was not statistically different between groups. CONCLUSION: There are no clinically important uroflowmetric differences between voiding in sitting and standing positions so voiding position may be left to personal preferences during uroflowmetric evaluation.

Presence of high grade tertiary Gleason pattern upgrades the Gleason sum score and is inversely associated with biochemical recurrence-free survival.

OBJECTIVES: Tumor heterogeneity is a common finding and led to realization of a tertiary Gleason component (TGC) in prostate cancer. In an attempt to further investigate its prognostic value, we analyzed the association of tertiary Gleason pattern in Gleason score ≤ 7 tumors with pathologic stage and biochemical disease-free survival. MATERIAL AND METHODS: A total of 331 radical prostatectomy specimens were analyzed retrospectively. The primary, secondary, and the tertiary patterns were evaluated by reviewing all of the pathologic slides. TGC was defined as Gleason grade pattern 4 or 5 for Gleason score < 7 tumors and Gleason grade pattern 5 for Gleason score 7 tumors. The pathologic prognostic factors, (extraprostatic extension, seminal vesicle and lymph node invasion, surgical margin status) of Gleason score < 7, 3+4, and 4+3 tumors with or without TGC were compared. Biochemical recurrence-free survival (BRFS) was calculated using Kaplan-Meier method with log rank test, and the influence of TGC was assessed in a Cox regression model. RESULTS: TGC observed more frequently with higher Gleason scores (21% of the GS < 7 cases, 23% of the GS 3+4 cases, and 58% of the GS 4+3 cases). In terms of adverse pathologic prognostic factors and BRFS, GS < 7 tumors with TGC behaved significantly worse than GS < 7 tumors without TGC (P = 0.01 and P = 0.001, respectively) with properties similar to GS 3+4 tumors without TGC. Gleason score 3+4 and 4+3 tumors without TGC were statistically similar and had better features than corresponding tumors of same Gleason score with TGC. Furthermore, Gleason score 7 tumors with TGC had similar features with GS 8-10 tumors. During follow-up, 73 (22%) subjects had PSA recurrence. In the Cox regression model TGC was an independent variable for BRFS (HR = 2.63, 95% CI = 1.39-4.98, P = 0.003). CONCLUSION: According to the present study, 3 different prognostic groups were observed; good prognostic group: GS < 7, intermediate prognostic group: GS < 7+TGC, GS 3+4, and GS 4+3, and finally bad prognostic group: GS (3+4)+TGC, GS (4+3)+TGC, GS > 7. Presence of a TGC appears to upgrade the total score and adjuvant treatment decisions may further be refined by considering the tertiary pattern.

An unresolved discussion: presence of premature ejaculation and erectile dysfunction in lumbar disc hernia.

PURPOSE: Premature ejaculation (PE) and erectile dysfunction (ED) are both frequent diseases with several questions about the aetiological factors for these disorders. Lumbar disc herniation (LDH), which can cause both neurological and physiological impairments, may be a causative reason. We prospectively tried to evaluate the presence of PE and ED in patients with LDH and identify the effect of both surgical and physical therapy treatments for LDH on PE and ED. METHODS: A total of 50 patients with LDH and a corresponding control group without LDH at an age of 18-50 years were included in the study. Both PE and ED were evaluated with premature ejaculation diagnostic tool (PEDT) and International Index of Erectile Function. Mean intravaginal ejaculatory latency time (IELT) was calculated at their 5 consecutive intercourse. Physical therapy or microdiscectomy was performed according to indication. After 6 months of follow-up, patients in treatment group were re-evaluated for PE and ED. RESULTS: Mean age of study and control group was 34.1 ± 3.3 and 34.2 ± 4.0 years, respectively (p = 0.979). In LDH group, IELT was <1 min in 12 (24 %), 1-2 (16 %) min in 8, 2-3 min in 7 (14 %), 3-4 min in 7 (14 %) and 4 or more minutes in 16 (32 %) patients. These numbers were 11 (22 %), 8 (16 %), 5 (10 %), 9 (18 %) and 17 (34 %) in control group, respectively. Mean PEDT score of patients who had IELT < 1 min was 11.9 ± 2.1 and 10.7 ± 2.1 in study and control group, whereas it decreased to 1.0 ± 2.8 and 0.5 ± 1.8 as IELT increased over 4 min, respectively. There were 11 (22 %) patients with ED in LDH group, whereas there were only 2 (4 %) in control group (p = 0.017). Twenty patients with LDH underwent surgery while 30 had been taken into physical therapy. After 6 months, patients with PE significantly decreased in both surgery and physical therapy group (p = 0.025 and p = 0.046). Patients with ED also decreased after treatment, but the numbers were so limited for statistical evaluation. CONCLUSION: Although ED was more frequent in patients with LDH, PE was similar in both study and control groups, but the treatment of LDH had positive effects on PE and ED.

A new cause of male infertility after cisplatin exposure: the effect of cisplatin on Y chromosomes.

OBJECTIVES: To investigate the impact of cisplatin (CP) on the testes-specific protein, Y-linked (TSPY) gene situated on the Y chromosome. METHODS: The control group consisted of 10 rats. Group IIA consisted of 15 rats that underwent orchiectomy and received three cycles of 1 mg/kg, 2.5 mg/kg, or 5 mg/kg CP. Group IIB was exposed to the same doses of three cycles of chemotherapy but was examined after 3 months of chemotherapy. Group III was exposed to the same doses of chemotherapy without initial orchiectomy. Reverse transcriptase polymerase chain reaction for TSPY messenger ribonucleic acid (mRNA) and immunohistochemical staining for histone 2B were performed on the testes. Results were evaluated by one-way analysis of variance. RESULTS: Compared with the controls, the expression of TSPY mRNA in Group IIA after exposure to 1 mg/kg CP did not change; however, mRNA levels after exposure to 2.5 mg/kg and 5 mg/kg CP were decreased by 40% and 78%, respectively. In Group III after exposure to the same doses of CP, mRNA levels decreased by 30%, 87.5%, and 88%, respectively. The expression of TSPY was at normal levels except in rats that received 5 mg/kg CP in Group IIB. Immunohistochemical study revealed that histone 2B expression was decreased in a dose-dependent manner. None of the rats from any of the groups died during the study period. CONCLUSIONS: Decreased TSPY expression after CP exposure might be another mechanism for male infertility.

Erectile function in prostate cancer-free patients who underwent prostate saturation biopsy.

OBJECTIVE: To evaluate the erectile function following transrectal ultrasound-guided saturation biopsies of the prostate. MATERIALS AND METHODS: Of the 150 patients included in the study, those with persistently elevated prostate-specific antigen (PSA) level underwent saturation biopsy. A median of 22-core (minimum: 20; maximum: 30) prostate saturation biopsies was taken. Patients were evaluated for erectile function prebiopsy with the 5-item version of the International Index of Erectile Function (IIEF-5) and the IIEF-Erectile Function (IIEF-EF) domain scoring. Concomitant systemic diseases and medications that would interfere with erectile function were recorded. Eighty-eight patients reported to be prostate cancer-free underwent further evaluation with the IIEF-5 questionnaire at 1 and 6 mo postbiopsy. Severity of erectile dysfunction (ED) was classified into four categories. RESULTS: The patients' ages, serum PSA levels, prostate volumes, and number of cores showed no significant correlation with changes in ED scores after the prostate saturation biopsies. According to the IIEF-5, for patients who were previously potent and found to be free of prostate cancer, the ED rates were 11.6% at the first month, and no ED was reported at the sixth month of evaluation. IIEF-5 and IIEF-EF domain scores displayed a statistically significant difference between baseline and first-month scores, but not between baseline and sixth-month scores, which returned to baseline values. CONCLUSIONS: Although saturation biopsy of the prostate is a safe procedure on the basis of erectile function, the minimal risk of temporary postbiopsy ED should be discussed with previously potent patients.

Effect of experimentally induced Escherichia coli epididymo-orchitis and ciprofloxacin treatment on rat spermatogenesis.

We investigated the effects of epididymo-orchitis and ciprofloxacin on rat testicular histology and spermatogenesis. The control group underwent left orchiectomy. The second group received oral ciprofloxacin (150 mg/kg/day) for 10 days. Escherichia coli (10(6) cfu/mL, 0.1 mL) was injected into the proximal right ductus deferens in the third group. The fourth group received ciprofloxacin treatment 48 h after E. coli inoculation. In groups 3 and 4, bilateral orchiectomy was performed 14 days after the challenge. In healthy rats, ciprofloxacin caused recognizable histological damage associated with a mild decrease in testicular volume and sperm concentration. Infected testicles in groups 3 and 4 revealed severe histological damage associated with severe testicular atrophy and impaired spermatogenesis that were more significant in infected rats which received ciprofloxacin treatment. Contralateral testicles in these animals showed similar histopathological changes to a lesser extent. The results of our study suggest a gonadotoxic potential for ciprofloxacin and this potential in humans should be addressed with further studies.